Category: Nevin Manimala

Matern Child Health J. 2024 Mar 1. doi: 10.1007/s10995-024-03924-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Shared sanitation facilities are used by over 500 million people around the world. Most research evidence indicates that shared sanitation conveys higher risk than household sanitation for many adverse health outcomes. However, studies often fail to account for variation between different types of shared facilities. As informal housing development outpaces sanitation infrastructure, it is imperative to understand which components of shared facilities may mitigate the health risks of shared sanitation use.

METHODS: This cross-sectional study determines whether sanitation improvement or compound hygiene were associated with stunting or diarrhoeal prevalence in children under five living in Maputo, Mozambique who rely on shared sanitation facilities. The study uses logistic and linear multivariable regression analysis to search for associations and control for potential confounding factors.

RESULTS: 346 children (43.9%) in the study population were stunted. Each unit increase in sanitation score was associated with an approximate decrease of 22% in the odds of stunting (OR: 0.78, CI: 0.66, 0.92), and an increase in height of 0.23 height-for-age z-scores (CI: 0.10, 0.36). There was no evidence that the compound hygiene score was associated with height as measured by stunting (OR: 1.05, CI: 0.87, 1.26) or z-score (-0.06, CI: -0.21, 0.09). Neither sanitation nor compound hygiene score were associated with diarrhoea in the population.

CONCLUSIONS: Use of an improved shared latrine is associated with decreased odds of stunting. There is no evidence of an association between latrine improvement and diarrhoea. Further investigation is necessary to isolate attributes of shared sanitation facilities that may reduce health risks.

PMID:38427278 | DOI:10.1007/s10995-024-03924-4

Methods Mol Biol. 2024;2761:397-419. doi: 10.1007/978-1-0716-3662-6_28.

ABSTRACT

Transcriptomics is a complex process that involves raw data extraction, normalization, differential gene expression, and analysis. The Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) is a repository of experimental datasets. Amyotrophic lateral sclerosis (ALS) datasets are deposited by various scientists and research investigators to expand the horizon of scientific knowledge. R-statistical tools are the most common ways for conducting these kinds of studies. The first step is the identification of appropriate datasets. Since the raw data is available in a variety of formats, a large array of software is used for extraction and analysis. Normalization is conducted for the datasets using NetworkAnalyst. Differential analysis is further conducted on the normalized data to identify significantly enriched genes. The significant genes are then grouped into pathways. The results were validated using yeast model of ALS in which the yeast is transformed with ALS plasmids encoding genes associated with ALS. The resulting GFP-tagged protein aggregates are imaged using fluorescence microscopy and subsequently validated using filter retardation assay and quantified using ImageJ software. Functional role of different genes is studied using metabolite treatment and knockout studies.

PMID:38427252 | DOI:10.1007/978-1-0716-3662-6_28

Methods Mol Biol. 2024;2785:321-344. doi: 10.1007/978-1-0716-3774-6_20.

ABSTRACT

Biological validation of preliminary findings is a key prerequisite in biomarker discovery. In recent years, the development of advanced large-scale sequencing technologies combined with high-throughput computational analysis methods led to the extraction of considerable amount of data from healthy and diseased tissues. Stored in large open-access repositories, these data can be accessed and interrogated by researchers aiming at understanding the biological rationale behind their results. These so called in silico analyses, in opposite to in vitro analyses, have gained increasing importance in recent years, becoming a major component of research projects and publications. However, making sense of the large amount of data available can be challenging and may lead to a misinterpretation of the data. To reduce the dimensionality of this data, recent years have seen the development of statistical methods and advanced graph analytics which help researchers summarize the available data and draw appropriate conclusions. In this chapter we will describe three in silico methods to investigate the biological underpinnings of a panel of seven blood-based biomarkers of Alzheimer’s disease.

PMID:38427203 | DOI:10.1007/978-1-0716-3774-6_20

J Interv Card Electrophysiol. 2024 Mar 1. doi: 10.1007/s10840-024-01738-6. Online ahead of print.

ABSTRACT

BACKGROUND: The importance of a wider circumferential isolation of the pulmonary veins (PV), which includes a large portion of the left atrial posterior wall (LAPW), has been suggested in several studies. However, the extended isolation area using a larger inflated visually guided laser balloon (VGLB) ablation remains to be elucidated.

METHODS: Seventy-eight patients with atrial fibrillation (AF) who underwent VGLB ablation were enrolled in this prospective study. An electroanatomic map of the left atrium was obtained before and after PV isolation (PVI) using a conventional-sized VGLB. The isolation areas were extended by the largest-sized VGLB ablation and remapped in the same manner. After the ablation, isolation areas were calculated with CARTO-3 system. The one-year atrial arrhythmia (Ata) recurrence was assessed. RESULTS: The largest-sized VGLB ablation yielded statistically greater areas of isolation in left-sided PV antrum (PVA) (11.5 ± 2.3 cm² vs. 15.9 ± 3.5 cm², P < .001) and right-sided PVA (14.2 ± 3.3 cm² vs. 20.6 ± 4.4 cm², P < .001) than the conventional-sized VGLB. Further, non-ablated LAPW (12.3 ± 4.4 cm² vs. 7.8 ± 3.9 cm², P < .001) was significantly reduced after largest-sized VGLB ablation, compared to the conventional-sized VGLB ablation. The one-year Ata freedom was 83.7% in patients with paroxysmal AF and 96.4% in those with persistent AF.

CONCLUSION: The largest-sized VGLB ablation technique can create a significantly wider isolation area of PVA and debulk a large amount of LAPW than the conventional-sized VGLB ablation. The one-year outcome was similarly high in paroxysmal and persistent AF.

PMID:38427180 | DOI:10.1007/s10840-024-01738-6

Diabetes Ther. 2024 Mar 1. doi: 10.1007/s13300-024-01551-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Semaglutide, the only glucagon-like peptide-1 receptor agonist (GLP-1 RA) available in subcutaneous and oral formulation for treatment of type 2 diabetes (T2D), has demonstrated clinically significant improvements in glycaemic control and weight in clinical trials. This study aimed to gain insights into the use of both formulations and evaluate their clinical effectiveness in a secondary care clinic in Wales.

METHODS: This was a retrospective observational analysis of adults with T2D initiated on oral or subcutaneous semaglutide. Changes from baseline in glycated haemoglobin (HbA_1c), weight and other metabolic parameters were evaluated.

RESULTS: At baseline, participants (n = 103) had a mean age of 57.3 years, mean HbA_1c of 79.1 mmol/mol (9.38%), mean weight of 111.8 kg and body mass index (BMI) of 39.6 kg/m² (no statistically significant differences between oral and subcutaneous groups). At 6-month follow-up, statistically significant improvements in HbA_1c (- 19.3 mmol/mol [- 1.77%] and – 20.8 mmol/mol [- 1.90%]), body weight (- 9.0 kg and – 7.2 kg), and BMI (- 3.3 kg/m² and – 2.5 kg/m²) were observed for oral and subcutaneous semaglutide, respectively. No statistically significant differences between the formulations were observed, and safety profiles were comparable.

CONCLUSIONS: Both formulations of semaglutide provided clinically and statistically significant reductions in HbA_1c and weight in real-world practice. Oral GLP-1 RA may offer a practical and effective option for the management of T2D.

PMID:38427165 | DOI:10.1007/s13300-024-01551-4

Diabetes Ther. 2024 Mar 1. doi: 10.1007/s13300-024-01542-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Optimal glycemic management after diabetes onset remains a challenge in Hispanic/Latino adults with type 2 diabetes (T2D), often resulting in poor health outcomes and higher rates of diabetes-related complications. The aim of this study was to examine and compare demographic and clinical characteristics, glycemic outcomes, health care resource utilization (HCRU), and costs among injection-naïve Hispanic/Latino adults with T2D initiating dulaglutide or basal insulin.

METHODS: This retrospective, observational study used administrative claims data from the Optum Research Database. Hispanic/Latino adults with T2D were assigned to dulaglutide or basal insulin cohorts on the basis of pharmacy claims and were propensity-score matched on demographic and baseline characteristics. Measures of glycemic management included 12 month follow-up glycated hemoglobin (HbA1c) and change in HbA1c from baseline. Follow-up all-cause and diabetes-related HCRU and costs, including costs per 1% change in HbA1c, were compared between cohorts.

RESULTS: The final propensity-score matched sample included 2872 patients: 1436 patients in each cohort. Mean (SD) reduction in HbA1c from baseline to 12 month follow-up was greater in the dulaglutide cohort compared with the basal insulin cohort [-1.40% (1.88) versus -0.92% (2.07); p < 0.001]. The dulaglutide cohort had significantly lower proportions of patients with ≥ 1 all-cause and diabetes-related outpatient visits, emergency room visits, and inpatient stays compared with the basal insulin cohort (p < 0.05). The dulaglutide cohort had significantly lower all-cause total costs per 1% HbA1c reduction than the basal insulin cohort ($13,768 versus $19,128; p < 0.001). Diabetes-related costs per 1% reduction were numerically lower for the dulaglutide cohort, but the difference was not statistically significant ($9737 versus $11,403; p = 0.081).

CONCLUSIONS: Dulaglutide demonstrated better glycemic outcomes and lower all-cause costs per 1% HbA1c reduction among Hispanic/Latino adults compared with those initiating basal insulin. Our real-world findings in the Hispanic/Latino population were consistent with results obtained from the overall population and confirm the glycemic benefits of dulaglutide observed in clinical settings.

PMID:38427164 | DOI:10.1007/s13300-024-01542-5

Lifetime Data Anal. 2024 Mar 1. doi: 10.1007/s10985-024-09622-1. Online ahead of print.

ABSTRACT

Linear mixed models are traditionally used for jointly modeling (multivariate) longitudinal outcomes and event-time(s). However, when the outcomes are non-Gaussian a quantile regression model is more appropriate. In addition, in the presence of some time-varying covariates, it might be of interest to see how the effects of different covariates vary from one quantile level (of outcomes) to the other, and consequently how the event-time changes across different quantiles. For such analyses linear quantile mixed models can be used, and an efficient computational algorithm can be developed. We analyze a dataset from the Acute Lymphocytic Leukemia (ALL) maintenance study conducted by Tata Medical Center, Kolkata. In this study, the patients suffering from ALL were treated with two standard drugs (6MP and MTx) for the first two years, and three biomarkers (e.g. lymphocyte count, neutrophil count and platelet count) were longitudinally measured. After treatment the patients were followed nearly for the next three years, and the relapse-time (if any) for each patient was recorded. For this dataset we develop a Bayesian quantile joint model for the three longitudinal biomarkers and time-to-relapse. We consider an Asymmetric Laplace Distribution (ALD) for each outcome, and exploit the mixture representation of the ALD for developing a Gibbs sampler algorithm to estimate the regression coefficients. Our proposed model allows different quantile levels for different biomarkers, but still simultaneously estimates the regression coefficients corresponding to a particular quantile combination. We infer that a higher lymphocyte count accelerates the chance of a relapse while a higher neutrophil count and a higher platelet count (jointly) reduce it. Also, we infer that across (almost) all quantiles 6MP reduces the lymphocyte count, while MTx increases the neutrophil count. Simulation studies are performed to assess the effectiveness of the proposed approach.

PMID:38427151 | DOI:10.1007/s10985-024-09622-1

J Gastrointest Cancer. 2024 Mar 1. doi: 10.1007/s12029-024-01028-4. Online ahead of print.

ABSTRACT

BACKGROUND: Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive.

METHODS: In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS.

RESULTS: Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment.

CONCLUSIONS: This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

PMID:38427147 | DOI:10.1007/s12029-024-01028-4

Pediatr Cardiol. 2024 Mar 1. doi: 10.1007/s00246-024-03440-w. Online ahead of print.

ABSTRACT

Pediatric cardiology fellows receive limited training on delivering serious news. This is a teachable skill through simulation-based communication. While studies have shown the use of communication courses in pediatrics, there have been none in pediatric cardiology. Pediatric cardiologists recognize the importance of good communication and desire further development of these skills. Based on an internal needs assessment, three cases were developed; fetal hypoplastic left heart syndrome, teenager with new hypertrophic cardiomyopathy, and young-adult with Fontan failure. A 4-h simulation course using evidence-based methods to teach delivering serious news was designed, consisting of a didactic session, case demonstration and small group case-based encounters with simulated patients. Trainees completed standardized pre/post-course surveys to assess perception of skill and preparedness. Paired survey responses were compared. Six pediatric cardiology fellows participated. Only 33% had received formal training in delivering serious news and 17% in techniques of responding to patient’s emotions. The proportion of participants who felt good about their ability to deliver serious news and deal with a family’s emotions increased from 0 to 83%. The proportion of participants who felt prepared to provide serious news about a patient’s illness increased from 17 to 67%. Given the small number of participants, results were not statistically significant. All participants felt that the course was valuable in improving communication skills. A formal communication course increased perception of skill and preparedness among trainees. We provide an evidence-based framework and clinical cases for delivering serious news in pediatric cardiology, which is generalizable to other training programs.

PMID:38427088 | DOI:10.1007/s00246-024-03440-w

Diabetologia. 2024 Mar 1. doi: 10.1007/s00125-024-06116-5. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.

METHODS: Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.

RESULTS: While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.

CONCLUSIONS/INTERPRETATION: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05095259.

PMID:38427076 | DOI:10.1007/s00125-024-06116-5