Tag: nevin manimala

Gut Pathog. 2023 May 10;15(1):22. doi: 10.1186/s13099-023-00546-z.

ABSTRACT

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay.

RESULTS: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes.

CONCLUSION: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.

PMID:37161621 | DOI:10.1186/s13099-023-00546-z

J Diabetes. 2023 May 9. doi: 10.1111/1753-0407.13399. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients.

METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia.

RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m² group and those without dyslipidemia.

CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

PMID:37161588 | DOI:10.1111/1753-0407.13399

BMC Cancer. 2023 May 9;23(1):422. doi: 10.1186/s12885-023-10863-w.

ABSTRACT

BACKGROUND: Postoperative adjuvant chemotherapy (AC) is now well-accepted as standard for high-risk stage II and stage III colorectal cancer (CRC) patients, however the optimal time to initiate AC remains elusive.

METHODS: A comprehensive literature search was performed using the PubMed and Embase databases. The Hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate primary endpoints. All analyses were conducted using Stata software version 12.0 with the Random-effects model.

RESULTS: A total of 30 studies were included in our study. Upon comparison on overall survival (OS), we identified that delaying the initiation of AC for > 8 weeks after operation was significantly associated with poor OS (HR: 1.37; 95% CI: 1.27-1.48; P < 0.01). The poor prognostic value of AC delay for > 8 weeks was not undermined by subgroup analysis based on region, tumor site, sample size and study quality. No obvious differences were observed in survival between AC within 5-8 weeks and ≤ 4 weeks (HR: 1.03; 95% CI: 0.96 -1.10; P = 0.46). Moreover, two studies both highlighted that the survival benefit of AC was still statistically significant when AC was applied 5-6 months after surgery compared with the non-chemotherapy group.

CONCLUSIONS: Delaying the initiation of AC for > 8 weeks after surgery was significantly associated with poor OS. AC started within 8 weeks after surgery brought more benefits to CRC patients. There were no obvious differences in survival benefits between AC within 5-8 weeks and ≤ 4 weeks. Compared to patients not receiving AC after surgery, a delay of approximately 5-6 months was still useful to improve prognosis.

PMID:37161562 | DOI:10.1186/s12885-023-10863-w

Ultrasound Obstet Gynecol. 2023 May 9. doi: 10.1002/uog.26245. Online ahead of print.

ABSTRACT

OBJECTIVES: Prediction models can support clinical decision-making and inform women and their partners regarding obstetric and neonatal management in complicated pregnancies. The first aim of this systematic review was to identify all prediction models on fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (i.e. gestational hypertension, pre-eclampsia, HELLP-syndrome or fetal growth restriction with its onset before 37 weeks of gestational age). The second aim was to appraise the quality of the models and their performance at external validation.

METHODS: A systematic literature search was performed in Pubmed, Web of Science and Embase. Studies describing prediction models on fetal or neonatal mortality, or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS-checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently.

RESULTS: Our literature search yielded 22,491 unique publications. Fourteen were included after full text screening. These fourteen studies derived 41 prediction models, four models in the setting of pre-eclampsia, two models in fetal growth restriction and/or pre-eclampsia and 35 models in fetal growth restriction. None of the models were externally validated and internal validation was performed by only two studies. Final models contained mainly ultrasound (Doppler) markers as predictors of fetal and neonatal mortality and morbidity. Discriminative properties were reported for 27/41 models (c-statistics between 0.6-0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly due to inappropriate statistical methods.

CONCLUSIONS: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered of low methodological quality, apart from one model (unclear quality). Higher quality models and external validation studies are needed to inform clinical decision-making based on prediction models. This article is protected by copyright. All rights reserved.

PMID:37161550 | DOI:10.1002/uog.26245

Evolution. 2023 May 10:qpad068. doi: 10.1093/evolut/qpad068. Online ahead of print.

ABSTRACT

We address the problem of defining selection and extracting the adaptive part of evolutionary change, originally formalized by Fisher and Price. Conventionally selection and adaptation are defined through fitness attributed to genes or genotypes chosen as units of selection. The construction through fitness is known to suffer ambiguities and omissions as a theory of change due to selection. We construct an alternative framing in which units of selection and fitness are replaced as the main abstractions by formal lifecycle models and reproduction rates through genetically distinct lifecycle realizations. Graphical representations of lifecycles express relations among reproductive stages that cannot be assigned to any one unit of selection. The lifecycle partition refines the statistics of overall reproductive success and resolves modes of selection that fitness either excludes or distorts through additive projections. We derive the Price equation in the basis of lifecycle realizations and compare it to the conventional Price equation for additive fitness of organisms. We show how the lifecycle approach recovers fitnesses acting concurrently at multiple levels, or contrasts forms of competition within and between levels that are invisible to additive fitness. Defining selection through lifecycles recasts population genetics from an object-focused to a construction- and process-focused representation.

PMID:37161529 | DOI:10.1093/evolut/qpad068

BMC Musculoskelet Disord. 2023 May 9;24(1):366. doi: 10.1186/s12891-023-06466-y.

ABSTRACT

PURPOSE: To systematically review the studies regarding to the safety, efficacy and application methods of PRP in promoting the talar cartilage repair.

METHODS: A systematic review was performed by searching PubMed, Web of Science, OVID and EMBASE to identify studies that compared the clinical efficacy of PRP for talar cartilage repair. Main outcome was the American Orthopedic Foot and Ankle Society (AOFAS) score for function and Visual Analog Scale (VAS) for pain was the second outcome.

RESULTS: A total of 10 studies were included in this systematic review, including 4 randomized controlled trials, 1 controlled trial, 3 case series and 2 cohort studies. Four RCTs were analyzed using meta-analysis. For all outcomes, statistical results favored PRP group (AOFAS: MD = 7.84; 95% CI= [-0.13, 15.80], I² = 83%, P < 0.01; VAS: MD = 1.86; 95% CI= [0.68, 3.04], I² = 85%, P < 0.01). There were almost no reports of adverse events related to PRP intervention. Subgroup analysis showed that whether PRP was used alone or combined with other treatments could result in high heterogeneity but no more specific factors were identified to contribute to this.

CONCLUSION: PRP is safe and effective for talar cartilage repair. In addition to the standardization of PRP preparation and application, it is necessary to distinguish the effects of PRP used alone or in combination with other treatments. In PRP studies, surgical treatment of talar cartilage repair remains the mainstream. The regulation of PRP in surgical applications are worth exploring. The most relative component is the mesenchymal stem cell because it is the only exposed chondrocyte precursor in the articular cavity whether it is microfracture or cell transplantation.

TRIAL REGISTRATION: The study was registered in the PROSPERO International prospective register of systematic reviews (CRD42022360183).

PMID:37161527 | DOI:10.1186/s12891-023-06466-y

Int J Surg. 2023 May 11. doi: 10.1097/JS9.0000000000000446. Online ahead of print.

ABSTRACT

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. We sought to investigate the relationship between open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications.

METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of operative approach with postoperative infectious complications including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI).

RESULTS: Among 3,876 patients, 845 (21.8%) and 3,031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9% versus 14.6% among patients who underwent LH versus OH, respectively (P<0.001). Of note, the incidences of incisional SSI (1.8% vs. 6.3%, P<0.001), organ/space SSI (1.8% vs. 4.6%, P<0.001), and RI (3.8% vs. 9.8%, P<0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9%, 1.8%, 1.8% and 3.8% vs. 18.5%, 8.4%, 5.2% and 12.8%, respectively) and IPTW (9.5%, 2.3%, 2.1% and 5.5% vs. 14.3%, 6.3%, 4.5% and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively.

CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

PMID:37161522 | DOI:10.1097/JS9.0000000000000446

Turk J Pharm Sci. 2023 May 9;20(2):100-107. doi: 10.4274/tjps.galenos.2022.50887.

ABSTRACT

OBJECTIVES: Aim of the current study was to evaluate the stress-protective effect of oligopeptides-homologues of the adrenocorticotropic hormone (ACTH) fragment 15-18 on morphogenetic signs of stress reaction of the adrenal glands under acute cold exposure (CE) in rats.

MATERIALS AND METHODS: The acute cold stress was reproduced by placing random-bred male rats in a freezer at a temperature of -18°C for 2 hours. The peptides-homologous of ACTH_15-18 acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) and acetyl-(D-Lys)-Lys-(D-Arg)-Arg-amide (KK-5) and the reference medicine (Sema) were administered intranasally in a dose of 20 mg/kg 30 minutes before and after CE. Rectal temperature was measured before and 10 min after CE. Zona glomeruloza, zona fasciculata, zona reticularis, and the area of cells and nuclei of adrenocorticocytes of the zona fasciculata were measured.

RESULTS: KK-1 significantly prevented structural changes in the adrenal cortex and medulla and stabilized the secretory activity of glucocorticoid-producing cells. However, the congestion of the capillaries of the zona fasciculata and zona reticularis remained in some locations. Zona fasciculata cells had a marked tendency to decrease, and the area of nuclei significantly decreased (p<0.05) recovering the width to control animals’ markers. KK-5 had a more marked recovery of the adrenal glands (a greater saturation of cytoplasm of adrenocorticocytes of zona glomerulosa and zona fasciculata). The number of chromaffin cells at rest was increased in the adrenal medulla. KK-5 statistically significantly normalized both the area of cells (p<0.05) and the area of nuclei (p<0.05) of the zona fasciculata, unlike KK-1, which reliably restored only the marker of the nuclei area. Some morphometric parameters of acute stress hypertrophy remained in the adrenal glands of rats receiving Sema.

CONCLUSION: KK-1 and KK-5 prevented the manifestation of acute stress reactions in the adrenal cortex of rats. KK-5 had a more marked stress-protective effect compared with the peptide KK-1. Both study substances exceeded the reference medicine Sema. KK-5 is a promising stres-sprotector and frigoprotector.

PMID:37161509 | DOI:10.4274/tjps.galenos.2022.50887

AIDS Res Ther. 2023 May 9;20(1):26. doi: 10.1186/s12981-023-00519-x.

ABSTRACT

BACKGROUND: Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.

METHODS: This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.

RESULTS: Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 – 149.95, p < 0.05).

CONCLUSIONS: The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

PMID:37161496 | DOI:10.1186/s12981-023-00519-x

AIDS Res Ther. 2023 May 9;20(1):27. doi: 10.1186/s12981-023-00517-z.

ABSTRACT

BACKGROUND: COVID-19 has not only taken a staggering toll in terms of cases and lives lost, but also in its psychosocial effects. We assessed the psychosocial impacts of the COVID-19 pandemic in a large cohort of people with HIV (PWH) in Washington DC and evaluated the association of various demographic and clinical characteristics with psychosocial impacts.

METHODS: From October 2020 to December 2021, DC Cohort participants were invited to complete a survey capturing psychosocial outcomes influenced by the COVID-19 pandemic. Some demographic variables were also collected in the survey, and survey results were matched to additional demographic data and laboratory data from the DC Cohort database. Data analyses included descriptive statistics and multivariable logistic regression models to evaluate the association between demographic and clinical characteristics and psychosocial impacts, assessed individually and in overarching categories (financial/employment, mental health, decreased social connection, and substance use).

RESULTS: Of 891 participants, the median age was 46 years old, 65% were male, and 76% were of non-Hispanic Black race/ethnicity. The most commonly reported psychosocial impact categories were mental health (78% of sample) and financial/employment (56% of sample). In our sample, older age was protective against all adverse psychosocial impacts. Additionally, those who were more educated reported fewer financial impacts but more mental health impacts, decreased social connection, and increased substance use. Males reported increased substance use compared with females.

CONCLUSIONS: The COVID-19 pandemic has had substantial psychosocial impacts on PWH, and resiliency may have helped shield older adults from some of these effects. As the pandemic continues, measures to aid groups vulnerable to these psychosocial impacts are critical to help ensure continued success towards healthy living with HIV.

PMID:37161481 | DOI:10.1186/s12981-023-00517-z