Effects of transcutaneous electrical nerve stimulation on recovery of gastrointestinal motility after laparotomy: A randomized controlled trial.

INTRODUCTION: Postoperative Ileus (POI) negatively impacts patient outcomes and increases healthcare costs. Transcutaneous electrical nerve stimulation (TENS) has been found to improve gastrointestinal (GI) motility following abdominal surgery. However, its effectiveness in this context is not well-established. This study was designed to evaluate the role of TENS on the recovery of GI motility after exploratory laparotomy. METHODS: Patients undergoing exploratory laparotomy were randomized in a 1:1 ratio into control (standard treatment alone) and experimental (standard treatment + TENS) arms. TENS was terminated after 6 days or after the passage of stool or stoma movement. The primary outcome was time for the first passage of stool/functioning stoma. Non-passage of stool or nonfunctioning stoma beyond 6 days was labeled as prolonged POI. Patients were monitored until discharge. RESULTS: Median (interquartile range) time to first passage of stool/functioning stoma was 82.6 (49-115) hours in the standard treatment group and 50 (22-70.6) hours in the TENS group [p < 0.001]. Prolonged POI was noted in 11 patients in the standard treatment group (35.5%) and one in the TENS group (3.2%) [p = 0.003]. Postoperative hospital stay was similar in the two groups. CONCLUSION: TENS resulted in early recovery of GI motility by shortening the duration of POI without any improvement in postoperative hospital stay. TRIAL REGISTRATION NUMBER: CTRI/2021/10/037054.

Arexvy: A Comprehensive Review of the Respiratory Syncytial Virus Vaccine for Revolutionary Protection.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.

The Role of Hindu Mandirs in Addressing Intimate Partner Violence Among South Asian American Communities.

There is a growing body of literature that documents high rates of intimate partner violence within South Asian American communities, indicating a critical need for research that can respond directly to this issue. From a socioecological perspective, Hindu temples can influence members' behaviors at multiple levels of change and thus may be important sites of collaboration for the prevention of intimate partner violence. Through in-depth qualitative interviews with South Asian families, temple leaders, and community stakeholders, this study indicates that Hindu temples have tremendous capacity to significantly impact intimate partner violence within South Asian American communities.

PHLPP1 regulates PINK1-parkin signalling and life span.

Adaptability to intracellular or extracellular cues is essential for maintaining cellular homeostasis. Metabolic signals intricately control the morphology and functions of mitochondria by regulating bioenergetics and metabolism. Here, we describe the involvement of PHLPP1, a Ser/Thr phosphatase, in mitochondrial homeostasis. Microscopic analysis showed the enhanced globular structure of mitochondria in PHLPP1-depleted HEK 293T and C2C12 cells, while forced expression of PHLPP1 promoted mitochondrial tubularity. We show that PHLPP1 promoted pro-fusion markers MFN2 and p-DRP1Ser637 levels using over-expression and knockdown strategies. Contrastingly, PHLPP1 induced mitochondrial fragmentation by augmenting pro-fission markers, t-DRP1 and pDrp1Ser616 upon mitochondrial stress. At the molecular level, PHLPP1 interacted with and caused dephosphorylation of calcineurin, a p-DRP1Ser637 phosphatase, under basal conditions. Likewise, PHLPP1 dimerized with PINK1 under basal conditions. However, the interaction of PHLPP1 with both calcineurin and PINK1 was impaired upon CCCP and oligomycin-induced mitochondrial stress. Interestingly, upon mitochondrial membrane depolarization, PHLPP1 promoted PINK1 stabilization and parkin recruitment to mitochondria, and thereby activated the mitophagy machinery providing a molecular explanation for the dual effects of PHLPP1 on mitochondria under different conditions. Consistent with our in-vitro findings, depletion of phlp-2, ortholog of PHLPP1 in C. elegans, led to mitochondrial fission under basal conditions, extended the lifespan of the worms, and enhanced survival of worms subjected to paraquat-induced oxidative stress.

Spatiotemporal evolution of sea ice and its teleconnections with large-scale climate indices over Antarctica.

Sea ice variability patterns are highly influenced by several large-scale ocean-atmospheric oscillations. We analysed both statistical and wavelet coherence methods to examine sea ice's interannual and interdecadal variability. During the past 42-year, the total Southern Ocean sea ice extent (SIE) has expanded, while the Amundsen-Bellingshausen Sea SIE has decreased. A wavelet coherence analysis (WCA) of El Niño Southern Oscillation (ENSO) and the SIE in various sectors revealed an out-of-phase correlation between the Indian Ocean and the Ross Sea. There are significant out-of-phase correlations between sea ice variability and Indian Ocean Dipole (IOD) on an interannual scale. A consistent phase relationship was seen between SIE and Southern Annular Mode (SAM) over the past decade, with in-phase relationships advancing to out-of-phase relationships. The Interdecadal Pacific Oscillation (IPO) shifted from positive to negative after the 1990s. In recent years, SAM has had a stronger impact on sea ice variability than ENSO.

Studies of high-membered two-dimensional Ruddlesden-Popper Cs7Pb6I19 perovskite nanosheets via kinetically controlled reactions.

Two-dimensional (2D) all-inorganic Ruddlesden-Popper (RP) perovskite Cs7Pb6I19 nanosheets (NSs) were successfully developed for the first time by employing a structural recrystallization process with additional passivation of small organic sulfide molecules. The structure of Cs7Pb6I19 NSs is confirmed by powder X-ray diffraction measurements, atomically-resolved STEM measurements and atomic force microscopy (AFM) studies. Cs7Pb6I19 NSs with a specific n value of 6 exhibits unique absorption and emission spectra with intense excitons at 560 nm due to quantum confinement effects in 2D perovskite slabs. The formation mechanisms of 2D Cs7Pb6I19 NSs and 3D γ-CsPbI3 phases were investigated by in situ photoluminescence (PL) spectroscopy and the activation energies of their formation reactions were calculated to be 151 kJ mol-1 and 95.3 kJ mol-1, respectively. The phase stability of 2D Cs7Pb6I19 NSs can be maintained at temperatures below 14 °C for more than 4 weeks. The overall results indicate that 2D Cs7Pb6I19 NSs demonstrate unique optical properties and structural stability compared with other 3D perovskite materials. We have opened a new path to the future discovery of 2D perovskite structures with metastable phases by using this recrystallization method and the assistance of sulfur-derived organic molecules.

PHLPPs: Emerging players in metabolic disorders.

That reversible protein phosphorylation by kinases and phosphatases occurs in metabolic disorders is well known. Various studies have revealed that a multi-faceted and tightly regulated phosphatase, pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP)-1/2 displays robust effects in cardioprotection, ischaemia/reperfusion (I/R), and vascular remodelling. PHLPP1 promotes foamy macrophage development through ChREBP/AMPK-dependent pathways. Adipocyte-specific loss of PHLPP2 reduces adiposity, improves glucose tolerance,and attenuates fatty liver via the PHLPP2-HSL-PPARα axis. Discoveries of PHLPP1-mediated insulin resistance and pancreatic ß cell death via the PHLPP1/2-Mst1-mTORC1 triangular loop have shed light on its significance in diabetology. PHLPP1 downregulation attenuates diabetic cardiomyopathy (DCM) by restoring PI3K-Akt-mTOR signalling. In this review, we summarise the functional role of, and cellular signalling mediated by, PHLPPs in metabolic tissues and discuss their potential as therapeutic targets.

Accelerated Formation of 2D Ruddlesden-Popper Perovskite Thin Films by Lewis Bases for High Efficiency Solar Cell Applications.

Various types of 2D organic-inorganic perovskite solar cells have been developed and investigated due to better electron transport behavior and environmental stability. Controlling the formation of phases in the 2D perovskite films has been considered to play an important role in influencing the stability of perovskite materials and their performance in optoelectronic applications. In this work, Lewis base urea was used as an effective additive for the formation of 2D Ruddlesden-Popper (RP) perovskite (BA)2(MA)n-1PbnI3n+1 thin film with mixed phases (n = 2~4). The detailed structural morphology of the 2D perovskite thin film was investigated by in situ X-ray diffraction (XRD), grazing-incidence small-angle X-ray scattering (GISAXS) and photoluminescence mapping. The results indicated that the urea additive could facilitate the formation of 2D RP perovskite thin film with larger grain size and high crystallinity. The 2D RP perovskite thin films for solar cells exhibited a power conversion efficiency (PCE) of 7.9% under AM 1.5G illumination at 100 mW/cm2.

Anticoagulation Management and Outcomes in Patients With Covid-19 With Propensity Score Matching: A Multicenter Retrospective Cohort Study.

BACKGROUND: Therapeutic doses of anticoagulation have been administered to patients with coronavirus-19 disease (Covid-19) without thromboembolism, although there is a lack of robust evidence supporting this practice. STUDY QUESTION: To compare outcomes between patients admitted to the hospital for Covid-19 who received full-dose anticoagulation purely for the indication of Covid-19 and patients who received prophylactic doses of anticoagulation. STUDY DESIGN: This is a multicenter retrospective cohort study, including 7 community hospitals in Michigan. Patients were >18 years of age, confirmed positive for Covid-19 by polymerase chain reaction, and admitted to the hospital between March 10 and May 3, 2020. Exposed group: Patients receiving therapeutic dose anticoagulation for Covid-19 for any duration excluding clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction; control group: Patients receiving prophylactic anticoagulation. Propensity score matching was used to adjust for the nonrandomized nature of the study. MEASURES AND OUTCOMES: The primary endpoint: 30-day in-hospital mortality. Secondary endpoints: intubation, length of hospital stay, and readmissions in survivors. RESULTS: A total of 115 exposed and 115 control patients were analyzed. Rates of 30-day in-hospital mortality were similar (exposed: 33.0% vs. control: 28.7%). Controlling for institution, there was no significant association between treatment and 30-day in-hospital mortality (hazard ratio: 0.63; 95% confidence interval: 0.37-1.06). Survivors had statistically similar length of hospital stay and readmission rates. CONCLUSIONS: We found no difference in mortality in patients with Covid-19 without clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction who received therapeutic versus prophylactic doses of anticoagulation.

Mechanisms of change in drinking following an alcohol-related injury: A qualitative examination of the sentinel event effect.

Background: Sentinel events are negative health-related events that trigger change in risky health behaviors. Despite its presumed major role in behavior change, the sentinel event effect has received little empirical attention. Through analysis of qualitative interviews, we explored how sentinel events trigger behavior change. Methods: Thematic analysis and concept mapping were used to develop a preliminary model of the sentinel event effect among a sample of 24 adult heavy drinking Mexican-origin men previously admitted to a hospital due to injury. The model was checked against cases that did versus did not report change in alcohol use following an alcohol-related negative event. Results: Findings suggest that sentinel events may arouse negative emotional reactions, encourage reflection on the negative consequences of drinking, and cause reevaluation of the severity and significance of drinking. These processes may increase motivation to change. Conclusions: Findings support the concept of the sentinel event as a natural intervention, and identifies potential social-cognitive and motivational mechanisms through which it influences change. Findings stand to inform research on mechanisms underlying brief intervention effects, and research that seeks to identify treatment targets.

Standardization of a cone beam computed tomography machine in evaluating bone density: a novel approach.

BACKGROUND: Advent of cone beam computed tomography (CBCT) in dentistry has brought us to a new era of precise imaging. Radiographic evaluation of a CBCT image is more informational when compared to CT. The density measurements in CBCT images are based on greyscale values, which are more accurate in CT and these values are inconsistent across various CBCT machines. Hence, we aim at standardizing a single CBCT scanner to evaluate or determine tissue density from the greyscale values. METHODS: A total of 8 halves of undamaged, dry goat mandibles are included in the study. Scans of the bone are obtained using the KODAK CBCT unit and the PHILLIPS CT machine respectively. Densities are evaluated at 96 points on both the CT scans and the CBCT scans, respectively, using the Radiant Dicom viewer. The obtained data is entered into the excel spreadsheet and subjected to statistical analysis. RESULTS: The greyscale values are obtained from each of the CBCT scans. Hounsfield units are calculated from CT images coinciding with the same points on CBCT scans. The collected data is subjected to linear regression analysis and an equation is derived to determine Hounsfield units (calculated HU units) from greyscale values of CBCT images. We found no significant difference between the mean original HU units and the mean calculated HU units, thus making the equation reliable for calculating HU units from CBCT greyscale values. CONCLUSIONS: Our results conclude that the technique was effective in calculating the Original density of tissues using grey standards of CBCT scans.

Lead exposure induces metabolic reprogramming in rat models.

Lead is a toxin of great public health concern affecting the young and aging population. Several factors such as age, gender, lifestyle, dose, and genetic makeup result in interindividual variations to lead toxicity mainly due to variations in metabolic consequences. Hence, the present study aimed to examine dose-dependent lead-induced systemic changes in metabolism using rat model by administering specific doses of lead such as 10 (low lead; L-Pb), 50 (moderate lead; M-Pb), and 100 mg/kg (high lead; H-Pb) body weight for a period of one month. Biochemical and haematological analysis revealed that H-Pb was associated with low body weight and feed efficiency, low total protein levels (p ≤ 0.05), high blood lead (Pb-B) levels (p ≤ 0.001), low ALAD (δ-aminolevulinate dehydratase) activity (p ≤ 0.0001), high creatinine (p ≤ 0.0001) and blood urea nitrogen (BUN) (p ≤ 0.01) levels, elevated RBC and WBC counts, reduced haemoglobin and blood cell indices compared to control. Spatial learning and memory test revealed that H-Pb exposed animals presented high latency to the target quadrant and escape platform compared to other groups indicating H-Pb alters cognition function in rats. Histopathological changes were observed in liver and kidney as they are the main target organs of lead toxicity. LC-MS analysis further revealed that Butyryl-L-carnitine (p ≤ 0.01) and Ganglioside GD2 (d18:0/20:0) (p ≤ 0.05) levels were significantly reduced in H-Pb group compared to all groups. Further, pathway enrichment analysis revealed abundance and significantly modulated metabolites associated with oxidative stress pathways. The present study is the first in vivo model of dose-dependent lead exposure for serum metabolite profiling.

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients.

BACKGROUND: Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. METHODS: We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. CONCLUSION: In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.

Haptoglobin improves acute phase response and endotoxin tolerance in response to bacterial LPS.

Sepsis is characterized by delayed acute phase response and lowered immune tolerance in patients. Acute phase serum proteins, like Haptoglobin (Hp), have been associated with increased mortality in bacteria mediated acute lung inflammation and sepsis in neonates. However, it's direct role in modulating the immune response by regulating pro-inflammatory mediators leading to immune tolerant state and if gender affects its expression levels during bacterial infection, especially in blood has not been fully explored. To understand its specific role in endotoxin-mediated immune response, we investigated the correlation between the rise in Hp levels on bacterial infection and its influence on the expression of pro-inflammatory mediators in male and female Whole blood (WHB) and PBMCs. Here, we observed pathogen-specific and gender-specific expression of Hp. Gonadal steroid hormones differentially influenced the Hp expression in LPS-induced WHB, where the addition of Estrogen increased Hp expression, with suppression of TNFα, in both genders. Further on evaluating, the influence of Hp on TNFα expression in endotoxin tolerance (ET), we show that increased Hp levels directly reduced TNFα expression in ET models. Interestingly, blockade of secreted Hp significantly reversed the (ET) state, confirmed by a significant rise in TNFα expression in both ex vivo and in vitro ET models, indicating a possible feedback inhibition by Hp on inflammatory mediators like TNFα. We also investigated the role of PKCδ in the regulation of LPS induced secretion of acute phase proteins (Hp) in serum, where inhibition of PKCδ, reduced secretion of anti-microbial proteins in response to LPS shown by restored bacterial growth. These findings clearly highlight the crucial role of Hp in maintaining immune tolerance via suppressing the pro-inflammatory mediators and also in preventing bacterial proliferation in blood during infection.

Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.

BACKGROUND: Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. METHODS: We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. RESULTS: We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a highly penetrant cause of speech/language disorder. CONCLUSIONS: Our findings highlight the importance of functional characterization of novel rare variants in FOXP2 in assessing the contribution of such variants to speech/language disorder and provide further insights into the molecular function of the FOXP2 protein.

A Study of Liver Function Tests in leprosy.

Leprosy is a chronic progressive granulomatous disease caused by Mycobacterium leprae. Hepatic involvement is seen in early stages of the disease. Administration of the hepatotoxic drugs like Rifampicin and Dapsone may further deteriorate the liver function. The present study was undertaken to evaluate hepatic status by studying the various liver function tests in leprosy patients and compared to healthy controls. Thirty untreated leprosy patients (18 Multibacillary, 12 Paucibacillary) with duration of illness varying from one month to three years were selected as cases. Twenty healthy age and sex matched persons were taken as controls. Hepatic functional status was evaluated by estimation of serum total bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase, total protein, albumin and globulin. Independent sample 't' test was used to compare the data. P < 0.05 was considered as significant. Except for serum total protein, there was a statistically significant difference between the mean values of all the parameters in cases when compared to controls. The present study revealed minimal derangement in hepatic function in leprosy patients. Therefore monitoring of liver function tests is very important to assess the functional status of the liver before administration of therapy in leprosy.