ARTICLE | doi:10.20944/preprints202009.0567.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: antimicrobial resistance; antimicrobial stewardship; barriers; perception; survey; veterinary practitioners
Online: 24 September 2020 (04:41:43 CEST)
Usage of antimicrobials in veterinary practices has always been under scrutiny due to the perceived risk of resulting in antimicrobial-resistant pathogens. This creates the necessity for understanding the role of the prescriber group. Hence, we conducted a cross-sectional survey among veterinary practitioners from August to November 2019 in the Chattogram district of Bangladesh, aiming to assess the practitioner’s perceptions regarding antimicrobial prescribing and antimicrobial resistance (AMR) issue. We collected responses from 100 veterinarians engaged in the treatment of the large animal, poultry, and pet animal through a self-administrated questionnaire. Proportions were calculated for categorical variables and the results are presented using visual aids. Our study revealed two key barriers - scarcity of enough information on antimicrobial used, and the lack of training in the proper prescription of antimicrobials. Participants recognized that prescribing too many varieties of antimicrobials and the use of an incomplete course of drugs as two very important causes for the development of antimicrobial resistance. In addition, prescription of inappropriate doses and incentives from pharmaceutical companies were dubbed as important causes. We also found that along with clinical features and types of organisms, the availability of drugs in the local market and the economic conditions of farmers have potential impacts on the antimicrobials prescribing decision of the veterinarians. However, all participants recognized the emerging threats of AMR. Results suggested that capacity building of veterinarians and the maintenance of strong coordination are crucial in ensuring the proper engagement of veterinarians as the front-line fighters for tackling the AMR issue.
REVIEW | doi:10.20944/preprints202009.0561.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: covid19; immunostimulant; immunomodulator; vitamin D; vitamin C; zinc
Online: 24 September 2020 (03:40:34 CEST)
Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.
Wed, 23 September 2020
BRIEF REPORT | doi:10.20944/preprints202009.0555.v1
Online: 23 September 2020 (17:44:21 CEST)
Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P < .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.
ARTICLE | doi:10.20944/preprints202008.0204.v2
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-Cov-2; epidemic surveillance; emerging infectious disease; epidemic threshold
Online: 23 September 2020 (11:10:15 CEST)
Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26th 2020 and the sanitary alert on March 3rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
CASE REPORT | doi:10.20944/preprints202009.0543.v1
Subject: Medicine & Pharmacology, Other Keywords: genetics； comparative genomics； phylogenetic analysis； osteopetrosis； CLCN7 gene
Online: 23 September 2020 (07:56:30 CEST)
Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular pathogenicity analysis are essential for precise diagnosis and new targets for preventive pharmacotherapy. Mutations in the CLCN7 gene give rise to the complete spectrum of osteopetrosis phenotypes and are responsible for about 75% of cases of autosomal dominant osteopetrosis. In this study, we report the identification of a novel variant in the CLCN7 gene in a patient diagnosed with osteopetrosis and provide evidence for its significance (likely deleterious) based on extensive comparative genomics, protein sequence and structure analysis. A set of automated bioinformatics tools used to predict consequences of this variant identified it as deleterious or pathogenic. Structure analysis revealed that the variant is located at the same “hot spot” as the most common CLCN7 mutations causing osteopetrosis. Deep phylogenetic reconstruction showed that not only Leu614Arg, but any non-aliphatic substitutions in this position are evolutionarily intolerant, further supporting the deleterious nature of the variant. The present study provides further evidence that reconstructing a precise evolutionary history of a gene helps predicting phenotypical consequences of variants of uncertain significance.
REVIEW | doi:10.20944/preprints202009.0541.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Endometriosis; ureter; bladder; ultrasound; magnetic resonance imaging; hydroureter.
Online: 23 September 2020 (07:44:27 CEST)
Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.
REVIEW | doi:10.20944/preprints202009.0539.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: brain aging; energy metabolism; neurodegeneration; neurodegenerative disorders
Online: 23 September 2020 (04:55:21 CEST)
A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
Subject: Medicine & Pharmacology, General Medical Research Keywords: Hyperthyroid; Hypothyroid; Euthyroid; Vitamin D; Bone Turn Over Markers; Bone Mineral Density
Online: 23 September 2020 (04:52:34 CEST)
Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.
Subject: Medicine & Pharmacology, General Medical Research Keywords: articles; bibliometric; causes; death; diseases; journals; Russia
Online: 23 September 2020 (04:48:32 CEST)
Societal changes have had effects on deaths from all causes in Russia. Up until now, deaths from all causes have been well researched, although several inconsistencies persist on the contributions of researchers. This study assessed research output, trends and topics that shaped deaths from all causes studies in Russia. Using bibliometric and topic modelling approaches, deaths from all causes in Russia published from 1914 to date was analysed using data on publications, citations, journals, keywords co-occurrence, year of publication, institutional affiliations, and country of origin from Scopus. Overall results indicate a steady growth of publications in Russia was documented after 1985. The h-index of some top 10 authors did not surpass single digits. A network visualisation map showed that ‘Russia’, ‘male’, ‘mortality’ and ‘human’ were the most commonly encountered vital terms. Of the ten most prolific authors, McKee M, Shkolnikov VM, Bobak M, Samorodskaya IV and Andreev E were the first five. Although the top 10 journals researching on death causes in Russia were Russian, these journals were not included in the most cited journals. The most prolific institutions studying deaths in Russia included; Tehran University of Medical Sciences, London School of Hygiene and Tropical Medicine, University College London, Max Planck Institute for Demographic Research and National Research University-Higher School of Economics. Findings suggest that deaths from all causes research attention in Russia increased in recent years, but the number of publications and research related engagements (e.g., networking and/ collaboration) does not match-up to other countries (e.g., UK, US, Germany). This research lag calls for more collaborative research between public health disciplines and networking among researchers (i.e., both national and international).
REVIEW | doi:10.20944/preprints202009.0535.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Pandemic; Global health; Health inequalities
Online: 23 September 2020 (04:13:51 CEST)
The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.
REVIEW | doi:10.20944/preprints202009.0534.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: breast cancer etiopathogenesis; breast cancer treatment; hydrogen ion dynamics of cancer; pH-related paradigm; H+-related therapeutics of breast cancer
Online: 23 September 2020 (04:04:24 CEST)
A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.
ARTICLE | doi:10.20944/preprints202009.0532.v1
Subject: Medicine & Pharmacology, Other Keywords: adipose derived regenerative cells; ADRCs; efficacy; point of care treatment; stem cells; stromal vascular fraction; tendon healing without scar formation; tendon regeneration
Online: 23 September 2020 (03:49:36 CEST)
Current clinical treatment options for symptomatic rotator cuff tear offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with autologous, adipose derived regenerative cells. Here we demonstrate, for the first time, a comprehensive histological and immunohistochemical analysis of the biopsy of a supraspinatus tendon of a 66-year-old subject with traumatic rotator cuff injury, taken ten weeks after local injection of fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs), prepared at the point of care. Our analysis demonstrated clear evidence towards regenerative healing of the injured supraspinatus tendon. Of note, no formation of adipocytes was observed. These findings indicate that injected autologous, unmodified stem cells can indeed form new tendon tissue and regenerate an injured human tendon.
Tue, 22 September 2020
ARTICLE | doi:10.20944/preprints202009.0517.v1
Subject: Medicine & Pharmacology, Other Keywords: chemonucleolysis; condoliase; chondroitin sulfate ABC endolyase; lumber disc herniation
Online: 22 September 2020 (10:02:01 CEST)
Background and Objectives: Chondroitin sulfate ABC endolyase (condoliase) was launched as a new drug for chemonucleolysis in 2018. There are few Few studies assessed regarding its clinical outcomes, and many important factors matters still remain unclear. The purpose of this This study aimed is to clarify clarify the preoperative conditionsfactors for in which condoliase could beis highly effective. Materials and Methods: Of the 47 patients who received condoliase, 34 patients were enrolled in this study. The mean age of the patients was 33 years. The average disease duration since the onset of the disease was 8.6 months. We evaluated the patients’patient’s low back and leg painpains using a numericalNumerical rating scale (NRS) score at two time points (before therapy and 3 months after therapyadministration). We divided the patients into two groups ([good group [(G]:): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%]. The parameters evaluatedSurvey items were age, disease disease duration, body mass index (BMI), and the presence or absence of positive or negative straight leg raising (SLR) test results. In additionMoreover, the loss of disc height loss and participation of preoperative radiological findings were also evaluated. Results: In terms of low back and leg pain, the G group were in 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients’. Patient’s age (low back pain G/P, 21.0/36.5 years)), was significantly loweryounger in the G group of low back pain (p = 0.001). High intensity change inof the protruded nucleus pulposus (NP) and the spinal canal occupancy by theof NP ≥ 40% were significantly highhighly observed in those withthe leg pain in the G groups (14/21,: p = 0.04; and 13/21,: p = 0.03, respectively). Conclusions: The efficacy of improvement inof leg pain was significantlyhighly correlated with high intensity change and size of the protruded NP. Condoliase was not significantly effective forto low back pain, but could might be expected have anthe effect onto younger patients.
REVIEW | doi:10.20944/preprints202007.0737.v3
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: oxidative stress; redox; antioxidant; multiple sclerosis; biomarker; neurodegenerative disease; personalized medicine
Online: 22 September 2020 (08:42:20 CEST)
Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the disturbance of reduction-oxidation (redox) homeostasis such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring a battery of reactive chemical species, oxidative enzymes, antioxidative enzymes and degradation products helps evaluate the redox status of MS patients to expedite building personalized treatment plans for the sake of better quality of life.
ARTICLE | doi:10.20944/preprints202009.0510.v1
Subject: Medicine & Pharmacology, Other Keywords: Hydrogel; pH-responsive; colon; targeted delivery; methotrexate
Online: 22 September 2020 (08:17:48 CEST)
The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.
ARTICLE | doi:10.20944/preprints202005.0305.v2
Subject: Medicine & Pharmacology, Pediatrics Keywords: sickle cell disease; feasibility; regular follow-up; remote area; Democratic Republic of Congo
Online: 22 September 2020 (08:12:05 CEST)
Background: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. If reference sickle cell centers have been implemented in capital-cities of African countries and have proven to be beneficial for SCD patients, it has never been set up ina rural area for families with very low sources of income. Method: A cohort of 143 children with SCD aged 10 years old (IQR [inter quartile range]: 6–15 years) (sex ratio male: female = 1.3) were clinically followed for 12 months without any specific intervention, outside management of acute events ,and then 12 months with a monthly medical visit , a biological follow-up and regular prophylaxis. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-up in a new sickle cell referral center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease of the lymphocytes count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusions: Creation of a sickle cell referral center and a regular follow-up of children with SCD are possible and applicable in the context of a remote city of an African country. Those simple and accessible measures can reduce the morbimortality of the sickle cell children.
Mon, 21 September 2020
ARTICLE | doi:10.20944/preprints202009.0502.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Anterior cruciate ligament, Electromyography, Isokinetic, Gastrocnemius, Hamstring
Online: 21 September 2020 (11:37:57 CEST)
Background: The optimisation of this return to athletic activity pass by a better understanding of the behaviour of the muscle involved in knee function.In this study, we focused on the muscular activity of the muscle involved in the flexion of the knee. Preciseley on the relation between the muscular activity of the gastrocnemius and the hamstring among the patient that underwent an anterior cruciate ligament reconstruction with hamstring graft.Objective : The objective of the study is to compare, the muscular activity of the flexor knee muscle in patient that underwent an anterior cruciate ligament reconstruction with hamstring autograft and the individuals that have not undergone surgery.Methods : The participants have been divided into two groups : an healthy group and an experimental group that underwent an anterior cruciate ligament recontruction with hamstring graft. The participants had to performe a strenght test on a isocinetik dynamometer. The activity of the medial gastrocnemius, lateral gastrocnemius, femoral biceps and the semitendinosus were mesured during this test.The muscular activity of the muscle mentioned of the individuals in the first group were compared to the ones in the second group via a statistical analysis. Then, a ratio of the activity of the gastrocnemius muscle on the activity of the hamstring was calculated The results of the experimental group were then compared to the results of the control groupResults : The results showed a significative difference activity of the medial gastrocnemius, the femoral biceps and the semitendinosus muscles : the experimental group results were superior to the control group results However the evaluation of the activity reporting has shown significant differences in the two groupsConclusion : This study has allowed us to show a difference in muscular activity of the gastrocnemius and hamstring muscle between patient that underwent an anterior cruciate ligament reconstruction surgery and the heathy participants. However our approch has not allowed us to identify the relation between a heihtened gastrocnemius activity and a diminished hamstring activity following an anterior cruciate ligament reconstruction with hamstring graft. Quite on the contrary, we observed a higher activity of the two muscle groups. Nevertheless, it seem to be necessary to have a variation in situations during the analysis of the gastrocnemius muscle to fully understans its purpose in the functional activity of the knee of patient that have undergone an anterior cruciate ligament reconstruction.
ARTICLE | doi:10.20944/preprints202009.0501.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: human arsenic exposure; water source; risk factors; Thailand
Online: 21 September 2020 (11:32:03 CEST)
Three decades ago, human arsenic (As) contamination has been recognized in Ron Phibun, a sub-district with tin mining activity in southern Thailand. Since then different government bodies have attempted to mitigate the As-contamination problem by providing safe water in households. The most recent study conducted during 2000-2002 reported only a small fraction of population still had high urinary As level. Less attention has been paid to this issue afterwards. The present study aimed to re-assess the current situation, including human As contamination, water use behavior as well as identify risk factors of elevated As concentration among residents of Ron Phibun. The survey of 560 participants living in Ron Phibun with urinary As assessment was conducted. The median urinary As concentration of study participants was higher than normal. Consumption of shallow well water, a source generally considered as As-contaminated, was higher than a previous survey. A significant association was observed between urinary As concentrations and water sources for drinking and cooking. Gender and educational level were found to be associated with urinary As concentration. Significant associations between urinary As concentration and certain diseases (respiratory diseases, dermatitis, and dyslipidemia) were observed. The findings suggested further investigation of all water sources in the area for As contamination.
REVIEW | doi:10.20944/preprints202009.0500.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; impact on society during COVID-19; behavioral impact of COVID-19; government policies against COVID-19; measures adopted by the government; COVID-19 Statistics; Infection rate and Data analysis
Online: 21 September 2020 (11:09:11 CEST)
Background: COVID-19 pandemic has pulled us all a few steps back, were we never shake hands or hug each other when we meet our friends and family after a gap, but instead we greet them by saying Namaste and joining our hands together. As we all know, COVID-19 spreads through air and the only way to shield ourselves is by maintaining a safe distance from one another. Methodology: In order to conduct a meta-analysis on the number of COVID-19 cases in Kerala and India, the data was retrieved from various sites hosted by the government bodies. The data for analysis was collected from May 2020 to July 2020. The average number of days required to reach every 5000 fresh cases were also calculated using this data. COVID-19 has affected all the economy holistically regardless of financial, behavioral, or societal aspects. Conclusion: Lifting of the lockdown in a step by step process keeping in mind the necessities for the nation was a thoughtful act, but the people who mistook this opportunity and did not remain in quarantine after coming from abroad was recognized as the reasons behind the sudden and uncontrolled rise in the number of COVID-19 cases in Kerala, India. The government authorities had no other option but to lift the restrictions to reduce the economic burdens that had already affected the daily wage worker and farmers prompting them to give up their lives.
REVIEW | doi:10.20944/preprints202009.0497.v1
Online: 21 September 2020 (07:20:59 CEST)
To evaluate the efficacy of fish oil for protection against coronary heart disease (CHD), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of fish oil for protection against CHD. We retrieved relevant articles published from January 1966 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. RCTs of fish oil in preventing CHD were selected. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. The first selection involved 350 citations. After screening and evaluation of suitability, 19 RCTs adjusted for clustering were included in the meta-analysis. All selected manuscripts considered that fish oil was effective in preventing CHD, secondary outcome measures included angina, sepsis and death. Compared with the control group, fish oil may confer significant protection against CHD (odds ratio = 0.84; 95% confidence interval: 0.72–0.98). There was no significant difference in the incidence of secondary outcomes between the observation group and the control group (P > 0.05). The above results show that fish oil plays an important role in reducing CHD and cardiovascular events. However, because of the suboptimal quality of the studies included into the meta-analysis, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients.
Sun, 20 September 2020
ARTICLE | doi:10.20944/preprints202009.0483.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: next-generation sequencing; colorectal cancer; ATM mutation; FBXW7 mutation
Online: 20 September 2020 (15:20:52 CEST)
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.
ARTICLE | doi:10.20944/preprints202009.0479.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: suboptimal health status; associated factors; high school students; Shanxi; Guangzhou; Tibet; China
Online: 20 September 2020 (14:50:30 CEST)
Suboptimal health status (SHS) is a state between health and disease, has several associated factors, although, its underlying mechanism is still unclear. This study aimed to investigate the status of SHS and its associated factors of high school students in three areas of China (Shanxi, Guangzhou, and Tibet). A multidimensional sub-health questionnaire of adolescent (MSQA) is used to evaluate SHS. Among 1461 respondents, females proportion 56.47% was higher than males 43.53% where SHS was higher in Shanxi followed by Tibet and then Guangzhou. The rural area, grade, lack of sleep, home visit in a week, lack of exercise, a heavy burden of study, smoking, drinking, and fewer friends were the risk factors of SHS, while, families living status, seeking help and extroversion were the protective factors. SHS is significantly associated with different influencing factors. For comprehensive prevention and control measures, reduce the risk factors and enhance the protective factors.
ARTICLE | doi:10.20944/preprints202009.0470.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: kynurenines; tryptophan; indoleamine 2,3-dioxygenase; single nucleotide polymorphisms; Parkinson’s diseases; neurodegenerative diseases
Online: 20 September 2020 (14:27:12 CEST)
Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.
Sat, 19 September 2020
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine & Pharmacology, Other Keywords: Novel coronavirus diseases 2019; vaccination; target population; China
Online: 19 September 2020 (05:02:54 CEST)
All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: SARS-CoV-2; COVID-19; CNS; infant; Choroid plexus
Online: 19 September 2020 (04:49:18 CEST)
Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis, meningitis and multiple organ damage related to thrombosis, a previous encephalopathy may have contributed to additional cerebral damage. SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.
Fri, 18 September 2020
REVIEW | doi:10.20944/preprints202009.0439.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: KAP; Dental professionals; COVID-19; Pandemic; risk of infection, SARS-CoV-2
Online: 18 September 2020 (12:15:24 CEST)
Background: Dental professions are at high risk of contracting novel corona virus (COVID-19) infections during the dental procedure due to the droplets and aerosols generated during various dental procedures on infected patients. To prevent and avoid the cross-infection of the infection to dental professionals or the patients attending the dental clinic, good knowledge of the infection and its prevention mechanisms is mandatory among the professionals. Until to date, there is no pooled estimate on the knowledge,attitude and practice (KAP) of dental professionals to COVID-19 in the globe. Hence, this study aimed to determine the pooled estimate of KAP of dental professionals in this pandemic disease. Methods: Article search was done electronically using Medline, Scopus, Web of Science, EMBASE, SciELO and Google Scholar from June 1, 2020 to August 20, 2020. All studies that assessed the KAP of dental professionals to COVID-19 were searched and included in this review after passing the inclusion criteria. The pooled analysis of their knowledge (sign and symptom, mode of transmission and prevention mechanisms), attitude (their concern, intention to treat suspected patients) and practice (face mask usage, hand washing and alcohol based hand rub usage, handshaking practice, deferred procedures and checkup of patients temperature) was computed using RevMan 5.3 and random effect model was used. The presence of publication bias was assessed using the funnel plot. Results: Twelve articles with a total of 5,362 study participants were included in this study. The pooled estimate revealed that 59.91% of the dental professionals had good knowledge of the signs and symptoms of COVID-19. Two-third of dental professionals know the prevention mechanisms of the infection, and 70.13% had enough knowledge of the transmission modalities of the infection. The professional attitude revealed that only 36.43% of the participants had intention to treat a patient with cough or suspected COVID-19 (36.43%, 95%CI: 8.57, 64.29). Moreover, 47.85% of the dentists were concerned about their life, and the fate of their profession due to this pandemic disease (47.85%, 95%CI: 26.74, 68.97). The pooled analysis showed only 50.86% (95%CI: 18.64, 83.09) of the study participants worn face mask and 52.63% (95%CI: 10.54, 94.71) had avoided handshaking practice during this pandemic period. Non-emergency dental procedures were canceled by 83.98%. Conclusion: The dental professional KAP is not optimal. Thus, dental professionals should be aware of the recently updated knowledge about COVID-19 and practice according to the standards of treatment guidelines, and the recommended infection control measures in dental settings. Moreover, as saliva and droplets are the major sources of infection, dentists should follow essential protocols to regulate droplet and aerosol contamination in the dental practice
ARTICLE | doi:10.20944/preprints202009.0435.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: PIMS; MIS-C; SARS-CoV-2; COVID-19; Kawasaki disease; survey
Online: 18 September 2020 (11:29:49 CEST)
Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (<5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.
ARTICLE | doi:10.20944/preprints202009.0430.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: anterior cruciate ligament; gait disorder; gait analysis; risk factors
Online: 18 September 2020 (11:17:01 CEST)
Today, rupture of the anterior cruciate ligament is the most common heavy injury in athletes, but it can also occur in sedentary subjects. Its treatment, always adapted to the lifestyle, age and will of the patient, often remains surgical. However, despite its frequency and universality, there are still walking disorders following the operation. These disorders sometimes persist for several months, or even several years after surgery. The present study is therefore interested in determining the risk factors linked to walking disorders following reconstruction of the anterior cruciate ligament. The objective of this study is to determine what risk factors associated with walking disorders are after reconstruction of the anterior cruciate ligament by hamstring graft. This study focused on factors that may exist at 3 and 6 months postoperatively. Two populations participated in this study, a healthy population and a population having benefited from reconstruction of the anterior cruciate ligament. The operated test group is divided into two subgroups, one with a postoperative period of 3 months and the second at 6 months. All subjects were subjected to the same protocol, their gait on the treadmill was analyzed and evaluated with an Optogait® analysis system. A univariate analysis was carried out first. Then, a multivariate analysis by adjustment method was carried out in order to eliminate the potential confounding factors. The comparison of the results between the populations in the univariate analysis shows an absence of significant results however there are trends. The statistical results of the multivariate analysis showed interactions in the two subgroups of the operated population.In fact, it turns out that at 3 months there is a tendency to worse gait disorders in subjects with a high BMI reflecting overweight, when an associated surgical procedure has taken place on the meniscus, in subjects over 35 years of age and males. On the other hand, at 6 months, the tendency to worsening is visible only in the strata represented by subjects with a BMI corresponding to overweight, as well as in subjects having benefited from a meniscal suture associated with ACL reconstruction. .The results of the present study show that there are certain factors which tend to increase the risk of these walking disorders after reconstruction of the anterior cruciate ligament by hamstring graft, these factors are different depending on the time postoperative.
ARTICLE | doi:10.20944/preprints202009.0427.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: brassica-associated liver disease; BALD; progoitrin; 1-cyano-2-hydroxy-3-butene; 1-cyano-2-hydroxy-3,4-epithiobutane; nitrile; toxicity; rabbits
Online: 18 September 2020 (10:07:03 CEST)
Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.
REVIEW | doi:10.20944/preprints202009.0425.v1
Online: 18 September 2020 (09:58:49 CEST)
The Coronavirus disease 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission of SARS-CoV-2. Government response was swift with the implementation of a travel ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis and HIV/AIDS, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes as well as the aged are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.
ARTICLE | doi:10.20944/preprints202009.0423.v1
Subject: Medicine & Pharmacology, Other Keywords: community-dwelling older adults; physical frailty; prevalence; risk factors
Online: 18 September 2020 (08:57:56 CEST)
Frailty is defined as a state of increased vulnerability to stressors, and it predicts the disability and mortality in the older population. This study aimed to investigate standardized prevalence and multidimensional risk factors associated with frailty among the Korean community-dwelling older adults. We analyzed the baseline data of 2,907 adults aged 70–84 years (mean age 75.8±3.9 years, 57.8% women) in the Korean Frailty and Aging Cohort Study. The Fried frailty phenotype was used to define frailty. Analyzed data included sociodemographic, physical, physical function, biological, lifestyle, health condition, medical condition, psychological, and social domains. Data were standardized using the national standard population composition ratio based on the Korean Population and Housing Census. The standardized prevalence of frailty and pre-frailty was 7.9% (95% confidence interval [CI] 6.8–8.9%) and 57.2% (95% CI 45.1–48.8%), respectively. The following 14 risk factors had a significant association with frailty: at risk of malnutrition, sarcopenia, severe mobility limitation, poor social capital, rural dwellers, depressive, poor self-perceived health, polypharmacy, elevated high-sensitivity C-reactive protein, elevated glycosylated hemoglobin, low 25-hydroxy vitamin D level, longer timed up and go, and low short physical performance battery score (p<0.05). Physico-nutritional, psychological, sociodemographic, and medical factors are strongly associated with frailty.
ARTICLE | doi:10.20944/preprints202009.0422.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: dog; ST131; ESBL; fecal colonization; Escherichia coli
Online: 18 September 2020 (07:15:23 CEST)
Background: Most drug-resistant Escherichia coli isolates in dogs come from diseased dogs. Prior to this study, the prevalence and risk factors of fecal carriage drug-resistant E. coli and epidemic clone sequence type (ST) 131 (including subtypes) isolates in dogs were unknown. Methods: Rectal swabs were used for E. coli isolation from 299 dogs in a veterinary teaching hospital in Taiwan. Antibiotic resistance and multiplex PCR analyses of E. coli for major STs were performed. Result: There were 43.1% cefazolin-resistant, 22.1% fluoroquinolone-resistant, and 9.4% extended-spectrum beta-lactamase-producing E. coli in our cohort. In the phylogenetic study, B2 was the predominant group (30.1%). The cefazolin-resistant group and ciprofloxacin-resistant group had greater antibiotic exposure in the last 14 days (P < 0.05). The age, sex, and dietary habits of the antibiotic-resistant and -susceptible groups were similar. In the seven isolates of ST131 in fecal colonization, the most predominant subtypes were FimH41 and FimH22. Conclusion: Recent antibiotic exposure was related to the fecal carriage of antibiotic-resistant E. coli isolates. Three major subtypes (FimH41, H22, and H30) of ST131 can thus be found in fecal carriage in dogs in Taiwan.
REVIEW | doi:10.20944/preprints202009.0421.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Infertility; mesenchymal stem cells (MSCs); reproductive system; Stem-cell therapy
Online: 18 September 2020 (07:09:31 CEST)
Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency and to improve reproductive health for a significant number of women worldwide.
REVIEW | doi:10.20944/preprints202009.0420.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; SARS-CoV-2; ACE2 receptor; spike glycoprotein; S glycoprotein immunogenic sequences; ACE2 polymorphism
Online: 18 September 2020 (04:56:02 CEST)
Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.
REVIEW | doi:10.20944/preprints202009.0417.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: schizophrenia; stress; drug policy; environment; contaminants; pesticides; fungi; prohibition
Online: 18 September 2020 (04:21:43 CEST)
Background: Most modern studies about human marijuana use have been made under a set of arbitrary cultural standards and policies not related to drug harm potential, loosely called Prohibition. Here we asked if potential health hazards generated by Prohibition are addressed in research design and analysis. Methods: For this, we have searched PubMed database (from inception to December 2017) for citations of prevalent contaminants of illegal street cannabis: fungi and pesticides. In addition, we performed full text evaluation of 23 studies selected from, and including, 2 meta-analysis reviews investigating potential health hazards from cannabis use. Results: Different combinations of the keywords cannabis, prohibition, pesticides, fungi, contaminants, cancer, schizophrenia, psychosis, show that these words coincide in less than 1% of the cannabis human studies within the database. In the scope of 141 abstracts in which the terms, cannabis and pesticides coincide, none is directed to distinguish cannabis and pesticide adverse effects on CNS. A similar picture emerges when fungi is the paired word. Full text evaluation shows that all but one of the studies analyzed, completely neglect or comment on the nature of cannabis source, legal status, or contamination as a confounding factor. Discussion: Our results show a potential bias on scientific investigation that may affect data reliability in informing about the health hazards of cannabis use. This finding suggests that other aspects of the Prohibition environment may also go unacknowledged. Conclusion: Prohibition related health risks usually go unacknowledged and unaccounted for in biomedical research on Cannabis.
Thu, 17 September 2020
ARTICLE | doi:10.20944/preprints202009.0390.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Recombinant protein; Protease; DPP4; Covid-19
Online: 17 September 2020 (08:44:17 CEST)
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulfate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.
ARTICLE | doi:10.20944/preprints202009.0389.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: Graves’ ophthalmopathy; exophatlmos; intraocular pressure; topical medications
Online: 17 September 2020 (08:35:17 CEST)
Purpose: The evaluation of the efficacy of topical hypotensive treatment and/or systemic corticosteroids therapy in patients with elevated intraocular pressure and Graves’ orbitopathy (GO). Methods: 172 eyes in 86 individuals with duration of GO ≥ 3 months, intraocular pressure in either eye ≥ 25.0 mmHg and GO ranked ≥ 3 at least in one eye in modified CAS form, were included. The study subjects were divided into three treatment subgroups: subgroup I was administered latanoprost QD; subgroup II was administered a combined preparation of brimonidine and timolol BID; subgroup III was the control group, not receiving any topical hypotensive treatment. All the study participants received systemic treatment – intravenous corticosteroid therapy at the same dose, according to the EUGOGO guideline Results: On the final visit, the mean IOP value was significantly lower in all treatment subgroups comparing to the initial values. In both subgroups receiving topical treatment the IOP reduction was higher than in the control group receiving systemic corticosteroids only. However, the latanoprost eye drops decreased intraocular pressure more effectively than drops containing brimonidine and timolol. Conclusion: Topical ocular hypotensive treatment is effective in reducing intraocular pressure in GO and decreases intraocular pressure more effectively than systemic corticosteroid therapy alone.
ARTICLE | doi:10.20944/preprints202009.0380.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: malignant pleural mesothelioma; CXCL12/CXCR4; EAAT1; glutamine synthetase; invasion; migraiton
Online: 17 September 2020 (07:29:16 CEST)
Purpose: To elucidate the mechanism of CXCR4/EAAT1/GS pathway in CXCL12 regulating invasion and migration in malignant pleural mesothelioma (MPM). Methods: Immunohistochemistry for CXCL12, CXCR4, EAAT1 and GS stainings and correlation analysis between them were conducted in MPM and normal tissues. Western blot and real-time PCR were performed to examine the CXCR4, EAAT1 and GS expression in H2052 cells. Wound healing and transwell assay were applied to determine the cell migration and invasion. MTT was utilized to assess cell viability. Results: CXCL12, CXCR4, EAAT1 and GS were highly expressed in MPM tissues and correlated with each other. CXCL12 upregulated both in protein and mRNA levels of CXCR4, EAAT1 and GS in H2052 cells. The EAAT1 and GS expression upregulated or not by CXCL12 were decreased by CXCR4 and EAAT1 knockdown. CXCR4 antagonist AMD3100 and EAAT1 antagonist TFB-TBOA also resulted in the same effects as CXCR4 and EAAT1 knockdown, respectively. CXCL12 promoted cell invasion and migration and increased the Matrix metalloproteinase 9 (MMP9) mRNA level. CXCR4 and EAAT1 knockdown suppressed all these functions. Furthermore, CXCL12 promoted H2052 cells growth in nude mice, both AMD3100 and TFB-TBOA inhibited this promotion. Conclusions: CXCL12 regulated the invasion and migration through CXCR4/EAAT1/GS pathway in H2052 cells.
REVIEW | doi:10.20944/preprints202008.0729.v2
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: p53; p73; MDM2; MDMX; tumor suppressor; drug repurposing; aspirin; protoporphyrin IX; verteporfin
Online: 17 September 2020 (07:23:37 CEST)
p53 and p73 are critical tumor suppressors often inactivated in human cancers through various mechanisms. Owing to high structural homology, the proteins have many common functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 form a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni Syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due to late diagnoses, the toxicity of current standard of care and marginal benefit of newly approved therapies. Presently, the endeavours focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.
ARTICLE | doi:10.20944/preprints202009.0375.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: co-infection; SARS-CoV-2; pike glycoprotein; stop mutations
Online: 17 September 2020 (05:33:59 CEST)
There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.
Wed, 16 September 2020
ARTICLE | doi:10.20944/preprints202009.0358.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: Covid-19; HVE; Aerosol; Dentistry; Particle; Suction; External; PM1; PM2.5; PM10; Drilling
Online: 16 September 2020 (11:12:31 CEST)
(1) Introduction: External high volume extraction devices may offer a way to reduce any aerosol particulate generated. The aim of this study was to measure the particle count during dental aerosol procedures and compare the results to when a High Volume Extraction device is used; (2) Methods: A comparative clinical study measuring the amount of PM1, PM2.5 and PM10 aerosol particulate with and without the use of an external High Volume Extraction device was undertaken. In total, 10 restorative procedures were monitored with an an industrial Trotec PC220 particle counter. The air sampler was placed at the average working distance of the clinicians involved in the study - 420mm.; (3) Results: In the present study aerosol particulate was recorded at statistically significantly increased levels during dental procedures without an external high volume extraction device versus with the device. The null hypothesis was rejected, in that significant differences were found between the results of the amount of aerosol particle count with and without a High Volume Extraction device.; (4) Conclusion: If the results of the present study are repeated in an in vivo setting, an external high volume suction device may potentially lower the risk of transmission of viral particulate.
ARTICLE | doi:10.20944/preprints202009.0356.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: SSI; MORBIDITY; MORTALITY; GASTROINTESTINAL; HPB; HOSPITAL STAY
Online: 16 September 2020 (08:38:38 CEST)
Aims: Primary AIM of the study was to evaluate effect of prolonged hospital stay on Surgical site infections We also evaluated effect of prolonged hospital stay on overall morbidity in Gastrointestinal and Hepatobiliary Surgery as secondary outcome. Methods: We retrospectively analysed all the patients who underwent gastrointestinal and hepatobiliary surgery between April 2017 to March 2020. On our analysis we found mean hospital stay in patient who did not develop SSI and/or morbidity was 4 days (Total hospital stay) vs 6 days who developed morbidity (hospital stay before diagnosis of SSI or diagnosis or morbid event). Based on this to avoid selection bias, we did 1:1 propensity score analysis between patients who had 4 or less than hospital stay vs patients who had 5 or more hospital stay before diagnosis of surgical site infection and/or morbid event. We took all the preoperative and intraoperative factors like Age, sex, malignant disease, ASA score, CDC grade of surgery, open or laparoscopic surgery, HPB surgeries, colorectal surgeries, Upper Gastrointestinal surgeries and small intestinal surgeries as covariates. We used nearest neighbor matching protocol with a calipher of 0.2. Cases were not reusable after matching. Statistical analysis was done using SPSS version 23. Results: We included 348 patients operated between April 2017 and March 2020 in our analysis. After 1:1 propensity score matching 58 patients included in study arm (prevent hospital stay more than 4 days) and 56 patients in control arm. Both groups were comparable with regard to Age, Sex, Surgery for malignant disease, ASA score, CDC grade of surgery, HPB surgeries, Small intestinal surgeries, Colorectal surgeries, upper gastrointestinal surgeries, intraoperative blood product requirement, intraoperative hypotension or any other event, operative time. Prolonged hospital stay (> 4 days) was significantly associated with surgical site infections (p<0.0001), morbidity (p=0.001). Open surgeries were associated with prolonged hospital stay. (p=0.032). Conclusion: Prolonged Hospital stay is associated with increase surgical site infection and morbidity in Gastrointestinal and Hepatobiliary Surgery.
ARTICLE | doi:10.20944/preprints202009.0354.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sleep apnoea; obstructive sleep apnoea; polysomnography; excessive day time sleepiness; obesity
Online: 16 September 2020 (07:19:33 CEST)
Objective: Identify factors associated with excessive day time sleepiness (EDS) in individuals with obstructive sleep apnea (OSA), and analyze the effects that obesity and gender have on excessive daytime sleepiness in such individuals. Methods: A total of 160 people were selected for this study. All the people have completed a clinical evaluation, and whose apnea-hypopnea index (AHI) > 10 events/hour of sleep on polysomnography were included in the study from the Department of otolaryngology. Results: The Mean age was 43.87±11.34 years, mean EDS score was 14.09± 4.91, and mean AHI was 43.88±20.66 events/hour of sleep. Male presented lower mean age, higher EDS scores, and more time in apnoea, whereas females presented with higher mean age, lower EDS scores, and less time in sleep apnea. The EDS score showed best correlation with duration of apnoea (r = 0.448; p < 0.01), peripheral oxygen saturation (SpO2; r = -0.458; p < 0.01) and AHI (r = 0.484; p < 0.01). The mean body mass index (BMI) was 27.41±3.86 kg/m2. Normal, Overweight, obese, and morbidly obese were observed in 20%, 61%, 18%, and 0.6% of cases, respectively. Severity of the disease best correlated with BMI (r = 0.421; p < 0.01). Conclusions: OSA is predominant in males (M/F 5:1), and obese population. Females diagnosed with OSA have higher mean age. However, EDS scores and time spent in sleep apnoea is lower in females. Higher BMI is associated with EDS, irrespective of gender.
ARTICLE | doi:10.20944/preprints202009.0350.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: anterior cruciate ligament; open kinetic chain; laxity; isokinetic
Online: 16 September 2020 (05:55:45 CEST)
Rehabilitation following anterior cruciate ligament reconstruction with hamstring graft allows the patient to regain his functional capacities and to support him in the resumption of sports activities. Rehabilitation also aims to minimize the risk of recurrence, which is why it ensures that the patient's muscular capacities develop properly until they return to sport. Isokinetics helps strengthen and assess the strength of muscle groups in the thigh, but controversy exists as to its use by resistance to the open kinetic chain knee extension that would cause the transplant to distend. The objective of this study is to determine the influence of isokinetic muscle strengthening on the possible laxity of the anterior cruciate ligament and to be able to determine risk factors. The study relates to a population having benefited from anterior cruciate ligament reconstruction with hamstring graft from 3 to 6 months after surgery. Two groups are differentiated, one group exposed to isokinetism during rehabilitation, the other group, named unexposed, undergoes rehabilitation without the use of isokinetism. An anterior knee laxity test is performed 6 months postoperatively using the GNRB® machine for all subjects according to the same protocol. The test results were statistically analyzed to determine a relative risk of transplant distension for each group in the study. Comparison of the results of each group by univariate analysis did not reveal any significant result. Multivariate analysis showed interactions in the two strata of the study. It was argued that the use of isokinetics seems to have no effect on the risk of developing distension for the majority of subjects in the exposed group. A tendency towards transplant protection was perceived for each variable except the age under 25 years (RRa = 1.07). The use of isokinetics does not appear to be a cause of transplant distension in patients undergoing an anterior cruciate ligament reconstruction when this method is introduced 3 months postoperatively.
ARTICLE | doi:10.20944/preprints202009.0347.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: mood disorders; depression; nitrosative and oxidative stress; IgM autoimmunity; neuro-immune; inflammation
Online: 16 September 2020 (04:17:25 CEST)
Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.
HYPOTHESIS | doi:10.20944/preprints202009.0346.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Sepsis; SIRS; oxic sulphidic oscillator; risk prediction; multiorgan failure; chemocline
Online: 16 September 2020 (04:07:17 CEST)
Life evolved in an euxinic world with subsequent oxic 'invasion' leading to two parallel but interconnected biospheres, hydrogen sulphide (H2S) and hydrogen peroxide (H2O2) exemplify these worlds respectively. Their concentration gradients have informational value in meromictic lakes. Similarly, it is posited, there exists a whole body chemocline in humans in which the two molecules form an inversely coupled oxic/sulphidic oscillator (OSO). The OSO is hormetic and characterised by a range of amplitudes and frequencies in health. Deviations from its baseline profile heralds the onset of SIRS before the appearance of clinical signs. Loss of oscillator status and transition to a steady state causes widespread intercellular and inter-organ communication failure presaging multi-organ dysfunction. The salient clinico-pathophysiological features of SIRS of any aetiology are emergent phenomena related to the OSO profile. Extent of recovery of organ function will mirror the recovery of the OSO profile thereby providing a tool to predict outcomes in SIRS.
ARTICLE | doi:10.20944/preprints202009.0341.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: flavonoid; polyphenols; orange extract; performance; endurance; aerobic; anaerobic; nutrigenomic; sport nutrition
Online: 16 September 2020 (03:10:12 CEST)
2S-hesperidin is a flavanone (flavonoid) found in high concentrations in citrus fruits. It has an antioxidant and anti-inflammatory effect, improving performance in animals. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on aerobic-anaerobic and metabolic performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500mg/day 2S-hesperidin and other taking 500 mg/day placebo (microcellulose) for 8 weeks. All participants completed the study. Performance and metabolic aerobic-anaerobic markers were measured using incremental and rectangular tests by indirect calorimetry. The anaerobic power was determined using Wingate tests. After 8 weeks supplementation, there was a significant increase in the incremental test in estimated functional threshold power (FTP) (3.23%; p≤0.05) and maximum power (2.68%; p≤0.05) with 2S-Hesperdin compared to placebo. In the rectangular test, there was a significant decrease in VO2 (-8.26%; p≤0.01) and VO2R (-8.88%; p≤0.01) at VT2 in placebo; however, there were no significant differences between groups. In the Wingate test, there was a significant increase (p≤0.05) in peak and relative power in both groups, but without significant differences between groups. Supplementation with an orange extract (2S-hesperdin) 500mg/day improves estimated FTP and maximum power performance in amateur cyclists.
ARTICLE | doi:10.20944/preprints202009.0339.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Great East Japan Earthquake; disaster; cardiovascular disease; psychological factors; evacuation; prospective study
Online: 16 September 2020 (03:01:44 CEST)
Evidence regarding the effect of psychological factors and evacuation on cardiovascular disease occurrence after large-scale disasters is limited. This prospective study followed up a total of 37,810 Japanese men and women aged 30–89 years from the Fukushima Prefecture with no history of stroke or heart disease at baseline (2012), until 2017. This period included 3000 cardiovascular events recorded through questionnaires and death certificates. The participants’ psychological distress, trauma reaction, and evacuation status were defined, and divided into four groups based on combinations of psychological factors and evacuation status. We calculated the hazard ratios and 95% confidence intervals for only psychological, only evacuation, or both of them compared with neither using Cox proportional hazard models. Psychological factors along with evacuation resulted in approximately 5% to 25% higher magnitude of stroke and heart disease risk than psychological factors only among men. Compared to neither, the multivariable hazard ratios of those with both psychological distress and evacuation were 1.75 for stroke and 1.49 for heart disease, and those of both trauma reaction and evacuation were 2.01 and 1.57, respectively, among men. Evacuation combined with psychological factors increased the risk of stroke and heart disease risks especially in men after the Great East Japan Earthquake.
Tue, 15 September 2020
REVIEW | doi:10.20944/preprints202009.0337.v1
Subject: Medicine & Pharmacology, Other Keywords: hand sanitizers; hand rubs; alcohol based; disinfection; hand hygiene; coronavirus; COVID-19
Online: 15 September 2020 (09:07:09 CEST)
The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.
ARTICLE | doi:10.20944/preprints202009.0335.v1
Subject: Medicine & Pharmacology, Other Keywords: active transportation; health impact assessment; physical activity; air pollution; traffic safety; carbon emissions; monetization; online tool
Online: 15 September 2020 (08:40:57 CEST)
The World Health Organization’s Health Economic Assessment Tool (HEAT) for walking and cycling is a user-friendly web-based tool to assess health impacts of active travel. HEAT, developed over 10 years ago, has been used by researchers, planners and policymakers alike in appraisals of walking and cycling policies of both national and more local scales. HEAT has undergone regular upgrades adopting the latest scientific evidence. This article presents the most recent upgrades of the tool. Health impacts of walking and/or cycling in a specified population are quantified in terms of premature deaths avoided (or caused). In addition to the calculation of benefits from physical activity, HEAT was recently expanded to include assessments of the burden associated with air pollution exposure and crash risks while walking or cycling. Further, impacts on carbon emissions from mode shift to active travel modes can now be assessed. Monetization of impacts using Value of Statistical Life and Social Costs of Carbon now uses country-specific values. As active travel inherently results in often substantial health benefits as well as not always negligible risks, assessments of active travel behaviour or policies are incomplete without considering health implications. The recent developments of HEAT make it easier than ever to obtain ballpark estimates of health impacts and carbon emissions related to walking and cycling.
ARTICLE | doi:10.20944/preprints202009.0330.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: bullying; dentofacial features; physical features; schoolchildren
Online: 15 September 2020 (04:48:47 CEST)
Context: bullying among schoolchildren is a serious phenomenon and a leading health concern. Aim: to determine the prevalence of bullying, its forms, and its effect on academic abilities and school attendance, as well as associated sociodemographic, physical, and dentofacial features among Saudi schoolchildren. Methods: this cross-sectional study recruited a sample of 1131 parents of schoolchildren 8-18 years old and requested them to complete internationally accepted questionnaires for their children. Chi-square test and logistic regression analysis were used to analyze the data (p<0.05). Results: a majority (89.2%) of schoolchildren were bully victims. Physical bullying (48.9%) was the most common form of bullying. The youngest schoolchildren (8-11 years), those who disliked school classes or neither liked nor hated them, as well as those who were truant from school were more likely to be victims. In addition, those who had worse grades because of bullying, and those who were very often bullied because of good grades or because they showed an interest in school were more likely to be victims. With regards to targeted physical features, teeth were the number one target, followed by the shape of the lips and strength, while teeth shape and color was the most common dentofacial target, followed by anterior open bite and protruded anterior teeth. Boys and the youngest schoolchildren were more often subjected to bullying because of these features (p<0.05). Conclusions: the prevalence of bullying, mainly in a physical form, was high among Saudi schoolchildren, with a negative influence on students’ academic abilities. Problems related to teeth, in particular, which can be treated, were targets, mainly for boys and the youngest schoolchildren. More studies are required in Saudi Arabia to explore the issue further among schoolchildren, themselves.
ARTICLE | doi:10.20944/preprints202009.0326.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: HepG2 cells; cytotoxicity; apoptosis; Hoechst staining; molecular dynamics
Online: 15 September 2020 (04:18:12 CEST)
The natural products and conventional chemotherapeutic drugs are believed to increase the cure rates of anti-cancer treatment while reducing their toxicity. The current study investigates the cytotoxic and apoptogenic effects of bioactive compounds from Monotheca buxifolia on Hep G2 cell lines. The effect on the viability of Hep G2 cells was evaluated by MTT assay; Morphological changes were studied, the apoptotic activity was demonstrated through Annexin-V-FITC/ PI, a molecular dynamics simulation study was conducted to explore the binding pattern of the compounds in the active site of the PPRAδ protein. The isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells, as determined by MTT assay and annexin V-FITC/PI. The IC50 value for lauric acid was 56.4584 ± 1.20 µg/ml, that for oleanolic acid was 31.9421 ± 1.03 µg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 µg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic. Morphological assay and Hoechst staining microscopy revealed the morphological alterations of cell membrane accompanied by nuclear condensation after treatment. The high fluctuation indicates the high potency and adopting various interactions, and vice versa, the oleanolic acid showed highly residues fluctuation, which remains stable in the active site of PPARδ protein and involved in various interactions while remaining locally fluctuated in the binding site the other two compounds. In conclusion, a significant apoptogenic effect was exhibited by lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate against HepG2 cells in inducing apoptosis. Our findings indicate that these bioactive compounds hold promise as potential therapeutic for hepatocellular carcinoma.
ARTICLE | doi:10.20944/preprints202009.0323.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID-19; lockdown; CNN; DLNN; GRU; mental anxiety; hybrid approach
Online: 15 September 2020 (02:56:33 CEST)
COVID-19 and new concept, lockdown, change social life of all classes of humans. Children partially feel the changes of daily life and this situation has been children’s free mind. Children are under a new type of restriction imposed on them by their parents. Normally they prefer play with their their friends than study and always waiting for holidays. They heard a new jargon i.e. lockdown where everything stands still. Very often they see peoples in the roads and few vehicles are moving in the roads. However, a peculiar thing happens now that they sit in front of computer to hear the virtual classes that are taken by the teachers. This also happens when there is no lockdown since COVID-19 still affects people. The environment is totally changed and they do not find any proper answers from the parents about the scenario.This study has been made an attempt to carry out the mental affairs of children in West Bengal, India. Several families are surveyed for collecting responses mostly from rural areas as well as urban areas for the time-period from April, 2020 to July, 2020. An effort has been given in this paper to predict the stress, depression and anxiety faced by children during the COVID-19. A Deep Learning Neural Network (DLNN) based method is applied to understand the stress level, depression level and anxiety level amongst the children. A hybrid DLNN has been presented in this research that combines both Convolutional Layer and Gated-Recurrent Unit (GRU) for obtaining the prediction of the mental health of children. The model obtains an accuracy of 89.57% for defeminizing mental anxiety of children.
Mon, 14 September 2020
ARTICLE | doi:10.20944/preprints202009.0322.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Hemophilia A; Prophylaxis; Factor VIII; Platelets; Microvesicles; Calcium
Online: 14 September 2020 (16:12:08 CEST)
Aim: In the present work we have studied the role of platelets and microvesicles in patients with severe hemophilia A (HA) treated under the regimen of prophylaxis. We have analyzed whether the administration of coagulation factor FVIII modifies this hemorrhagic phenotype in a cohort of 16 patients with diagnosis of severe HA, who were on prophylactic treatment with recombinant FVIII. Methods: Blood tests were performed before (72h without FVIII, baseline sample) and after 15 minutes of FVIII infusion. As a control group, 15 healthy subjects were studied. Platelet aggregation was determined by closure time, optical aggregation, impedance aggregation and flow cytometry. We also studied the expression of the platelet activation markers P-selectin, CD63, platelet-tissue factor, formation of platelet-leukocyte aggregates and tissue factor exposure. The total number of platelet and endothelial microvesicles were also analyzed by flow cytometry, as well as platelet cytosolic Ca2+ mobilization. Results: We found no significant differences in platelet function in patients with severe HA in prophylactic treatment before and after FVIII infusion. After FVIII administration, patients presented fewer endothelial microvesicles, indicating that the treatment does not increase one of the possible thrombotic risk markers of these patients. The total amount of plasma microvesicles and the platelet microvesicles were decreased in patients with HA compared to the control group. Conclusions: Our results do not support any effect of FVIII on platelet function in patients with severe HA treated under the regime of prophylaxis.
ARTICLE | doi:10.20944/preprints202009.0321.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: CoViD-19; COVID; Mortality; Weekly Cycle; Weekly Mortality Cycle
Online: 14 September 2020 (12:03:12 CEST)
Background. The Weekly Mortality Cycle among CoViD-19 patients has been studied.Methods. Mortality data obtained from the 'Worldometer' website were analyzed with a comparison of absolute values, percentages, and p-value. Results. For patients suffering from CoViD-19, the most favorable or the safest days of the week were Sundays and Mondays. Conclusion. The weekly cycle with decreased mortality on Sundays and Mondays is a unique phenomenon observed among victims of CoViD-19. Presumably the decreased mortality on certain days of the week related to the optimized therapeutic protocols used on the "safest days".
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Parkinson’s disease; precision medicine; personalized medicine; GBA; Glucocerebrosidase; GCase; LRRK2; Leucine-rich repeat kinase-2; Dopamine; PD drug trials; PD risk variants
Online: 14 September 2020 (00:22:59 CEST)
Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.
CASE REPORT | doi:10.20944/preprints202009.0309.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Mycobacterium chelonae/abscessus; crocodile; mycobacteriosis; Non-tuberculous mycobacteria
Online: 14 September 2020 (00:12:29 CEST)
A 40 years old male Nile crocodile (Crocodylus niloticus) was diagnosed with pulmonary mycobacteriosis caused by a member of Mycobacterium chelonae/abscessus group. Post-mortem examination showed a severe systemic visceral granulomatous involvement, with lesions in lungs, heart, liver, spleen and kidneys. Histopathological examination of lung, spleen, heart and liver revealed multifocal to coalescing granulomas showing eterophils in central zone and outer rim of epithelioid histiocytes, multinucleated giant cells and lymphocytes. The Ziehl–Neelsen histological staining revealed rare vacuoles containing numerous alcohol-acid resistant bacteria. Mycobacterial infection was confirmed by culture and PCR targeting rRNA 16S gene. Sequence analysis of the DNA amplicon revealed a 100% homology with the M. chelonae/ abscessus group. Even if the classification of the memebrr of this group is still on updating, to the best of our knowledge, this is the first report of M. chelonae/abscessus member infection in a Nile crocodile species.
Sun, 13 September 2020
CASE REPORT | doi:10.20944/preprints202009.0297.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: SARS-CoV-2; COVID-19; CNS; infant; Choroid plexus
Online: 13 September 2020 (16:16:59 CEST)
Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis, meningitis and multiple organ damage related to thrombosis, a previous encephalopathy may have contributed to additional cerebral damage. SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.
ARTICLE | doi:10.20944/preprints202009.0281.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: coil resistance; ecigarette; electronic nicotine delivery system; pod-style; atomizer
Online: 13 September 2020 (11:56:34 CEST)
In Electronic Nicotine Delivery System (ENDS), coil resistance is an important factor in the generation of heat energy used to change e-liquid into vapor. An accurate and unbiased method for testing coil resistance is vital for understanding its effect on emissions and reporting results that are comparable across different types and brands of ENDS and measured in different laboratories. This study proposes a robust, accurate and unbiased method for measuring coil resistance. An apparatus is used which mimics the geometric configuration and assembly of ENDS pods and power control units. The method is demonstrated on two commonly used ENDS devices, the ALTO by Vuse and JUUL. Analysis shows that the proposed method is stable and reliable. The two-wire configuration introduced a positive measurement bias of 0.086 [ohm], which is a significant error for sub-ohm coil designs. The four-wire configuration is far less prone to bias error. We observed a significant difference in coil resistance of 0.593 [ohm] (p<0.001) between the two products tested. The mean resistance and standard deviation of the pod coil assemblies was shown to be 1.031 (0.067) [ohm] for ALTO and 1.624 (0.033) [ohm] for JUUL. The variation in coil resistance between products and within products can have significant impacts on aerosol emissions.
ARTICLE | doi:10.20944/preprints202009.0280.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: MDS; immune cell repertoire; prognosis; multiplex immunohistochemistry; stem cell niche
Online: 13 September 2020 (11:51:13 CEST)
Purpose: Myelodysplastic syndromes (MDS) are caused by a stem cell failure, but the relationship between immune dysregulation and the course of disease has not yet been analyzed in detail. Experimental design: To get insights into the pathophysiologic and clinical relevance of the histotopography of immune cell subpopulations in this process, the immune cell infiltrate with focus on its spatial distribution was determined by multispectral imaging (MSI) in 147 bone marrow biopsies from MDS or secondary acute myeloid leukemia (sAML) patients and healthy controls (HC). In addition, the data were correlated to genetic alterations and clinical features of these patients including therapy response. Results: A high inter-tumoral heterogeneity in the frequency and spatial distribution of CD3+CD8+, CD3+CD8-, CD3+FOXP3+ T cell subsets, MUM1p+CD3- post-germinal B/plasma cells and CD34+ blasts was found in MDS and sAML samples. In HC only few B cells/plasma cells, but no T cell subpopulations were detected in the proximity to CD34+ blasts. In contrast, the frequency of these lymphocytes was increased in proximity to CD34+ blasts in both MDS and sAML independent of the karyotype, genetic alterations frequently detected in MDS, clinical risk stratification systems or treatment response to hypomethylating agents. Furthermore, an increased frequency of CD3+CD8+ T cells and MUM1p+ CD3- B cells was found in responders to epigenetic drugs. Conclusions: Thus, we conclude that (i) T cell subsets do not belong to the normal stem cell niche, (ii) the presence of T and B cell subpopulations not directly affect the course of MDS, (iii) lymphocytes in the proximity to CD34+ blasts might indicate defective stem cell properties and (iv) the number of lymphocytes is a predictor of therapy response to hypomethylating agents.
Sat, 12 September 2020
COMMUNICATION | doi:10.20944/preprints202009.0264.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Fibromyalgia; Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); Pressure Point Threshold (PPT); Physiotherapy; Manual Therapy (MT)
Online: 12 September 2020 (04:14:19 CEST)
Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient´s health deterioration and chronic drug use to an eventual lack of patient´s response. Emerging evidence support that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves, or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled manual protocol on FM hyperalgesia/allodynia, fatigue and patient´s quality of life. The results show that patient´s baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Thus, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient´s response to physiotherapy programs based on mechanical triggers, as the one evaluated here. These unexpected findings grant further explorations including the study of gene expression profiles associating to patient´s treatment response in the blood collection of samples generated by this study.
Fri, 11 September 2020
ARTICLE | doi:10.20944/preprints202008.0329.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Geospatial Regression; Health Disparities; Public Health
Online: 11 September 2020 (09:48:57 CEST)
COVID-19 is a potentially fatal viral infection. This study investigates geography, demography, socioeconomics, health conditions, hospital characteristics, and politics as potential explanatory variables for death rates at the state and county levels. Data from the Centers for Disease Control and Prevention, the Census Bureau, Centers for Medicare and Medicaid, Definitive Healthcare, and USAfacts.org were used to evaluate regression models. Yearly pneumonia and flu death rates (state level, 2014-2018) were evaluated as a function of the governors’ political party using repeated measures analysis. At the state and county level, spatial regression models were evaluated. At the county level, we discovered a statistically significant model that included geography, population density, racial and ethnic status, three health status variables along with a political factor. State level analysis identified health status, minority status, and the interaction between governors’ parties and health status as important variables. The political factor, however, did not appear in a subsequent analysis of 2014-2018 pneumonia and flu death rates. The pathogenesis of COVID-19 has greater and disproportionate effect within racial and ethnic minority groups, and the political influence on the reporting of COVID-19 mortality was statistically relevant at the county level and as an interaction term only at the state level.
REVIEW | doi:10.20944/preprints202009.0254.v1
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: dental care; emotions; health personnel; health services; human needs; motivation; patient reported outcome measures; patient satisfaction; personal satisfaction; theory of satisfaction
Online: 11 September 2020 (09:44:11 CEST)
There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Retinitis Pigmentosa; Cell Surgery; Growth Factors; Mesenchimal Cells; oxidative stress
Online: 11 September 2020 (08:18:37 CEST)
Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenge in the ophthalmological research field. Although this inherited retinal dystrophie is still incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidences about the cell therapies effectiveness, especially based on mesenchymal cells, in RP and focus on their therapeutic actions: limitation of both oxidative stress and apoptotic processes triggered by the disease, promoting cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: COVID-19; SARS-CoV-2; hepatic encephalopathy; CIGB-258
Online: 11 September 2020 (05:49:43 CEST)
Hepatic encephalopathy is a complex life-threatening neuropsychiatric syndrome, which can be associated with acute inflammation. It can be found in cases of acute liver failure caused by a viral infection. Reports of patients infected with SARS-CoV-2 have described hepatic encephalopathy. Therapy with immunomodulators can be an effective choice for this clinical condition. CIGB-258 is an immunomodulatory peptide with anti-inflammatory properties derived from cellular stress protein 60 (HSP60). We report a case of a 55-years-old woman diagnosed with COVID-19 and hepatic encephalopathy characterized by episodes of anxiety, delirium, confusion and seizure, according to her clinical history, laboratory and radiological data. Levels of aspartate aminotransferase, alanine aminotransferase , plasma ammonia and alkaline phosphatase were increased and inflammatory biomarkers such as interleukin 6 and 10 were over the normal range. The patient received an intravenous administration of 1 mg of CIGB-258, every 12 hours during four days, followed by 1 mg daily for another three days without adverse reactions. Neurological symptoms disappeared completely at by the fourth days after starting therapy, and inflammatory biomarkers noticeably decreased, but not all of them reach the normal values. This case highlights the outcomes of a severe COVID-19 patient with hepatic encephalopathy, treated with CIGB-258. The patient recovered successfully and the liver enzymes, plasma ammonia and biomarkers associated with hyperinflammation were reduced. These results support clinical investigations of CIGB-258 as a therapeutic agent in COVID-19.TRIAL REGISTRATION: RPCEC00000313
ARTICLE | doi:10.20944/preprints202009.0242.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COPD; COVID-19; prevalence; prognosis
Online: 11 September 2020 (05:47:59 CEST)
Patients with COPD have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from January 1st to May 10th, 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2,51%; CI95% 2,33 – 2,68) was significantly higher than in the general population aged > 40 years (1,16%; 95%CI 1,14 – 1,18); P < .001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31,1 % vs 39,8%: OR 1,57; 95%CI 1,14 – 1,18) and mortality (3,4% vs 9,3%: OR 2,93; 95%CI 2,27 – 3,79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (P<0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.
ARTICLE | doi:10.20944/preprints202009.0241.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: prebiotic; oligosaccharides; gut microbiota; fatty liver; metabolism; mitochondria
Online: 11 September 2020 (04:17:52 CEST)
Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.
ARTICLE | doi:10.20944/preprints202009.0239.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: Cutaneous Melanoma; Immunotherapy; Lymphocytes; Monocytes; Macrophages; RNAseq; tumor immune microenvironment
Online: 11 September 2020 (04:02:03 CEST)
Background: Cutaneous Melanoma (SKCM) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of SKCM (n=328) was utilized. The immune microenvironment was characterized using CIBERSORTX to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Samples were separated into those obtained from the primary tumor site and regional skin or soft tissue (locoregional), or distant metastasis and regional lymph node (metastatic). Analysis of overall survival (OS) was performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by lymphocyte:monocyte (L:M) ratio, monocyte-enrichment, and M0-macrophage-enrichment (L:MLow, MonocyteHigh, M0High; L:MLow, MonocyteMid, M0Low; L:MMid, MonocyteLow, M0Low; L:MHigh, MonocyteLow, M0Low). The L:MLow, MonocyteHigh, M0High cluster demonstrated significantly worse OS than clusters 2-4 in the locoregional group (HR 2.804, 95% CI 1.262–6.234, p=0.0114). Membership in the L:MLow, MonocyteHigh, M0High cluster was an independently poor prognostic factor for survival (HR 3.03, 95% CI 1.12–8.20, p=0.029). The L:MLow, MonocyteHigh, M0High cluster correlated with higher rates of metastasis and decreased predicted response to immune checkpoint blockade compared to the other clusters as determined by the Tumor Immune Dysfunction and Exclusion tool (TIDE). Conclusion: Distinct tumor immune clusters with a M0-macrophage-enriched, L:M ratio low phenotype in the primary melanoma tumor site independently characterize an aggressive phenotype that may differentially respond to treatment.
Thu, 10 September 2020
ARTICLE | doi:10.20944/preprints202009.0238.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: oral squamous cell carcinoma; HLA class I; antigen processing machinery; immune cell infiltration; immune escape; prognosis
Online: 10 September 2020 (11:37:28 CEST)
Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance with growing evidence of its underlying molecular mechanisms and its interaction with the immune cell control. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 consecutive human papilloma virus (HPV)-negative OSCC lesions and correlated to tumor specific parameters, the intratumoral immune cell response and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was seen in OSCC sections when compared to non-neoplastic cells. Based on the expression levels of HLA-I APM components three main OSCC subgroups were detected and categorized into HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh phenotypes. In the HLA-Ihigh/APMhigh group, the highest frequency of intratumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3 cells was found. Despite being associated with the highest T cell infiltration, patients within this group presented the most unfavorable survival, which was most evident in stage T2 tumors. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.
ARTICLE | doi:10.20944/preprints202009.0237.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: game-based therapy; neuromotor disability; cerebral palsy; subjective assessment; patient-centered assessment; caregiver burden; ankle range of motion; ankle strengthening; home exercise program
Online: 10 September 2020 (11:28:00 CEST)
Technological advances in game-mediated robotics provide an opportunity to engage children with CP and other neuromotor disabilities in more frequent and intensive therapy by making personalized, programmed interventions available 24/7 in children’s homes. Though shown to be clinically effective and feasible to produce, little is known of the subjective factors impacting acceptance and of such assistive/rehabilitative gamebots by their target populations and their families. This research describes the conceptualization phase of an effort to develop a valid and reliable instrument to guide the design of A/R gamebots. We conducted in-depth interviews with 8 children with CP and their families who had trialed an A/R gamebot for 28 days in their homes to understand how existing theories and instruments were either appropriate or inappropriate to measuring the subjective experience of A/R gamebots. Key findings were the importance of differentiating the paradigm of rehabilitative from that of assistive technology, the need to incorporate the differing perspectives of children with CP and those of their parents into A/R gamebot evaluation, and the potential conflict between the goals of preserving the quality of the experience of game play for the child while also optimizing the intensity and duration of therapy provided during play.
BRIEF REPORT | doi:10.20944/preprints202009.0229.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; pneumonia; low-dose whole-lung irradiation; SpO2
Online: 10 September 2020 (08:36:57 CEST)
Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO2, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO2 upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO2 ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO2. Five patients were discharged (median 6th day, range 2nd-14th day), and four patients died (median 7th day, range 3rd-10th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.
ARTICLE | doi:10.20944/preprints202009.0227.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: keratin 1; keratin 2; keratin 10; epidermolytic ichthyosis; keratinopathic ichthyoses; congenital reticular ichthyosiform erythroderma; ichthyosis en confetti; revertant mosaicism; epidermolytic nevus, mosaicism
Online: 10 September 2020 (07:52:13 CEST)
Mutations in KRT1 (keratin 1) or KRT10 (keratin 10) underlie a spectrum of diseases known as keratinopathic ichthyoses. Epidermolytic ichthyosis (EI) is caused by heterozygous missense mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 (keratin 2) lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. Epidermolytic ichthyosis is also present in a mosaic pattern known as epidermolytic (acantholytic) nevus, isolated or diffuse. In the latter case, gonadic involvement is possible, leading to a rare pedigree in which a parent with diffuse epidermolytic nevus (linear EI) gives birth to a child affected by EI. We present here an update on the phenotypic presentations of keratinopathic ichthyoses and their molecular mechanisms.
ARTICLE | doi:10.20944/preprints202009.0220.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: feasibility; acceptability; adherence; attrition rate; periodontal therapy; milk fortification; pregnancy
Online: 10 September 2020 (04:44:05 CEST)
This study aims to assess the acceptability, adherence, and retention of a feasibility trial on milk fortification with calcium and vitamin D (Ca+VitD) and periodontal therapy (PT) among low income Brazilian pregnant women with periodontitis (IMPROVE trial). This 2x2 factorial feasibility trial used a mixed-methods evaluation. 69 pregnant women were randomly allocated to four groups: 1.fortified sachet with Ca+VitD and milk plus early PT (throughout gestation); 2.placebo and milk plus early PT; 3.fortified sachet with Ca+VitD and milk plus late PT after childbirth; 4.placebo and milk plus late PT. Data were collected via questionnaires, field notes, participant flow logs, treatment diary, and focal group discussions. Quantitative and qualitative data were analysed using appropriate descriptive statistics and content analysis, respectively. Eligibility rate (12%) was below the target of 15%, but participation (76.1%) and recruitment rate (2 women/week) exceeded the targets. Retention rate (78.6%) was slightly below the target (80%). Adherence to the PT was significantly higher in the early treatment groups (98.8%) compared to the late treatment groups (29%). All women accepted the random allocation and baseline groups were balanced. There was no report of adverse events. This multi-component intervention is acceptable, well-tolerated, and feasible among low-risk pregnant women in Brazil.
Wed, 9 September 2020
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2 COVID-19; lung damage mechanisms; leukecyte recruitment; viral infection; immune response; temperature and humidity; interstitial pressure change
Online: 9 September 2020 (11:32:55 CEST)
To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.
ARTICLE | doi:10.20944/preprints202009.0205.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Franz-Bampa; BCS drugs; biomimetic membrane; Franz cell; passive drug transport
Online: 9 September 2020 (10:25:54 CEST)
A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-Bampa) was validated using Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-Bampa were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for the 14 BCS class I-IV drugs cited in the FDA guidance (including other drugs as acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-Bampa. Apparent permeability (Papp) was compared to literature fraction dose absorbed in humans (Fa%). Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-Bampa performance. Mannitol and metoprolol Papp values across Franz-Bampa were lower (3.20 x 10-7 and 1.61 x 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 x 10-5 and 2.55 x 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed similar log linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-Bampa method for use during drug discovery process.
ARTICLE | doi:10.20944/preprints202008.0267.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; intensive care; trends; United Kingdom; mortality; mechanical ventilation
Online: 9 September 2020 (09:28:49 CEST)
Rationale: Examining trends in patient characteristics, processes of care and outcomes, across an epidemic, provides important opportunities for learning. Objectives: To report and explore changes in admission rates, patient characteristics, processes of care and outcomes for all patients with COVID-19 admitted to intensive care units (ICUs) in England, Wales and Northern Ireland. Methods: Population cohort of 10,287 patients with COVID-19 in the Case Mix Programme national clinical audit from 1 February to 2 July, 2020. Analyses were stratified by time period (pre-peak, peak, post-peak) and geographical region. Multivariable logistic regression was used to estimate differences in 28-day mortality, adjusting for patient characteristics over time. Main results: Admissions to ICU peaked simultaneously across regions on 1 April, with ongoing admissions peaking ten days later. Compared with pre- and post-peak periods, patients admitted during the peak were slightly younger but had greater respiratory and renal dysfunction. Use of invasive ventilation and renal replacement reduced over time. Twenty-eight-day mortality reduced from 43.5% (95% CI 41.6% to 45.5%) pre-peak to 34.3% (95% CI 32.3% to 36.2%) post-peak; a difference of −8.8% (95% CI: −5.2%, −12.3%) after adjusting for patient characteristics. London experienced the highest admission rate and had higher mortality during the peak period but a greater reduction in post-peak mortality. Conclusion: This study highlights changes in patient characteristics, processes of care and outcomes, during the UK COVID-19 epidemic. After adjusting for the changes in patient characteristics and first 24-hour physiology, there was substantial improvement in 28-day mortality over the course of the epidemic.
ARTICLE | doi:10.20944/preprints202009.0200.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: spatiotemporal parameters; gait; gender; age; Body Mass Index
Online: 9 September 2020 (07:12:18 CEST)
Studies on the gait's parameters have been identified on the patients population. Most researchers confirm that the patients walk differently than normal people and they may have a risk for falls. Consistent finding and description of gender, age, and body mass index differences in gait studies is rare in healthy subjects. A cross-sectional study with forty-five young adult (F = 20, M = 25) was conducted. Stadiometer and Physilog 4 inertial sensors were used for data collection. A gait analyser 5.2 software (GaitUp, S.A. Lausanne, Switzerland) was used to determine spatiotemporal parameters. No statistically significant differences were found in any bilateral foot gait parameters with respect to gender, age, and body mass index. Females are found with higher total double support and cadence than males. Cadence also increases with age. Obese people showed lower gait speed, cadence, and total double support. These findings may be beneficial to those who have abnormal gait pattern due to age, body mass index differences, decreased muscle strength, spasticity, and joint mobility. This important informations should be considered to rehabilitate patients with abnormal gait patterns to controlling dynamic balance and riks to falling.
Tue, 8 September 2020
ARTICLE | doi:10.20944/preprints202009.0180.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cancer; alternative medicine; complementary medicine; health behaviours
Online: 8 September 2020 (10:11:37 CEST)
An increasing number of persons with cancer decide to choose complementary and alternative medicine. The purpose of the paper was to check the status of the use of complementary and alternative medicine methods in oncological patients and to compare health behaviours of patients using Complementary and Alternative Medicine (CAM) with those using neither of these methods. The studies were conducted from August till January 2020 in the Oncology Center in the south-eastern Poland. A cross-sectional study was conducted in a group of 208 oncological patients. The authors' own questionnaire and the standardized Health Behaviour Inventory were used. Most of the patients (85,09%) declared that they used complementary and alternative medicine methods. The most common methods chosen by the respondents included vitamin C, green tea and prayer. The vast majority of the respondents did not inform their oncologist about the use of CAM. 45,19% of the respondents had a high rate of health behaviours. It was observed that there was no communication related to the use of CAM among the patients and healthcare staff. Patients using CAM demonstrated more positive health behaviours than those who were not using these methods.
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; zinc; zn; zinc-deficiency; cytokine storm
Online: 8 September 2020 (10:09:19 CEST)
Since the discovery of the first reported case with Zinc-deficiency in Iran1 by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response 2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency4. In the western world, Zinc deficiency is more prevalent among the geriatric population3, vegans/vegetarians, and people with certain underlying conditions4such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders4,5. Zinc and Zinc deficiency has been associated with several infectious diseases 2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21st century6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.
ARTICLE | doi:10.20944/preprints202009.0174.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: cesarean section; urinary catheterization; urinary tract infection
Online: 8 September 2020 (06:06:44 CEST)
Objective: Urinary catheters are known cause of urinary morbidities. The longer the catheter is retained, the greater the risk for contamination and infection. An increasing body of literature suggests routine practice of catheterization and retaining it for 24 hours does not add any procedural advantage. Thus, we sought to study outcomes in relation to early vs. delayed removal of urinary catheters following cesarean section. Methods: We randomly assigned 116 patients into early and delayed removal of urinary catheter groups. In the early group, catheter was removed immediately after the procedure and in the delayed removal group, catheter was removed 24 hours later. Clinical outcomes were measured in terms of significant bacteriuria 72 hours postop, voiding difficulties, urinary retention, mobilization time, length of hospital stay, and patient satisfaction. Results: Study revealed higher incidence of bacteriuria in the delayed removal group (32.8% vs. 15.5%, P = 0.030). Urinary frequency was also higher (34.6% Vs. 8.6%, P=0.001). However, there were no difference between the two groups in other urinary complaints including dysuria and urgency (P = 0.103 & P = 0.087). Urinary retention was more frequent in the early group, but difference was not significant (P = 0.080). Patients with immediate removal of the urinary catheter had early ambulation and early discharge from hospital (P = 0.001 and P = 0.040) and were generally satisfied with the procedure (P= 0.010). Conclusion: Our study showed that immediate removal of urinary catheter was associated with lower urinary complications, shorter length of hospitalization and associated cost.
Mon, 7 September 2020
ARTICLE | doi:10.20944/preprints202009.0159.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Nicotine; Cotinine; Corticosterone; LCMS; Sex; C57BL/6J mouse; CYP2A5; Plasma Levels; Subcutaneous Injection
Online: 7 September 2020 (08:08:54 CEST)
We assessed if there were any sex-related differences in the ability of nicotine to increase plasma corticosterone secretion after single or repeated nicotine administration. For single-dose studies, male and female mice were habituated to the test room for 1 h and injected with saline or nicotine (0.25 or 1 mg/kg, s.c.). In repeated-dosing studies, mice were injected with saline or nicotine (1 mg/kg, s.c.) once daily for six days, and, on day 7, received nicotine (1 mg/kg, s.c.). The mice were euthanized 15 min later, and trunk blood was collected for the measurement of corticosterone, nicotine, and cotinine. Our results showed that saline or nicotine each significantly increased plasma corticosterone levels in both male and female mice, with a greater response in female mice. Plasma corticosterone levels were increased in male but not female mice after repeated compared to single nicotine administration. The level of cotinine, a biomarker of nicotine use, was significantly higher in female than in male mice. Taken together, these novel findings suggest that female mice responded to nicotine and stress of handling more than male mice and provide for the first-time quantitative data on the male-female differences in nicotine-induced elevations of corticosterone and of cotinine.
ARTICLE | doi:10.20944/preprints202004.0227.v3
Subject: Medicine & Pharmacology, Cardiology Keywords: global myocardial injury; BMSCs; active cardiac support device (ASD); stem cell treatment; epicardial delivery
Online: 7 September 2020 (07:30:47 CEST)
Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; two weeks later, the labeled cells were transplanted into ISO-induced heart-injury rats through the tail vein or ASD device for five days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson’s trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after three days of transplantation, there were many BMSCs on the epicardial surface, and after five days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD+BMSCs-three days treated group and ASD+BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P<0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.
REVIEW | doi:10.20944/preprints202009.0153.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Virus; Vaccine; SARS-CoV-2; Coronavirus; Covid-19; Covid-19 vaccine
Online: 7 September 2020 (03:46:59 CEST)
This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Disabled Persons; Health Status; Iran; Psychometrics; Quality of Life; Reliability
Online: 7 September 2020 (03:24:54 CEST)
Aim: The aim of this study was to assess the performance of the SF-36 health survey (SF-36) in a sample of subjects with physical disabilities. Material and Methods: 305 patients recruited using the convenient sampling method from September 2019 to March 2020 in Kermanshah, Iran. Another similar 300 patients were selected to assess the confirmatory factor analysis (CFA). Results: The Cronbach’s α ranged from 0.70 to 0.93, and intra-class correlation coefficients from 0.71 to 0.88; and with the no ceiling and floor effect for two main subscales. Convergent validity was supported by moderate to good correlation between SF-36 subscales and Moorong self-efficacy subscales (r= 0.25- 0.53). The SF-36 divergently validated with HADS total score and subscales (r= -0.24- -0.65), concurrently validated with its subscales (r=0.49- 0.88), and physically discriminated between persons with different level of disability (t-test: p<0.001). Factorial analysis identified seven factors, confirmed with second-order in another 300 samples (chi-square (χ2/df) = 2.61(p < .001); RMSEA = 0.07 (90% CI = 0.07–0.08); AGFI=0.75; GFI = 0.78; CFI= 0.85; and NFI = 0.78). Conclusions: the SF-36 is a reliable and valid tool in physical disables. However, SF-36 shows insufficient eight-factor validity. Future studies should focus on evaluating other psychometric properties, such as sensitivity to change in subjects with physical disabilities.
Sun, 6 September 2020
ARTICLE | doi:10.20944/preprints202009.0149.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Smartphone Addiction; Middle School Students; Smartphone Usage Types; Depression; Parenting Attitude
Online: 6 September 2020 (16:27:01 CEST)
The purpose of this study was to examine the relationships between smartphone addiction of middle school students and smartphone usage types, depression, attention deficit hyperactivity disorder (ADHD), stress, interpersonal problems, and parenting attitude. This study was also performed with the aim of verifying the relationships among depression, ADHD, perceived stress, interpersonal problems, and parenting attitude, which are predictors of smartphone addiction. The subjects of this study were 487 local middle school students (234 males and 253 females). The measurement instruments used were the smartphone addiction scale, depression scale (PHQ-9), ADHD scale (K-ARS), perceived stress scale (PSS), interpersonal problem scale (KIIP-SC), and the parenting attitude scale. This study identified the relationships between the variables with correlation analysis and examined the predictors of smartphone addiction with hierarchical multiple regression analysis. According to the study results, the factors that influenced smartphone addiction were gender, stress, and interpersonal problems. In addition, when the confounding variables of smartphone addiction were controlled to examine the effects of smartphone usage types on smartphone addiction, social media use and music/videos were found to have a positively significant effect on smartphone addiction while study had a negatively significant effect. The order of the usage types with the highest influence on smartphone addiction was enjoying music/videos, social media use, and study. This suggests that selective intervention depending on the main smartphone usage type can be effective.
REVIEW | doi:10.20944/preprints202009.0146.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: homocysteine; small vessel disease; neuroinflammation; neurodegneration; endothelium
Online: 6 September 2020 (15:53:11 CEST)
Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.
Sat, 5 September 2020
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Cannabis; Metabolite; Principal Component Analysis; Random Forest
Online: 5 September 2020 (07:51:50 CEST)
The many strains of Cannabis spp. are associated with many effects on users and contain many different potentially psychoactive metabolites, but the links between metabolite profiles and user effects are unclear. Here we take a statistical approach to linking cause (i.e. metabolites) to effects in Cannabis spp. through the prism of strains, using quantitative data for metabolite composition and user effects. We find that species (indica vs. sativa) explains <2% of the variability in metabolite profiles, while strain explains 1/3 of variability, indicating species is nonindicative of metabolite composition, while strain is approximately indicative. Using random forests we generate a table of potential metabolite-effect links. We also find that effect-weighted metabolite composition can effectively be described in terms of four values representing the concentrations of pairs or triplets of particular compounds.
Subject: Medicine & Pharmacology, Urology Keywords: Immune cell; DNA CpGs; Bladder cancer; Subtype; mutation; CNV; Immune score; Immune Checkpoints
Online: 5 September 2020 (06:00:06 CEST)
Background: Bladder cancer (BC) development is highly related to immune cell infiltration and inflammation. This study aimed to construct a new classification of bladder cancer (BC) molecular subtypes based on immune cells-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then methylation sites corresponding to immune cells-associated genes were acquired. Differentially methylation sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylation sites was performed to divide into several subtypes. Then the potential mechanism of different subtypes was exploded. Result: Bladder cancer patients were divided into three groups. Cluster 3 (methylation-L) subtype had the best prognosis. Cluster 1 (methylation-M) had the worst prognosis. The distribution of immune cells, level expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC_co_inhibition, APC_co_stimulation, HLA, MHC_class_I, Type_I_IFN_Reponse, and Type_II_IFN_Reponse were significant difference among three subgroups. The distribution of genomic alterations was different among them. Conclusion: The classification was accurate and stable. BC patients could be divided into three subtypes based on the immune cells-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were various among three subgroups. High level immune infiltration was a correlation with high level methylation. The lower RNAss score was associated with higher immune infiltration and higher level expression of CD274.
ARTICLE | doi:10.20944/preprints202009.0114.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Poly (ADP-Ribose) Polymerase-1; E2F1 transcription factor; cell cycle; neoplasm; glioma; animal disease models
Online: 5 September 2020 (04:39:42 CEST)
In recent years, poly (ADP-ribose) polymerase (PARP) inhibitors have heen evaluated for treating homologous recombination-deficient tumors, taking advantage of synthetic lethality. However, increasing evidence indicates that PARP proteins exert several cellular functions unrelated with their role on DNA repair, including function as a co-activators of transcription through protein-protein interaction with E2F1. Since the RB/E2F1 pathway is among the most frequently mutated in many tumours types, we investigated whether the absence of PARP activity could counteract the consequences of E2F1 hyperactivation. Our results demonstrate that genetic ablation of Parp1 extends the survival of Rb-null embryos, while genetic inactivation of Parp1 results in reduced development of pRb-dependent tumors. Our results demonstrate that PARP1 plays a key role as a transcriptional co-activator of the transcription factor E2F1, an important component of the cell cycle regulation. Furthermore, impairment of PARP results in a reduction of tumor growth, that is not depending of the activity of PARP on DNA repair. Considering that most oncogenic processes are associated with cell cycle deregulation, the disruption of this PARP1-E2F1 interaction could provide a new therapeutic target of great interest and a wide spectrum of indications.
ARTICLE | doi:10.20944/preprints202009.0107.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Coxiella burnetii; dairy cattle; beef cattle; grazing; ELISA; IS1111
Online: 5 September 2020 (03:47:14 CEST)
This study was conducted to investigate the prevalence of Coxiella burnetii infection according to cattle breeds and growth types. A total of 491 cattle [cattle breed: 216 dairy cattle and 275 beef cattle; according to growth type: indoor housing (n = 294) and grazing (n = 197)] were tested for the presence of C. burnetii DNA and antibodies against C. burnetii using a commercial enzyme-linked immunosorbent assay (ELISA). Overall, 10.8% and 8.8% of the cattle were positive by PCR and for C. burnetii antibodies, respectively. The prevalence of C. burnetii was significantly higher in beef cattle than in dairy cattle using PCR (13.6% vs 7.4%; P = 0.032) and ELISA (14.6% vs 1.4%; P = 0.000), respectively. The overall infection rate of C. burnetii was significantly high in grazing cattle (PCR: 24.9%, ELSIA: 21.3%; P = 0.000) compared with housing cattle (PCR: 1.4%, ELISA: 0.3%). The results indicate that beef cattle have a significantly higher risk of contracting C. burnetii infection compared with dairy cattle (21.5% vs. 7.9%, χ2 = 5.82, P = 0.000, odds ratio = 3.197, 95% CI: 1.80-5.67). In addition, the infection of C. burnetii was significantly associated with grazing (P = 0.000). Moreover, a risk of contracting C. burnetii infection in grazing cattle was increased by 32.57-fold (95% CI: 12.84-82.60, P = 0.000) compared with indoor housed cattle. The phylogenetic analysis based on the IS111 gene revealed that our isolates were grouped together with humans, ticks, goats, and cattle isolates found in several countries. C. burnetii isolates circulating in the Republic of Korea exhibit genetic variations. Consequently, our results suggest that cattle are potential reservoirs for C. burnetii infection and most importantly, grazing acts as a high risk factor for the occurrence and transmission of this infection.
Fri, 4 September 2020
ARTICLE | doi:10.20944/preprints202009.0104.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: attitudes; clinicians; hospital; in-patient; obesity; perceptions
Online: 4 September 2020 (12:27:25 CEST)
While obesity is recognized as a key global public health issue, there has been no research to date on the perceptions of care for people with this condition held by individuals in positions of organizational power. The aim of this study was therefore to describe the perceptions and experiences of clinical leaders and managers of providing care to inpatients with obesity at a metropolitan public health service. This study applied an interpretative phenomenological analysis (IPA) approach to qualitative research, conducting interviews with 17 participants. Their perceptions of care for inpatients with obesity encompassed both their personal understanding as an individual, and their observations about the organizational, patient and carer perspectives. Three overall themes were identified: 1) The problem of inpatients with obesity, 2) Inpatients with obesity as sources of risk and 3) Personal and professional perceptions of inpatients with obesity. While clinical leaders and managers were aware of potential impact of stigma and weight bias on the care given to this cohort, elements of implicit bias, stereotyping, ‘othering’ and ambivalence were frequently present in the data. Ongoing efforts to improve care for patients with obesity must therefore include efforts to address perceptions and attitudes at all organisational levels of the workforce.
REVIEW | doi:10.20944/preprints202009.0103.v1
Subject: Medicine & Pharmacology, Other Keywords: climate change; vector-borne disease; artificial intelligence; explainable AI; geospatial modeling; infectious disease; arbovirus
Online: 4 September 2020 (12:21:32 CEST)
As recent history has shown, changing climate not only threatens to increase the spread of known disease, but also the emergence of new and dangerous phenotypes. This occurred most recently with West Nile virus: a virus previously known for mild febrile illness rapidly emerged to become a major cause of mortality and long-term disability throughout the world. As we move forward, into increasingly uncertain times, public health research must begin to incorporate a broader understanding of the determinants of disease emergence – what, how, why, and when. The increasing mainstream availability of high-quality open data and high-powered analytical methods presents promising new opportunities. Up to now, quantitative models of disease outbreak risk have been largely based on just a few key drivers, namely climate and large-scale climatic effects. Such limited assessments, however, often overlook key interacting processes and downstream determinants more likely to drive local manifestation of disease. Such pivotal determinants may include local host abundance, human behavioral variability, and population susceptibility dynamics. The results of such analyses can therefore be misleading in cases where necessary downstream requirements are not fulfilled. It is therefore important to develop models that include climate and higher-level climatic effects alongside the downstream non-climatic factors that ultimately determine individual disease manifestation. Today, few models attempt to comprehensively address such dynamics: up until very recently, the technology simply hasn’t been available. Herein, we present an updated overview of current perspectives on the varying drivers and levels of interactions that drive disease spread. We review the predominant analytical paradigms, discuss their strengths and weaknesses, and highlight promising new analytical solutions. Our focus is on the prediction of arboviruses, particularly West Nile virus, as these diseases represent the pinnacle of epidemiological complexity – solution to which would serve as an effective “gatekeeper”. We present the current state-of-the-art with respect to known drivers of arbovirus outbreak risk and severity, differentially highlighting the impact of climate and non-climatic drivers. The reality of multiple classes of drivers interacting at different geospatial and temporal scales requires advanced new methodologies. We therefore close out by presenting and discussing some promising new applications of AI. Given the reality of accelerating disease risks due to climate change, public health and other related fields must begin the process of updating their research programs to incorporate these much needed, new capabilities.
CASE REPORT | doi:10.20944/preprints202009.0096.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: body composition; inflammatory bowel disease; J pouch; physical activity levels
Online: 4 September 2020 (11:02:04 CEST)
This case study examined changes in body composition, resting metabolic rate (RMR), aerobic capacity, and daily physical activity in a patient who had ulcerative colitis who underwent ileal pouch‒anal anastomosis (IPAA) surgery. Body composition, RMR, and VO2 peak were assessed prior to, 4, 8, and 16 weeks after IPAA surgery. Daily physical activity data was extracted from a wrist-worn activity tracker preoperatively and 16 months postoperatively. At baseline, total body mass was 95.3 kg; body fat, 11.6 %; lean body mass, 81.1 kg; RMR, 2,416 kcal/d; and V̇O2peak, 42.7 mL/kg/min. All values decreased from baseline at 4 weeks postoperatively, body mass was 85.2 kg (-10.5%); body fat, 10.9% (-6.0%); lean body mass, 73.1 kg (-9.9%); RMR 2,210 kcal/d (-8.5%) and V̇O2peak, 25.5 mL/kg/min (-40.3%). At 16 weeks postoperatively, most parameters were near their baseline levels (within 1%-7%); exceptions were V̇O2peak, which was 20.4% below baseline, and RMR, which increased to nearly 20% above baseline. After the patient had an IPAA surgery, his total and lean body masses, RMR, and aerobic capacity were markedly decreased. Daily physical activity decreased postoperatively and likely contributed to the decreased aerobic capacity, which may take longer to recover compared to body composition and RMR parameters.