Accreditation and professional integration experiences of internationally qualified dentists working in the United Kingdom.

INTRODUCTION: Regulatory processes for Oral health care professionals are considered essential for patient safety and to ensure health workforce quality. The global variation in their registration and regulation is under-reported in the literature. Regulatory systems could become a barrier to their national and international movement, leading to loss of skilled human resources. The General Dental Council is the regulatory authority in the UK, one of the nine regulators of health care overseen by the Professional Standards Authority. AIM: The aim of this paper is to present the professional integration experiences of internationally qualified dentists (IQDs) working in the UK, against the background of regulation and accreditation nationally. METHODS: Registration data were obtained from the General Dental Council to inform the sampling and recruitment of research participants. Semi-structured interviews of 38 internationally qualified dentists working in the United Kingdom were conducted between August 2014 and October 2017. The topic guide which explored professional integration experiences of the dentists was informed by the literature, with new themes added inductively. A phenomenological approach involving an epistemological stance of interpretivism, was used with framework analysis to detect themes. RESULTS: Internationally qualified dentist's professional integration was influenced by factors that could be broadly classified as structural (source country training; registration and employment; variation in practising dentistry) and relational (experiences of discrimination; value of networks and support; and personal attributes). The routes to register for work as a dentist were perceived to favour UK dental graduates and those qualifying from the European Economic Area. Dentists from the rest of the world reported experiencing major hurdles including succeeding in the licensing examinations, English tests, proving immigration status and succeeding in obtaining a National Health Service performer number, all prior to being able to practice within state funded dental care. CONCLUSION: The pathways for dentists to register and work in state funded dental care in UK differ by geographic type of registrant, creating significant inconsistencies in their professional integration. Professional integration is perceived by an individual IQD as a continuum dictated by host countries health care systems, workforce recruitment policies, access to training, together with their professional and personal skills. The reliance of the UK on internationally qualified dentists has increased in the past two decades, however, it is not known how these trends will be affected by UK's exit from the European Union and the COVID-19 pandemic.

Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association.

South Asians (from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka) make up one quarter of the world's population and are one of the fastest-growing ethnic groups in the United States. Although native South Asians share genetic and cultural risk factors with South Asians abroad, South Asians in the United States can differ in socioeconomic status, education, healthcare behaviors, attitudes, and health insurance, which can affect their risk and the treatment and outcomes of atherosclerotic cardiovascular disease (ASCVD). South Asians have higher proportional mortality rates from ASCVD compared with other Asian groups and non-Hispanic whites, in contrast to the finding that Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) aggregated as a group are at lower risk of ASCVD, largely because of the lower risk observed in East Asian populations. Literature relevant to South Asian populations regarding demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies, is summarized. The evidence to date is that the biology of ASCVD is complex but is no different in South Asians than in any other racial/ethnic group. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially those related to insulin resistance, and no unique risk factors in this population have been found. This scientific statement focuses on how ASCVD risk factors affect the South Asian population in order to make recommendations for clinical strategies to reduce disease and for directions for future research to reduce ASCVD in this population.

LFA-1/ICAM-1 Ligation in Human T Cells Promotes Th1 Polarization through a GSK3ß Signaling-Dependent Notch Pathway.

In this study, we report that the integrin LFA-1 cross-linking with its ligand ICAM-1 in human PBMCs or CD4(+) T cells promotes Th1 polarization by upregulating IFN-γ secretion and T-bet expression. LFA-1 stimulation in PBMCs, CD4(+) T cells, or the T cell line HuT78 activates the Notch pathway by nuclear translocation of cleaved Notch1 intracellular domain (NICD) and upregulation of target molecules Hey1 and Hes1. Blocking LFA-1 by a neutralizing Ab or specific inhibition of Notch1 by a γ-secretase inhibitor substantially inhibits LFA-1/ICAM-1-mediated activation of Notch signaling. We further demonstrate that the Notch pathway activation is dependent on LFA-1/ICAM-1-induced inactivation of glycogen synthase kinase 3ß (GSK3ß), which is mediated via Akt and ERK. Furthermore, in silico analysis in combination with coimmunoprecipitation assays show an interaction between NICD and GSK3ß. Thus, there exists a molecular cross-talk between LFA-1 and Notch1 through the Akt/ERK-GSK3ß signaling axis that ultimately enhances T cell differentiation toward Th1. Although clinical use of LFA-1 antagonists is limited by toxicity related to immunosuppression, these findings support the concept that Notch inhibitors could be attractive for prevention or treatment of Th1-related immunologic disorders and have implications at the level of local inflammatory responses.

Pepper and cinnamon improve cold induced cognitive impairment via increasing non-shivering thermogenesis; a study.

Despite an understanding that a major effect of cold exposure is a fall in core body temperature which is responsible for the observed decrements in the performance, it is surprising that thermogenic supplements are seldom evaluated to verify if they can aid in improving the performance during cold exposure. Following evidence from our previous study indicating the ability of pepper and cinnamon to improve cold endurance, we investigated further here if the improved endurance had advantages in real time where they could positively affect cognitive performance (assessed by Novel object test) when exposed to cold in albino wistar rats. In order to delineate if the observed improvement if any, was due to their cognitive enhancing ability or thermogenic potential, distinctive room temperature (RT) and cold temperature (CT) groups were used. Cold exposure impaired cognitive performance which improved following treatment with both the spices. We noted an increased rate of cold adaptive thermogenesis in CT treated group as evidenced by an elevated norepinephrine, free fatty acid levels in blood, increased expression of UCP1 in brown adipose tissue, the net effect being a decreased fall in the core body temperature. Absence of any notable effect in these parameters in the RT treated group ascertained that at least in the current experimental set up the observed improvement in performance in CT treated group is due to the thermogenic potential of the spices alone. In conclusion, our results demonstrate that the cognitive impairment caused by exposure to cold can be effectively countered by agents with thermogenic potential.

Migration motives and integration of international human resources of health in the United Kingdom: systematic review and meta-synthesis of qualitative studies using framework analysis.

OBJECTIVE: The aim of this review was to examine the migration motives, the barriers to and facilitators of integration of international dental graduates, compared with nurses and doctors in the United Kingdom. METHODS: Electronic databases Ovid MEDLINE, EMBASE, PubMed, Web of Knowledge and OECD publications were systematically searched for English language publications from January 2000 to January 2017. A total of 31 qualitative studies were selected and quality appraised and meta-synthesis of the qualitative data was carried out using framework synthesis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to present the findings. RESULTS: There were no studies on migration motives and one study on integration experiences of international dentists in the UK. The nursing literature had the highest volume and quality of evidence on nursing workforce, whilst there was limited literature on international doctors in the UK. Migration of health professionals to the UK is determined by personal and professional factors, together with source country-specific and UK drivers. Active recruitment, post graduate training and financial gain act as strong common macro, meso and micro drivers that perpetuate migration into the UK, but the extent to which each of these drivers influence nurses' and doctors' migration is different. Integration experiences for international nurses and doctors differed based on their source country experiences and the work environment they entered. Nurses reported a wider knowledge and skills gap, more multi-level discrimination and less career progression compared to the doctors. The migrants' integration experiences depend on their cultural awareness, discrimination exposure, English language and communication skills, social and professional support networks, social integration and personal attributes. CONCLUSION: Migration of international health professionals is motivated by macro, meso and micro drivers at the international, national, professional and personal levels. The UK has strong common macro pull factors which attract nurses, doctors and dentists and may impact on the effectiveness of policies to restrict their migration. The integration experiences of nurses and doctors differ and further research is required to understand the integration experiences of dentists, in order to retain these professionals by tailoring policies to each of these professions.

Highly Efficient Supramolecular Aggregation-Induced Emission-Active Pseudorotaxane Luminogen for Functional Bioimaging.

The direct tracking of cells using fluorescent dyes is a constant challenge in cell therapy due to aggregation-induced quenching (ACQ) effect and biocompatibility issues. Here, we demonstrate the development of a biocompatible and highly efficient aggregation-induced emission (AIE)-active pseudorotaxane luminogen based on tetraphenylethene conjugated poly(ethylene glycol) (TPE-PEG2) (guest) and α-cyclodextrin (α-CD) (host). It is capable of showing significant fluorescent emission enhancement at the 400-600 nm range when excited at 388 nm, without increasing the concentration of AIE compound. The fluorescent intensity of TPE-PEG2 solution was effectively enhanced by 4-12 times with gradual addition of 1-4 mM of α-CD. 2D NOSEY 1H NMR revealed clear correlation spots between the characteristic peaks of α-CD and PEG, indicating the interaction between protons of ethylene glycol and cyclodextrin, and the structures are mainly based on threaded α-CD. The host-guest complex exhibits boosted fluorescent emission because the PEG side chains are confined in "nano-cavities" (host), thus, applying additional restriction on intermolecular rotation of TPE segments. In vitro cell experiments demonstrated the potential of AIE-active pseudorotaxane polymer as a biocompatible bioimaging probe.

Incidence of cutaneous adverse drug reactions among medical inpatients of Sultanah Aminah Hospital Johor Bahru.

INTRODUCTION: Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. OBJECTIVE: To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. METHODS: A prospective study was conducted among medical inpatients from July to December 2014. RESULTS: A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. CONCLUSION: The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.

Clinical features and prognostic factors of cutaneous vasculitis among dermatology patients in Johor Bahru, Malaysia.

BACKGROUND: Cutaneous vasculitis is common, yet the risk factors for its chronicity have not been established. OBJECTIVE: To describe the clinical spectrum and identify risk factors for chronicity of cutaneous vasculitis. METHODS: Retrospective data analysis of 275 patients diagnosed with cutaneous vasculitis from January 2008 to December 2013. RESULTS: The mean age was 33.7 (±17.89) years, with female predominance. The majority of patients were Malays (67.3%). Skin biopsy was performed in 110 (40%) patients. The commonest sign was palpable purpura (30.6%). The aetiology remained elusive in 51.3% of patients. Common identifiable causes include infection (19.7%) and connective tissue disease (10.2%). Extracutaneous features were noted in 46.5% of patients. Erythrocyte sedimentation rate and antinuclear antibody were raised in 124 of 170 and 27 of 175 patients with documented results respectively. Cutaneous vasculitis was the presenting symptom in seven patients with newly diagnosed systemic lupus erythematosus. Anti Streptolysin O Titre was positive in 82 of 156 patients with documented results. Despite antibiotics, 31.7% of them had chronic lesions. Prednisolone alone was used in 20% of patients while 16.4% needed steroid-sparing agents. Most patients who needed systemic therapy (62%) had unidentifiable aetiology. Among the 155 patients who remained under follow up, 36.4% had chronic disease, one patient succumbed due to septicaemia, and the rest fully recovered within three months. The presence of ulcerative lesion was significantly associated with developing chronic vasculitis (p=0.003). CONCLUSION: The clinical spectrum of cutaneous vasculitis in our population was similar to other studies. Ulcerative lesion predicts a chronic outcome.

Radix entomolaris: 2 case reports and clinical guidelines for endodontic management.

Variations in dental anatomy and root canal systems are often reported in the dental literature. Among them, Radix entomolaris (RE) is the presence of an additional lingual root in mandibular molars. Though RE appears relatively infrequently, knowledge of the condition will aid in its management. This article presents 2 case reports of RE and clinical guidelines for endodontic management.

Detection and mitigation of coordinated cyber-physical attack in CPPS.

Cyber-Physical Power System (CPPS) refers to a system in which the elements of the internet and the physical power system communicate and work together. With the use of modern communication and information technology, grid monitoring and control have improved. However, the components of a cyber system are extremely vulnerable to cyberattacks via cyber connections due to inadequate cyber security measures. Therefore, an adaptive defence strategy is required for the analysis and mitigation of the coordinated attack. The conventional approach of using an offline controller requires tuning for changes in the operating conditions of the system, which is inappropriate for the modern CPPS. To counter the coordinated attack, a framework that integrates STATCOM based Adaptive Model Predictive Controller with RPME and time delay compensator is proposed. This paper addresses attack impact, detection, and mitigation methods in CPPS. In both time domain and frequency domain simulations the case studies are conducted for three distinct situations namely physical attack, cyberattack, and coordinated attack. Convolutional Neural Network (CNN), Support Vector Machine (SVM), Random Forest (RF), and K Nearest Neighbour (KNN) are four data-driven methods used for the detection of anomalies in PMU measurement data. Simulation studies show that CNN performs better in anomaly detection than other classifiers based on assessed performance metrics. For coordinated attack mitigation the proposed STATCOM based Adaptive Model Predictive Controller with RPME quickly recovers the system than the STATCOM based conventional lead-lag controller. The efficacy of the proposed strategy is validated on the WSCC 3 machine 9 bus system.

Role of Network Pharmacology in Prediction of Mechanism of Neuroprotective Compounds.

Network pharmacology is an emerging pioneering approach in the drug discovery process, which is used to predict the therapeutic mechanism of compounds using various bioinformatic tools and databases. Emerging studies have indicated the use of network pharmacological approaches in various research fields, particularly in the identification of possible mechanisms of herbal compounds/ayurvedic formulations in the management of various diseases. These techniques could also play an important role in the prediction of the possible mechanisms of neuroprotective compounds. The first part of the chapter includes an introduction on neuroprotective compounds based on literature. Further, network pharmacological approaches are briefly discussed. The use of network pharmacology in the prediction of the neuroprotective mechanism of compounds is discussed in detail with suitable examples. Finally, the chapter concludes with the current challenges and future prospectives.

Optimized self-attention based cycle-consistent generative adversarial network adopted melanoma classification from dermoscopic images.

Skin is the exposed part of the human body that constantly protected from UV rays, heat, light, dust, and other hazardous radiation. One of the most dangerous illnesses that affect people is skin cancer. A type of skin cancer called melanoma starts in the melanocytes, which regulate the colour in human skin. Reducing the fatality rate from skin cancer requires early detection and diagnosis of conditions like melanoma. In this article, a Self-attention based cycle-consistent generative adversarial network optimized with Archerfish Hunting Optimization Algorithm adopted Melanoma Classification (SACCGAN-AHOA-MC-DI) from dermoscopic images is proposed. Primarily, the input Skin dermoscopic images are gathered via the dataset of ISIC 2019. Then, the input Skin dermoscopic images is pre-processed using adjusted quick shift phase preserving dynamic range compression (AQSP-DRC) for removing noise and increase the quality of Skin dermoscopic images. These pre-processed images are fed to the piecewise fuzzy C-means clustering (PF-CMC) for ROI region segmentation. The segmented ROI region is supplied to the Hexadecimal Local Adaptive Binary Pattern (HLABP) to extract the Radiomic features, like Grayscale statistic features (standard deviation, mean, kurtosis, and skewness) together with Haralick Texture features (contrast, energy, entropy, homogeneity, and inverse different moments). The extracted features are fed to self-attention based cycle-consistent generative adversarial network (SACCGAN) which classifies the skin cancers as Melanocytic nevus, Basal cell carcinoma, Actinic Keratosis, Benign keratosis, Dermatofibroma, Vascular lesion, Squamous cell carcinoma and melanoma. In general, SACCGAN not adapt any optimization modes to define the ideal parameters to assure accurate classification of skin cancer. Hence, Archerfish Hunting Optimization Algorithm (AHOA) is considered to maximize the SACCGAN classifier, which categorizes the skin cancer accurately. The proposed method attains 23.01%, 14.96%, and 45.31% higher accuracy and 32.16%, 11.32%, and 24.56% lesser computational time evaluated to the existing methods, like melanoma prediction method for unbalanced data utilizing optimized Squeeze Net through bald eagle search optimization (CNN-BES-MC-DI), hyper-parameter optimized CNN depending on Grey wolf optimization algorithm (CNN-GWOA-MC-DI), DEANN incited skin cancer finding depending on fuzzy c-means clustering (DEANN-MC-DI). RESEARCH HIGHLIGHTS: This manuscript, self-attention based cycle-consistent. SACCGAN-AHOA-MC-DI method is implemented in Python. (SACCGAN-AHOA-MC-DI) from dermoscopic images is proposed. Adjusted quick shift phase preserving dynamic range compression (AQSP-DRC). Removing noise and increase the quality of Skin dermoscopic images.

A typology of internationally qualified dentists in the United Kingdom.

Introduction: The Global Strategy for Human Resources for Health 2030, requires member states to half their dependency on an international workforce by 2030. In order to design policies towards that goal, country-specific research on migration motivations of the health workforce is required. The United Kingdom (UK) is a net importer of health professionals and whilst there is a body of research on doctors' and nurses' migration, there is no research on the migration motivations of migrant dentists in the UK. This research explored the migration motivations of internationally qualified dentists (IQDs) in the UK and presents a typology to understand the global migration of dentists in the context of oral health workforce. Methods: The paper presents qualitative data from semi-structured interviews conducted between August 2014 and October 2017, of IQDs working in the United Kingdom. The topic guide for interviews was informed by the literature, with new themes added inductively. A phenomenological approach involving an epistemological stance of interpretivism, was used with framework analysis. Results: A total of 38 internationally qualified dentists (M = 18, F = 20), migrating from the five World Health Organization regions, and working in general practice, NHS hospitals and in community dental services across the four nations of the UK were interviewed. Seven types of internationally qualified dentists were identified working in the UK. They were livelihood migrants, career-orientated migrants, dependant migrants, backpacker migrants, commuter migrants, undocumented migrants, and education-tourist migrant. The categories were based on their migration motivations, which were complex, multifactorial, and included personal, professional, national, and international drivers. The typology, based on their migration motivations, offered a structured, comprehensive understanding of the migrant dental workforce. This typology involving dentists provides additional dimensions to commuter and undocumented migrants described in the context of other health professionals. The education-tourist migrant is a new category proposed as an extension to existing typology in health professional migration. Conclusions: The typology of internationally qualified dentists has congruency with other health professionals' typology in categories previously described and demonstrates that each of these categories are complex, fluid and change in response to policy changes. The new category of education-tourist migrant along with oral health dimensions of commuter and undocumented migrants adds to the existing typology in health professional migration.

Modulation of nuclear receptor 4A1 expression improves insulin secretion in a mouse model of chronic pancreatitis.

OBJECTIVES: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to insulin secretory defects and associated metabolic alterations. Owing to lack of molecular understanding, no pharmacotherapies to treat insulin secretory defects have been approved to date. We aimed to delineate the molecular mechanism of ß-cell dysfunction in CP. METHODS: Transcriptomic analysis was conducted to identify endocrine specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis on NovaSeq 6000 of NR4A1 overexpressed (OE) MIN6 cells was performed to identify aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure. Downstream effect of NR4A1OE was examined by Fura2 AM based fluorometric and imaging studies of intracellular calcium. Mice with CP were treated with IFN-γ neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion. RESULTS: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 µg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 µg/mg protein/minute, p = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold (p = 0.03), improved insulin secretion (4.4 ± 0.2-fold, p = 0.01), associated with increased Ca2+ levels (2.39 ± 0.06-fold, p = 0.009). CONCLUSIONS: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.

Survival after Trastuzumab Therapy in Patients with Locally Advanced or Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of Randomized Controlled Trials.

Background: In the Trastuzumab for Gastric Cancer study, it was found that trastuzumab combined with doublet chemotherapy (fluoropyrimidine and platinum) was the gold-standard treatment for gastroesophageal adenocarcinoma (GEA) that was locally advanced, unresectable, or metastatic (HER2+). Materials and Methods: We performed a meta-analysis of randomized phase II/III studies testing trastuzumab in combination or alone. Results: This meta-analysis's findings involved 2048 patients in total. The treatment arm and hormone receptor status were used to stratify the combined HR. Overall, the PFS (Random model) HR [0.80] and 95% confidence intervals (CI) [0.68-0.95] were significantly higher for regimens containing trastuzumab, fluoropyrimidine, and platinum compared to regimens containing fluoropyrimidine and platinum. Conclusions: The results of this meta-analysis provide additional support for trastuzumab's use in treating HER2-positive GEA, particularly in cases where the disease lacks a HER2+ receptor.

Nocardiopsis sp. SD5: a potent feather degrading rare actinobacterium isolated from feather waste in Tamil Nadu, India.

Feather waste, generated in large quantities as a byproduct of commercial poultry processing, is nearly pure keratin protein, and keratin in its native state is not degradable by common proteolytic enzymes. The aim of the study was to find a potent feather degrading actinobacteria from feather waste soil. Out of 91 actinobacterial isolates recorded from feather waste soil in Tiruchirappalli and Nammakkal District, Tamil Nadu, India, isolate SD5 was selected for characterization because it exhibited significant keratinolytic activity. On the basis of the phenotypic, biochemical characterization and 16S rRNA gene-sequencing studies, the isolate was identified as Nocardiopsis sp. SD5. Protease and keratinase activity of Nocardiopsis sp. SD5 were analyzed. The enzyme was more stable over the neutral pH and the temperature of 40 °C. The optimum temperature and pH for both proteolytic and keratinolytic activity was determined at 50 °C and pH 9, respectively. Enzyme inhibitors, detergents and chelator declined the enzyme activity with increasing concentration. Nondenaturing polyacrylamide gel electrophoresis and zymogram elucidated the presence of 30 and 60 kDa protease enzymes. These findings indicated that thermo alkaliphilic feather degrading strain Nocardiopsis sp. SD5 could be used to control the feather waste pollution and to convert keratin rich feather waste into useful feedstock for poultry industry.

Association of Cardiovascular Events with COVID-19 Vaccines using Vaccine Adverse Event Reporting System (VAERS): A Retrospective Study.

BACKGROUND: COVID-19 vaccines have played a crucial role in reducing the burden of the global pandemic. However, recent case reports have indicated the association of the COVID- 19 vaccines with cardiovascular events but the exact association is unclear so far. OBJECTIVE: Therefore, the objective of the current study is to find out the association of cardiovascular events with COVID-19 vaccines. METHODS: The COVID-19 Vaccine Knowledge Base (Cov19VaxKB) tool was used to query the Vaccine Adverse Event Reporting System (VAERS) database. The proportional reporting ratio [PRR (≥2)] with associated chi-squared value (>4), and the number of cases > 0.2% of total reports, was used to assess the association of COVID-19 vaccines with cardiovascular events. RESULTS: A total of 33,754 cases of cardiovascular events associated with COVID-19 vaccines were found in the Cov19VaxKB tool. The cases were observed in different age groups (18-64, and 65 years and above) and gender. The disproportionality measures indicate a statistically significant association between cardiovascular events and COVID-19 vaccines. CONCLUSION: The current study identified a signal of various cardiovascular events with the COVID-19 vaccines. However, further causality assessment is required to confirm the association.

Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure.

AIMS: Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascular wall, down-regulates the sphingolipid de novo biosynthesis via serine palmitoyltransferase (SPT), first and rate liming enzyme, to impact vascular functions and blood pressure. Nogo-A, a splice isoform of Nogo, is transiently expressed in cardiomyocyte (CM) following pressure overload. Cardiac Nogo is up-regulated in dilated and ischaemic cardiomyopathies in animals and humans. However, its biological function in the heart remains unknown. METHODS AND RESULTS: We discovered that Nogo-A is a negative regulator of SPT activity and refrains ceramide de novo biosynthesis in CM exposed to haemodynamic stress, hence limiting ceramide accrual. At 7 days following transverse aortic constriction (TAC), SPT activity was significantly up-regulated in CM lacking Nogo-A and correlated with ceramide accrual, particularly very long-chain ceramides, which are the most abundant in CM, resulting in the suppression of 'beneficial' autophagy. At 3 months post-TAC, mice lacking Nogo-A in CM showed worse pathological cardiac hypertrophy and dysfunction, with ca. 50% mortality rate. CONCLUSION: Mechanistically, Nogo-A refrains ceramides from accrual, therefore preserves the 'beneficial' autophagy, mitochondrial function, and metabolic gene expression, limiting the progression to HF under sustained stress.

Nocardiopsis sp. SD5: A potent feather degrading rare actinobacterium isolated from feather waste in Tamil Nadu, India.

Feather waste, generated in large quantities as a byproduct of commercial poultry processing, is nearly pure keratin protein, and keratin in its native state is not degradable by common proteolytic enzymes. The aim of the study was to find a potent feather degrading actinobacteria from feather waste soil. Out of 91 actinobacterial isolates recorded from feather waste soil in Tiruchirappalli and Nammakkal District, Tamil Nadu, India, isolate SD5 was selected for characterization because it exhibited significant keratinolytic activity. On the basis of the phenotypic, biochemical characterization and 16S rRNA gene-sequencing studies, the isolate was identified as Nocardiopsis sp. SD5. Protease and keratinase activity of Nocardiopsis sp. SD5 were analyzed. The enzyme was more stable over the neutral pH and the temperature of 40 °C. The optimum temperature and pH for both proteolytic and keratinolytic activity was determined at 50 °C and pH 9, respectively. Enzyme inhibitors, detergents and chelator declined the enzyme activity with increasing concentration. Non denaturing poly acrylamide gel electrophoresis and zymogram elucidated the presence of 30 kda and 60 kda protease enzymes. These findings indicated that thermo alkaliphilic feather degrading strain Nocardiopsis sp. SD5 could be used to control the feather waste pollution and to convert keratin rich feather waste into useful feedstock for poultry industry. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).