Tag: nevin manimala

BMC Psychiatry. 2022 Nov 30;22(1):749. doi: 10.1186/s12888-022-04392-2.

ABSTRACT

BACKGROUND: Depressive symptoms among adolescents are a serious health concern around the world. Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been reported to regulate stress response, which has been reported to be closely associated with depressive symptoms. However, most of the contributing studies have been conducted among adults and relatively few studies have considered the effect of disparate social influences and sex differences on the DNA methylation of FKBP5 in persons with depressive symptoms. The present study aimed to test the associations of FKBP5 DNA methylation and depressive symptoms among adolescents and explore possible sex differences in the foregoing associations.

METHODS: This study was conducted using a nested case-control design within a longitudinal cohort study from January 2019 to December 2019. Adolescents aged 12 to 17 years from 69 classes in 10 public high schools located in Guangdong province of China participated in this research. Students with persistent depressive symptoms that reported having depressive symptoms at both baseline and follow-up were treated as the case group, and those without depressive symptoms were randomly selected as the control group. Our study finally included 87 cases and 151 controls. Quantitative methylation analyses of the selected gene were carried out by MassARRAY platform System.

RESULTS: The overall DNA methylation trend of FKBP5 CpG sites in the case group was lower in comparison to the control group. Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with persistent depressive symptoms after adjusting for covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021), although the statistical significance of the difference was lost after false discovery rate correction (q > 0.05). In addition, the hypomethylation of FKBP5-12 CpG 1 was approaching significance after adjustment for social-environmental factors (aOR = 0.77; P = 0.055), which indicated that no independent association was detected between hypomethylation of FKBP5 CpG sites and persistent depressive symptoms. Furthermore, in the present study, we were unable to identify sex differences in the association of FKBP5 gene methylation with depressive symptoms.

CONCLUSION: The decreased methylation level of FKBP5 was observed in adolescents with persistent depressive symptoms, albeit non-significant after correction for multiple testing. Our results presented here are preliminary and underscore the complex gene-environment interactions relevant to the risk for depressive symptoms.

PMID:36451133 | DOI:10.1186/s12888-022-04392-2

BMC Geriatr. 2022 Nov 29;22(1):918. doi: 10.1186/s12877-022-03545-y.

ABSTRACT

BACKGROUND: The Internet is considered an important channel for providing health information to older adults. We developed an intervention to improve eHealth literacy in older adults according to the information-motivation-behavioral skills (IMB) theory and Intervention Mapping. This study aimed to analyze the effect of a developed intervention on information, motivation, behavioral skills, and behaviors related to eHealth information in older adults.

METHODS: Forty-six older adults over the age of 65 were recruited from two senior welfare centers in a city in South Korea. We divided the participants into four groups and conducted one intervention per group from March to December 2019. One intervention consisted of 5 sessions and was performed once a week (2 h/1 time) for 5 weeks, culminating in a total lecture time of 10 h. One lecture instructor and two assistant instructors supported the participants in the computer practices.

RESULTS: Participants’ computer/web knowledge, perceived ease of use, perceived enjoyment, and attitude toward eHealth information showed statistically significant increases. The eHealth literacy efficacy score, searching performance score, and understanding score were also significantly increased. However, there was no significant difference in perceived usefulness.

CONCLUSION: The application of the current theory-based methodology can improve the quality of research in eHealth literacy. Additionally, various interventions should be developed and continuously applied to improve eHealth literacy among older adults.

PMID:36451127 | DOI:10.1186/s12877-022-03545-y

BMC Psychiatry. 2022 Nov 30;22(1):750. doi: 10.1186/s12888-022-04407-y.

ABSTRACT

BACKGROUND: The present study aimed to identify profiles of social constraints among Chinese breast cancer patients and to explore the variables associated with these patterns.

METHODS: The study recruited 133 Chinese breast cancer patients in Liaoning Province, China, between June 2021 and February 2022. The questionnaire package included the Social Constraints Scale (SCS), the Multidimensional Scale of Perceived Social Support (MSPSS), the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and the Social Impact Scale (SIS). The methods of statistical analysis used included latent profile analysis (LPA) and multinomial logistic regression.

RESULTS: Three latent patterns of social constraints were found: class 1-the low social constraints group (51.9%), class 2-the moderate social constraints group (35.3%), and class 3-the high social constraints group (12.8%). Patients with high social support were more likely to report a low level of social constraint, while patients with a greater fear of progression were more likely to report a moderate or high level of social constraints. Significant differences existed among the latent classes identified by reference to social constraint in terms of education.

CONCLUSION: These results suggest that breast cancer patients’ perceptions of social constraints vary and exhibit individual differences. Health care providers should take into account patients’ fear of progression as well as their social support when developing interventions for patients with a high level of social constraints.

PMID:36451108 | DOI:10.1186/s12888-022-04407-y

BMC Genomics. 2022 Nov 30;23(1):786. doi: 10.1186/s12864-022-09036-z.

ABSTRACT

BACKGROUND: Average backfat thickness (BFT) is a critical complex trait in pig and an important indicator for fat deposition and lean rate. Usually, genome-wide association study (GWAS) was used to discover quantitative trait loci (QTLs) of BFT in a single population. However, the power of GWAS is limited by sample size in a single population. Alternatively, meta-analysis of GWAS (metaGWAS) is an attractive method to increase the statistical power by integrating data from multiple breeds and populations. The aim of this study is to identify shared genetic characterization of BFT across breeds in pigs via metaGWAS. RESULTS: In this study, we performed metaGWAS on BFT using 15,353 pigs (5,143 Duroc, 7,275 Yorkshire, and 2,935 Landrace) from 19 populations. We detected 40 genome-wide significant SNPs (Bonferroni corrected P < 0.05) and defined five breed-shared QTLs in across-breed metaGWAS. Markers within the five QTL regions explained 7 ~ 9% additive genetic variance and showed strong heritability enrichment. Furthermore, by integrating information from multiple bioinformatics databases, we annotated 46 candidate genes located in the five QTLs. Among them, three important (MC4R, PPARD, and SLC27A1) and seven suggestive candidate genes (PHLPP1, NUDT3, ILRUN, RELCH, KCNQ5, ITPR3, and U3) were identified.

CONCLUSION: QTLs and candidate genes underlying BFT across breeds were identified via metaGWAS from multiple populations. Our findings contribute to the understanding of the genetic architecture of BFT and the regulating mechanism underlying fat deposition in pigs.

PMID:36451102 | DOI:10.1186/s12864-022-09036-z

BMC Gastroenterol. 2022 Nov 30;22(1):496. doi: 10.1186/s12876-022-02592-4.

ABSTRACT

BACKGROUND: Gastric cancer is one of the leading cancer-related death causes. Enormous efforts have been focused on this field in these years. However, clinical trial failure is becoming a massive obstacle for researchers to apply their research results for clinical use. This study aimed to analyze the reasons behind clinical failures and identify potential risk factors of clinical trial failures.

METHODS: On December, 1, 2021, we queried ClinicalTrials.gov for gastric cancer listed in phase II/III. We included trials specifying their interests in “stomach cancer”, “Stomach Neoplasms”, “Gastric Cancer”, “Gastric Neoplasms”, “Gastric Carcinoma”, “Stomach Carcinoma”, “Gastroesophageal Junction Cancer”. Exclude criteria are: (1) Trials that start prior to 01/01/2007 and start after 12/01/2020; (2) Trials with “not yet recruiting”, “suspended”, “withdrawn”, or “unknown” status; (3) Trials do not provide an anticipated accrual number or a start date.

RESULTS: A total of 567 trials are included. 10.2% of these trials are failed. 16 (2.82%) were terminated for good reasons, and 42 (7.41%) were terminated for bad reasons. Multi-centre (P-value = 0.088) and anticipated accrual (P-value = 0.099) are potential risk factors for clinical failures in the simple logistic regression model. After considering the interaction between multi-centre and anticipated accrual, the odds ratio of anticipated accrual is 0.60 (P-value = 0.009) in single centre trials. In multi-centre trials, the odds ratio of anticipated accrual is 0.72 (P-value = 0.025). The primary reason for gastric cancer trial terminations is recruitment failure.

CONCLUSION: The rate that trials terminated in gastric cancer has decreased compared to previous studies. Comparing to other types of oncology trials, poor accrual continues to be the predominant reason, followed by business or sponsor reasons. Single-center trials with smaller anticipated accrual number are more likely to be terminated which may resulted by limited resources invested to the trial. Single-center design exacerbated the difficulty of participant recruitment. Future studies need to continue tracking the rate of trial termination across oncology and whether the reasons behind them have changed.

PMID:36451088 | DOI:10.1186/s12876-022-02592-4

BMC Ecol Evol. 2022 Nov 30;22(1):140. doi: 10.1186/s12862-022-02091-w.

ABSTRACT

BACKGROUND: The number of interactions between a transferable gene or its protein product and genes or gene products native to its microbial host is referred to as connectivity. Such interactions impact the tendency of the gene to be retained by evolution following horizontal gene transfer (HGT) into a microbial population. The complexity hypothesis posits that the protein product of a transferable gene with lower connectivity is more likely to function in a way that is beneficial to a new microbial host compared to the protein product of a transferable gene with higher connectivity. A gene with lower connectivity is consequently more likely to be fixed in any microbial population it enters by HGT. The more recently proposed simplicity hypothesis posits that the connectivity of a transferable gene might increase over time within any single microbial population due to gene-host coevolution, but that differential rates of colonization of microbial populations by HGT in accordance with differences in connectivity might act to counter this and even reduce connectivity over time, comprising an evolutionary trade-off.

RESULTS: We present a theoretical model that can be used to predict the conditions under which gene-host coevolution might increase or decrease the connectivity of a transferable gene over time. We show that the opportunity to enter new microbial populations by HGT can cause the connectivity of a transferable gene to evolve toward lower values, particularly in an environment that is unstable with respect to the function of the gene’s protein product. We also show that a lack of such opportunity in a stable environment can cause the connectivity of a transferable gene to evolve toward higher values.

CONCLUSION: Our theoretical model suggests that the connectivity of a transferable gene can change over time toward higher values corresponding to a more sessile state of lower transferability or lower values corresponding to a more itinerant state of higher transferability, depending on the ecological milieu in which the gene exists. We note, however, that a better understanding of gene-host coevolutionary dynamics in natural microbial systems is required before any further conclusions about the veracity of the simplicity hypothesis can be drawn.

PMID:36451084 | DOI:10.1186/s12862-022-02091-w

BMC Cardiovasc Disord. 2022 Nov 30;22(1):511. doi: 10.1186/s12872-022-02891-4.

ABSTRACT

BACKGROUND: In the latest reports, atherogenic indices have been related to acute coronary syndromes, stable coronary artery disease, heart failure and future cardiac events. Conventional atherosclerosis risk factors have been associated with mitral annular calcification (MAC), but data on the relationship between atherogenic indices and MAC are lacking. We aimed to investigate a possible relationship between MAC and atherogenic indices.

METHODS: In total 741 patients (n = 427 with MAC and n = 314 without MAC) who were examined in our cardiology clinic from February 2016 to October 2021 were recruited in the study. Mitral annular calcification was diagnosed by transthoracic 2-dimensional echocardiography. The atherogenic coefficient (AC), Castelli risk index 1 (CRI-1), Castelli risk index 2 (CRI-2) and atherogenic index of plasma (AIP) were calculated by utilizing standard lipid test values.

RESULTS: There was no statistically significant difference in sex, age, diabetes and hypertension status between the patient and the control groups. Serum triglyceride level, AIP, Hs-CRP, smoking and BMI were independently significantly associated with MAC in multiple regression analysis (p < 0.001).

CONCLUSION: Higher AIP was related to the existence of MAC and also predict the presence of MAC independently. Studies evaluating the modification of these indices are needed.

PMID:36451082 | DOI:10.1186/s12872-022-02891-4

Rheumatol Ther. 2022 Dec 1. doi: 10.1007/s40744-022-00510-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The association between diabetes mellitus (DM) and risk of osteoarthritis (OA) is inconsistent based on published observational studies. This study aimed to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal link between glycated hemoglobin (HbA1c) level and OA risk.

METHODS: Genome-wide association studies (GWAS) summary statistics were obtained from the publicly available Integrative Epidemiology Unit (IEU) OpenGWAS database. A series of screening processes were performed to select qualified instrumental single-nucleotide polymorphisms (SNPs) strongly related to exposure. The inverse-variance-weighted method, weighted-median method, and MR-Egger method were performed to ensure robust and reliable results. The MR-Egger intercept test, Cochran’s Q test, and the leave-one-out sensitivity analysis were utilized to assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants for OA. Odds ratio (OR) and 95% confidence interval (CI) were calculated.

RESULTS: MR analyses found a robust causal association of genetically determined HbA1c with knee OA (OR = 1.561; 95% CI 1.110-2.197; P = 0.011), but not with hip OA (OR = 1.073; 95% CI 0.674-1.710; P = 0.766) or overall OA (OR = 1.141; 95% CI 0.904-1.441; P = 0.804). Sensitivity analyses showed that there was a strong association between SNPs and HbA1c (F = 21.138), no evidence of heterogeneity (Q = 150.625, P = 0.402), and no potential SNPs affecting the causal link.

CONCLUSION: Our MR study supported a causal effect of genetically increased HbA1c on knee OA risk.

PMID:36451030 | DOI:10.1007/s40744-022-00510-4

Cancer Chemother Pharmacol. 2022 Dec 1. doi: 10.1007/s00280-022-04495-3. Online ahead of print.

ABSTRACT

PURPOSE: The current idea of how oral mucositis (OM) develops is primarily based on hypotheses and the early events which precede clinically established OM remain to be demonstrated. Cryotherapy (CT) continues to have considerable promise in clinical settings to reduce chemotherapy-induced OM. Although being effective, the knowledge is scarce regarding the ideal temperature for prevention of OM. Thus, the present study had two main objectives: (i) to develop an animal model to investigate the early events of OM; (ii) to study at what cooling temperature these early events could be abolished.

METHODS: Male Sprague-Dawley rats were anaesthetized and given an intravenous bolus dose with the cytostatic drug fluorouracil (5-FU). During the first hour following injection with 5-FU, the oral cavity of the rats was cooled to a mucosal temperature at the range of 15-30 ^○C, or left uncooled (35 ^○C), serving as control. After 3-5 days, the rats were euthanized, and the buccal mucosa was excised. Subsequently, mucosal thickness and expression of IL-6 and TNF-α were analyzed with immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).

RESULTS: Five days following treatment with 5-FU, a statistically significant thickening of the oral mucosa occurred, and a distinct expression of both IL-6 and TNF-α were observed. The cryo-treated groups (15-30 °C) displayed statistically significantly thinner mucosa as compared to the control group (35 °C). The ELISA showed an increase in expression of the proinflammatory cytokines IL-6 and TNF-α in tissues exposed to 5-FU that were treated with increasing temperatures (15-30 °C).

CONCLUSION: Bolus i.v. injection with 5-FU in rats can be used to create a functional animal model for chemotherapy-induced OM. Further, moderate temperature reduction is sufficient to reduce the early events which may precede clinically established OM.

PMID:36451020 | DOI:10.1007/s00280-022-04495-3

Cardiovasc Intervent Radiol. 2022 Nov 30. doi: 10.1007/s00270-022-03300-1. Online ahead of print.

ABSTRACT

PURPOSE: To assess occlusion success and adverse events associated with the use of a self-expanding device for peripheral artery embolization.

METHODS: This prospective, single-arm, feasibility study was conducted using the Caterpillar™ Arterial Embolization Device composed of opposing nitinol fibers and a flow-occluding membrane. Twenty patients (24 embolization sites) were treated at four investigational centers in New Zealand and Australia and followed for 30 days. Embolization sites included mesenteric, accessory renal, and iliac arteries and their branches. Primary outcome measures were peri-procedural occlusion confirmed by angiography and freedom from device-related serious adverse events (SAEs) at 30 days. Secondary observations included time to occlusion and assessment of adverse events.

RESULTS: Peri-procedural occlusion was 100%, and freedom from a device-related SAE was 94.7% at 30 days. One patient had abdominal bloating that required hospitalization deemed possibly related to the device or procedure. Twenty-two of 24 embolization sites were occluded with one device (91.7%). Mean procedure duration was 11.7 ± 8.6 min (device deployment time: 1.8 ± 1.0 min), and mean fluoroscopy time was 241 ± 290.7 s. All embolization sites occluded during the procedure with 62.5% occluded within three minutes and 91.6% occluded within ten minutes. No devices migrated or required re-embolization. Freedom from device- and procedure-related adverse events was 84.2%. One patient died from aortic rupture during a subsequent adjunctive abdominal aortic endovascular procedure deemed unrelated to the embolization device or procedure.

CONCLUSIONS: This first-in-human study of the Caterpillar embolization device achieved peri-procedural occlusion in all patients with a 94.7% freedom from device-related SAE at 30 days.

LEVEL OF EVIDENCE: Level 2b-prospective, multicenter, single-arm, first-in-human clinical study. Pre-specified endpoints were analyzed using descriptive statistics.

PMID:36450994 | DOI:10.1007/s00270-022-03300-1