ARTICLE | doi:10.20944/preprints202112.0051.v1
Online: 3 December 2021 (11:00:57 CET)
Total edentulism is the loss of all teeth for any cause by a multifactorial process that involves biological and patient-related factors. Studies on edentulism and risk factors in Mexico are limited, and the epidemiological surveillance data is scarce and controversial since official governmental reports are not statistically representative of the country. We estimate the distribution for edentulism according to sociodemographic and socioeconomic variables in adults from a low-income state in 2003 and its progress in Mexico. We analyzed data from the National Performance Evaluation Survey in Oaxaca, Mexico, and the annual reports of the Epidemiological Surveillance System of Oral Pathologies in 2009-2019 using X2. Oaxacan patients older than 75 y.o (17.9%, p<0.05), those with lower schooling (11.2%), and diabetes (14.5%) presented the highest percentage of edentulism. We do not observe differences in edentulism between sex or residence (p>0.05). From 2009 to 2019, country data reports the lowest rate of edentulism in adults over 20 y.o (0.32%; 95% CI 0.18%-0.48%) and the most affected population over 79 y.o. (7.29%; 95% CI 5.2%-9.30%). As it is a cumulative phenomenon, it is necessary to establish better surveillance, prevention, and treatment programs to improve the oral health of older thus reducing edentulism.
ARTICLE | doi:10.20944/preprints202112.0050.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: cystic fibrosis; newborn bloodspot screening; CFTR-related metabolic syndrome; cystic fibrosis screen positive; inconclusive diagnosis
Online: 3 December 2021 (10:50:20 CET)
The main aim of the present study was to explore health professionals’ reported experiences and approaches to managing children who receive a designation of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive inconclusive diagnosis following a positive NBS result for cystic fibrosis. An online questionnaire was distributed via Qualtrics Survey Software and circulated to a purposive, international sample of health professionals involved in managing children with this designation. In total, 101 clinicians completed the online survey; 39 from the US, six from Canada and 56 from Europe (including the UK). Results indicated that while respondents reported minor deviations in practice, they were cognizant of recommendations in the updated guidance and for the most part, attempted to implement these into practice consistently internationally. Where variation was reported, the purpose of this appeared to be to enable clinicians to respond to either clinical assessments or parental anxiety in order to improve outcomes for the child and family. Further research is needed to determine if these findings are reflective of both a wider audience of clinicians and actual (rather than reported) practice.
REVIEW | doi:10.20944/preprints202107.0129.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: HOCl; hypochlorous; antimicrobial; antiinflammatory; SARS-CoV-2; infections; sanitisation
Online: 3 December 2021 (10:13:20 CET)
Sanitisation has become a major component of everyday life, with emphasis on the hands and surfaces. The face remains unsanitised due to the lack of an acceptable sanitiser. The use of masks has been mandated to reduce the spread of the pathogens by covering the face, however, there remain issues with the use of personal protective equipment. The face remains a harbour for upper respiratory tract infections, with constant deposition of microbes. By reducing microbial load, the risk of both infection and severity are reduced. HOCl has proven antimicrobial and anti-inflammatory activity, including efficacy against SARS-CoV-2. A facial sanitiser, alongside hand sanitisers and masks, improves protection against SARS-CoV-2. The advantages of regular sanitising of the face and mask include reduced level of microbial contamination, risk of biofilm formation, and respiratory tract and skin infections. HOCl was reviewed as a face and mask sanitiser, concluding that it was an ideal product.
ARTICLE | doi:10.20944/preprints202112.0041.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Vascular inflammation; Peripheral arterial disease (PAD); Chronic limb-threatening ischemia (CLTI); GHAS trial; TNF-α; hs-CRP; Neutrophil-to-lymphocyte ratio (NLR); NOX4; eNOS; VEGF-A.
Online: 3 December 2021 (09:44:42 CET)
Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.
Thu, 2 December 2021
ARTICLE | doi:10.20944/preprints202112.0032.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Acute bronchiolitis; Lung ultrasound; Echocardiography; Point of care ultrasonography; Cardi-opulmonary ultrasound; Cardiopulmonary interactions; Pulmonary hypertension; Myocardial strain; NT-proBNP
Online: 2 December 2021 (11:22:02 CET)
We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants < 12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients under-went clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 hours of hospital admission. The existence of significant correlation between car-diac and respiratory parameters was the primary outcome. The association of different cardio-pulmonary variables with the need of respiratory support higher than O2, the length of stay hos-pitalization, the PICU stay, and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bron-chiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction. Up to 36 (32%) infants required respira-tory support during the hospitalization. This group presented with higher lung ultrasound score (p<0.001), and increased values of Tei index (p<0.001) and pulmonary artery pressures (p<0.001). All the analyzed respiratory and cardiac variables showed moderate to strong correlations with the LOS hospitalization and the time of respiratory support. Lung ultrasound and echocardiog-raphy showed a moderate to strong predictive accuracy for the need of respiratory support in the ROC analysis, with AUC varying from 0.74 to 0.87. Conclusion: Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ul-trasonography could be a good strategy to easily identify high-risk population for a complicated acute bronchiolitis hospitalization.
ARTICLE | doi:10.20944/preprints202112.0026.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Leukocyte telomere length; Mitochondrial DNA; Relapsing- Remittent Multiple Sclerosis; Disability; Aging
Online: 2 December 2021 (10:08:35 CET)
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.
Wed, 1 December 2021
ARTICLE | doi:10.20944/preprints202112.0018.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastatic breast cancer; metastasis; causal learning; machine learning
Online: 1 December 2021 (13:40:33 CET)
Background: Risk of metastatic recurrence of breast cancer after initial diagnosis and treatment depends on the presence of a number of risk factors. Although most univariate risk factors have been identified using classical methods, machine-learning methods are also being conducted to tease out non-obvious contributors to a patient’s individual risk of developing late distant metastasis. Bayesian-network algorithms may predict not only risk factors but also interactions among these risks, which consequently lead to metastatic breast cancer. We proposed to apply a previously developed machine-learning method to predict risk factors of 5-, 10- and 15-year metastasis. Methods: We applied a previously validated algorithm named the Markov Blanket and Interactive risk factor Learner (MBIL) on the electronic health record (EHR)-based Lynn Sage database (LSDB) from the Lynn Sage Comprehensive Breast Cancer at Northwestern Memorial Hospital. This algorithm provided an output of both single and interactive risk factors of 5-, 10-, and 15-year metastasis from LSDB. We individually examined and interpreted the clinical relevance of these interactions based on years to metastasis and the reliance on interactivity between risk factors. Results: We found that with lower alpha values (low interactivity score), the prevalence of variables with an independent influence on long term metastasis was higher (i.e., HER2, TNEG). As the value of alpha increased to 480, stronger interactions were needed to define clusters of factors that increased the risk of metastasis (i.e., ER, smoking, race, alcohol usage). Conclusion: MBIL identified single and interacting risk factors of metastatic breast cancer, many of which were supported by clinical evidence. These results strongly recommend the development of further large data studies with different databases to validate the degree to which some of these variables impact metastatic breast cancer in the long term.
REVIEW | doi:10.20944/preprints202112.0017.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: frailty; muscle volume; nutritional status; prognostic factor; sarcopenia; skeletal muscle mass; stroke; temporal muscle thickness.
Online: 1 December 2021 (13:12:03 CET)
Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.
ARTICLE | doi:10.20944/preprints202112.0016.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Nutrition program; vendor system; qualitative study; obesity; non-communicable diseases
Online: 1 December 2021 (13:10:10 CET)
Globally, noncommunicable diseases (NCDs) were responsible for 41 million deaths in 2016, with the majority of these occurring in low and middle-income countries. These diseases were on the rise as a result of unhealthy, low-quality, and unbalanced diets, which resulted in overweight and obesity. The National School Nutrition Programme (NSNP) was created to regulate the foods sold to schoolchildren. To ascertain school management teams' perspectives on the relationship between the NSNP and the development of lifestyle diseases. A phenomenological qualitative study using Focus Group Discussions among 16 purposively selected members of the School Management Teams were conducted in Mt Frere, Eastern Cape in 2016. The narrative data was analyzed using Tesch's eight-phase thematic analysis approach. The data analysis revealed two themes (NSNP and the vendor system) and six sub-themes. The NSNP was viewed as making a significant contribution to children's food security, thereby improving academic output. However, reengineering of the NSNP was need through improved budgeting and inclusion of breakfast in the menu to control NCDs risk factors. The current implementation of the vendor system did not support reduction of NCDs risk factors. Improved implementation of the guide to vendor system is needed.
REVIEW | doi:10.20944/preprints202112.0014.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Pediatrics; Gait; Rehabilitation; Anti-gravity; Treadmill
Online: 1 December 2021 (12:57:48 CET)
The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.
ARTICLE | doi:10.20944/preprints202112.0010.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: infrared thermal imaging; infrared thermography; veterinary thermal imaging; pain assessment; osteoarthritis; canine back pain; canine brief pain inventory; photobiomodulation therapy; laser therapy
Online: 1 December 2021 (11:25:21 CET)
Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. Sequential infrared thermal images (IRTIs) objectively measure the patient’s physiological response after a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially IRT imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. IRT images provided an objective assessment of the physiologic status of each patient after the PBMT regimen. The thermal changes in IRT images correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CSU-CCPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (CBPI-PS) and Pain Interference Score (CBPI-PI). This proof-of-concept study demonstrates that IRTI provides an objective evaluation of response to PBMT treatment and correlates with observed and measured clinical response.
ARTICLE | doi:10.20944/preprints202112.0009.v1
Subject: Medicine & Pharmacology, Other Keywords: neutrophils; priming; innate immunity; immune-memory
Online: 1 December 2021 (11:00:01 CET)
Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.
ARTICLE | doi:10.20944/preprints202112.0008.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: aggressive treatment; Liver transplant; nonaggressive treatment; Primary Hepatic Angiosarcoma; tumor resection
Online: 1 December 2021 (10:57:24 CET)
Background and Aims: Of all primary liver tumors, primary hepatic angiosarcoma (PHA) is a rare and aggressive malignant vascular tumor. The standard therapeutic care for hepatic angiosarcoma remains unclear. This study compared the survival outcomes of aggressive treatment (resection and liver transplant) and nonaggressive treatment (chemotherapy, transarterial chemoembolization [TACE], and conservative treatments) for patients with PHA and analyzed the prognostic factors influencing survival. Materials and Methods: Data of patients diagnosed as having PHA at our facility were retrospectively reviewed. The primary outcome was survival time. The secondary outcome was calculated baseline characteristics. Results: We included a total of 19 patients, who were divided into 2 treatment groups: aggressive (8 patients had undergone resection or transplants) and nonaggressive (11 patients had undergone TACE, chemotherapy, or conservative treatment). The mean survival time was 233.1 ± 189.7 days in the aggressive treatment group and 146.5 ± 115.8 days in the nonaggressive treatment group. A Kaplan-Meier plot revealed no significant difference in survival time between the 2 treatment groups (P = .3256). Conclusions: The survival time of patients receiving aggressive treatment was longer than that of those receiving nonaggressive treatment. The long term survival time in some selective cases of aggressive treatment will be achieved. Thought a difference was not significant between the groups. Because the number of patients was limited, more cases are required to confirm these findings.
ARTICLE | doi:10.20944/preprints202112.0001.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: pancreatic ductal adenocarcinoma; deep-learning; early detection
Online: 1 December 2021 (10:14:14 CET)
Early detection improves prognosis in pancreatic ductal adenocarcinoma (PDAC) but is challenging as lesions are often small and poorly defined on contrast-enhanced computed tomography scans (CE-CT). Deep learning can facilitate PDAC diagnosis, however current models still fail to identify small (<2cm) lesions. In this study, state-of-the-art deep learning models were used to develop an automatic framework for PDAC detection, focusing on small lesions. Additionally, the impact of integrating surrounding anatomy was investigated. CE-CT scans from a cohort of 119 pathology-proven PDAC patients and a cohort of 123 patients without PDAC were used to train a nnUnet for automatic lesion detection and segmentation (nnUnet_T). Two additional nnUnets were trained to investigate the impact of anatomy integration: (1) segmenting the pancreas and tumor (nnUnet_TP), (2) segmenting the pancreas, tumor, and multiple surrounding anatomical structures (nnUnet_MS). An external, publicly available test set was used to compare the performance of the three networks. The nnUnet_MS achieved the best performance, with an area under the receiver operating characteristic curve of 0.91 for the whole test set and 0.88 for tumors <2cm, showing that state-of-the-art deep learning can detect small PDAC and benefits from anatomy information.
Tue, 30 November 2021
ARTICLE | doi:10.20944/preprints202111.0578.v1
Subject: Medicine & Pharmacology, Other Keywords: DPI; Mitochondria; Leukaemia; Oxidative stress; OxPhos; Ara-C
Online: 30 November 2021 (21:37:18 CET)
Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.
ARTICLE | doi:10.20944/preprints202111.0567.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Nurses; Leadership; COVID-19; Management; Communication
Online: 30 November 2021 (12:14:55 CET)
Purpose: To evaluate nursing leaders' perception towards communication and relationship management competencies while using digital platforms during the COVID-19 pandemic. Background: Communication and relationship management competencies among nursing leaders will ensure healthcare models are successfully implemented. Nursing leaders can achieve effective leadership by mastering these competencies leading to an overall improvement in the quality of nursing care. However, digital platforms have been rapidly evolving in the healthcare ecosystem and have been significant during the battle with COVID-19. It is crucial to ensure that nursing leaders can use digital platforms to communicate and practice efficient management in their op-erations, especially during a crisis when their services are vital. Design: Descriptive, comparative study. Methods: The study was conducted between February to March 2021. A 5-item Linkert-type questionnaire was adopted from the American Organization for Nursing Executives (2005) and was sent to identified nursing leaders in Hamad Medical Corporation through the official email. Results: Two hundred fifty nurse leaders were invited to participate, but only 116 responded positively, translating to a response rate of 46.4%. The male participants represented a larger proportion of 64.10%, while the female was 35.90%. Regarding the questionnaire, the Cronbach alpha was α ˃ 0.987, indicating that all items revealed a sufficient level of internal consistency. The respondents had a minimum of 0 and a maximum of 52.6n in the communication and relationship management items. Influencing behavior, relationship management, and effective communica-tion had the lowest scores, which indicate low competency. The F value in ANOVA analysis was close to 1.0, implying that the null hypothesis is true. The significance value is <0.5 implying that there is a difference in response on effective communication proficiency of nurse leaders. Conclusions: Digital platforms are communication tools that are widely adopted to engage and reach nurses on numerous topics. Nurse leaders should capitalize on their benefits and generate critical discussions. The continued need to research nursing leadership competencies is critical as healthcare continues to change and evolve. Educational institutions and healthcare organizations must understand that nursing leaders should strive for professional development and knowledge acquisition to improve their communication and management.
ARTICLE | doi:10.20944/preprints202111.0554.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Metabolic syndrome; Mental disorders; Obesity; Multimorbidity
Online: 30 November 2021 (10:38:08 CET)
Background: Metabolic syndrome (MS) is associated with a greater risk of morbimortality. Ob-jective: To estimate the prevalence of Metabolic Syndrome (MS) and associated factors in patients of a Psychosocial Care Center (CAPS) in the city of Salvador, state of Bahia, Brazil. Method: Cross-sectional study set at CAPS in the city of Salvador-Bahia, between August 2019 and February 2020. MS was evaluated according to the National Cholesterol Education Program's Adult Treatment Panel III. In addition to descriptive statistics, gross and adjusted prevalence ratios were described. Results: MS was found in 100 (35.2%) individuals, 116 (40.9%) were obese and 165 (58.1%) had increased waist circumference. Polypharmacy was identified in 63 (22.3%) patients and 243 (85.9%) used antipsychotics. In the gross evaluation, the female (PR = 1.88; 95% CI: 1.35-2.63) and the use of antidepressants (PR = 1.41; 95%CI: 1.05-1.88) were associated with MS. After logistic re-gression, depression (PR = 1.86; 95%CI: 1.38-2.51), acanthosis (PR = 1.50; 95%CI: 1.18 - 1.90), use of antipsychotics (PR = 1.88; 95%CI: 1.13 - 2.75) and the hypertriglyceremic waist (PR = 3.33; 95%CI: 2.48- 4.46) were associated with MS. Conclusion: The prevalence of MS alerts to multimorbidity among individuals with mental disorders and the need for clinical screening.
Mon, 29 November 2021
ARTICLE | doi:10.20944/preprints202111.0552.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: ozone; ozone therapy; cytokines; biomarkers; IL-6; inflammation; chronic inflammation; IGF-1; anabolism; knee osteoarthritis; pain; function; c-reactive protein; uric acid
Online: 29 November 2021 (19:08:10 CET)
Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.
ARTICLE | doi:10.20944/preprints202111.0547.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: biocompatible 3D printing; photopolymers; orthodontics; distalizer; CAD/CAM; personalized treatment; computer modeling
Online: 29 November 2021 (15:38:51 CET)
Aim of this research paper is to introduce a novel method of hybrid orthodontic tooth-borne distalizer treatment of class II malocclusion by using 3D printed biocompatible personalized distalizer. Explains 3D designing, printing and clinical application of individualized biocompatible medical device dedicated for orthodontic teeth distalization. Compares such distalizer manufactured from two different biocompatible photopolymers (white and transparent). Evaluates their clinical performance and also patients’ aesthetical perception. Clinical part includes comparison of treatment debonding on the set of 12 complete orthodontic treatments with uni-lateral class II malocclusion managed with hybrid approach (CAT-Invisalign with 3D printed distalizer). Paper offers an evaluation of the personalized distalizer functioning in regard to current publications and comparison to conventional prefabricated alternatives like Carriere® Distalizer™ appliance. Results showed no significance of material differences on clinical performance of such individualized distalizers. Research showed preference of patients towards transparent biocompatible photopolymer instead of white A2 shade.
ARTICLE | doi:10.20944/preprints202111.0540.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Probiotics; Dysbiosis; Obesity; High Fat Diet; Lactobacillus plantarum; Enterococcus faecium
Online: 29 November 2021 (12:59:43 CET)
Fat reduction and anti-inflammation are commonly claimed properties of probiotics. Lactobacillus plantarum and Enterococcus faecium were tested in high fat-induced obesity mice and in vitro experiments. After 16 weeks of probiotics, L. plantarum outperforms E. faecium on the anti-obesity property as indicated by body weight, regional fat accumulation, serum cholesterol, inflammatory cytokines (in blood and colon tissue), and gut barrier defect (FITC-dextran assay). With fecal microbiome analysis, L. plantarum but not E. faecium reduced fecal abundance of pathogenic Proteobacteria without an alteration in total Gram-negative bacteria when compared with non-probiotics obese mice. With palmitic acid induction, the condition media from both probiotics similarly attenuated supernatant IL-8, improved enterocyte integrity and down-regulated cholesterol absorption-associated genes in Caco-2 cell (an enterocyte cell line) and reduced supernatant cytokines (TNF-α and IL-6) with normalization of cell energy status (extracellular flux analysis) in bone-marrow-derived macrophages. Because the anti-inflammatory effect of the condition media of both probiotics on palmitic acid-activated enterocytes was neutralized by amylase, the active anti-inflammatory molecules might, partly, be exopolysaccharides. As L. plantarum out-performed E. faecium in anti-obesity property, possibly through the reduced fecal Proteobacteria, with a similar anti-inflammatory exopolysaccharide; L. plantarum is a potentially better option for anti-obesity than E. faecium.
REVIEW | doi:10.20944/preprints202111.0531.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: brain tumors; glioblastoma; angiogenesis; metformin
Online: 29 November 2021 (12:30:08 CET)
Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.
REVIEW | doi:10.20944/preprints202107.0507.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; chronic autoimmune thyroiditis; BDNF
Online: 29 November 2021 (12:03:01 CET)
Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukines (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) and brain derived neurotrophic factor (BDNF). Similar disturbances in the cytokine profile are seen in AHT patients and their relatives. Disclosure of the relationship between the co-existence of depression and autoimmune subclinical thyroiditis indicates that the pathomecha-nism of depression may be related to the changes in the immune system, it is possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly sup-ported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid auto-antibodies, and cytokine profile, which could bring us closer to understanding the interrelation-ships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psy-chiatric. We consider the above issues insufficiently investigated but of great importance. This ar-ticle is an overview of the available literature as well as an introduction to our research project.
ARTICLE | doi:10.20944/preprints202111.0525.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Occupational Health; Quality of Life; Nurses; Working Conditions; Work; Primary Health Care.
Online: 29 November 2021 (11:54:29 CET)
Background: The concept of Quality of Work Life (QWL) has been built multidimensionally through social reproduction; it is impacted by the perceptions of each individual and by the relationship between workers and the work environment. Objective: to analyze the Work Process and QWL of assisting nurses in public health. Methods: Research in a critical paradigm, descriptive, exploratory with a qualitative approach. The population corresponds to Nurses who work in care work. Semi-structured guiding questions were applied and were analyzed with content analysis. Results: seven participants declared female; all Chilean; seven are young adults; six singles; only one has children, and one has a person dependent on her care; six are heads of household, and five receive help with housework. All have a nursing degree, five have a diploma, but none have a postgraduate. Work Process has three subcategories: work object, instrument, organization, and work conditions; the QWL category has six subcategories: definition and perception of QWL, QWL potentiating factors, QWL exhausting factors, QWL improvement strategies, the emotional burden associated with QWL, and Health problems. Conclusions: In this way, the lifestyle built by the assistance in the health area has repercussions on the quality of life and health in general.
CASE REPORT | doi:10.20944/preprints202111.0513.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: lung ultrasound; LUS, children; asthma; personalized medicine
Online: 29 November 2021 (07:48:13 CET)
In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.
Fri, 26 November 2021
ARTICLE | doi:10.20944/preprints202111.0506.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: endometrial cancer; fertility-sparing management; molecular classification; reproductive age; pregnancy
Online: 26 November 2021 (12:42:15 CET)
Conclusions: Molecular classification could provide reliable supplementary information for evaluating prognostic and contribute to treatment option decision-making in EEC patients. Fertility-sparing treatment is not recommended for EEC patients with CNH and MSI-H. Furthermore, fertility-sparing treatment can be attempted in EEC patients with CHL, but regular follow-up should be carried out to early detection of EC relapse and prevention of disease progression.
ARTICLE | doi:10.20944/preprints202111.0502.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Stem Cell; Embryo; Zebrafish; Neurosensory Hearing Loss; Tissue Regeneration
Online: 26 November 2021 (10:52:49 CET)
Hearing dysfunctions can be classified by type, degree, configuration, time of onset, aetiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and sensorineural. Conductive hearing loss (CHL) results from interference with the mechanical transmission of sound through the external and middle ear; it can be congenital, as a consequence of anatomic abnormalities, but it can commonly be acquired following middle ear inflammatory pathologies. Sensorineural hearing loss (SNHL) results from failure to transduce vibrations to neural impulses in the cochlean and is a consequence of an irreversible damage to the differentiated cells which make up the organ of hearing and the acoustic paths at various levels. Mixed hearing loss involves a combination of these two types in the same ear. Studies in neuroscience field have shown that the prevention of cell degeneration is only possible if all the factors taken at the different stages of stem cells’ multiplication and differentiation are administered together. We have demonstrated this in a recent study on the ability of SCDSFs to prevent neurodegeneration in hippocampal cells of the CA1 zone in mice. This study confirms previous findings demonstrating that early developmental zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues. These findings have open a promising way for the approaches promoting the rejuvenation and regeneration of different tissues, by-passing stem cell transplantation. In the present clinical trial we have used SCDSFs to study the possible reversion of neurosensory hearing loss, until now considered an irreversible condition.
REVIEW | doi:10.20944/preprints202111.0500.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Abdominal wall; Transversus abdominis plane block; Comparative anatomy; Animal models
Online: 26 November 2021 (10:47:30 CET)
With the increased use of simulation based training using animal models for the education of surgical and anaesthetic techniques, an increased understanding of the anatomy of such models and how they compare to humans is required. The transversus abdominis plane block is a regional anaesthetic technique that requires an understanding of the abdominal wall anatomy along with proficient ultrasound use. The current review aims to compare the anatomy of the abdominal wall across species, particularly focussing on the pertinent differences within the class of mammals, and secondarily, it aims to address the implications of these differences for simulation based training of the transversus abdominis plane block. To achieve this, the PubMed, Web of Science and Google Scholar databases were searched for relevant literature. The mammalian abdominal wall differs in its musculature, vasculature or innervation from that of amphibians, birds or reptiles, however, among species of mammals, the structure of the abdominal wall follows a similar framework. Particular differences among mammals include the additional muscular layer of the panniculus carnosus found in most mammals other than humans, the variable arterial origins and dominant vascular supply of the abdominal wall and the number of thoracolumbar nerves innervating the abdominal wall. When using animal models for simulation based training, the pig is recommended for the transversus abdominis plane block given its closely homologous abdominal wall structure, availability and larger comparative size.
ARTICLE | doi:10.20944/preprints202111.0498.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: bortezomib; IL-13; IL-1Ra; IL-4; multiple myeloma; OS; PFS
Online: 26 November 2021 (10:31:50 CET)
Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The aim of the present study was to assess the impact of pretreatment serum levels of 27 selected cytokines on progression-free survival (PFS) and overall survival (OS) in MM patients before first-line therapy with bortezomib-based regimens. Serum cytokine levels were assayed with a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad) including IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. A total of 61 MM patients were examined. Most patients received a bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy regimen. In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240-0.8291, p = 0.0302), and ASCT (HR 0.3722, 95% CI: 0.1826-0.7585, p=0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046-0.438, p=0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471-9.949, p=0.0059) and two cytokine levels- IL-1Ra (HR 1.017, 95% CI: 1.004-1.030, p= 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037-0.698, p = 0.0147) were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.
Thu, 25 November 2021
REVIEW | doi:10.20944/preprints202111.0490.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: CAD/CAM; dental ceramics; dental technology; digital dentistry; dental education; dental innovation; disruptive technology
Online: 25 November 2021 (20:06:23 CET)
Digital dentistry, including CAD/CAM dentistry, is perhaps the most disruptive innovation in dentistry to date. The rapid development of digital dentistry technologies over the past several decades has enabled clinicians to improve patient care by significantly reducing the time necessary for the restorative phase of treatment. Advancements in intra-oral scanning and computer-aided design and manufacturing (CAD/CAM), in conjunction with new dental CAD/CAM ceramic materials, have simplified patient care and made same-day dentistry a reality. This review aims to present the most recent advancements described in current literature as well as to document the successful implementation of digital dentistry into a predoctoral program. The overall process of CAD/CAM same-day dentistry and the accompanying advancements in software and materials were presented and discussed. Implementation of technology and personnel requirements were reviewed. CAD/CAM dentistry has been influential in shaping and improving dental practice and education, and this influence will only continue with time.
ARTICLE | doi:10.20944/preprints202111.0435.v2
Subject: Medicine & Pharmacology, Other Keywords: cost benefit analysis; vaccination; COVID-19; health economics; economic appraisal; pharmacoeconomics
Online: 25 November 2021 (15:21:36 CET)
(1) Background: in epidemiological terms, it has been possible to calculate the savings in health resources and the reduction in health effects of COVID vaccines. From the point of view of economic evaluation, some studies have estimated its cost-effectiveness with the vaccination showing highly favorable results, which in some cases is cost-saving; (2) Methods: a cost-benefit analysis of the vaccination campaign in the North Metropolitan Health Region (Catalonia). An epidemiological model based on observational data and before and after comparison is used. The information on the doses used and the resources assigned (conventional hospital beds, ICU, number of tests) has been extracted from administrative data from the largest Primary Care provider in the region (Catalan Institute of Health). A distinction is made between the social perspective and the health system; (3) Results: the costs of vaccination are estimated at 137 million euros (€48.05/dose administered). This figure is significantly lower than the positive impacts of the vaccination campaign, which are estimated at 470 million euros (€164/dose administered). Of these, 18% corresponds to the reduction of ICU discharges, 16% to the reduction in conventional hospital discharges, 5% to the reduction in PCR tests and 1% to the reduction of RAT tests. Monetization of deaths and cases with sequelae avoided account for 53% and 5% of total savings, respectively. The benefit/cost ratio is estimated at 3.4 from a social perspective and 1.41 from a health system perspective. The social benefits of vaccination are estimated at €116.67 per dose of vaccine given (€19.93 from the point of view of the health system); (4) Conclusions: the mass vaccination campaign against COVID is cost-saving. From a social perspective, most of these savings come from the monetization of the reduction in mortality and cases with sequelae, although the intervention is equally widely cost-effective from the point of view of the health system thanks to the reduction in the use of resources. It is concluded that, from an economic perspective, the vaccination campaign has high social returns.
ARTICLE | doi:10.20944/preprints202111.0478.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Long COVID; data acquisition source; post-infectious; longitudinal cohort study; patient-powered
Online: 25 November 2021 (13:51:54 CET)
ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.
ARTICLE | doi:10.20944/preprints202111.0476.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: female; HIV infections; breastfeeding; vertical transmission; patient’s autonomy.
Online: 25 November 2021 (12:55:13 CET)
Background: Vertical transmission of HIV infection can occur during pregnancy, during childbirth or through breastfeeding. The recommendations issued by the various international guidelines (WHO 2010, EACS 2017, DHHS 2017) on the safety of breastfeeding of HIV-infected women in effective antiretroviral treatment do not provide univocal indications referring to individual countries the choice to advise or advise against such procedure. Methods: A retrospective study was conducted in a small cohort of HIV-infected pregnant women who, despite the information received, decided to breastfeed their children. The observation was carried out in the period between March 2017 and June 2021. In all newborns, prophylaxis therapy was initiated at birth, according to the treatment guidelines, the scheme adopted involved the administration of zidovudine (AZT) orally for 4 weeks, started immediately after the childbirth. Breastfeeding time was, on average, 5 months. Results: No contagion was diagnosed. All infants were tested for HIV-RNA at birth, 1, 3, and 6 months after birth, and 1, 3 and 3 months after stopping breastfeeding. Conclusions: The data obtained represent, in our opinion, a solicitation to discuss and re-evaluate scientific evidence that starting from "Undetectable Equals Untransmittable" (U = U) can open a scientific and cultural review of breastfeeding.
ARTICLE | doi:10.20944/preprints202111.0471.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: aerobic threshold; anaerobic threshold; exercise prescription; threshold detection; threshold-based training
Online: 25 November 2021 (12:01:01 CET)
The aim of this study was to determine the extent to which the Tyme Wear smart shirt is as reliable and valid in detecting personalized ventilatory thresholds when compared to the Parvo Medics TrueOne 2400. In this validation study, 19 subjects were recruited to conduct two graded exercise test (GXT) trials. Each GXT trial was separated by seven to ten days of rest. During the GXT, gas exchange and heart rate data were collected by the TrueOne 2400 (TRUE) in addition to the ventilation data collected by the Tyme Wear smart shirt (S-PRED). Gas exchange data from TRUE was used to detect VT1 and VT2. TRUE and S-PRED VT1 and VT2 were compared to determine the reliability and validity of the smart shirt. Of the 19 subjects, data from 15 subjects were used during analysis. S-PRED exhibited excellent (ICC > 0.90) reliability for detection of VT1 and VT2 utilizing time point and workload and moderate (0.90 > ICC > 0.75 ) reliability utilizing heart rate. TRUE exhibited excellent reliability for detection of VT1 and VT2 utilizing time point, workload, and heart rate. When compared to TRUE, S-PRED appears to underestimate the VT1 workload (p > 0.05) across both trials and heart rate (p < 0.05) for trial 1. However, S-PRED appears to underestimate VT2 workload (p < 0.05) and heart rate (p < 0.05) across both trials. The result from this study suggests that the Tyme Wear smart shirt is less valid but is comparable in reliability when compared to the gold standard. Moreover, despite the underestimation of S-PRED VT1 and VT2, the S-PRED detected personalized ventilatory thresholds will provide an adequate training workload for most individuals. In conclusion, the Tyme Wear smart shirt provides easily accessible testing to establish threshold-guided training zones but does not devalue the long-standing laboratory equivalent.
Wed, 24 November 2021
REVIEW | doi:10.20944/preprints202111.0461.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: juvenile idiopathic arthritis; X-Ray; ultrasound; MRI; passive microwave radiometry (MWR).
Online: 24 November 2021 (16:11:24 CET)
Juvenile idiopathic arthritis (JIA) is a disease with unknown causes within all forms of arthritis in children under 16 years of age. The diagnosis is made when another joint pathology is excluded. Difficulties in early and differential diagnosis lead to the rapid disability of patients and an unfavourable life prognosis. Therefore, timely diagnosis is necessary to prevent irreversible damage to the joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, which includes X-ray, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring disease activity, prognosis during the course, and outcome in children with JIA. Each method has its own advantages and disadvantages. The introduction of the method of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.
ARTICLE | doi:10.20944/preprints202111.0460.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Maintenance hemodialysis (MHD) patient; Low-phosphate meal; CKD-MBD (chronic kidney disease-related mineral and bone disorder); Proinflammatory cytokine; TNF-α (tumor necrosis factor-alpha)
Online: 24 November 2021 (15:27:03 CET)
High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p<0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p<0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p<0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.
ARTICLE | doi:10.20944/preprints202111.0455.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: child anxiety disorders; screening; SCARED-C; psychometrics; dental practice
Online: 24 November 2021 (12:48:07 CET)
SCARED-C instrument (the child version, 41 items) is used for screening anxiety in children between 8 to 18 years old and has been first introduced by Birmaher & collab. in 1995, with good psychometric data - internal consistency from α =.74 to .93 - and good discriminative validity indices in the original versions (1997, 1999). Since then, many countries have adopted the scale, for its utility in identifying five subsets of anxiety disorders (subscales): somatic/panic disorder, generalized anxiety, separation anxiety, social phobia, and school avoidance. The present study contains the first Romanian translated and adapted version of the SCARED-C instrument on a community sample of 477 children (8-18 years old) from Mureș county schools. The instrument showed moderate to good internal consistency (α Cronbach from to .63 to .91 for the total scale) and good test-retest reliability (.70) on a subset of 85 children sample. A confirmatory factorial analysis (CFA) was conducted to test the factor structure of the Romanian version of SCARED-C; results showed that SCARED-C has good psychometric properties to be used for screening anxiety in Romanian children and adolescents. The implications for using SCARED-C in dental practice are discussed. Future studies need to be conducted for exploring convergent and discriminative validity of the instrument and the sensitivity to current DSM-V criteria. Application on a dental pediatric sample is also required.
REVIEW | doi:10.20944/preprints202111.0454.v1
Subject: Medicine & Pharmacology, Allergology Keywords: supportive supervision; health systems strengthening; document analysis; LMIC; maternal and child health
Online: 24 November 2021 (12:45:25 CET)
Background: Supportive supervision has lately been gaining traction in various national health systems as an effective way of boosting the performance of community health workers in a constructive and sustainable way. However, not much is known about the basis/mandate of supportive supervision and its approach in maternal and child health programs in India. The current analysis contributes to a clearer understanding of the paradigms within which supportive supervision is envisioned to operate within India and identifies potential strengths and areas requiring attention. Method: Document analysis of implementation documents such as guidelines/ operational manuals/operationalization modules/ training modules of nationally implemented maternal and child health programs, with data extraction according to a pre-determined domain-based template. Results: Many of the documents reviewed do not mention supportive supervision at all. In the few documents where supportive supervision is mentioned, the paradigms within which it is supposed to operate (who will do it, when will it be done, how to do it, training and logistic support, reporting formats, etc.) have not been clearly identified in most programs. Conclusion: Even though supportive supervision is being increasingly identified as an effective way of performative improvement in national health programs in India, more effort needs to be put into identifying and enforcing the tenets of supportive supervision in practice, in order to bring about the desired change.
COMMUNICATION | doi:10.20944/preprints202106.0364.v2
Subject: Medicine & Pharmacology, Other Keywords: Diabetic foot infection; Sonication Method; Microbiological diagnosis.
Online: 24 November 2021 (11:51:36 CET)
We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).
ARTICLE | doi:10.20944/preprints202111.0447.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Immunotherapy; immune-checkpoint inhibitor; response prediction; men and women; pembrolizumab; nivolumab; atezolizumab; ECOG; CRP; chemo-immunotherapy
Online: 24 November 2021 (09:02:46 CET)
Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n=228) or ICI-CHT combination treatment (n=80) for advanced NSCLC. Kaplan-Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10-3.29, p=0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00-1.11, p=0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32-3.15, p=0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03-1.14, p=0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41-11.2, p=0.009) significant for PFS; ECOG≥2 (HR 5.58, 95%CI: 1.88-16.5, p=0.002) and CRP (HR 1.19, 95%CI: 1.06-1.32, p=0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, ECOG≥2 had a significant interaction with OS (HR 1.90, 95%CI 1.04-3.46, p=0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02-1.16, p=0.007) and OS (HR 1.11, 95%CI: 1.03-1.19, p=0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.
ARTICLE | doi:10.20944/preprints202111.0442.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Men's Health; COVID-19; Mental Disorders; Stress, Psychological; Social Support
Online: 24 November 2021 (08:13:48 CET)
Objective: to analyze the relationships between sociodemographic variables, intolerance to uncertainty (INT), social support and psychological distress (i.e., indicators of Common Mental Disorders [CMDs] and perceived stress [PS]) in Brazilian men during the COVID-19 pandemic. Methods: a cross-sectional study with national coverage, of the web survey type, and conducted with 1,006 Brazilian men during the period of social circulation restriction imposed by the health authorities in Brazil, for suppression of the coronavirus and control of the pandemic. Structural equation modeling analysis was performed. Results: Statistically significant direct effects of race/skin color (λ=0.268; p-value<0.001), socioeconomic status (SES) (λ=0.306; p-value<0.001), household composition (λ=0.281; p-value<0.001), PS (λ=0.513; p-value<0.001) and INT (λ=0.421; p-value<0.001) were evidenced in the occurrence of CMDs. Black-skinned men, with higher SES, living alone and with higher PS and INT levels presented higher prevalence values of CMDs. Conclusions: high levels of PS and INT were the factors that presented the strongest associations with the occurrence of CMDs among the men. It is necessary to implement actions to reduce the stress-generating sources, as well as to promote an increase in resilience and the development of intrinsic reinforcements to deal with uncertain threats.
Tue, 23 November 2021
ARTICLE | doi:10.20944/preprints202111.0438.v1
Subject: Medicine & Pharmacology, Other Keywords: Systemic Sclerosis; Raynaud’s phenomenon; ultrasound; microvascular imaging; blood flow
Online: 23 November 2021 (16:15:51 CET)
Systemic sclerosis is an autoimmune disease characterized by organ fibrosis and vasculopathy. Almost all patients suffer from Raynaud’s phenomenon (RP). Currently, several imaging techniques are available; nailfold video capillaroscopy (NVC) is the most widely available, but flow quantification is not possible with NVC. Novel imaging techniques are of interest in this population. We performed a single-center feasibility study using Micro Vascular Imaging (MVI) as a novel imaging technique for flow quantification of small fingertip vessels. We compared a group of 20 healthy controls (HCs) with 20 Systemic Sclerosis (SSc) patients. In HCs, flow measurements assessed with MVI were statistically significantly higher in individual fingers and combined for all fingers (p<0.0001). As a cut-off value to discriminate HCs from SSc, a peak systolic (PS) flow velocity of <6.9 cm/s and an end-diastolic (ED) flow velocity of <2.68 cm/s was determined. Test characteristics for PS flow velocity showed moderate sensitivity (0.69, 95% CI 0.58-0.78) but high specificity (0.88, 95% CI 0.79-0.93). Similar test characteristics for ED flow velocity were obtained. The optimal cut-off point was estimated at <2.68 cm/s, sensitivity was moderate (0.65, 95% CI 0.53-0.75), specificity was 0.80 (95% CI 0.70-0.87). Here, we present the first study on the use of MVI to assess blood flow in the fingertips with high specificity in SSc patients. Future studies need to investigate correlations with the risk for organ complications, such as digital ulcers or pulmonary arterial hypertension.
ARTICLE | doi:10.20944/preprints202111.0437.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: freshman; weight gain; body composition; diet; physical activity
Online: 23 November 2021 (16:13:38 CET)
Background: Students in the United States gain weight significantly during their first year of university, but limited data is available for Australian students. Methods: This 12-month observational study was conducA 12-Month Prospective Observational Study of Body Weight, Dietary Intake, and Physical Activity Levels in Australian First-Year University Studentsted to monitor monthly body weight and body composition, as well as quarterly eating behaviours, dietary intake, physical activity, sedentary behaviours, and basal metabolic rate changes amongst first-year Australian university students. Participants were first-year university students over 18 years. Results: Twenty-two first-year university students (5 males, 17 females) completed the study. Female students gained weight significantly at two, three and four-months (+0.9 kg; +1.5kg; +1.1 kg, p <0.05). Female waist circumference (2.5cm increase at two-months, p=0.012) and body fat also increased (+0.7%, p=0.04 at two-months; +0.9%, p=0.026 at three-months). Intake of sugar, saturated fat (both >10% of total energy) and sodium exceeded recommended levels (>2300 mg) at 12-months. Greater sedentary behaviours were observed amongst male students throughout the study (p <0.05). Conclusions: Female students are at risk of unfavourable changes in body composition during the first year of university, while males are at risk of increased sedentary behaviours. High intakes of saturated fat, sugars and sodium warrant future interventions in such a vulnerable group.
ARTICLE | doi:10.20944/preprints202111.0435.v1
Subject: Medicine & Pharmacology, Other Keywords: cost benefit analysis; vaccination; COVID-19; health economics; economic appraisal; pharmacoeconomics
Online: 23 November 2021 (15:35:06 CET)
(1) Background: in epidemiological terms, it has been possible to calculate the savings in health resources and the reduction in health effects of COVID vaccines. From the point of view of economic evaluation, some studies have estimated its cost-effectiveness with the vaccination showing highly favorable results, which in some cases is cost-saving; (2) Methods: a cost-benefit analysis of the vaccination campaign in the North Metropolitan Health Region (Catalonia). An epidemiological model based on observational data and before and after comparison is used. The information on the doses used and the resources assigned (conventional hospital beds, ICU, number of tests) has been extracted from administrative data from the largest Primary Care provider in the region (Catalan Institute of Health). A distinction is made between the social perspective and the health system; (3) Results: the costs of vaccination are estimated at 137 million euros (€48.05/dose administered). This figure is significantly lower than the positive impacts of the vaccination campaign, which are estimated at 470 million euros (€164/dose administered). Of these, 18% corresponds to the reduction of ICU discharges, 16% to the reduction in conventional hospital discharges, 5% to the reduction in PCR tests and 1% to the reduction of RAT tests. Monetization of deaths and cases with sequelae avoided account for 53% and 5% of total savings, respectively. The benefit/cost ratio is estimated at 3.4 from a social perspective and 1.2 from a health system perspective. The social benefits of vaccination are estimated at €116.67 per dose of vaccine given (€19.93 from the point of view of the health system); (4) Conclusions: the mass vaccination campaign against COVID is cost-saving. From a social perspective, most of these savings come from the monetization of the reduction in mortality and cases with sequelae, although the intervention is equally widely cost-effective from the point of view of the health system thanks to the reduction in the use of resources. It is concluded that, from an economic perspective, the vaccination campaign has high social returns.
REVIEW | doi:10.20944/preprints202111.0428.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: protein synthesis initiation; neural signaling; Anterior Piriform Cortex; transfer RNA; GCN2
Online: 23 November 2021 (14:51:31 CET)
Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAA) that must be available in the diet, along with those AAs that the cells can synthesize, the dispensable amino acids. Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.
ARTICLE | doi:10.20944/preprints202111.0427.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: ethyl loflazepate; idiopathic taste disorder; psychogenic taste disorder
Online: 23 November 2021 (14:49:20 CET)
Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for >14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al , and treatment efficacy was evaluated using the Visual Analogue Scale, wherein patients gave subjective ratings for their symptoms (reductions by >50% after administration of EL for 4 weeks were defined as mprovements). Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55% and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases of sleepiness and one case of dizziness). We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.
ARTICLE | doi:10.20944/preprints202111.0420.v1
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: Midbrain; postexertional malaise; PEM, arousal; exercise; fMRI; autonomic; postural tachycardia; Myalgic Encephalomyelitis / Chronic Fatigue Syndrome; ME/CFS; Gulf War Illness; GWI
Online: 23 November 2021 (10:53:55 CET)
Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Gulf War Ill-ness (GWI) and control subjects had fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction Methods: Activated midbrain nuclei were inferred by re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI had greater activation during cognition than ME/CFS in left pedunculotegmental nucleus. Postexercise ME/CFS had greater activation than GWI for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI indicating reciprocal patterns of activation. Controls had no changes. Conclusions: Exercise caused opposite effects with increased activation in ME/CFS but decreased activation in GWI indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.
Mon, 22 November 2021
ARTICLE | doi:10.20944/preprints202111.0407.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: HpSA; H. pylori; diagnostic values; sensitivity; specificity; accuracy; PPV; NPV
Online: 22 November 2021 (14:26:56 CET)
Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions
ARTICLE | doi:10.20944/preprints202111.0403.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: anticancer agent; cytotoxicity; cell viability test; QSAR
Online: 22 November 2021 (14:18:14 CET)
2-(Morpholin-4-yl)-4,5-bis(2’’,2’’,2’’-trinitroethoxy)-1,3,5-triazine having QSAR-predicted anti-tumor activity was tested for the cytotoxicity using MTT and LDH cell viability tests. The experiments were conducted using human fibroblasts, peripheral blood mononuclear cells and breast cancer cells and allowed to identify effective cytotoxic concentration ant therapeutic range of this compound. The data obtained suggest the feasibility of the further studies of the test compound as a potential anti-cancer agent.
ARTICLE | doi:10.20944/preprints202111.0399.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: clinical assistants; pediatric oncology; assistance activity; new roles; skill mix
Online: 22 November 2021 (14:00:03 CET)
Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.
ARTICLE | doi:10.20944/preprints202111.0398.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Aspergillus giganteus; Aspergillosis; Antagonism; Sarcin; ADMET; GC-MS
Online: 22 November 2021 (13:56:36 CET)
Fungal infections are more predominant in agricultural and clinical fields. Aspergillosis caused by Aspergillus fumigatus leads to respiratory failure in patients along with various illnesses. Due to the limitation of antifungal therapy and antifungal drugs, there is an emergence to develop efficient antifungal compounds from natural sources to cure and prevent fungal infections. The present study deals with the investigation of the mechanism of active compounds from our candidate agonist Aspergillus giganteus for aspergillosis. The integrity of treated Aspergillus fumigatus cell membrane and nuclear membrane was analyzed by determining the release of cellular materials. The antagonistic potential of antifungal compounds on the pathogen was confirmed by SEM analysis. The effective concentration of antifungal compounds (AFCs) was found to be 250µg/ml. The GC-MS profiling has revealed the bioactive metabolites responsible for the antagonistic nature of Aspergillus giganteus. The bioavailability and toxicological properties of pathogenesis related proteins have proved the efficiency of pharmacokinetic properties of selected compounds. Interaction of sarcin, thionin, chitinase and its derivatives from Aspergillus giganteus with the virulence proteins of UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase have proved the druggable nature of the antifungal compounds.
BRIEF REPORT | doi:10.20944/preprints202111.0392.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: oral leukoplakia; Bayesian Networks; malignant transformation
Online: 22 November 2021 (13:05:31 CET)
Oral squamous cell carcinoma often arises from an oral potentially malignant disorder called oral leukoplakia (OL). With this work we aimed to develop a novel data-driven predictive model based on gene expression profiles to distinguish OL patients who underwent malignant transformation from those who did not. We used the Tree Augmented Naïve (TAN) Bayes classifier to predict the posterior probability of having oral cancer given the data. 86 patients were included with a median follow-up of 7.11 years. Fifty-one patients (51/86; 59%) underwent malignant transformation. We found that 16 genes were predictors of oral cancer in patients with OL and these included SLC7A11, SPINK6, SERPINA12, VIT, ATP1B3, CST6, FLRT2, ELMOD1, AZGP1, RNASE13, DIO2, ECM1, CYP4F11, SYTL4, AKR1C1, and AKR1C3. In conclusion, we showed that Bayesian gene networks are a data-driven approach which could be used also in other predictor models in oncology.
ARTICLE | doi:10.20944/preprints202111.0391.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: celiac disease; orthorexia; eating disorders; ORTHO-15; nutrition
Online: 22 November 2021 (12:56:59 CET)
Evidence points to a link between gluten-free diet or celiac disease and eating disorders, but not with orthorexia. This study is the first to examine adults with celiac disease in terms of the prevalence of risk of orthorexia. The study included 130 adults diagnosed with celiac disease. The standardized ORTHO-15 questionnaire was used to assess the risk of orthorexia. Cronbach's alpha test was used to determine the reliability of the ORTHO-15 questionnaire. Eating habits of the subjects were assessed using a questionnaire. The effect of celiac disease on diet was assessed on a 5-point scale. A risk of orthorexia was found in 69% of subjects with celiac disease. A statistically significant (p<0.005) positive correlation was observed between age and ORTHO-15 test scores (rho=0.37). In the group with orthorexia risk, meals were more often self-prepared (93.3%) compared to those without orthorexia (80%) (p=0.023). For 80% of those at risk for orthorexia versus 20% without risk, mood was a factor influencing dietary choices (p=0.001). The study observed a strong association between celiac disease and the presence of orthorexia risk. The numerous risk factors for orthorexia suggest the need for holistic care, including nutritional and psychological support among individuals with celiac disease.
ARTICLE | doi:10.20944/preprints202111.0390.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: osteosarcoma; hallmarks of cancer; predictive model; immune escape; ribosome biogenesis; RPS28
Online: 22 November 2021 (12:38:38 CET)
Osteosarcoma (OSA) is the most common primary malignant bone tumor. More than 40% of patients with OSA have poor prognoses. We aimed to discover a biomarker for patient stratification and therapeutic targets for these high-risk patients. Using Single Sample Gene Set Enrichment Analysis (ssGSEA) and univariate Cox analysis, six hallmarks were identified as significant prognostic factors for overall survival (OS). Three were selected to construct a multivariate Cox model. Then, WGCNA, univariate Cox regression, Kaplan-Meier (KM) survival analyses, and multivariate Cox analyses were combined to filter promising candidates and establish a seven-gene signature to predict OS, whose prognostic value was validated internally and externally. Subsequently, Differential Expression Analysis was conducted between high- and low-risk patients, and the Robust Rank Aggregation algorithm was used to determine the robust DEGs. Metascape was used to perform pathway and process enrichment analyses as well as construct protein-protein interaction (PPI) networks. Finally, RPS28 was identified as an independent risk factor by using univariate and multivariate Cox regression, which was preliminarily validated as a promising therapeutic target by using RNA interference. In conclusion, we might contribute to optimizing risk stratification and an excellent therapeutic target for high-risk patients with OSA.
ARTICLE | doi:10.20944/preprints202111.0387.v1
Subject: Medicine & Pharmacology, Other Keywords: Aging; Accidental Falls; Frail Elderly; Postural Balance
Online: 22 November 2021 (11:50:39 CET)
This study aimed to characterize the risk of falling in low, moderate and high risk participants from two different geographical locations using a portable force-plate. A sample of 390 older adults from South and North America were matched for age, sex, height and weight. All participants performed a standardized balance assessment using a force plate. Participants were classified in low, moderate and high risk of falling. No differences were observed between South and North American men, nor comparing North American men and women. South American women showed the significantly shorter center of pressure path length compared to other groups. The majority of the sample was categorized as having low risk of falling (male: 65.69 % and female: 61.87 %), with no differences between men and women. Also, no differences were found between North vs. South Americans, nor for falls risk levels when male and female groups were compared separately. In conclusion, South American women had better balance compatible with the status of the 50-59 years’ normative age-range. The prevalence of low falls risk was ~ 61-65 % and the prevalence of moderate to high risk was ~ 16-19 %. The frequency of fall risk did not differ significantly between North and South Americans, nor between males and females.
REVIEW | doi:10.20944/preprints202111.0384.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Alcohol abuse; cell signaling; FDA-approved drugs; oxidative stress; therapy
Online: 22 November 2021 (11:41:50 CET)
Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.
Fri, 19 November 2021
ARTICLE | doi:10.20944/preprints202111.0368.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Long Covid; rehabilitation; virtual methods; multi-disciplinary team
Online: 19 November 2021 (15:00:47 CET)
Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.
ARTICLE | doi:10.20944/preprints202111.0366.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: β-Apopicropodophyllin; Radiosensitizer; Topoisomerase inhibitor; ROS, Apoptosis; Colorectal cancer
Online: 19 November 2021 (14:54:40 CET)
β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.
ARTICLE | doi:10.20944/preprints202109.0216.v2
Subject: Medicine & Pharmacology, Other Keywords: Rural Health; Twitter Messaging; Social Media; Covid-19, SARS-CoV-2; coronavirus; social network analysis
Online: 19 November 2021 (14:41:47 CET)
Individuals from rural areas are increasingly using social media as a means of communication, receiving information, or actively complaining of inequalities and injustices. This study captured 57 days’ worth of Twitter data from June to August 2021 related to rural health using English language keywords. The study utilised social network analysis and natural language processing to analyse the data. It was found that Twitter served as a fruitful platform to raise awareness of problems faced by those living in rural areas. Overall, Twitter was utilised in rural areas to express complaints, to debate, and share information. Twitter could be leveraged as a powerful social listening tool for individuals and organisations who want to gain insight into popular narratives around rural health.
ARTICLE | doi:10.20944/preprints202111.0361.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: swimming; COVID-19; swim performance
Online: 19 November 2021 (14:34:46 CET)
The COVID-19 pandemic caused significant training disruptions during the 2020-21 season due to lockdowns, quarantines, and strict adherence to pandemic protocols. The main purpose of this study was to determine how pandemic training restrictions affected training volume and performance in one collegiate swim team. Cumulative training volume data, across a 28-week season, were compared between a pandemic (2020-2021) versus non-pandemic (2019-2020) season. Swimmers were categorized into three groups (Sprinters, Mid-Distance, and Long-Distance) based on training group. Performance times in 25 swimmers who competed in Regional Championships, during both the non-pandemic and pandemic year, were compared via 1-way ANOVA. 26 male and 22 female swimmers commenced the 2020-21 (pandemic) season, with 23% of swimmers voluntarily opting out. Three COVID-19 cases were confirmed (2%) by the medical staff with no long-term effects. Significant reductions in average swim volume were verified in Sprinters (32,867±10,135 vs.14,800±7,995yards;p<0.001), Mid-Distance (26,457±10,692 vs.17,054±9.923yards;p<0.001), and Long-Distance (37,600±14,430 vs.22,254±14,418yards;p<0.001) swimmers (non-pandemic vs. pandemic season, respectively). In the Regional performance analyses, the Sprinters swam faster (n=8;-0.5±0.6secs), while Mid-Distance (n=10;0.17±2.1secs) and Long-Distance (n=7;6.0±4.9secs) swimmers swam slower (F=11.76;p=0.0003;r2=0.52). Thus, the pandemic caused significant reductions in swim training volume, with Sprinters performing better and Long-Distance swimmers performing worse at Regional Championships.
REVIEW | doi:10.20944/preprints202111.0346.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Ascending aorta aneurysm (AsAA); reactive oxygen species (ROS); oxidative stress; onset and progression of sporadic AsAA; management of AsAA; biomarkers and targets
Online: 19 November 2021 (11:19:37 CET)
Ascending aorta aneurysm (AsAA) is a complex disease, currently defined an inflammatory disease. In the sporadic form, AsAA has, indeed, a complex physiopathology with a strong inflammatory basis, significantly modulated by genetic variants in innate/inflammatory genes, acting as independent risk factors and as largely evidenced in our recent studies performed during the last 10 years. Based on these premises, here, we want to revise the impact of reactive oxygen species (ROS) and oxidative stress on AsAA pathophysiology and consequently on the onset and progression of sporadic AsAA. This might consent to add other important pieces in the intricate puzzle of the pathophysiology of this disease with the translational aim to identify biomarkers and targets to apply in the complex management of AsAA, by facilitating the AsAA diagnosis currently based only on imaging evaluations, and the treatment exclusively founded on surgery approaches.
ARTICLE | doi:10.20944/preprints202111.0343.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Corrosive burn; esophageal stricture; TGF-β1
Online: 19 November 2021 (09:39:39 CET)
Corrosive burns lead to progressive esophageal stricture and dysphagia. There are many trials to prevent Esophageal stricture formation after corrosive burn. This study aimed to access the effects of EW-7197 on prevention for esophageal stricture formation after corrosive esophageal burn. animal study were classified divided into three groups: a healthy group, a control group (corrosive burn without EW-7197), and a treatment group (corrosive burn with EW-7197). Corrosive esophageal burns were produced using 30% NaOH on the lower esophagus. For 3 weeks, the control group received vehicle and the treatment group received 20 mg/kg/day EW-7197. Treatment efficacy was assessed by measuring the stenosis ratio by esophagogram with contrast media on day 21. histologic staining was performed to evaluate the fibrosis area ratio, and western blotting was performed to evaluate fibrotic markers. Among 20 rats that underwent surgery, 14 survived. Three in the treatment group died because of esophageal perforation, and three in the control group died due to their debilitating status. The esophageal stenosis ratio was significantly lower in the treatment group than in the control group (12.1 ± 9.5% and 42.2 ± 8.3%, respectively; p = 0.001). The histologic fibrosis area ratio was also significantly lower in the treatment group (12.5 ± 3.0% and 21.6 ± 2.1%, respectively; p = 0.001). The treatment group showed lower expressions of profibrogenic proteins such as TGF-β1, pSmad3, and α-SMA. EW-7197 may be a good alternative for the prevention esophageal stricture formation after corrosive burn.
ARTICLE | doi:10.20944/preprints202111.0342.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Type 2 Diabetes Mellitus; Chronic Kidney Diseases; Hypertension; Risk Factors; Bangladesh
Online: 19 November 2021 (09:26:12 CET)
Diabetes and chronic kidney disease (CKD) are a major public health burden in low-and-middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on estimated Glomerular Filtration Rate using the ‘Modification of Diet in Renal Disease’ equations and presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model Factors associated with CKD were: aged 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34); being female (2.2, 1.2-3.8), hypertensive (1.9, 1.1-3.5) and household income between 128.2-256.4 US$ (2.9, 1.0-8.2) compared with income ≤128.2$. However, after adjustment of other covariates, only duration of hypertension and household income (128.2-256.4 US$) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.
Thu, 18 November 2021
ARTICLE | doi:10.20944/preprints202111.0336.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: therapeutic hypothermia; newborn; QTc interval; QTc prolongation; pharmacovigilance.
Online: 18 November 2021 (17:26:05 CET)
Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker to assess safety during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). Results: We retrieved 94 QTc intervals [during TH (n=50, until day 3) or subsequent normothermia (n=44, day 4-7)] in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We added a relevant non-maturational covariate (TH, °C dependent) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.
CASE REPORT | doi:10.20944/preprints202111.0331.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: wearable sensor; pulse oximetry; sleep disturbance; blood oxygenation; haptic feedback; home care; oxygen concentration
Online: 18 November 2021 (14:32:09 CET)
The study reports about a case of a lung cancer patient with increasing difficulties in falling asleep and frequent periods of wakefulness. Severe dyspnea related to pneumonitis caused as a side effect of immunotherapy worsened the situation. Eventually, fear of falling asleep developed, including panic attacks and anxiety of choking, which was shown to lead to nights of complete wakefulness. The patient did not only sleep poorly; he did not sleep at all at night for several days, as evidenced by the notes he made during the night. Polygraphy showed no evidence of sleep-disordered breathing, but frequent periods of wakefulness and reduced basal saturation around 90% during sleep due to lung changes such as extensive functional failure of the left upper lobe with position-dependent shunts. The authors hypothesized that the symptoms described were causally related to a drop in oxygen saturation in the patient's blood. Therefore, they pursued the goal of finding a measurement technique that is as inexpensive as possible and that the patient can operate without outside assistance and great effort. So the patient started using a low-cost wearable device that allows simultaneous measurements of blood oxygen content, pulse rate and movement intensity. It consists of a finger ring with pulse oximetry sensor and a wristband with the control unit containing a vibration motor. The described device reliably warned of disturbances in oxygen concentration in the blood during the night with its vibration alarm. By use of that device during the whole night at home, the events of reduced oxygen saturation and the anxiety symptoms were reduced. Sleep disturbances with sudden awakenings did not occur when using the device. The patient benefited from the security gained in this way and slept much more peacefully, and he could spend nights without waking up again. In conclusion, wearable oximeters with vibration alarm can be recommended for patients’ home care in lung cancer patients.
ARTICLE | doi:10.20944/preprints202111.0330.v1
Subject: Medicine & Pharmacology, Other Keywords: Tdap; flow cytometry; acellular pertussis vaccine; whole cell pertussis vaccine; plasma cells
Online: 18 November 2021 (14:18:35 CET)
Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole cell to acellular pertussis vaccines, although other factors may also contribute. To develop future vaccines and improve current vaccination strategies, it is critical to understand factors influencing the generation of immunological memory. We applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. These findings were correlated to vaccine-specific plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days post-vaccination was the most prominent cellular change in all age groups, and was most pronounced for more mature IgG1+ plasma cells. Cellular responses were stronger in individuals primed with whole cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ plasma cell expansion weakly correlated with Prn- and PT- specific serum IgG levels. Our study points at plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and priming backgrounds.
CONCEPT PAPER | doi:10.20944/preprints202111.0328.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: platelets; cytokines; angiogenesis; embryo; menopause; fertility
Online: 18 November 2021 (13:56:53 CET)
The first published description of intraovarian platelet-rich plasma (PRP) appeared in mid-2016, when a new experimental technique was successfully used in adult human ovaries to correct the reduced fertility potential accompanying advanced maternal age. Considering the potential therapeutic scope of intraovarian activated PRP and/or condensed platelet cytokines would likely cover both menopause treatment and infertility, the mainstream response has ranged from skeptical disbelief to welcome astonishment. Indeed, reports of restored menses in menopause (as an alternative to conventional hormone replacement therapy) and healthy term livebirths for infertility patients (either with IVF or as unassisted conceptions) after intraovarian PRP injection continue to draw notice. Yet any proper criticism of ovarian PRP applications will be difficult to rebut given the heterogenous patient screening, varied sample preparations, wide differences in platelet incubation and activation protocols, surgical/anesthesia techniques, and delivery methods. Notwithstanding these features, no adverse events have been reported thus far and ovarian PRP appears well tolerated by patients. Here, early research guiding the transition of ‘ovarian rejuvenation’ from experimental to clinical is outlined. Likely mechanisms are presented to explain results observed in both veterinary and human ovarian PRP research. Current and future challenges for intraovarian cytokine treatment are also discussed.
ARTICLE | doi:10.20944/preprints202111.0323.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Suicide; questionnaire; validity; reliability
Online: 18 November 2021 (11:17:37 CET)
Objective: Our goal is to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got KMO = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates RMSEA= 0.000 and CFI=1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors in the pandemic time.
ARTICLE | doi:10.20944/preprints202111.0322.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: binding agent; disintegrating agent; natural polymer; mucilage; Coccinia grandis
Online: 18 November 2021 (11:14:32 CET)
Mucilage from Coccinia grandis was extracted, isolated by maceration technique and precipitated, accordingly. The mucilage was evaluated for its physicochemical, binding, and disintegrant properties in tablets using paracetamol as a model drug. The crucial physicochemical properties such as flow properties, solubility, swelling index, loss on drying, viscosity, pH, microbial load, cytotoxicity were evaluated and the compatibility was analysed using sophisticated instrumental methods (TGA, DTA, DSC, and FTIR). The binding properties of the mucilage were used at three different concentrations and compared with starch and PVP as standard binders. The disintegrant properties of mucilage were used at two different concentrations and compared with standard disintegrants MCCP, SSG, and CCS. The wet granulation technique was used for the preparation of granules and was evaluated for the flow properties. The tablets were punched and evaluated for their hardness, friability, assay, disintegration time, in vitro dissolution profiles. In vitro cytotoxicity study of the mucilage was performed in human embryonic kidney (HEK) cell line using cytotoxic assay by MTT method. The outcome of the study indicated that the mucilage had good performance when compared with starch and PVP. Further, the mucilage acts as a good disintegrant than MCCP, SSG and CCS to paracetamol tablets. Moreover, the in vitro cytotoxicity evaluation results demonstrated that the mucilage is non-cytotoxic to human cells and is safe.
ARTICLE | doi:10.20944/preprints202111.0320.v1
Subject: Medicine & Pharmacology, Other Keywords: Arteriogenesis; Arterial structure; extracellular matrix; peripheral arterial disease; collateral circulation
Online: 18 November 2021 (10:59:12 CET)
When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.
Wed, 17 November 2021
REVIEW | doi:10.20944/preprints202111.0315.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: ROR2; cancer; oncogene; tumor-suppressor gene.
Online: 17 November 2021 (23:39:15 CET)
The Wnt pathway plays an essential role in the initiation and progression of various types of cancer. ROR1 and ROR2 are Wnt receptors that are critical for β-catenin-independent (non-canonical) pathways and have been linked to processes driving tumor development and progression, such as cell proliferation, survival, invasion, and therapy resistance. Both receptors have garnered interest as potential therapeutic targets since they are largely absent in adult tissue, are overexpressed in several cancers, and, as members of the receptor tyrosine kinase family, are easier to target than all other components of the pathway. Unlike ROR1 which always promotes tumorigenesis, ROR2 has a very complex role in cancer acting either to promote or inhibit tumor progression in different tumor types. In the present article, we summarize the findings on ROR2 expression in cancer patients and its impact on clinical outcome. Further, we review the biological processes and signaling pathways regulated by ROR2 that explain its dual role in cancer. Finally, we describe the ongoing strategies to target ROR2 in cancer.
ARTICLE | doi:10.20944/preprints202111.0313.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: PRDX6; inflammation; NRF2; HGFs.
Online: 17 November 2021 (23:34:15 CET)
Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin6 (PRDX6) is an antioxidant enzyme and has been identified as a regulator in redox balance. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS) induced inflammation and its mechanisms. Here, both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and NRF2 by Immunohistochemistry and Western blotting. Furthermore, HGFs were stimulated with LPS, MJ33 (PRDX6 phospholipase A2 inhibitor), or ML385 (NRF2 inhibitor). The expression levels of inflammatory cytokines were measured by RT-qPCR and ELISA, and reactive oxygen species (ROS) was detected using DCFH-DA. PRDX6 was downregulated in inflamed gingival tissues. In HGFs, LPS induced inflammatory cytokines and ROS was upregulated in PRDX6 knockdown cells. Furthermore, co-treatment with MJ33 alleviated LPS-induced inflammatory cytokines and ROS, while inhibiting NRF2 upregulated those in HGFs. Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signaling, alleviates LPS- induced periodontitis in human gingival fibroblasts.
ARTICLE | doi:10.20944/preprints202111.0309.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: psoriasis; cutaneous nervous system; axon development; myelination
Online: 17 November 2021 (12:54:23 CET)
An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related processed. Our in silico analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators.
ARTICLE | doi:10.20944/preprints202111.0307.v1
Subject: Medicine & Pharmacology, Other Keywords: Histoplasmosis; Antigen; HIV; Opportunistic infections
Online: 17 November 2021 (12:44:23 CET)
Among people with HIV, histoplasmosis represents an important cause of mortality. Previous studies have provided estimates of the disease incidence. Here, we compared those estimates with the results obtained from a screening program implemented in Guatemala, which included histoplasmosis detection for people with HIV. To compare the results of this program, with previous estimations, a literature search was done and reports about histoplasmosis incidence were analyzed. The screening program enrolled 6,366 patients. The overall histoplasmosis incidence in the screening program was 7.4%, which was almost double than those estimated by the previous studies. From 2017 to 2019, the screening program showed an upward trend in histoplasmosis cases from 6.5% to 8.8%. Histoplasmosis overall mortality among those who were newly HIV diagnosed showed a decrease at 180 days from 32.8% in 2017 to 21.2% in 2019. The screening approach using rapid diagnostic assays detects quickly more cases of histoplasmosis, allowing a specific treatment, which decreases the mortality of the disease. Therefore, the use of these new techniques, especially in endemic areas of histoplasmosis, must be implemented.
ARTICLE | doi:10.20944/preprints202111.0306.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID-19 Pandemic; Dietary patterns; BMI; Nutrition; Vitamins; Healthy Food; Dietary Supplements; Factor analyses; Internal Consistency; weight gain
Online: 17 November 2021 (12:09:58 CET)
Since its inception in 2019, COVID-19 has been associated with significant changes in lifestyle-related behavior, including physical activity, diet, and sleep, which are vital to maintaining our well-being. This study measures lifestyle-related behavior during the COVID-19 pandemic lockdown using a 21-item questionnaire. The responses were collected from March 2021 to September 2021. Four hundred sixty-seven participants were engaged in assessing the changes caused by the pandemic and their effect on BMI. The validity and reliability of the questionnaire were tested for 71 participants. Cronbach's alpha values for the questionnaire all exceeded 0.7, demonstrating good validity and internal consistency for it. The effect of each question regarding physical activity and dietary habits over the BMI difference was studied using ANOVA. The study shows that more than half of the participants reported snacking more between meals and increased their sitting and screen time, while 74% felt more stressed and anxious. These indications were the cause of the increase in the BMI rate for individuals in the lockdown. In contrast, 62% of the participants showed more awareness about their health by increasing the intake of immunity-boosting foods, and 56% of the participants showed an increase in the consumption of nutrition supplements. Females and married individuals tended to be healthier, so their BMI showed stability compared to others based on their gender and marital status.
ARTICLE | doi:10.20944/preprints202111.0301.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: ductal carcinoma in situ (DCIS); invasive breast carcinoma; breast; biopsy; overtreatment; active surveillance.
Online: 17 November 2021 (11:03:55 CET)
Background: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. Methods: 3100 VABBs were retrospectively reviewed among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients’ features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate analysis. Finally, we developed a predictive multivariable model based on the features which were significantly associated with the univariate analysis outcome. Results: the upgrade rate to invasive carcinoma was 10.8 %. At univariate analysis, the risk of upgrade was significantly lower in the absence of post- biopsy residual lesion (p<0.001), age > 50 (p=0.029), and in presence of low-grade DCIS only in specimens with microcalcifications (p=0.002). According to the final multivariable model, the predicted probability of diagnostic underestimation for a patient with all the three favourable features selected at univariate analysis was 1% (95% CI: 0.3%-4%). Conclusions: An easy to use predictive model of radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.
REVIEW | doi:10.20944/preprints202111.0300.v1
Subject: Medicine & Pharmacology, Other Keywords: Endocrine disruptors; gender; female; atherosclerosis; Cadmium; Bisphenol A; inflammatory cytokines; cardiovascular diseases
Online: 17 November 2021 (10:53:12 CET)
The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.
Tue, 16 November 2021
ARTICLE | doi:10.20944/preprints202111.0280.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: eDNA; antibiotic resistance; biofilms; biocides; disinfectant; alcohols; hydrogen peroxide; quaternary ammonium compounds; PHMG-Cl
Online: 16 November 2021 (09:07:41 CET)
The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here we investigated how different biocides affected the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides including alcohols, hydrogen peroxide, quaternary ammonium compounds, and polymeric guanidines were evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA-PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after four weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain which demonstrates the potential of PHMG-Cl as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.
Mon, 15 November 2021
ARTICLE | doi:10.20944/preprints202111.0264.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: exercise; marriage; sedentary behavior; gender; age groups; behavioral risk factors surveillance system
Online: 15 November 2021 (13:44:23 CET)
Abstract: The aim of the present study was to identify the age and sex-related associations between marital status with PA and TV time. We used data from Vigitel, an annual telephone survey started in 2006 in Brazil. We applied a complex sample logistic regression model to estimate the odds for PA and TV time comparing marital statuses according to age and sex subgroups, independent of obesity, hypertension, diabetes, self-assessed poor health, and smoking. Our sample included 561,837 individuals with a TV time > 3 h/day (prevalence = 25.2%) and PA > 150 min/week (prevalence = 35%). Compared to single individuals, married men and women were less likely to watch TV more than 3 h/day in participants > 30 years old. When compared to single, married participants were less likely to do more than 150 min of PA/week at younger age groups. Married women older than 40 years were more likely to do more than 150 min of PA/week than the single ones, while there were no differences among married men by age group. In conclusion, married individuals are less likely to spend more than 3 hours a day watching TV than single individuals. Single men and women were more likely to do more than 150 min of PA/week at younger age groups and married women older than 40 years were more likely to do 150 min of PA/week than single women.
ARTICLE | doi:10.20944/preprints202111.0263.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Pregnancy; Diabetes; Screening, Lifestyle
Online: 15 November 2021 (13:40:25 CET)
Basildon and Thurrock University Hospital witnessed rapidly increasing numbers of pregnant women with diabetes, causing overburdened specialist clinics, poorer patient experience and worsening clinical outcomes. This prompted the multidisciplinary team’s remodelling of care pathways, launching the General ownership of Diabetes (GooD) Pregnancy Network in 2014. Contrary to conventional limitation of care to specialist diabetes antenatal clinics, this novel initiative highlights contemporary necessity to equip and empower all maternity stakeholders to deliver basic care of gestational diabetes (GDM). It strategically connects a Midwife Tele-Clinic “hub” to Educating Gestational diabetics Group Sessions (EGGS) and standard antenatal clinics. Patients were key partners, regularly participating in feedback surveys and promoting public awareness by co-producing local newspaper articles that served up their stories as case studies. Furthermore, the EGGS “faculty” includes a former GDM patient whose video testimony has inspired almost 2000 patients and their families; aiming to foster long term healthy lifestyle changes. Final summative evaluation in November 2019 showed the new culture of wider consciousness has shortened ‘diagnosis to first consultation’ intervals, eliminated overbooked specialist clinics (none since January 2016), substantially improved clinical outcomes, boosted research recruitment and avoided additional running costs to the tune of £66,384 a year.
ARTICLE | doi:10.20944/preprints202111.0257.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastatic melanoma; targeted therapy; immune checkpoint inhibitor therapy; survival; statutory health insurance data
Online: 15 November 2021 (11:50:07 CET)
(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about 2 million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e. distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.
REVIEW | doi:10.20944/preprints202111.0253.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Cell therapy; chronic limb-threating ischemia; peripheral artery disease; diabetes; atherosclerosis obliterans; thromboangiitis obliterans; personalized medicine; artificial intelligence; machine learning; genome-wide association studies; transcriptome-wide association studies; clonal hematopoiesis of indeterminate potential.
Online: 15 November 2021 (11:18:43 CET)
Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.
ARTICLE | doi:10.20944/preprints202111.0249.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: cervical cancer screening; HPV self-sampling; sub-Saharan Africa; preference
Online: 15 November 2021 (10:55:02 CET)
Human papillomavirus (HPV) self-sampling (Self-HPV) is a promising strategy to improve cervical cancer screening coverage in low-income countries. However, issues associated with women who prefer conventional HPV clinical-sampling over HPV self-sampling may affect screening participation. To address this issue, our study assessed factors associated with women’s preferences related to Self-HPV. This study was embedded in a large clinical trial recruiting women aged 30–49 years in a primary HPV-based study termed “3T-Approach” (for Test-Triage-Treatment), launched in 2018 at Dschang District Hospital, West Cameroon. Participants were invited to perform a Self-HPV. After the sampling and before receiving the results, participants completed a questionnaire about cervical cancer screening and their preferences and perceptions around Self-HPV. The median age of the 2201 participants was 40.6 (IQR 35–45) years. Most (1693 (76.9%)) preferred HPV self-sampling or had no preference for either method and 508 (23.1%) preferred clinician-sampling. Factors associated with an increased likelihood of reporting a clinician-sampling preference were tertiary educational level (14.4% CI: 12.8–16.1 vs 29.5% CI: 25.6–33.6) and being an employee with higher grade professional or managerial occupations (5.5% CI: 3.8–7.9 vs 2.6% CI: 2.3–2.8). The main reported reason for women preferring clinician-sampling was a lack of “self-expertise”. Most women (>99%) would agree to repeat HPV self-sampling and would recommend it to their relatives. HPV self-sampling in the cultural context of central Africa was well accepted by participants, but some participants would prefer to undergo clinician sampling. Health systems should support well-educated women to increase self-confidence in using HPV self-sampling.
REVIEW | doi:10.20944/preprints202109.0446.v2
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: ischemic stroke; safety; cerebrolysin; neurorehabilitation
Online: 15 November 2021 (10:46:02 CET)
We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis was conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p>0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.
Fri, 12 November 2021
ARTICLE | doi:10.20944/preprints202111.0237.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Colorectal cancer; Cerebrovascular-specific mortality; Cerebrovascular-specific diseases; Incidence; Risk factors
Online: 12 November 2021 (16:47:45 CET)
Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.
ARTICLE | doi:10.20944/preprints202111.0229.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Total metabolic tumor volume; bone marrow to liver ratio; PET/CT; overall survival; immunotherapy; immune checkpoint inhibitor; standardized uptake value; response prediction
Online: 12 November 2021 (14:59:35 CET)
Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.
ARTICLE | doi:10.20944/preprints202111.0222.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Takayasu arteritis; echocardiography; immune cell infiltration; vascular stiffness; T helper like cells; regulatory T lymphocytes
Online: 12 November 2021 (13:40:14 CET)
Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.
ARTICLE | doi:10.20944/preprints202111.0219.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Diabetic Ketoacidosis; Mental health; Type 1 diabetes; Transition; Glycemia
Online: 12 November 2021 (12:04:43 CET)
The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .
ARTICLE | doi:10.20944/preprints202111.0217.v1
Subject: Medicine & Pharmacology, Other Keywords: Diabetes Technology; CGM; Accuracy; Type 1 Diabetes; Sustainability
Online: 12 November 2021 (11:58:57 CET)
Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.
REVIEW | doi:10.20944/preprints202111.0090.v2
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: adipose-derived regenerative cells; ADRCs; adipose-derived stem cells; ADSCs; bone regeneration, cartilage regeneration; efficacy; point of care treatment; stem cell; tendon healing without scar formation; tendon regeneration; vaPS cells
Online: 12 November 2021 (11:44:31 CET)
Background: Recently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine. Methods: Based on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible. Results: The ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient’s body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells). Conclusions: The use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which - albeit less efficiently - also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.
REVIEW | doi:10.20944/preprints202111.0216.v1
Online: 12 November 2021 (11:37:40 CET)
MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.
Thu, 11 November 2021
ARTICLE | doi:10.20944/preprints202111.0210.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: CRISPR-Cas, Nucleic acid detection, Klebsiella pneumonia
Online: 11 November 2021 (12:57:06 CET)
Klebsiella pneumonia (K. pneumoniae) is a Gram-negative bacterium that causes nosocomial infections in the lung, bloodstream, and urinary tract. Therefore, detecting K. pneumoniae in early time is important in preventing severe infections. However, clinical detection of K. pneumoniae requires a long time of agar plate culture. Nucleic acid detection like qPCR is precise but requires expensive equipment. Recent research reveals that collateral cleavage activity of CRISPR-LbCas12a has been applied in nucleic acid detection. In this study, PCR combined with CRISPR-LbCas12a targeting the K. pneumoniae system was established. This system showed excellent detection specificity and sensitivity in both bench work and clinical samples. Due to its advantages, its application can meet different detection requirements in health centers where qPCR is not accessible.
Wed, 10 November 2021
REVIEW | doi:10.20944/preprints202111.0207.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: exercise intensity; training impulse; training strain; exercise volume
Online: 10 November 2021 (14:30:55 CET)
The International System of Units (SI) was adopted in 1960 as a universal measuring system to be used for all areas of science. Sports Science papers have shown lots of inaccurate and inappropriate terms for quantification of athletes’ performance and the psychobiological responses to exercise (e.g., internal load). In biomechanics, external and internal loads are forces acting externally and internally, inducing stress and strain in the biological tissues. Therefore, the current review present simple proposals to correct the inappropriate terms: 1) do not use the term external load when referring to the assessment of exercise time, distance, displacement, speed, velocity, acceleration, torque, work, power, impulse, etc.; 2) do not use the term internal load when referring to the assessment of psychobiological stress markers (i.e., session rating of perceived exertion, heart rate, blood lactate, oxygen consumption, etc.); 3) do not use the term impulse when expressing other calculus than integrating force with respect to time, and neither strain, when expressing other phenomena than the body deformation. Instead, the term exercise intensity is universal and can be used to describe all forms of exercise. Finally, duration should precisely be described according to physical quantities (e.g., time, distance, displacement, speed, velocity, acceleration, force, torque, work, power, impulse, etc.) and the units accomplish by use of the SI. These simple quantifications can be performed for the exercises, sessions, microcycles, mesocycles and macrocycles of the athletes. Such standardization will provide a consistent and clear communication among sports scientists and all areas of science.
REVIEW | doi:10.20944/preprints202109.0453.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: boron neutron capture therapy (BNCT); boron imaging; biological dosimetry; radiation therapy
Online: 10 November 2021 (14:29:43 CET)
The success of boron neutron capture therapy (BNCT) depends mainly on sufficient spatial biodistribution of boron (B-10) localized around or within neoplastic cells to produce a high dose gradient between the tumor and healthy tissue. Contrary to what is usual in radiotherapy, BNCT proposes treatment planning directed at the cell rather than the tumor mass. However, it is not yet possible to precisely determine the concentration of B-10 in a specific tissue in real-time using non-invasive methods. Some critical issues still need to be resolved if BNCT is to become a valuable, minimally invasive, and efficient cancer treatment. This review article provides an overview of the funda-mental principles, recent advances, and future directions of BNCT as a cell-targeted cancer therapy. The main emphasis is on topics related to biological dosimetry, methods for assessing boron concentration, mechanisms of action of BNCT, and its physical bases for clinical implementation.
REVIEW | doi:10.20944/preprints202111.0201.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: psychedelics; language; consciousness; cognition; pharmacology; semantics
Online: 10 November 2021 (09:45:20 CET)
Psychedelics are drugs capable of eliciting profound alterations in the subjective experience of the users, sometimes with long-lasting consequences. Because of this, psychedelic research tends to focus on human subjects, given their capacity to construct detailed narratives about the contents of their consciousness experiences. In spite of its relevance, the interaction between serotonergic psychedelics and language production is comparatively understudied in the recent literature. This review is focused on two aspects of this interaction: how the acute effects of psychedelic drugs impact on speech organization regardless of its semantic content, and how to characterize the subjective effects of psychedelic drugs by analyzing the semantic content of written retrospective reports. We show that the computational characterization of language production is an emergent powerful tool to predict the therapeutic outcome of individual experiences, relate the effects elicited by psychedelics with those associated with other altered states of consciousness, draw comparisons between the psychedelic state and the symptomatology of certain psychiatric disorders, and investigate the neurochemical profile and mechanism of action of different psychedelic drugs. We conclude that researchers studying psychedelics can considerably expand the range of their potential scientific conclusions by analyzing brief interviews obtained before, during and after the acute effects. Finally, we list a series of questions and open problems that should be addressed to further consolidate this approach.
ARTICLE | doi:10.20944/preprints202111.0195.v1
Subject: Medicine & Pharmacology, Other Keywords: airway model; DPI; inhalation; aerosol testing; drug delivery; porcine lung
Online: 10 November 2021 (08:39:55 CET)