Effect of intrapartum azithromycin on gut microbiota development in early childhood: A post hoc analysis of a double-blind randomized trial.

Intrapartum azithromycin prophylaxis has shown the potential to reduce maternal infections but showed no effect on neonatal sepsis and mortality. Antibiotic exposure early in life may affect gut microbiota development, leading to undesired consequences. Therefore, we here assessed the impact of 2 g oral intrapartum azithromycin on gut microbiota development from birth to the age of 3 years, by 16S-rRNA gene profiling of rectal samples from 127 healthy Gambian infants selected from a double-blind randomized placebo-controlled clinical trial (PregnAnZI-2). Microbiota trajectories showed, over the first month of life, a slower community transition and increase of Enterobacteriaceae (p = 0.001) and Enterococcaceae (p = 0.064) and a decrease of Bifidobacterium (p < 0.001) in the azithromycin compared to the placebo arm. Intrapartum azithromycin alters gut microbiota development and increases proinflammatory bacteria in the first month of life, which may have undesirable effects on the child.

Leukocyte mitochondrial DNA copy number and cardiovascular disease: A systematic review and meta-analysis of cohort studies.

Increasing cohort studies have examined the link between mitochondrial DNA copy number (mtDNA-CN) and cardiovascular disease (CVD), with inconsistent findings. We searched PubMed, EMBASE, and Web of Science up to July 11, 2023 and used a random-effects model to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). This systematic review and meta-analysis included 8 articles encompassing 29 studies with 646,398 participants. Individuals with the lowest mtDNA-CN had a summary HR of 1.27 (95% CI 1.02-1.59) for CVD, 1.18 (95% CI 0.92-1.50) for coronary heart disease (CHD), 1.10 (95% CI 0.89-1.37) for stroke, and 1.30 (95% CI 1.07-1.56) for heart failure (HF). Decreased mtDNA-CN is linked to an increased risk of CVD and HF but not CHD and stroke. These findings suggest mtDNA-CN from leukocytes may be a potential early biomarker for CVD. However, more prospective studies with long follow-up are needed.

Characteristics of calcified nodule attributable to culprit lesion in acute coronary syndrome: A systematic review and meta-analysis.

The presence of calcified nodule (CN) is a significant characteristic of atherothrombosis in acute coronary syndrome (ACS). However, its characteristics continue to be understudied. This review aimed to further investigate these characteristics. This study found that CN was a distinctive feature of an atheromatous plaque, representing 6.3% of ACS. CN was more common in NSTE-ACS than in STEMI patients (9.4% vs. 6.6%). CN was also chiefly observed in the left anterior descendant artery (48%), followed by the right coronary (40.4%) and left circumflex (14.5%) arteries. Higher prevalence of hypertension (78.8%), diabetes mellitus (50.8%), multivessel disease (71.7%), and kidney disease (26.43%) were noted in CN compared to non-CN patients. CN-associated ACS also 6-fold increased the risk of target lesion revascularization compared to those without CN.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

[Looking back on 100 years of board certification for urology in Germany : Formation of a medical subject in the context of specialization and professionalization]. / 100 Jahre Facharzt für Urologie : Zur Ausbildung eines medizinischen Faches im Kontext von Spezialisierung und Professionalisierung.

This article examines the development of urology as an independent medical discipline in Germany, with a particular focus on professionalization and specialization in the 19th and 20th centuries. Based on historical sources, the text illuminates the importance of the German medical profession's further training regulations as an instrument of medical self-administration and the classification of urology as a medical specialty in the Bremen guidelines of 1924, which established board certification in diseases of the urinary organs (urology).

Plasma endocannabinoidome and fecal microbiota interplay in people with HIV and subclinical coronary artery disease: Results from the Canadian HIV and Aging Cohort Study.

Chronic HIV infection is associated with accelerated coronary artery disease (CAD) due to chronic inflammation. The expanded endocannabinoid system (eCBome) and gut microbiota modulate each other and are key regulators of cardiovascular functions and inflammation. We herein investigated the interplay between plasma eCBome mediators and gut microbiota in people with HIV (PWH) and/or subclinical CAD versus HIV-uninfected individuals. CAD was determined by coronary computed tomography (CT) angiography performed on all participants. Plasma eCBome mediator and fecal microbiota composition were assessed by tandem mass spectrometry and 16S rDNA sequencing, respectively. HIV infection was associated with perturbed plasma eCBome mediators characterized by an inverse relationship between anandamide and N-acyl-ethanolamines (NAEs) versus 2-AG and 2-monoacylglycerols (MAGs). Plasma triglyceride levels were positively associated with MAGs. Several fecal bacterial taxa were altered in HIV-CAD+ versus controls and correlated with plasma eCBome mediators. CAD-associated taxonomic alterations in fecal bacterial taxa were not found in PWH.

Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic ß-cells.

KCNQ1/Kv7, a low-voltage-gated K+ channel, regulates cardiac rhythm and glucose homeostasis. While KCNQ1 mutations are associated with long-QT syndrome and type2 diabetes, its function in human pancreatic cells remains controversial. We identified a homozygous KCNQ1 mutation (R397W) in an individual with permanent neonatal diabetes melitus (PNDM) without cardiovascular symptoms. To decipher the potential mechanism(s), we introduced the mutation into human embryonic stem cells and generated islet-like organoids (SC-islets) using CRISPR-mediated homology-repair. The mutation did not affect pancreatic differentiation, but affected channel function by increasing spike frequency and Ca2+ flux, leading to insulin hypersecretion. With prolonged culturing, the mutant islets decreased their secretion and gradually deteriorated, modeling a diabetic state, which accelerated by high glucose levels. The molecular basis was the downregulated expression of voltage-activated Ca2+ channels and oxidative phosphorylation. Our study provides a better understanding of the role of KCNQ1 in regulating insulin secretion and ß-cell survival in hereditary diabetes pathology.

Targeted dephosphorylation of TFEB promotes its nuclear translocation.

Reversible phosphorylation of the transcription factor EB (TFEB) coordinates cellular responses to metabolic and other stresses. During nutrient replete and stressor-free conditions, phosphorylated TFEB is primarily localized to the cytoplasm. Stressor-mediated reduction of TFEB phosphorylation promotes its nuclear translocation and context-dependent transcriptional activity. In this study, we explored targeted dephosphorylation of TFEB as an approach to activate TFEB in the absence of nutrient deprivation or other cellular stress. Through an induction of proximity between TFEB and several phosphatases using the AdPhosphatase system, we demonstrate targeted dephosphorylation of TFEB in cells. Furthermore, by developing a heterobifunctional molecule BDPIC (bromoTAG-dTAG proximity-inducing chimera), we demonstrate targeted dephosphorylation of TFEB-dTAG through induced proximity to bromoTAG-PPP2CA. Targeted dephosphorylation of TFEB-dTAG by bromoTAG-PPP2CA with BDPIC at the endogenous levels is sufficient to induce nuclear translocation and some transcriptional activity of TFEB.

Mapping the Locations of Medical Specialists in the Ministry of Health's Hospitals in Malaysia by Specialty, Subspecialty and Area of Interest.

Mapping the distribution of medical specialists in the Ministry of Health (MOH) Malaysia facilities is expected to be more complex as the demand for specialty and subspecialty services increases in the future. A more robust and definitive gap analysis is needed to facilitate planning and resource allocation. The Medical Development Division developed a master list of framework of specialties, subspecialties and areas of interest, and Specialist Database Module in the Medical Programme Information System (MPIS) as tools to facilitate mapping of services. Relational database of specialists' location, facilities, workload, population profile and other relevant parameters were developed to provide data visualisation in specific dashboard. Needs versus supply ratio is proposed as one of parameters to visualise specialised medical services distribution by geographical localities.

Integrated single cell-RNA sequencing and Mendelian randomization for ischemic stroke and metabolic syndrome.

Although more and more evidence has supported that metabolic syndrome (MS) is linked to ischemic stroke (IS), the molecular mechanism and genetic association between them has not been investigated. Here, we combined the existing single-cell RNA sequencing (scRNA-seq) data and mendelian randomization (MR) for stroke to understand the role of dysregulated metabolism in stroke. The shared hub genes were identified with machine learning and WGCNA. A total of six upregulated DEGs and five downregulated genes were selected for subsequent analyses. Nine genes were finally identified with random forest, Lasso regression, and XGBoost method as a potential diagnostic model. scRNA-seq also show the abnormal glycolysis level in most cell clusters in stroke and associated with the expression level of hub genes. The genetic relationship between IS and MS was verified with MR analysis. Our study reveals the common molecular profile and genetic association between ischemic stroke and metabolic syndrome.

Cerebrospinal fluid and plasma concentrations of the inflammatory marker soluble CD27 in a large surgical population.

Soluble CD27 (sCD27) is a potential biomarker for diseases involving immune dysfunction. As there is currently little data on cerebrospinal fluid (CSF) sCD27 concentrations in the general population we measured CSF and plasma concentrations in 486 patients (age range 18-92 years, 57% male) undergoing spinal anesthesia for elective surgery. Across the complete cohort the median [range] sCD27 concentrations were 163 [<50 to 7474] pg/mL in CSF and 4624 [1830 to >400,000] pg/mL in plasma. Plasma sCD27, age and Qalb were the factors most strongly associated with CSF sCD27 levels. Reference sCD27 concentration intervals (central 95% of values) in a sub-group without the indication of neuropsychiatric, inflammatory or systemic disease (158 patients) were <50 pg/mL - 419 pg/mL for CSF and 2344-36422 pg/mL for plasma. These data provide preliminary reference ranges that could inform future studies of the validity of sCD27 as a biomarker for neuro- and systemic inflammatory disorders.

Gender Inequity in Clinical Clerkships and its Influence on Career Selection: A Cross-Sectional Survey.

Objective: The aim of this study was to identify the frequency, form, and underlying factors contributing to gender inequity experienced by medical undergraduates and assess its influence on their career choices. Method: This was a cross-sectional, retrospective survey with a 100% response rate. This survey was distributed among medical students of clinical years in Karachi's private and government medical colleges from September 10th, 2021-March 30th, 2022. 430 participants were enrolled using a simple-random-sampling-technique. Chi-square/Fisher's Exact tests are employed to assess the relationships between gender and gender-based inequity in various specialties, including their characteristics, influence on career choices, adverse psychological effects, and potential mitigation strategies. Results: Among 430 respondents, 28.6% were male, and 71.4% were female. 89.1% reported gender inequity, evenly distributed in government (80.4%) and private institutions (88.1%). The general surgery and gynecology disciplines stood out, each with a 56% prevalence. In gynecology and surgery clinical-clerkships, both genders experienced similar rates, with females at 54.5% and 42.3%, and males at 56.7% and 61.6%, respectively (P-value = .000*). Disrespect from staff/professors/patients (48.8%) was the most common manifestation, driven by factors like preferences (73.7%), gender superiority (62.6%), societal attitudes (54%), and cultural norms (50.9%). Furthermore, 82.6% of students reported that gender inequity had a negative impact on their career decision (Male = 82.9%;Female = 82.4%, P-value = .899). Additionally, gender inequity also caused demotivation (78.1%), poor self-esteem (67.2%), helplessness/hopelessness (48.6%), and frustration (45.8%). Conclusions: Gender inequity is widely prevalent in the clinical-clerkships, affecting medical students' career decisions and mental health, stressing the need to prioritize and implement solutions at the undergraduate clinical-clerkship level.

Epidemiology of 369 diseases and injuries attributable to 84 risk factors: 1990-2019 with 2040 projection.

The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990-2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.

Evolution of interconsultal activity to endocrinology and nutrition in hospitalization floor in a third level hospital.

INTRODUCTION: Endocrinology and Nutrition (EyN) is an outpatient and hospital medical specialty. This study aims to understand the evolution of the activity of interdepartmental consultation (IC) carried out by EyN in hospitalization floor of a third level hospital, comparing its evolution with other medical specialties, and comparing endocrine IC with nutritional IC. MATERIAL AND METHODS: Longitudinal and retrospective study which analyzes IC notes of EyN and other medical specialties between 01-01-2013 and 31-12-2022. RESULTS: A total of 76093 IC notes (12623 patients) were performed by the EyN service (average age 65.4 years; 59% male) with an average of 4.8 notes per patient. Average annual growth was 7% in notes and 4% in patients (versus 6% and 3% of all other medical services, differences statistically significant). Of all patients hospitalized for 4 or more days, EyN went from attending 7.9% (2013) to 12.3% (2022). 66% of the IC performed by EyN was for nutritional cause and 34% for other pathologies. CONCLUSIONS: The EyN service is the one that most patients attend in hospital IC activity, with growth over the last few years greater than other medical specialties. Nutritional pathology is the main reason for IC.

Zanubrutinib delays selinexor resistance evolution in biopsy sample-derived primary central nervous system lymphoma models.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.

How does guided group reflection work to support professional identity formation in postgraduate medical education: A scoping review.

PURPOSE: In postgraduate medical education, guided group reflection is often applied to support professional identity formation. However, little is known about how guided group reflection is shaped and how it works. Our scoping review synthesizes existing evidence about various approaches for guided group reflection, their aims, components and potential working mechanisms. METHODS: We conducted a scoping review using JBI (Joanna Briggs Institute) guidelines for conducting scoping reviews. We searched PubMed, PsycINFO, EMBASE and ERIC databases for all research articles published in English or Dutch in an iterative team approach. The articles were extracted and summarized quantitatively and qualitatively. RESULTS: We included 71 papers (45 primary research papers and 26 non-empirical papers including program descriptions, theoretical concepts and personal experiences). We identified a diversity of approaches for guided group reflection (e.g. Balint groups, supervised collaborative reflection and exchange of experiences), applied in a variety of didactic formats and aims. We distilled potential working mechanisms relating to engagement in reflection, group learning and the supervisor's role. CONCLUSIONS: There are significant knowledge gaps about the aims and underlying mechanisms of guided group reflection. Future systematic research on these topics is needed to understand the effectiveness of educational methods, that can help facilitate learning conditions to best shape professional identity formation (PIF) in educational curricula.

Medical specialists' use and opinion of video consultation in Denmark: a survey study.

BACKGROUND: The COVID-19 pandemic accelerated the use of telemedicine which is seen as a possibility to reduce the pressure on healthcare systems globally. However, little research has been carried out on video as a consultation medium in medical specialists' practice. This study investigated the use of and opinion on video consultation among specialists in Denmark. METHODS: An online survey on use of video consultation, as well as relevance of and opinion on video consultation, was distributed to all 963 medical specialists in private practice in Denmark throughout May and June 2022, resulting in 499 complete answers (response rate: 51.8%). Data were analysed using descriptive and logistic regression analyses, and data from open text fields were analysed using thematic network analysis. RESULTS: Among the respondents, 62.2% had never used video consultation, while 23.4% were currently using video consultation, most particularly among psychiatrists. A total of 47.3% found video consultation medically irrelevant to their specialty, especially radiologists, plastic surgeons, ophthalmologists and otorhinolaryngologists. According to the specialists, video consultation was most suitable for follow-up consultations and simple medical issues, where the patient had an established diagnosis. In these cases, mutual trust remained present in video consultations. Better access for the patients and fewer cancellations, especially for psychiatrists, were highlighted as benefits. IT problems were reported as obstacles hindering optimal use of video consultation. CONCLUSION: The political aspiration to digitization in healthcare systems should be rooted in professionals' and patients' perceptions and experiences with video consultation which emphasize that it is not a standard tool for all consultations.

The Effect of the COVID-19 Pandemic on the Factors Influencing Iranian Medical Residents' Specialty Selection: A Qualitative Study.

Background: Medical students' specialty selection influences the composition of the physician workforce and the effectiveness of health systems. Therefore, the identification of factors that influence the choice of specialty is critical for an evidence-based health policy. This study aimed to investigate the effect of the Coronavirus Disease 2019 (COVID-19) pandemic on the determinants of specialty choice among Iranian medical residents. Methods: In early 2022, this qualitative study was conducted among Iranian medical residents in seven provinces, including Tehran, Isfahan, Fars, Khorasan Razavi, Kerman, Kermanshah, and Khuzestan. The participants were selected using a purposeful sampling method. Data were collected using 74 semi-structured in-depth face-to-face interviews. Finally, a thematic content analysis (conventional content analysis) method was applied for data synthesis. Results: The participant's mean age was 28.7±2.5 years, and more than 52% (N=39) were men. Following data synthesis, 10 sub-themes and four main themes were identified, including educational aspects affected by the pandemic, career-related hazards, personal and professional lifestyles affected by the disease, and experiences and beliefs regarding the pandemic. Conclusion: The COVID-19 pandemic has had a significant impact on medical students' educational, professional, and personal aspects of specialty choices. This study demonstrated how the disease affected the choice of specialty. Therefore, the findings could be used for developing national health policy and planning.

Factors Affecting Turkish Medical Students' Pursuit of a Career in Neurosurgery: A Single Center Survey Study.

BACKGROUND: Statistics show that over the past 2 decades, even in high-income countries, fewer and fewer students have listed neurosurgery as their top career option. Literature on medical students' pursuit of neurosurgical careers in middle- and low-income countries are scarce. The aim of this research, conducted in Turkey with a middle-income economy, was to contribute insights relevant to medical education and neurosurgery across the world. METHODS: A survey was conducted with a target sample of fourth-year (167 students), fifth-year (169 students), and sixth-year (140 students) medical students (476 in total) from the Medical School at Istanbul Medeniyet University in Turkey. The response rates of the fourth-, fifth-, and sixth-year students were 62% (104/167), 53% (90/169), and 50% (70/140), respectively (in total, 266, including 147 female and 119 male). RESULTS: In terms of the genuine intention, only 2.5% of men and 2.7% of women were committed to specializing in neurosurgery. This study further revealed that possible reasons for these students' low motivation to specialize in neurosurgery were their beliefs that in neurosurgery, the physical and psychological demands were high, and the night shifts were intense, meaning they would not have a social life or spare time for their hobbies; that morbidity/mortality were high; and that financial incentives were insufficient, especially in public institutions. CONCLUSION: Turkish medical students did not rank neurosurgery at the top of their career choices. Possible reasons for this are socioeconomic factors and the inadequate introduction of neurosurgery to medical students.