Category: Nevin Manimala

J Alzheimers Dis. 2023 Jan 28. doi: 10.3233/JAD-220894. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetes increases the risk for cognitive decline, but the mechanisms behind this association remain unknown. Impaired early insulin secretion in elderly men and insulin resistance, both of which are pathophysiological features of type 2 diabetes, have previously been linked to Alzheimer’s disease.

OBJECTIVE: To examine if the early insulin response to oral glucose load predicts cognitive performance after 10 years in men and women aged 45-74 years.

METHODS: This study was based on a subpopulation of the Health 2000 Survey, a Finnish nationwide, population-based health examination study, and its follow-up, the Health 2011 Study. In total, 961 45-74-year-old individuals (mean age at baseline 55.6 years, 55.8% women) were examined. An oral glucose tolerance test was performed in 2001-2002, and early insulin response was defined as the ratio of the 30-min increment in insulin concentration to that of glucose concentration. Cognitive function was evaluated at baseline and follow-up with categorical verbal fluency, word-list learning, and word-list delayed recall. Statistical analyses were performed using multivariable linear models adjusted for age, sex, education, APOE&z.epsi;4 genotype, vascular risk factors including diabetes, and depressive symptoms.

RESULTS: A lower early insulin response to glucose load predicted lower performance (β: 0.21, p = 0.03) and greater decline (β: 0.19, p = 0.03) in the word-list delayed recall test. Baseline early insulin response did not predict verbal fluency or word-list learning (all p-values≥0.13).

CONCLUSION: Our results suggest that decreased early insulin secretion predicts episodic memory decline in middle-aged to elderly men and women.

PMID:36744339 | DOI:10.3233/JAD-220894

J Alzheimers Dis. 2023 Feb 2. doi: 10.3233/JAD-220727. Online ahead of print.

ABSTRACT

BACKGROUND: The oxidative stress hypothesis is challenging the dominant position of amyloid-β (Aβ) in the field of understanding the mechanisms of Alzheimer’s disease (AD), a complicated and untreatable neurodegenerative disease.

OBJECTIVE: The goal of the present study was to uncover the oxidative stress mechanisms causing AD, as well as the potential therapeutic targets and neuroprotective drugs against oxidative stress mechanisms.

METHODS: In this study, a systematic workflow combining pharmacological experiments and computational prediction were proposed. 222 drugs and natural products were collected first and then tested on SH-SY5Y cells to obtain phenotypic screening data on neuroprotection. The preliminary screening data were integrated with drug-target interactions (DTIs) and multi-scale biomedical data, which were analyzed with statistical tests and gene set enrichment analysis. A polypharmacology network was further constructed for investigation.

RESULTS: 340 DTIs were matched in multiple databases, and 222 cell viability ratios were calculated for experimental compounds. We identified significant potential therapeutic targets based on oxidative stress mechanisms for AD, including NR3C1, SHBG, ESR1, PGR, and AVPR1A, which might be closely related to neuroprotective effects and pathogenesis. 50% of the top 14 enriched pathways were found to correlate with AD, such as arachidonic acid metabolism and neuroactive ligand-receptor interaction. Several approved drugs in this research were also found to exert neuroprotective effects against oxidative stress mechanisms, including beclometasone, methylprednisolone, and conivaptan.

CONCLUSION: Our results indicated that NR3C1, SHBG, ESR1, PGR, and AVPR1A were promising therapeutic targets and several drugs may be repurposed from the perspective of oxidative stress and AD.

PMID:36744334 | DOI:10.3233/JAD-220727

J Alzheimers Dis. 2023 Feb 2. doi: 10.3233/JAD-220599. Online ahead of print.

ABSTRACT

BACKGROUND: Our understanding of the pathophysiology underlying Alzheimer’s disease (AD) has benefited from genomic analyses, including those that leverage polygenic risk score (PRS) models of disease. The use of functional annotation has been able to improve the power of genomic models.

OBJECTIVE: We sought to leverage genomic functional annotations to build tissue-specific AD PRS models and study their relationship with AD and its biomarkers.

METHODS: We built 13 tissue-specific AD PRS and studied the scores’ relationships with AD diagnosis, cerebrospinal fluid (CSF) amyloid, CSF tau, and other CSF biomarkers in two longitudinal cohort studies of AD.

RESULTS: The AD PRS model that was most predictive of AD diagnosis (even without APOE) was the liver AD PRS: n = 1,115; odds ratio = 2.15 (1.67-2.78), p = 3.62×10-9. The liver AD PRS was also statistically significantly associated with cerebrospinal fluid biomarker evidence of amyloid-β (Aβ 42:Aβ 40 ratio, p = 3.53×10-6) and the phosphorylated tau:amyloid-β ratio (p = 1.45×10-5).

CONCLUSION: These findings provide further evidence of the role of the liver-functional genome in AD and the benefits of incorporating functional annotation into genomic research.

PMID:36744333 | DOI:10.3233/JAD-220599

Biomed Mater Eng. 2023 Jan 31. doi: 10.3233/BME-222513. Online ahead of print.

ABSTRACT

BACKGROUND: Acrylic resins used in dental and biomedical applications do not have antimicrobial properties, their surface is susceptible to colonization of microorganisms.

OBJECTIVE: The aim of this study was to evaluate the antibiofilm properties of silver nanoparticles (AgNPs) deposited in a polymethyl methacrylate (PMMA) surface against a Staphylococcus aureus biofilm.

METHODS: The PMMA was impregnated with AgNPs by using the in-situ polymerization method. To determine the solubility of the incorporated silver (Ag+) atomic absorption spectrophotometry was used (AAS) at 24 h, 48 h, 7 days, and 30 days. Thirty specimens of PMMA with AgNPs and without NP (control group) were assembled in the CDC Biofilm Bioreactor system with a cell suspension of S. aureus. The specimens were removed at 6, 12, 24, 48, and 72 h to determine the viability profile and quantify the Arbitrary Fluorescence Units (AFU).

RESULTS: The AgNPs showed an irregular and quasispherical shape with an average size of 25 nm. AAS analysis demonstrated a low solubility of Ag+. The formation of the S. aureus biofilm increased as the evaluation periods continued up to 72 h. The experimental group showed poor growth, and a decrease in the intensity of the fluorescence demonstrated a statistically significant inhibition of the formation of the biofilm (P < 0.05) in relation to the control group at 6, 12, 24, 48, and 72 h.

CONCLUSION: AgNPs incorporated into PMMA decreased the growth and maturation of S. aureus biofilm.

PMID:36744329 | DOI:10.3233/BME-222513

Cardiol Young. 2023 Feb 6:1-4. doi: 10.1017/S1047951123000136. Online ahead of print.

ABSTRACT

OBJECTIVES: When cardiac muscle damage occurs, cardiac troponins are released to blood and their detection is used as a marker in clinical setting. The prognostic value of the quantitative levels of blood troponin I in cases of myocarditis and myopericarditis is unclear. The aim of this study was to analyse whether troponin quantitative blood levels can be correlated with the course of hospitalisation and prognosis.

METHODS: Retrospective data was collected from all consecutive patients aged ≤30 hospitalised with a diagnosis of acute myocarditis or acute myopericarditis in our health Care Campus between the years 2010-2016.

RESULTS: Ninety-three patients with myocarditis and myopericarditis were identified. Higher peak troponin levels correlated with longer hospitalisation times in the cardiac or paediatric wards (p = 0.03, Pearson correlation: r -0.23), and median troponin level at admission correlated with longer overall hospitalisation (p = 0.026, Pearson correlation: r = 0.23). Patients admitted to ICU, received oral cardiac supportive therapy or that were discharged with cardiac drugs had higher median troponin compared to patients who were not but this was not statistically significant. A small group of patients that needed intravenous cardiac support had significantly lower median peak troponin levels (n = 4, 0.375ng/ml, p = 0.048). Only two patients needed extracorporeal membrane oxygenation support, and one died. The small number of patients precludes statistical analysis.

CONCLUSION: Higher troponin levels correlated significantly with longer hospitalisation, lower troponin values correlated with intravenous cardiac support, while other variables related to the severity of disease could not be significantly related to higher troponin levels.

PMID:36744328 | DOI:10.1017/S1047951123000136

Med Educ Online. 2023 Dec;28(1):2172744. doi: 10.1080/10872981.2023.2172744.

ABSTRACT

PURPOSE: International studies document that lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI+) patients face significant health disparities. Studies exploring the attitudes, knowledge, preparedness and comfort levels of healthcare students towards LGBTQI+ health have been conducted in the United States, United Kingdom and Malaysia. This study aims to investigate stigma in healthcare for LGBTQI+ patients in Singapore, and possible upstream factors within medical education.

METHODS: This mixed-methods study adopts a convergent parallel design. The Health Stigma and Discrimination Framework was referenced to devise in-depth interviews with representatives from 13 LGBTQI-affirming non-governmental organisations, analysed through thematic analysis. 320 clinical medical students were surveyed about attitudes, knowledge, comfort, preparedness, and perceived importance of/towards LGBTQI+ health, analysed via descriptive statistics and multivariate regression.

RESULTS: Prevailing stigma in Singaporean society against LGBTQI+ individuals is exacerbated in healthcare settings. Doctors were cited as unfamiliar or uncomfortable with LGBTQI+ health, possibly from lack of training. Among medical students surveyed, the median composite attitudes, comfort and preparedness index was 3.30 (Interquartile Range (IQR) = 0.50), 3.17 (IQR = 0.83), 2.50 (IQR = 1.00) respectively. Only 12.19% of students answered all 11 true-false questions about LGBTQI+ health correctly.

CONCLUSION: Medical students in Singapore have scored sub-optimally in their knowledge and preparedness towards LGBTQI+ health, while interpersonal and structural stigma in healthcare towards LGBTQI+ people in Singapore negatively affects health and wellbeing. These findings are an impetus to improve medical training in this area. High scores among medical students in attitudes, comfort and perceived importance of LGBTQI+ topics demonstrate that there is space for LGBTQI+ health in the local medical education curriculum. Curricular interventions can prioritise content knowledge, communication skills and sensitivity.

PMID:36744296 | DOI:10.1080/10872981.2023.2172744

Front Pharmacol. 2023 Jan 19;14:1081724. doi: 10.3389/fphar.2023.1081724. eCollection 2023.

ABSTRACT

Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.

PMID:36744248 | PMC:PMC9892634 | DOI:10.3389/fphar.2023.1081724

Front Pharmacol. 2023 Jan 20;14:1024807. doi: 10.3389/fphar.2023.1024807. eCollection 2023.

ABSTRACT

Background: No consensus exists on the antibiotic treatment course for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Former studies indicate that shorter courses might have the same efficacy with fewer adverse events, which is inconsistent with guidelines and general practice. Existing evidence allows us to conduct a systematic review and Bayesian analysis on this topic. Methods: Four databases were searched from their inception to January 5, 2023. All statistical estimations were performed using R. “Gemtc” was the core package of analysis. CINeMA was used to assess the grade of confidence of the results. Results: Fourteen studies were included in the Bayesian meta-analysis. No difference in the clinical success rate of antibiotic treatment was observed from a super short course (1-3 days) to a long course (≥10 days). Considering the adverse events, the short course (4-6 days) might be the safest. The majority of results were of high or moderate confidence grade. Conclusion: Short course might cause the fewest adverse events. The clinical efficacy of antibiotics might not depend on the course length. Undeniably, more systematic explorations are warranted to investigate the clinical application of a shorter course of antibiotic treatment.

PMID:36744244 | PMC:PMC9895851 | DOI:10.3389/fphar.2023.1024807

Contracept Reprod Med. 2023 Feb 6;8(1):11. doi: 10.1186/s40834-022-00207-7.

ABSTRACT

BACKGROUND: Even if long term contraceptives are more effective, efficient and tolerable choices, method shifting from long to short term contraceptives continued as a global challenge including Ethiopia. There is limited evidence on the proportion and factors associated with method shifting from long term to short term contraceptives in the country, specifically in the study area. Therefore, this study assessed the proportion and associated factors of method shifting from long term to short term contraceptives in Gondar city administration, northwest Ethiopia.

METHODS: Institution based cross-sectional study was conducted from February to June 2018 among reproductive age women who were long term contraceptive users. A total of 407 women of reproductive age were selected using systematic random sampling technique. Data were entered through Epi Info version 3.5.3 and analyzed using SPSS version 20. Bivariable and multivariable logistic regression analyses were employed to investigate factors associated with method shifting. Adjusted Odds Ratio with the corresponding 95% confidence intervals were used to show the presence and strength of association. Variables with P-value of < 0.05 in the multivariable model were considered to have statistically significant association with method shifting.

RESULTS: The overall proportion of method shifting from long to short term contraceptives was 48.5% [CI: 43.8, 53.3]. Having secondary level educational status [AOR = 0.18, CI = 0.07, 0.51], using long acting contraceptives for limiting purposes [AOR = 0.26, CI = 0.11, 0.60], and having enough counseling on long acting contraceptives during ANC visits [AOR = 0.20, CI = 0.08, 0.50] were factors negatively associated with method shifting, while receiving information about long acting contraceptives from colleague [AOR = 6.67, CI = 1.89, 23.52] was positively associated with method shifting.

CONCLUSION: The proportion of method shifting from long to short term contraceptives was 48.5%. Women’s educational level, source of information, the aim behind using long acting contraceptives, and counseling adequacy were the main factors associated with method shifting. Therefore, health care providers better consider women’s educational level, provision of accurate information and adequate counseling are crucial in the provision of long acting contraceptive methods.

PMID:36740707 | DOI:10.1186/s40834-022-00207-7

Contracept Reprod Med. 2023 Feb 6;8(1):13. doi: 10.1186/s40834-022-00211-x.

ABSTRACT

BACKGROUND: Unmet need for family planning among adolescent girls and young women (AGYW) is a common cause of the low contraceptive utilization in developing countries, including Ethiopia. To address problems associated with unmet for family planning among adolescent girls and young women nationally available evidences are essential. However, there is limited evidence regarding factors associated with the unmet need for family planning among adolescent girls and young women in Ethiopia. Hence, this study aims to assess the prevalence and associated factors of unmet need for family planning among adolescent girls and young women in Ethiopia.

METHODS: Our analysis was based on secondary data using the 2016 Ethiopian Demographic and Health Survey data. A total weighted sample of 1086 adolescent girls and young women was included in this study. A multi-level mixed-effect logistic regression analysis was fitted. Adjusted odds ratios with 95% confidence intervals were used to show the strength and direction of the association. Statistical significance was declared at a p-value less than 0.05.

RESULTS: The prevalence of unmet need for family planning was 28.3% (95% CI: 25.7, 31.0). Adolescent girls and young women age 15-19 years (aOR: 2.4, 95%CI: 1.3, 4.3), household wealth quantile; poor (aOR: 5.6, 95%CI: 2.8, 11.1) and middle (aOR: 2.9, 95%CI: 1.4, 6.0), had no media exposure (aOR: 2.1, 95%CI: 1.1, 4.1), and adolescent girls and young women from developing regions (aOR: 5.1, 95%CI: 1.1, 14.5) were significantly associated with unmet need for family planning.

CONCLUSIONS: Unmet need for family planning was high among adolescent girls and young women when compared to the national average and the United Nations sphere standard of unmet need for family planning. Age, wealth quantile, media exposure, and region were significantly associated with unmet need for family planning. Hence, there is the need to implement consistently effective family planning policies among AGYW living in developing regions of Ethiopia. Moreover, Public health policies and interventions that improve the existing strategies to improve media exposure of AGYW on family planning issues and increase the wealth status of households should be designed and implemented to reduce the unmet need for family planning in Ethiopia.

PMID:36740700 | DOI:10.1186/s40834-022-00211-x