Category: Nevin Manimala

Int J Geriatr Psychiatry. 2023 Feb;38(2):e5877. doi: 10.1002/gps.5877.

ABSTRACT

OBJECTIVES: To determine the relationship between alcohol consumption and cognitive decline, and to further explore the potential regulatory role of education, socio-economic status (SES), and social or intellectual activity in this relationship.

METHODS: 6197 participants aged 45-75 years with four repeated measures data from 2011 to 2018 were included. A mixed-effect model was used to explore the relationship between alcohol consumption and the rate of change in cognitive decline, a latent class growth mixed model (LCGMM) was applied to determine the potential trajectory of cognitive decline, and finally, the mediating and moderating analyses were used to determine the regulatory effect of all four variables on the relationship between alcohol consumption and potential trajectory.

RESULTS: Compared to never-drinkers, moderate alcohol consumption was a protective factor for overall cognitive function (β = 0.13, 95% CI: 0.04-0.20, p < 0.001), but there was no statistical correlation with the decline rate of cognitive function. And this protective effect was no longer significant after additional adjustments for education, SES, social and intellectual activity. The LCGMM model divided participants into two trajectories, a high-level-to-decline group including 79.75% of participants (quadratic: β [SE]: -0.90 [0.07], p < 0.001), and a low-level-to-decline group including 20.25% participants (linear: β [SE]: -3.05 [0.49], p < 0.001). With the latter as the reference, SES played a reverse regulation role in the harmful effect of heavy drinking on cognitive trajectories (odd ratio [OR] = 0.46, 95% CI: 0.23-0.93, p < 0.05). Social and intellectual activities played a negative mediating role in the harmful effect of alcohol consumption on cognitive trajectories (light: OR = 0.96, p < 0.001; moderate: OR = 0.96, p < 0.001; heavy: OR = 0.97, p < 0.01).

CONCLUSIONS: Alcohol itself has no protective effect on the decline of longitudinal cognitive trajectory. But the regulatory effect of SES, social and intellectual activities slows down the harm of alcohol consumption on the decline of cognitive function.

CLINICAL TRIAL REGISTRATION: The data used in this study are from publicly available databases. They are retrospective cohort studies without any intervention. Therefore, no clinical trial registration has been conducted.

PMID:36734162 | DOI:10.1002/gps.5877

Basic Clin Pharmacol Toxicol. 2023 Feb 3. doi: 10.1111/bcpt.13840. Online ahead of print.

ABSTRACT

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and three months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81±0.93 vs. 2.68±0.87), CYP2C19 (0.420 ± 0.360 vs. 0.687 ± 0.558), and CYP3A4/5 (0.487 ± 0.226 vs. 0.633 ± 0.254) significantly decreased in T2D subjects compared to the control group (p<0.05). CYP2C9 (0.089±0.037 vs. 0.069±0.017) activities slightly increased in diabetic subjects, and no difference was observed regarding CYP1A2 (0.154±0.085 vs. 0.136±0.065), CYP2D6 (1.17 ± 0.56 vs. 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P>0.05). Several covariables, such as inflammatory markers (IL-1β and IL-6), genotypes, diabetes, and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.

PMID:36734157 | DOI:10.1111/bcpt.13840

J Clin Endocrinol Metab. 2023 Feb 3:dgad058. doi: 10.1210/clinem/dgad058. Online ahead of print.

ABSTRACT

CONTEXT: Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause.

OBJECTIVE: We aimed to assess efficacy/safety of fezolinetant for treatment of moderate-to-severe VMS associated with menopause.

METHODS: In this double-blind, placebo-controlled, 12-week (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40-65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks’ once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to W4 and W12 in VMS frequency and severity. Safety was also assessed.

RESULTS: Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P<.05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P <.05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.

CONCLUSIONS: Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause.

PMID:36734148 | DOI:10.1210/clinem/dgad058

J Hepatobiliary Pancreat Sci. 2023 Feb 3. doi: 10.1002/jhbp.1316. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition.

METHOD: Data from 1,506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3,092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database.

RESULTS: The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, Tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs 39 months, p<0.001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database.

CONCLUSION: Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.

PMID:36734142 | DOI:10.1002/jhbp.1316

Histol Histopathol. 2023 Jan 23:18590. doi: 10.14670/HH-18-590. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, 3′-phosphoadenosine-5′-phosphosulfate synthase 1 (PAPSS1) has been found to be highly expressed in some cancers and significantly associated with prognosis. Nevertheless, the role of PAPSS1 in esophageal squamous cancer (ESCC) is poorly understood.

METHODS: In this study, PAPSS1 expression in ESCC samples was researched through real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot (WB) techniques. siRNA technology was then used to inhibit PAPSS1 expression in ESCC cells, and cytologic tests were conducted to research gene affection on cell apoptosis, proliferation, and migration. Then, the expression of Bcl2, Ki67, and Snail was detected using qPCR and WB tests. These experimental data were analyzed by GraphPad software, where the P-value<0.05 was statistically significant.

RESULTS: The results showed that PAPSS1 expression level in ESCC tissues was higher than in the adjacent tissues. The data also showed that PAPSS1 was significantly correlated with N stage, and that the patients with high expressions had longer survival time. After transfection for 48 hours, the cell apoptosis rate of siRNA-PAPSS1 transfected groups decreased significantly, whereas the cell proliferation rate and migration ability increased relative to the control. At the same time, the expression levels of Bcl2, Ki67 and Snail were all upregulated by siRNA-PAPSS1. PAPSS1, however, was suppressed.

CONCLUSIONS: PAPSS1 may be an ESCC suppressor gene, and its specific molecular mechanism in ESCC needs to be further studied.

PMID:36734141 | DOI:10.14670/HH-18-590

Health Expect. 2023 Feb 3. doi: 10.1111/hex.13706. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to understand the provision and need, quality of and trust in COVID-19 vaccines information from the perspectives of people who have had COVID-19 infection.

METHOD: People who have had a COVID-19 infection were approached via their general practice and invited to participate in the Nivel Corona Cohort. They completed questionnaires at baseline (Q1), and at three months (Q2). Outcome measures were based on health information-seeking behaviour, as used in the Comprehensive Model of Information Seeking. Antecedents (i.e., gender, age, education level, health literacy) were used from Q1, and one’s beliefs and experiences (i.e., trust in the information and healthcare system, how applicable the information is), information carrier factors (i.e., information quality perceptions and via which sources), health-information seeking actions (i.e., decision to vaccinate and information sufficiency) and vaccination status from Q2. Data were analysed using descriptive analyses, analysis of variance tests (F-tests) and χ² tests with the statistical software STATA.

RESULTS: Of the respondents (N = 314), 96% were vaccinated at least once, mostly after having had the virus. Most retrieved information about COVID-19 vaccines on the website of the National Institute for Public Health and the Environment (79%), broader via the internet (56%), or from family and friends (35%). Almost all had trust in the information (89%) and healthcare system (94%). Most found the information applicable to their situation (67%). Moreover, most perceived the information as correct (71%) and did not perceive the information to be misleading (85%), while fewer people found the information reliable (59%) and clear (58%). Overall, the majority indicated that the information met their expectations to make a well-informed decision to vaccinate (89%).

CONCLUSION: Different characteristics of people who had COVID-19 and sought information were identified, which is important to offer tailored information. People who had COVID-19 in this study, mainly middle-aged, vaccinated and highly educated, were generally positive about the vaccines information, but overall the reliability and clarity could be improved. This is important for a high vaccination uptake, booster programs and coming pandemics.

PATIENT OR PUBLIC CONTRIBUTION: The questionnaire was reviewed by patients who had COVID-19, one of whom is a health services researcher.

PMID:36734131 | DOI:10.1111/hex.13706

Lett Appl Microbiol. 2022 Dec 19:ovac056. doi: 10.1093/lambio/ovac056. Online ahead of print.

ABSTRACT

Postbiotics are soluble metabolites that are liberated from the structure of lysing bacteria or are produced by live bacteria; these byproducts give the host increased biological activity and certain physiological effects. In the current study, the anti-Staphylococcus properties of postbiotics isolated from Lactobacillus acidophilus,L.paracasei,and L.plantarum were investigated in vitro, and pasteurized milk. Potential activity of postbiotics was performed via agar-disk diffusion method. Besides, the effect of heat and pH on the postbiotics antibacterial activity was measured via the agar-well diffusion method. To determine the antioxidant effect and the free radical scavenging potential of the postbiotics, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) method was utilized. The postbiotics chemical composition was identified via gas chromatography-mass spectrometry. The antibacterial activity was mainly associated with lactic acid, laurostearic acid, and isopropylidene-3,3-dimethyl. Also, postbiotics showed strong antioxidant activity. Postbiotics derived from L.plantarum showed the highest antioxidant properties compared to L.paracasei and L.acidophilus. Lower minimum effective concentrations of postbiotic were altered in food model, and substantially, a low minimum effective( MEC) concentrations index (15 mg/mL) was identified for postbiotic of L.plantarum. The Lactobacillus spp. postbiotic, in particular L.plantarum, may have useful functional characteristics (possible antibacterial and antioxidant) in in vitro and food model.

PMID:36734084 | DOI:10.1093/lambio/ovac056

Toxicol Ind Health. 2023 Feb 3:7482337231154636. doi: 10.1177/07482337231154636. Online ahead of print.

ABSTRACT

Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84-0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.

PMID:36734071 | DOI:10.1177/07482337231154636

J Clin Periodontol. 2023 Feb 3. doi: 10.1111/jcpe.13785. Online ahead of print.

ABSTRACT

AIM: This study investigated the relationships of plant-based diet indices with periodontitis and serum IgG antibodies against periodontopathogens in the US population.

MATERIALS AND METHODS: This study analyzed cross-sectional data on 5,651 participants ≥40 years of age from the Third National Health and Nutrition Examination Survey. Food frequency questionnaire data were used to calculate the overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). Periodontitis was defined using a half-reduced CDC/AAP (Centers for Disease Control and Prevention and American Academy of Periodontology) case definition. Serum antibodies against 19 periodontopathogens were used to classify the population into two subgroups using hierarchical clustering. Survey-weighted multivariable logistic regressions were applied to assess the associations of PDI/hPDI/uPDI z-scores with periodontitis and hierarchical clusters after adjusting for potential confounders.

RESULTS: A total of 2,841 (50.3) participants were defined as having moderate/severe periodontitis. Overall PDI z-score was not significantly associated with the clinical and bacterial markers of periodontitis. By considering the healthiness of plant foods, we observed an inverse association between hPDI z-score and periodontitis (odds ratio [OR] = 0.925, 95% confidence interval = 0.860 to 0.995). In contrast, higher uPDI z-score (adherence to unhealthful plant foods) might increase the risk of periodontitis (OR = 1.100, 1.043 to 1.161). Regarding antibodies against periodontopathogens, the participants in cluster 2 had higher periodontal antibodies than those in cluster 1. The hPDI z-score was positively associated with cluster 2 (OR = 1.192, 1.112 to 1.278). In contrast, an inverse association between uPDI z-score and cluster 2 was found (OR = 0.834, 0.775 to 0.896).

CONCLUSION: Plant-based diets were associated with periodontitis, depending on their quality. A healthy plant-based diet was inversely related to an increased risk of periodontitis but positively related to elevated antibody levels against periodontopathogens. For an unhealthy plant-based diet, the opposite trends were observed. This article is protected by copyright. All rights reserved.

PMID:36734066 | DOI:10.1111/jcpe.13785

Asian Cardiovasc Thorac Ann. 2023 Feb 2:2184923231152107. doi: 10.1177/02184923231152107. Online ahead of print.

ABSTRACT

INTRODUCTION: Effective treatment of patients with ischemic cardiomyopathy (ICM) is one of the most challenging issues in modern cardiac surgery. The aim of this study was to assess the state of cardiomyocytes and myocardial extracellular matrix, as well as to identify informative markers of an unfavorable prognosis for surgical treatment of ICM.

MATERIALS AND METHODS: We retrospectively reviewed patients who underwent surgical treatment of ICM between 2011 and 2018 at a single center. Patients were divided into groups depending on the presence of repeated left ventricle (LV) remodeling in one-year follow-up after surgical reconstruction of the LV in ICM patients.

RESULTS: A total of 45 patients with ICM were reviewed. The mean age of the patients was 57.9 ± 7.8 years. According to the results of the study, the area of cardiomyocyte nuclei differed statistically significantly among the regions with varying degrees of impaired local contractility (p = 0.042). According to the results of the pairwise comparison in dyskinetic areas of the myocardium, the area of cardiomyocyte nuclei was higher than in normokinetic areas (p = 0.042). A moderate positive correlation was found between the LV ejection fraction measured in one-year follow-up period after surgery and the number of CD163-positive cells (p = 0.012).

CONCLUSION: In the myocardium of patients with LV reverse remodeling in the long-term postoperative period, perivascular fibrosis occurs more frequently than in patients with progressive LV remodeling. The number of M2-anti-inflammatory macrophages prevails in the myocardium of the patients with reverse remodeling compared with patients with progressive remodeling.

PMID:36734055 | DOI:10.1177/02184923231152107