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Background--Gall bladder cancer is endemic in Indo gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed Background--Gall bladder cancer is endemic in Indo Gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed incidentally. Fate of these patients is vastly different and there are no standard treatment guidelines for the same. We attempted to study these patients with an aim to understand this entity better. Methods: Records of all gall bladder cases registered in the department of radiotherapy between 2015 and 2016 were retrospectively analyzed. Of the 167 cases, 36 were incidentally diagnosed. Results: They were predominantly females (Male: Female =0.2:1) with mean age of 49.5 years(±10.1 SD, Range 25-66 years ) and 35% being <\=45 years. Baseline KPS ranged from 50-90, and mean baseline weight was 53kg (± 9.2SD, Range 35-74kg ). All patients presented with pain and underwent surgery because of associated cholelithiasis in 32 (89%). Post initial diagnosis, 67% of the cases underwent resurgery at our institute and surgeries performed were radical cholecystectomy in 18(50%), open simple cholecystectomy in 8 (21%), laparoscopic simple cholecystectomy in 4 (11%) and staging laparotomy in 6 (18%) patients. Consequently stage assessment was not possible in 33% cases, 36% were stage IV while remaining 31% were stage I-III. There were 9 (25%) N1 and 2 (5%) N2 patients. Metastases were found subsequently in 11 (31%) patients. Moderately differentiated adenocarcinoma was the most common histology in 19 (53%) patients. 15(42%) patients were lost to follow up after surgery, 2(5%) were kept under observation, 15(42%) received adjuvant chemotherapy and 4 (11%) received palliative chemotherapy. Platinum based doublet was the most common regimen used in 16 (45%) patients. For a median follow up of 07 months (0-28 months), there were 9 relapses, 5 (55%) were locoregional and 4 (45%) distant. The median overall survival was 24 months. Conclusions--incidentally diagnosed gall bladder cases tend to behave differently. However locoregional and distant relapses highlight the need for aggressive surgery along with effective systemic treatment in order to alter the fate of these patients. [ABSTRACT FROM AUTHOR]

Purpose: Prospective assessment of variation in quality-of-life (QoL) in locally advanced cancer esophagus patients receiving neoadjuvant chemotherapy (NACT) versus neoadjuvant chemoradiation (NACTRT). Methods: Patients randomly allocated to NACT and NACTRT arms were assessed using validated EORTC QLQ-C30 (ver 3) and EORTC QLQ-OES18 questionnaires in hindi delivered pre and post neoadjuvant treatment. Domains assessed were Global health status (QoL), Physical (PF) and Role functioning (RF), Nausea vomiting (NV), Fatigue (FA), Eating (OESEAT), Reflux (OESRFX) and Dysphagia (OESDYS). Results: 39 fit patients of mean age 54.6 (± 10.1 SD) years were treated with NACT (n=24) or NACTRT (n=15). Pretreatment baseline scores in both arms were comparable. Post neoadjuvant treatment, significant changes in QOL, PF, RF, OESRFX, OESDYS were documented in both arms. Post NACTRT, there was worsening of FA and NV while OESEAT scores failed to improve significantly. FI did not change with either treatment. Conclusion: Both NACT and NACTRT improved dysphagia, reflux and global QOL with consequent improvement in related domains. However, fatigue, nausea-vomitting and eating were adversely affected by the treatment intensification in chemoradiation arm. Longer follow up is required to assess sustained differences. TABLE: Domain Treatment arm Pretreatment Post neoadjuvant treatment Pre vs Post treatment significance QOL NACT 47.2 ± 6.3 77.0 ± 8.2 P< 0.05 NACTRT 45.5 ± 9.8 79.9 ± 6.8 P< 0.05 PF NACT 72.2 ± 15.5 83.3 ± 11.2 P< 0.05 NACTRT 75.1 ± 12.9 87.9 ± 11 P< 0.05 RF NACT 56.2 ± 15.3 36.1 ± 36.9 P< 0.05 NACTRT 58.9 ± 13.8 30 ± 34.6 P< 0.05 FA NACT 40.2 ± 13.8 34.7 ± 18.3 P= 0.4 NACTRT 39.9 ± 13.8 51.1 ± 17.2 P< 0.05 NV NACT 29.8 ± 24 20.8 ± 16.4 P= 0.06 NACTRT 19.9 ± 21 42.2 ± 29.4 P< 0.05 FI NACT 76.3 ± 18.3 72.2 ± 12.6 P= 0.5 NACTRT 64.4 ± 19.7 68.8 ± 8.6 P= 0.1 OESEAT NACT 41.3 ± 10.8 30.2 ± 6.8 P<0.05 NACTRT 37.7 ± 7.6 33.8 ± 9.6 P= 0.6 OESRFX NACT 19.4 ± 16.7 9.7 ± 15.4 P<0.05 NACTRT 28.8 ± 11 17.7 ± 17.1 P<0.05 OESDYS NACT 59.2 ± 22 75.4 ± 29.8 P<0.05 NACTRT 57 ± 24.4 68.1 ± 33.8 P<0.05 [ABSTRACT FROM AUTHOR]

Background--Gall bladder cancer is endemic in Indo gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed Background--Gall bladder cancer is endemic in Indo Gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed incidentally. Fate of these patients is vastly different and there are no standard treatment guidelines for the same. We attempted to study these patients with an aim to understand this entity better. Methods: Records of all gall bladder cases registered in the department of radiotherapy between 2015 and 2016 were retrospectively analyzed. Of the 167 cases, 36 were incidentally diagnosed. Results: They were predominantly females (Male: Female =0.2:1) with mean age of 49.5 years(±10.1 SD, Range 25-66 years ) and 35% being <\=45 years. Baseline KPS ranged from 50-90, and mean baseline weight was 53kg (± 9.2SD, Range 35-74kg ). All patients presented with pain and underwent surgery because of associated cholelithiasis in 32 (89%). Post initial diagnosis, 67% of the cases underwent resurgery at our institute and surgeries performed were radical cholecystectomy in 18(50%), open simple cholecystectomy in 8 (21%), laparoscopic simple cholecystectomy in 4 (11%) and staging laparotomy in 6 (18%) patients. Consequently stage assessment was not possible in 33% cases, 36% were stage IV while remaining 31% were stage I-III. There were 9 (25%) N1 and 2 (5%) N2 patients. Metastases were found subsequently in 11 (31%) patients. Moderately differentiated adenocarcinoma was the most common histology in 19 (53%) patients. 15(42%) patients were lost to follow up after surgery, 2(5%) were kept under observation, 15(42%) received adjuvant chemotherapy and 4 (11%) received palliative chemotherapy. Platinum based doublet was the most common regimen used in 16 (45%) patients. For a median follow up of 07 months (0-28 months), there were 9 relapses, 5 (55%) were locoregional and 4 (45%) distant. The median overall survival was 24 months. Conclusions--incidentally diagnosed gall bladder cases tend to behave differently. However locoregional and distant relapses highlight the need for aggressive surgery along with effective systemic treatment in order to alter the fate of these patients. [ABSTRACT FROM AUTHOR]

Sydenham chorea (SC) is the neurological manifestation associated with acute rheumatic fever (ARF). ARF and rheumatic heart disease (RHD) are autoimmune complications triggered by a group A streptococcal (GAS) infection. In ARF/RHD and SC, tissue cross-reactive antibodies and T-cells generated against GAS antigens have been implicated in the pathogenesis. In SC, antibodies against GAS antigens are known to cross-react with neuronal proteins causing neurological manifestations including choreiform movements and neuropsychiatric symptoms such as irritability, attention deficit, and obsessive-compulsive disorder. Previous studies in a rat autoimmune valvulitis (RAV) model of RHD, have shown that injection of streptococcal M protein could cause both cardiac and neurological symptoms. In this study it was shown that adoptive transfer of serum with anti-GAS M antibodies to naive rats caused carditis but failed to demonstrate neurobehavioral symptoms. However, when the blood-brain barrier (BBB) was disrupted using lipopolysaccharide, all animals that received anti-GAS M protein antibodies, developed neurobehavioral defects in addition to carditis. This highlights that impaired BBB integrity is essential for the development of neurobehavioral symptoms. The use of the RAV model and the disruption of BBB required for the development of neurobehavioral changes provides a platform to further investigate the mechanisms that lead to antibodies binding to basal ganglia structures that cause SC., (© 2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Anosmia, the complete loss of olfactory perception, has been associated with sensory compensation in non-chemical senses such as vision and hearing, but its relationship with tactile perception remains unclear. This study investigates whether isolated congenital anosmia (ICA)-a rare condition in which individuals are born without a sense of smell but are otherwise healthy-is linked to heightened self-reported tactile sensitivity compared to healthy controls. Drawing on sensory compensation theory and anecdotal evidence from related studies, we hypothesized that individuals with ICA would report increased tactile sensitivity, particularly in response to discomfort. To test this hypothesis, we surveyed individuals with ICA (n = 40) and healthy controls (n = 40), matched for sex and age, using standardized questionnaires and a specially developed questionnaire focused on discomfort related to materials, food textures, stickiness, and pressure. Contrary to our pre-registered hypothesis, the results revealed no significant differences in overall self-reported touch sensitivity between the groups. However, exploratory analysis indicated that individuals with ICA exhibit greater sensitivity to temperature sensations and to overall tactile discomfort, specifically in response to pressure and food textures, compared to controls. We propose that individuals with ICA may compensate for their olfactory loss through heightened sensitivity to certain tactile stimuli related to discomfort, as both touch and olfaction play overlapping roles in the detection of aversive stimuli. These exploratory findings underscore the need for further investigation into the sensory compensation mechanisms of olfaction on touch., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The establishment of a biobank in the Caribbean represents a vital opportunity to enhance biomedical research and tackle health issues in the area. The Caribbean's unique genetic diversity, shaped by migration and environmental factors, underscores a well-managed biobank's potential impact on global health, especially for underrepresented groups. This paper examines biobanking's potential in the Caribbean, focusing on precision medicine, public health improvements and regional scientific self-sufficiency. It analyzes successful models such as the UK Biobank, the All of Us Research Program at the United States' National Institutes of Health, and Human Heredity and Health in Africa (known as H3Africa), hosted at the University of Cape Town, pinpointing key lessons on data-sharing, ethical governance and infrastructure that could be applied to the Caribbean context. The UK Biobank and H3Africa are relevant examples due to their contributions to large-scale data and health research in diverse populations. The UK Biobank project is a large-scale study with deep genetic and phenotypic data from about 500 000 participants in the United Kingdom. It offers unprecedented insights into health data through extensive follow up and collection of genome-wide genotype data. H3Africa focuses on genomics research that addresses health disparities among African populations, which parallels the Caribbean's challenges. Its ethical governance and community engagement focus are crucial for Caribbean biobank development. This article highlights the challenges of developing biobanks, including ensuring sufficient sample storage and data security, and the need for strong governance. It recommends solutions that involve regional collaboration, stakeholder engagement and increased investment in infrastructure. Establishing a Caribbean biobank with equitable data-sharing principles can significantly enhance global genomic data sets and ensure that the benefits of precision medicine reach the Caribbean. This study promotes a strategic, ethical and inclusive approach to biobanking for long-term success., Competing Interests: Conflicts of interest. None declared.

Background: Vitamin D deficiency is linked to adverse pregnancy outcomes like gestational diabetes mellitus (GDM), but its effects across ethnic groups are unclear. This study examines the relationship among vitamin D levels, glucose tolerance, GDM prevalence, and neonatal outcomes in a multi-ethnic cohort of pregnant women. Methods: We conducted a retrospective analysis of 252 pregnant women from antenatal clinics between 2018 and 2022. Participants were divided into four groups based on serum vitamin D levels: severely deficient (<25 nmol/L), deficient (25-50 nmol/L), insufficient (51-75 nmol/L), and sufficient (>75 nmol/L). The analysis included multivariate linear regression models adjusted for age, ethnicity, BMI, gestational diabetes status, and seasonality. An area under the receiver operating characteristic (AUROC) analysis identified the vitamin D threshold linked to an increased GDM risk. Results: Women classified as severely deficient had higher fasting glucose levels (5.73 ± 1.24 mmol/L) than those in other groups ( p = 0.003, adjusted). The AUROC analysis identified a vitamin D threshold of 45 nmol/L associated with an elevated GDM risk (AUROC = 0.78, CI: 0.70-0.85). South Asian women had lower vitamin D levels (41.17 ± 18.03 nmol/L vs. 45.15 ± 16.75 nmol/L) and higher glucose tolerance test (GTT) levels than Caucasian women, despite having lower BMIs. Moreover, vitamin D levels positively correlated with neonatal birth weight ( p = 0.02). Conclusions: There is a strong link between vitamin D deficiency and increased GDM risk, especially among South Asian women. These findings underscore the need for targeted interventions to improve vitamin D levels in high-risk ethnic groups.

Objective: To explore the experiences and perceptions of rural and metropolitan applicants preparing for and completing all admission components for a provisional entry regional medical pathway., Setting: Provisional entry regional medical pathway., Participants: Provisional entry (school-leaver) applicants (N = 18) who completed a Multiple Mini-Interview (MMI)., Design: Applicants were invited to participate in a semi-structured interview regarding their experiences of the admissions process relative to their background (rural/metropolitan origin). A constructivist approach with a social accountability lens was taken for these semi-structured interviews., Results: Themes were related to whether the applicants were classified as rural or metropolitan origin and the impact of the applicant's geographical location and connections to the local community, differences in local school and social support, and challenges in allocating medical school preferences., Conclusion: Overall, applicant perceptions and experiences of the admissions process were influenced both positively and negatively by whether they were of rural or metropolitan origin. Strategies are required to ensure applicants with genuine rural interest, whether they are of rural or metropolitan origin, have access to sufficient support and resources while applying to regional medical pathways to ensure they are not disadvantaged, thus meeting admissions goals of the program., (© 2024 National Rural Health Alliance Ltd..)

Certain interoceptive hunger cues are caused by gut physiology. These interoceptive cues may have psychological consequences, namely an ability to enhance the desire to eat, which are independent of their physiological cause. Testing this idea is difficult because the physiological processes are normally linked to any consequence. In this preliminary report we attempted to induce an interoceptive hunger cue (a stomach rumble), to examine its psychological consequences independent from its physiological cause. In three online Studies (1-3), participants viewed images of food while listening to different sounds including quiet stomach rumbles and judged the source of the sound, and their desire to eat the depicted foods. In Studies 1-3, irrespective of when they last ate and their reported level of hunger, and relative to control sounds, stomach rumble sounds enhanced desire to eat depicted foods, especially when they were mislocalised to the participants' own stomachs. In Study 1 49% of participants reported some degree of mislocalisation, 74% in Study 2, and 77% in Study 3. Overall, around 40% reported mimicry, where they felt that hearing the computer-generated stomach rumble sound induced the same in themselves. In Study 3 heart beat sounds were included. These too were mislocalised, and enhanced desire to eat depicted foods. In sum, this preliminary report suggests it may be possible to psychologically induce interoceptive cues, including one specific to hunger, and that these cues may then enhance food desire when mislocalised to self. In addition, the findings support the idea that interoceptive hunger cues may have associative properties that augment desire to eat., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To examine (1) how much participation is represented in the benchmark Unified Medical Language System (UMLS) resource, and (2) to what extent that representation reflects the definition of child and youth participation and/or its related constructs per the family of Participation-Related Constructs framework., Materials and Methods: We searched and analysed UMLS concepts related to the term "participation." Identified UMLS concepts were rated according to their representation of participation (i.e., attendance, involvement, both) as well as participation-related constructs using deductive content analysis., Results: 363 UMLS concepts were identified. Of those, 68 had at least one English definition, resulting in 81 definitions that were further analysed. Results revealed 2 definitions (2/81; 3%; 2/68 UMLS concepts) representing participation "attendance" and 18 definitions (18/81; 22%; 14/68 UMLS concepts) representing participation "involvement." No UMLS concept definition represented both attendance and involvement (i.e., participation). Most of the definitions (11/20; 55%; 9/16 UMLS concepts) representing attendance or involvement also represent a participation-related construct., Conclusion(s): The representation of participation within the UMLS is limited and poorly aligned with the contemporary definition of child and youth participation. Expanding ontological resources to represent child and youth participation is needed to enable better data analytics that reflect contemporary paediatric rehabilitation practice.

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography-assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from ten cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan-Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real-time-polymerase chain reaction (RT-PCR). Out of 5714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors, such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival (OS). Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.

Background: Various studies have observed an association between interleukin-6 (IL-6), serum ferritin, d-dimer, and in-hospital mortality in COVID-19 patients. However, multivariate regression analysis was not done in the majority of the studies, Also, the role of interleukin-6 (IL-6), serum ferritin, and d-dimer in hospitalized COVID-19 patients was not adequately studied and reported from our region., Method: It was a retrospective cohort study in which the serum IL-6, serum ferritin, and d-dimer of 305 hospitalized COVID-19 patients were analyzed, and their association with mortality was determined., Results: In COVID-19 patients, the levels of IL-6 (P = 0.007), serum ferritin (P = 0.011), and d-dimer (P = 0.004) were significantly elevated in patients with severe SARS-CoV-2 illness (SpO2 < 90 % at admission). IL-6 levels were significantly elevated (186 pg/ml vs. 215 pg/ml, P = 0.003) in non-survivors compared to survivors. However, d-dimer (mg/ml) (P = 0.129) and serum ferritin (mg/ml) (P = 0.051) levels were similar between the two groups. The ROC curve (receiver operating characteristic curve) analysis showed a significant but poor area under the curve (AUC) between elevated IL-6 (>208 pg/ml) and in-hospital mortality (P < 0.008, AUC = 0.61). Kaplan-Meir survival analysis showed poor survival in patients with elevated IL-6 (>208 pg/ml) (Pby log-rank: 0.010) and elevated d-dimer (>1780 mg/ml) (P by log-rank: 0.036). The multivariate cox-regression analysis did not show any association between IL-6, serum ferritin, d-dimer, and in-hospital mortality (P > 0.05). Also, no association was found between serum levels of IL-6, serum ferritin, d-dimer, and the use of a ventilator (P > 0.05) and the severity of SARS-CoV-2 illness (P > 0.05) on multivariate binary logistic regression analysis., Conclusion: In this study, the serum levels of IL-6, serum ferritin, and d-dimer were not associated with in-hospital mortality in hospitalized COVID-19 patients on multivariate cox-regression analysis, and were the markers of severe SARS-CoV-2 illness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to understand the pharmacotherapy and electroconvulsive therapy (ECT) prescription of women with depression and anxiety admitted to an Australian inpatient psychiatric mother-baby unit (MBU) and compare prescription to national clinical practice guidelines., Method: A retrospective audit was conducted on women diagnosed with depression or anxiety admitted to a public psychiatric inpatient MBU from March 2017 to July 2019. Data was captured at three time points to assess demographic, clinical and pharmacotherapy treatment characteristics. Descriptive statistics were completed., Results: Of the 74 women, 57 women had depression, with 73% prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) and 14% provided ECT during admission. For women with anxiety ( n = 17), 23% were prescribed a benzodiazepine with concurrent antidepressant prescription. SSRI prescription increased, with other antidepressant prescription up trending through admission. Atypical antipsychotic prescription was increased initially and trended downwards at discharge., Conclusions: This study explored the therapeutic armamentarium employed for the treatment of mothers admitted to an inpatient psychiatric MBU with depression and anxiety. The results point to the intricate prescribing practices in a naturalistic setting and highlight that prescribing practices were in line with national guidelines., Competing Interests: DisclosureThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Percutaneous pulmonary valve implantation (PPVI) has emerged as a promising treatment for congenital right ventricular outflow tract (RVOT) dysfunction and restoring conduit graft viability., Methods: This is a single-centre retrospective study of 41 patients (18 men, 23 women; mean age 26.1 ± 10.2 years) who underwent PPVI between December 2007 and November 2014 and were evaluated for right ventricular pressures and exercise tolerance., Results: PPVI significantly reduced mean baseline RVOT gradients across different pathologies: stenosis (45 vs 18.4 mmHg), regurgitation (19.2 vs 7.6 mmHg), and mixed disease (32.5 vs 12 mmHg). Furthermore, mean right ventricular (RV) systolic pressures decreased from 61.6 ± 2.3 to 41.9 ± 2 mmHg ( p  < 0.001), while RV diastolic pressures decreased by about 60% from 14.3 ± 1.1 to 8.6 ± 1.4 mmHg ( p  < 0.001). Echocardiography revealed significant improvements in pulmonary and tricuspid valve velocities ( p for trend < 0.01). Additionally, there was a consistent reduction in the main pulmonary artery maximum pressure gradient measured pre-procedure. No significant changes were observed in PR, QRS, or QTc interval duration on follow-up electrocardiograms. Similarly, no changes were noted in cardiopulmonary exercise test performance during follow-up., Conclusion: The study highlights the effectiveness of PPVI using Medtronic Melody and Edwards SAPIEN valves in patients with various pulmonary diseases. Immediate improvements in right ventricular pressures and functional outcomes suggest that PPVI is a valuable treatment option for individuals with RVOT dysfunction. Multi-centre collaborations are crucial for further elucidating the long-term effects of PPVI on cardiac function, exercise tolerance, and quality of life in RVOT dysfunction., Competing Interests: The authors declare that they have no competing interest., (Copyright ©2024 The Author(s).)

Background: The zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans., Methods: We performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel's connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed., Results: We identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant's magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient's core symptoms (mean improvement 21%)., Conclusions: We present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The growing interest in using ChatGPT (OpenAI, San Francisco, CA) in the medical field highlights the need for in-depth knowledge of its potential and constraints, especially when it comes to anatomy education (AE). Because of its sophisticated natural language processing abilities, it can understand the nuances of anatomical concepts, provide advanced as well as contextually relevant information, and could be a helpful tool for medical students and educators. This study aimed to analyze the capabilities and limitations of ChatGPT and its best possible application in AE., Methodology: The study incorporated 34 questions that were inquired to ChatGPT after acquiring an online subscription to the 4th version. The questions were arbitrarily formulated after consensus among the researchers. The chatbot's replies were recorded and evaluated with reference to perfection, validity, and appropriateness., Results: ChatGPT was observed to be a useful interactive tool for medical students to comprehend the clinical importance and characteristics of anatomical structures. The chatbot clarified the anatomical basis of ischemic heart disease and adequately tabulated the differences between the arteries and veins. Even though ChatGPT-4 was able to produce images of different anatomical structures, it fell short of accurately displaying the necessary features. Further, the chatbot generated quizzes, including multiple-choice, true-false, fill-in-the-blank, matching, and case-based questions, formulated a relevant overview of the lecture, and also analyzed answers to anatomy questions with adequate reasoning., Conclusions: ChatGPT can be a useful educational resource for medical students with the potential to play a crucial role in AE if employed in a methodical way. It imparts significant aid to the anatomy teachers during the execution of the medical curriculum and enhances their jobs while it never takes the place of an educator., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saluja et al.)

Context: This study aimed to study feto-maternal outcomes in women with preterm prelabor rupture of membranes (PTPROM) on expectant management versus delivery at 34 weeks of gestation and correlate the period of latency and inflammatory markers with delivery outcomes. We have chosen this research topic as there is a paucity of specific guidelines regarding the optimal period of gestation for delivering women with PTPROM., Aim: The study correlated the feto-maternal outcomes in women with PTPROM on expectant management till 37 weeks versus delivery at 34 weeks with a period of latency and maternal inflammatory markers., Methods and Materials: This was a prospective observational study conducted on 262 women with PTPROM from 28-33+6 weeks of gestation. Women were monitored till 37 weeks with biweekly total leukocyte count and weekly C-reactive protein, urine routine microscopy, urine culture, high vaginal culture sensitivity, and ultrasound. Women were monitored expectantly till 37 weeks. However, intervention was done at any time during the feto-maternal compromise. There were 52 women who delivered <34 weeks and 210 women who delivered ≥34 weeks. Feto-maternal outcomes were documented. Group A was assigned to women who delivered before 34 weeks and Group B was assigned to women who delivered after 34 weeks. Statistical analysis was done using SPSS software. A p-value <0.05 was considered significant., Results: Among the study group, 238 (90.8%) women were managed expectantly while 24(9.1%) required intervention. A latency of 3-4 weeks was observed in 131(50%) women. Chorioamnionitis developed in 7 women (4.4%) in group A and 13 women (4.9%) in group B. Neonates developed sepsis in 5.7% in group A and 5.8 % in group B and were comparable in both the groups (p=1.000). Early neonatal death (END) occurred in 10 (3.8%) among which seven died because of low birth weight (LBW), two due to sepsis, and one due to respiratory distress. LBW was significantly associated with END (p<0.001) Conclusion: Expectant management beyond 34 weeks with close monitoring can improve neonatal outcomes without increasing maternal morbidity in women with PTPROM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Vardhaman Mahavir Medical College and Safdarjung Hospital issued approval IEC/VMMC/SJH/THESIS/2020-11/CC-177. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jha et al.)

This study utilized UK Biobank data from 144 286 participants and employed whole-genome sequencing (WGS) data and time-to-event data over a 12-year follow-up period to identify susceptibility in genetic variants associated with hypertension. Following genotype quality control, 6 319 822 single nucleotide polymorphisms underwent analysis, revealing 31 significant variant-level associations. Among these, 29 were novel - 15 in Fibrillin-2 ( FBN2 ) and 4 in Junctophilin-2 ( JPH2 ). Mendelian randomization utilizing two identified variants (rs17677724 and rs1014754) suggested that a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression were causally linked to hypertension. Phenome-wide association (PheWAS) analysis using the FinnGen dataset confirmed positive associations of rs17677724 and rs1014754 with hypertension, assessed across 2727 traits in 377 277 individuals. Lastly, rs1014754 positively associated with kallistatin, whereas rs17677724 negatively associated with renin in the Fenland study, suggesting a counterregulatory response to high blood pressure. This study, employing WGS data, identified novel genetic loci and potential therapeutic targets for hypertension., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types., (© 2024 Wiley Periodicals LLC.)

Background: Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum., Methods: We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India. Patients aged over 18 years with low perioperative risk (ASA I & II) were randomised to receive MO or CA care. Prior to the trial, MOs underwent task-based anaesthesia training, inclusive of remotely accessed lectures, simulation-based training and directly observed anaesthetic procedures and intraoperative care. The primary outcome measure was spinal anaesthesia failure with a non-inferiority margin of 5%. Secondary outcome measures consisted of incidence of perioperative and postoperative complications., Findings: Between 12 July 2019 and 8 June 2020, a total of 422 patients undergoing surgical procedures amenable to spinal anaesthesia care were randomised to receive either MO (231, 54.7%) or CA care (191, 45.2%). Spinal anaesthesia failure rate for MOs (7, 3.0%) was non-inferior to those of CA (5, 2.6%); difference in success rate of 0.4% (95% CI=0.36-0.43%; p=0.80). Additionally, there were no statistically significant differences observed between the two groups for intraoperative or postoperative complications, or patients' experience of pain during the procedure., Interpretation: This study demonstrates that failure rates of spinal anaesthesia care provided by trained MOs are non-inferior to care provided by CAs in low-risk surgical patients. This may support policy measures that use task-sharing as a means of expanding anaesthesia care capacity in rural Indian hospitals., Trial Registration Number: NCT04438811., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This article provides an overview of presentations and discussions from the inaugural Healthcare Delivery Science: Innovation and Partnerships for Health Equity Research (DESCIPHER) Symposium., Methods: The symposium brought together esteemed experts from various disciplines to explore models for translating evidence-based interventions into practice., Results: The symposium highlighted the importance of disruptive innovation in healthcare, the need for multi-stakeholder engagement, and the significance of family and community involvement in healthcare interventions., Conclusions: The article concluded with a call to action for advancing healthcare delivery science to achieve health equity., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Author(s). Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Care managers (CM) for low-income disabled clients may address COVID-19 vaccine hesitancy with specific training., Objective: To assess the Partners in Vaccination (PIV) that trained CMs of a homecare program for disabled adults to promote COVID-19 vaccination., Methods: We randomized 78 CMs to PIV intervention (N = 38) or control (N = 40). PIV featured motivational interviewing (MI) skills and educational materials for unvaccinated clients. The primary outcome was first COVID-19 vaccination between December 1, 2021 and June 30, 2022 for clients of intervention CMs versus control CMs. Mixed method analysis included key informant interviews conducted from 5/24/22 to 7/25/22 with CMs, administrators, and clients about the PIV intervention., Results: Among 1939 clients of 78 study CMs, 528 (26.8 %) were unvaccinated by December 1, 2021 (274 clients of intervention CMs; 254 clients of control CMs). These clients' mean age was 62.3 years old (SD = 22.4) and 54 % were Black or Hispanic/Latino. First vaccination rate did not differ for intervention and control groups (6.2 % vs. 5.9 %, p = .89) by 6/30/2022. Barriers to addressing COVID-19 vaccination from interviews with 7 CMs and administrators were competing responsibilities and potentially antagonizing clients. Seven interviewed clients (five vaccinated and two unvaccinated) cited concerns about vaccination they heard from their family/friends and belief that risks of COVID-19 infection may be less than vaccination. Yet, some clients were receptive to physician recommendations., Conclusion: Training CMs to promote COVID-19 vaccination for disabled clients did not increase first vaccination rates. CMs preferred their usual role of coordinating care and, even after the training, expressed discomfort with this potentially polarizing topic., Competing Interests: Declaration of competing interest There is no conflict of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Problem & Background: Medical education has acknowledged the impact of structural societal factors on health, prompting the need for curricula seeking to eliminate health inequities upstream while simultaneously caring for downstream effects of existing inequities. The Keck School of Medicine of USC (KSOM) implemented one such comprehensive curriculum, Health Justice and Systems of Care (HJSC), integrating health systems science, structural competency, and service-learning in a required course spanning the pre-clerkship and clerkship phases with an optional post clerkship elective., Approach: The HJSC course addresses topics including racism in medicine, health inequities, and health systems science. Using transformative learning theory, it fosters critical consciousness and structural competency. Assessments include case analyses, reflections, team-based learning sessions, and group projects related to social justice in healthcare. The program aims to instill cultural humility and practical application, fostering a holistic approach to medical education that implores physicians to become advocates for health justice., Outcomes of the Innovation: Feedback from students indicated generally positive perceptions of the curriculum. Students provided overall positive comments about discussions with guest speakers. However, students expressed a desire for more concrete examples of how health inequities can be remedied. Some found small-group activities less engaging. Other challenges included providing students of different readiness levels with tailored experiences and seamlessly integrating HJSC content within basic and clinical sciences courses., Critical Reflection: Next steps include continuing to integrate content into the science curriculum and clerkships, improving opportunities for meaningful student interactions, and enhancing faculty development to address health justice concerns in clinical settings., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Problem : U.S. medical schools are searching for ways to address issues of health justice in undergraduate medical education. Physicians have not typically received training in how to be effective advocates for systemic change and individuals in policy fields are not usually equipped to understand the complex issues of health science and their intersection with the health system and society. To address this gap, medical school faculty partnered with school of public policy faculty on a collaborative learning model that engaged MD and Master of Public Policy students together to strengthen their collective knowledge of the healthcare landscape, and to build skills to work for health justice. Intervention: We hypothesized that pairing medical students with public policy students to learn about the intersections of health justice and advocacy could enhance the efficacy of each group and provide a new model of collaboration between medical and policy professionals. The students collaborated on a health justice advocacy project through which they provided consultation to an established community organization. Context : The 8-week course took place in the spring of 2021 in Los Angeles, California. Due to Covid-19 the course was taught online and included asynchronous learning modules and live Zoom sessions. The project also served as a pilot for the post-clerkship phase of a new longitudinal health justice curriculum for MD students that launched in August 2021. Impact : Analysis of student work products, course evaluations, partner interviews, and student focus groups showed that students valued learning through their interdisciplinary collaborative work which gave them new perspectives on health justice issues. The community partners indicated that the students consultative work products were useful for their initiatives, and that they found working with MD and MPP students to be a valuable way to think about how to build stronger and more inclusive coalitions to advocate for health justice. This project has the potential for national impact as it aligns with the Association of American Medical Colleges' renewed focus on the responsibility of academic medicine to partner with communities for health justice. The project also contributed to the national conversation on how to align health systems science education with the aims of health justice through our participation in the American Medical Association Accelerating Change in Medical Education Consortium. Lessons Learned : Leveraging faculty relationships with community partners was crucial for developing meaningful projects for students. Cultivating and expanding community partner networks is necessary to sustain and scale up this type of intervention. Centering the needs of communities and supporting their on-going work for health justice is essential for becoming an effective advocate. Learning communities that bring interdisciplinary students, healthcare providers, policy professionals, and community partners together to learn from one another can create key opportunities for ameliorating health inequities.

Clinical parameters used for hemodynamic assessment and titration of vasopressor therapy in neonates with septic shock have several limitations. Functional echocardiography is an emerging tool for bedside assessment of cardiac function and may be useful for diagnosis of shock and assessing the response to therapy. Data regarding echocardiographic parameters in neonates with shock is lacking. This prospective observational study was conducted in a Level III NICU with the primary objective of comparing echocardiographic characteristics of neonates with septic shock at diagnosis, following fluid boluses, and after maximum inotropic support [A1]. Additionally, we compared these characteristics with those of healthy stable neonates who were gestation and postnatal age-matched. A total of 36 neonates with septic shock and 30 gestation and postnatal age-matched controls were enrolled. The mean (SD) gestation and birth weight of neonates with septic shock were 30.6 (4.0) weeks and 1538 (728) g, respectively. Gram-negative bacilli constituted 78.9% of all isolates. At presentation, there was no significant difference between neonates with shock and controls in terms of ventricular outputs, shortening fraction, ratio of early to late diastolic trans-mitral flow velocity, and myocardial performance indices. The distensibility index of inferior vena cava was higher in neonates with shock compared to controls, (17% vs 10%, (p < 0.01)). Left ventricular output was 209 (92) and 227 (102) ml/kg/min (p = 0.53) and right ventricular output was 427 (203) and 459 (227) ml/kg/min, (p = 0.03), respectively, before and after inotropic therapy.     Conclusion: Echocardiographic parameters may not differentiate neonates with septic shock from hemodynamically stable neonates. Neonates with shock associated with predominantly gram-negative sepsis are not able to augment cardiac functions, either at the onset or after administration of inotropes.      Trial registration: (CTRI/2017/12/010766). What is known: • For neonates with shock, echocardiography is becoming increasingly popular as an objective method of evaluating hemodynamics. • In healthy preterm neonate, cardiac output has been known to increase in response to altered hemodynamics during states of increased oxygen demand. What is new: •  In the setting of septic shock induced by gram-negative organisms, echocardiographic parameters are less likely to assist in the assessment of the response to vasoactive agents. Cytokines, induced by gram-negative organisms, may alter adrenoreceptors in myocardium and vasculature., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hematopoiesis is a tightly regulated process that produces all adult blood cells and immune cells from multipotent hematopoietic stem cells (HSCs). HSCs usually remain quiescent, and in the presence of external stimuli like infection or inflammation, they undergo division and differentiation as a compensatory mechanism. Normal hematopoiesis is impacted by systemic inflammation, which causes HSCs to transition from quiescence to emergency myelopoiesis. At the molecular level, inflammatory cytokine signaling molecules such as tumor necrosis factor (TNF), interferons, interleukins, and toll-like receptors can all cause HSCs to multiply directly. These cytokines actively encourage HSC activation, proliferation, and differentiation during inflammation, which results in the generation and activation of immune cells required to combat acute injury. The bone marrow niche provides numerous soluble and stromal cell signals, which are essential for maintaining normal homeostasis and output of the bone marrow cells. Inflammatory signals also impact this bone marrow microenvironment called the HSC niche to regulate the inflammatory-induced hematopoiesis. Continuous pro-inflammatory cytokine and chemokine activation can have detrimental effects on the hematopoietic system, which can lead to cancer development, HSC depletion, and bone marrow failure. Reactive oxygen species (ROS), which damage DNA and ultimately lead to the transformation of HSCs into cancerous cells, are produced due to chronic inflammation. The biological elements of the HSC niche produce pro-inflammatory cytokines that cause clonal growth and the development of leukemic stem cells (LSCs) in hematological malignancies. The processes underlying how inflammation affects hematological malignancies are still not fully understood. In this review, we emphasize the effects of inflammation on normal hematopoiesis, the part it plays in the development and progression of hematological malignancies, and potential therapeutic applications for targeting these pathways for therapy in hematological malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saluja, Bansal, Bhardwaj, Beg and Palanichamy.)

One prediction derived from the disease avoidance account of disgust is that proximal disgust cues (smells, tastes and touches) should elicit this emotion more intensely than distal disgust cues (sights and sounds). If correct, then memories of disgusting experiences should involve smelling, tasting or touching to a greater degree than seeing or hearing. Two surveys were conducted on university students to test this idea, drawing upon their naturalistic experiences. Survey 1 ( N = 127) asked participants to detail their most memorable disgusting, fear-provoking, morally repulsive and yucky/gross experience, with each recollection self-rated for sensory involvement. Survey 2 ( N = 89) employed the same task, but this time, participants recollected their most common disgusting, fear-provoking, morally repulsive and yucky/gross experience in the preceding week. The majority of disgusting experiences were core disgusts-i.e. related to disease/pathogen presence or stimuli. The proximal and distal sensory cues contributed equally to individuals' most memorable core disgust experiences, but the proximal senses were more involved than the distal senses in individuals' most common core disgust experiences. Further, the proximal sensory cues, as compared with the distal sensory cues, were signficantly more involved in core disgust experiences than in morally repulsive and fear-provoking experiences. The implications of these findings for a disease avoidance account of disgust, for multi-sensory disgust research, and core disgust's classification as an emotion or a drive, are discussed., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension., (© 2024. The Author(s).)