Mental stress represents a pivotal factor in cardiovascular diseases. The mechanism by which stress produces its deleterious effects is still under study but one of the most explored pathway is cell senescence. In this scenario, circulating microRNAs appear to be mobile regulatory elements of the telomerase activity and alternative splicing within the ”senectome” network. Anti-stress techniques seem to be able to slow-down aging process. As we have recently verified how the practice of Relaxation Response (RR), counteracting psychological stress, determines favorable changes of some inflammatory genes expression, of some neurotransmitters, hormones, cytokines and inflammatory circulating microRNAs, we aimed to verify a possible change even in serum levels of 4 senectome micro-RNAs (SE-miRNAs -20, -30, -410, -515), testing the activity of telomerase in peripheral blood mononuclear cells-PBMCs. We analyzed also alternative splicing microRNAs 134 and 183. According to our data, miRNA-20 and -30 levels and PBMCs-telomerase activity increase during the RR while -410 and -515 levels decrease. Moreover, during the RR sessions both miRNA-134 and -183 decrease. The mediators considered in this work seem to vary rapidly according to a (stress)-relaxation condition showing that psychic activity should be part of the study of aging factors.

We extend our high-resolution MRI-based Finite Element (FE) head model, previously presented and validated in [1–3], by considering the heterogeneities of the white matter structures captured through the use of Magnetic Resonance Elastography (MRE). This approach imparts more sophistication to our numerical model and yields results that more closely match experimental results. It is found that the peak pressure more closely matches the experiments as compared to the heterogeneous case. Qualitatively, we find differences in stress wave propagation near the corpus callosum and the corona radiata, which are stiffer on average than the global white matter. We are able to study the effects of these stiff structures on transient stress wave propagation within the cerebrum, something that cannot be done with a homogenized material model.

Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O₃SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18^rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O₃SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O₃SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O₃SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O₃SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O₃SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.

Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

Wearable computing is a fast evolving segment of computing that includes smart watches, head mounted wearables such as Magic Leap headsets, Microsoft Hololens, and VR goggles from various vendors. In this report, we present ideas for a smart wearable device that also doubles as a virus protection device. Instead of using the filtering approach that is predominantly used by virus protection equipments such as face masks, we propose to use a computational approach where the device maintains an awareness of the real-time virus spread and use that information to steer the wearer away from the virus. As the wearable has a head enclosing design, viral infection can only happen through the air that is inhaled by the wearer. The objective of the smart wearable is to maintain a repository for clean air and switch the operating modes between stored and fresh air modes depending on the environmental conditions. It can augment this basic operating procedure by recycling the exhaled air to maximize it operating capacity (i.e., time duration for which it could supply the wearer with safe air) and by cleaning the stored air using UVC to further reduces the chance of infection. To maintain an awareness of the virus spread in the environment, the smart wearable will rely on an edge computing framework that will be distributed to cover areas frequented by people. The smart wearable will have modular design so that it can be reconfigured to add or subtract functionality that the wearer wants for a particular situation so that the design remains relevant even after the virus threat recedes.

Covid-19 disease is caused by SARS Cov-2 virus. Despite its high transmissibility, the CFR (Case Fatality Rate) of COVID-19 seems to be lower than the SARS (9,5%) and MERS (34,4%) ones⁹³ , but higher than the influenza one (0-1%)^94,95 . The disease is asymptomatic or paucisymptomatic in most of the patients, although in few cases it can be characterized by serious complications. The main causes of hospitalization in intensive care are represented by ALI (Acute Lung Injury), ARDS (Acute Respiratory Distress Syndrome), cardiovascular problems and coagulopathies (diffuse thrombosis, microthrombosis, embolisms, myocarditis, arrhytmias, heart failure, stroke)^96-98, acute nephropathy^99,100 and encephalopathies¹⁰¹. The virus presence in the vascular wall can cause endotheliitis, which triggers the process of diffuse coagulation that can lead to a worsening of the systemic inflammation. The exaggerated inflammatory response seems to be connected with the development of ARDS, MOF (Multiple Organ Failure) and coagulopathies^102-107.

Immune checkpoint inhibitors (ICI) have been widely used in melanoma, but to identify melanoma patients with survival benefit from ICI is still a big challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of cancer patients. We used data from EMBL-EBI database and analyzed RNA-seq information and clinical profiles in melanoma. Weighted gene co-expression network analysis (WGCNA) was used to identify the key module, then nonnegative matrix factorization (NMF) was conducted to cluster patients into two different cluster and compared them regarding overall survival (OS) and progression-free survival (PFS). Subsequently, the differentially expressed genes (DEGs) between different clusters were identified, and their function and pathway annotation were performed. 91 melanoma biopsies with complete survival information were included in our analyses and we first identified the key module (magenta) by WGCNA, then identified nine prognostic lncRNAs (ENSG00000258869, ENSG00000179840, ENSG00000206344, ENSG00000226777, ENSG00000205018, ENSG00000204261, ENSG00000163597, ENSG00000197536, and ENSG00000263069) signature that predicted for OS and PFS in patients treated with ICI by NMF. Finally, enrichment analysis showed that the functions of DEGs between two consensus clusters were mainly related to the immune process and treatment. In summary, the nine lncRNAs signature is a novel effective predictor for OS and PFS in melanoma patients treated with ICI.

The COVID-19 crisis has resulted in a shortage of personal protective equipment (PPE) [1]. COVID-19 is currently the leading cause of death in the United States[2]. Health care providers caring for COVID-19 patients or at high risk of being exposed to the SARS-CoV-2 virus benefit from a face shield to protect against aerosol droplets that could hit the face and minimize the chance of inadvertently touching the face with contaminated hands, and air filtration to filter out aerosolized SARS-CoV-2. Adapting commercially available full-faced snorkel masks has been proposed as an alternative to narrow the gap in PPE [3]. Here we explore a full-faced snorkel mask with commercially available particulate filters.

Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.

To evaluate the dependency of COVID-19 on the temperature, by analyzing secondary data, considering temperature as the only dependent environmental factor. Taking the mean temperature and number of cases from 02nd March to 26th May 2020. We find out the relationship between the number of cases of COVID-19 and mean temperature in Rajasthan by finding the mean and percentage increase of both, and we evaluate that there is no any effect of temperature on coronavirus disease cases in Rajasthan there may be some other environmental factor and extraneous factors which may affect the number of cases.

Since the beginning of the year 2020, the global healthcare system has been challenged by the threat of the SARS-COV 2 virus. Molecular, antigen, and antibody testing are the mainstay to identify infected patients and fight the virus. Molecular and antigen tests that detect the presence of the virus are relevant in the acute phase only. Serological assays detect antibodies to the Sars-CoV-2 virus in the recovering and recovered phase. Each testing methodology has its advantages and disadvantages. To evaluate the test methods, sensitivity (percent positive agreement - PPA) and specificity (percent negative agreement – PNA) are the most common metrics utilized, followed by the positive and negative predictive value (PPV and NPV), the probability that a positive or negative test result represents a true positive or negative patient. In this paper, we illustrate how patient risk and clinical costs are driven by false-positive and false-negative results. We demonstrate the value of reporting PFP (probability of false positive results), PFN (probability of false negative results), and costs to patients and healthcare. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by one positive SARS COV-2).

This study reports a correlation between EEG and structural brain changes in patients after severe traumatic brain injury in a coma. The novelty of our approach was based on the combination of structural visualization (MRI) and functional neuroimaging (EEG) during tactile stimulation. The structural morphometry indicated a decrease of whole-brain cortical thickness, the gray-matter volume of the cortex, and subcortical structures in comatose patients compared to healthy subjects. In resting-state EEG, coma patients had significantly higher power of the slow-wave activity of 2-6 Hz and significantly less power of the alpha and beta rhythm. Importantly, coma patients showed a significant decrease of theta-rhythm power in tactile stimulation compared to the resting state, and this EEG pattern was not found in the control group. The decrease of the theta-rhythm power significantly correlated with the better outcome from a coma. Spectral changes in EEG in response to tactile stimuli showed no association with brain morphometric measures in healthy controls. In patients, decreasing theta-rhythm power correlated positively with the volume of whole-brain gray matter, right putamen, and insula; and negatively with the volume of damaged brain tissue. Increasing beta-rhythm power, specific tactile EEG response for a healthy brain, correlated with the cortical thickness of the somatosensory Paracentral and Precentral area. The observed decrease of gray-matter volume indicates brain atrophy in coma patients, which could be associated with neurodegeneration induced by injury. Our results also demonstrate that slow-wave desynchronization, as a nonspecific response to tactile stimulation, can serve as a sensitive index of morphometric changes after brain injury and coma outcome.

Background: The novel emerging virus SARS-CoV-2 has affected all human-kind during the first half of 2020. The aim of the study was to survey the actual circumstances from January until May. Methods: The data are collected and released systematically, by law, from the National Epidemiological Surveillance of Infectious Disease (NESID). Findings: Analysis of these data revealed that the infection spread in Japan from late March to early April 2020. The SARS-CoV-2 infection rate at its peak was estimated to be 10%. Thus, the size of the population who may have been exposed to the novel virus in Japan is estimated at 0.2 million, which is relatively small. The number of related deaths is likely to converge on 1,000 people. Interpretation: Applying the law of large numbers allows estimation of the infection rate as well as of the size of the affected population by statistical analysis. How to collect the data must be defined before the data analysis is suggested to be important to reflect the actual circumstances about COVID-19.

The semi-logarithmic plot of the cumulative number of cases of epidemics resembles the response of a first-order systems for a step load. This similarity was utilized to develop a first order model that can be used for extracting information about the dynamics of infectious disease epidemics. The developed model was validated using COVID-19 data of China. It was also heuristically fitted to other 13 countries. Obtained results indicated that the model can reliably forecasts the number of infected person, epidemic growth speed towards steady-state condition (process time constant, T), and time to reach steady-state condition (4T). The developed model will help public health authorities in developing more effective control strategies of epidemics.

This study presents a novel technique utilizing high frequency vibration to shorten treatment time and preserve alveolar bone in challenging orthodontic cases treated with Invisalign® clear aligners. Four non-growing orthodontic patients (age range 14-47 years old) with Class II skeletal patterns (convex profiles with retrognathic mandibles) who sought correction of their crowded teeth and non-surgical correction of their convex profiles were included in this study. These patients were treated using Invisalign clear aligners together with high frequency vibration (HFV) devices (120 Hz) (VPro5™) that were used by all patients for five minutes per day during active orthodontic treatment. Vertical control and forward rotation of the mandible for each patient was achieved through pre-programming the Invisalign to produce posterior teeth intrusion. Successful forward rotation of the mandibles achieved in all patients led to improvement of their facial convex profiles (ANB improved 2.1 + 0.5 degrees; FMA improved 1.2 +1.1 degrees). Dental decompensation was achieved by lingual tipping of the lower incisors and palatal root torque of upper incisors. The use of HFV together with Invisalign facilitated achieving these results within a 12+6 month period. In addition, more bone labial to the lower incisors after their lingual movement was noted. In conclusion, the use of HFV concurrent with SmartTrack Invisalign aligners allowed complex tooth movement and forward projection without surgery in non-growing patients with skeletal Class II relationships. The clinical impact and implications of this case series is that the use of HFV facilitates complex orthodontic tooth movement including posterior teeth intrusion and incisor decompensation in addition to increased bone formation labial to lower incisors that may minimize future gum recession due to their labial inclination.

Given the pace of SARS-CoV-2 transmission and its relatively high mortality rate, COVID-19, has the potential to become the most severe pandemic in recent times. This virus’s spread across international borders has triggered different responses in countries around the globe with a spectrum of mild, moderate to severe outcomes. Nigeria, Africa’s most populous country with many densely populated cities, presents a unique situation for the explosive spread of SARS-CoV-2. However, at the point of this writing, the number of reported confirmed infection and mortality is comparatively lower to other countries with dense urban populations. The exact reasons for this are not clear but include societal, political and infrastructural factors that will influence the course of the outbreak in Nigeria. In this perspective, we have described the ongoing COVID-19 outbreak and its associated peculiarities. We identify critical steps that remain to be taken to contain and control the outbreak in Nigeria.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

Motivation: UCSC Xena platform provides huge amounts of processed cancer omics data from big public projects like TCGA or individual reserach groups for enabling unprecedented research opportunities. In 2019, we developed UCSCXenaTools, an R package for retrieval of UCSC Xena data. However, an easier dataset exploration and analysis tool is still lack, especially for researchers without programming experience. Results: We develop UCSCXenaShiny, an R Shiny package to quickly explore, download all datasets from UCSC Xena data hubs. In addiction, a module based analysis framework is constructed to analyze and visualize data. Availability: https://github.com/openbiox/UCSCXenaShiny or https://cran.r-project.org/package=UCSCXenaShiny.

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases NHL. Analysis of the tumour microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we have analyzed the role of different cellular components of the tumour microenvironment, including mast cells, macrophages, lymphocytes, in tumour progression of DLBCL. We examined several approaches to confront the available pieces of evidence; three key points emerged. DLBCL is a disease of malignant B-cells spreading and accumulating both at nodal and in extranodal sites. Both in patients with nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. DLBCL cell interaction with mature stromal cells and vessels confers tumour protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL-milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression.

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

With a mild Mediterranean-type climate, Corsica is endemic for canine vector-borne diseases (CVBDs) such as dirofilariosis (a mosquitoes borne-diseases: MBDs), leishmaniosis and ehrlichiosis. The aim of this present study was to evaluate a monthly multi-modal prophylactic strategy (MMP) against CVBDs occurring in Corsica. The study was conducted as a comparative field trial in which eighty dogs allocated into two groups were included: (i) Group 1 consisted of 25 dogs under the MMP [per-os administration of 1.5 tablet of milbemycine oxime-praziquantel and a topical line-on application of a 3.6 mL solution of dinotefuran-permethrin-pyriproxyfen] and (ii) Group 2 under various real-life prophylactic treatment (RLP) based on the use of ectoparasiticide products [different formulations: deltamethrin, fluralaner, fipronil] and/or macrocyclic lactones based-products [milbemycin oxime/praziquantel, milbemycin oxime, moxidectin] during the period ranging from June to October 2017. All animals were followed for one year and had blood drawn at day 0, followed by follow-up at 6 and 12 months. Samples were screened for filariosis using molecular tools as well as for leishmaniosis and ehrlichiosis using indirect immunofluorescence assay (IFA). At the end of the study, no new cases of CVBDs were recorded within Group 1. In Group 2, the cumulative incidence of CVBDs was 20.0% (n= 11; p= 0.015) including dirofilarioses due to Dirofilaria immitis and/or D. repens, with 16.4% (n= 9; p=0.027). Ehrlichiosis was 5.5% (n= 3; p=0.241). No new cases of leishmaniosis were detected in Group 2. The data illustrated that, unlike the RLP treatment which failed to protect at least 20% of dogs, the MMP based on the concurrent administration of milbemycine oxime-praziquantel and dinotefuran-permethrin-pyriproxyfen is efficient to protect dogs against CVBDs in a high-risk area.

The involvement of macular function in its preganglionic elements, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group), 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery of BCVA (MS-ON-P Group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20- 25° (R5), and from retinal sectors [superior, nasal, inferior and temporal] between 0-15° and 0- 25°. In MS-ON-P Group, mean mfERG RADs detected from R1 (0-5°) and from the central nasal quadrant (0-15°) were significantly reduced (p<0.01) with respect to those of Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M= 20/3) was compared before (T0) and after 3 months (T3) of the nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, the GM characterization confirmed the typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction of the body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, we observed an increased abundance in several Bacteroidetes taxa (i.e. Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and depletion of many Firmicutes taxa (i.e. Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas). In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of a moderate caloric restriction in counteracting the gut dysbiosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

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.

Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer of chimeric antigen receptor (CAR) expressing T cells has gained FDA approval in hematologic malignancy. However, limited efficacy has been observed utilizing CAR-T therapy in solid tumors. Natural killer (NK) cells are crucial for tumor surveillance and exhibit potent killing capacity of aberrant cells in an antigen-independent manner. Adoptive transfer of unmodified allogeneic or autologous NK cells has shown limited clinical benefit due to factors including low cell number, low cytotoxicity and failure to migrate to tumor sites. To address these problems, immortalized and autologous NK cells have been genetically engineered to express high affinity receptors (CD16), CARs directed against surface proteins (PD-L1, CD19, Her2, etc.) and endogenous cytokines (IL-2 and IL-15) that are crucial for NK cell survival and cytotoxicity, with positive outcomes reported by several groups both preclinically and clinically. With a multitude of NK cell-based therapies currently in clinic trials, it is likely they will play a crucial role in next-generation cell therapy-based treatment. In this review we will highlight the recent advances and limitations of allogeneic, autologous and genetically enhanced NK cells used in adoptive cell therapy.

Therapeutic proteins are used to successfully treat hemophilia, Crohn’s Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous works demonstrated that cavitation might occur in therapeutic vials subjected to agitation or accidentally dropped, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion for when particulate will form, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and fluid properties were performed. The results of this research show that reducing the turbulence in a fluid system will reduce the likelihood of cavitation. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.

The widely spread CoronaVirus Disease (COVID)- 19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

SARS-CoV-2 infections underlie the current Coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. Mortality risk from severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n=166) from COVID-19 patients (n=33) were collected consecutively and analysed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r=0.7758, p<0.001), pointing to an insufficient Se status for optimal selenoprotein expression. In comparison to reference data from a European cross sectional analysis (EPIC, n=1915), the patients showed a pronounced deficit in total serum Se (mean±SD, 50.8±15.7 vs. 84.4±23.4 µg/L) and SELENOP (3.0±1.4 vs. 4.3±1.0 mg/L). A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors (Se; 53.3±16.2 vs. 40.8±8.1 µg/L, SELENOP; 3.3±1.3 vs. 2.1±0.9 mg/L). We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion on a relevant role of Se for COVID convalescence, and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

Disgust evolved as a way to protect one’s self from illness. DS-R measures disgust propensity of three kinds of disgust (Core, Animal Reminder and Contamination). Although the DS-R scale was refined mainly with young and largely female student population its impact on educational orientation has not been assessed. In the present study we examined the DS-R scoring and the choice of postgraduate studies in medical (n= 94) and psychology (n= 97) students. They responded to an anonymous web-based survey and completed the DS-R and a questionnaire on their demographics and plans for postgraduate studies. Female students outnumbered males (3:1) and scored higher in Total DS-R score (median: 59 vs. 50, p<0.05). Psychology students scored higher in all three kinds of disgust (p<0.05), indicating a higher level of disease avoidance. Medical students willing to follow Internal Medicine scored higher in Core Disgust (p<0.05) while psychology students willing to study Experimental Psychology scored lower in Animal Reminder subscale (p<0.001). Also, the higher the psychology students scored in Core Disgust scale the higher was the probability to choose Experimental Psychology. In conclusion, disgust propensity as rated by DS-R differentiates medical from psychology students and is also related to orientation preferences in postgraduate studies.

The advancement of the pediatric traumatic brain injury (TBI) knowledge base requires biospecimens and data from large samples. This study seeks to describe a novel clinical research modality to establish best practices for enrolling a diverse pediatric TBI population and quantifying key information on enrollment into biobanks. Screening form responses were standardized and cleaned through Google Sheets. Data was used to analyze total individuals at each enrollment stage. R was utilized for final analysis, including chi-square goodness of fit and proportion statistical tests, to determine further significance and relationships. Issues throughout data cleaning shed light on limitations of the consent modality. Results suggest that through a diverse research team, the recruited sample exceeds traditional measures of representation (e.g. sex, race, ethnicity). Sex demographics of the study are representative of the local population. Screening for candidates is critical to the success of the consent modality. The consent modality may be modified to increase diversity of study population and accept bilingual candidates. Researchers must implement best practices, including increasing inclusivity of bilingual populations, utilizing technology, and improving participant follow-up, to improve health disparities for understudied clinical populations.

Introduction: Osteoarthritis (OA) and age-related degeneration (ARD) are stimulants for the development of the fabella in the knee joint. This meta-analysis updates previous studies and reviews on the prevalence of the fabella in OA or ARD knee joints. In addition, it provides a quantitative estimation of the fabellar prevalence in knees having OA and ARD. Methodology: Twenty studies comprising of data from 11,056 knee joints were included in the analysis, consisting of 6,819 Knees of OA subjects (including those with age more than 40 years) and 4,237 knees of non-OA subjects (including less than 40years) knees, respectively. 2,434 knees had fabellae present in OA subjects (including more than 40years), and 844 fabellae were present in non-OA subjects (including less than 40years). The Odds and Risk Ratios were calculated. Sensitivity analysis and cumulative analysis were conducted to assess the robustness of the findings. Results: Prevalence of fabella was found to be higher in OA knees, where the Risk Ratio of developing fabella was 2.50 (2.07-3.01). Compared with this, the Risk Ratio for the incidence of fabella in OA with ARD knee was 1.84 (1.66-2.03). The bilateral occurrence of fabella was more common than unilateral. The risk of developing fabella in individuals aged less than forty-year was 63% less than individuals aged more than forty years. Conclusion: OA and ARD would increase the prevalence of fabella by 84%, thus acting as stimulants and risk factors for ossified fabella.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.

High levels of air pollution can contribute to high rate of the COVID-19 outbreaks. Air pollutants induce oxidative stress, inflammatory process, immune imbalance and coagulation at systemic level, making the organism susceptible to complications caused by various pathogens, including viruses, resulting in a possible important damage co-factor. Sperm cells are highly sensitive to the pro-oxidant effects of environmental pollutants, and may represent an important alarm bell indicating that the burden of environmental pressure in a certain area is causing damage to humans. A comparison of the maps of COVID-19 case fatality rates, male infertility rates and air pollution may suggest a way to understand the dynamics of the virus impact. Semen quality may be considered as an early and sensitive environmental marker, and also a potential susceptibility indicator to viral insults (including SARS-CoV-2 ) in heavily polluted areas. Therefore, assessing the burden of environmental exposure of a given population and its potential susceptibility to insults through early biological stress indicators may be helpful for predicting the risk of the adverse effects by the SARS-CoV-2 epidemic .

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed with damage of vascular endothelial glycocalyx, an extracellular matrix-bound to and encapsulating the endothelial cell lining the blood vessel wall. Unfavorable lifestyle; smoking and physical inactivity, also induces glycocalyx degradation. Moreover, the vascular endothelial glycocalyx is damaged by various unfavorable disease conditions like as dehydration, acute infectious disease, trauma, sepsis, ARDS, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. The vascular endothelial glycocalyx has been shown to be important not only as a physical cytoprotective barrier for vascular endothelial cells but also as a mechanism that regulates intracellular cell signaling. Therefore, vascular endothelial glycocalyx has great potential to explore new strategies for assessing the benefit conditions of our healthy vasculature.

In the last few decades, the dynamics of tumor cells and their growths are presented via clinical, experimental, and theoretical approaches, which leads to the development of the new idea of multiple cancer therapies to control and reduce the death rate for earlier detection. In this paper, we discussed the dynamics of tumor cell growth and its treatment process. We analyzed some simple mathematical models and generalized the study to understand the growth of tumor cells. The main proposed model is a system of ordinary differential equations which combines interactions among natural killer cells, dendritic cells and cytotoxic CD8+ T cells. The model is solved numerically to explain how the tumor cells spread and become more dangerous as well as the treatment process of cancer. It is also studied that how the cell behaves in the presence of different therapy and drugs. The optimal control of chemotherapy has been discussed. It has also been explained how much the model is effective in reducing tumor cells over time. Finally, a couple of spatially distributed models are discussed for tumor cell growth.

The coronavirus disease 2019 (COVID-19), the pandemic is an unprecedented health emergency never seen in the recorded history of humankind due to its sheer scale, rapid spread, and subsequent shock to the global economy. The past respiratory viral pandemics of the 21st century (SARS-CoV-2 in 2003, Influenza AH1N1 in 2009) have revealed seasonality in environmental factors to play a role in the dynamics of their spread. Here, we report the observed state-level relationship between environmental factors such as temperature (T), relative humidity (RH), specific humidity (SH), and solar radiation (SR) on the COVID-19 spread over the Indian region. The results show that T and RH have a significant impact on the disease growth rate and doubling time. Every degree rise in temperature corresponds to a 0.99 % decrease in the number of cases and an increase in doubling time by ~ 1.13 days implying a slowing down of spread. A similar analysis for RH reveals that more moisture leads to a higher growth rate and reduced doubling time. Lower SH and higher surface-reaching SR are found to reduce the spread and increase the doubling time similar to that of temperature. The range of average state-level T (RH) encountered during this period was between 24 and 35^oC (30 and 87%) which implies that environmental impact is still effective at all these T (RH) and is not limited to specific T (RH) ranges. The progression of the season towards monsoon, post-monsoon, and thereafter winter with a continuous reduction in temperature will prove a major challenge for health workers and policymakers attempting to enforce mitigation and control measures.

Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.

Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.

Background: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. About two-thirds of the severe cases may be rescued by extracorporeal membrane oxygenation (ECMO). However, about half of the patients supported by ECMO suffer major complications. High volume hemofiltration (HVHF) is a depurative extracorporeal support that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. Methods: We implemented HVHF prior to ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if ECMO was avoided and nonresponders if ECMO support was needed. Results: The first two patients required ECMO, while the last three did not. Patients had a maximum serum lactate of 8.4 [4.3-14] mMol/L and a lowest cardiac index of 1.76 [1.45-2.9] L/min/m2. Nonresponders were connected later to HVHF, displayed progressive tachycardia and decreasing stroke volume. The opposite was true for HVHF-responders who also received targeted-HVHF compounded by aggressive hyperoncotic albumin, sodium bicarbonate and calcium supplementation plus ultrafiltration to avoid fluid overload. All patients survived, but one of the ECMO patients suffered a vascular complication. Conclusion: HVHF may contribute to support severe HCPS patients avoiding the need for ECMO in some of them. Early connection and targeted-HVHF may increase the chance of success.

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

Patient group engagement is increasingly used to inform the design, conduct, and dissemination of clinical trials and other medical research activities. However, the priorities of industry sponsors and patient groups differ, and there is currently no framework to help these groups identify mutually beneficial engagement activities. Methods: We conducted 28 qualitative, semi-structured interviews with representatives from research sponsor organizations (n=14) and patient groups (n=14) to determine: 1) how representatives define benefits and investments of patient group engagement in medical product development and, 2) to refine a list of 31 predefined patient group engagement activities. Results: Patient group and sponsor representatives described similar benefits: engagement activities can enhance the quality and efficiency of clinical trials by improving patient recruitment and retention, reduce costs, and help trials meet expectations of regulators and payers. All representatives indicated that investments include both dedicated staff time and expertise, and financial resources. Factors to consider when evaluating benefits and investments were also identified as were suggestions for clarifying the list of engagement activities. Discussion: Using these findings, we refined the 31 engagement activities to 24 unique activities across the medical product development lifecycle. We also developed a web-based prioritization tool (https://prioritizationtool.ctti-clinicaltrials.org/) to help clinical research sponsors and patient groups identify high priority engagement activities. Use of this tools can help sponsors and patient groups identify the engagement activities that they believe will provide the most benefit for the least investment and may lead to more meaningful and mutually beneficial partnerships in medical product development.

Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-67; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

Abstract Background: The highest incidence rate of covid-19 in Iran was reported from Shahroud County. This study was conducted by geographic information systems (GIS) to determine the geographical distribution of Covid-19 in 60 days. Study design: A cross-sectional study Methods: This study was conducted in counties covered by Shahroud University of Medical Sciences, namely Shahroud and Mayami, from February 20, 2020 to April 18, 2020. The GIS can better show the spread of epidemics. This software indicates geographical distribution of disease spread and is very helpful in controlling the epidemics. Therefore, maps of spatial distribution and risk of infection to COVID-19 were prepared in different regions of Shahroud county using Arc-GIS software to better implement health policies. Results: During this sixty-day period, 529 confirmed cases were detected, of which 51% were men and the average age was 55 years. The maps showed high-risk to risk-free regions. Shahroud and Bastam cities were known as the coronavirus hot spots. The eastern region of Shahroud has the highest number of cases but some high risk areas are spread throughout the Shahroud city due to high infectivity of virus. Risk-based time maps indicated a reduction in the risk of infection at the end of the research period due to some mitigation and suppression strategies. Conclusions: Shahroud and Bastam are the most dangerous cities that, the number of patients and dissemination has decreased over time because of tracking definite patients and people in contact with them and implementation of preventive care.

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.

Safely resuming sporting events while the coronavirus is spreading is challenging – yet possible – if the science is taken into account. Two main ways the coronavirus can spread among football players is through air-suspended microdroplets (and possibly aerosols), and via contact with contaminated surfaces. Here we estimated virus survival in dried saliva droplets on a football pitch (i.e., on the grass) and on the ball itself, and compared these measures between mid-day and nighttime matches. We find, based on experiments with the enveloped phage Phi6 – a surrogate for SARS-Cov-2 – that while the virus survives reasonably well on both pitch and ball during a nighttime match (~10% survival), virtually no viruses survived the 90-minute duration of a mid-day match on a hot, sunny day. These results, taken together with studies reporting rapid deactivation of coronavirus in aerosols by sunlight, suggest that playing football in mid-day reduces the likelihood of transmission between players, and thus increases players’ safety.

Ovarian hypofunction or primary ovarian insufficiency (POI) is a common cause in the etiology of female infertility. It is a heterogeneous disorder, affecting approximately 1% of women before the age of 40. The characteristics of POI are menstrual disorders, including amenorrhea and delayed menstruation, accompanied by a raised gonadotrophin level and decreased estradiol level. In recent years, electrophysiology (EP) technology has been advancing rapidly in the diagnosis and treatments of numerous diseases. According to studies, bioelectrical stimulation (BES) therapy is an electrophysiology technology that plays significant roles in numerous diseases, including on the thin endometrium in patients with POI. In this review, the overall research progress of this electrophysiological technology has been discussed in relation to the advancement of primary ovarian insufficiency.

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.

Mucosal irritation caused by cusps of upper and lower teeth represents a source of persistent, low grade mechanical trauma. This type of trauma can initiate and/or perpetuate oral lichen planus in a few susceptible patients. Here, we report a rare case of bilateral white linear striations in the buccal mucosa of a young patient, associated with sharp cusps. Oral lesions demonstrated a unique cuspal signature highlighting the causal role of subtle mucosal trauma in the genesis of reticular-oral lichen planus. Lesions appeared to be exacerbated by significant psychological distress experienced by the patient. Although the Koebner phenomenon is well reported in the cutaneous lichen planus literature, such presentations are relatively rare in the oral cavity. This report emphasizes the potential role of low-grade cuspal trauma/irritation in conjunction with psychological distress in the genesis of oral lichen planus.

Background: The COVID-19 pandemic is the global public health emergency concern and had an impact on the day to day life of individuals. Its effect on an individual’s mental health is significant to the extent of suicide. Objective: This study aimed to assess the magnitude of psychological problems and their associated factor among communities living in Dilla town in response to the pandemic. Methods: From Apr 1- Apr 15, 2020, a community-based cross-sectional study was conducted using multi-stage sampling techniques. Self-administered the questioner, Depression, Anxiety and Stress Scale (DASS-21), and logistic regression analysis (95% CI, p-value <0.05) was used. Results: This study included 445 respondents with a 94% non- response rate who was living in Dilla town. In total, 34.4% of respondents had a psychological problem (11.4 % mild and 23% moderate level of the psychological problem). Female, Greater secondary level of education, monthly income below 500 ETB, more than three family size, and wearing face mask were variables associated with the outcome variable (p < 0.05). Conclusions: Nearly one-third of the respondents had mild to moderate psychological among communities living in Dilla town. There is a need for mental health support on those identified groups of peoples to enhance their resilience in response to the pandemic.

Introduction: The SARS-CoV2 pandemic has led to an worldwide shortage of Personal Protection Devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO₂) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A ‘fit’ test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO₂ and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO₂ was noted, remaining within physiological limits. Masks with specific adaptors (3D printed or provided by the manufacturer) are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts and choice of filter are important.

Background: Maternal mortality (MM) is a matter of serious concern in low income developing countries (LDCs). Perspective: A great reduction has been observed regarding the maternal deaths globally after huge efforts since 1990 todate. However, the situation continues to be either stagnant or worsening in developing countries, suggesting that the efforts to cope with this issue are either insufficient or not properly implemented. We need to first diagnose the problem areas that are a great hurdle in the road to success towards the reduction of MM. Postpartum haemorrhage and preeclampsia are one of the most common causes of MM. Malnutrition, neurological dysfunction and cancer are among the non-obstetric causes. Trained medical and paramedical staff can be of great help in this regard by increasing awareness among masses at grass root level. Target set by Millennium Development goal has minimized the MM by 44%. But it has not met the target set by Millenium Development Goals 5 and a lot of measures need to be taken in this regard. Conclusions: Majority of the MDs are preventable and can be avoided by adopting appropriate frameworks, linked data sets, surveillance, birth attendants training, preparation for births, etc. Delay in decision to get healthcare, access to healthcare center and receiving these facilities are the main factors in MM.

Brain Tumor is one of the severe diseases and occurrence of this disease threats human life. Detection of brain tumor in advance can secure patient’s life from unwanted loss. Well-timed and swift disease detection and treatment strategy can lead to improved quality of life in these patients. This paper attempts to use Machine Learning based ensemble approaches for recognising patients with brain tumor. Ensemble technique based AdaBoost classifier and 10-fold stratified cross-validation method are assembled in single platform is proposed in this paper for prediction of brain tumor. This prediction is compared against three baseline classifiers such as Gradient Boost, Random Forest and Extra Trees classifier. Experimental result implies the superiority of this model with an accuracy of 98.97%, f1-score of 0.99, kappa statistics score of 0.95 and MSE of 0.0103.

The iodine intake in a pregnant woman has been closely correlated with development of transient congenital hypothyroidism which leads to decline in neurocognitive abilities of the child later in life as the effects are very subtle at birth. Both low and excess ingestion of iodine has been found to contribute to this cause, although iodine deficiency is more commonly observed in women of underdeveloped nations. It poses risks not only to the foetus but also to the mother leading to obstetric complications such as still birth and spontaneous abortions. It can be prevented using WHO recommended daily iodine supplementation in deficient regions or decreasing the excess load in groups exposed to high iodine. Programmes designed to screen the new-born at birth can also help in improving the quality of life of the child. The deficient iodine condition is managed by administration of levothyroxine in dosage range of 10-15 mcg/kg/day. Generally, the prognosis of infants starting treatment early in life have a better neurocognitive outcome as compared to the treated infants late age at a later age. Avoidance of agents causing iodine exposure has resulted in decrease in the abnormal thyroid function levels.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

The main manifestation of new coronavirus disease 2019 (COVID-19) is respiratory disease. The new coronavirus (SARS-CoV-2) attacks the lungs and may result in severe acute respiratory syndrome. In such cases, the infected person has difficulty breathing, which impairs oxygen uptake in the body. If pneumonia or another respiratory illness develops, and the host immune system is unable to combat SARS-CoV-2, the infected person may eventually die. Meanwhile, reports on unexpected symptoms in organs other than the nasal cavity, throat, and lungs are emerging. To elucidate the causes of such symptoms, we analyzed the expression status of angiotensin-converting enzyme 2 (ACE2), the host receptor used by SARS-CoV-2, in various tissues. This study confirmed that alveolar macrophages appear to be involved in pneumonitis and thrombus formation. In this report, we introduce some new symptoms.

Stroke often results in impaired gait, which can limit community ambulation and the quality of life. Recent works have shown the feasibility of transcranial Direct Current Stimulation (tDCS) as an adjuvant treatment to facilitate gait rehabilitation. Since the cerebellum plays an essential role in balance and movement coordination, which is crucial for independent overground ambulation, so, we investigated the effects of cerebellar tDCS (ctDCS) on the post-stroke overground gait performance in chronic stroke survivors. Fourteen chronic post-stroke male subjects were recruited based on convenience sampling at the collaborating hospitals where ten subjects finally participated in the ctDCS study. We evaluated the effects of two ctDCS montages with 2mA direct current, a) optimized configuration for dentate stimulation with 3.14cm² disc anode at PO10h (10/5 EEG system) and 3.14cm² disc cathode at PO9h (10/5 EEG system), and b) optimized configuration for leg lobules VII-IX stimulation with 3.14cm² disc anode at Exx8 (electrodes defined by ROAST) and 3.14cm² disc cathode at Exx7. We found ctDCS to be acceptable by all the exposed subjects. The ctDCS intervention had an effect on the 'Normalised Step length Affected side' (p=0.1) and 'Gait Stability Ratio' (p=0.0569), which was found using Wilcoxon signed-rank test at 10% significance level. Also, ctDCS montage specific effect was found using a two-sided Wilcoxon rank-sum test at a 5% significance level for 'Step Time Affected Leg' (p=0.0257) and '%Stance Time Unaffected Leg' (p=0.0376). Moreover, the changes in the quantitative gait parameters across both the montages were found to be correlated to the mean electric field strength in the lobules based on partial least squares regression analysis (R² statistic = 0.6574) where the mean electric field strength at the cerebellar lobules, Vermis VIIIb, Ipsilesional IX, Vermis IX, Ipsilesional X, had the most loading. In conclusion, our feasibility study indicated the potential of a single session of ctDCS to contribute to the immediate improvement in the balance and gait performance in terms of gait-related indices and clinical gait measures.

Background and Objectives: In Libya, prescription medicines can easily be dispensed without a prescription, as self-medication with the subsequent of potential misuse and unnecessary risk for patients. This systematic review and meta-analysis explored the prevalence of self-medication among citizens in Libya. Methods: We systematically searched PubMed, ISI Web of Knowledge, EMBASE, Medline, Scopus, google scholar and ResearchGate databases for studies published in Libya reporting the prevalence of non-prescription use of medicines in community pharmacies, targeting studies published from Jan 2008 until Dec 2019. A random meta-analysis was performed to analyze pooled estimates of non-prescription usage of medicines. Results: Out of 63 articles identified, a total of 13 papers from 7 cities were met the inclusion criteria and involved a total of 4741 subjects. The overall pooled proportion of self-medication of drugs was 53.6% (95% CI: 0.93% - 1.08%), with low heterogeneity and the P-value of the whole population tasted was found to be = 1.000 (df = 12). Seven out of the 13 studies reported data on self-medication for antibiotics without prescription. The records ranged from 15.3% (95% CI 0.61–1.65) in Misurata to 76.6% (95% CI 0.80–1.25) in Tripoli. Conclusion: Self-medication use of medicines among Libyan population is a common phenomenon involving a high proportion use of antibiotics. This misuse of medications could enhance the development and spread of antibiotic resistance.

Lung cancer is known as lung carcinoma. It is a disease which is malignant tumor leading to the uncontrolled cell growth in the lung tissue. Lung Cancer disease is one of the most prominent cause of death in all over world. Early detection of this disease can assist medical care unit as well as physicians to provide counter measures to the patients. The objective of this paper is to approach an automated tool that takes influential causes of lung cancer as input and detect patients with higher probabilities of being affected by this disease. A neural network classifier accompanied by cross-validation technique is proposed in this paper as a predictive tool. Later, this proposed method is compared with another baseline classifier Gradient Boosting Classifier in order to justify the prediction performance.

The aim of the present research to identify the differences between the social acceptance, attention, and emotional and social loneliness feeling in women suffering from Alzheimer's and normal. The sample was analyzed in this study included 39 women age 51 to 69 years with the scope of that 19 of them with Alzheimer's disease (AD) and 18 people had normal cognitive function and healthy in the city of Gorgan in the winter 1395 in the study. Identification of Alzheimer's sufferers and healthy based on the diagnosis of the physician and cognitive status questionnaire (SPMSQ) and they were asked to answer the social acceptance of the scale questionnaire Marlow and Craven, affective and social adults alone feel scale (SELSA-S), Spotlight questionnaire (FAQ). The data using analysis of variance, multivariate factor test method (MANOVA) were studied. The results of this test indicate that it is totally focused attention between petty scale, the Spotlight focused on the notion of social acceptance of social interaction and social-emotional feeling lonely scale in women suffering from Alzheimer's and normal according to the analysis of the one-way variance of a significant difference in the context of manova level (P < 0.001). But in the other scale retail spotlight focused on his research, a significant difference was not observed. According to the results of the research in general can be found stating that to provide family-centered care and the implementation of the health-welfare interventions by relevant organs with different educational, supportive, emotional and consultation approaches, can be effective on health promotion of public health and the actual need in the community.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

This short note proposes a national Geographic Information System (GIS) - based health infrastructure to deal with epidemics and pandemics. Currently, there is no pan-India health infrastructure available that can compile, update, and report the spread of epidemic diseases. It not only curtails the opportunity of finding the real-time data on the spatial distribution of a disease but prevents one to inquire into the causes of the disease through epidemiological analysis. The proposed infrastructure in this study is a pan-India one and can broadly be divided into two parts, hotspot mapping and accessibility to services. In the first part, hospitals are proposed to act as nodes of data collection, sending data to a national GIS portal. This portal shall have the capabilities of plotting the data using map rendering services such as Google and Bing Maps. This way, hotspots can be visualized in no time, benefitting the government and common citizenry alike. The second part deals with the accessibility of citizenry to a wide range of services, i.e., healthcare services, grocery outlets, emergency services, baby food, and many other essential services of the day to day life. In order to implement this, we propose that the government need to enforce a mandatory submission of locational coordinates of all Goods and Services Tax (GST) enrolled service providers. Once the coordinates are submitted, the government can effectively control the opening and closing of services and inform the citizenry at the same time. The proposed infrastructure is going to help deal with the extraordinary situations during epidemic and pandemics similar to what the world is currently facing in the form of Corona Virus Disease 2019 (COVID-19). Furthermore, the infrastructure can be scaled up or down as per the spread of a disease. The health-GIS platform proposed in this concept paper, shall help India in controlling and managing the epidemic more efficiently.

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

The COVID-19 pandemic and increased rates of documented Emerging Infectious Diseases (EIDs) in human populations over the last century have drawn attention on understanding pathogens spill over to humans and their zoonotic origin. In this paper we argue that we need to change the thinking about the fundamental cause of zoonoses. Our premise is that deforestation is the primary cause of EIDs events and that, to prevent future pandemics, it needs to be addressed without further delays. Therefore, we review recent trends of proximate and underlying determinants of deforestation, forest degradation and related biodiversity losses while seeking to clarify their links to the determinants of EIDs events. Acknowledging the magnitude of the challenge, we propose responses to stop global deforestation from a trans-disciplinary, intersectoral perspective led by indigenous people. While we envisage that stopping deforestation is the most important approach with long term direct and indirect effects on human, animal and plants health, providing climate changes mitigation and preventing otherwise difficult to predict EID events, we argue that such an initiative may usefully be complemented by reducing contacts between humans and wildlife animals and regulating rather than banning markets where wild animals are sold alive.Finally, we discuss transformative changes to improve planetary-wide forests preservation, soil, plants, animal, and human protection, together with a further understanding of EIDs transmission dynamics, public health veterinary and human disease surveillance, for improved global collective preparedness and action for the management of zoonotic EIDs.

Plants and plant-derived food products have been used for medicinal purposes since the ancient. Medicinal Plant-based functional foods or plant-based dietary compounds are a re-emerged interest for their therapeutic benefits and nutritive supports which has implicated in healthcare systems across the world. Neurological disorders are one of the greatest threats to public health and according to the World Health Organization, about 100 million people are affected globally by several neurological and mental ailments. In a traditional medication system, medicinal plants have been applied as both neuro-therapeutic purposes and micro-macro nutrients provider for the wellbeing of psychological states e.g. anti-depressant, anti-anxiety, anti-convulsions, anti-dementia, anti-psychotic, etc. Herein, it is a topic of great interest to present a conceptual aspect by reviewing relevant scientific literature about the plant-based functional foods or bioactive phytochemicals for the prevention and treatment of mental and neurological disorders. From the literature assessment, we have found that nutritional neuroscience is becoming an advanced research discipline and there has been a growing pile of evidence concerning the therapeutic use of plant-based functional foods and/or plant-derived food compounds for the management of neurologic health, evolving with promising impact over the time.

Frauds and misconducts have been common in the history of science. Recent events connected to the COVID-19 pandemic have highlighted how the risks and consequences of this are no longer acceptable. Two papers, addressing the treatment of COVID-19, have been published in two of the most prestigious medical journals. In both, the authors declared to have analysed electronic records from a private corporation, which apparently collected data of tens of thousands of patients, coming from thousands of hospitals. Both papers have been retracted a few weeks later. When such events happen, the confidence of the population in scientific research is likely to be weakened. The objective of this paper is to highlight how the current system endangers not only the reliability of scientific research, but also the very foundations of the trust system on which modern healthcare is based. Having shed the light on the dangers of a system without appropriate monitoring, we propose to improve the research process using the promising aspects of the distributed ledger technology which, thanks to the characteristics of immutability, decentralization and transparency, appears among the best solutions to avoid the repetition of the mistakes linked to the recent and past history of research.

Microbe laden air particles, known as bio-aerosols, are routinely generated, in clinical dentistry due to the operative instrumentation within a milieu rich in salivary organisms. As the major mode of transmission of SARS-CoV-2 appears to be airborne aerosols and droplets, there has been an intense focus on such aerosol generating procedures (AGP). As there has been no systematic reviews on the efficacy of bio-aerosol reducing measure in dentistry, the objective of this systematic review was to evaluate the literature on three major AGPs, rubber dam application, pre-procedural oral rinse, and high-volume evacuation (HVE) aimed at reducing dental bio-aerosols. Method: PubMed via Ovid MEDLINE, EBSCO host, Cochrane Library, and Web of Science databases between January 01, 1985, and April 30, 2020, were searched.Results: A total of 156 records in the English language literature were identified, of which 17 clinical studies with 724 patients were included in the final analyses. The eligible reviewed articles revealed the inadequacy of the afore mentioned three principal AGPs used in contemporary dental practice to minimise bio-aerosols. HVE appears to be the most efficacious method, although no single approach provides total elimination of bio-aerosols. Conclusion:This, the first systematic review on methods of controlling bio-aerosols in dental operatory settings, indicates that employing combination strategies of rubber dam, with a pre-procedural antimicrobial oral rinse, and HVE can significantly minimize bio-aerosols. As the quality of the currently available data on dental bio-aerosols are rather poor, further, controlled, multi-centre studies are essential to address this critical issue.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based studies using these datasets require thoughtful modification to sample selection and analytic strategies, relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings. This paper offers some practical guidance to the full analytical process, demonstrates methods for estimating causal treatment effects on several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying repeated measures outcomes, and aims to increase transparency and reproducibility. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity.Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C).Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C.Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.

Since its inception in December 2019, Covid-19 has challenged the global scientific community. Some treatments were used in this infection, but doubts still persist regarding the use of medications ¹. More severe cases complicate with endothelial dysfunction, excess thrombin synthesis and decreased fibrinolysis which, associated with hypoxemia, lead to a hypercoagulability state ² and some authors indicate the use of anticoagulants for these ³. For mild cases, doubts remain regarding this indication. We will report the case of a patient with mild symptoms of covid-19, complicated by inferior mesenteric vein thrombosis.

Anxiety, chronical stress and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck’s Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10, n=23) and a Control group (<10, n=23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes: i.e. corticotropin-releasing hormone (CRH), 11β-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender and birthweight. A significant dysregulation of gene expression for CRH, AVP and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11β-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho= 0.54; p<0.01) and the sex of the newborn in pregnancies perceived as stressful (Index, p<0.05). Gene expression of CRH correlated with both AVP (Rho= 0.79; p<0.001) and HSD11B2 (Rho= 0.45; p<0.03), and also between AVP with both HSD11B2 (Rho= 0.6; p<0.005) and NR3C1 (Rho= 0.56; p<0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated COVID-19 disease has become a global pandemic causing significant mortality and morbidity. In the absence of vaccines and effective therapeutics, reliable serological testing can be a key element of public health policy to control further spread of the disease and gradually ease quarantine measures. However, prior to launch of large-scale seroprevalence studies to assess herd immunity, it is critical to understand the limits and potential of current SARS-CoV-2 serological tests on the market. In this study, we provide an overview of serological testing and conduct a systematic review of independent evaluations of SARS-CoV-2 serological tests performance. Our findings show significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid diagnostic tests with high performance level in detecting SRAS-CoV-2 specific antibodies. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests.

Objective: SARS-Cov-2 infection or COVID-19 is a global pandemic. From the time of identification to till, multiple clinical symptoms and parameters have been identified by the researchers of various countries and regions regarding the diagnosis and presentations of COVID-19 disease. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients. Methodology: We have collected the disease history of mild to moderate degree of COVID-19 patients; hematological and biochemical on admission reports of moderate degree COVID-19 patients. All of them were tested positive for SARS-CoV-2 by RT-PCR in different institutes in Bangladesh. Results: According to this study though COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat, but symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100⁰F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were found increased among 53.85%, 80.43, 44%, and 25% patients respectively. 17.39% of the patients had leukocytosis and neutrophilia. 28.26% of patients presented with lymphocytopenia. 62.52% of patients had mild erythrocytopenia. Conclusion: Despite some similarities, our study has evaluated a different expression in presenting symptoms in the case of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be initial diagnostic hematological findings and assessment for prognosis COVID-19 disease. Also, gender variations have a different scenario of clinical and laboratory appearance in this region.

The link between scoliotic deformity and bone metabolism in adolescent idiopathic scoliosis (AIS) has not been well researched. Moreover, the data concerning the cross-talk between fat tissue content/hormonal activity and bone markers in this group of patients are lacking. The objective of this study was to correlate the extent of scoliotic-curve severity with the bone turnover vs. leptin level and nutritional status in girls with AIS. The study encompassed 77 AIS girls, aged 14.7 ± 2.17 years. Scoliotic curve severity assessed by Cobb’s angle was categorized as mild (10-19o) moderate (20-39º) or severe (≥40º). Corrected height, weight, waist and hip circumferences were measured and body mass index (BMI), corrected height Z-score, BMI Z-score and waist/height ratio (WHtR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM) and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. Bone turnover markers (osteocalcin (OC) and amino terminal of collagen cross-links NTx) and leptin levels were assessed in serum. Multiple regression analysis showed that, OC, NTx (negatively with p<0.05) and leptin (positively with p<0.01) were significantly associated with curve severity in AIS girls. Moreover, Cobb’s angle was positively correlated with W/HtR (p<0.01)and FAT (p<0.05). One-way analysis of variance (ANOVA) revealed significant differences in leptin (p<0.05 vs. mild only), OC (p<0.05 vs. mild and moderate)) and W/HtR (p<0.01 and p<0.05 vs. mild and moderate respectively) between the three AIS severity subgroups. OC was significantly lower in the severe AIS subgroup, while leptin and W/HtR were significantly higher. Significant correlations between leptin and anthropometrical parameters as BMI z-score and W/HtR were shown. Leptin level correlated also significantly with BMI z score (p<0.001), W/HtR (p<0.0001) and body composition parameters (p<0.000001). Moreover, there was a significant negative correlation between NTx and leptin level (p<0.05). Bone metabolism in AIS girls seems to be altered and significantly related to the scoliotic curve severity. Leptin may be a crucial link in the cross-talk between bone turnover and body composition in this group of patients. Further studies concerning this topic are needed.

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na⁺/K⁺ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na⁺/K⁺ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na⁺/K⁺ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.

Understanding the clinical conditions and outcomes of Covid-19 infected patients with immunodeficiency like HIV will be an information for improving management and treatment modalities. It was reported a patient of HIV plus clinical confirmed Covid-19 in this presentation.

The present study explored the effects of a Second-generation mindfulness-based intervention known as Flow Meditation (Meditación-Fluir) in the improvement of life habits. A sample of university students (n = 51) in Spain were randomly assigned to a seven-week mindfulness treatment or a waiting list control group. Results showed that compared to the control group, individuals in the mindfulness group demonstrated significant improvements across all outcome measures, including healthy eating habits (balanced diet, intake rate, snacking between meals, decrease in consumption by emotional states negative, increased consumption by negative emotional states, amount of consumption, meal times, consumption of low-fat products), tobacco, alcohol and cannabis consumption, and resting habits. There were differences between males and females in some of these variables and a better effect of the treatment was evident in the females of the experimental group as compared to males. The Flow Meditation program shows promise for fostering healthy life habits, thus decreasing behaviors related to maladaptive eating, tobacco, alcohol and drug consumption, as well as negative resting habits, in university students. This mindfulness program can significantly contribute in the treatment of eating disorders and addictions, wherein negative emotional states and impulsivity are central features of the condition.

Three patients with severe life-threatening COVID-19 who failed to achieve substantial improvement on tocilizumab, received pulse therapy with corticosteroids (methylprednisolone, 1000 mg/day IV for three consecutive days) and intravenous immunoglobulin (20 g/day IV). This was associated with a prompt resolution of respiratory failure, elimination of cytokine release syndrome, and reversal of pulmonary CT changes. The treatment was generally safe and well tolerated. There was no evidence of protracted persistence of the virus in the patients who received pulse therapy. Randomized controlled trials are necessary to specify the efficacy and safety of high-dose methylprednisolone and intravenous immunoglobulin in the treatment of severe life-threatening COVID-19 separately or in combination.

Typhoid fever is a communicable disease transmitted by the bacteria Salmonella typhi, related to serotype paratyphi A, B and C. The disease is of a significant health concern in most developing countries especially Cameroon. Objectives: The study aimed at determining the prevalence and associated risk factors of typhoid fever in children ( 0-18 years) attending the “Deo Gratias” hospital in Douala. Method: A hospital base cross sectional study from August to September 2018 was carried out in patients’ age 0-18 years suffering from typhoid fever at the Deo gratias Catholic hospital. Widal slide agglutination test was the diagnostic test used. Positive tested patients were administered questionnaires to evaluate the level of knowledge, attitude and practice toward the disease, as well as their self-management abilities. Data obtained from respondents was analysed by descriptive statistics. One-way ANOVA and means comparison using Tukey’s test (α = 0.05) was performed to check whether the population of respondents differed significantly across risk factor practices. Results were finally presented on bar charts, tables and pie chart. Results: Typhoid fever was more prevalent in females (52.3%) than in males (47.7%), with a high proportion in the ages 5-9 years (38.6%). A significant difference was observed in population of respondents across risk factor practices. Conclusion: Water quality have a great impact on the burden of typhoid fever among children. The identification of risk factors associated to the disease is of great importance in the development of rational control strategies of the disease.

Background: It is unclear why certain countries have been more severely affected by COVID-19 than other countries. Methods: In this ecological study we compared COVID-19 mortality and incidence/100,000 as well as 4 putative explanatory factors by WHO world region. Linear regression was then used to assess the country-level predictors of COVID-19 mortality/100,000 and incidence/100,000 in 204 countries with available data. Results: COVID-19 incidence and mortality/capita were greater in Europe than other regions. This was despite a higher testing rate in Europe than other regions. Europe had an older population than all other regions and a higher prevalence of obesity than Africa, South East Asia and the Eastern Mediterranean. Country level multiple linear regression revealed positive associations between mortality/capita and testing rate, percent of the population 65 years or older, and Europe compared to Western Pacific and South East Asia (all P<0.005). Results for the analyses with cases/100,000 as outcome variable were similar. Conclusion: Our results suggest that older populations as well as other undefined regional and national factors, possibly related to efficacy of control efforts, are responsible for differences in national severity COVID-19 epidemics.

Coronavirus disease 2019 (COVID-19) fatal outcomes have been associated with multiple cardiovascular risk factors. In new epidemic areas, such as Latin America, there is a lack of studies about this. Here, we evaluated those factors in a retrospective cohort of patients in a national reference hospital of Lima, Peru. Design. A retrospective cohort observational study was done. For this study, information was obtained from clinical records of the hospital for the cases that were laboratory-diagnosed and related, during March 6^th and April 30^th, 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs at the National Institute of Health. Calculation of the odds ratio (OR) with the respective 95% confidence interval (95% CI) was done, also logistic regression for adjusted OR (multivariate) was done. Values of p < 0.05 were considered significant for all analyses. Results. One hundred six hospitalized patients were evaluated. The mean age of patients was 61.58 years (SD 16.81). Cardiovascular risk factors among them were hypertension (46.2%), diabetes (28.3%), and obesity (28.3%), among others. Fifty-six patients died (52.8%). Mortality associated factors at the multivariate analysis were arterial hypertension (OR=1.343, 95% 1.089-1.667), myocardial injury (OR=1.303, 95% 1.031-1.642), and mechanical ventilation (OR 1.262, 95% 1.034-1.665), as associated factors. Conclusion. As observed in other regions of the world, cardiovascular risk factors represent a significant and independent threat to be considered in patients with COVID-19. Further studies and interventions in Peru and Latin America are expected.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

Estimation of the reality can easily be flawed, hence, in order to result in accurate and useful estimates the process has to be protected from bias and confounding and should follow other methodological milestones inherent to different types of empirical observations. Candidate-gene association studies are a specific form of observations that have been rather extensively applied in psychiatry yielding valuable information on various aspects – when methodologically adequate and used in appropriate settings. However, certain flaws that may occur in such studies might not be bluntly obvious, at least not at first glance, and may pass unnoticed by researchers and reviewers. This case study uses two recent published candidate-gene association reports suggesting involvement of cannabinoid receptor type 1 and of heat shock protein single nucleotide polymorphisms in development of neurocognitive performance and psychopathology in a cohort of adult first episode psychosis patients to point-out the types of flaws inevitably resulting in inaccurate and useless estimates.

Consumption of milk contaminated with antibiotic residues above the maximum residue limit (MRL) causes direct toxicity to humans and the development of superbugs that leads to the failure of antibiotic therapy and threatens human life. Besides, long-duration exposure might alter the nature of gut microflora results in the enhancement of many diseases. Therefore, we examined 300 raw and processed packet milk samples using thin layer chromatography (TLC) and ultra high performance liquid chromatography (UHPLC) method against five veterinary antibiotics and assessed the risk for consumers in Chattogram, Bangladesh. Risk analysis was calculated by using hazard quotient on the basis of 165 ml per capita milk consumption. We found a total of 7% prevalence of antibiotic residues in raw milk samples which were higher (8%) in individual samples than the pooled samples (4%). However, we did not find any processed packet milk samples as positive. The mean concentration of oxytetracycline residue was detected 61.29 µg/l and amoxicillin was 124 µg/l in individual milk samples. Risk analysis showed the hazard quotient values of 0.0056 for oxytetracycline and 0.0017 for amoxicillin residue which was confirmed that, no significant health risk associated with the consumption of milk produced and marketed in the study area. Our study might fill the gap of knowledge to measure the safety status of milk regarding public health issues.

Presepsin is a diagnostic and prognostic biomarker of sepsis; however, elevated presepsin levels have also been documented without sepsis. This study aims to retrospectively analyze the laboratory parameters and Sequential Organ Failure Assessment (SOFA) score affecting presepsin levels in 567 patients. Some patients with elevated presepsin levels exhibited renal dysfunction or elevation of biliary enzymes despite a low SOFA score. The univariate regression analysis revealed a close correlation between presepsin levels and SOFA score, serum creatinine (CRE), blood urea nitrogen, and biliary enzymes. In addition, a multivariate regression analysis revealed that SOFA score, alkaline phosphatase (ALP), and CRE independently affected presepsin levels significantly. The analysis of covariance (ANCOVA) revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Besides, we found that patients who presented with the dilatation of intra- or extrahepatic bile ducts and the elevation of ALP or total bilirubin exhibited remarkable high presepsin levels in the bile. Furthermore, the presepsin production in the liver’s Kupffer cells was established by immunostaining in patients who received surgical liver resection. Overall, this study elucidates that biliary enzymes’ elevation affects presepsin levels, presepsin exists in high concentrations in the bile, and is positive in Kupffer cells.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Early detection, isolation, and management of COVID-19 patients are crucial to contain the current pandemic. The CDC in USA recently included "sudden loss of taste (dysgeusia/ageusia) and smell (anosmia/hyposmia)” as symptoms of COVID-19. If these symptoms are reliable forerunner symptoms of COVID-19, then it may facilitate early detection and containment of the disease. Hence, we systematically evaluated the contemporary evidence on dysgeusia and anosmia as trigger symptoms in COVID-19. Ovid MEDLINE, EBSCO host, and Web of Science databases were searched between December 25, 2019-May 30, 2020.Of the 13 identified records, eight (totaling 11,054 COVID-19 patients), were included, as per the selection criteria. The studies emanated mostly from the European community, as well as China, the USA, and Iran. In total, anosmia and dysgeusia symptoms were present in 74.9 % and 81.3% ambulatory as well as hospitalized, mild-to-severe cases of COVID-19 patients, respectively. The European, US, and Iran data indicate that olfactory, and gustatory symptoms appear prior to general COVID-19 symptoms in a majority of the patients. To our knowledge, this is the first systematic review analyzing the prevalence of chemosensory dysfunction in COVID-19. Further, studies are essential to evaluate their utility as harbingers of COVID-19 onset, and to establish clinical practice guidelines.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

Motivation: The SARS-Cov-2 pandemic has gripped the entire world and a race to find either a cure or a vaccine for this pandemic is on. The public databases have a deluge of information in terms of genomic sequences and protein structures making it possible to study the minute details in terms of conserved motifs and super-motifs in its proteins. In this study we have identified the hidden features of the Spike protein and the Main protease (Mpro) of SARS-Cov2. These domains have been identified using the standard bioinformatics tools and the pfam database. We found four domains reported in the pfam database are present in the spike protein and the Mpro of SARS-Cov2 but have not been reported earlier. These domains are specific to human strains of SARS-Cov2 and are not present in SARS-Cov or the coronaviruses of other animals. Using RIN we also identified the motifs and super-motifs in these two proteins that are important in understanding species wise changes as well as evolution driven variation in amino acids. Our results highlight several interesting features of the spike protein and Mpro of SARS-Cov2 that can be exploited for the development of various drug and vaccine therapies.

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.