Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases.

Understanding kinase-inhibitor selectivity continues to be a major objective in kinase drug discovery. We probe the molecular basis of selectivity of an allosteric inhibitor (MSC1609119A-1) of the insulin-like growth factor-I receptor kinase (IGF1RK), which has been shown to be ineffective for the homologous insulin receptor kinase (IRK). Specifically, we investigated the structural and energetic basis of the allosteric binding of this inhibitor to each kinase by combining molecular modeling, molecular dynamics (MD) simulations, and thermodynamic calculations. We predict the inhibitor conformation in the binding pocket of IRK and highlight that the charged residues in the histidine-arginine-aspartic acid (HRD) and aspartic acid-phenylalanine-glycine (DFG) motifs and the nonpolar residues in the binding pocket govern inhibitor interactions in the allosteric pocket of each kinase. We suggest that the conformational changes in the IGF1RK residues M1054 and M1079, movement of the ⍺C-helix, and the conformational stabilization of the DFG motif favor the selectivity of the inhibitor toward IGF1RK. Our thermodynamic calculations reveal that the observed selectivity can be rationalized through differences observed in the electrostatic interaction energy of the inhibitor in each inhibitor/kinase complex and the hydrogen bonding interactions of the inhibitor with the residue V1063 in IGF1RK that are not attained with the corresponding residue V1060 in IRK. Overall, our study provides a rationale for the molecular basis of recognition of this allosteric inhibitor by IGF1RK and IRK, which is potentially useful in developing novel inhibitors with improved affinity and selectivity.

Genomic and functional insights into antibiotic resistance genes floR and strA linked with the SXT element of Vibrio cholerae non-O1/non-O139.

The emergence and spread of antibiotic-resistant bacterial pathogens are a critical public health concern across the globe. Mobile genetic elements (MGEs) play an important role in the horizontal acquisition of antimicrobial resistance genes (ARGs) in bacteria. In this study, we have decoded the whole genome sequences of multidrug-resistant Vibrio cholerae clinical isolates carrying the ARG-linked SXT, an integrative and conjugative element, in their large chromosomes. As in others, the SXT element has been found integrated into the 5'-end of the prfC gene (which encodes peptide chain release factor 3 involved in translational regulation) on the large chromosome of V. cholerae non-O1/non-O139 strains. Further, we demonstrate the functionality of SXT-linked floR and strAB genes, which confer resistance to chloramphenicol and streptomycin, respectively. The floR gene-encoded protein FloR belongs to the major facilitator superfamily efflux transporter containing 12 transmembrane domains (TMDs). Deletion analysis confirmed that even a single TMD of FloR is critical for the export function of chloramphenicol. The floR gene has two putative promoters, P1 and P2. Sequential deletions reveal that P2 is responsible for the expression of the floR. Deletion analysis of the N- and/or C-terminal coding regions of strA established their importance for conferring resistance against streptomycin. Interestingly, qPCR analysis of the floR and strA genes indicated that both of the genes are constitutively expressed in V. cholerae cells. Further, whole genome-based global phylogeography confirmed the presence of the integrative and conjugative element SXT in non-O1/non-O139 strains despite being non-multidrug resistant by lacking antimicrobial resistance (AMR) gene cassettes, which needs monitoring.

Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.

The allosteric inhibition of insulin-like growth factor receptor 1 kinase (IGF1RK) is a potential strategy to overcome selectivity barriers for targeting receptor tyrosine kinases. We constructed structural models of a series of 12 indole-butyl-amine derivatives that have been reported as allosteric inhibitors of IGF1RK. We further studied the dynamics and interactions of each inhibitor in the allosteric pocket via all-atom explicit-solvent molecular dynamics (MD) simulations. We discovered that a bulky carbonyl substitution at the R1 indole ring is structurally unfavorable for inhibitor binding in the IGF1RK allosteric pocket. Moreover, we found that the most potent derivative (termed C11) acquires a distinct conformation: forming an allosteric pocket channel with better shape complementarity and interactions with the receptor. In addition to a hydrogen-bonding interaction with V1063, the cyano derivative C11 forms a stable hydrogen bond with M1156, which is responsible for its unique binding conformation in the allosteric pocket. Our findings show that the positioning of chemical substituents with different pharmacophore features at the R1 indole ring influences molecular interactions and binding conformations of indole-butyl-amine derivatives and, hence, dramatically affects their potencies. Our results provide a structural framework for the design of allosteric inhibitors with improved affinities and specificities against IGF1RK.

Molecular insights into the genome dynamics and interactions between core and acquired genomes of Vibrio cholerae.

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

Spatio-temporal investigation of physico-chemical water quality parameters based on comparative assessment of QUAL 2Kw and WASP model for the upper reaches of Yamuna River stretching from Paonta Sahib, Sirmaur district to Cullackpur, North Delhi districts of North India.

An accurate investigation of bio-physical and chemical parameters as proxy of in situ water quality conditions in the Himalayan region is highly challenging owing to cumbersome, strenuous, and physically exhausting sampling exercises at high altitude locations. The upper stretches of Yamuna River in the Himachal Pradesh are typical examples of such sampling locations that have rarely been examined in the past studies. A widely accepted and recognized QUAL 2Kw model is applied for estimating the water quality parameters on the upper segment of the Yamuna River from Paonta Sahib to Cullackpur. These water quality indicators mainly included electric conductivity, pH, dissolved oxygen, temperature, carbonaceous biological oxygen demand (CBOD), inorganic suspended solids, total nitrogen, total phosphorus, and alkalinity, which were systematically investigated for predicting the spatio-temporal trends during the year 2018. A total of 12 distantly located river sites were identified for sample collection and data validation using QUAL 2Kw model. The present investigation attempts to reveal long-term degraded impact of untreated wastewater and biased agricultural practices on the water quality conditions over the upper stretches of Yamuna River. The QUAL 2Kw-derived values for selected variables were inter-compared with in situ values, and any deviation from measured values was ascertained based on meaningful statistical measures. The lower error of RMSE, MRE, and BIAS, corresponding to < 15%, ± 10%., ± 20%, and ~ 1 slope evidently indicated better matchup of values, wherein, higher slope correlation coefficient (R2) of ~ 90% indicated the robust performance of the QUAL 2Kw algorithm in accurately predicting the chosen variables. A comparative assessment of QUAL 2Kw and WASP has been performed to justify aptness of water quality model in scenarios of lean flow.

Deciphering the role of residues in the loops nearing the active site of OXA-58 in imparting beta-lactamase activity.

The existence of OXA-58 carbapenemase alone or in combination with other beta-lactam resistance factors poses significant beta-lactam resistance. The exact mechanism of action of OXA type beta-lactamases is debatable due to the involvement of multiple residues within or outside the active site. In the present work, we have elucidated the relative role of residues present in the putative omega (W169, L170, K171) and ß6-ß7 (A226 and D228) loops on the activity of OXA-58 by substituting into alanine (and aspartate for A226) through site-directed mutagenesis. E. coli cells harbouring OXA-58, substituted at the putative omega loop, manifest a significant decrease in the beta-lactam resistance profile than that of the cells expressing OXA-58. Further, a reduction in the catalytic efficiency is observed for the purified variants of OXA-58 carrying individual substitutions in the putative omega loop than that of OXA-58. However, the addition of NaHCO3 (for carbamylation of K86) increases catalytic efficiency of the individual protein as revealed by nitrocefin hydrolysis assay and steady state kinetics. Moreover, W169A and K171A substitutions show significant effects on the thermal stability of OXA-58. Therefore, we conclude that the putative omega loop residues W169, L170 and K171, individually, have significant role in the activity and stability of OXA-58, mostly by stabilising carbamylated lysine of active site.

Pseudomonas aeruginosa isolate PM1 effectively controls virus infection and promotes growth in plants.

A bacterial isolate PM1 obtained from the rhizosphere of healthy plants was identified as Pseudomonas aeruginosa by biochemical characteristics and 16S rRNA gene sequence (GenBank ID OL321133.1). It induced resistance in Nicotiana tabacum cv. Xanthi-nc and Cyamopsis tetragonoloba, against Tobacco mosaic virus (TMV) and Sunn-hemp rosette virus (SRV), respectively. Foliar treatment with isolate PM1 curbed TMV accumulation in susceptible N. tabacum cv. White Burley. PM1 was more effective as a foliar than a root/soil drench treatment, evident through a comparative decrease in ELISA values, and reduced viral RNA accumulation. Foliar and soil drench treatment with PM1 resulted in a disease index of 48 and 86 per cent, and a control rate of 48.9 and 8.5 per cent, respectively. PM1 exhibited phosphate solubilization, produced siderophores, auxins, HCN, and ammonia, all important plant growth-promoting traits. Foliar treatment with PM1 enhanced growth in tobacco, while its volatiles significantly promoted seedling growth in C. tetragonoloba. Of the several metabolites produced by the isolate, many are known contributors to induction of systemic resistance, antibiosis, and growth promotion in plants. Soluble metabolites of PM1 were less effective in inducing antiviral resistance in N. tabacum cv. Xanthi-nc in comparison with its broth culture. PM1 and its metabolites were antagonistic to Gram-positive Bacillus spizizenii and Staphylococcus aureus, and fungi Fusarium oxysporum, Aspergillus niger, and Rhizopus stolonifer. Its volatiles were inhibitory to F. oxysporum and R. stolonifer. Thus, PM1 exhibited considerable potential for further evaluation in plant virus control and production of diverse metabolites of use in agriculture and medicine.

In silico identification and in vitro antiviral validation of potential inhibitors against Chikungunya virus.

The Chikungunya virus (CHIKV) has become endemic in the Africa, Asia and Indian subcontinent, with its continuous re-emergence causing a significant public health crisis. The unavailability of specific antivirals and vaccines against the virus has highlighted an urgent need for novel therapeutics. In the present study, we have identified small molecule inhibitors targeting the envelope proteins of the CHIKV to interfere with the fusion process, eventually inhibiting the cell entry of the virus particles. We employed high throughput computational screening of large datasets against two different binding sites in the E1-E2 dimer to identify potential candidate inhibitors. Among them, four high affinity inhibitors were selected to confirm their anti-CHIKV activity in the in vitro assay. Quercetin derivatives, Taxifolin and Rutin, binds to the E1-E2 dimer at different sites and display inhibition of CHIKV infection with EC50 values 3.6 µM and 87.67 µM, respectively. Another potential inhibitor with ID ChemDiv 8015-3006 binds at both the target sites and shows anti-CHIKV activity at EC50 = 41 µM. The results show dose-dependent inhibitory effects of Taxifolin, Rutin and ChemDiv 8015-3006 against the CHIKV with minimal cytotoxicity. In addition, molecular dynamics studies revealed the structural stability of these inhibitors at their respective binding sites in the E1-E2 protein. In conclusion, our study reports Taxifolin, Rutin and ChemDiv 8015-3006 as potential inhibitors of the CHIKV entry. Also, this study suggests a few potential candidate inhibitors which could serve as a template to design envelope protein specific CHIKV entry inhibitors.

Genomic plasticity associated with antimicrobial resistance in Vibrio cholerae.

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. Vibrio cholerae, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in V. cholerae has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in V. cholerae Here we present details of AMR profiles of 443 V. cholerae strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) V. cholerae to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of V. cholerae to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of V. cholerae evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.

Antimicrobial resistance and virulence in Helicobacter pylori: Genomic insights.

Microbes evolve rapidly by modifying their genome through mutations or acquisition of genetic elements. Antimicrobial resistance in Helicobacter pylori is increasingly prevalent in India. However, limited information is available about the genome of resistant H. pylori isolated from India. Our pan- and core-genome based analyses of 54 Indian H. pylori strains revealed plasticity of its genome. H. pylori is highly heterogenous both in terms of the genomic content and DNA sequence homology of ARGs and virulence factors. We observed that the H. pylori strains are clustered according to their geographical locations. The presence of point mutations in the ARGs and absence of acquired genetic elements linked with ARGs suggest target modifications are the primary mechanism of its antibiotic resistance. The findings of the present study would help in better understanding the emergence of drug-resistant H. pylori and controlling gastric disorders by advancing clinical guidance on selected treatment regimens.

Evaluation of air pollution tolerance index and anticipated performance index of selected roadside tree species in Ludhiana, India.

Air quality has deteriorated in most big cities and becoming the fifth major cause of mortality in India. Among others, vehicle gaseous emission is a major contributor. Plants have different tolerance levels, which can be identified based on Air Pollution Tolerance Index (APTI). The objectives were to study the morphological and biochemical parameters for Air Pollution Tolerance Index (APTI) of selected roadside tree species (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Cassia fistula, Cassia siamea, Dalbergia sissoo, Heterophragma adenophyllum, and Putranjiva roxburghii) at control (PAU campus) and polluted sites (roadside) during summer and winter seasons. The total chlorophyll content, ascorbic acid, leaf extract pH, leaf relative water content, total soluble sugar, phenols, and carotenoids ranged from 0.59 to 4.16 mg g-1, 1.03 to 3.75 mg g-1, 3.16 to 7.04, 46.01 to 71.65%, 10.78 to 23.83 mg g-1, 0.51 to 1.35 mg -1, and 0.19 to 1.96 mg g-1, respectively. The Air Pollution Tolerance Index of the selected trees ranged between7.65 and 11.19 and followed an order of Cassia fistula > Acacia auriculiformis > Dalbergia sissoo > Alstonia scholaris > Putranjiva roxburghii > Heterophragma adenophyllum > Cassia siamea > Chukrasia tabularis. The evaluation of Anticipated Performance Index (API) categorized the trees into poor (Dalbergia sissoo and Cassia siamea), moderate (Cassia fistula), and good (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Heterophragma adenophyllum, and Putranjiva roxburghii) categories.

A comparative study of human betacoronavirus spike proteins: structure, function and therapeutics.

Coronaviruses are the paradigm of emerging 21st century zoonotic viruses, triggering numerous outbreaks and a severe global health crisis. The current COVID-19 pandemic caused by SARS-CoV-2 has affected more than 51 million people across the globe as of 12 November 2020. The crown-like spikes on the surface of the virion are the unique structural feature of viruses in the family Coronaviridae. The spike (S) protein adopts distinct conformations while mediating entry of the virus into the host. This multifunctional protein mediates the entry process by recognizing its receptor on the host cell, followed by the fusion of the viral membrane with the host cell membrane. This review article focuses on the structural and functional comparison of S proteins of the human betacoronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we review the current state of knowledge about receptor recognition, the membrane fusion mechanism, structural epitopes, and glycosylation sites of the S proteins of these viruses. We further discuss various vaccines and other therapeutics such as monoclonal antibodies, peptides, and small molecules based on the S protein of these three viruses.

Absence of the glycosyltransferase WcaJ in Klebsiella pneumoniae ATCC13883 affects biofilm formation, increases polymyxin resistance and reduces murine macrophage activation.

Multidrug-resistant Klebsiella pneumoniae has emerged as one of the deadliest opportunistic nosocomial pathogens that forms biofilm for the establishment of chronic K. pneumoniae infections. Herein, we made an attempt to identify the genes involved in biofilm formation in the strain K. pneumoniae ATCC13883. To achieve this, we constructed mini-Tn5 transposon insertion mutants and screened them for biofilm production. We observed that the biofilm formation was enhanced in the mutant where the wcaJ gene was disrupted. WcaJ is the initiating enzyme of colanic acid synthesis and loads the first sugar (glucose-1-P) on the lipid carrier undecaprenyl phosphate. The absence of this glycosyltransferase results in the absence of colanic acid, which renders a non-mucoid phenotype to the mutant. Further, to determine the effect of mucoidy on antibiotic susceptibility, we tested the sensitivity of the strains towards different groups of antibiotics. Unlike the mucoid strains, the resistance of the non-mucoid cells was greater for polymyxins, but less for quinolones. Capsular polysaccharides are known to have a protective effect against phagocytosis, therefore we assessed the role of colanic acid in virulence by conducting infection studies on murine macrophages. Surprisingly, the ΔwcaJ strain was less efficient in macrophage activation and was not readily phagocytosed. Thus, the presence of colanic acid appeared to increase the immunogenicity of K. pneumoniae. Overall, the results indicate that the presence of colanic acid increases the vulnerability of K. pneumoniae towards both polymyxins and macrophages, implying that the mucoid strains are less threatening as compared to their high biofilm forming non-mucoid counterparts.

Molecular Insights into Antimicrobial Resistance Traits of Commensal Human Gut Microbiota.

Antimicrobial resistance (AMR) among bacterial species that resides in complex ecosystems is a natural phenomenon. Indiscriminate use of antimicrobials in healthcare, livestock, and agriculture provides an evolutionary advantage to the resistant variants to dominate the ecosystem. Ascendency of resistant variants threatens the efficacy of most, if not all, of the antimicrobial drugs commonly used to prevent and/or cure microbial infections. Resistant phenotype is very common in enteric bacteria. The most common mechanisms of AMR are enzymatic modifications to the antimicrobials or their target molecules. In enteric bacteria, most of the resistance traits are acquired by horizontal gene transfer from closely or distantly related bacterial population. AMR traits are generally linked with mobile genetic elements (MGEs) and could rapidly disseminate to the bacterial species through horizontal gene transfer (HGT) from a pool of resistance genes. Although prevalence of AMR genes among pathogenic bacteria is widely studied in the interest of infectious disease management, the resistance profile and the genetic traits that encode resistance to the commensal microbiota residing in the gut of healthy humans are not well-studied. In the present study, we have characterized AMR phenotypes and genotypes of five dominant commensal enteric bacteria isolated from the gut of healthy Indians. Our study revealed that like pathogenic bacteria, enteric commensals are also multidrug-resistant. The genes encoding antibiotic resistance are physically linked with MGEs and could disseminate vertically to the progeny and laterally to the distantly related microbial species. Consequently, the AMR genes present in the chromosome of commensal gut bacteria could be a potential source of resistance functions for other enteric pathogens.

Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.

The allosteric inhibition of Insulin-like Growth Factor Receptor 1 Kinase (IGF1RK) is a potential strategy to overcome selectivity barriers in targeting receptor tyrosine kinases. We constructed structural models of a series of 12 indole-butyl-amine derivatives which have been reported as allosteric inhibitors of IGF1RK. We further studied dynamics and interactions of each inhibitor in the allosteric pocket via all-atom explicit-solvent molecular dynamics (MD) simulations. We discovered that a bulky carbonyl substitution at the R1 indole ring is structurally unfavorable for inhibitor binding in the IGF1RK allosteric pocket. Moreover, we found that the most potent derivative (termed C11) acquires a distinct conformation, forming an allosteric pocket channel with better shape complementarity and interactions with the receptor. In addition to a hydrogen bonding interaction with V1063, the cyano derivative C11 forms a stable hydrogen bond with M1156, which is responsible for its unique binding conformation in the allosteric pocket. Our findings show that the position of chemical substituents at the R1 indole ring with different pharmacophore features influences molecular interactions and binding conformations of the indole-butyl-amine derivatives, hence dramatically affecting their potencies. Our results provide a structural framework for the design of allosteric inhibitors with improved affinities and specificities against IGF1RK.

Multilocular cystic nephroma in an adult: a diagnostic quandary.

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry.

Undiagnosed Intra-articular Synovial Hemangioma: A Rare Cause of Knee Pain and Swelling.

INTRODUCTION: Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the primary skeleton tumors. A delay in diagnosis results in joint degeneration and osteoarthritic damage because of infiltrating tumor growth. CASE PRESENTATION: We presented a rare case of an intra-articular synovial hemangioma in a 13- year-old pediatric patient who was asymptomatic for 5 years. She attended orthopedics OPD at AIIMS, Mangalagiri. Surgical excision of the mass and partial synovectomy was done. Synovial hemangioma came out to be the diagnosis following a histologic study. CONCLUSION: As radiography has limited diagnostic ability, synovial hemangiomas are difficult and challenging to identify on an outpatient basis. Histological examination and magnetic resonance imaging are extremely helpful. To minimize the hemarthrosis risks, early complete excision can be used as the best treatment modality.

Collinsella aerofaciens linked with increased ethanol production and liver inflammation contribute to the pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity: Insights from national inpatient sample 2020.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels. AIM: To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity. METHODS: COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease -10 CM codes in the 2020 National Inpatient Sample database. Overweight and Obesity Classes I, II, and III (body mass index 30-40) were compared. Major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) were compared between groups. Multivariable regression analyses adjusted for sociodemographic, hospitalization features, and comorbidities. RESULTS: Our analysis comprised 13260 hospitalizations, 7.3% of which were overweight, 24.3% Class I, 24.1% Class II, and 44.3% Class III. Class III obesity includes younger patients, blacks, females, diabetics, and hypertensive patients. On multivariable logistic analysis, Class III obese patients had higher risks of MACCE, inpatient mortality, and respiratory failure than Class I obese patients. Class II obesity showed increased risks of MACCE, inpatient mortality, and respiratory failure than Class I, but not significantly. All obesity classes had non-significant risks of MACCE, inpatient mortality, and respiratory failure compared to the overweight group. CONCLUSION: Class III obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class I. Using the overweight group as the reference, unfavorable outcomes were not significantly different. Morbid obesity had a greater risk of MACCE regardless of the referent group (overweight or Class I obese) compared to overweight NAFLD patients admitted with COVID-19.