Category: Nevin Manimala

J Ren Nutr. 2022 Apr 2:S1051-2276(22)00058-9. doi: 10.1053/j.jrn.2022.03.004. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the association between fluid overload (FO) evaluated by a new FO indicator, the bioelectrical impedance analysis (BIA) derived whole-body extracellular to intracellular water ratio (ECW/ICW) and sarcopenia in maintenance hemodialysis (MHD) patients.

METHODS: A multicenter, cross-sectional study included 3320 adult MHD patients was conducted in XX from June 1, 2020 to September 30, 2020. The diagnosis of sarcopenia was based on the Asian Working Group’s definition of sarcopenia (AWGS). Multiple logistic regression models, stratified analyses and interactive analyses were conducted.

RESULTS: A total of 3196 participants were included in the final analysis. The prevalence of sarcopenia was 36.2% in the total population. Prevalence of sarcopenia was increased with increasing quartiles of ECW/ICW (18.1%, 33.3%, 37.8% and 55.4% for the first, second, third and fourth quartiles, respectively). Increased ECW/ICW was significantly associated with sarcopenia. The association remained statistically significant even after adjusting for age, sex, BMI, dialysis vintage, C-reactive protein (CRP) and various medical histories. The ORs were 2.11 (1.41,3.14), 1.83 (1.22,2.76) and 3.45 (2.21,5.39) for ECW/ICW quartiles 2-4, respectively (P for trend＜0.001). The interaction analysis showed that history of diabetes had an interactive role in the association between ECW/ICW and sarcopenia (P for interaction = 0.034). The association stably existed across subgroups and was more prominent in older patients, those with higher BMI and a history of diabetes.

CONCLUSIONS: Elevated ECW/ICW was associated with increased sarcopenia risk independent of BMI, prealbumin, CRP and other potential confounders in MHD patients. The association was more prominent in older patients and those with higher BMI and a history of diabetes, suggesting that controlling volume balance may help to reduce the occurrence of sarcopenia in these populations.

PMID:35381328 | DOI:10.1053/j.jrn.2022.03.004

J Ethnopharmacol. 2022 Apr 2:115251. doi: 10.1016/j.jep.2022.115251. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrochepala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb’s anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats.

AIM OF THE STUDY: To investigate the anti-gastritis activities of Am-EE and explore the mode of action.

MATERIALS AND METHODS: Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGE₂ ELISA kit was employed to detect prostaglandin E₂ (PGE₂). Enzyme activities and protein contents were examined by immunoblotting. Luciferase reporter gene assays (LRA) were employed to observe nuclear transcription factor (NF)-κB activity. The SPSS (SPSS Inc., Chicago, Illinois, United States) application was used for statistical examination.

RESULTS: HPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The mRNA and protein synthesis of inducible cyclooxygenase (COX)-2 and NO synthase (iNOS) was down-regulated following treatment in RAW cells. Am-EE decreased NF-κB (p50) nuclear protein levels and inhibited NF-κB-stimulated LRA activity in RAW cells. Lastly, Am-EE decreased the up-regulated levels of phosphorylated IκBα and AKT proteins in rat stomach lysate and in LPS challenged RAW cell samples.

CONCLUSION: Our study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer.

PMID:35381310 | DOI:10.1016/j.jep.2022.115251

Environ Pollut. 2022 Apr 2:119132. doi: 10.1016/j.envpol.2022.119132. Online ahead of print.

ABSTRACT

Plume chasing is cost-effective, measuring individual, on-road vehicular emissions. Whereas, wake-flow-generated turbulence results in intermittent, rapid pollutant dilution and substantial fluctuating concentrations right behind the vehicle being chased. The sampling duration is therefore one of the important factors for acquiring representative (average) concentrations, which, however, has been seldom addressed. This paper, which is based on the detailed spatio-temporal dispersion data after a heavy-duty truck calculated by large-eddy simulation (LES), examines how sampling duration affects the uncertainty of the measured concentrations in plume chasing. The tailpipe dispersion is largely driven by the jet-like flows through the vehicle underbody with approximate Gaussian concentration distribution for x ≤ 0.6h, where x is the distance after the vehicle and h the characteristic vehicle size. Thereafter for x ≥ 0.6h, the major recirculation plays an important role in near-wake pollutant transport whose concentrations are highly fluctuating and positively shewed. Plume chasing for a longer sampling duration is more favourable but is logistically impractical in busy traffic. Sampling duration, also known as averaging time in the statistical analysis, thus has a crucial role in sampling accuracy. With a longer sampling (averaging) duration, the sample mean concentration converges to the population mean, improving the sample reliability. However, this effect is less pronounced in long sampling duration. The sampling accuracy is also influenced by the locations of sampling points. For the region x > 0.6h, the sampling accuracy is degraded to a large extent. As a result, acceptable sample mean is hardly achievable. Finally, frequency analysis unveils the mechanism leading to the variance in concentration measurements which is attributed to sampling duration. Those data with frequency higher than the sampling frequency are filtered out by moving average in the statistical analyses.

PMID:35381304 | DOI:10.1016/j.envpol.2022.119132

Immunol Lett. 2022 Apr 2:S0165-2478(22)00039-6. doi: 10.1016/j.imlet.2022.03.006. Online ahead of print.

ABSTRACT

Mass spectrometry proteomics has become an important part of modern immunology, making major contributions to understanding protein expression levels, subcellular localizations, posttranslational modifications, and interactions in various immune cell populations. New developments in both experimental and computational techniques offer increasing opportunities for exploring the immune system and the molecular mechanisms involved in immune responses. Here, we focus on current computational approaches to infer relevant information from large mass spectrometry based protein profiling datasets, covering the different steps of the analysis from protein identification and quantification to further mining and modelling of the protein abundance data. Additionally, we provide a summary of the key proteome profiling studies on human CD4⁺ T cells and their different subtypes in health and disease.

PMID:35381305 | DOI:10.1016/j.imlet.2022.03.006

J Affect Disord. 2022 Apr 2:S0165-0327(22)00317-2. doi: 10.1016/j.jad.2022.03.070. Online ahead of print.

ABSTRACT

BACKGROUND: Altered metabolism of acylcarnitines – transporting fatty acids to mitochondria – may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization.

METHODS: Summary statistics were obtained from large GWAS: the Fenland Study (N = 9363), and the Psychiatric Genomics Consortium (246,363 depression cases and 561,190 controls). Two-sample Mendelian randomization analyses tested the potential causal link of 15 endogenous acylcarnitines with depression.

RESULTS: In univariable analyses, genetically-predicted lower levels of short-chain acylcarnitines C2 (odds ratio [OR] 0.97, 95% confidence intervals [CIs] 0.95-1.00) and C3 (OR 0.97, 95%CIs 0.96-0.99) and higher levels of medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.01-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06) were associated with increased depression risk. No reverse potential causal role of depression genetic liability on acylcarnitines levels was found. Multivariable analyses showed that the association with depression was driven by the medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.02-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06), suggesting a potential causal role in the risk of depression. Causal estimates for C8 (OR = 1.05, 95%CIs = 1.02-1.07) and C10 (OR = 1.05, 95%CIs = 1.02-1.08) were confirmed in follow-up analyses using genetic instruments derived from a GWAS meta-analysis including up to 16,841 samples.

DISCUSSION: Accumulation of medium-chain acylcarnitines is a signature of inborn errors of fatty acid metabolism and age-related metabolic conditions. Our findings point to a link between altered mitochondrial energy production and depression pathogenesis. Acylcarnitine metabolism represents a promising access point for the development of novel therapeutic approaches for depression.

PMID:35381295 | DOI:10.1016/j.jad.2022.03.070

J Allergy Clin Immunol. 2022 Apr 2:S0091-6749(22)00439-0. doi: 10.1016/j.jaci.2022.03.019. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate.

OBJECTIVE: To identify genetic interaction associated with the development of childhood asthma.

METHODS: We performed an exhaustive search for pairwise interaction between genetic variants, single nucleotide polymorphisms (SNPs), using 1204 cases with a specific phenotype of early childhood asthma with severe exacerbations (age 2-6 years) combined with 5328 non-asthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts.

RESULTS: We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci, CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation.

CONCLUSIONS: We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.

PMID:35381269 | DOI:10.1016/j.jaci.2022.03.019

Sci Total Environ. 2022 Apr 2:154992. doi: 10.1016/j.scitotenv.2022.154992. Online ahead of print.

ABSTRACT

Decision-making processes for clean-up of contaminated sites are often highly complex and inherently uncertain. It depends not only on hydrological and biogeochemical site variability, but also on the associated health, environmental, economic, and social impacts of taking, or not taking, action. These variabilities suggest that a dynamic framework is required for promoting sustainable remediation. For this, the decision support system DynSus is presented here for integrating a predeveloped contaminant fate and transport model with a sustainability assessment tool. Implemented within a system dynamics framework, the new tool uses model simulations to provide remediation scenario analysis and handling of uncertainty in various data. DynSus was applied to a site in south Sweden, contaminated with pentachlorophenol (PCP). Simulation scenarios were developed to enable a comparison between alternative remediation strategies and combinations of these. Such comparisons are provided for selected sustainability indicators and remediation performance (in terms of concentration at the recipient). This leads to identifying the most critical variables to ensure that sustainable solutions are chosen. Simulation results indicated that although passive practices, e.g., natural attenuation, were more sustainable at first (5-7 years after beginning remediation measures), they failed to compete with more active practices, e.g., bioremediation, over the entire life cycle of the project (from the beginning of remedial action to achieving the target concentration at the recipient). In addition, statistical tools (clustering and genetic algorithms) were used to further assess the available hydrogeochemical data. Taken together, the results reaffirmed the suitability of the simple analytical framework that was implemented in the contaminant transport model. DynSus outcomes could therefore enable site managers to evaluate different scenarios more quickly and effectively for life cycle sustainability in such a complex and multidimensional problem.

PMID:35381250 | DOI:10.1016/j.scitotenv.2022.154992

Obes Rev. 2022 Apr 5:e13454. doi: 10.1111/obr.13454. Online ahead of print.

NO ABSTRACT

PMID:35381113 | DOI:10.1111/obr.13454

N Engl J Med. 2022 Apr 5. doi: 10.1056/NEJMoa2201570. Online ahead of print.

ABSTRACT

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).

METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.

RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.

CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.

PMID:35381126 | DOI:10.1056/NEJMoa2201570

Endokrynol Pol. 2022;73(1):35-42. doi: 10.5603/EP.a2021.0110.

ABSTRACT

INTRODUCTION: The aim of this study was to test the effect of aripiprazole on leptin, insulin, acute phase proteins, and selected cytokines levels in patients with chronic schizophrenia. Additionally, levels of leptin, insulin, acute phase proteins, and cytokines were compared with body mass and body composition indexes.

MATERIAL AND METHODS: Levels of leptin, insulin, serum amyloid A (SAA), tumour necrosis factor alpha (TNF-α), and interleukins 17A (IL-17A) and 18 (IL-18) in blood serum were measured for 17 patients before and after 28 days of administering aripiprazole by means of enzyme-linked immunosorbent assay (ELISA). Before and after the study, body mass and waist circumference (WC) were also measured, and body mass index (BMI) and body fat percentage (BF%) were estimated. The sex of each patient was taken into account.

RESULTS: After administration of aripiprazole the reduction of levels of leptin, insulin, SAA, and TNF-a were statistically significant, similarly to body mass reduction and decrease in WC, BMI, and BF%, which were also statistically significant. A positive correlation between leptin and BF% and negative correlation between insulin and body mass and body composition indexes were observed before and after the study. High sensitivity C-reactive protein (hsCRP) and hsCRP/albumin positively correlated with BMI before the treatment. In the group of women a statistically significant positive correlation between TNF-α and IL-17A and body mass and body composition indexes was observed, and in the group of men a negative correlation between IL-18 and BMI, WC, and BF% was noted.

CONCLUSIONS: The effect of aripiprazole is connected to its anti-inflammatory activity. A 28-day treatment resulted in reduction of adipose tissue, and in the group of women it returned their leptin sensitivity to normal levels. A change of psychotropic treatment and administration of aripiprazole reduces cardiometabolic risks.

PMID:35381103 | DOI:10.5603/EP.a2021.0110