With the advancement of epigenetic tools and technologies associated with intervention medicine, stroke research has entered into a new fertile, dynamic era of epigenetic studies, a wide plethora of intervention procedure, administration of tissue plasminogen activator, the introduction of mechanical thrombectomy, clinical studies, and drug developments over the last decennium. Against this vivid background of newly emerging pieces of knowledge, there is little to none advancement in the overall outcome of the disease. The stroke involves an overabundance of inflammatory responses arising in part due to the body's immune response to brain injury. Neuroinflammation contributes to significant neuronal cell death and the development of functional impairment and death in stroke patients. Recent studies demonstrated epigenetic plays a key role in the overall outcome of the disease. In this review, we summarize the progress of epigenetics which provides an overview of recent advancements on the emerging key role of epigenetics over the last decade contributing to the regulation of neuroinflammation in stroke, potential epigenetic targets that might be key factors in the development of stroke therapies and their relation in respect to clinical practice.

P2Y receptors (P2YRs), a δ group of rhodopsin-like G protein-coupled receptors (GPCRs), have many essential functions in physiology and pathology, such as platelet aggregation, immune responses, neuroprotective effects, inflammation, and cellular proliferation; thus, they are among the most researched therapeutic targets for use in the clinical treatment of diseases (e.g., clopidogrel, an antithrombotic drug, and Prolacria, a treatment for dry eye). Over the past two decades, GPCRs have been revealed to transmit signals as dimers to increase the diversity of signalling pathways or pharmacological activities. Many studies have frequently confirmed dimerization between P2YRs and other GPCRs due to their functions in cardiovascular and cerebrovascular processes in vivo and in vitro. Recently, some P2YR dimers that dynamically balance physiological functions in the body were shown to be involved in effective signal transduction and exert pathological pharmacological effects. In this review, we summarize the types, pharmacological changes, and active regulators of P2YR-related dimerization. In summary, our review delineates that P2YR-related dimers have new functions and pharmacological activities and maybe a novel direction to improve the effectiveness of medications such as thrombotic events associated with COVID-19.

Objective: Describe & validate flow index (FiO2×flow rate/weight) to report the degree of respiratory support to children on high flow nasal cannula (HFNC) Methods: Retrospective chart review. Children managed with HFNC from 01/01/15 to 12/31/19. Variables included in the flow index (weight, FiO2, flow rate) and outcomes (hospital and ICU length of stay [LOS], escalation to the ICU) extracted from medical records. Max flow index defined by the earliest timestamp when patients FiO2×Flow rate was maximum. Step-wise regression used to determine the relationship between outcome (length of stay and escalation to ICU) and flow index Results: 1537 patients met the study criteria. Median 1st and maximum flow index of the population 24.1 and 38.1, respectively. Both 1st and maximum flow indexes showed a significant correlation with the LOS (r 0.25 and 0.31). Correlation for the index was stronger than that of the variables used to calculate them and remained significant after controlling for age, race, sex, and diagnoses. Mild, moderate, and severe categories of 1st and max flow index derived using quartiles and showed significant age and diagnosis independent association with LOS. Patients with 1st flow index >20 and maximum flow index >59.5 had increased odds ratio of escalation to ICU (OR 2.39 and 8.08). The 1st flow index had a negative association with rapid response activation. Conclusions: Flow index is a valid measure for assessing the degree of respiratory support for children on HFNC. High flow index associated with longer hospital LOS and the risk of escalation to ICU.

Bird strike is a significant threat to the parts of the flying aircrafts. The wing is a central part, which provides stability to the aircraft. Mostly at wing, bird attack the leading edge. Worldwide aviation regulation FRA, EASA, required 4Ib bird strike on the wing of aircraft, and after this bird strike, aircraft is able to be safely landed. This study aims to investigate the resistance of the wing against the bird strike and damage analysis of the high-velocity bird collision on the model wing, inner structure, spar, and ribs. By using the Coupled Eulerian-Lagrangian (CEL) approach in ABAQUS/Explicit. Our contribution 1) bird strike on a wing with assembled inner structure by aluminium and outer skin composed of unidirectional fiber-reinforced composite material. 2) bird strike on-wing which is similar with the first test in which the difference is of spar designed layers of horizontal plates like a comb. 3) bird strike on-wing which is similar with second model wing difference in this wing put an aluminium leading edge on the skin leading-edge, final to analyze the damage of bird impact on the wing, the velocity of bird strike is 200m/s and analyze the behavior of the bird at this velocity. Resistance behavior of composite skin After penetration in the wing, analyze the impact on the spar and stress on the inner structure. Analysis of the kinetic and internal energy graph and Comparison all of these results and check the performance, which gives an excellent result at this velocity. based on these results suggest which inner part is sensitive.

Objective To assess the prevalence of endometriosis using pelvic ultrasound examination in women attending for early pregnancy care Design Prospective observational study. Setting A dedicated early pregnancy unit. Population We included 1341 consecutive women who attended for an early pregnancy assessment and had transvaginal ultrasound scans performed by a single clinician. Methods In addition to the presence of endometriosis on ultrasound scan, we collected data on patient demographics and concurrent gynaecological conditions. Data analysis was performed using logistic regression and multivariate analysis. Main outcome measures The prevalence of endometriosis in addition to possible associations with demographic and clinical variables. Results The prevalence of endometriosis in women attending the early pregnancy unit was 4.9% (95% CI 3.8 – 6.2); In 33/66 (50%, 95% CI 37.9 – 62.1) women with endometriosis, this was a new diagnosis made for the first time during their early pregnancy scan. The presence of endometriosis was strongly associated with congenital uterine anomalies (p < 0.001; OR 5.69, 95% CI 2.17 – 14.9) and uterine fibroids (p = 0.004; OR 2.37, 95% CI 1.31, 4.28). Conclusions Endometriosis is present in nearly 5% of women attending for early pregnancy assessment. In half of the women with endometriosis, the diagnosis was made for the first time during pregnancy. We propose that ultrasound may be a useful tool for the detection of endometriosis and to identify pregnant women who may benefit from specialist antenatal care. Funding No funding was obtained for this work. Keywords Endometriosis, Prevalence, Pregnancy, Ultrasonography

Background. The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the cannabinoid receptor in the placenta and the incidence of preterm birth.Methods. This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, i.e., Group 3, consisted of 14 women who delivered at term and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, CBR2).Results. The study used reverse transcription and Real-Time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1 and CBR1a receptors was significantly lower in the placentas of women after preterm birth compared to those after term births, p = 0.038, 0.033 and 0.034, respectively.Conclusions. The presence of CBR mRNA in the human placental tissue was confirmed. The decreased expression of cannabinoid receptors could serve as an indicator in predicting PTB. KEYWORDS: Cannabinoid receptor; CBR1; CBR2; ECS; preterm birth; PTB.

Studying complex metazoan communities requires taxonomic expertise and laborious work if done using the traditional morphological approach. Nowadays, the popular use of molecular-based methods accompanied by massively parallel sequencing (MPS) provides rapid and higher resolution diversity analyses. However, diversity estimates derived from the molecular-based approach can be biased by the co-detection of environmental DNA (eDNA), pseudogene contamination, and PCR amplification biases. Here, we constructed microcrustacean zooplankton mock communities to compare species diversity and composition estimates from PCR-based methods using genomic (gDNA) and complementary DNA (cDNA), metatranscriptomic transcripts, and morphology data. Mock community analyses show that gDNA mitochondrial cytochrome c oxidase I (mtCOI) amplicons inflate species richness due to environmental and nontarget species sequence contamination. Significantly higher amplicon sequence variant (ASV) and nucleotide diversity in gDNA amplicons than cDNA indicated the presence of putative pseudogenes. Last, PCR-based methods failed to detect the most abundant species in mock communities due to priming site mismatch. Overall, metatranscriptomic transcripts provided estimates of species richness and composition that closely resembled morphological data. The use of metatranscriptomic transcripts was further tested in field samples. The results showed that it could provide consistent species diversity estimates among biological and technical replicates while allowing monitoring of the zooplankton temporal species composition changes using different mitochondrial markers. These findings show that community characterization based on metatranscriptomic transcripts reflects the actual community more than PCR-based approaches.

Student's queries play a significant role in improving the service delivery for IT students at CPUT Department of Information Technology. It is imperative to know how to handle student requests efficiently. Currently student's lodge their complaints, selecting from a list of topics their query gets captured, the student query might not get addressed on time or in a certain time frame to support ITIL-based continual service improvement. This study will look at implementing the key service-level processes of ITIL and discuss how to integrate it successfully.

This manuscript has been published on the 29 th of May 2020 by the honorable BMJ as a rapid response to a related article. However since a DOI has not been assigned and two subsequent manuscripts have cited it, I'm preprinting a copy wishing it might reach all the interested colleagues and researchers in an easier way.

Background: Early-life exposures to geohelminths may protect against the development of wheeze/asthma and atopy. Objective: Study effect of maternal geohelminths and infections in children during the first 5 years of life on atopy, wheeze/asthma, and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2,404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO), and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1,933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and in 45.5% of children to 5 years. Frequencies of outcomes at 8 years were: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%), and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced prevalence of SPT (OR 0.72). Childhood T. trichiura infections were associated with reduced wheeze (OR 0.57) but greater parasite burdens with A. lumbricoides were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).

i. Rationale, Aims and Objectives: Despite guideline recommendations against their use, clinicians prescribe benzodiazepines for various symptoms to patients with posttraumatic stress disorder (PTSD). Clinicians’ reasons in making these decisions are not fully understood. This qualitative study sought to characterize factors identified by prescribing clinicians in clinical decision making in PTSD regarding the use of benzodiazepines. ii. Methods: The descriptive study involved semi-structured interviews with 26 prescribing clinicians across thirteen VA medical centers. Our overall aim in the study was to explore clinicians’ benzodiazepine practices in veterans with a PTSD diagnosis. We audio-recorded, transcribed, and analyzed the interviews using grounded theory methodology. iii. Results: Facilitators and barriers that contribute to benzodiazepine prescribing to veterans with PTSD included organizational, provider, and patient aspects. Most providers interviewed indicated that they inherited patients already on these medications initiated by other clinicians. These providers, as well as others interviewed, voiced concerns that tapering benzodiazepines may cause more harm than the risks of maintenance, particularly in older patients. Clinicians who noted consistent treatment practices among their hospital colleagues found it easier to decrease both new and maintenance benzodiazepine prescribing. iv. Conclusions: Patients with PTSD at increased risk of harms, such as older patients, are still receiving benzodiazepines suggesting that innovative solutions are now needed to decrease use. Specific protocols for inherited patient caseloads, increased dissemination of effective psychotherapies for symptoms such as insomnia and anxiety and the use of direct to consumer educational materials should help to foster needed culture change and increased evidence-based PTSD practice.

Background: Revascularization has been considered the gold standard treatment for critical limb ischemia (CLI). Due to the high morbidity and mortality associated with intervention, evidence has emerged recently supporting the suitability of conservative management as a primary option to achieve amputation-free survival (AFS) in CLI patients even when revascularization is technically feasible. Methods: A prospective database of CLI patients was developed during pre-screening of patients for a phase 1 stem cell therapy clinical trial. The overall survival (OS) and AFS rates for patients treated with revascularization were compared to those treated conservatively. Statistical significance was set as p value < 0.05. OS and AFS for the two groups were estimated by Kaplan-Meier survival curves. Results: Patients in the conservative group were more likely to have Rutherford Class 5 and be diabetic while they were less likely to be active smokers or have hyperlipidemia (Table 1). There were no significant differences between the two groups in mortality, amputation, overall AFS or one-year AFS rates. Kaplan-Meier cumulative OS and AFS over the 3 years follow-up period of the study demonstrated significant differences between the conservative and revascularization groups (Log Rank: 0.031 & 0.045; respectively). This statistical significance was not detected when one-year AFS was evaluated (Log Rank 0.096). Conclusion: Conservative management can be a suitable management option to achieve one-year AFS for some CLI patients. Further studies are needed to identify robust clinical criteria for identifying patients who will benefit from conservative management.

On the same day the results of the RECOVERY study was published; July 17, 2020, we have submitted a letter to New England Journal of Medicine (NEJM, ID 20-25534) representing some concerns about this study and its status was with editor until November 29, 2020 on which a withdrawal request has been sent to NEJM and was promptly accepted on the following day. Notably, four emails were sent to NEJM, once every month wondering about this unprecedent delay in publishing a short letter and the response was that the editor has been contacted on multiple occasions but he/she is busy because of the large number of COVID-19 related submissions.  

RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. Here, we report for the first time a homozygous mutation of RAPGEF1 in a consanguineous family with two siblings affected by neuropsychiatric disorder. To confirm the correlation of the mutation and the phenotype, we utilized in silico analysis and established a zebrafish model. Survival rate was reduced in the rapgef1a-knockdown model, and the zebrafish showed global morphological abnormalities, particularly of brain and blood vessels. Co-application of human RAPGEF1 wildtype mRNA effectively rescued the abnormal phenotype, while that of RAPGEF1 mRNA carrying the human mutation did not. This work is the first report of a human Mendelian disease associated with RAPGEF1 and the first report of a zebrafish model built for this gene. The phenotype of zebrafish model provides further evidence that defective RAPGEF1 may lead to global developmental delay in human patients.

Nepal is a mountainous country sandwiched between China and India that extends along the Hind Kush Himalayan range. The entire country sits on a geological formation that has witnessed massive transformation in the past several decades. Land degradation is active in Nepal. This study reviews the causes of land degradation in Nepal based on publicly available reports, books, journal articles, and government policy and regulations. The review also uses publicly available global datasets to contextualize local conditions. The review shows that topography; land use and cover change driven by population growth and urbanization; traditional agricultural practice in steep slope; soil erodibility due to unscientific ways of farming; use of chemical fertilizers and, pest and disease control techniques; unsustainable land management by the government; unscientific infrastructure development has been the proximate causes of land degradation in the majority of the cases. While underlying causes include population and poverty; out migration; deforestation; land tenure and property rights, non-farm employment; and technological change. The situation when combined with the Landslide Susceptibility Index and Land Cover data shows that the country needs to make concerted effort to stop and minimize the damage of land degradation in the country.

The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology (ACMG/AMP) have proposed a set of evidence-based guidelines to support sequence variant interpretation. The ClinGen hearing loss expert panel (HL-EP) introduced further specifications into the ACMG/AMP framework for genetic hearing loss. This study developed a tool named VIP-HL, aiming to semi-automate the HL ACMG/AMP rules. VIP-HL aggregates information from external databases to automate 13 out of 24 ACMG/AMP rules specified by HL-EP, namely PVS1, PS1, PM1, PM2, PM4, PM5, PP3, BA1, BS1, BS2, BP3, BP4, and BP7. We benchmarked VIP-HL using 50 variants where 83 rules were activated by the ClinGen HL-EP. VIP-HL concordantly activated 96% (80/83) rules, significantly higher than that of by InterVar (47%; 39/83). Of 4948 ClinVar star 2+ variants from 142 deafness-related genes, VIP-HL achieved an overall variant interpretation concordance in 88.0% (4353/4948). VIP-HL is an integrated online tool for reliable automated variant classification in hearing loss genes. It assists curators in variant interpretation and provides a platform for users to share classifications with each other. VIP-HL is available with a user-friendly web interface at http://hearing.genetics.bgi.com/.

Identifying phenotypic characteristics of evolutionarily fit individuals provides important insight into the evolutionary processes that cause range shifts with climate warming. Female beluga whales (Delphinapterus leucas) from the Canadian high Arctic (BB) residing in the core region of the species’ geographic range are 14% larger than their conspecifics at the southern periphery in Hudson Bay (HB). We investigated the causal mechanism for this north (core)-south (periphery) difference as it relates to fitness by combining morphometric data with ovarian corpora counted in female reproductive tracts. We found evidence for reproductive senescence in older HB females from the southern peripheral population but not for BB whales. Female beluga whale fitness in the more-northern BB increased faster with age (48% partial variation explained) versus a more gradual slope (25%) in HB. In contrast, body length in HB female beluga accounted for five times more of the total variation in fitness compared to BB whales. We speculate that female HB beluga fitness was more strongly linked with body length due to higher density, as larger body size provides survival advantages during seasonal food limitations. Understanding the evolutionary mechanism of how fitness changes will assist conservation efforts in anticipating and mitigating future challenges to peripheral populations.

We conduct a phylogeographic and population genetic study of the Asiatic Toad (Bufo gargarizans) to understand its evolutionary history, and the influence of geology and climate of the region. A total of 292 individuals from 94 locations were genotyped for two mitochondrial DNA loci (cytb, ND2 gene) and five nuclear introns (Sox9-2, Rho-3, CCNB2-3, UCH-2, DBI-2). We performed a suite of phylogenetic, population genetic, and divergence dating analyses. The phylogenetic trees constructed using mitochondrial loci inferred B. gargarizans being divided into two major groups: West (China mainland) and Northeast (Northeast China, Russia and Korean Peninsula). As with previous studies of this species, we recover population genetic structure not tied to geographic region. Additionally, we discover a new genetic clade restricted to Northeast Asia that points towards the Korean Peninsula being a glacial refugium during the Pleistocene. The weak phylogeographic pattern of B. gargarizans is likely the result of multiple biological, anthropogenic, and historical—robust dispersal abilities as a consequence of physiological adaptations, human translocation, geologic activity, and glacial cycles of the Pleistocene. We highlight the complex geologic and climatic history of Northeast Asia and encourage further research to understand its impact on the biodiversity in the region.

Rainfall-Runoff modeling is a hydrological modeling which is extremely important for water resources planning, development, and management. In this paper, Natural Resource Conservation Service-Curve Number (NRCS-CN) method along with Geographical Information System (GIS) approach was used to evaluate the runoff resulting from the rainfall of four stations, namely, Bilodra, Kathlal, Navavas and Rellawada of Sabarmati River basin. The rainfall data were taken for 10 years (2005-2014). The curve number which is the function of land use, soil and antecedent moisture condition (AMC) was generated in GIS platform. The CN value generated for AMC- I, II and III were 57.29, 75.39 and 87.77 respectively. Using NRCS-CN method, runoff depth was calculated for all the four stations. The runoff depth calculated with respect to the rainfall for Bilodra, Kathlal, Navavas and Rellawada shows a good correlation of 0.96. The computed runoff was compared with the observed runoff which depicted a good correlation of 0.73, 0.70, 0.76 and 0.65 for the four stations. This method results in speedy and precise estimation of runoff from a watershed.

Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.

Background: Brazil is an upper-middle-income country in South America with the world’s sixth largest population. Little is known on the volume, outcomes and trends of coronary artery bypass grafting (CABG) in Brazil’s public health system. Objective: The aim of this study was to evaluate the outcome of CABG in the public health system in from January 2008 to December 2017 through the database DATASUS. Methods: This study is based on publicly available material obtained from DATASUS, the Brazilian Ministry of Health’s data processing system, on numbers of surgical procedures, death rates, length of stay, and costs. Only isolated CABG procedures were included in our study. We used the TabNet software from the DATASUS website to generate reports. Chi-square test was used to compare death rates. A p-value of <0.05 was considered statistically significant. Results: We identified 226,697 CABG procedures performed from January 2008 to December 2017. The overall in-hospital mortality over the 10-year period was 5.7%. We observed statistically significant differences in death rates between the five Brazilian macro regions. Death rates by state ranged from 2.6% to 13.1%. The national average mortality rate remained stable over the course of time. Conclusion: Over 10 years, a high volume of CABG was performed in the Brazilian Public Health System with significant differences in mortality, number of procedures, and distribution of surgeries by region. Future databases involving all centers that perform CABG and carry out risk-adjusted analysis will help improve Brazilian results, and enable policymakers to adopt appropriate health care policies for greater transparency and accountability.

We present a case of a 75-year-old woman with typical myocardial infarction, however coronary angiogram was negative. Echocardiography identified the rare cause of chest pain, as a mobile mass of aortic valve was found to obstruct the coronary ostium. histopathology revealed a papillary fibroelastoma (PFE). Chest pain was relieved after surgical resection of the mass.

Lipomatous Hypertrophy of the Interatrial Septum (LHIS) is an unusual condition that can be presented as a mass-like bulge that typical spares of the fossa ovalis. We describe a 73-year-old overweight woman with dyspnea on exertion and two episodes of paroxysmal atrial fibrillation for the last eight months. A big sessile mass was detected in the interatrial septum measuring 3.7 x 4.7cm during transesophageal echocardiography. The patient underwent resection of the mass and pericardial patch reconstruction of the defect with significant improvement of her clinical status during the follow-up period. The histopathological analysis suggested LHIS.

Catheter-related DVT under the setting of TTP or TTP recovery stage may be presented as a more fulminant form. Certain guidelines for anticoagulation and antiplatelet therapy for thrombosis early should be further established. We present here a case of a patient presented with Comb (+) TTP and developed catheter-associated deep vein thrombosis (DVT). The patient was firstly diagnosed with Evans syndrome. However, he was refractory to a methylprednisolone pulse therapy with a combination of platelet transfusion and eventually developed microangiopathy of central nerve system. The immediate start of PEX (1500ml/d) induced a complete remission of acquired TTP and disappearance of neurological signs and symptoms. However, external iliac and femoro-popliteal venous thrombosis was diagnosed subsequently, inferior vena cava filter (IVC) filter was immediately planting accompanied with anticoagulation therapy. Meanwhile, PEX session was sustained as well as oral anticoagulant (rivaroxaban). 14 days later, the patient got full recovery. Our report aims at raising awareness of Catheter-related DVT under the setting of TTP should be cautious. It is necessary to start anticoagulation and antiplatelet therapy for thrombosis early, especially in such cases when PLT count > 50×109/L.