Genome wide identification and expression profiling of ATP binding cassette (ABC) transporters gene family in lentil (Lens culinaris Medikus) under aluminium stress condition.

Adenosine triphosphate-binding cassette transporters (ABC transporters) are involved in regulating plant growth, development and tolerance to environmental stresses. In this study, a total of 138 ABC transporter genes were identified in the lentil genome that were classified into eight subfamilies. Four lentil ABC transporters from subfamily B and I were clustered together with the previously characterized ABC transporter proteins related to aluminium (Al) detoxification. Lentil ABC transporter genes were distributed across the chromosomes. Tandem duplication was the main driving force for expansion of the ABC gene family. Collinearity of lentil with soybean indicated that ABC gene family is closely linked to Glycine max. ABC genes in the same subfamily showed similar gene structure and conserved motifs. The ABC promoter regions harboured a large number of plant hormones and multiple stress responsive cis-regulatory elements. The qRT-PCR showed that ABC genes had varied expression in roots of lentil at different time points under Al stress. This is the first report on genome wide identification and expression analyses of genes encoding ABC transporter genes in lentil which has provided in-depth insight for future research on evolution and elucidation of molecular mechanisms for aluminium tolerance.

Physiological and proteomic characterization revealed the response mechanisms underlying aluminium tolerance in lentil (Lens culinaris Medikus).

Aluminium (Al) toxicity causes major plant distress, affecting root growth, nutrient uptake and, ultimately, agricultural productivity. Lentil, which is a cheap source of vegetarian protein, is recognized to be sensitive to Al toxicity. Therefore, it is important to dissect the physiological and molecular mechanisms of Al tolerance in lentil. To understand the physiological system and proteome composition underlying Al tolerance, two genotypes [L-4602 (Al-tolerant) and BM-4 (Al-sensitive)] were studied at the seedling stage. L-4602 maintained a significantly higher root tolerance index and malate secretion with reduced Al accumulation than BM-4. Also, label-free proteomic analysis using ultra-performance liquid chromatography-tandem mass spectrometer exhibited significant regulation of Al-responsive proteins associated with antioxidants, signal transduction, calcium homeostasis, and regulation of glycolysis in L-4602 as compared to BM-4. Functional annotation suggested that transporter proteins (transmembrane protein, adenosine triphosphate-binding cassette transport-related protein and multi drug resistance protein), antioxidants associated proteins (nicotinamide adenine dinucleotide dependent oxidoreductase, oxidoreductase molybdopterin binding protein & peroxidases), kinases (calmodulin-domain kinase & protein kinase), and carbohydrate metabolism associated proteins (dihydrolipoamide acetyltransferase) were found to be abundant in tolerant genotype providing protection against Al toxicity. Overall, the root proteome uncovered in this study at seedling stage, along with the physiological parameters measured, allow a greater understanding of Al tolerance mechanism in lentil, thereby assisting in future crop improvement programmes.

A Comparative Prospective Study Between Conventional Chemo-Radiotherapy and Pure Accelerated Radiotherapy With Concurrent Chemotherapy for the Treatment of Locally Advanced Head and Neck Cancer.

BACKGROUND: The established standard treatment for locally advanced head and neck squamous cell carcinoma is concurrent chemoradiotherapy, but the optimum radiotherapy schedule for best disease control and acceptable toxicity is still evolving. Tumor control probability decreases with each day's prolongation of treatment time. Shortening the overall treatment time of radiation by pure accelerated radiotherapy may be a good option. MATERIAL AND METHODS: One hundred and sixty-five patients with histopathologically proven squamous cell carcinoma of the head and neck were included in the study and were assigned into two groups from January 2017 to June 2019. The total dose of 70 Gy was given, 2 Gy/fraction/day. Treatment was given five days a week (conventional radiotherapy) and six days a week (pure accelerated radiotherapy). Both groups received weekly concurrent injections of cisplatin. RESULTS:  The stage (p=0.006) and fractionation of radiation (p=0.018) were the independent factors affecting disease-free survival (DFS). There was a statistically significant difference (p=0.019) in the recurrence of patients in different fractionation schedules. The median DFS was 39 months with a 95% CI of 31.44 - 46.55. One- and three-year DFS was 51% and 8.5% respectively in the five fractions/week schedule arm while 54.5% and 9.5% respectively in the six fractions/week schedule group. CONCLUSION: Pure accelerated radiotherapy is more efficacious in terms of disease control with comparable mildly increased acute side effects.

Sutureless valves versus aortic root enlargement for aortic valve replacement in small aortic annulus: A systematic review and pooled analysis.

BACKGROUND: Very few studies provide direct comparisons between aortic root enlargement and sutureless valve implantation in patients with a small aortic annulus who underwent aortic valve replacement. This study aims to provide comparative outcomes between the two in such a subset of patients, through a systematic review and pool analysis. METHODS: The PubMed, Scopus and Embase databases were searched using the appropriate terms. The data from original articles mentioning aortic root enlargement and sutureless valves in a single or comparative study with another group of patients with a small aortic annulus were pooled and analyzed using descriptive statistics. RESULTS: Both cardiopulmonary bypass (68.4 vs. 125.03 min, p < 0.001) and aortic cross-clamp times were significantly shorter in the sutureless valve group, along with a concomitantly higher number of minimally invasive surgeries. The incidence of permanent pacemaker implantation (9.76% vs. 3.16%, p < 0.00001), patient prosthesis mis-match and paravalvular leak was significantly higher in the sutureless valve group. In comparison, the incidence of re-exploration for bleeding was higher in the aortic root enlargement group (5.27% vs. 3.16%, p < 0.02). The two groups had no differences in the duration of hospital stays or mortality. CONCLUSIONS: Sutureless valves demonstrated a comparable hemodynamic outcome with aortic root enlargement in patients with a small aortic annulus. In addition to this, it greatly facilitated minimally invasive surgery. However, the high incidence of pacemaker implantation is still a concern for the widespread recommendation of sutureless valves, especially in young patients with a small aortic annulus.

Piperazine-1,2,3-triazole scaffolds: design, synthesis, anticancer and antimicrobial evaluation.

Aim: The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer activities. Materials & methods: Twenty-four scaffolds were synthesized via a click-inspired synthetic protocol and were assayed for anticancer activity using the methyl thiazolyl tetrazolium assay and for antimicrobial potency by serial dilution. Results: Among all the tested 1,2,3-triazole scaffolds, compounds 7i (IC50: 5.22 ± 0.05 µM) and 7a (IC50: 5.34 ± 0.13 µM) exhibited good anticancer activity, and 7x also showed notable antimicrobial activity. Molecular docking studies of potent analogs 7i and 7a were performed to provide an insight into their binding interactions. Conclusion: Compound 7x is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.

Exogenous hydrogen sulfide alleviates chromium toxicity by modulating chromium, nutrients and reactive oxygen species accumulation, and antioxidant defence system in mungbean (Vigna radiata L.) seedlings.

Chromium (Cr), a highly toxic redox-active metal cation in soil, seriously threatens global agriculture by affecting nutrient uptake and disturbing various physio-biochemical processes in plants, thereby reducing yields. Here, we examined the effects of different concentrations of Cr alone and in combination with hydrogen sulfide (H2S) application on the growth and physio-biochemical performance of two mungbeans (Vigna radiata L.) varieties, viz. Pusa Vishal (PV; Cr tolerant) and Pusa Ratna (PR; Cr sensitive), growing in a pot in hydroponics. Plants were grown in the pot experiment to examine their growth, enzymatic and non-enzymatic antioxidant levels, electrolyte balance, and plasma membrane (PM) H+-ATPase activity. Furthermore, root anatomy and cell death were analysed 15 days after sowing both varieties in hydroponic systems. The Cr-induced accumulation of reactive oxygen species caused cell death and affected the root anatomy and growth of both varieties. However, the extent of alteration in anatomical features was less in PV than in PR. Exogenous application of H2S promoted plant growth, thereby improving plant antioxidant activities and reducing cell death by suppressing Cr accumulation and translocation. Seedlings of both cultivars treated with H2S exhibited enhanced photosynthesis, ion uptake, glutathione, and proline levels and reduced oxidative stress. Interestingly, H2S restricted the translocation of Cr to aerial parts of plants by improving the nutrient profile and viability of root cells, thereby relieving plants from oxidative bursts by activating the antioxidant machinery through triggering the ascorbate-glutathione cycle. Overall, H2S application improved the nutrient profile and ionic homeostasis of Cr-stressed mungbean plants. These results highlight the importance of H2S application in protecting crops against Cr toxicity. Our findings can be utilised to develop management strategies to improve heavy metal tolerance among crops.

Capillary haemangioma of the tricuspid valve annulus: A rare presentation.

INTRODUCTION AND IMPORTANCE: To the best of our knowledge, very few tricuspid valves (TV) haemangiomas have been reported to date in the literature due to the avascular nature of the cardiac valve. We report the case of an otherwise healthy male presented with unexplained shortness of breath who was found to have tricuspid valvular haemangioma. CASE PRESENTATION: 52-year-old male who presented with progressive dyspnoea on exertion for 6 months. Echocardiography revealed an echo-dense mass attached to the heart's anterior leaflet of the tricuspid valve. A cardiac MRI suggested it as pulmonary fibroelastoma, but a surgical excision biopsy revealed it to be a capillary haemangioma. Patient symptoms improved after surgery. CLINICAL DISCUSSION: Cardiac valve tumour-like haemangiomas are rare, with the involvement of the tricuspid valve even rarer. Most TV haemangiomas are detected incidentally, however, they may present with a range of symptoms. Echocardiography is the mainstay of diagnosis however definitive diagnosis is by histopathology. Surgical excision is the treatment of choice, though surgery in asymptomatic patients is still controversial. CONCLUSION: Cardiac haemangiomas are rare, with the involvement of the tricuspid valve even rarer. They should undergo surgical excision due to the risks of embolism, rupture, and sudden death.

Benzopyrano-Fused Phenanthridine-Based Columnar Mesogens: Synthesis, Self-organization and Charge-Transport Properties.

Columnar mesogens constitute a fascinating class of supramolecular nano-architectures owing to the exceptional properties induced by their self-assembling behavior. Extending the π-conjugated core in such systems by incorporating heteroatoms extensively influences their mesomorphic, photophysical properties, etc., presenting them as potential candidates for optoelectronic applications. In the present work, a series of novel nitrogen and oxygen-incorporated chromenonaphthophenanthridine-based elliptical dimers have been synthesized through tandem Pictet-Spengler cyclization followed by ipso-aromatic substitution in one-pot. Mesophase characterization has been carried out by employing POM, DSC, and X-ray diffraction studies. Photophysical properties were investigated using UV-vis and emission spectroscopy. Furthermore, the charge transport properties were analyzed by time-of-flight measurements, and the observed ambipolar mobilities were found to be of the order of 10-3  cm2 V-1 s-1 . The high solubility, excellent thermal stability, self-organizing properties, and ambipolar charge transport characteristics make them promising candidates for applications in organic electronics.

Ethnobotany, botany, phytochemistry and ethnopharmacology of the genus Thalictrum L. (Ranunculaceae): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Thalictrum (Ranunculaceae) is known for its important alkaloids which have been reported to exhibit various pharmacological activities, viz. antitumor, antimicrobial, antitussive, antiamebic, hypotensive effects, HIV antiviral, etc. Throughout the world, the plant has been used as a tonic, purgative, stimulant, aperient and is utilized in various systems of medicine in the treatment of various ailments like snake bite, jaundice, rheumatism, stomachache, wounds, swellings, uterine tumors, paralysis, joints pain, nervous disorders, toothache, diarrhea, piles, fever, peptic ulcer, ophthalmic, headache, diuretic, dyspepsia, convalescence, etc. AIMS OF THIS REVIEW: To bring together all the information regarding the botany, phytochemistry, ethnobotany and ethnopharmacology of Thalictrum and identify the gaps in the existing studies so that full medicinal potential of the genus can be realized. METHODS: Available literature on botany, geography, traditional uses, phytochemicals, and pharmacology was gathered by referring to library and electronic searches in PubMed, Science Direct, Google Scholar, relevant journals and books. RESULTS: A variety of phytochemicals like alkaloids, essential oils, glycosides, phenols and terpenoids have been reported from Thalictrum species. Alkaloids are the most dominant diverse group with 178 different types. The crude extracts and isolates exhibit a gamut of pharmacological activities, namely anticancer, antimalarial, antioxidant, antipyretic, anti-tumor, ant-influenza virus, contraceptive and immunosuppressive. Northalrugosidine, an alkaloid from T. alpinum shows in vivo antileishmanial activity. So far, cytotoxic effects of only three Thalictrum species, viz. T. dasycarpum, T. foliolosum and T. simplex have been reported. Thl isolated from T. simplex is found to be 50% toxic (CC50%) at the concentration ranging from 53 to 95 µM. CONCLUSIONS: Thalictrum has tremendous medicinal values used in many traditional systems of medicine. It has multiple chemical components and still there is scope to explore more. Multiple chemical constituents and its utilization signify its high demand in the drug markets or pharmaceutical companies. In depth phytochemical studies along with in vitro studies with respect to their active principles can help in tapping the full medicinal potential of the genus.

Ewing's Sarcoma of the Talus in an Adolescent Female: An Unusual Case Presentation With Review of Literature.

Ewing's sarcoma is an aggressive primary malignant bone tumor that affects long and flat bones and is commonly seen in children and adolescents. The involvement of the foot especially the talus is an extremely rare entity with less than 15 cases reported in the literature. The rarity and atypical symptoms often lead to delays in diagnosis affecting the prognosis and survival. We present a 14-year-old female with pain and swelling of the left ankle for 18 months. She was being treated previously for an ankle sprain and was later suspected of avascular necrosis of the talus, before presenting to us. Clinicoradiology-pathological workup confirmed the diagnosis of Ewing sarcoma of the talus. Further, the metastatic workup revealed multiple skeletal metastases at the time of diagnosis. The metastatic lesion of the right femur required prophylactic fixation, otherwise, the patient was treated with palliative chemotherapy and radiotherapy. Ewing's sarcoma of the foot involving the talus is extremely rare and is a commonly misdiagnosed entity, affecting the overall prognosis of the patient. A high index of suspicion and a multidisciplinary approach is imperative for its early diagnosis and definitive management.

Silencing of a mannitol transport gene in Phelipanche aegyptiaca by the tobacco rattle virus system reduces the parasite germination on the host root.

Root parasitic weed Phelipanche aegyptiaca is an obligate plant parasite that causes severe damage to host crops. Agriculture crops mainly belong to the Brassicaceae, Leguminosae, Cruciferae, and Solanaceae plant families affected by this parasitic weed, leading to the devastating loss of crop yield and economic growth. This root-specific parasitic plant is not able to complete its life cycle without a suitable host and is dependent on the host plant for nutrient uptake and germination. Therefore, selected parasitic genes of P. aegyptiaca which were known to be upregulated upon interaction with the host were chosen. These genes are essential for parasitism, and reduced activity of these genes could affect host-parasitic interaction and provide resistance to the host against these parasitic weeds. To check and examine the role of these parasitic genes which can affect the development of host resistance, we silenced selected genes in the P. aegyptiaca using the tobacco rattle virus (TRV) based virus-induced gene silencing (VIGS) method. Our results demonstrated that the total number of P. aegyptiaca parasite tubercles attached to the root of the host plant Nicotiana benthamiana was substantially decreased in all the silenced plants. However, silencing of the P. aegyptiaca MNT1 gene which encodes the mannitol transporter showed a significantly reduced number of germinated shoots and tubercles. Thus, our study indicates that the mannitol transport gene of P. aegyptiaca plays a crucial role in parasitic germination, and silencing of the PaMNT1 gene abolishes the germination of parasites on the host roots.

Translation and reliability of the caregiver quality of life index-cancer (CQOLC) Scale in Hindi and it's association with the Kessler psychological distress scale (K10) for cancer caregivers at a tertiary radiotherapy centre in India.

BACKGROUND: With increasing incidence of cancer worldwide and increasing burden of treatment over the patients with cancer, the caregivers of those patients with cancer also suffer from psychological distress which ultimately affects their Quality of Life (QOL). This aspect is often overlooked which may ultimately lead to compromised patient care. PURPOSE: To translate the Caregiver Quality of Life Index-Cancer (CQOLC) Scale in Hindi and assess its association with Kesslers's psychological distress scale (K-10) for determining the quality of life (QoL) of caregivers of patients with cancer in India. METHODS: This is a single institute, hospital based cross sectional study performed from July 2020 to March 2021. Caregiver Quality of Life Index-Cancer (CQOLC) Scale, employing standard 'forward-backforward' translation procedure, the English-language version of the questionnaire was translated into Hindi-language by experts and administered to each caregiver. Cronbach's alpha was used for internal consistency. Kesslers's psychological distress scale (K-10) was analysed on interview basis. RESULTS: A total evaluated responders were 264. The hindi versions of the CQOLC was validated by cronbach's alpha method with internal consistency between 0.8 and 0.91. The majority of the caregivers were of the age group 31-40 yrs (42.05%). The male to female ratio was 6.54:1. CQOLC good score(0-45) was obtained in 27.27%, fair(46-90) in 55.30% and poor(91-140) in 17.42%. For K-10 distress scale very mild(10-19), mild(20-24), moderate(25-29) and severe(30-50) was observed in 47.73%, 11.74%, 11.74% and 28.79% respectively. A strong relation was found between the caregivers with poor CQOLC score and severe K-10 score(p<0.001). CONCLUSION: The Hindi version of CQOLC was accepted and its correlation with the point psychological distress predictor (K-10) scale was a valuable method to identify caregivers with poor QOL and severe distress levels.

Percutaneous CT-guided radiofrequency ablation of osteoid osteoma: Potential Pitfalls and complications and how to avoid them.

Targeted cannulation of the nidus and subsequent thermal ablation is the basis of CT-guided radiofrequency ablation (RFA) of osteoid osteoma, which is considered nowadays as the treatment of choice. The majority of complications during this procedure are due to thermal injury of adjacent structures. Specific measures as per the anatomical location of osteoid osteoma can avoid the majority of complications. This article enlists the possible complications and their necessary precautions and remedies to avoid these complications during CT-guided radiofrequency ablation of osteoid osteoma.

Glycine betaine modulates chromium (VI)-induced morpho-physiological and biochemical responses to mitigate chromium toxicity in chickpea (Cicer arietinum L.) cultivars.

Chromium (Cr) accumulation in crops reduces yield. Here, we grew two chickpea cultivars, Pusa 2085 (Cr-tolerant) and Pusa Green 112 (Cr-sensitive), in hydroponic and pot conditions under different Cr treatments: 0 and 120 µM Cr and 120 µM Cr + 100 mM glycine betaine (GB). For plants grown in the hydroponic media, we evaluated root morphological attributes and plasma membrane integrity via Evans blue uptake. We also estimated H+-ATPase activity in the roots and leaves of both cultivars. Plants in pots under conditions similar to those of the hydroponic setup were used to measure growth traits, oxidative stress, chlorophyll contents, enzymatic activities, proline levels, and nutrient elements at the seedling stage. Traits such as Cr uptake in different plant parts after 42 days and grain yield after 140 days of growth were also evaluated. In both cultivars, plant growth traits, chlorophyll contents, enzymatic activities, nutrient contents, and grain yield were significantly reduced under Cr stress, whereas oxidative stress and proline levels were increased compared to the control levels. Further, Cr uptake was remarkably decreased in the roots and leaves of Cr-tolerant than in Cr-sensitive cultivars. Application of GB led to improved root growth and morpho-physiological attributes and reduced oxidative stress along with reduced loss in plasma membrane integrity and subsequently increase in H+-ATPase activity. An increment in these parameters shows that the exogenous application of GB improves the Cr stress tolerance in chickpea plants.

Interim Analysis of Impact of Adding Low Dose Pulmonary Radiotherapy to Moderate COVID-19 Pneumonia Patients: IMpaCt-RT Study.

Background: Treatment for coronavirus disease 2019 (COVID-19) pneumonia remains largely supportive till date and multiple clinical trials took place within the short span of time to evaluate the role of investigational therapies. The anti-inflammatory effect of low dose whole lung radiation in treating pneumonia has been documented earlier. This clinical trial analyzed the effect of low dose radiation therapy (LDRT) in a moderately affected COVID-19 pneumonia patient cohort and has evaluated its effect in stopping the conversion of moderate disease into severe disease. Methods: Patients with moderate COVID-19 pneumonia as characterized by the Ministry of Health and Family Welfare (MOHFW), Government of India, were randomized (1:1) to low dose whole lung radiation versus no radiation. All treatment of patients was concurrently being given as per institutional protocol. Patients were followed up with clinical and laboratory parameters monitored on Days 1, 3, 7, and 14. Computed tomography scan (CT scan) of thorax was performed on Days 1 and 7. Patients were evaluated for conversion of moderate into severe disease as per National Early Warning Score-2 (NEWS-2 score) as the primary end point. The secondary endpoints included changes in ratio between peripheral capillary oxygen saturation and fraction of inspired oxygen (SpO2/FiO2), biochemical markers, 25-point CT severity score, and radiation induced acute pulmonary toxicities. Findings: At the interim analysis, there were seven patients in the radiation arm and six in the control. A whole lung LDRT improved the outcome of SpO2/FiO2 at Day 3; however it did not convert into a statistically significant improvement for the NEWS-2 score. The serum levels of LDH, CRP, Ferritin and D-dimer were significantly reduced on 14 days in the LDRT arm in comparison to the baseline value but were not significant between the two groups. Interpretation: LDRT seems to have the potential to prevent moderate COVID-19 pneumonia from a deteriorating to severe category. However, further randomized clinical trial with an adequate number of such patients is warranted to establish the definitive role of LDRT in the management of COVID-19 pneumonia. Funding: An intramural research project bearing code: I-27/621, was sanctioned from the All India Institute of Medical Sciences, Patna, India. Clinical Trial Registration: Clinical Trials Registry-India (CTRI/2021/06/033912, 25th May 2021) ctri.nic.in/Clinicaltrials/login.php.

Profile and Clinical Outcome of Children with Wilms' Tumor treated at a Tertiary Care Centre, India.

Pritanjali SinghBackground Wilms' tumor (WT) is the most common kidney tumor of the pediatric age group. The outcome of WT has improved due to the evolution of the treatment approach. A prospective observational study was conducted at All India Institute of Medical Sciences (AIIMS), Patna, to analyze the clinical profile along with the response and outcome to neoadjuvant chemotherapy according to the International Society of Pediatric Oncology (SIOP) protocol. Materials and Methods In total, 28 patients of WT visited the radiotherapy department from January 2015 to December 2019. Results Gender distribution showed male preponderance with a median age at diagnosis was 31 months. The abdominal lump was the dominant clinical presentation. The median volume of tumor at diagnosis was 359.48 mL (52.67-1805.76). Radiological staging workup shows that stage I, II, III, IV, and V were 7.1%, 39.3%, 39.3%, 10.7%, and 3.6% respectively. Neoadjuvant chemotherapy (NACT) was received by all patients. Also, 71.4% of patients showed > 50% of tumor volume reduction, while 28.6% of patients showed < 50% of tumor mass reduction. There was a statistically significant decrease in the tumor volume reduction following neoadjuvant chemotherapy ( p < 0.001). There was a statistically significant stage down ( p = 0.018) of the disease. Bivariate correlation studies showed recurrence was correlating statistically significantly with age < 24 months ( p = 0.049), locoregional lymph nodes ( p = 0.008), histopathological subtypes ( p < 0.001), stage of the disease ( p = 0.003), and risk groups ( p < 0.001). In addition, 25% of patients developed recurrence during the median follow-up of 25 months. The median disease-free survival (DFS) and overall survival (OS) were not reached. The mean DFS and OS were 48 and 59.13 months, respectively. One- and 3-year DFS were 100% and 64.1%, respectively. One- and 3-year OS were 100% and 75% respectively. Conclusion Our study suggests that most of the patients presented at an advanced stage, thus rendering most of the cases difficult to undergo surgery at presentation. Neoadjuvant chemotherapy followed by surgery may be considered a well-balanced approach with a comparable response and survival outcomes.

Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

INTRODUCTION: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. METHODS: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. RESULTS: From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5. CONCLUSION: Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit

ABSTRACT Objective: Thyroid functions in preterm newborns may be altered in the first week of life. Hypothyroxinemia has been commonly reported in these babies, which could be due to the immaturity of the hypothalamic pituitary thyroid axis or acute illness. It could have a long-term impact on the developing brain of these babies. We conducted this study to estimate the incidence of transient hypothyroxinemia of prematurity (THOP) and to determine its risk factors. Materials and methods: We analyzed thyroid stimulating hormone (TSH) and free T4 levels of 64 preterm neonates admitted in the neonatal intensive care unit. TSH and free T4 levels were measured in the first week and then at 14-21 days of life to estimate the incidence of THOP and determine its risk factors. We also estimated the incidence of congenital hypothyroidism (CH) and delayed TSH elevation in CH. Risk analysis was conducted using simple and multiple logistic regression, and numerical data was compared using the Mann Whitney U test and t test. Results: THOP was seen in 25% of the preterm babies. Caesarean delivery, presence of one or more morbidities, mechanical ventilation, birth weight ≥ 1,500 g, and gestational age ≥ 32 weeks were identified as risk factors for THOP based on simple logistic regression. In multiple regression, mechanical ventilation and gestational age ≥ 32 weeks were significantly associated with THOP. CH was seen in 2 (3.1%) babies, and 1 of these cases had delayed TSH elevation. Conclusion: Thyroid abnormalities are common in preterm admitted neonates. Mechanical ventilation is an independent risk factor for development of THOP.

Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity.

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China's Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency's (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100-150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.