Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function.

Nervous system function rests on the formation of functional synapses between neurons. We have identified TRMT9B as a new regulator of synapse formation and function in Drosophila. TRMT9B has been studied for its role as a tumor suppressor and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Whereas Trm9 homolog ALKBH8 is ubiquitously expressed, TRMT9B is enriched in the nervous system. However, in the absence of animal models, TRMT9B's role in the nervous system has remained unstudied. Here, we generate null alleles of TRMT9B and find it acts postsynaptically to regulate synaptogenesis and promote neurotransmission. Through liquid chromatography-mass spectrometry, we find that ALKBH8 catalyzes canonical tRNA wobble uridine methylation, raising the question of whether TRMT9B is a methyltransferase. Structural modeling studies suggest TRMT9B retains methyltransferase function and, in vivo, disruption of key methyltransferase residues blocks TRMT9B's ability to rescue synaptic overgrowth, but not neurotransmitter release. These findings reveal distinct roles for TRMT9B in the nervous system and highlight the significance of tRNA methyltransferase family diversification in metazoans.

Predicting psoriasis severity using machine learning: A systematic review.

In dermatology, the applications of machine learning (ML), an artificial intelligence (AI) subset that enables machines to learn from experience, have progressed past the diagnosis and classification of skin lesions. A lack of systematic reviews exists to explore the role of ML in predicting the severity of psoriasis. This systematic review aims to identify and summarize the existing literature on predicting psoriasis severity using ML algorithms and identify gaps in current clinical applications of these tools. OVID Embase, OVID MEDLINE, ACM Digital Library, Scopus, and IEEE Xplore were searched from inception to August, 2024. A total of 30 articles met our inclusion criteria and were included in this review. One article used serum biomarkers, while the remaining 29 used image-based models. The most common severity assessment score employed by these ML models was the Psoriasis Area Severity Index score, followed by Body Surface Area, with fifteen and five articles, respectively. The small size and heterogeneity of the existing literature are the primary limitations of this review. Progress in assessing skin lesion severity through ML in dermatology has advanced, but prospective clinical applications remain limited. ML and AI promise to improve psoriasis management, especially in non-image-based applications requiring further exploration. Large-scale prospective trials using diverse image datasets are necessary to evaluate and predict the clinical value of these predictive AI models.

Robotic-Assisted Surgery-a Highly Effective Modality for Vesicovaginal Fistula Repairs.

PURPOSE OF REVIEW: To summarize recent experience with robotic vesicovaginal fistula repair and describe the contemporary technique. RECENT FINDINGS: Robotic vesicovaginal repair has been tested at multiple centers, with similar outcomes to open surgery. It has benefits including decreased hospital stay, less blood loss, and similar long-term outcomes. As long as the surgeon is experienced in robotic surgery, this technique appears to be promising. Robotic vesicovaginal repair results in similar outcomes to open surgery with decreased morbidity.

Active and productive ageing in India: evidence from the time use pattern of ageing adults.

BACKGROUND: With the increasing proportion of older adults in India, it becomes essential to get an insight into the various influencing factors of successful ageing. However, the literature on successful ageing is minuscule in the Indian context. The present study attempted to understand successful ageing in terms of active and productive ageing by exploring their determining factors. METHODS: The data were extracted from the Longitudinal Ageing Study in India (LASI) Wave-1 (2017-2018). We utilized self-reported time use information from the experimental module of the LASI. A total of 7837 ageing adults were included in the study. We employed descriptive statistics, bivariate analysis and a multinominal logistic regression model to examine the prevalence and the determinants of active and productive ageing. RESULTS: The prevalence of inactive ageing was higher among the Indian ageing population (57.47%), followed by active ageing (29.59%) and productive ageing (12.94%). Poor sleep quality and the prevalence of morbidity and disability limited the ageing population from attaining active and productive ageing. Engagement in physical activity was significantly associated with active and productive ageing (ß = 0.83, 99% CI: -0.72-0.94 and ß = 0.82, 99% CI: 0.66-0.98), respectively. Rural ageing adults were more likely to attain active ageing and less likely to attain productive ageing. CONCLUSION: Engagement in physical activities among the ageing population shall be promoted to attain active and productive ageing. Since the rural ageing population were less likely to attain productive ageing than their urban counterparts, opportunities to participate in more formal economic activities in rural areas could be promoted for the wellbeing of the second demographic dividend.

Distress return migration amid COVID-19: Kerala's response.

Emigrants from Kerala, India, were among the international migrants affected by the displacing consequences of COVID-19 - job losses, decreasing wages, inadequate social protection systems, xenophobia and overall uncertainty - which led to large-scale return migration to India. Returning home due to exogenous shocks calls into question the voluntary nature of return, the ability of returnees to reintegrate and the sustainability of re-embedding in the home country. The role of return migrants in the development of their societies of origin is also unclear. In this commentary, we explore the circumstances of return migration since the beginning of the COVID-19 pandemic by focusing on a case study of Kerala and provide insights on the future of emigration from this corridor along with policy suggestions. The role of return migrants in the development of their societies of origin requires further research and policy interventions.

Correlation of arterial PaCO2 to end tidal CO2 in children undergoing laparoscopic abdominal surgery: An observational study.

Background and Aims: The reliability of end tidal carbon dioxide (ETCO2) as a measure of arterial carbon dioxide (PaCO2) in pediatric laparoscopy is unclear. We evaluated the correlation of arterial to end tidal P(a-ET) CO2 during pediatric laparoscopy at two hours of pneumoperitoneum as the primary objective. We also compared P(a-ET) CO2 and alveolar to arterial oxygen gradient P(A-a) O2 and haemodynamics at fixed time points during surgery. Material and Methods: A cross-sectional study was conducted in 25 children undergoing laparoscopic abdominal surgery. Arterial blood gases were drawn at T0, baseline, T10: ten minutes, T1h: 1 hour, T2h: 2 hours of pnuemoperitoneum and T 10d: 10 mins after deflation. The P(a-ET) CO2, P(A-a) O2, were measured from the blood gas and ETCO2 and FiO2 values on the monitor. The Pearson's correlation coefficient, the Wilcoxon rank test and Chi square test were used for statistical analysis. Results: At T2h moderate correlation of P(a-ET) CO2 (r = 0.605, P = 0.001) with 40% children documenting accurate P(a-ET) CO2, -1 to +1 mm Hg was seen. Moderate correlation was also seen at T0, T10, T 10d but poor correlation at T 1h. The P(A-a) O2 increased progressively with surgery and did not correlate with P(a-ET) CO2. Heart rate was stable, but systolic blood pressures at T 10 and diastolic at T10, T 1h, T 2h were higher than baseline. Conclusion: Moderate correlation was seen between PaCO2 and ETCO2 at 2 h of pnuemoperitoneum and at T0, T 10, and T 10d. P(A-a) O2 increased with surgery but did not correlate with P(a-ET) CO2.

Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial.

BACKGROUND: The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. METHODS: In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. RESULTS: Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III-IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). CONCLUSION: Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.

Computer-Based Substance Use Reporting and Acceptance of HIV Testing Among Emergency Department Patients.

More than 10 years after the Centers for Disease Control and Prevention recommended routine HIV testing for patients in emergency departments (ED) and other clinical settings, as many as three out of four patients may not be offered testing, and those who are offered testing frequently decline. The current study examines how participant characteristics, including demographics and reported substance use, influence the efficacy of a video-based intervention designed to increase HIV testing among ED patients who initially declined tests offered by hospital staff. Data from three separate trials in a high volume New York City ED were merged to determine whether patients (N = 560) were more likely to test post-intervention if: (1) they resembled people who appeared onscreen in terms of gender or race; or (2) they reported problem substance use. Chi Square and logistic regression analyses indicated demographic concordance did not significantly increase likelihood of accepting an HIV test. However, participants who reported problem substance use (n = 231) were significantly more likely to test for HIV in comparison to participants who reported either no problem substance use (n = 190) or no substance use at all (n = 125) (x2 = 6.830, p < 0.05). Specifically, 36.4% of patients who reported problem substance use tested for HIV post-intervention compared to 30.5% of patients who did not report problem substance use and 28.8% of participants who did not report substance use at all. This may be an important finding because substance use, including heavy alcohol or cannabis use, can lead to behaviors that increase HIV risk, such as sex with multiple partners or decreased condom use.

Machine Learning-Based Segmentation of Left Ventricular Myocardial Fibrosis from Magnetic Resonance Imaging.

PURPOSE OF REVIEW: Myocardial fibrosis (MF) arises due to myocardial infarction and numerous cardiac diseases. MF may lead to several heart disorders, such as heart failure, arrhythmias, and ischemia. Cardiac magnetic resonance (CMR) imaging techniques, such as late gadolinium enhancement (LGE) CMR, enable non-invasive assessment of MF in the left ventricle (LV). Manual assessment of MF on CMR is a tedious and time-consuming task that is subject to high observer variability. Automated segmentation and quantification of MF is important for risk stratification and treatment planning in patients with heart disorders. This article aims to review the machine learning (ML)-based methodologies developed for MF quantification in the LV using CMR images. RECENT FINDINGS: With the availability of relatively large labeled datasets supervised learning methods based on both conventional ML and state-of-the-art deep learning (DL) methods have been successfully applied for automated segmentation of MF. The incorporation of ML algorithms into imaging techniques such as 3D LGE CMR permits fast characterization of MF on CMR imaging and may enhance the diagnosis and prognosis of patients with heart disorders. Concurrently, the studies using cine CMR images have revealed that accurate segmentation of MF on non-contrast CMR imaging might be possible. The application of ML/DL tools in CMR image interpretation is likely to result in accurate and efficient quantification of MF.

Immune activation markers in individuals with HIV-1 disease and their correlation with HIV-1 RNA levels in individuals on antiretroviral therapy.

BACKGROUND: Currently CD4+ T lymphocyte counts and HIV-1 RNA levels are being utilized to predict outcome of human immunodeficiency virus (HIV) disease. Recently, the role of immune activation in HIV disease progression and response to treatment is being investigated. This study focused on the expression of CD38 and HLA-DR on lymphocyte subsets in various groups of HIV-infected individuals and to determine their association with HIV-1 disease progression. METHODS: Ninety-eight cases of patients with HIV/AIDS in different disease stages and twenty-four healthy HIV-negative individuals were included in the cross-sectional study. Their immune function and abnormal immune activation markers (CD38 & HLA-DR) were detected using a flowcytometer, and HIV-1 RNA levels in individuals receiving antiretroviral drugs were estimated. RESULTS: The immune activation marker levels were significantly different between patients with different disease stages (P < 0.001). A significant negative correlation was observed between peripheral blood CD4+ T cell counts and immune activation markers. Also, a significant positive correlation was observed between HIV-1 RNA levels and CD38+CD8+ T lymphocyte. CONCLUSION: Immune activation markers (CD38 & HLA-DR) increase with disease progression. CD38+ on CD8+ T lymphocyte correlates well with HIV1 RNA levels in individuals failing on antiretroviral therapy.

Fog Computing Employed Computer Aided Cancer Classification System Using Deep Neural Network in Internet of Things Based Healthcare System.

Computer assisted automatic smart pattern analysis of cancer affected pixel structure takes critical role in pre-interventional decision making for oral cancer treatment. Internet of Things (IoT) in healthcare systems is now emerging solution for modern e-healthcare system to provide high quality medical care. In this research work, we proposed a novel method which utilizes a modified vesselness measurement and a Deep Convolutional Neural Network (DCNN) to identify the oral cancer region structure in IoT based smart healthcare system. The robust vesselness filtering scheme handles noise while reserving small structures, while the CNN framework considerably improves classification accuracy by deblurring focused region of interest (ROI) through integrating with multi-dimensional information from feature vector selection step. The marked feature vector points are extracted from each connected component in the region and used as input for training the CNN. During classification, each connected part is individually analysed using the trained DCNN by considering the feature vector values that belong to its region. For a training of 1500 image dataset, an accuracy of 96.8% and sensitivity of 92% is obtained. Hence, the results of this work validate that the proposed algorithm is effective and accurate in terms of classification of oral cancer region in accurate decision making. The developed system can be used in IoT based diagnosis in health care systems, where accuracy and real time diagnosis are essential.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Molecular analysis of anthocyanin biosynthesis pathway genes and their differential expression in mango peel.

Mango fruit is cherished by masses for its taste and nutrition, contributed by color, flavor, and aroma. Among these, peel color is an important trait contributing to fruit quality and market value. We attempted to elucidate the role of key genes of the anthocyanin biosynthesis pathway related to fruit peel color from the leaf transcriptome of mango cultivar Amrapali. A total of 108 mined transcript sequences were assigned to the phenylpropanoid-flavonoid pathway from which 15 contigs representing anthocyanin biosynthesis genes were annotated. Alternate splice variants were identified by mapping against genes of Citrus clementina and Vitis vinifera (closest relatives) and protein subcellular localization was determined. Phylogenetic analysis of these pathway genes clustered them into distinct groups aligning with homologous genes of Magnifera indica, C. clementina, and V. vinifera. Expression profiling revealed higher relative fold expressions in mature fruit peel of red-colored varieties (Arunika, Ambika, and Tommy Atkins) in comparison with the green-peeled Amrapali. MiCHS, MiCHI, and MiF3H alternate splice variants revealed differential gene expression. Functionally divergent variants indicate availability of an allelic pool programmed to play critical roles in peel color. This study provides insight into the molecular genetic basis of peel color and offers scope for development of biomarkers in varietal improvement programs.

Steroid administration after anaesthetic induction with etomidate does not reduce in-hospital mortality or cardiovascular morbidity after non-cardiac surgery.

BACKGROUND: We tested the primary hypothesis that corticosteroid administration after etomidate exposure reduces a composite of in-hospital mortality and cardiovascular morbidity after non-cardiac surgery. METHODS: We evaluated ASA physical status III and IV patients who had non-cardiac surgery with general anaesthesia at the Cleveland Clinic. Amongst 4275 patients in whom anaesthesia was induced with etomidate, 804 were also given steroid intraoperatively, mostly dexamethasone at a median dose of 6 mg. We successfully matched 582 steroid patients with 1023 non-steroid patients. The matched groups were compared on composite of in-hospital mortality and cardiovascular morbidity using a generalized-estimating-equation model. Secondly, the matched groups were compared on length of hospital stay using a Cox proportional hazard model, and were descriptively compared on intraoperative blood pressures using a standardized difference. RESULTS: There was no significant association between intraoperative steroid administration after anaesthetic induction with etomidate and the composite of in-hospital mortality or cardiovascular morbidity; the estimated common odds ratio across the two components of the composite was 0.86 [95% confidence interval (CI): 0.64, 1.16] for steroid vs non-steroid, P=0.33. The duration of postoperative hospitalisation was significantly shorter amongst steroid patients [median (Q1, Q3): 6 (3, 10) days] than non-steroid patients [7 (4, 11) days], with an estimated hazard ratio of 0.89 (0.80, 0.98) for steroid vs non-steroid, P=0.01. Intraoperative blood pressures were similar in steroid and non-steroid patients. CONCLUSIONS: Steroid administration after induction of anaesthesia with etomidate did not reduce mortality or cardiovascular morbidity.

Causes, consequences, and policy responses to the migration of health workers: key findings from India.

BACKGROUND: This study sought to better understand the drivers of skilled health professional migration, its consequences, and the various strategies countries have employed to mitigate its negative impacts. The study was conducted in four countries-Jamaica, India, the Philippines, and South Africa-that have historically been "sources" of health workers migrating to other countries. The aim of this paper is to present the findings from the Indian portion of the study. METHODS: Data were collected using surveys of Indian generalist and specialist physicians, nurses, midwives, dentists, pharmacists, dieticians, and other allied health therapists. We also conducted structured interviews with key stakeholders representing government ministries, professional associations, regional health authorities, health care facilities, and educational institutions. Quantitative data were analyzed using descriptive statistics and regression models. Qualitative data were analyzed thematically. RESULTS: Shortages of health workers are evident in certain parts of India and in certain specialty areas, but the degree and nature of such shortages are difficult to determine due to the lack of evidence and health information. The relationship of such shortages to international migration is not clear. Policy responses to health worker migration are also similarly embedded in wider processes aimed at health workforce management, but overall, there is no clear policy agenda to manage health worker migration. Decision-makers in India present conflicting options about the need or desirability of curtailing migration. CONCLUSIONS: Consequences of health work migration on the Indian health care system are not easily discernable from other compounding factors. Research suggests that shortages of skilled health workers in India must be examined in relation to domestic policies on training, recruitment, and retention rather than viewed as a direct consequence of the international migration of health workers.

Refugee child oral health.

The number of people forced to flee their homes and move around the world is increasing rapidly. Such refugee populations are not only more likely to have poor physical, mental and social health outcomes but also to experience difficulties accessing health services in their new country. In particular, children from refugee backgrounds are at increased risk of poor oral health which in time is associated with poor adult oral health and impacts on child health (e.g. growth and development) and well-being. To date, there is little evidence about the nature and extent of their oral health problems nor interventions to improve their oral health status. This article summarises the evidence surrounding the oral health status of children from refugee backgrounds. In addition, a systematic review of the international literature over the past 10 years is presented which identifies interventions to improve the oral health of these vulnerable paediatric populations. Based on this evidence, potential strategies available to dental service providers to optimise provision of responsive dental care are discussed.

Perioperative factors associated with acute kidney injury after partial nephrectomy.

BACKGROUND: Partial nephrectomy is performed with the aim to preserve renal function. But the occurrence of postoperative acute kidney injury (AKI) can interfere with this goal. Our primary aim was to evaluate associations between pre-specified modifiable factors and estimated glomerular filtration rate after partial nephrectomy. Our secondary aims were to evaluate associations between pre-specified modifiable factors and both serum creatinine concentration and type of nephrectomy. METHODS: The records of 1955 patients who underwent partial nephrectomy were collected. Postoperative estimated glomerular filtration rate (eGFR) was used as the primary outcome measure. Twenty modifiable risk factors were studied. A repeated-measures linear model with autoregressive within-subject correlation structure was used. The interaction between all the factors and type of nephrectomy was also studied. RESULTS: A total of 1187 (61%) patients had no kidney injury, 647 (33%) had stage I, 80 (4%) had stage II, and 41 (2%) had stage III injury. The mean eGFR increased an estimated 0.83 (99.76% CI 0.79-0.88) ml min(-1) 1.73 m(-2) for a unit increase in baseline eGFR. Mean eGFR was 2.65 (99.76% CI: 0.13, 5.18) ml min(-1) 1.73 m(-2) lower in patients with hypertension. Mean eGFR decreased 0.42 (99.76% CI: 0.22, 0.62) ml min(-1) 1.73 m(-2) for a 10-minute longer in duration of procedure and decreased 2.09 (99.76% CI: 1.39, 2.80) ml min(-1) 1.73 m(-2) for a 10-minute longer in ischemia time. It was 3.53 (99.76% CI: 0.83, 6.23) ml min(-1) 1.73 m(-2) lower for patients who received warm ischemia as compared to cold ischemia. CONCLUSION: Potentially modifiable factors associated with AKI in the postoperative period were identified as baseline renal function, preoperative hypertension, longer duration of surgical time and ischaemia time, and warm ischaemia.

Variation of phytoplankton assemblages of Kongsfjorden in early autumn 2012: a microscopic and pigment ratio-based assessment.

Phytoplankton species distribution and composition were determined by using microscopy and pigment ratios in the Kongsfjorden during early autumn 2012. Variation in sea surface temperature (SST) was minimal and matched well with satellite-derived SST. Nutrients were generally limited. Surface phytoplankton abundance ranged from 0.21 × 10(3) to 10.28 × 10(3) cells L(-1). Phytoplankton abundance decreased with depth and did not show any significant correlation with chlorophyll a (chl a). Column-integrated phytoplankton cell counts (PCC) ranged from 94.3 × 10(6) cells m(-2) (Kf4) to 13.7 × 10(6) cells m(-2) (Kf5), while chl a was lowest at inner part of the fjord (6.3 mg m(-2)) and highest towards the mouth (24.83 mg m(-2)). Biomass from prymnesiophytes and raphidophytes dominated at surface and 10 m, respectively. The contribution of Bacillariophyceae to biomass was low. Generally, heterotrophic dinoflagellates were great in abundance (12.82 %) and ubiquitous in nature and were major contributors to biomass. Various chl pigments (chl b, chl c, phaeopigments (phaeo)) were measured to obtain pigment/chl a ratios to ascertain phytoplankton composition. Phaeo were observed only in inner fjord. Chl b:a ratios and microscopic observations indicated dominance of Chlorophyceae at greater depths than surface. Furthermore, microscopic observations confirmed dominance of chl c containing algae throughout the fjord. The study indicates that pigment ratios can be used as a tool for preliminary identification of major phytoplankton groups. However, under the presence of a large number of heterotrophic dinoflagellates such as Gymnodinium sp. and Gyrodinium sp., pigment signatures need to be supplemented by microscopic observations.