Category: Nevin Manimala

Arterioscler Thromb Vasc Biol. 2024 Feb 22. doi: 10.1161/ATVBAHA.123.319789. Online ahead of print.

ABSTRACT

BACKGROUND: ANGPTL3 (angiopoietin-like protein 3) is a circulating protein with a key role in maintaining lipoprotein homeostasis. A monoclonal antibody against ANGPTL3 is an approved and well-tolerated treatment to reduce lipoproteins in familial hypercholesterolemia homozygotes. However, the reduction of hepatic ANGPTL3 synthesis using an antisense oligonucleotide unexpectedly resulted in a dose-dependent increase in liver lipid content and circulating transaminases, resulting in the termination of the clinical trial. Meanwhile, the use of silencing RNAs remains an area of active investigation. Our study sought to investigate whether intracellular downregulation of ANGPTL3 may lead to a primary increase in neutral lipids within the hepatocyte.

METHODS: We downregulated ANGPTL3 by silencing RNA in primary human hepatocytes 3-dimensional spheroids, HepG2/LX-2 3-dimensional spheroids, and in HepG2, Hep3B2, and Huh7 cultured in 2 dimensions.

RESULTS: ANGPTL3 downregulation increased neutral lipids in all models investigated. Interestingly, ANGPTL3 induced lower intracellular deiodinase type 1 protein levels resulting in a reduction in beta-oxidation and causing an increase in triglycerides stored in lipid droplets.

CONCLUSIONS: In conclusion, intracellular ANGPTL3 downregulation by silencing RNA led to an increase in triglycerides content due to a reduction in energy substrate utilization resembling a primary intracellular hepatocyte hypothyroidism.

PMID:38385290 | DOI:10.1161/ATVBAHA.123.319789

Womens Health (Lond). 2024 Jan-Dec;20:17455057241231420. doi: 10.1177/17455057241231420.

ABSTRACT

BACKGROUND: Menstrual hygiene management plays a significant role in the achievement of sustainable development goals, including good health and well-being, quality education, gender equality, women’s empowerment, and sanitation. Even though the United Nations emphasizes menstrual hygiene management as a global public health and human rights issue, studies from different parts of the world have shown there is a lack of policies in this area that affects adolescent girls.

OBJECTIVE: The study aimed to assess the menstrual-related knowledge and practices of adolescent girls (10-18 years) attending urban and rural public schools of district Khairpur of province Sindh of Pakistan.

DESIGN: This research is an analytical cross-sectional study design.

METHODS: Adolescent girls (n = 310), 159 girls from urban and 159 girls from rural schools, were enrolled. Data were collected through self-administered questionnaires. Knowledge was considered satisfactory if the participant scored ⩾12/20, and <12/20 was considered unsatisfactory knowledge. Practice scores were considered good for >10 and poor for <10. Statistical Package for the Social Science (SPSS) version 20.0 was used for data analysis. Descriptive statistics such as mean and standard deviation were calculated. The chi-square test was used to assess and compare the differences between practices and knowledge of menstrual hygiene management between urban and rural adolescent school girls.

RESULTS: We found significant differences in menstrual hygiene management among adolescent girls between urban and rural areas. Approximately two-thirds of the total school girls thought that school management had inadequate resources and toilet facilities (rural: 76% versus urban: 62%). The major source of knowledge in adolescent rural and urban girls for menstrual-related matters was mothers. More girls from the urban school (81%) were aware of using sanitary pads during menstruation. The majority of the girls from urban areas showed satisfactory knowledge whereas only 38% of rural girls were shown to have satisfactory results. Nearly 71% of urban girls were found to have good practices when compared with rural girls (12%).

CONCLUSION: With further importance by the United Nations on female education in less developed regions, where the health of women is usually given less importance, policies are required on the inclusion of reproductive health of female adolescents in the curriculum.

PMID:38385267 | DOI:10.1177/17455057241231420

J Biosoc Sci. 2024 Feb 22:1-24. doi: 10.1017/S0021932024000051. Online ahead of print.

ABSTRACT

A barrier to meeting the goal of universal health coverage in India is the inequality in utilisation of health services between indigenous and non-indigenous people. This study aimed to explore the determinants of utilisation, or non-utilisation, of public healthcare services among the Santals, an indigenous community living in West Bengal, India. The study holistically explored the utilisation of public healthcare facilities using a framework that conceptualised service coverage to be dependent on a set of determinants – viz. the nature and severity of the ailment, availability, accessibility (geographical and financial), and acceptability of the healthcare options and decision-making around these further depends on background characteristics of the individual or their family/household. This cross-sectional study adopts ethnographic approach for detailed insight into the issue and interviewed 422 adult members of Santals living in both rural (Bankura) and urban (Howrah) areas of West Bengal for demographic, socio-economic characteristics and healthcare utilisation behaviour using pre-tested data collection schedule. The findings revealed that utilisation of the public healthcare facilities was low, especially in urban areas. Residence in urban areas, being female, having higher education, engaging in salaried occupation and having availability of private allopathic and homoeopathic doctors in the locality had higher odds of not utilising public healthcare services. Issues like misbehaviour from the health personnel, unavailability of medicine, poor quality of care, and high patient load were reported as the major reasons for non-utilisation of public health services. The finding highlights the importance of improving the availability and quality of care of healthcare services for marginalised populations because these communities live in geographically isolated places and have low affordability of private healthcare. The health programme needs to address these issues to improve the utilisation and reduce the inequality in healthcare utilisation, which would be beneficial for all segments of Indian population.

PMID:38385266 | DOI:10.1017/S0021932024000051

Int J Occup Med Environ Health. 2024 Feb 21:177286. doi: 10.13075/ijomeh.1896.02197. Online ahead of print.

ABSTRACT

OBJECTIVES: In recent years numerous initiatives aimed at reducing air pollution have been undertaken in Poland. The general objective was to examine the correlation between air pollution measured by the level of particulate matter ≤10 μm in diameter (PM₁₀) and emergency hospitalizations due to chronic obstructive pulmonary disease (COPD) and asthma in 16 Polish cities (capitals of the regions).

MATERIAL AND METHODS: The authors aimed to diagnose the situation across 16 cities over a 5‑year period (2014-2019). Data on the number of hospitalizations was retrieved from the national public insurance system, the National Health Fund. A total number of 22 600 emergency hospitalizations was analyzed (12 000 and 10 600 in 2014 and 2019, respectively). The data on air pollution was accessed via the public register of the Chief Inspectorate for Environmental Protection air quality database. The authors of this article have used the data on PM₁₀ daily exposure in each of the 16 cities in 2014 and 2019. Statistical methods included: non-parametric tests, a 2-stage modelling approach for time-series data, and multivariate meta-analysis of the results.

RESULTS: The results indicated that there was a statistically significant decrease in PM₁₀ concentration in 2019 in comparison to 2014 in all cities, mainly in the autumn and winter season. However, the correlation between the improvement in the air quality and a decrease in emergency hospitalizations due to asthma and COPD turned out to not be as strong as expected. The authors observed a strong correlation between PM₁₀ concentrations and hospitalizations due to asthma and COPD, but only when air quality norms were significantly above acceptable levels.

CONCLUSIONS: Air pollution measured by PM₁₀ concentration might be used as one of the predictors of the asthma and COPD emergency hospitalization risk, yet other factors like respiratory tract infection, health care organizational aspect, patient self-control, compliance and comorbidities should also be taken into consideration. Int J Occup Med Environ Health. 2024;37(1).

PMID:38385199 | DOI:10.13075/ijomeh.1896.02197

Am J Sports Med. 2024 Feb 22:3635465241227440. doi: 10.1177/03635465241227440. Online ahead of print.

ABSTRACT

BACKGROUND: Suture and screw fixations are widely used to treat tibial eminence fractures (TEFs). Although a few biomechanical and clinical studies have compared suture fixation (SF) and screw fixation in the treatment of TEFs in children, no comparative clinical studies are available regarding headless screw fixation (HSF).

PURPOSE: To evaluate the clinical and functional outcomes of children with TEF who underwent SF and HSF.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: The study included 24 patients treated with either SF (11 patients) or HSF (13 patients) within 1 month of TEF (type 2 or 3) without associated ligamentous and bone injury between 2015 and 2020. All patients were evaluated at a minimum 2-year follow-up in terms of Lysholm score, Tegner activity level, International Knee Documentation Committee subjective score, and isometric strength test. Knee stability was compared based on the Lachman test, pivot-shift test, and KT-1000 arthrometer side-to-side difference.

RESULTS: No significant differences were found between the 2 groups in terms of Lysholm score, Tegner activity level, and International Knee Documentation Committee subjective score at follow-up. All patients were able to resume their daily activities within 6 months after the injury. However, flexion deficits (6°-10°) were found in 2 patients in the SF group and 1 patient in the HSF group, and extension deficits (3°-5°) were found in 3 patients in the SF group and 1 patient in the HSF group, without significant intergroup difference. Stability based on the Lachman test, pivot-shift test, and KT-1000 arthrometer side-to-side difference was also similar between the 2 groups at follow-up. No statistically significant difference was found between the 2 groups in isometric tests performed.

CONCLUSION: The present study is the first to compare the clinical and functional results of SF and HSF techniques. The HSF technique demonstrated comparable clinical and functional outcomes, suggesting its potential as an alternative to the SF technique.

PMID:38385198 | DOI:10.1177/03635465241227440

Hypertens Pregnancy. 2024 Dec;43(1):2312165. doi: 10.1080/10641955.2024.2312165. Epub 2024 Feb 22.

ABSTRACT

BACKGROUND: Predicting severe preeclampsia with need for intensive care is challenging. To better predict high-risk pregnancies to prevent adverse outcomes such as eclampsia is still an unmet need worldwide. In this study we aimed to develop a prediction model for severe outcomes using routine biomarkers and clinical characteristics.

METHODS: We used machine learning models based on data from an intensive care cohort with severe preeclampsia (n=41) and a cohort of preeclampsia controls (n=40) with the objective to find patterns for severe disease not detectable with traditional logistic regression models.

RESULTS: The best model was generated by including the laboratory parameters aspartate aminotransferase (ASAT), uric acid and body mass index (BMI) with a cross-validation accuracy of 0.88 and an area under the curve (AUC) of 0.91. Our model was internally validated on a test-set where the accuracy was lower, 0.82, with an AUC of 0.85.

CONCLUSION: The clinical routine blood parameters ASAT and uric acid as well as BMI, were the parameters most indicative of severe disease. Aspartate aminotransferase reflects liver involvement, uric acid might be involved in several steps of the pathophysiologic process of preeclampsia, and obesity is a well-known risk factor for development of both severe and non-severe preeclampsia likely involving inflammatory pathways..[Figure: see text].

PMID:38385188 | DOI:10.1080/10641955.2024.2312165

Hosp Pract (1995). 2024 Feb 22. doi: 10.1080/21548331.2024.2320067. Online ahead of print.

ABSTRACT

OBJECTIVES: Presbycusis is highly prevalent, affecting between a third and two thirds of elderly populations. Effective communication between patient and physician has been shown to directly correlate with the quality of patient care.The Reverse Stethoscope Technique (RST) involves placing the earpieces into the patient’s ears and speaking into the diaphragm. Here we aim to show the RST is a simple and effective method to communicate with patients suffering from presbycusis in inpatient settings.

METHODS: Medical inpatients aged >60 years old without cognitive impairment were included in the study. A simple repetition exercise of basic English sentences was performed with and without the RST to assess hearing ability. Patients then undertook a short questionnaire.

RESULTS: Our study included 109 patients with varied ‘self-reported’ hearing. 50.5% of our cohort reported past communication difficulties with healthcare professionals due to hearing difficulties.We identified that the RST increased the mean number of sentences a patient could repeat from 2.6 to 3.5 representing a statistically significant increase (p < 0.001). The technique was most beneficial for patients with ‘okay’ and ‘poor’ hearing. The majority of patients (77/109) also stated the technique reduced background noise. The RST was equally effective with facemasks.

CONCLUSION: Current techniques to enhance communication with patients with hearing loss are often underutilized or poorly accessible. Our study identified that the RST is a quick and effective solution that can be easily implemented for patients struggling to communicate with healthcare professionals in inpatient scenarios.

PMID:38385177 | DOI:10.1080/21548331.2024.2320067

Gut Microbes. 2024 Jan-Dec;16(1):2315631. doi: 10.1080/19490976.2024.2315631. Epub 2024 Feb 22.

ABSTRACT

Immune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein, we report that supplementation with CBM588 led to an improved responsiveness to antibody targeting programmed cell death protein 1 (aPD-1). This was statistically associated with a significant decrease in α-diversity of gut microbiota from CBM588-treated mice upon PD-1 blockade. At the level of the tumor-draining lymph node, such combination of treatment significantly lowered the frequency of microbiota-modulated subset of regulatory T cells that express Retinoic Orphan Receptor gamma t (Ror$\gamma$t⁺ Treg). Specifically, this strongly immunosuppressive was negatively correlated with the abundance of bacteria that belong to the family of Ruminococcaceae. Accordingly, the colonic expression of both indoleamine 2,3-Dioxygenase 1 (IDO-1) and interleukin-10 (IL-10) were heightened in mice with greater PD-1 blockade efficacy. The CBM588-induced ability to secrete Interleukin-10 of lamina propria mononuclear cells was heightened in tumor bearers when compared with cancer-free mice. Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8⁺ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

PMID:38385162 | DOI:10.1080/19490976.2024.2315631

Synth Syst Biotechnol. 2024 Feb 8;9(2):196-208. doi: 10.1016/j.synbio.2024.01.012. eCollection 2024 Jun.

ABSTRACT

The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites. Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method. S. baarensis MH-133 is significantly influenced by elicitation, yeast extract, inoculum size, and incubation period in terms of antibacterial activity. A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design. The analyses revealed that the model was highly significant (p < 0.001), with a lack-of-fit of 0.212 and a coefficient determination (R2) of 0.9224. Additionally, the model predicted that the response as inhibition zone diameter would reach a value of 27 mm. Under optimal conditions, S. baarensis MH-133 produced 18.0 g of crude extract to each 35L and was purified with column chromatography. The active fraction exhibiting antibacterial activity was characterized using spectroscopic analysis. The MIC and MBC values varied between 37.5 and 300 μg/ml and 75 and 300 μg/ml, respectively. In conclusion, the biostatistical optimization of the active fraction critical variables, including environmental and nutritional conditions, enhances the production of bioactive molecules by Streptomyces species.

PMID:38385149 | PMC:PMC10876617 | DOI:10.1016/j.synbio.2024.01.012

Front Cardiovasc Med. 2024 Feb 7;11:1279890. doi: 10.3389/fcvm.2024.1279890. eCollection 2024.

ABSTRACT

BACKGROUND: An increase in deaths has been perceived during the pandemic, which cannot be explained only by COVID-19. The actual number of deaths far exceeds the recorded data on deaths directly related to SARS-CoV-2 infection. Data from early and short-lived pandemic studies show a dramatic shift in cardiovascular mortality. Grounded in the post-pandemic era, macroscopic big data on cardiovascular mortality during the pandemic need to be further reviewed and studied, which is crucial for cardiovascular disease prevention and control.

METHODS: We retrieved and collected data associated with cardiovascular disease mortality from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform based on the ICD-10 codes. We applied regression analysis to characterize overall cardiovascular disease mortality trends from 2010 to 2023 and built a time series model to predict mortality for 2020-2023 based on mortality data from 2010 to 2019 in order to affirm the existence of the excess deaths by evaluating observed vs. predicted mortality. We also conducted subgroup analyses by sex, age and race/ethnicity for the purpose of obtaining more specific sociodemographic information.

RESULTS: All-cause age-standardised mortality rates (ASMRs) for CVD dramatically increased between 2019 and 2021[annual percentage change (APC) 11.27%, p < 0.01], and then decreased in the following 2021-2023(APC: -7.0%, p < 0.01). Subgroup analyses found that the ASMR change was most pronounced in Alaska Indians/Native American people (APC: 16.5% in 2019-2021, -12.5% in 2021-2023, both p < 0.01), Hispanics (APC: 12.1% in 2019-2021, -12.2% in 2021-2023, both p < 0.05) and non-Hispanic Black people (APC:11.8% in 2019-2021, -10.3% in 2021-2023, both p < 0.01)whether during the increasing or declining phase. Similarly, the ASMR change was particularly dramatic for the 25-44 age group (APC:19.8% in 2019-2021, -15.4% in 2021-2023, both p < 0.01) and males (APC: 11.5% in 2019-2021, -7.6% in 2021-2023, both p < 0.01). By the end of 2023, the proportion of COVID-related excess death remained high among the elderly (22.4%), males (42.8%) and Alaska Indians/Native American people(39.7%). In addition, we did not find the presence of excess deaths in the young (25-44) and middle-aged cohort (45-64) in 2023, while excess deaths remained persistent in the elderly.

CONCLUSIONS: All-cause ASMRs for CVD increased notably during the initial two years of the COVID-19 pandemic and then witnessed a decline in 2021-2023. The cohorts (the young, males and minorities) with the steepest rise in mortality decreased at the fastest rate instead. Previous initiatives to promote cardiovascular health were effective, but further research on cardiovascular healthcare for the elderly and racial disparities should be attached to priority considering the presence of sociodemographic differences in CVD death.

PMID:38385134 | PMC:PMC10879411 | DOI:10.3389/fcvm.2024.1279890