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Background/Aim: Glioblastomas (GBM) are infiltrative malignant brain tumors which mostly recur within a year’s time following surgical resection and chemo-radiation therapy. Studies on glioblastoma cells following radiochemotherapy, have been demonstrated to induce transdifferentiation, cellular plasticity, activation of DNA damage response and stemness. As glioblastomas are heterogenous tumors that develop treatment resistance and plasticity, we investigated if there exist genome-wide DNA methylation changes in recurrent tumors. Materials and Methods: Utilizing genome-wide DNA methylation arrays, we compared the DNA methylation profile of 11 primary (first occurrence) tumors with 13 recurrent (relapsed) GBM, to delineate the contribution of epigenetic changes associated with therapy exposure, therapy resistance, and relapse of disease. Results: Our data revealed 1,224 hypermethylated- and 526 hypomethylated-probes in recurrent glioblastomas compared to primary disease. We found differential methylation of solute carrier and ion channel genes, interleukin receptor/ligand genes, tumor-suppressor genes and genes associated with metastasis. We functionally characterized one such hypomethylated-up-regulated gene, namely anthrax toxin receptor 1/tumor endothelial marker 8 (ANTXR1/TEM8), whose expression was validated to be significantly up-regulated in recurrent glioblastomas compared to primary tumors and confirmed by immunohistochemistry. Using overexpression and knockdown approaches, we showed that TEM8 induces proliferation, invasion, migration, and chemo-radioresistance in glioblastoma cells. Additionally, we demonstrated a novel mechanism of β-catenin stabilization and activation of the βcatenin transcriptional program due to TEM8 overexpression via a Src/PI3K/AKT/GSK3β/β-catenin pathway. Conclusion: We report genome-wide DNA methylation changes in recurrent GBM and suggest involvement of the TEM8 gene in GBM recurrence and progression. [ABSTRACT FROM AUTHOR]

The IFIH1 gene, encoding melanoma differentiation‐associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation in weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain‐of‐function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi–Goutieres and Singleton–Merten syndromes, while biallelic loss causes immunodeficiency. In this study, nine patients suffering from recurrent infections, inflammatory diseases, severe COVID‐19 or multisystem inflammatory syndrome in children (MIS‐C) were identified with putative loss‐of‐function IFIH1 variants by whole‐exome sequencing. All patients revealed signs of lymphopaenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin and IL‐6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID‐19 or MIS‐C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS‐C. There was a significant association between IFIH1 monoallelic loss of function and susceptibility to infections in males. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with Poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss‐of‐function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS‐CoV‐2‐related disorders. [ABSTRACT FROM AUTHOR]

The aim of this investigation is to arrange partial differential equations (PDEs) into simplified form for gradients (mass and thermal) in the inclined magneto hydrodynamic flow of hybrid (CuO–TiO2/Water) nanoliquid in a permeable media. The modeled term is extremely nonlinear with the boundary conditions. So, this research focuses on numerical solution by using bvp4c solver in MATLAB software and by applying similarity transformation. Simulations have been done to discover the dynamics of stream and the transport of heat and mass under parametric deviation. To examine the impact of a temperature gradient on the transport of mass and the role of a concentration gradient on the transport of heat energy, outcomes have been documented in tabular form and shown through graphs. Remarkable changes in motion, temperature and concentration are noted when Dufour and Soret numbers vary. [ABSTRACT FROM AUTHOR]

The purpose of this study is to accelerate green consumerism efforts by assisting green marketers in identifying the homogeneous and significant eco-friendly customer segments emerging in India. The study determines the antecedents driving customers to purchase green products, which can be leveraged while targeting the studied customer group and designing promotional strategies for these microgreen segments. Non-probability criterion-based sampling technique was used in collecting the data across Pan India through various online platforms like LinkedIn, Twitter, and Facebook. The exploratory factor analysis, followed by the cluster and discriminant analysis, is conducted for inferential results. The results reveal eight major factors influencing green consumer behavior, out of which green habit, green culture awareness and attitude, interpersonal influence, and green purchase intention/behavior emerged as the most significant factors. The study establishes two important clusters of green consumers, that is, "Green Dads"-generation Y males and "Green Janes"-generation Z females, with social media marketing and subjective norms as the most influential factors in discriminating between these two clusters. This research magnifies the importance of profiling customers based on demographics, psychographics, behavioral variables, and external marketing cues. The varied combinations of factors concerning ecological behavior imply the focus on micro variables by marketers, hence promulgating the projected granularity of green market segmentation and consequential consumer behavior. [ABSTRACT FROM AUTHOR]

Retailers use artificial intelligence (AI) to serve customers better. This study examines the role of chatbots in shaping attitudes of customers relating to usefulness, usability, and trust when shopping for groceries online. Automated conversational agents, or chatbots, not only understand customers, but also provide them product knowledge, and promote behavioral change. Chatbots, automated and cost-effective as they are, provide efficient first-level support because a human employee cannot answer the whole range of customer questions round the clock. For Analysis, Structural Equation Modeling (SEM) with the AMOS analysis programme version 23 is used in this investigation. The online questionnaire was circulated via Google forms (N-375) promoted on social media to respondents who are at least 18 years of age and have completed online transactions, selecting them using a sampling quota in the survey procedure. A novel model will be tested and compared to prior research. According to the study's findings, attitudes are significantly influenced by usefulness, usability, and trust, whereas attitudes have a major impact on decisions. However, it appears that trust has little impact on consumers' views about online purchasing. This conclusion could be yet more support for previous research that consistently claims that trust affects customer purchases. In the case of online purchasing, not only is the trust element important for customers to make a choice, but it also matters more than the attitude factor because attitude is a product of many different aspects. Significantly consumer confidence in internet retailers is the factor that most affects attitude. The quantitative investigation revealed that a deep majority of respondents were apprehensive about employing AI and online-retail (e-retail) chatbots, primarily due to concerns about their accuracy and security, but would like to seek the advice of chatbots for informative purposes. [ABSTRACT FROM AUTHOR]

Surgery for excision of juvenile nasopharyngeal angiofibroma (JNA) carries the possibility of massive life-threatening haemorrhage. Anaesthetic management aims to maintain haemodynamic stability and reduce blood loss. This case series describes the application of the bundled approach as a multimodal blood loss prevention bundle (MBLPB). Twenty patients underwent 23 surgeries with MBLPB. The blood loss and the number of units of blood transfused were recorded. The surgeon satisfaction score was assessed. The median [interquartile range (IQR)] estimated blood loss was 1300 (650-2350) ml. Patients with tumours in stages I and II had a median (IQR) blood loss of 550 (270-750) ml compared to patients with higher grades of tumours (stages III, IV) with a median (IQR) blood loss of 2100 (1300-2500) ml. Median (IQR) units of packed red cells transfused was 1 (0-3). The surgeon's satisfaction score was high when MBLPB was applied for JNA. However, it does not appear to reduce blood loss markedly. [ABSTRACT FROM AUTHOR]

Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we clinically characterize a case series of patients with COVID-19, who were otherwise healthy, young adults (N = 55; mean age 34.1 ± SD 5.0 years) from 16 Asian, Middle Eastern, and North African countries. Using whole exome sequencing, we identify rare, likely deleterious variants affecting 16 immune-related genes in 17 out of 55 patients (31%), including 7 patients (41% of all carriers or 12.7% of all patients) who harbored multiple such variants mainly in interferon and toll-like receptor genes. Protein network analysis as well as transcriptomic analysis of nasopharyngeal swabs from an independent COVID-19 cohort (N = 50; 42% Asians and 22% Arabs) revealed that most of the altered genes, as identified by whole exome sequencing, and the associated molecular pathways were significantly altered in COVID-19 patients. Genetic variants tended to be associated with mortality, intensive care admission, and ventilation support. Our clinical cases series, genomic and transcriptomic findings suggest a possible role for interferon pathway genes in severe COVID-19 and highlight the importance of extending genetic studies to diverse populations to better understand the human genetics of disease. [ABSTRACT FROM AUTHOR]

Missense variants in the RNF13 gene have been previously known to cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive through a gain‐of‐function disease mechanism. Here, we identify a nonsense variant, expected to result in protein truncation, in a similarly affected patient. We show that this nonsense variant, residing in the terminal exon, is likely to escape nonsense‐mediated decay while removing a critical region for protein function, thus resulting in a gain‐of‐function effect. We review the literature and disease databases and identify several other affected individuals with overlapping phenotypes carrying distinct truncating variants in the terminal exon upstream of the putative critical region. Furthermore, we analyze truncating variants from the general population, namely, the Genome Aggregation Database (gnomAD), and provide additional evidence supporting our hypothesis, and ruling out haploinsufficiency as an alternative disease mechanism. In summary, our case report, literature review, and analysis of disease and population databases strongly support the hypothesis that heterozygous gain‐of‐function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive. [ABSTRACT FROM AUTHOR]

Neurofibromatosis (NF1) is a relatively common multi-system genetic disorder. NF1 increases the risk of hypertension, and vasculopathy is a common finding. Extracranial vertebral artery aneurysm, though rare, can rupture and cause fatal hemorrhage. Pregnancy in NF1 is known to be associated with hypertension, preeclampsia, Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We report anesthesia management of a primigravida with 30 weeks of gestation with neurofibromatosis presenting with severe preeclampsia and acute onset vertebral artery aneurysm, who underwent urgent cesarean section. We opted for general anesthesia over regional due to the risk of aneurysm rupture and technical difficulty with vigilant hemodynamic control. Postoperative course was complicated with HELLP and sepsis but was successfully managed. Knowledge, careful preoperative evaluation, appropriate technique, and management of anesthesia, and close postoperative monitoring are of utmost importance. [ABSTRACT FROM AUTHOR]

Objective: This is a comprehensive characteristic study of Kawasaki disease (KD) and Multi system inflammatory syndrome in children (MIS-C) in the Middle East that creates a formula to differentiate between the two. Methods: We conducted a descriptive comparative study of KD and MIS-C in the United Arab Emirates. Retrospective MIS-C and KD cohorts were recruited between January 2017 until August 2021.We compared clinical and laboratory characteristics between both groups. Our data were compared with 87 patients with KD or MIS-C from the literature. Results: We report on123 patients. Sixty-seven (54%) met the criteria for KD (36 male, 43 Arab), and fifty-six (46%) met the criteria for MIS-C (28 male, 35 Arab). The median age was 2.2 years range (0.15–10.7) in the KD group and 7.3 years (0.7–15.2) in the MIS-C group (P < 0.001). The clinical features on admission showed an increase in gastrointestinal manifestations in MIS-C compared with KD (84% vs. 31%, P < 0.001). Laboratory tests on admission revealed a significant increase in the following tests in KD compared with MIS-C; white blood cells (mean 16.30 10(3) µcL vs. 11.56 10(3) µcL, P < 0.001), absolute neutrophils (mean 10.72 10(3) µcL vs. 8.21 10(3) µcL, P 0.008), absolute lymphocytes (mean 3.92 10(3) µcL vs. 2.59 10(3) µcL, P 0.003), erythrocyte sedimentation rate (mean 73 mm/hr vs. 51 mm/hr, P < 0.001) and platelets (median {390 10(3) µcL vs. 236 10(3) µcL, P < 0.001}). In contrast, procalcitonin and ferritin were increased in the MIS-C group (2.4)ng/mL, 370 ng/mL; P < 0.001). Cardiac dysfunction and admission to the pediatric intensive care unit were higher in MIS-C than in KD (21% vs. 8% and 33% vs. 7.5%, respectively, P < 0.001). Conclusion: This study showed vast similarities between KD and MIS-C, suggesting that they lie along the same clinical spectrum. However, there are several differences between the two disease entities suggesting that MIS-C most likely represents a new severe variant of KD. Based on our findings in this study, we created a formula to differentiate between KD and MIS-C. [ABSTRACT FROM AUTHOR]

Background and Aims: Neurological complications (NCs) are significantly associated with reduced regional cerebral saturation (rSO2) in patients undergoing cardiac surgeries, as assessed with cerebral oximetry (COx). However, limited evidence is available in patients undergoing balloon mitral valvotomy (BMV). Thus, we evaluated the utility of COx in patients undergoing BMV, the incidence of BMV-related NCs and the association of >20% reduction in rSO2 with NCs. Methods: This pragmatic, prospective, observational study was performed after ethical approval, over November 2018 to August 2020, in the cardiology catherization laboratory of a tertiary care hospital. The study involved 100 adult patients undergoing BMV for symptomatic mitral stenosis. The patients were evaluated at initial presentation, pre-BMV, post-BMV and 3 months after the BMV. Results: The incidence of NCs was 7%, including transient ischaemic attack (n = 3), slurred speech (n = 2) and hemiparesis (n = 2). A significantly greater proportion of patients with NCs had a > 20% decrease in the rSO2 (P value = 0.020). At >20% cut-off, the COx had a sensitivity and specificity of 57.1% and 80%, respectively, in the prediction of NCs. Female sex (P value = 0.039), history of cerebrovascular episodes (P value < 0.001) and number of balloon attempts (P value < 0.001) were significantly associated with NCs. Patients with and without NCs had a significantly greater post-BMV mean % change in rSO2 than pre-BMV (both right and left sides), but the magnitude of mean % change was greater in those with NCs. Conclusions: COx alone has low sensitivity and specificity in the prediction of NCs and cannot reliably predict the development of post-BMV NCs. [ABSTRACT FROM AUTHOR]

The motive of this study is to investigate the spinning fluid-flow due to revolving disk for the magnetic unsteady Brownian motion of viscous nanofluid. Here the disk is assumed to have an inverse linear angular velocity. In this paper mass transfer is incorporated in the analysis with the existing problem. The array of equation for the unsteady flow firstly converted into dimensionless non-linear equation using appropriate transformation and then the dimensionless system of equation is further solved numerically utilizing MAPLE software. The different emerging parameters mainly magnetic parameter, variable viscosity, Prandtl number, Eckert number, thermophoresis, and Brownian motion parameter has been investigated through graphs and shown in tabular form also. [ABSTRACT FROM AUTHOR]

Background: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. Methods: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P <.05 was considered statistically significant. Results: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7–35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7–37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. Conclusions: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of experiential marketing on audience perception in Indian performing art educational institutions. For this purpose, data were collected between August 2022 to January 2023 from 311 students of the National School of Drama (NSD), Shriram Bharatiya Kala Kendra, Kathak Kendra, and Triveni Kala Sangam. The study focused on experiential marketing strategies incorporated into digital platforms. In this study, structural equation modelling and regression analysis were employed to analyze the impact of experiential marketing on audience perception, and the results indicated a positive relationship between perception and the quality of Interactive Experiences. However, no statistically significant results were found for the relationships between Perception and Immersive Experiences and Perception and Educational Value, suggesting the need for more specific and tailored measures. The results had important implications for designers and developers of digital experiences, who might benefit from prioritizing interactivity and tailoring content to enhance user perception of immersive experiences and educational value on behalf of their educational clientele. [ABSTRACT FROM AUTHOR]

We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children's intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital's genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients. [ABSTRACT FROM AUTHOR]

Persons with type 2 diabetes born in the regions of famine exposures have disproportionally elevated risk of vision-threatening proliferative diabetic retinopathy (PDR) in adulthood. However, the underlying mechanisms are not known. In the present study, we aimed to investigate the plausible molecular factors underlying progression to PDR. To study the association of genetic variants with PDR under the intrauterine famine exposure, we analyzed single nucleotide polymorphisms (SNPs) that were previously reported to be associated with type 2 diabetes, glucose, and pharmacogenetics. Analyses were performed in the population from northern Ukraine with a history of exposure to the Great Ukrainian Holodomor famine [the Diagnostic Optimization and Treatment of Diabetes and its Complications in the Chernihiv Region (DOLCE study), n = 3,583]. A validation of the top genetic findings was performed in the Hong Kong diabetes registry (HKDR, n = 730) with a history of famine as a consequence of the Japanese invasion during WWII. In DOLCE, the genetic risk for PDR was elevated for the variants in ADRA2A , PCSK 9, and CYP2C19*2 loci, but reduced at PROX1 locus. The association of ADRA2A loci with the risk of advanced diabetic retinopathy in famine-exposed group was further replicated in HKDR. The exposure of embryonic retinal cells to starvation for glucose, mimicking the perinatal exposure to famine, resulted in sustained increased expression of Adra2a and Pcsk9 , but decreased Prox1. The exposure to starvation exhibited a lasting inhibitory effects on neurite outgrowth, as determined by neurite length. In conclusion, a consistent genetic findings on the famine-linked risk of ADRA2A with PDR indicate that the nerves may likely to be responsible for communicating the effects of perinatal exposure to famine on the elevated risk of advanced stages of diabetic retinopathy in adults. These results suggest the possibility of utilizing neuroprotective drugs for the prevention and treatment of PDR. [ABSTRACT FROM AUTHOR]

Objective: Oral submucous fibrosis (OSF) is a debilitating potentially malignant condition of the buccal cavity characterized by extensive extracellular matrix deposition resulting in stiffness and trismus. As OSF is a progressive disease, we hypothesized that there would be extensive epigenetic changes in OSF tissues. Materials and Methods: Using the Infinium HumanMethylation450 BeadChip Array, we analyzed gross DNA methylation changes in seven OSF tissues compared to five controls. Comparison with transcriptomic data and pathway analyses was conducted to find commonly regulated genes. Results: A total of 3,294 differentially methylated regions mapping to 857 genes were identified. Comparison with transcriptome data revealed 38 downregulated‐hypermethylated genes and 55 hypomethylated‐upregulated genes. Using methylation‐specific and qRT‐PCR, aberrant hypomethylation and increased expression of FGF13, RPS6KA3, and ACSL4 genes were confirmed. Pathways involved in insulin signaling, ubiquitin‐mediated proteolysis, nicotine addiction, and RAS/MAPK pathways were dysregulated, among others. Intriguingly, numerous genes located on the X chromosome were dysregulated in OSF tissues as the transcript for XIST gene was downregulated due to hypermethylation of the XIST promoter. Conclusions: This study highlights global epigenetic dysregulation of tissues of the oral cavity in OSF patients and hints at possible X chromosomal dysregulation, previously not implicated in the pathogenesis of OSF. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infections are mostly treated empirically with broad-spectrum antibiotics which have resulted in development of multi-drug resistant strains. Limited options of newer antibiotics have necessitated the reintroduction of some old antimicrobial agents such as fosfomycin. Aim: To evaluate the in-vitro activity of fosfomycin against uropathogenic E.coli. Method: A total of 145 E.coli isolates were identified by conventional microbiological procedures and antimicrobial susceptibility performed by Kirby-Bauer disk diffusion method. They were screened for extended spectrum β-lactamase (ESBL) production and screen positives were confirmed by phenotypic confirmatory test (CLSI). Results: Out of 145 isolates, 91 (62.76 %) were found in males and 54 (37.24%) from females. Majority of the isolates were detected in the age group of 21-30 years 48.96%. A very high susceptibility of 94.48% was observed with fosfomycin. Suceptibility to tigecycline and nitrofurantoin was 87.58 % and 77.24 % respectively. Multi-drug resistance was observed in 85.51% isolates and 45.51% were ESBL producers. Conclusion: Fosfomycin showed an excellent in vitro activity against MDR and ESBL producing E.coli, therefore it should be considered as a potential therapeutic alternative in the treatment of UTI. [ABSTRACT FROM AUTHOR]

Purpose: Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long‐term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR). Methods: We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932–1933) and the WWII (1941–1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942–1945. Results: During the Holodomor and WWII, perinatal famine was associated with a 1.76‐fold (p = 0.019) and 3.02‐fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66‐fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (padditive interaction < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05). Conclusion: In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications. [ABSTRACT FROM AUTHOR]

Genetic variation in populations of Middle Eastern origin remains highly underrepresented in most comprehensive genomic databases. This underrepresentation hampers the functional annotation of the human genome and challenges accurate clinical variant interpretation. To highlight the importance of capturing genetic variation in the Middle East, we aggregated whole exome and genome sequencing data from 2116 individuals in the Middle East and established the Middle East Variation (MEV) database. Of the high-impact coding (missense and loss of function) variants in this database, 53% were absent from the most comprehensive Genome Aggregation Database (gnomAD), thus representing a unique Middle Eastern variation dataset which might directly impact clinical variant interpretation. We highlight 39 variants with minor allele frequency >1% in the MEV database that were previously reported as rare disease variants in ClinVar and the Human Gene Mutation Database (HGMD). Furthermore, the MEV database consisted of 281 putative homozygous loss of function (LoF) variants, or complete knockouts, of which 31.7% (89/281) were absent from gnomAD. This set represents either complete knockouts of 83 unique genes in reportedly healthy individuals, with implications regarding disease penetrance and expressivity, or might affect dispensable exons, thus refining the clinical annotation of those regions. Intriguingly, 24 of those genes have several clinically significant variants reported in ClinVar and/or HGMD. Our study shows that genetic variation in the Middle East improves functional annotation and clinical interpretation of the genome and emphasizes the need for expanding sequencing studies in the Middle East and other underrepresented populations. [ABSTRACT FROM AUTHOR]

The paper provides the description on medical sector organizations which emphasize on quality management for example reducing waiting lines, good medical services to patients within reasonable price and time; Applying queuing theory to reduce waiting lines, maintaining a continuous improvement program; Trained employees in hospitals on reducing delay time in services and low-cost services to patients need. Medical sectors are seen to be less effective, inefficient and inadequate. Generally, those organizations, which are aware about quality and upgrade the quality time to time, will obtain the highest consumer acceptance and support. The 'Quality Management', as it is referred to reduce waiting lines, medical costs. To improve efficiency, quality and performance. It also considers customer satisfaction which is also a major part of medical sector when several sources of variation represent. Analyzing medical processes for removing wastage of time, money and rework. Quality management led to significant reductions in waiting lines and medical costs. The use of qualityassurance strategies and statistical tools can be directly applied in medical sector organizations with improved quality of service providing and the results of care from the customer's point of view. [ABSTRACT FROM AUTHOR]

In major/life-threatening bleeding, administration of timely and appropriate reversal agents is imperative to reduce morbidity and mortality. Due to complexities associated with the use of reversal agents, a clinical pharmacist-driven anticoagulation reversal program (ARP) was developed. The goal of this program was to ensure appropriateness of reversal agents based on the clinical scenario, optimize selection and avoid unintended consequences. This study describes the impact of a pharmacist-driven anticoagulation program on patient outcomes and cost. A single center retrospective chart review of adult patients whom the ARP was consulted from October 2018 to January 2020 was performed. Patients were included in the efficacy analysis if they were > 18 years of age and presented with acute bleeding. Patients were excluded from the efficacy analysis if the recommended reversal agent was not administered, if a repeat head CT was not available for patients who presented with intracranial hemorrhage (ICH), or if the patient was not bleeding. All patients were included in the economic evaluation. The primary outcome was the percentage of patients who achieved effective hemostasis within 24 h of anticoagulation reversal. Secondary outcomes include incidence of thromboembolic events, in-hospital mortality, and cost avoidance. One hundred twenty-one patients were evaluated by the ARP with 92 patients included in the efficacy analysis. The primary sites of bleeding were ICH in 46% and gastrointestinal (GI) in 29%. Hemostasis was achieved in 84% of patients. Thrombotic events occurred in 7.4% of patients and in-hospital mortality was 26.4%. Total cost avoidance was $1,005,871.78. To our knowledge, this is the first study to evaluate the impact of a pharmacist-driven ARP on clinical and economic outcomes. Implementation of a pharmacist-driven ARP was associated with favorable outcomes and cost savings. [ABSTRACT FROM AUTHOR]

Consumer engagement studies are increasingly becoming extremely important as fragmented consumers attention and (re) purchase decisions are being influenced by social media content. This study provides a fresh perspective about the mediating effect of the behavioural dimension of consumer engagement, among social media content creation and (re) purchase intention with respect to international fast fashion brands in India. An online sample was undertaken and Structural equation modelling (SEM) via R studio was used for data analysis. The result of the dataset indicate that there is a significant relationship between social media content creation and (re) purchase intention of apparel brands, and behavioural dimension of consumer engagement being seen to partially mediate between the two. Consumer involvement is leading marketers to deploy new online led communication strategies and therefore, this study explores how creating of social media content particularly across Facebook, Instagram and YouTube, affects the (re) purchase intention of a brand and is mediated by consumer engagement. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Electronic consultation (eConsult) communications between primary care physicians (PCPs) and rheumatologists may reveal common knowledge gaps and educational opportunities. The aim of our study was to identify content themes in PCP questions and rheumatology recommendations through analysis of eConsult and the need for rheumatology appointments and facilitated urgent visits post‐eConsult. Methods: A descriptive cross‐sectional study involving qualitative and quantitative analysis of rheumatology eConsults in a single center was performed from May 1, 2019, to January 9, 2020. Conventional content analysis was used to derive content themes in PCP questions and rheumatology recommendations. We evaluated the proportion of eConsults, which included a need for rheumatology appointments and expedited visits through frequency counts. Results: Among 120 rheumatology eConsults, six PCP questions and five rheumatology recommendation content themes were identified. The most common PCP question themes were the following: 1) joint pain, 2) suspected rheumatic disease differential, and 3) abnormal laboratory tests. The most common rheumatology recommendation or teaching themes were the following: 1) education on differential diagnoses of rheumatic diseases, 2) education on the specific rheumatic disease, and 3) laboratory test interpretation. The majority of eConsults (82%) recommended a subsequent rheumatology appointment, and 27% facilitated an expedited appointment. Conclusion: In this analysis of eConsults, we identified common knowledge gaps in PCPs and rheumatology educational topics, including differentiating inflammatory from noninflammatory arthritis, using caution in interpreting abnormal laboratory tests without clinical manifestations, managing chronic gout, evaluating elevated creatine phosphokinase levels, and differentiating C‐reactive protein (CRP) from high‐sensitivity CRP. Timely feedback through eConsult recommendations may allow for focused educational opportunities. [ABSTRACT FROM AUTHOR]

Extracellular electron transfer by Geobacter species through surface appendages known as microbial nanowires1 is important in a range of globally important environmental phenomena2, as well as for applications in bio-remediation, bioenergy, biofuels and bioelectronics. Since 2005, these nanowires have been thought to be type 4 pili composed solely of the PilA-N protein1. However, previous structural analyses have demonstrated that, during extracellular electron transfer, cells do not produce pili but rather nanowires made up of the cytochromes OmcS2,3 and OmcZ4. Here we show that Geobacter sulfurreducens binds PilA-N to PilA-C to assemble heterodimeric pili, which remain periplasmic under nanowire-producing conditions that require extracellular electron transfer5. Cryo-electron microscopy revealed that C-terminal residues of PilA-N stabilize its copolymerization with PilA-C (to form PilA-N–C) through electrostatic and hydrophobic interactions that position PilA-C along the outer surface of the filament. PilA-N–C filaments lack π-stacking of aromatic side chains and show a conductivity that is 20,000-fold lower than that of OmcZ nanowires. In contrast with surface-displayed type 4 pili, PilA-N–C filaments show structure, function and localization akin to those of type 2 secretion pseudopili6. The secretion of OmcS and OmcZ nanowires is lost when pilA-N is deleted and restored when PilA-N–C filaments are reconstituted. The substitution of pilA-N with the type 4 pili of other microorganisms also causes a loss of secretion of OmcZ nanowires. As all major phyla of prokaryotes use systems similar to type 4 pili, this nanowire translocation machinery may have a widespread effect in identifying the evolution and prevalence of diverse electron-transferring microorganisms and in determining nanowire assembly architecture for designing synthetic protein nanowires.Structural, functional and localization studies reveal that Geobacter sulfurreducens pili cannot behave as microbial nanowires, instead functioning in a similar way to secretion pseudopili to export cytochrome nanowires that are essential for extracellular electron transfer. [ABSTRACT FROM AUTHOR]

Background: E.coli is the most common organism causing UTI. Inappropriate and widespread use of broad-spectrum antibiotics has resulted in development of multi-drug resistance and β-lactamases producing strains. Aims and Objective: To assess β-lactamase production and multi-drug resistance among uropathogenic E.coli isolates. Materials and Methods: A total of 145 E.coli urinary isolates were included in this study. The isolated organisms were identified by conventional microbiological procedures. Antimicrobial susceptibility was performed by Kirby Bauer disk diffusion method. Isolates were screened for extended spectrum β-lactamase production and confirmed by phenotypic confirmatory double disc synergy test. Isolates resistant to cefoxitin were considered potential AmpC producers confirmed by AmpC disc test and modified three dimensionsl test. Isolates resistant to imipenem and meropenem were considered potential carbapenemase producers and confirmed by mCIM test. Results: Out of 145 isolates 91 (62.76%) were isolated from males and 54 (37.24%) from females. Majority of the isolates were obtained from the age group of 21-30 years (48.96%) followed by 31-40 years (14.48%). Highest susceptibility was seen towards fosfomycin (94.48%), tigecycline (87.59%), nitrofurantoin (77.24%). Highest resistance of 81.38% was observed against ampicillin while more than 70.0% resistance observed with cefazolin, cefotaxime, ciprofloxacin, levofloxacin and amoxiclav. Multi-drug resistance was observed in 85.51% isolates and 4.14% were found to be possible XDR. Among these isolates frequency of β-lactamase production was ESBL (45.51%), AmpC (28.96%) and carbapenamase (28.96%). Conclusion: Drug resistance due to β-lactamases production is emerging as a serious threat in UTI; routine screening of these β-lactamases will prevent treatment failures. [ABSTRACT FROM AUTHOR]

Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life. Surprisingly, the most stable and highest-expressing mRNAs in our test set have modest initiation/elongation rates and ribosome loads, leading to minimal translation-dependent mRNA decay. These findings are of potential interest for optimization of protein output from therapeutic mRNAs, which may be achieved by attenuating rather than maximizing ribosome load. [Display omitted] • Exogenously delivered mRNAs undergo translation-dependent decay through deadenylation • Nonoptimal codons lead to slow elongation, high ribosome load, and fast mRNA decay • mRNAs with fast initiation rates have high ribosome loads and fast mRNA decay • The most stable mRNAs are those with optimal codons and moderate ribosome loads Bicknell et al. demonstrate that exogenously delivered mRNAs are degraded in a translation-dependent manner at a rate that correlates with ribosome load. ORF sequences leading to high ribosome load cause faster translation-dependent decay. The most stable mRNA sequences are those with the fewest ribosomes due to slower rates of translation initiation. [ABSTRACT FROM AUTHOR]

Objective: Patients with coronavirus disease 2019 (COVID‐19) can progress to a state of unregulated inflammation called cytokine storm syndrome (CSS). We describe formation and operation of a COVID‐19 multidisciplinary consultation service that was allowed to individualize treatment for critically ill patients with COVID‐19 during the pandemic. Methods: Institutional experts from different subspecialties formed a COVID‐19 CSS task force at Montefiore Medical Center, Bronx, NY. They agreed on a set of four clinical and six laboratory parameters that can help early identify COVID‐19 CSS. We describe the formation and implementation of the COVID‐19 task force. The case series description of the COVID‐19 CSS consultation cohort highlights consultation volume, baseline characteristics, clinical and laboratory parameters, and how biologic treatments were allocated to these patients. Results: Between April 4,2020, and May 7,2020, the COVID‐19 CSS task force was formed, consisting of adult and pediatric rheumatologists and allergy and immunology physicians. The task force evaluated a total of 288 patients, of whom 197 (68%) were male, the median (interquartile range [IQR]) age was 62 (51‐70) years, 122 (42%) were Hispanic, and 88 (31%) were Black or African American. The common presenting symptoms in all referred patients were dyspnea (85%) and diarrhea (80%). Thirty‐one patients who received biologic therapy were younger, with a median (IQR) age of 53 (32‐63) years, as opposed to 62.5 (52‐70) years in the nonbiologic group (P = 0.008). A higher proportion receiving biologics was in the critical care setting (26 [84%] vs 151 [59%]; P = 0.006). Conclusion: To the best of our knowledge, this is the first multidisciplinary collaborative effort to provide individualized patient recommendations for evaluation and treatment of patients with COVID‐19 who may have CSS. This working model helped to devise an approach that may have identified patients who were most likely to benefit from biologic therapy in the absence of evidence‐based guidelines. [ABSTRACT FROM AUTHOR]

Background: Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the ‘One Health approach’ in which multiple sectors coordinate and work together to achieve better public health outcomes. Objective: We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019. Methods: Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders. Findings & Conclusion: The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate the potential determinants of sustainable consumption behavior. This study describes lifestyle of health and sustainability (LOHAS) tendency and the effects of such lifestyles on the behavioral intentions for sustainable consumption in sharing economy. Design/methodology/approach: This research adapts LOHAS tendency, consumer attitude, subjective norm, perceived behavioral control and consumers' behavioral intention for sustainable consumption scale in Indian context to describe the sustainable consumption behavior by extending the theory of planned behavior (TPB). Data of 627 individuals collected through a questionnaire, after the scales validation process and thereafter a structural equation analysis has been performed. Findings: The findings confirm the extended TPB, wherein LOHAS tendency has emerged as an antecedent to consumer attitudes for taking part in sustainable consumption. Results highlight that consumer attitudes, subjective norms and perceived behavioral control are significant determining factors of consumers' sustainable consumption behavior. Research limitations/implications: This study has examined the sustainable consumption behavior by considering the lifestyle tendency. A few other limitations are also discussed. Originality/value: Consumer behavior in sharing economy is surely one of the emerging research areas; there is dearth of research to understand Indian consumers' sustainable consumption, particularly from lifestyle perspective. This research establishes relationship between LOHAS tendency and sustainable consumption, which may serve as a contributor to sharing economy in terms of LOHAS consumer's lifestyle and their sustainable consumption behavior. [ABSTRACT FROM AUTHOR]

The purpose of this research work is to formulate and evaluate the Orodispersible tablet of Fluvastatin Sodium to enhance the bioavailability and effectiveness of the drug. The objectives of the drug work were to formulate and evaluate Orodispersible tablets of Fluvastatin Sodium, having adequate mechanical strength, rapid disintegration, and fast action. Precompression parameters like angle of repose, bulk density, tapped density, compressibility index & post-compression parameters like wetting time, water absorption ratio, in-vitro disintegration, and in-vitro dispersion time were studied. The hardness, friability, and drug content of all the formulations were found to be within the limits. The best formulation PK09 has shown good disintegration time, dissolution time, and dispersion time. The optimized formulation of batch PK9 gave the best in-vitro release of 99.60% in 3min in phosphate buffer pH 6.8. The release of the drug followed the matrix diffusion mechanism as compared to the commercial formulation. Formulation PK9 gives quick disintegration and better drug release. Hence it can be concluded that the formulation of PK9 is stable and effective for quick action and it is an alternative to the conventional tablets. [ABSTRACT FROM AUTHOR]

The potentiometric method is adopted to determine formation constants of complexes and used with a new numerical scheme. This study deals with the coordination behaviour of L-DOPA ((3,4-dihydroxyphenyl)alanine) in Hg(II)/Pb(II)/Cd(II)-DOPA-L-alanine/glycine/L-phenylalanine (1:1:1) systems. DOPA is recognized as a neurotransmitter, and used in the treatment of Parkinson's disease. All the selected ligands are biologically active and play a vital role in the physiological processes. All the systems were investigated pH-metrically at 20±1°C and 30±1°C at three different ionic strengths in aqueous medium. Stability Constants of Generalized Species' computer program was used to obtain refined values of formation constants. Thermodynamic parameters (logkμ→ 0, ΔGo, ΔHo, ΔSo) for biligand systems were calculated. The speciation of different species in mixed coordinated systems was obtained up to a specific pH in particular system. High values of formation constants support the formation of stable ternary complexes. Biligand complexes involving alanine were found to be the most stable, while those of phenylalanine were the least with lowest concentration at a particular pH in specific conditions. Results obtained are helpful in understanding the physiological behaviour of these systems. [ABSTRACT FROM AUTHOR]

Introduction Treatment options are limited for nonsurgical chronic refractory cases of adhesive capsulitis. We describe a novel percutaneous tenotomy technique for coracohumeral ligament interruption with cadaveric validation. Objective The objective of this study was to describe and validate a novel technique for percutaneous interruption of the coracohumeral ligament. Design Cadaveric study. Setting Academic tertiary care center. Methods Eight cadavers underwent ultrasound (US)-guided percutaneous incision of the coracohumeral (CHL) ligament. Performance of the procedure requires that the practitioner make oscillatory motions with a needle that uses ultrasound energy to cut through tissue. Each pass removes a pinhead-sized amount of tissue. The number of passes and the cutting time are recorded during the procedure. As a standard for this procedure does not exist, the authors created their own based on the preclinical information presented here. Postprocedure dissection was performed to assess the extent of CHL interruption and injury to surrounding tissue. Results The average resection time was seven minutes, requiring 500 passes. The technique described in this paper completely interrupted the CHL in all subjects. Cadaveric analysis demonstrated interruption of the CHL with respect to control shoulders requiring an average of seven minutes of cutting time and ∼500 micro-perforations. Conclusion US-guided percutaneous CHL ligament sectioning is possible with a commercially available ultrasonic probe. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. Further, patients with T1D have 3–4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naïve to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care. [ABSTRACT FROM AUTHOR]

Herein, we present the surface electronic structure and morphological evolution under reduction and oxidation conditions for Pd@Co (PC) core‐shell nanoparticles with different Pd : Co ratio (PC=2 : 1, 1 : 1 and 1 : 2). Extensive measurements have been made with NAPXPS (near ambient pressure x‐ray photoelectron spectroscopy) under oxidising and reducing conditions, and ex‐situ HRTEM. It has been demonstrated that PC catalysts are thermally stable towards morphological changes, at least up to 575 K. Nonetheless, it shows a significant surface electronic structure changes under reaction environments, which are highly relevant to heterogeneous catalysis. As expected, high (low) population of metallic (oxidised) Co was observed, while retaining core shell structure under reduction (H2 and vacuum annealing) environment. Interestingly, the Pd−Co metallic interface helps to overcome the pyrophoric nature of cobalt and stabilised a significant amount of metallic Co at Pd−Co interface even in the presence of 0.1 mbar O2 up to 575 K. The presence of Pd−Co and Pd−Co@Co3O4 interfaces in reaction environment makes the catalyst dual functional. The proof of concept has been explored in terms of oxidation of CO in the presence of H2 or O2. [ABSTRACT FROM AUTHOR]

Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D. [ABSTRACT FROM AUTHOR]

Aims: The aim of present study is to develop Paclitaxel nanoparticles for injectable suspension, an anti-neoplastic drug formulation. Study design: Mention the design of the study here. Place and Duration of Study: Sagar Institute of Research & Technology- Pharmacy, Ayodhya Bypass Road, Bhopal, between June 2017 and June2018. Methodology: The Human serum albumin (HSA) is the most abundant plasma protein in the human blood with a half -life of 19 days. It can reversibly bind hydrophobic drug substances, transport them in the body and release drugs at cell surface. The formulation is prepared by homogenization at high-pressure of paclitaxel in the presence of human serum albumin into a nanoparticle colloidal suspension. Paclitaxel nano particles have been stabilized by human albumin and maintain the average size of 100 nm Results: The particle size of the reconstituted solution is checked using the laser diffraction Technique the particle is White to yellow lyophilized after reconstitution the particle become homogeneous milky suspension without visible particulates. Reconstitution time NMT 25 minutes 20.45 sec. The assay was performed by HPLC and found to be 90.0% to 110.0% of label. The retention time of Paclitaxel peak obtained in sample corresponds to the respective standards obtained from standards the pH NLT 6.00 to NMT 8.00 Particle size NLT 100 nm - NMT 200 nm. Sterility test was comply as per USP <71> Conclusion: The nano-delivery systems could have the potential to be free of Cremophor EL and ethanol, enhance Paclitaxel solubility, improve Paclitaxel pharmacokinetic profiles in vivo, decrease its side effects, passively or actively target to tumor sites due to the EPR (Enhanced Permeability and Retention) effect and the use of targeting ligands, respectively, nanotechnology is a very active research area in both academic and industrial settings. [ABSTRACT FROM AUTHOR]

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. The Novel coronavirus (SARS-CoV-2) caused pneumonia in Wuhan, China in December 2019 is a highly contagious disease. The World Health Organization (WHO) has declared it as a global public health emergency. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. Currently, the research on novel coronavirus is still in the primary stage. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan by Bats, snakes and pangolins have been cited as potential carriers. On the basis of current published evidence, we systematically summarize the epidemiology, clinical characteristics, diagnosis, treatment and prevention of COVID-19. This review in the hope of helping the public effectively recognize and deal with the novel coronavirus (SARS-CoV-2) and providing a reference for future studies. [ABSTRACT FROM AUTHOR]

Changes in business environments continually create opportunities for entrepreneurs to target specific emerging needs of their customers. The first disposable female urination device (FUD) PeeBuddy was launched in the Indian market in response to the emergent need among the urban women for a product facilitating safe usage of public washrooms, especially during travel. PeeBuddy is among the many social innovations (Alvord et al., 2004, p. 262), making prominent appearances in emerging economies battling resource constraints (Austin et al., 2006). The purpose of this case is to understand the ideation and execution of this social innovation in the context of countries like India where cultural traditions and subjective norms are held in high regards. In India, issues surrounding women's personal hygiene are considered taboo for public communiqué. This case explores the use of social media marketing approaches used to circumvent extant cultural barriers hindering the adoption of PeeBuddy, which may be considered as a taboo product in the context of the Indian market. This case is aimed at students undertaking advanced marketing management and consumer behaviour courses to sensitize them about subjective norms and their deep integration within culturally dominated communities. It will establish the need for adopting innovative methods for marketing taboo products and how creativity can be used to retail such products. [ABSTRACT FROM AUTHOR]

Necrotising myopathy with pipestem capillaries is a distinct form of inflammatory myopathy exhibiting only sparse inflammation on biopsy, with clinical presentation and histopathological profile entirely different from dermatomyositis, polymyositis or inclusion body myositis. A 51-year-old non-diabetic man presents with progressively worsening shortness of breath and myalgias with only mild proximal muscle weakness and elevated serum creatine kinase. Autoimmune workup, ordered after ruling out infectious and cardiac aetiologies, returned positive for Sjögren’s syndrome antibody (SSA/Ro-52). Lung imaging and biopsy were suggestive of cryptogenic organising pneumonia and muscle biopsy showed myositis with pipestem capillaries and abnormal deposition of membrane attack complex with only sparse inflammation. The patient received high-dose steroids, mycophenolate mofetil, intravenous immunoglobulin and rituximab with improvement in muscle symptoms. However, his pulmonary findings progressed, requiring evaluation for a lung transplant. This case emphasises the need for further research to better understand this disease entity and improve mortality and morbidity in these patients. [ABSTRACT FROM AUTHOR]