Addition of Mask to High-flow Nasal Oxygen: A Strategy to Improve Oxygenation in Hypoxemic Respiratory Failure Secondary to COVID-19.

PURPOSE: High-flow nasal cannula (HFNO) reduces the need for invasive mechanical ventilation in COVID-19 patients with hypoxemic-respiratory failure. During HFNO entrainment of room air dilutes the delivered fractional inspiratory oxygen (FiO2), thereby preventing improvement in oxygenation. The placement of a mask over HFNO to improve oxygenation has provided conflicting results. We aimed to determine and compare the effect of placing various mask types over HFNO on oxygen saturation (SPO2). MATERIALS AND METHODS: In this prospective physiological study 40 patients with COVID-19-associated hypoxemic respiratory failure on HFNO with O2 concentration <92% were included. The effect of placing different masks over HFNO on oxygenation, respiratory rate, heart rate, blood pressure, patient comfort, and partial pressure of carbon dioxide level (pCO2) was recorded after a prespecified time interval. RESULTS: We observed a significantly higher mean SPO2 and lower mean respiratory rate on using various study masks over HFNO compared to HFNO alone. On comparing various mask types, the use of N95 masks and nonrebreather (NRB) masks with O2 showed a significant increase in O2 concentration and reduction in respiratory rate compared to surgical mask (SM) and NRB without O2. The proportion of patients who achieved SPO2 of >92% was higher with the use of N95 masks (47.5%) or NRB with O2 (45%) over HFNO compared to SM (35%) and NRB without O2 (35%). No significant change was observed in heart rate, blood pressure, and CO2 level with the use of any mask over HFNO. CONCLUSION: This study demonstrates improvement in oxygenation and reduction in respiratory rate with the use of various masks over HFNO in patients of COVID-19-related hypoxemic-respiratory-failure. Significantly greater benefit was achieved with the use of N95 or NRB with O2 compared to SM or NRB without O2.

Exploring psychiatric patient restraints: Balancing safety, ethics, and patient rights in mental healthcare.

Restraint, often linked with limiting an individual's freedom of movement, has become a focal point of extensive discussion and evaluation within the realm of mental healthcare. Striking a delicate balance between ensuring individual safety and minimizing reliance on restraint methods poses a significant challenge. In mental health inpatient settings, the prevalent forms of restraint encompass physical, chemical, environmental, and psychological methods. Paradoxically, the consequences of employing restraint can be severe, ranging from injuries and cognitive decline to sedation and, in extreme cases, fatalities. This paper seeks to offer a nuanced exploration of the landscape surrounding psychiatric patient restraints, considering both global perspectives and specific insights from the Indian context. The guidelines outlined in India's Mental Healthcare Act of 2017, which governs the use of restraint on individuals suffering with mental illnesses, are also examined in detail.

VEXAS syndrome presenting as diffuse alveolar haemorrhage.

We report the case of a man in his late 30s who presented with a history of breathlessness and cough with haemoptysis. Complete blood counts revealed pancytopenia. High-resolution CT showed diffuse bilateral ground glass opacities. Sequential bronchoalveolar lavage confirmed alveolar haemorrhage. Bone marrow aspiration showed vacuoles in erythroid and myeloid precursor cells. The genome was sequenced, and the UBA1 gene revealed a c.121 A>G mutation (p.Met41Val), confirming vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The patient was managed with high-dose prednisolone pulse therapy. He improved with the complete resolution of the alveolar haemorrhage and an improvement in lung function and cytopenias.

Utilizing sinapic acid as an inhibitory antiviral agent against MERS-CoV PLpro.

Concerns about the social and economic collapse, high mortality rates, and stress on the healthcare system are developing due to the coronavirus onslaught in the form of various species and their variants. In the recent past, infections brought on by coronaviruses severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) as well as middle east respiratory syndrome coronavirus (MERS-CoV) have been reported. There is a severe lack of medications to treat various coronavirus types including MERS-CoV which is hazard to public health due to its ability for pandemic spread by human-to-human transmission. Here, we utilized sinapic acid (SA) against papain-like protease (PLpro), a crucial enzyme involved in MERS-CoV replication, because phytomedicine derived from nature has less well-known negative effects. The thermal shift assay (TSA) was used in the current study to determine whether the drug interact with the recombinant MERS-CoV PLpro. Also, inhibition assay was conducted as the hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of SA to determine the level of inhibition of the MERS-CoV PLpro. To study the structural binding efficiency Autodock Vina was used to dock SA to the MERS-CoV PLpro and results were analyzed using PyMOL and Maestro Schrödinger programs. Our results show a convincing interaction between SA and the MERS protease, as SA reduced MERS-CoV PLpro in a dose-dependent way IC50 values of 68.58 µM (of SA). The TSA showed SA raised temperature of melting to 54.61 °C near IC50 and at approximately 2X IC50 concentration (111.5 µM) the Tm for SA + MERS-CoV PLpro was 59.72 °C. SA was docked to MERS-CoV PLpro to identify the binding site. SA bound to the blocking loop (BL2) region of MERS-CoV PLpro interacts with F268, E272, V275, and P249 residues of MERS-CoV PLpro. The effectiveness of protease inhibitors against MERS-CoV has been established and SA is already known for broad range biological activity including antiviral properties; it can be a suitable candidate for anti-MERS-CoV treatment.

Assessment of flusilazole residues on apples: Detection, quantification and health risk implications.

Apple, a major fruit of temperate Himalayas, is sprayed with chemical pesticides around 12 times during the cropping season. Various systemic and contact fungicides are applied for the management of major diseases. In order to manage disease, flusilazole 40 EC is frequently used. However, excessive chemical application has been found to be detrimental for consumer safety. Keeping in view consumer safety, risk assessment, the half-life and waiting period for flusilazole 40 EC were evaluated on the Red Velox variety of apple. The QuEChERS (quick, easy, cheap, effective, rugged and safe) method and high-performance liquid chromatography were adapted for sample processing and analysis, respectively. The recovery percentages of flusilazole at three fortification levels (0.04, 0.09 and 0.50 mg kg-1) were 98.85, 99.83 and 98.98%, respectively. Flusilazole at the recommended dose (80 g a.i. ha-1) left an initial deposit of 0.733 mg kg-1, which dissipated by 93.45% in 60 days and was non-detectable beyond this period. Meanwhile flusilazole at double the recommended dose (160 g a.i. ha-1) left an initial deposit of 0.913 mg kg-1, which dissipated by 93.43% in 70 days and was non-detectable beyond this period. Based on the maximum residue limit of 0.3 mg kg-1 as prescribed by the Codex Alimentarius Commission, a waiting period of 28.74 and 46.03 days was recorded for single and double doses, respectively. Moreover, in order to assess the consumer risk, theoretical maximum residue contributions (TMRCs) were derived using flusilazole residues (average and maximum) recorded at various time intervals and compared with the maximum permissible intake, which was found to be 0.42 mg per person per day. Based on the average per capita daily consumption of 6.76 g apple in India, the TMRC values were computed. Although the values of TMRC decreased below maximum permissible intake at the first day after application, indicating minimal consumer health risks, fruits sprayed with a double dose of flusilazole carried the risk even up to the tenth day after flusilazole application. The results of the present study will be valuable for safe and timely use of flusilazole on apple.

Inflammatory protein signatures in individuals with obesity and metabolic syndrome.

There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity.

Assessing the impacts of climate change on streamflow dynamics: A machine learning perspective.

This study investigates changes in river flow patterns, in the Hunza Basin, Pakistan, attributed to climate change. Given the anticipated rise in extreme weather events, accurate streamflow predictions are increasingly vital. We assess three machine learning (ML) models - artificial neural network (ANN), recurrent neural network (RNN), and adaptive fuzzy neural inference system (ANFIS) - for streamflow prediction under the Coupled Model Intercomparison Project 6 (CMIP6) Shared Socioeconomic Pathways (SSPs), specifically SSP245 and SSP585. Four key performance indicators, mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2), guide the evaluation. These models employ monthly precipitation, maximum and minimum temperatures as inputs, and discharge as the output, spanning 1985-2014. The ANN model with a 3-10-1 architecture outperforms RNN and ANFIS, displaying lower MSE, RMSE, MAE, and higher R2 values for both training (MSE = 20417, RMSE = 142, MAE = 71, R2 = 0.94) and testing (MSE = 9348, RMSE = 96, MAE = 108, R2 = 0.92) datasets. Subsequently, the superior ANN model predicts streamflow up to 2100 using SSP245 and SSP585 scenarios. These results underscore the potential of ANN models for robust futuristic streamflow estimation, offering valuable insights for water resource management and planning.

Intercomparison of SWAT and ANN techniques in simulating streamflows in the Astore Basin of the Upper Indus.

The current research work was carried out to simulate monthly streamflow historical record using Soil and Water Assessment Tool (SWAT) and Artificial Neural Network (ANN) at the Astore Basin, Gilgit-Baltistan, Pakistan. The performance of SWAT and ANN models was assessed during calibration (1985-2005) and validation (2006-2010) periods via statistical indicators such as coefficient of determination (R2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS), and root-mean-square error (RMSE). R2, NSE, PBIAS, and RMSE values for SWAT (ANN with Architecture (2,27,1)) models during calibration are 0.80 (0.88), 0.73 (0.82), 15.7 (0.008), and 79.81 (70.34), respectively, while during validation, the corresponding values are 0.71 (0.86), 0.66 (0.95), 17.3 (0.10), and 106.26 (75.92). The results implied that the ANN model is superior to the SWAT model based on the statistical performance indicators. The SWAT results demonstrated an underestimation of the high flow and overestimation of the low flow. Comparatively, the ANN model performed very well in estimating the general and extreme flow conditions. The findings of this research highlighted its potential as a valuable tool for accurate streamflow forecasting and decision-making. The current study recommends that additional machine learning models may be compared with the SWAT model output to improve monthly streamflow predictions in the Astore Basin.

Neuroepigenetics of ageing and neurodegeneration-associated dementia: An updated review.

Gene expression is tremendously altered in the brain during memory acquisition, recall, and forgetfulness. However, non-genetic factors, including environmental elements, epigenetic changes, and lifestyle, have grabbed significant attention in recent years regarding the etiology of neurodegenerative diseases (NDD) and age-associated dementia. Epigenetic modifications are essential in regulating gene expression in all living organisms in a DNA sequence-independent manner. The genes implicated in ageing and NDD-related memory disorders are epigenetically regulated by processes such as DNA methylation, histone acetylation as well as messenger RNA editing machinery. The physiological and optimal state of the epigenome, especially within the CNS of humans, plays an intricate role in helping us adjust to the changing environment, and alterations in it cause many brain disorders, but the mechanisms behind it still need to be well understood. When fully understood, these epigenetic landscapes could act as vital targets for pharmacogenetic rescue strategies for treating several diseases, including neurodegeneration- and age-induced dementia. Keeping this objective in mind, this updated review summarises the epigenetic changes associated with age and neurodegeneration-associated dementia.

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case-control study.

OBJECTIVES: To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways. METHODS: We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications. RESULTS: We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome. CONCLUSIONS: The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications.

Cathepsin-B inhibitor CA-074 attenuates retinopathy and optic neuritis in experimental autoimmune encephalomyelitis induced in SJL/J mice.

The complicated multiple sclerosis (MS) can exhibit subacute sight deterioration and can lead to total deprivation of vision. In the current work, we explored the therapeutic outcome of Cathepsin B inhibitor (CA-074) against retinopathy and optic neuritis (ON) caused by experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP) in female SJL/J mice. A daily dose of 10 mg/kg CA-074 was administered to the EAE mice intraperitoneally for 14 days from day 14 post-immunization until day 28. The Western blot and immunofluorescence analyses show inflammation in the optic nerve through the elevation of iNOS and NFkB markers in EAE mice. Optic neuritis was reported which is a consequence of demyelination and axon injury, estimated with the reduction in myelin basic protein (MBP). The glial fibrillary acidic protein (GFAP) expression level was found to be elevated in the retina of EAE mice which confirmed the retinopathy. The administration of CA-074 ameliorated optic neuritis and retinopathy by reducing inflammation. The treatment with CA-074 also reduced the demyelination and axonal injuries in the EAE mice. The findings of this study have shown the protective effect of CA-074 in the case of retinopathy and ON inflicted by EAE in SJL/J mice.

Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult.

Repulsive guidance molecule-a (RGMa) inhibits angiogenesis and increases inflammation. Animal models of cerebral ischemia have shown that an increased expression of RGMa leads to larger infarction and its inhibition attenuates effects of ischemia. We report on the relationship of RGMa to stroke types and severity. This is a prospective study in patients admitted to the stroke service in Qatar. We collected the clinical determinants, including NIHSS at admission, imaging and outcome at discharge and 90-days. RGMa levels were determined by measuring mRNA levels extracted from peripheral blood mononuclear cells (PBMCs) within 24 h of onset and at 5 days. There were 90 patients (lacunar: 64, cortical: 26) and 35 age-matched controls. RGMa mRNA levels were significantly higher in the stroke patients: day 1: 1.007 ± 0.13 versus 2.152 ± 0.19 [p < 0.001] and day-5: 3.939 ± 0.36 [p < 0.0001]) and significantly higher in patients with severe stroke (NIHSS ≥ 8) compared to milder symptoms (NIHSS < 8) at day 1 (NIHSS ≥ 8: 2.563 ± 0.36; NIHSS < 8: 1.947 ± 0.2) and day 5 (NIHSS ≥ 8: 5.25 ± 0.62; NIHSS < 8: 3.259 ± 0.419). Cortical stroke patients had marginally higher RGMa mRNA levels compared to lacunar stroke at day 1 (cortical stroke: 2.621 ± 0.46 vs lacunar stroke: 1.961 ± 0.19) and day 5 (cortical stroke: 4.295 ± 0.76 vs lacunar stroke: 3.774 ± 0.39). In conclusion, there is an increase in the level of RGMa mRNA in patients with acute stroke and seen in patients with lacunar and cortical stroke. The increase in RGMa mRNA levels is related to the severity of the stroke and increases over the initial 5 days. Further studies are required to determine the effects of the increase in RGMa on stroke recovery.

Muscle Tension Dysphonia: Experience from a Conflict Zone.

We sought to explore the frequency of stress among OPD attending Kashmiri public diagnosed as muscle tension dysphonia (MTD) and determine the subjective consequences of voice therapy in management of muscle tension dysphonia. 72 subjects that attended to ENT and HNS OPD with change of voice were prospectively evaluated and also underwent an extensive otolaryngological examination. Patients identified as MTD were provided a questionnaire which was split into 3 parts: First part dealt with the identification of the subject (age, geography, gender, profession) and also provided evaluation of perceived anxiety using Perceived Stress Scale-10. In the next part the individuals needed to assess their vocal quality based on parameters of GRBAS 4-point score scale before and also after the treatment. In the final component the subjects also needed to answer the VHI-10 (Voice Handicap Index) and also the outcome was compared with those acquired at the assessment before the beginning of the treatment. The mean age of the cohort was 30.31 ± 07.43 (age range, 12-71) and every subject was an indigenous Kashmiri. As expected, vast majority of subjects were females (43 patients). In the pooled information set, women had numerically higher PSS-10 scores than males. For women, the typical stress score was M = 18.6 and for men the average stress score was M = 16.65. In a healthy population, the typical PSS stress score is described to be 13.7 (SD = 6.6) for women and 12.1 (SD = 5.9) for men. At the Wilcoxon test for paired data, we observed a significant difference between the VHI pretreatment (mean = 19.7) and VHI post-treatment, that's at time of the research (mean = 9.73; P = 0.017). The grade (G) was assessed in terms of improvement of the vocal quality as opposed with before treatment and also the individuals demonstrated a high level of satisfaction (mean = 0.65). When looking at roughness (R) as well as breathiness (B), the individuals remember that their speech is seldom rough (mean = 0.62) and also less breathy (median = 0.44). Patients likewise noted improvement in other variables of GRBAS scale. Stress is persistent, pervasive and nearly unavoidable in contemporary life. The decades old perplexing and mind baffling pandemonium hovering around the Kashmiri population has had a tremendous impression on the psychological development of people in this region. A careful conclusion is the fact that emotional stress might play a major role in the upkeep of MTD. MTD has to be approached in a multidisciplinary environment in which closer cooperation between a laryngologist, a speech language pathologist and also a psychologist is likely.

Platelet-Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi.

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.

Review of Modeling Techniques for Analysis and Assessment of RC Beam-Column Joints Subjected to Seismic Loads.

Beam-column connections are the most critical components of reinforced concrete (RC) structures. They serve as a load transfer path and take a significant portion of the overall shear. Joints in RC structures constructed with no seismic provisions have an insufficient capacity and ductility under lateral loading and can cause the progressive failure of the entire structure. The joint may fail in the shear prior to the connecting beam and column elements. Therefore, several modeling techniques have been devised in the past to capture the non-linear response of such joints. Modeling techniques used to capture the non-linear response of reinforced-concrete-beam-column joints range from simplified lumped plasticity models to detailed fiber-based finite element (FE) models. The macro-modeling technique for joint modeling is highly efficient in terms of the computational effort, analysis time, and computer memory requirements, and is one of the most widely used modeling techniques. The non-linear shear response of the joint panel and interface bond-slip mechanism are concentrated in zero-length linear and rotational springs while the connecting elements are modeled through elastic elements. The shear response of joint panels has also been captured through rigid panel boundary elements with rotational springs. The computational efficiency of these models is significantly high compared to continuum models, as each joint act as a separate supe-element. This paper aims to provide an up-to-date review of macro-modeling techniques for the analysis and assessment of RC-beam-column connections subjected to lateral loads. A thorough understanding of existing models is necessary for developing new mechanically adequate and computationally efficient joint models for the analysis and assessment of deficient RC connections. This paper will provide a basis for further research on the topic and will assist in the modification and optimization of existing models. As each model is critically evaluated, and their respective capabilities and limitations are explored, it should help researchers to improve and build on modeling techniques both in terms of accuracy and computational efficiency.

Dysregulated Metabolic Pathways in Subjects with Obesity and Metabolic Syndrome.

Background: Obesity coexists with variable features of metabolic syndrome, which is associated with dysregulated metabolic pathways. We assessed potential associations between serum metabolites and features of metabolic syndrome in Arabic subjects with obesity. Methods: We analyzed a dataset of 39 subjects with obesity only (OBO, n = 18) age-matched to subjects with obesity and metabolic syndrome (OBM, n = 21). We measured 1069 serum metabolites and correlated them to clinical features. Results: A total of 83 metabolites, mostly lipids, were significantly different (p < 0.05) between the two groups. Among lipids, 22 sphingomyelins were decreased in OBM compared to OBO. Among non-lipids, quinolinate, kynurenine, and tryptophan were also decreased in OBM compared to OBO. Sphingomyelin is negatively correlated with glucose, HbA1C, insulin, and triglycerides but positively correlated with HDL, LDL, and cholesterol. Differentially enriched pathways include lysine degradation, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, and galactose metabolism. Conclusions: Metabolites and pathways associated with chronic inflammation are differentially expressed in subjects with obesity and metabolic syndrome compared to subjects with obesity but without the clinical features of metabolic syndrome.

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome.

Background: Obesity-associated dysglycemia is associated with metabolic disorders. MicroRNAs (miRNAs) are known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with clinical features in obese Qatari individuals. Methods: We analyzed a dataset of 39 age-matched patients that includes 18 subjects with obesity only (OBO) and 21 subjects with obesity and metabolic syndrome (OBM). We measured 754 well-characterized human microRNAs (miRNAs) and identified differentially expressed miRNAs along with their significant associations with clinical markers in these patients. Results: A total of 64 miRNAs were differentially expressed between metabolically healthy obese (OBO) versus metabolically unhealthy obese (OBM) patients. Thirteen out of 64 miRNAs significantly correlated with at least one clinical trait of the metabolic syndrome. Six out of the thirteen demonstrated significant association with HbA1c levels; miR-331-3p, miR-452-3p, and miR-485-5p were over-expressed, whereas miR-153-3p, miR-182-5p, and miR-433-3p were under-expressed in the OBM patients with elevated HbA1c levels. We also identified, miR-106b-3p, miR-652-3p, and miR-93-5p that showed a significant association with creatinine; miR-130b-5p, miR-363-3p, and miR-636 were significantly associated with cholesterol, whereas miR-130a-3p was significantly associated with LDL. Additionally, miR-652-3p's differential expression correlated significantly with HDL and creatinine. Conclusions: MicroRNAs associated with metabolic syndrome in obese subjects may have a pathophysiologic role and can serve as markers for obese individuals predisposed to various metabolic diseases like diabetes.

The molecular genetics of human appendicular skeleton.

Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.

Role of Epigenetics in Modulating Phenotypic Plasticity against Abiotic Stresses in Plants.

Plants being sessile are always exposed to various environmental stresses, and to overcome these stresses, modifications at the epigenetic level can prove vital for their long-term survival. Epigenomics refers to the large-scale study of epigenetic marks on the genome, which include covalent modifications of histone tails (acetylation, methylation, phosphorylation, ubiquitination, and the small RNA machinery). Studies based on epigenetics have evolved over the years especially in understanding the mechanisms at transcriptional and posttranscriptional levels in plants against various environmental stimuli. Epigenomic changes in plants through induced methylation of specific genes that lead to changes in their expression can help to overcome various stress conditions. Recent studies suggested that epigenomics has a significant potential for crop improvement in plants. By the induction and modulation of various cellular processes like DNA methylation, histone modification, and biogenesis of noncoding RNAs, the plant genome can be activated which can help in achieving a quicker response against various plant stresses. Epigenetic modifications in plants allow them to adjust under varied environmental stresses by modulating their phenotypic plasticity and at the same time ensure the quality and yield of crops. The plasticity of the epigenome helps to adapt the plants during pre- and postdevelopmental processes. The variation in DNA methylation in different organisms exhibits variable phenotypic responses. The epigenetic changes also occur sequentially in the genome. Various studies indicated that environmentally stimulated epimutations produce variable responses especially in differentially methylated regions (DMR) that play a major role in the management of stress conditions in plants. Besides, it has been observed that environmental stresses cause specific changes in the epigenome that are closely associated with phenotypic modifications. However, the relationship between epigenetic modifications and phenotypic plasticity is still debatable. In this review, we will be discussing the role of various factors that allow epigenetic changes to modulate phenotypic plasticity against various abiotic stress in plants.