Abstract The aim of this research is to conduct a systematic review analysing the role of the physiotherapy interventions in palliative care. PRISMA as a critical appraisal tool was utilised for the selection of the research articles. The inclusion criteria were based on the year of publication, ease of availability, language, geographical location, and study type. To ensure the credibility, databases such as Elsevier, Proquest, and EBSCO Host were used to filter the grey content. Data published in the past ten years (2009-onwards) was only included to ensure the selection of the most recent interventions used by the physiotherapists. A total of 11 articles were selected which determined that physiotherapy interventions involving breathing exercises, aerobic exercises, manual therapies, and educational awareness were critical to promoting the functional capability and empower the patients.

The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 2 m from other persons to avoid the spread of COVID-19. The exposure to the bioaerosol can result in the deposition of the pathogen in the respiratory tract of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic diameter (size) of particles in carrying RNA copies of the novel coronavirus. A SARS-CoV-2 carrier person talking, sneezing, or coughing at distance of 2 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far from the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.

Coronavirus-infected diseases have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections. Our literature annotations identified 110 chemical drugs and 26 antibodies effective against at least one human coronavirus infection in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

Introduction: The term 3D printing is commonly used to depict an assembling method whereby the final form of an object is the result of the addition of different layers to build the frame of an object. This procedure is more accurately portrayed as additive manufacturing and is likewise alluded to as fast prototyping. The term 3D printing, in any case, is generally new and has been an active part of current developments in Dentistry. Much publicity encompasses the evolution of 3D printing, which is hailed as an innovation that will perpetually change CAM manufacturing, including in the dental sector. This review is the first part in a 3D Printing series that looks at the history of 3D Printing, the technologies available and reviews the literature relating to the accuracy of these technologies. Conclusions: The recent advancement in digital dentistry to incorporate these tools has modernised dental practices by paving the way for computer-aided design (CAD) technology and rapid prototyping. The use of 3D printing has led to 3D digital models produced with intraoral scanners (IOS), which can be manipulated easily for diagnosis, treatment planning, mockups, and a multitude of other uses. Combining 3D Printing with a 3D intraoral scan eliminates the need for physical storage but makes it to retrieve a 3D models for use within all dental modalities.

Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Materials & Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of 10 control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR) methods. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11,791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern. This study analyzed and discussed 70 research articles published until January 31, 2020 for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are effective for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Although these studies had relevance to control a public emergency, more research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short- and long- term.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

Baobab (Adansonia digitata) leaves are usually used in dry form in the preparation of a soup known as ‘miyan kuka’ in Northern Nigeria. The leaves are believed to have nutritional and medicinal benefits and have been used for those purposes in Africa and Asia. However there has been limited research on the detailed constituents of the dry leaves. In this study, phytochemical, elemental and proximate analyses of stored, sun and shade-dried baobab leaves were conducted. The results revealed a great variation in the nutritional contents of the leaves. The study reveals that the leaves are rich in phytochemicals such as glycosides, saponins, steroids and flavonoids while alkaloids, tannins and resins are absent. Also, they are important source of minerals such as zinc, copper, iron and manganese. In addition, they are rich in fibre, crude protein, nitrogen and ash. Contrasting responses were obtained in the samples studied. The implications of these responses are discussed in relation to crop yield.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. We investigated the incidence of objectively confirmed venous thromboembolism (VTE) in 198 hospitalized patients with COVID-19 in a single-center cohort study. Seventy-four patients (37%) were admitted to the intensive care unit (ICU). At time of data collection, 58 (29%) were still hospitalized and 14% had died. During a median follow-up of 5 days (IQR, 3-9), 33 patients (17%) were diagnosed with VTE of whom 22 (11%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7 and 14 days were 15% (95% CI, 9.3-22) and 34% (95% CI, 23-46), respectively. For symptomatic VTE, these were 11% (95% CI, 5.8-17) and 23% (95% CI, 14-33). VTE appeared to be associated with death (adjusted HR, 2.9; 95% CI, 1.02-8.0). The cumulative incidence of VTE was higher in the ICU (25% at 7 days 95% CI, 15-36, and 48% at 14 days, 95% CI, 33-61) than on the wards (any VTE and symptomatic VTE 6.5 % at 7 days (95% CI, 1.5-17) and 10% at 14 days (95% CI, 2.9-24)).The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Determination of antibody titre of dogs vaccinated against canine distemper in Jos North and South local Government Areas of Plateau State was carried out by collection of sera of vaccinated dogs and administration of well-structured questionnaires to dog owners. The samples collected were analyzed using the immune-blot ELISA Kit to determining the antibody titre (immunoglobulin G). It indicated that dogs vaccinated against the disease mounted adequate protective immunity. The result revealed that 54 (90.0%) of the sampled dogs have protective immunity, with those given more than one dose having higher level of protective antibody. Statistically, the result showed that the antibody titre did not differ significantly in relation to immunity and sex, breed, age and location but significant difference was seen in relation to number of primary vaccination. The result also revealed that those dogs that received booster doses (secondary vaccination) had more protective antibody. The study was aimed at evaluating the antibody titre of dogs vaccinated against canine distemper in Jos, Plateau State.

Background - Chronic kidney disease with unknown aetiology (CKDu) is a progressing disease which is affecting many Sri Lankans’ yearly, this disease is slow progressive, irreversible and asymptomatic disease. Patients suffering from CKDu over the past two decades have been evaluated using the estimated glomerular filtration rate (e-GFR). This is the standard test performed under WHO guidelines to investigate and grade the CKDu, and this creatinine clearance is measured in this in order to grade the patient. Backache has been a common symptom presented in most of the chronic kidney disease patients (CKD), patients with CKDu are liable to get backache due to the renal failure that takes place (Jayathilake et al., 2013; Redmon et al., 2016). Objective – To detect a correlation between serum creatinine values and level of backache presented in the patient. Method -Using an interview based questionnaire to assess patients’ body condition and the degree of backache is assessed, 59 patients were part of the study for a period of five months and had an average age of 60.3 years. The questionnaire answers are scaled into four main types of backache from the least to the most painful based on the pain scale adapted from Kapkia. Serum creatinine is measured using an automated analyzer which is measured using Jaffe’s reaction. Using Pearson R correlation, the relationship was determined between serum creatinine and backache (Kafkia et al., 2011). Results – The results were obtained for 58 patients (n=58), where the mean backache score was 2.30 and mean serum creatinine value 2.77. The Pearson R value obtained was 0.01 which is indicating almost no relationship between backache and serum creatinine. Patients with stage 3 kidney disease (n=14) had an average E-GFR of 38.0, stage 4 (n=38) with 22.3 and stage 5 (n=6) with 14.0. Conclusion – Backache can be used an indicator of CKDu since it is presented in most patients’ suffering from the disease but unable to be used to determine the stage of CKDu suffered by the patient due to the external causes that leads to backache. Several predisposing factors such as temperature, water source and agricultural activity can influence the backache.

Pneumonia caused by a new coronavirus SARS-CoV-2 has caused serious harm to people's lives and health in Wuhan, China. By February 26, 2020, over 80,000 people were infected and 2,814 died from the infection. The initial route of infection is the binding of the spike protein (S protein) of the virus to the angiotensin-converting enzyme 2 (ACE2). From bioinformatics analysis, we found that the S protein of SARS-CoV-2 produced an evolutionary mutation of K403R compared with the S protein of SARS-CoV, forming an adjacent RGD motif at the interaction surface. As the RGD motif is considered as a ligand for many cell surface integrins, we proposed that the binding of S protein of SARS-CoV-2 with integrins may facilitate the infection process of the virus. Therefore, high-throughput virtual screening was performed by choosing the key residues of S protein interface of SARS-CoV-2 and the adjacent RGD motif as potential binding site, to search for the potential agents targeting interaction of S protein of SARS-CoV-2 with both ACE2 and integrins as potential therapeutic drugs. Various libraries including the FDA-approved drugs etc. were screened, and Nadide, Losartan, 9'''-Methyllithospermate B and Leonurine etc. were identified as representative potential drugs candidate for COVID-19.

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic for which there is no established treatment available yet, has caused more than 68,000 deaths so far. Following the SARS-CoV outbreak in 2003, an Italian group described a hypothesis about the efficacy of two old drugs: Chloroquine (CQ) and Hydroxychloroquine (HCQ), against SARS-CoV and its future emergents. Later, this hypothesis was shown to be relevant in-vitro. Due to the high genetic similarity of SARS-CoV-2 and SARS-CoV, the hypothesis introduced by Savarino et al. and the further supportive in-vitro evidence served a rational ground for three different Chinese groups to test the efficacy of CQ or HCQ against SARS-CoV-2 in-vitro. These studies showed promising in-vitro efficacy of CQ and HCQ against SARS-CoV-2. Unfortunately, in the absence of sufficient clinical data on the (in)efficacy of CQ and HCQ in SARS-CoV-2 patients, the compassionate and off-label use of these medications is becoming politicized. Herein, we underline some critical features of the CQ/HCQ mechanism of action concerning SARS-CoV-2. Moreover, we put forward a hypothesis based on three lines of evidence on a probable link between zinc-deficiency/zinc correction and response to CQ/HCQ- and possibly other SARS-CoV-2 treatments.

Reliable methods to confirm the diagnosis of COVID-19 are essential to the successful management and containment of the virus. Current diagnostic options are limited in type, supply, and reliability. This article explores the controversial unreliability of existing diagnostic methods and maintains that more reliable diagnostic methods, combinations, and sequencing are necessary to effectively assist in reducing the occurrence of discharge of the patient on false negative test results. This reduction would in effect reduce transmission of the disease.

A novel coronavirus (SARS-CoV-2) that is initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has killed 2,718 people in China by February 26, 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS-Cov-2 infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS, two homologous models were established for virtual screening in the present study, namely NSP12-NSP7 interface model and NSP12-NSP8 interface model. Seven compounds (Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All seven compounds can combine well with NSP12-NSP7-NSP8 in the homologous model, providing drug candidates for the treatment and prevention of SARS-CoV-2.

In the end of April nearly 100 cases of children aged between 6 month and 9 years with Kawasaki like disease were reported (mostly in Europe) probably linked to COVID-19. With the increasing awareness of this condition the number of cases reported is increasing worldwide. We aim to sum up the known data about this new entity based on published data (in a case report, a series of 8 cases and in newspapers and society statement) and using our knowledge of classical Kawasaki disease. It seems to be a post infectious disease with an onset between 2-4 weeks after the infection, probably in genetically predisposed children aged between 6 month to 17 years. A very rough estimation of incidence based on current data from Bergamo, Italy, and New York State and a lot assumption is between 0.016% (95% CI:0.013-0.02%) - 0.31% (95% CI: 0.2-0.47%) of infected children. Clinical signs overlaps with Kawasaki disease in some children, but another feature is prominent gastrointestinal manifestations. For the 9 detailed patients most had incomplete presentation for Kawasaki disease (with a mean 1.7 (+/-1.2) criteria per patient for the 5 non fever criterion) and only one had a classical form. In some cases, presentation is closer to toxic shock syndrome or isolated myocarditis. Persistent fever seems to be constant and biological exploration are consistent with inflammation (elevated CRP, ferritin and D-Dimers). Management is described as supportive and children seem to improve rapidly, but can require cardiac or respiratory support. In date of 11 may 2020 there is 4 deaths confirmed linked to these new entities (1 in UK and 3 in New York). Paediatricians and general practitioners need to be aware of these possible evolution following COVID-19 infection. However it seems to be rare and children are probably still spared from most morbidities and mortality linked to COVID-19 infection .There are need of published detailed cohorts to better delineate these entities.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation is Science and Technology (COST) (https://www.cost.eu/cost-actions/what-are-cost-actions/ ) - COST action 15111 - from 2016 to 2020. The main goal of the Cost Action was to assess the existing fragmented knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report on the recommendations for clinical diagnosis, heath services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS (https://www.cost.eu/actions/CA15111/#tabs|Name:overview).

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

The SARS-CoV-2 was confirmed to cause the regional outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. The 3C-like protease (3CL^pro), an essential enzyme for viral replication, is a valid target to compacts SARS-CoV and MERS-CoV. In this research, an integrated library consisting of 1000 compounds from Asinex Focused Covalent (AFCL) library and 16 FDA-approved protease inhibitors were screened against SARS-CoV-2 3CL^pro. Top compounds with significant docking scores and making stable interactions with catalytic dyad residues were obtained. The screening results in identification of compound 621 from AFCL library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of SARS-CoV-2 3CL^pro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CL^pro were characterized using 50 nanoseconds (ns) molecular dynamic (MD) simulation approach. The identified compounds are potential inhibitors worthy of further development as SARS-CoV-2 3CLpro inhibitors/drugs. Importantly, the identified FDA-approved therapeutics could be ready for clinical trials to treat infected patients and help to curb the COVID-19.

Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cell line than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC₅₀ values against these cancer cells were approximately 10000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Imidazoline derivatives, such as xylometazoline, naphazoline, tetryzoline, tramazoline or oxymetazoline play an important pharmacological role as nasal drops in the symptomatic treatment of rhinitis. When comparing the toxicological data of these substances, it is noticeable that Oxymetazoline has an LD₅₀ value which is two orders of magnitude lower than all other imidazoline derivatives. Thus, ten vials of commercially available oxymetazoline nasal drops already contain a lethal amount. An explanation for this unusually high toxicity has not yet been found.

The designed radar sensor realizes the healthcare monitoring capable of short-range to detect the chest-wall movement of the subject caused by cardiopulmonary activities, and wirelessly estimating the distance from the sensor to the subject without any devices being attached to the body. Ensemble empirical mode decomposition (EEMD) based denoise method and 1-D continuous-wavelet transform (CWT) are applied for improving on the detection SNR so that accurate respiration rate and heartbeat rate can be acquired in time domain or frequency domain with further distance. No choosing the conventional Doppler radar only able to capture the Doppler signatures due to the lack of bandwidth information as noncontact sensor, we take full advantages of ultra-wideband (UWB) impulse radar to make it low power consumed and portable conveniently, with flexible detection range and preferable accuracy. This noncontact healthcare sensor system addressed proves the commercial feasibility and vast availability of using compact impulse radar for emerging biomedical applications. Compared with traditional contact measurement devices, experimental results utilizing the 2.3 GHz bandwidth transceiver, demonstrate 100% similar results.

This article offers an overview of congenital and acquired vascular anomalies involving the portal venous system in dogs and cats, as determined by multidetector-row computed tomography angiography. Congenital absence of the portal vein, portal vein hypoplasia, portal vein thrombosis and portal collaterals are described. Portal collaterals are further discussed as high- and low-flow connections, and categorized in hepatic arterioportal malformation, arteriovenous fistula, end-to-side and side-to-side congenital portosystemic shunts, acquired portosystemic shunts, cavoportal and porto-portal collaterals. Knowledge of different portal system anomalies helps understand the underlying physiopathological mechanism and is essential for surgical and interventional approaches.

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent pre-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .

Coronaviruses such as SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome), and newly emerged SARS-CoV-2, also called 2019-nCoV and COVID 19, have caused worldwide outbreaks in different time periods. There are many studies about chemical and natural drugs to treat these coronaviruses by inhibiting their proteases or their protein receptors through binding to amino acid residues. Plants secondary and primary metabolites are considered as potential drugs to inhibit various types of coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity) and molecular docking score and binding energy are parameters to understand the metabolites ability to inhibit the specific virus. In this study we did review on more than 110 papers on plant metabolites effect on different coronaviruses. Secondary plant metabolites such as polyphenols (flavonoids, coumarins, stilbenes), alkaloids, terpenoids, organosulfur compounds saponins, saikosaponins, lectins, essential oils, nicotianamine and primary metabolites such as vitamins.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Ever since pharmacy has become a profession, pharmacist's role has been continuously subjected to changes due to specific influences from historical, socio-economic, political, and scientific context. Nowadays the classic perception of pharmaceutical profession in Community Pharmacy is facing worldwide extinction due to many factors. Modern services, such as online, mail-order, and telephone-order pharmacies are increasingly gaining ground thanks to their ability to facilitate customer demand. However, at the same time, they are endangering “face-to-face” contact, affecting the building of customer loyalty based on direct “human” interaction, and consequently reducing pharmacists to mere commercial figures. Communication is in fact emphasized as the essential element to build a solid and appropriate interpersonal relationship with the client, to make the consultancy process effective, and to strengthen pharmacist's professionalism in community pharmacy. The aim of this work is to analyze pharmacist’s role in modern society by pinpointing the factors affecting pharmacy profession practice. Specific purpose will be improving both the academic training of future professionals and their capacity to approach public relations through a deepened study and practice of behavioral, communication, educational, and sociological methodologies and techniques that would allow the development of more effective communication skills useful for providing an efficient consultancy service.

For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

Background: The prevalence of postpartum haemorrhage (PPH) is increasing globally that is from 6.5% in 2000 to 11% in 2016. But there are regional variations where there is decrease of PPH in some parts of Asia and increase in Africa and developed countries. Objectives: The main objective of this study was to assess the prevalence, causes and associated factors for postpartum haemorrhage at St. Joseph referral hospital in Peramiho- Songea from November 2017 to December 2019. Method: The retrospective cross-sectional hospital-based study was used and data was obtained from maternity hospital registry book/data base of St. Joseph mission hospital in Peramiho Songea, from November 2017 to November 2019. Descriptive data was analysed by tables and graphs. Results: The prevalence of PPH in Peramiho referral hospital was 1.3% in 2017, 1.26% in 2018 and 1.4% in 2019. The overage prevalence for the three years is 1.3%. However, 73.3% of total prevalence is from home deliveries in rural areas. The main cause of PPH in the hospital was uterus atony (42%), retained placenta (15.5%), 3^rd and 4^th grade tears (11.2%), uterine rupture (8.1%) and coagulopathy (5.6%). The main attributing factors were age >35years (34%), other antenatal pregnancy complication (27%), previous PPH (18.6%), Antenatal anaemia (16%), placenta previa, Eclampsia, preeclampsia (12%) each. Conclusion: The prevalence of PPH from this study is slightly high with the main cause being uterine atony and affected mainly those undergone SVD where about two quarter were home deliveries. However further research studies are needed to investigate the main reason for higher home deliveries in Peramiho residence and nearby area.

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, is unprecedented in recent history and threatens the lives and livelihoods of billions worldwide. The rapid spread and lack of modern parallels have left governments, health agencies, and the public racing to understand how to best mitigate and ultimately suppress the pandemic, but we are still working to understand the strengths and weaknesses of various interventions at our disposal. Few issues have been as contentious as the public use of face masks to control the pandemic’s spread. There is ongoing debate about their effectiveness, but an increasing body of evidence suggests that masks could be a useful in preventing the spread of coronavirus, leading several governments and health agencies to review and revise their policies. Here, we review the theory and evidence behind use of masks. The theory behind masks is that they prevent the spread of viral particles by infected persons, and inhalation of viral particles by uninfected persons. Even assuming masks are not 100% effective in preventing infection, they may reduce severity of infection by reducing viral dosing. Laboratory studies suggest masks may be effective in stopping both exhalation and inhalation of viral particles. However, real-world studies provided limited evidence for the use of masks in controlling influenza transmission and highlight potential problems associated with their misuse, such as poor compliance or improper use. Evidence for efficacy of face masks against the first SARS virus, SARS-CoV-1, implies that they may be effective against the current outbreak of SARS-Cov-2 virus. This is important as mathematical modeling suggests that even small reductions of in transmission rates can make a large difference over time, potentially slowing the pace of viral pandemics and limiting their spread. Perhaps the strongest argument for the use of masks is that countries with early adoption of masks have tended to see flatter pandemic curves, even without strict nationwide lockdowns. There is little evidence that respirators are more effective than surgical masks, but this may be due to misuse or poor compliance. Studies suggest some non-medical masks perform on par with medical masks. Improvised masks are less effective than medical masks, but may provide better protection than nothing at all. While many governments now encourage the use of improvised face coverings, more will need to be known about material, design, and who needs to wear masks, and when, to ensure effectiveness. Proper use of masks will also be important; if masks are used improperly or infrequently they may provide limited protection. It is important that public health policy makers consider the debate and the potential of masks as part of multi-faceted coronavirus control strategies.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

Plant-based alternative medicine is normally grounded on empiric cultural perception, as the main objective, these practices intent to either maintain good health or to provide a route to turn-the-tide on a specific disease or ailment. Amongst the thousands of plants that have been used and studied, Neem (Azadirachta indica) seems to have a very interesting tale to tell, since its properties to ward-off certain diseases have overtime, and in a rigorous way, been proven. The preceding concise review is a collection of some of the most relevant studies today, not only focusing on the health benefits obtained by its use, but digging into the molecular mechanisms of how the properties come about. In particular, we take a look over antioxidant properties and how these mediate and mitigate important molecules such as IL-6 and TNF-, leading the way in reducing systematic damage by oxidative stress. Further, we relate this oxidative reduction to other systemic diseases such as cancer and diabetes, as these are currently becoming the most rampant killers. As of yet not all is known about the different ways of extracting or the total composition of an extract, as these may be from different parts of the plant. Therefore, we also allude to an important cautionary view where toxicological effects and conflicting outcomes arise. Overall, presented results show a great potential for the different extracts of Neem as their antioxidant activity can be taken advantage off, and potentially used in modern medicine.

The world is facing a major health crisis, the global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus, for which no approved antiviral agents or vaccines are currently available. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available via Addgene. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

Tarsal tunnel syndrome is a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches. Brief mention is made in the literature of the use of corticosteroid injections for this condition. The basic technique of hydrodissection is used for other nerve entrapments and includes identifying the region of nerve compression, and the injection of a fluid medium to dissect between structures or fascial planes. We introduce our treatment protocol using a methylprednisolone/sterile water/ropivacaine hydrochloride injectate mix and peripheral nerve stimulation to a perform hydrodissection technique for tarsal tunnel syndrome.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from January to May 2022 were retrospectively collected and analyzed according to age groups and vaccination status and the relative risk (RR) for all-cause mortality was calculated in comparison to the corresponding unvaccinated groups. All-cause mortality RR was also calculated from January to May 2021 for vaccinated people. Results show that the all-cause mortality RR was higher in people who received one or two doses of COVID-19 vaccines throughout the whole period and in any of the age groups considered. People vaccinated with three doses more than 21 days earlier had RRs lower than unvaccinated people, which however linearly increased over time. RR in vaccinated people of all ages in comparison to unvaccinated people were lower in January-May 2021, however they steadily grew over time. The finding that all-cause mortality RR in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, all the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and mass vaccination campaigns should be suspended.

Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.

There is a relatively high risk of virus transmission in dental procedures and oropharyngeal examinations. We investigated the effects of mouthwashes on covid-19 viral load reduction during dental practices and oro-pharyngeal assessments. We performed a systematic search in PubMed, EMBASE, Scopus, Web of Science, Cochrane library for relevant studies up to February 2021. Papers evaluating patients with covid-19 infection (patients) who rinse mouthwashes (intervention) compared to patients who don’t rinse them (comparison) for reducing covid-19 viral load or reducing cross-infection of covid-19 (outcome) in the randomized and non-randomized clinical trial and quasi-experimental studies (study) were included due to PICOS question. Three independent authors conducted literature screening and data extraction. We extracted the most relevant data and we evaluated the risk of bias from the included studies. Out of 344 potentially eligible articles, six studies were included in this systematic review. Regarding viral load and negative cycle threshold (ct) values, 1% PVP_I and Listerine mouthwash were effective. 0.12% CHX mouthwash was effective 0-2 hours post rinsing, but it was not effective after 2 hours. A mixture solution of 0.2% Chlorhexidine gluconate and 6% Hydrogen peroxide was effective on day 5 of intervention. Gargling 1% hydrogen peroxide, 0.075% Cetylpiridinum Chloride (CPC), 0.5%PVP-I and 0.2% CHX mouthwashes was not effective on SARS-COV-2. It cannot be guaranteed that rinsing a specific kind of mouthwash prevents cross-infection of covid-19; however, the viral load of SARS-COV-2 in saliva will be decreased after rinsing mouthwashes containing 1%PVP-I and Listerine.

The beginning of 2020 has seen the emergence of coronavirus outbreak caused by a novel virus called SARS-CoV-2. The sudden explosion and uncontrolled worldwide spread of COVID-19 show the limitations of existing healthcare systems to timely handle public health emergencies. In such contexts, innovative technologies such as blockchain and Artificial Intelligence (AI) have emerged as promising solutions for fighting coronavirus epidemic. On the one hand, blockchain can combat pandemics by enabling early detection of outbreaks, protecting user privacy, and ensuring reliable medical supply chain during the outbreak tracking. On the other hand, AI provides intelligent solutions for identifying symptoms caused by coronavirus for treatments and supporting drug manufacturing. Motivated by these, in this paper we present an extensive survey on the use of blockchain and AI for combating coronavirus (COVID-19) epidemics based on the rapidly emerging literature. First, we introduce a new conceptual architecture which integrates blockchain and AI specific for COVID-19 fighting. Particularly, we highlight the key solutions that blockchain and AI can provide to combat the COVID-19 outbreak. Then, we survey the latest research efforts on the use of blockchain and AI for COVID-19 fighting in a wide range of applications. The newly emerging projects and use cases enabled by these technologies to deal with coronavirus pandemic are also presented. Finally, we point out challenges and future directions that motivate more research efforts to deal with future coronavirus-like epidemics.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. In addition, it is the largest ionic calcium reservoir in cells, tightly regulating the levels of this second messenger according to cellular necessities. Disturbed ER homeostasis triggers the activation of an intricate and conserved molecular machinery, termed the unfolded protein response (UPR). Given the impact of this signaling network upon an extensive list of cellular processes, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the tools available design a study of this nature.

There is an urgent need to advance safe and affordable COVID-19 vaccines for low- and middle-income countries of Asia, Africa and Latin America. Such vaccines rely on proven technologies such as recombinant protein-based vaccines to facilitate its transfer for emerging market vaccine manufacturers. Our group is developing a two-pronged approach to advance recombinant protein-based vaccines to prevent COVID-19 caused by SARS CoV2 and other coronavirus infections. One vaccine is based on a yeast-derived (Pichia pastoris) recombinant protein comprised of the receptor binding domain (RBD) of the SARS-CoV formulated on alum and referred to as the CoV RBD219-N1 Vaccine. Potentially this vaccine could be used as a heterologous vaccine against COVID-19. A second vaccine specific for COVID-19 is also being advanced using the corresponding RBD of SARS-CoV-2. The first antigen has already undergone cGMP manufacture and is therefore “shovel ready” for advancing into clinical trials, following vialing and required GLP toxicology testing. Evidence for its potential efficacy to cross-protect against SARS-CoV-2 includes cross-neutralization and binding studies using polyclonal and monoclonal antibodies. Evidence in support of its safety profile include our internal assessments in a mouse challenge model using a lethal mouse adapted SARS strain, which show that SARS-CoV RBD 291N1 (when adsorbed to Alhydrogel®) does not elicit eosinophilic lung pathology. Together these findings suggest that recombinant protein-based vaccines based on the RBD warrant further development to prevent SARS, COVID-19 or other coronaviruses of pandemic potential.

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

Diabetes mellitus is the fifth deadliest disease in the developing countries. Even with all the research and new drugs available, combating diabetes is still challenging. There are successes in finding new cost effective drugs without side effects, even if not perfect. In our investigation we studied binding mechanism of secondary metabolite of T. chebula in silico. It was observed that three compounds out of 16 have a higher binding affinity for the target proteins. Ellagic acid showed highest binding affinity with alpha amylase, beta glucosidase and alpha glucosidase with lesser binding energies -4.5kcal/mol, -5.36kcal/mol and -4.48kcal/mol respectively. Arjungenin has lesser binding energy of 4.77 kcal/mol with glucokinase while luteoline has binding energy of -7.25kcal/mol for enzyme glycogen synthase kinase. These entire compounds interacted with non-covalent interaction. Petroleum ether extract showed the significant alpha amylase inhibitory activity i.e. 51.22% as compared to standard drug (65.99%).TLC analysis revealed the presence of total 9 compounds in different plant extracts one of them might be a lead compound which could be further exploited for the development of novel safer and potent antidiabetic drug.

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology and the role of interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, and metformin. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention for spike protein related diseases; with broad implications for human health. This review presents the therapeutic possibility of using autophagy to treat spike protein related diseases, and details the interventions to deploy this therapeutic modality.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

Nutrigenetics concerns individual differences in the reaction to food based on the genetic factors. Nutrigenomics analyses direct influences of nutrients on gene expression. Both terms are explained in our review article. Nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and of new ‘omic’ technologies. It is often difficult to appreciate their relevance in the practice of preventive approaches for optimizing health, delaying onset of disease and diminishing its severity. This paper represents a review about the current research on Nutrigenomics and Nutrigenetics, and provide scientific data for a new integrated clinical approach.

POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

During the period of health emergency linked to the current COVID-19 pandemic, the management of children's oral health presents specific problems related to the infectious spread of the disease. These problems must be faced on the one hand by acting on the oral health prevention methods, and on the other by implementing specific protocols relating both to the conditions of oral pathologies that normally do not represent an emergency, and to those clinical situations that fall into the category of pediatric dental emergencies. In this perspective, in addition to defining rigorous and highly effective infection control protocols in the dental settings, it is of fundamental importance to work on remote communication and education aimed at maintaining the oral health of the children. This article, after an analysis of the risk factors from COVID-19 associated with pediatric dental treatment, presents a series of considerations on potential oral prevention strategies and on the management of emergency and non-emergency dental procedures in a context of disease transmission control, proposing new approaches and models of treatment based also on remote interaction techniques which will then retain their usefulness even at the end of the current emergency period.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.

Play therapy is an approach to providing assistance in overcoming problems using media such as toys, art media, games, and communication. The purpose of this paper is to find out that play therapy can reduce anxiety in children. The research design used in this study was a study-literature review. The data used in this research comes from the results of research that have been conducted and published in national and international online journals. The method of analysis used in this study is the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) method.

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

Snakebite envenomation, cognized as a neglected tropical disease, is a dread public health concern with the most susceptible groups being herdsmen, the elderly, active farmers, hunters, fishers, firewood collectors, 10 to 14-year old working children and individuals with limited access to education and health care. Snakebites are fragmentarily documented in Uganda primarily because most occur in rural settings where traditional therapists end up being the first line defence for treatment. Ethnobotanical surveys in Uganda have unveiled that some plants are used to antagonize the activity of various snake venoms. This review was sought to compile the sporadic information on the vegetal species reported as antivenins in Uganda. Electronic data indicate that no study entirely reported on antivenin plants in Uganda. A total of 77 plant species belonging to 65 genera, distributed among 42 botanical families claimed as antiophidic in Uganda are used for treatment of snakebites. Majority of these species belong to family Fabaceae (30.9%), Euphorbiaceae (14.3%), Asteraceae (11.9%), Amaryllidaceae (9.5%) and Solanaceae (9.5%). The antiophidic species listed are shrubs (40.5%), trees (32.9%) and herbs (17.7%), usually found in the wild and uncultivated. Antivenin extracts are primarily prepared from roots and leaves, through decoctions, infusions, powders and juices and administered orally or topically. The most frequently encountered therapeutically important species are Allium cepa L., Carica papaya L., Securidaca longipedunculata Fres., Harrisonia abyssinica Oliv. and Nicotiana tabacum L. Baseline epidemiological data on snake envenomation and antivenin plants in Uganda remain incomplete due to inadequate research and diverse ethnic groups in the country. There is a dire need to isolate and characterize the bioactive compounds in the claimed plants to enable their adroit utilization in handling the plague of snake envenomation. More baseline data should be collected on snake ecology and human behaviour as well as antivenin plants in Uganda. Indigenous knowledge on the use of plant preparations in traditional medicine in Uganda is humongous, but if this is not quickly researched and appropriately documented, indications as to the usefulness of this vegetal treasure house will be lost in the not so distant future.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Evidence has shown that the state of the patient care environment has a direct impact in heightening the risks of hospital acquired infections among patients admitted in hospitals. And in view of the sub-optimal standard of cleanings by housekeeping staff, the quest for a better approach to reliably disinfect environmental surfaces in healthcare facilities. The ultraviolet light has been known for its antimicrobial property, and have been used in water treatment, food processing and in-duct cleaning of ventilations. A recent introduction of its use for surface decontamination has raised interest among hospitals.However, studies have shown that, in spite of its relative success in other applications, there is doubt in its efficacy in decontaminating shadowed areas of the room, and therefore, would not be seen as justifying its capital intensiveness.

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

SHANK3 encodes scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+inhibitory neurons – the key players in generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response(ASSR). Here we describe a clinical and neurophysiological phenotype of a 15-years old girl (SH01) with microduplication of 16389 bp in 22q13.33, affecting the SHANK3 gene in comparison to typically developing children (n=32). EEG were recorded during the binaurally presentation of 40-Hz clicks’ trains lasting for 500 ms with inter-trial intervals 500-800 ms. SH01 was diagnosed with mild mental retardation and learning disabilities(F70.88) and had problems with reading and writing, as well as smaller vocabulary than TD peers. Her clinical phenotype generally resembled the phenotype of previously described patients with 22q13.33 microduplication. SH01 had mild autistic symptoms but below the threshold for ASD diagnosis. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential(ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. Absence of 40-Hz ASSR in patient with microduplication, affected SHANK3 gene, indicates deficient temporal resolution of the auditory system, that might underlie language problems, and represent neurophysiological biomarker of SHANK3 abnormalities.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

Vernonia mespilifolia is widely used in folk medicine in the Eastern Cape Province, South Africa. The aim of this study was to evaluate the biological activity of the acetone, aqueous and ethanol extracts of Vernonia mespilifolia using brine shrimp hatchability and lethality assay. The result showed hatching success in this order: aqueous extract (48.6%) > acetone extract (38.2%) > ethanol extract (26.8%). The LC₅₀ of the lethality assay were in this order: acetone extract (67.8 µg/mL) > aqueous extract (132 µg/mL) > ethanol extract (383 µg/mL). According to Meyer’s toxicity index (using brine shrimps), LC₅₀ < 1000 µg/ mL is toxic. Therefore, the results of the three solvent extracts could be said to be toxic as do have LC₅₀ < 1000 µg/ mL. However, the toxicity of the crude extracts could suggest or confer some antitumor properties, hence further in vitro, in vivo and antitumour assays are recommended to further substantiate these claims.

The COVID-19 pandemic changed the world of medical education, moving it years ahead of time into the future. Many concepts needed to be changed, so did the methodologies. Nevertheless, clinical assessment remained tricky. This work highlights the outcome of the work of College of Medicine and Medical Sciences at the Arabian Gulf University in Bahrain in performing virtual clinical examination using Zoom™. Tips in this article are meant to help plan, implement and evaluate clinical assessments virtually.

Purpose: National Institute for Health and Care Excellence (NICE) has recently published quality standards for assessment of fall risk and preventing further falls. According to the standards, multifactorial fall risk assessments should include: identification of falls history; analysis of gait, balance, mobility and muscle strength, among other factors. Despite being based on subjective analysis or simple timing and not being multifactorial, physiotherapists and physicians quite often use these tests as reference scales to differentiate between lower and higher risk of falling. Instrumented TUG has been recently reported to provide important additional information to the overall score. Objective: To explore a case-based approach of fall risk assessment to identify the most relevant and informative risk factors that in combination could better define a person risk profile. Materials and Methods: A multifactorial assessment of fall risk through questionnaires, standard functional tests, tests instrumented with inertial sensors, and force platforms has been studied within a group aged 55-80 years old. Different fall risk factors and fall risk assessment methods were analyzed in a case-based descriptive study. Results & Discussion: Subjects at higher risk of falling were identified based on their detailed profiles. A set of features were obtained from the instrumented standard tests differing significantly between subjects presenting higher or lower fall risk. Therefore, instrumenting conventional tests with wearables containing inertial sensors and force platforms gives more detailed and quantitative insights. This information can be used to better define and tailor fall prevention exercises and to improve the follow-up of the evolution of the subject.

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

The spillover of a virus from one host species to another requires both molecular and ecological risk factors to align. While extensive research both before and after the emergence of SARS-CoV-2 in 2019 implicates horseshoe bat as the significant reservoir genus for the new coronavirus, it remains unclear why it emerged at this time. One massive disruption to human-animal contact in 2019 is linked to the on-going African swine fever virus (ASFV) pandemic. This began in Georgia in 2007 and was introduced to China in 2018. Pork is the major meat source in the Chinese diet. Severe fluctuations in the pork market prior to December 2019, may have increased the transmission of zoonotic pathogens, including severe acute respiratory syndrome–related coronaviruses, from wildlife to humans, wildlife to livestock and non-local animals to local animals. The major production and consumption regions for pork are geographically separated in China. The dramatic shortage of pork following restrictions of pig movement and culling resulted in price increases, leading to alternative sources of meat and unusual animal and meat movements nationwide often involving wildlife and thus greatly increased opportunities for human-Sarbecovirus contacts. Pork prices were particularly high in southern provinces (Guangdong, Guangxi, Fujian, Jiangxi, Hunan, and Hubei), where wildlife is farmed on different scales and more frequently consumed. Shandong experienced the biggest losses in pork production (~1.7 million metric tons), which is also the largest mink farming province. Hence, human exposure to SARS-CoV-2 from wildlife or infected animals are more likely to have taken place in 2019, when China was experiencing the worst effects of the ASFV pandemic.

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

The pharmacology of azithromycin, and the actions of certain bee products, suggest the possibility of overlap with the pathophysiology of COVID-19 at several points in the disease process. First, intercellular epithelial tight junctions of the respiratory tract serve as a critical barrier to invaders. Pathophysiological factors capable of disrupting this epithelial barrier include viral virulence factors such as those observed for other coronaviruses; virulence factors derived from potentially synergistic pathogens such as Candida albicans and Porphyramonas gingivalis; and imbalances in the host inflammatory response. Azithromycin, and to a lesser extent, certain bee products, appear to have actions that oppose such processes. Second, the matrikine PGP or its derivatives may contribute to risk in individuals at high risk for serious COVID-19 infection, especially during reactivation; but azithromycin is capable of modulating PGP in some contexts. Third, the most serious COVID-19 infections are associated with massive upregulation of inflammatory cytokines such as IL-6, TNF alpha, and other inflammatory cytokines. The anti inflammatory actions of azithromycin and bee derived products such as melittin are potentially capable of modulating these processes, as well. Azithromycin is already in current use as a treatment for COVID-19; however, it's utility as a protector of epithelial barrier function would be most likely to be realized in prophylactic context rather than in a treatment context. Similarly, since the anti inflammatory effects of bee products take time, their effectiveness of melittin and other bee products would be expected to be maximized in a prophylactic context. In the context of the current pandemic, prophylaxis with azithromycin, bee products, or both, might be warranted for individuals at high risk for serious COVID-19 infection.

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PF4) autoantibodies.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly which make noninvasive glucose sensors highly demanded. In this review paper, we discuss several advanced electromagnetic (EM) wave based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherent tomography (OCT) and microwave sensing. Development and progress of each method are discussed regarding fundamental principle, system setup and experimental results. Despite the promising achievements reported previously, there is no established product to obtain FDA approval or survive marketing test. Limitations and prospects of these techniques are discussed at the end of this review.

Spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) made a historic transition between December 2019 to March 2020. In the present scenario SARS-CoV-2 as becomes a major burden on public health and economic stability of societies around the globe. From the substantial evidences gained from the pandemic of SARS-CoV-2 and MERS-CoV (Middle East respiratory syndrome coronavirus), scientists and clinicians strongly believes that these pathogenic viruses share common homology of some biologically active enzymes which includes RNA-dependent RNA polymerase (RdRP), 3-chymotrypsin-like protease (3CL^pro), papain-like protease (PL^pro) etc. RdRP relatively grabs higher level of clinical importance in comparison with other enzyme target. Indian system of traditional medicine pioneering the therapy towards infectious disease since several centuries. In view of this potential therapeutic leads from some of the Indian medicines along with standard drug favipiravir subjected to docking investigation targeting SARS-CoV-2- RNA dependent RNA polymerase (RdRp). Residual proximity analysis reveals 18 out of 28 compounds reveals potential binding affinity of about 100% with the target amino acid residue (618 ASP, 760 ASP,761 ASP), 7 out of 28 reveals 75% binding efficacy and 3 out of 28 reveals 25% binding efficacy with that of the target residue. Hence further clinical validation may be warranted with proper in-vitro and in-vivo studies prior to the clinical recommendation in treating COVID-19 patient’s.

We are experiencing an unprecedented urbanization process that alongside with physical, social and economic developments is having a significant impact on population’s health. Due to higher apprehensions of pollution, violence and poverty, our modern cities no longer ensure a good quality of life so they become unhealthy environments. This study aims to measure the socio-environmental and hematologic profile of residents of Santo André’s landfill – “Bairro Espírito Santo” by using the contextualization of the studied area. The research method is Observational type and from Retrospective cohort and by convenience sampling in Santo André in the Greater ABC region. The study determined a socio environmental profile and the hematologic diseases screening related to a close location to the landfill. The disease manifests itself within a broad spectrum of symptoms that causes changes in blood count parameters. The full blood counts analysis was performed, indicating that the blood counts of residents living near the landfill led to positive hematological changes and diseases like Leukopenia, Anemia, Neutropenia and lymphocytosis were the most common changes. However it is considered that the proof of the relation of cause- effect to environmental exposures that may trigger chronic manifestations in humans requires specific studies that are often complicated.

Corona Virus disease 2019 (COVID-19) is a new strain of coronavirus that causes respiratory illnesses with a start of flu like symptoms. This disease is fatal and is spread all over the world. The Scientist are working day and night to find vaccine or a cure. World Health Organisation has declared COVID-19 as pandemic [1]. In the view of the pandemic many treatments are being tried on the patients and various treatment modalities are being followed, the traditional medicine has shown a major role to manage this disease. The traditional medicines include the use of herbs, nutrition and spices that are freely available in Asian countries. These are used in day to day life by Asian population [2]. In this paper we have compiled and reviewed the role of various herbs and spices such as Oregano, Ashwagandha, Ginseng, Basil, Sage, Curcumin, Fenugreek, Ginger and Garlic in building immunity and also in curing pathogenic invasions based on evidence based researches. As there is no cure available for COVID-19 till now so supportive therapy is playing a major role for the patients to fight with this pandemic. The AYUSH ministry has also promoted the use of above herbs for a patient suffering from this disease. The corona virus is present in respiratory system as shown by different studies and it has different strains. The guidelines laid by the ICMR and WHO shows that use of herbs, spices and nutrients can be helpful to manage this virus by increasing the immunity in patients. Hence we are not claiming any cures but the herbs and spices used in day to day life are very much effective in management of COVID-19. World Health Organisation (WHO) has recognised the use of alternative and traditional medicine in the management of COVID-19 but the herbs should be used in prescribed amounts and overdose of them can be harmful for health [1,3]. Therefore the present article will enlighten the readers about the role of herbs, spices and nutrients in improving the conditions in COVID-19.

The current report represents a case of a 77-year-old man with Parkinson’s disease who died three weeks after receiving his third COVID-19 vaccination in January 2022. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov- 19 vector vaccine, followed by two more doses with the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to the ambivalent clinical features noted before death. The underlying illness (Parkinson’s disease) was confirmed by autopsy. However, no sign of a florid COVID-19 was discovered. Meanwhile, the immunohistochemical staining of the brain and heart revealed previously undiagnosed conditions. The brain, in distinctive, revealed multifocal necrotizing encephalitis with massive inflammatory lymphocyte infiltrates. In addition, the heart showed signs of serious myocarditis. Finally, immunohistochemical staining revealed that the SARS-CoV-2 spike protein was evident in the tissues investigated. Based on these immunohistochemical findings, it appears that the inflammatory changes in the patient's brain tissues are most likely the result of immunological processes. Concurrently, the absence of SARS-CoV-2 nucleocapsid-protein was evidenced, indicating that the detected spike-protein is unrelated to a SARS-CoV-2 infection. If such an infection was the cause of the spike protein, the SARS-CoV-2 nucleocapsid protein would also be detectable. As a consequence, the confirmed presence of the spike protein had to be attributed to the previous vaccination with the BNT162b2 mRNA vaccine that the deceased patient had received.

Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot and cold stored parboiled rice to widely available medium grain white rice. Method: Twenty-eight healthy volunteers participated in a three treatment experiment where postprandial blood glucose was measured over 120 minutes after consumption of 140g of rice. Three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 ºC. All rice was served warm at 65 ºC. Chewing time was recorded. Results: The 24-hours cold-stored and reheated parboiled rice resulted in a 42% and 12% lower blood glucose concentration trajectory than freshly cooked medium-grain white rice and freshly cooked parboiled rice. Chewing time for 10g cold stored parboiled rice was 6 seconds (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium grain (all P<0.05). Conclusions:. For regular consumers of rice reheating cooked rice after cold storage would lower the dietary glycaemic load and long term may reduce risk for type 2 and gestational diabetes. More trials are needed to identify the significance.

Background: Meniere's disease (MD) has been recently linked to gluten assumption. Approximately 75% of MD patients show positive skin test to food and about 50% of the positive responses are specific to the gliadin acid extract fraction. Aim of this study was to investigate the humoral immune responses to wheat antigens and related autoantigens in MD patients. Methods. We assessed the reactivity of sera from 28 patients with definite MD and 100 healthy controls against a repertoire of 51 antigens usually associated with immune reaction to gluten. Results. MD patients showed an increase of anti-wheat IgA, anti-cerebellar peptide IgA and anti-glutamic acid decarboxylase (GAD) 65 IgM compared to healthy controls. In particular, the increase of anti-wheat IgA and GAD 65 IgM has been confirmed in a subgroup of MD patients symptomatically responding to a gluten free diet (GFD). Conclusion. In MD patients, an increase of the antibody production against gluten biomarkers was observed; in particular, anti-wheat IgA seems to be associated to clinical response to GFD.

Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers [1]. However, many lung cancers are diagnosed in never smokers [2], and most smokers do not develop lung cancer [3,4].

To address the question whether there is evidence that drinking water in general or mineral water in particular is effective in preventing diabetes; we performed a literature search of randomized controlled trials (PubMed). The search resulted in very few trials (N = 9) investigating this topic: one trial investigates the effect of increasing water consumption on glycemic control in diabetic patients; two trials investigate the effect of drinking water with a meal in diabetic patients; while six trials compare the effect of mineral rich water with that of low mineralized water on glucose metabolism in healthy subjects. There is evidence that increasing water consumption can improve glucose metabolism and randomized controlled trials with mineral water suggest that waters containing relevant amounts of magnesium can exert an additional effect. The role of bicarbonate; which is present in all the mineral waters used in the trials; will be discussed. Future research needs to investigate the effect of mineral water in prediabetic individuals or individuals with impaired glycemic control.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Globally, humans are struggling with the double threat of communicable and non-communicable diseases, which are presenting new challenges to public health. Public health problems are generally studied and addressed at primary, secondary and tertiary levels. Most effective results are seen with primary interventions. Public health is becoming more aware of the importance of environment-gene interactions in the ontology of health and disease using epigenetics. Epigenetics is the study of altered gene expression without change in base pairs. Be it physical, social, behavioral, or economic factors; they all influence quality of life and health of individuals and populations. That environments are changing the human health phenotype and these changed phenotypes are heritable is of concern for the future of the human race. Knowing the causes of non-communicable human diseases using epigenetics will contribute to the development of new policies to encourage prevention using primary public health initiatives. Research and application of epigenetics shows great promise for improving population health. Continued advances in epigenetics will enhance how we understand and address the way environments are affecting the human health phenotype. For some time, health systems have been and continue to be tertiary in nature. Epigenetic changes can provide information necessary to better understand how social determinants of health can be used to build societies focused on equitable health for all people, rather than continuing to focus on treatment of diseases in the tertiary phase that leads to health disparities. Understanding mechanisms of social determinants of disease, will allow society to evolve in a health-oriented rather than a disease-oriented world. For this reason, we must enhance and apply epigenetics (physical, social, behavioral, economic) research to policy development. We will discuss how bringing social determinants together with biology can be used as new tools for public health policy.