Unravelling the obesity maze in diabetic patients: A comparative analysis of classification methods.

Background: Obesity is a significant health concern among individuals with type 2 diabetes mellitus (T2DM). Emerging evidence suggests that alternative measures, such as abdominal girth (AG) and body fat percentage (BF%), can provide a more accurate reflection of obesity-related metabolic risks in diabetic populations. This study aimed to compare the accuracy of different obesity classification methods, including BMI, AG, and BF%, among individuals with T2DM. Methodology: This was an observational cross-sectional study conducted among T2DM patients who came to the non-communicable diseases clinic of GG Govt Hospital, Jamnagar, Gujarat during the period of March-April 2023. Demographic and anthropometric information was collected. Body fat analysis was done using a validated Omron fat analyzer. Results: The study found the sensitivity of BMI in males and females as 41.6% and 45% against BF%, respectively. It also showed that the sensitivity of BMI in males and females was 38% and 40.7%, respectively, against AG. The present study also found a moderate positive correlation (r = 0.575) between AG and BF% in individuals with T2DM. Conclusion: The findings indicate that BF% and AG provide valuable insights into adiposity, surpassing the limitations of BMI as a measure of body composition. BF% is an indicator of body fat content, whereas AG serves as a proxy for central adiposity. The correlations between BF% and AG suggest that excess abdominal fat accumulation signifies increased body fat. By incorporating measures such as BF% and AG alongside BMI, clinicians can obtain a more comprehensive understanding of body composition and its relationship with metabolic abnormalities.

The Hidden Battle Within: Shedding Light on the Co-existence of Sarcopenia and Sarcopenic Obesity among Participants with Type 2 Diabetes in a Tertiary Care Hospital, Gujarat.

Introduction: Type 2 diabetes (T2DM) is characterised by chronic hyperglycaemia due to abnormal insulin secretion and/or utilisation. Currently, sarcopenia has emerged as a new complication of T2DM, which increases the risk of physical disability, and even death. The study aims to estimate the prevalence of sarcopenia and sarcopenic obesity (SO) as well as their association with various other factors related to T2DM. Methods: The study was an observational hospital-based cross-sectional study conducted among diabetic patients who came to the non-communicable diseases (NCD) clinic of a tertiary care hospital in Gujarat, India, from April 2023 to June 2023. Adult patients with T2DM attending follow-ups were included, with a diagnosis of T2DM for at least 1 year from the date of their electronic medical records, regardless of their mode of therapeutic treatment. They were on regular medical reviews with two or more visits to the study site in the past 1 year. Then a self-structured standard questionnaire was used to collect the data, containing socio-demographic characteristics, clinical profiles, anthropometric assessment (comprising weight, height and body mass index [BMI]), bio-impedance indices like body fat%, skeletal muscle% and handgrip by hand dynamometer. Results: In the study, a total of 404 participants participated. Their mean age was 55 ± 13.5 years and their mean body fat (BF) % was 30 ± 7.4%. BF%-defined obesity was found in 260 (64.4%) participants. A total of 362 (89.6%) had possible sarcopenia, 183 (45.3%) had sarcopenia and 124 (30.7%) had SO. Age (OR: 2.6, CI: 1.7-3.9), duration of diabetes for more than 7 years (OR: 7.5, CI: 3.65-15.4) and BF%-defined obesity (OR: 2.2, CI: 3.6-15) were statistically associated with Sarcopenia, in similar pattern age (OR: 2.4, CI: 1.5-3.7), and duration of diabetes more than 7 years (OR: 18.9, CI: 5.7-62) were associated with SO (P < 0.05). Conclusion: Older age, longer diabetes duration and BF%-defined obesity are associated with an increased likelihood of developing sarcopenia and sarcopenic obesity. Healthcare providers should prioritise regular screening for sarcopenia and SO in elderly individuals with diabetes to facilitate early detection and intervention.

The triad of physiological challenges: investigating the intersection of sarcopenia, malnutrition, and malnutrition-sarcopenia syndrome in patients with COPD - a cross-sectional study.

BACKGROUND: One of the most prevalent respiratory disorders in modern society is chronic obstructive pulmonary disease (COPD). Frequent comorbidities in patients with COPD are abnormal nutritional status and body composition variations. Malnutrition-sarcopenia syndrome, which occurs when the 2 conditions - malnutrition and sarcopenia - coexist, raises the risk of death more than either condition alone. The current study sought to determine the prevalence of malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in patients with COPD as well as the association between these diseases and the severity of COPD. METHODS: The study was an analytical cross-sectional study conducted on hospitalized patients with COPD. The sample size of the study was calculated to be 160. A self-structured questionnaire was used to collect the data, containing sociodemographic characteristics, clinical profiles, anthropometric assessment, and bioimpedance indices. Sarcopenia was diagnosed with low muscle strength and muscle mass by the EWGSOP2 recommendations. Muscle mass is measured by BIA and muscle strength (Handgrip) was measured by a Hand Dynamometer. Assessment of the risk of malnutrition was performed using the Mini Nutritional Assessment-Short Form questionnaire and was confirmed by GLIM criteria. The COPD assessment test (CAT) tool determined the severity of the condition. For the data analysis, comparisons were made using Student's t test and Mann-Whitney test in bivariate analysis. Multivariate logistic regression analyses were performed considering the outcomes of patients with COPD by CAT scores, prolonged length of stay, and hospital readmission 6 months after discharge. RESULTS: The mean age of the participants was 48 ± 5 years. Approximately 61.9% were found to be sarcopenic. Approximately 45.6% of participants had malnutrition. Malnutrition sarcopenia syndrome was diagnosed in 32.5% of patients. The study analysis revealed that patients with COPD with malnutrition-sarcopenia syndrome had more than twice the odds of prolonged hospital stay, re-admission within 6 months, and higher CAT scores. CONCLUSION: The study revealed a high prevalence of sarcopenia, malnutrition, and malnutrition sarcopenia syndrome in patients with COPD. These conditions were found to be statistically significant with prolonged length of stay, re-admission within 6 months, and CAT scores. The findings highlight the importance of addressing these conditions as part of the management of the patients.

Considerations for Potential Global Expansion of Serum Institute of India.

In a time of global vaccine shortages, especially for COVID-19 products, Serum Institute of India (SII) is straining to meet demand for vaccines in India. While this organization is not known worldwide, they entered into a recent alliance with AstraZeneca, who is partnered with Oxford University for COVID-19 vaccine, to manufacture their supply of vaccines for distribution in India. Several other such partnerships are also underway. And, SII is considering plans to become a much larger player, not only in India, but globally. This commentary is focused on if, when, where, why, and how global expansion could proceed. Our work was carried out as a class project to identify options and strategies appropriate for expansion and has been expanded subsequently as events continued to develop.

VA TECHNOLOGY TRANSFER PROGRAM RESPONDS TO COVID-19 PANDEMIC.

The COVID-19 pandemic stressed healthcare systems all over the world. Two primary challenges that healthcare systems faced were a shortage of personal protective equipment and the need for new technologies to handle infection prevention for staff and patients. The Department of Veteran's Affairs (VA) Technology Transfer Program responded by prioritizing the development of innovations in the Technology Transfer Assistance Project which addressed the pandemic. This paper describes several innovations that addressed the needs of the VA healthcare system during the pandemic and how they were rapidly developed.

A Dual-Functioning 5'-PPP-NS1shRNA that Activates a RIG-I Antiviral Pathway and Suppresses Influenza NS1.

Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral replication, morbidity, and mortality. We show that silencing NS1 with in-vitro-transcribed 5'-triphosphate containing NS1 short hairpin RNA (shRNA) (5'-PPP-NS1shRNA), designed using the conserved region of a number of influenza viruses, not only prevented NS1 expression but also induced RIG-I activation and type I interferon (IFN) expression, resulting in an antiviral state leading to inhibition of influenza virus replication in vitro. In addition, administration of 5'-PPP-NS1shRNA in prophylactic and therapeutic settings resulted in significant inhibition of viral replication following viral challenge in vivo in mice with corresponding increases of RIG-I, IFN-ß, and IFN-λ, as well as a decrease in NS1 expression.

Interference with the lower gut-liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis.

The gut-liver axis describes the complex interactions between gut microbiota, the small and large bowel, the immune system and the liver. Current evidence associates abnormalities within the gut-liver axis with liver disease such as primary sclerosing cholangitis (PSC). PSC is believed to be an immune-mediated disease though the exact mechanism of its pathogenesis remains unknown. Here, we report a case of a 66 -year-old woman with treatment-resistant ulcerative colitis and PSC which continued to be active following subtotal colectomy. Interestingly, her PSC achieved full remission after proctectomy for treatment-resistant proctitis in the rectal stump. This case report supports existing hypotheses that PSC is an immune-mediated disease triggered by antigens within the gut. More notably, it suggests the yet unidentified pathogens may be localised to the lower gastrointestinal tract including the rectum.

Gold nanoparticle-polymer nanocomposites synthesized by room temperature atmospheric pressure plasma and their potential for fuel cell electrocatalytic application.

Conductive polymers have been increasingly used as fuel cell catalyst support due to their electrical conductivity, large surface areas and stability. The incorporation of metal nanoparticles into a polymer matrix can effectively increase the specific surface area of these materials and hence improve the catalytic efficiency. In this work, a nanoparticle loaded conductive polymer nanocomposite was obtained by a one-step synthesis approach based on room temperature direct current plasma-liquid interaction. Gold nanoparticles were directly synthesized from HAuCl4 precursor in poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). The resulting AuNPs/PEDOT:PSS nanocomposites were subsequently characterized under a practical alkaline direct ethanol fuel cell operation condition for its potential application as an electrocatalyst. Results show that AuNPs sizes within the PEDOT:PSS matrix are dependent on the plasma treatment time and precursor concentration, which in turn affect the nanocomposites electrical conductivity and their catalytic performance. Under certain synthesis conditions, unique nanoscale AuNPs/PEDOT:PSS core-shell structures could also be produced, indicating the interaction at the AuNPs/polymer interface. The enhanced catalytic activity shown by AuNPs/PEDOT:PSS has been attributed to the effective electron transfer and reactive species diffusion through the porous polymer network, as well as the synergistic interfacial interaction at the metal/polymer and metal/metal interfaces.

Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.

During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. Such degradation subsequently results in the inhibition of type I interferon production in the infected cell. Our data demonstrate a mechanism by which cGAS senses cellular damage upon DENV infection.

NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.

The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection.

ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA.

The cytosolic antiviral innate immune sensor RIG-I distinguishes 5' tri- or diphosphate containing viral double-stranded (ds) RNA from self-RNA by an incompletely understood mechanism that involves ATP hydrolysis by RIG-I's RNA translocase domain. Recently discovered mutations in ATPase motifs can lead to the multi-system disorder Singleton-Merten Syndrome (SMS) and increased interferon levels, suggesting misregulated signaling by RIG-I. Here we report that SMS mutations phenocopy a mutation that allows ATP binding but prevents hydrolysis. ATPase deficient RIG-I constitutively signals through endogenous RNA and co-purifies with self-RNA even from virus infected cells. Biochemical studies and cryo-electron microscopy identify a 60S ribosomal expansion segment as a dominant self-RNA that is stably bound by ATPase deficient RIG-I. ATP hydrolysis displaces wild-type RIG-I from this self-RNA but not from 5' triphosphate dsRNA. Our results indicate that ATP-hydrolysis prevents recognition of self-RNA and suggest that SMS mutations lead to unintentional signaling through prolonged RNA binding.

Enhanced Dispersion of TiO2 Nanoparticles in a TiO2/PEDOT:PSS Hybrid Nanocomposite via Plasma-Liquid Interactions.

A facile method to synthesize a TiO2/PEDOT:PSS hybrid nanocomposite material in aqueous solution through direct current (DC) plasma processing at atmospheric pressure and room temperature has been demonstrated. The dispersion of the TiO2 nanoparticles is enhanced and TiO2/polymer hybrid nanoparticles with a distinct core shell structure have been obtained. Increased electrical conductivity was observed for the plasma treated TiO2/PEDOT:PSS nanocomposite. The improvement in nanocomposite properties is due to the enhanced dispersion and stability in liquid polymer of microplasma treated TiO2 nanoparticles. Both plasma induced surface charge and nanoparticle surface termination with specific plasma chemical species are proposed to provide an enhanced barrier to nanoparticle agglomeration and promote nanoparticle-polymer binding.

RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus.

UNLABELLED: In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5'-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. IMPORTANCE: CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I.

Activation and regulation of pathogen sensor RIG-I.

Cells are equipped with a large set of pattern recognition receptors or sensors that detect foreign molecules such as pathogenic nucleic acids and initiate proinflammatory and antimicrobial innate immune responses. RIG-I is a cytosolic sensor that detects 5'-triphosphate double-stranded RNAs produced during infection. RIG-I is responsible for mounting an antimicrobial response against a variety of viruses and intracellular bacteria. RIG-I contains an intricate structural architecture that allows for efficient signaling downstream in the pathway and autoregulation. The RIG-I-mediated antimicrobial pathway is highly regulated in cells requiring various cofactors, negative regulators, and posttranslational modifications. Modulation of RIG-I and RIG-I-mediated signaling in cells by pathogens to evade recognition and activation of the antimicrobial pathway highlights the essential nature of RIG-I in the innate immune response.

Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.

Type I interferons (IFN-I) are essential antiviral cytokines produced upon microbial infection. IFN-I elicits this activity through the upregulation of hundreds of IFN-I-stimulated genes (ISGs). The full breadth of ISG induction demands activation of a number of cellular factors including the IκB kinase epsilon (IKKε). However, the mechanism of IKKε activation upon IFN receptor signaling has remained elusive. Here we show that TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacted with IKKε and promoted induction of IKKε-dependent ISGs. TRIM6 and the E2-ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked polyubiquitin chains, which activated IKKε for subsequent STAT1 phosphorylation. Our work attributes a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response.

Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α-actinin-4 for viral replication.

Influenza A virus (IAV), similar to other viruses, exploits the machinery of human host cells for its survival and replication. We identified α-actinin-4, a host cytoskeletal protein, as an interacting partner of IAV nucleoprotein (NP). We confirmed this interaction using co-immunoprecipitation studies, first in a coupled in vitro transcription-translation assay and then in cells either transiently co-expressing the two proteins or infected with whole IAV. Importantly, the NP-actinin-4 interaction was observed in several IAV subtypes, including the 2009 H1N1 pandemic virus. Moreover, immunofluorescence studies revealed that both NP and actinin-4 co-localized largely around the nucleus and also in the cytoplasmic region of virus-infected A549 cells. Silencing of actinin-4 expression resulted in not only a significant decrease in NP, M2 and NS1 viral protein expression, but also a reduction of both NP mRNA and viral RNA levels, as well as viral titers, 24 h post-infection with IAV, suggesting that actinin-4 was critical for viral replication. Furthermore, actinin-4 depletion reduced the amount of NP localized in the nucleus. Treatment of infected cells with wortmannin, a known inhibitor of actinin-4, led to a decrease in NP mRNA levels and also caused the nuclear retention of NP, further strengthening our previous observations. Taken together, the results of the present study indicate that actinin-4, a novel interacting partner of IAV NP, plays a crucial role in viral replication and this interaction may participate in nuclear localization of NP and/or viral ribonucleoproteins.

RIG-I detects mRNA of intracellular Salmonella enterica serovar Typhimurium during bacterial infection.

The cytoplasmic helicase RIG-I is an established sensor for viral 5'-triphosphorylated RNA species. Recently, RIG-I was also implicated in the detection of intracellular bacteria. However, little is known about the host cell specificity of this process and the bacterial pathogen-associated molecular pattern (PAMP) that activates RIG-I. Here we show that RNA of Salmonella enterica serovar Typhimurium activates production of beta interferon in a RIG-I-dependent fashion only in nonphagocytic cells. In phagocytic cells, RIG-I is obsolete for detection of Salmonella infection. We further demonstrate that Salmonella mRNA reaches the cytoplasm during infection and is thus accessible for RIG-I. The results from next-generation sequencing analysis of RIG-I-associated RNA suggest that coding bacterial mRNAs represent the activating PAMP. IMPORTANCE S. Typhimurium is a major food-borne pathogen. After fecal-oral transmission, it can infect epithelial cells in the gut as well as immune cells (mainly macrophages, dendritic cells, and M cells). The innate host immune system relies on a growing number of sensors that detect pathogen-associated molecular patterns (PAMPs) to launch a first broad-spectrum response to invading pathogens. Successful detection of a given pathogen depends on colocalization of host sensors and PAMPs as well as potential countermeasures of the pathogen during infection. RIG-I-like helicases were mainly associated with detection of RNA viruses. Our work shows that S. Typhimurium is detected by RIG-I during infection specifically in nonimmune cells.

Three-stranded antiviral attack.

Mitochondrial antiviral signalling proteins form an intricate three-stranded helical filament that has a central role in the response of cells to viruses.

Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses.

UNLABELLED: Recognition of viral pathogens by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family results in the activation of type I interferon (IFN) responses. To avoid this response, most viruses have evolved strategies that target different essential steps in the activation of host innate immunity. In this study, we report that the nonstructural protein NSs of the newly described severe fever with thrombocytopenia syndrome virus (SFTSV) is a potent inhibitor of IFN responses. The SFTSV NSs protein was found to inhibit the activation of the beta interferon (IFN-ß) promoter induced by viral infection and by a RIG-I ligand. Astonishingly, we found that SFTSV NSs interacts with and relocalizes RIG-I, the E3 ubiquitin ligase TRIM25, and TANK-binding kinase 1 (TBK1) into SFTSV NSs-induced cytoplasmic structures. Interestingly, formation of these SFTSV NSs-induced structures occurred in the absence of the Atg7 gene, a gene essential for autophagy. Furthermore, confocal microscopy studies revealed that these SFTSV NSs-induced structures colocalize with Rab5 but not with Golgi apparatus or endoplasmic reticulum markers. Altogether, the data suggest that sequestration of RIG-I signaling molecules into endosome-like structures may be the mechanism used by SFTSV to inhibit IFN responses and point toward a novel mechanism for the suppression of IFN responses. IMPORTANCE: The mechanism by which the newly described SFTSV inhibits host antiviral responses has not yet been fully characterized. In this study, we describe the redistribution of RIG-I signaling components into virus-induced cytoplasmic structures in cells infected with SFTSV. This redistribution correlates with the inhibition of host antiviral responses. Further characterization of the interplay between the viral protein and components of the IFN responses could potentially provide targets for the rational development of therapeutic interventions.