The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation

The Drosophila protein brain tumor (Brat) forms a complex with Pumilio (Pum) and Nanos (Nos) to repress hunchback (hb) mRNA translation at the posterior pole during early embryonic development. It is currently thought that complex formation is initiated by Pum, which directly binds the hb mRNA and subsequently recruits Nos and Brat. Here we report that, in addition to Pum, Brat also directly interacts with the hb mRNA. We identify Brat-binding sites distinct from the Pum consensus motif and show that RNA binding and translational repression by Brat do not require Pum, suggesting so far unrecognized Pum-independent Brat functions. Using various biochemical and biophysical methods, we also demonstrate that the NHL (NCL-1, HT2A, and LIN-41) domain of Brat, a domain previously believed to mediate protein–protein interactions, is a novel, sequence-specific ssRNA-binding domain. The Brat-NHL domain folds into a six-bladed β propeller, and we identify its positively charged top surface as the RNA-binding site. Brat belongs to the functional diverse TRIM (tripartite motif)-NHL protein family. Using structural homology modeling, we predict that the NHL domains of all TRIM-NHL proteins have the potential to bind RNA, indicating that Brat is part of a conserved family of RNA-binding proteins.     

In silico CD4+ T-cell epitope prediction and HLA distribution analysis for the potential proteins of Neisseria meningitidis Serogroup B—A clue for vaccine development

Neisseria meningitidis, an exclusive human pathogen, is a major cause of mortality due to meningococcal meningitis and sepsis in many developing countries. Three meningococcal serogroup B proteins, i.e. T-cell stimulating protein A (TspA), autotransporter A (AutA), and IgA-specific serine endopeptidase (IGA1) elicits CD4+ T-cell response and may enhance the effectiveness of meningococcal vaccines by acting as protective immunogens. A very limited data on T-helper cell epitopes in MenB proteins is available. Hence, in silico prediction of peptide sequences which may act as helper T lymphocyte epitopes in MenB proteins was carried out by NetMHCIIpan web server. HLA distribution analysis was done by using the population coverage tool of Immune Epitope Database to determine the fraction of individuals in various populations expected to respond to a given set of predicted T-cell epitopes based on HLA genotype frequencies. Six epitopic core sequences, two from each MenB proteins, i.e. AutA, TspA and IgA1 protease were predicted to associate with a large number of HLA-DR alleles. These six peptides may act as T-cell epitope in more than 95% of populations in 8 out of 12 populations considered. The T-cell stimulation potential of these predicted peptides containing the core epitopic sequences is to be validated by using laboratory experiments for their efficient use as peptide vaccine candidates against N. meningitidis serogroup B.     

Activated protein C resistance assay detects thrombotic risk factors other than factor V Leiden

Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism. FVL is considered responsible for up to 95% of APC resistance; however, other factor V polymorphisms and elevated factor VIII levels also have been implicated. We assessed whether additional mechanisms contribute to APC resistance in a blinded case-control study of 65 subjects by measuring APC resistance using 3 methods: 2 activated partial thromboplastin time-based methods with and without dilution in factor V-deficient plasma and 1 Russell viper venom-based assay (RVV). Without factor V-deficient plasma, 24 subjects were APC resistant; with factor V-deficient plasma, the assay identified fewer APC-resistant subjects, as did RVV. All assays detected the 7 heterozygous FVL subjects. Thirteen subjects had factor VIII levels above 150% (1.50). After excluding subjects with FVL or elevated factor VIII levels, 4 subjects still had APC resistance. VTE risk trended higher for subjects with APC resistance in the absence of FVL. Measurement of APC resistance without dilution in factor V-deficient plasma is needed to assess for potentially important thrombotic risk factors other than FVL.     

Missed Opportunities for Screening and Management of Dysglycemia among Patients Presenting with Acute Myocardial Infarction in North India: The Prospective NORIN STEMI Registry

Background:Dysglycemia is a major and increasingly prevalent cardiometabolic risk factor worldwide, but is often undiagnosed even in high-risk patients. We evaluated the impact of protocolized screening for dysglycemia on the prevalence of prediabetes and diabetes among patients presenting with ST-segment elevation myocardial infarction (STEMI) in North India.Methods:We conducted a prospective NORIN STEMI registry-based study of patients presenting with STEMI to two government-funded tertiary care medical centers in New Delhi, India, from January to November 2019. Hemoglobin A1c (HbA1c) was collected at presentation as part of the study protocol, irrespective of baseline glycemic status.Results:Among 3,523 participants (median age 55 years), 855 (24%) had known diabetes. In this group, baseline treatment with statins, sodium-glucose cotransporter 2 inhibitors, or glucagon-like peptide-1 receptor agonists was observed in 14%, <1%, and 1% of patients, respectively. For patients without known diabetes, protocolized inpatient screening identified 737 (28%) to have prediabetes (HbA1c 5.7–6.4%) and 339 (13%) to have newly detected diabetes (HbA1c ≥ 6.5%). Patients with prediabetes (49%), newly detected diabetes (53%), and established diabetes (48%) experienced higher rates of post-MI LV dysfunction as compared to euglycemic patients (42%). In-hospital mortality (5.6% for prediabetes, 5.1% for newly detected diabetes, 10.3% for established diabetes, 4.3% for euglycemia) and 30-day mortality (8.1%, 7.6%, 14.4%, 6.6%) were higher in patients with dysglycemia. Compared with euglycemia, prediabetes (adjusted odds ratio (aOR) 1.44 [1.12–1.85]), newly detected diabetes (aOR 1.57 [1.13–2.18]), and established diabetes (aOR 1.51 [1.19–1.94]) were independently associated with higher odds of composite 30-day all-cause mortality or readmission.Conclusions:Among patients presenting with STEMI in North India, protocolized HbA1c screening doubled the proportion of patients with known dysglycemia. Dysglycemia was associated with worse clinical outcomes at 30 days, and use of established pharmacotherapeutic risk-reduction strategies among patients with known diabetes was rare, highlighting missed opportunities for screening and management of dysglycemia among high-risk patients in North India.     

Extraction of Natural Dye from Aerial Parts of Argy Wormwood Based on Optimized Taguchi Approach and Functional Finishing of Cotton Fabric

The aerial parts of the Argy Worm Wood (AWW) plant have been used in different Chinese foods as a colorant and a taste enhancer for a long time. Despite its application as a food colorant, it has rarely been considered for the coloration of textiles. Keeping in mind the variation in color strength due to the change in phytochemical contents by seasonal change and other variables, the extraction of AWW aerial parts was optimized using the Taguchi method. Optimization was performed on the basis of total phytochemical contents (phenols, flavonoids, and tannins) in the extracted solutions. For this purpose, two different solvent systems, namely sodium hydroxide/water (NaOH/water) and ethanol/water (EtOH/water), were applied through a simple aqueous extraction method at varying levels of solvent concentration, and extraction temperature and duration. Maximum phytochemicals yield of 21.96% was obtained using NaOH/water system with 9 g/L NaOH/water at 85 °C for 20 min and 25.5% with 75% aqueous ethanol at 85 °C for 40 min. Optimized extracts were characterized by UV-Vis and FTIR spectrophotometry, which showed the presence of multiple phytochemicals in the extracts. The dyeing temperature and time were also optimized. Dyed cotton fabrics showed medium to high colorfastness to washing and excellent antibacterial and UV radiation absorption properties. The effect of pre-mordanting with salts of iron and copper was also studied on the color fastness properties. Cotton fabrics dyed with two different solvent system extracts displayed various shades of brown with NaOH/water, and green with aqueous ethanol with and without pre-mordanting. The present study provides the textile industry with a promising source of functional bio-colorant and a value-adding approach for the AWW plant industry.     

Clinical Application of Detecting COVID-19 Risks: A Natural Language Processing Approach

The clinical application of detecting COVID-19 factors is a challenging task. The existing named entity recognition models are usually trained on a limited set of named entities. Besides clinical, the non-clinical factors, such as social determinant of health (SDoH), are also important to study the infectious disease. In this paper, we propose a generalizable machine learning approach that improves on previous efforts by recognizing a large number of clinical risk factors and SDoH. The novelty of the proposed method lies in the subtle combination of a number of deep neural networks, including the BiLSTM-CNN-CRF method and a transformer-based embedding layer. Experimental results on a cohort of COVID-19 data prepared from PubMed articles show the superiority of the proposed approach. When compared to other methods, the proposed approach achieves a performance gain of about 1–5% in terms of macro- and micro-average F1 scores. Clinical practitioners and researchers can use this approach to obtain accurate information regarding clinical risks and SDoH factors, and use this pipeline as a tool to end the pandemic or to prepare for future pandemics.     

Efficacy and safety of a new insulin infusion protocol adapted for the target glycemic range of 140–180 mg/dl in adult critical care units: a tertiary care centre experience

International Journal of Diabetes in Developing Countries - In critical care setting, insulin infusion rather than subcutaneous insulin is recommended to maintain the blood glucose (BG) level in...     

Quality of life assessment in survivors of breast cancer

Aim: The aim was to assess the health-related quality of life (HRQOL) and its temporal variation at first visit and subsequent visits among breast cancer patients. Design and Setting: The prospective study was carried out in Outpatient Department of Radiation Oncology, University Teaching and Tertiary Referral Hospital. Material and Methods: After clearance from the ethical committee and EORTC group, 81 surgically treated female breast cancer patients referred to the Outpatient Department of Radiation Oncology for chemoradiation and hormonal therapy were included in the study after informed written consent, irrespective of the age and stage of disease. The patients were interviewed as per the EORTC QLQ-C30 Questionnaire module at four levels at the first visit and at subsequent follow-up visits at 6, 12, and 24 months, respectively, and are still on follow-up. Statistical Analysis: The data collected were expressed as mean/raw score (RS), standard deviation (SD), and percent mean/scale score expressed on the linear transformation scale, derived as per the calculations and equations of the EORTC QLQ-C30 Scoring Manual. Intragroup comparison (IGC) was done at four levels/visits, a, b, c and d. A P-value of <0.05 was considered significant. Results: The mean age at presentation was 46.6 ± 10.2 years. The study showed that the physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning, global health status, and symptomatology showed statistically significant improvement over time (P < 0.001). Conclusion: The survivors of female breast cancer over the long-term follow-up showed significant improvement and coping mechanisms involved in a majority of HRQOL parameters.