Endometriosis.
K. Zondervan, C. Becker, S. Missmer
From the Endometriosis Care and Research (CaRe) Centre, Nuffield Department of Women’s and Reproductive Health (K.T.Z., C.M.B.), and Wellcome Centre for Human Genetics (K.T.Z.), University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; the Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, and the Department of Epidemiology, Harvard T.H. Chan School of Public Health — all in Boston (S.A.M.); and the Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.). Address reprint requests to Dr. Zondervan at the Nuffield Department of Women’s and Reproductive Health, University of Oxford Women’s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom, or at krina . zondervan@ whr . ox . ac . uk.
European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support.
C. Deakin, J. Nolan, J. Soar
et al.
Antimicrobial resistance: a One Health perspective
Laura H. Kahn
Effect of emotional regulation on performance of shooters during competition: An ecological momentary assessment study.
Zhou Lulu, Liu Huimin, Su Hua
<h4>Objective</h4>The purpose of this study was to examine the effect of emotion regulation on shooting performance in shooting athletes.<h4>Method</h4>Ecological momentary assessment was used to track and examine the dynamic relationship between pre-competition and in-competition emotions, emotion regulation strategy selection and use, and shooting performance in 57 shooting athletes.<h4>Results</h4>Female athletes used more regulation strategies than male athletes and had lower mean shooting scores when using disengagement strategies and lower good ten-ring percentages when using engagement strategies compared to male athletes. Elite athletes had a higher percentage of ten-ring scores when using engagement strategies than did first-level athletes, but a lower percentage of ten-ring scores when using disengagement strategies. The use of emotion regulation strategies and situational demands were not strongly related. Athletes had low flexibility in emotion regulation and were better at using disengagement strategies, but disengagement strategies were not beneficial for shooting performance.<h4>Conclusions</h4>First-level athletes have a higher contextual demand for emotion regulation and tend to use disengagement strategies more frequently to regulate emotions. Elite-level athletes have higher average ring values and ten-ring ratios when using engagement strategies under lower contextual demand and using disengagement strategies under higher contextual demand. Enhancing flexible emotional regulation training that improves situation-strategy fit may be beneficial for enhancing sports performance.
Improving follow-up visits among individuals with hypertension: Quality Improvement project in the District Hospital, Seoni, Madhya Pradesh, India, 2021–2022
Prabhdeep Kaur, Rupali Bharadwaj, Mogan Kaviprawin
et al.
Background In India, to achieve a 25% relative reduction in the prevalence of raised blood pressure (BP) by 2025, approximately 4.5 crore additional people with hypertension will need to have their BP effectively treated. We conducted a Quality Improvement (QI) initiative to improve follow-up and reduce missed visits among individuals with hypertension registered under India Hypertension Control Initiative, District Hospital, Seoni, Madhya Pradesh, India, in 2022.Methods We conducted a quasiexperimental study from January to September 2022 in the District Hospital in Seoni, Madhya Pradesh. Following the Ishikawa diagram, the major root causes for missed visits were identified, and countermeasures were developed. The packages under Plan-Do-Study-Act (PDSA) included (i) training urban Accredited Social Health Activists to conduct house visits for individuals with missed visits and (ii) triangulating the follow-up records from various information systems. The review meetings for QI initiatives were conducted fortnightly to follow-up PDSAs. We calculated the proportion of individuals who were followed-up monthly, and the proportion of missed visits among those registered quarterly.Results Cumulatively, 2850 individuals were registered with hypertension till September 2022. Following the intervention, the monthly follow-up proportion increased from 21% in January to 37% in September 2022. Missed visit proportion decreased from 66% (228/345) in quarter four, 2021, to 22% (40/180) in quarter three, 2022. Of the 1438 individuals counselled by ASHA home visits, 74.9% returned for follow-up.Conclusion In our setting, QI initiatives suggested that missed visits decreased during the intervention period. However, the interventions must be implemented continuously for better monitoring and use in similar settings.
lab2clean: a novel algorithm for automated cleaning of retrospective clinical laboratory results data for secondary uses
Ahmed Medhat Zayed, Arne Janssens, Pavlos Mamouris
et al.
Abstract Background The integrity of clinical research and machine learning models in healthcare heavily relies on the quality of underlying clinical laboratory data. However, the preprocessing of this data to ensure its reliability and accuracy remains a significant challenge due to variations in data recording and reporting standards. Methods We developed lab2clean, a novel algorithm aimed at automating and standardizing the cleaning of retrospective clinical laboratory results data. lab2clean was implemented as two R functions specifically designed to enhance data conformance and plausibility by standardizing result formats and validating result values. The functionality and performance of the algorithm were evaluated using two extensive electronic medical record (EMR) databases, encompassing various clinical settings. Results lab2clean effectively reduced the variability of laboratory results and identified potentially erroneous records. Upon deployment, it demonstrated effective and fast standardization and validation of substantial laboratory data records. The evaluation highlighted significant improvements in the conformance and plausibility of lab results, confirming the algorithm’s efficacy in handling large-scale data sets. Conclusions lab2clean addresses the challenge of preprocessing and cleaning clinical laboratory data, a critical step in ensuring high-quality data for research outcomes. It offers a straightforward, efficient tool for researchers, improving the quality of clinical laboratory data, a major portion of healthcare data. Thereby, enhancing the reliability and reproducibility of clinical research outcomes and clinical machine learning models. Future developments aim to broaden its functionality and accessibility, solidifying its vital role in healthcare data management. Graphical Abstract
Computer applications to medicine. Medical informatics
Editorial: Hirschsprung disease: genetic susceptibility, disease mechanisms and innovative management in the multi-omics era
Consolato M. Sergi, Consolato M. Sergi, Josef Hager
Editorial Board
Gynecology and obstetrics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentration via regulating the Nrf2 signaling pathway
Francesca Mancuso, Iva Arato, Catia Bellucci
et al.
IntroductionAmong substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl2 could counteract the toxic effects induced by Cd in an in vitro model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl2 for 48 h.Materials and MethodsApoptosis, cell cycle, and cell functionality were assessed. The gene expression of Nrf2 and its downstream antioxidant enzymes, ERK1/2, and AKT kinase signaling pathways were evaluated.Materials and ResultsWe found that Zn, in co-treatment with subtoxic and toxic Cd concentration, increased the number of metabolically active SCs compared to Cd exposure alone but restored SC functionality only in co-treatment with subtoxic Cd concentration with respect to subtoxic Cd alone. Exposure of Cd disrupted cell cycle in SCs, and Zn co-treatment was not able to counteract this effect. Cd alone induced SC death through apoptosis and necrosis in a dose-dependent manner, and co-treatment with Zn increased the pro-apoptotic effect of Cd. Subtoxic and toxic Cd exposures activated the Nrf2 signaling pathway by increasing gene expression of Nrf2 and its downstream genes (SOD, HO-1, and GSHPx). Zn co-treatment with subtoxic Cd attenuated upregulation on the Nrf2 system, while with toxic Cd, the effect was more erratic. Studying ERK1/2 and AKT pathways as a target, we found that the phosphorylation ratio of p-ERK1/2 and p-AKT was upregulated by both subtoxic and toxic Cd exposure alone and in co-treatment with Zn.DiscussionOur results suggest that Zn could counteract Cd effects by increasing the number of metabolically active SCs, fully or partially restoring their functionality by modulating Nrf2, ERK1/2, and AKT pathways. Our SC model could be useful to study the effects of early Cd exposure on immature testis, evaluating the possible protective effects of Zn.
Diseases of the endocrine glands. Clinical endocrinology
Traditional medicine
Xuegao Li
Living standard and access to tetanus toxoid immunization among women in Bangladesh
Ummay Nayeema Islam, Kanchan Kumar Sen, Wasimul Bari
Abstract Background Although Bangladesh has an impressive track record in the reduction of maternal and child mortality, tetanus, a dreadful disease, impedes the way to achieve Sustainable Development Goal (SDG) in this respect. Sufficient doses of tetanus toxoid containing vaccine during pregnancy ensure immunity against tetanus to mothers as well as newborns. Since inequalities persist across vaccination programs globally, in this paper, an attempt has been made to examine whether tetanus toxoid immunization (TTI) status among the women of reproductive age in Bangladesh for their most recent live birth born preceding 2 years of the survey changes with their living standard index (LSI). Methods Five domains of deprivation such as energy use, improved sanitation, drinking water, housing and assets ownership were used to compute the LSI using a approach proposed by Alkire and Foster. The adjusted association between LSI and TTI was established by using logistic regression model. For the purpose of statistical analysis, a nationally representative cross-sectional data extracted from Bangladesh Multiple Indicator Cluster Survey (BMICS), 2019 have been used. Result The bivariate analysis revealed that 79.5% (95% CI 78.0–81.0) of women with low and 83.1% (95% CI 81.3–84.9) with moderate living standards had sufficient vaccination coverage for their most recent pregnancies while this percentage was higher for the women who belonged to high living standard (85.2, 95% CI = 84.2–86.2). A strong evidence for greater odds of sufficient immunization with TT among the women maintaining a high standard of living (AOR = 1.24, 95% CI = 1.08–1.42, p < 0.01) was found from regression analysis. Conclusion The results depict existing living standard disparity with respect to TT vaccination coverage among women in Bangladesh. Present research suggests that immunization campaigns need to be conducted especially for the disadvantaged people to improve their health care and immunization service utilization among women within the age bracket of 15 to 49. This study proposed a scientific way to enhance TT vaccination among Bangladeshi women, which could help Bangladesh attain a widespread tetanus protection and thus, meet the SDGs for maternal and child mortality reduction.
Public aspects of medicine
Parents of minor children lose less weight during a behavioral weight loss intervention: Findings from the Rural LEAP trial
Christie A. Befort, Kathryn M. Ross, David M. Janicke
et al.
Abstract Objective The transition to parenthood is associated with worsening health behaviors, yet the impact of parental status on successful weight loss has rarely been examined. The purpose of this study was to examine the effect of parental status of minor children on weight loss and behavioral adherence in a rural community‐based weight loss intervention. Methods Five hundred and twenty‐eight adults (age 21–75 years, body mass index [BMI] 30–45 kg/m2) were enrolled in a group‐based weight loss intervention consisting of 16 weekly sessions delivered in face‐to‐face group sessions at Cooperative Extension Service (CES) offices. Participants who were parents with at least one minor child (≤18 years old) in the home were compared to participants with no minor children in the home. Measures included percent weight loss, session attendance, adherence to self‐monitoring, and achieving calorie and physical activity goals. Results Compared to participants without minor children, parents with minor children lost significantly less weight (7.5% vs. 6.2%, respectively; p = 0.01), and were less likely to lose ≥5% of baseline weight (59.2% vs. 70.2%, respectively; p = 0.02). In addition, parents with minor children attended significantly fewer sessions, had lower adherence to self‐monitoring, and met calorie and step goals less often (all ps < 0.001). The association between parental status and percent weight loss was not significantly moderated by gender of the parent. Conclusions Parents of minor children had greater difficulty adhering to intervention goals and lost less weight than participants without minor children. Future research should investigate whether tailoring intervention to meet the unique needs of parents can enhance outcomes, especially given the large segment of the population represented by this group.
Generation of proximal tubule spheroids for nephrotoxicity assessment
Dae Hun Kim, Jung Hwa Lim, Cho-Rok Jung
et al.
Background To date, nephrotoxicity in new drug development has been evaluated through two-dimensional culture of representative cell lines, such as HK-2 and human proximal tubule epithelial cells (hPTECs). Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of nephrotoxicity. Methods and Results Here, we established proximal tubule cell lines from immortalized mixed primary renal cells and generated functional proximal tubule cell spheroids, which expressed all apical basolateral transporters and showed epithelial polarity. Moreover, they showed a more sensitive drug response than hPTECs, which have been commonly used as in vitro kidney models. Conclusion Taken together, the proximal tubule cells described in this study provide a more stable, reproducible, and accurate in vitro kidney model for predicting nephrotoxicity, which could help early compound development.
Biotechnology, Miscellaneous systems and treatments
Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists
Asiyeh Shojaee, Fatemeh Ejeian, Abbas Parham
et al.
Objective: Tendon repair strategies usually are accompanied by pathological mineralization and scar tissue formation that increases the risk of re-injuries. This study aimed to establish an efficient tendon regeneration method simultaneously with a reduced risk of ectopic bone formation.Materials and Methods: In this experimental study, tenogenic differentiation was induced through transforming growth factor- β3 (TGFB3) treatment in combination with the inhibiting concentrations of bone morphogenetic proteins (BMP) antagonists, gremlin-2 (GREM2), and a Wnt inhibitor, namely sclerostin (SOST). The procedure’s efficacy was evaluated using real-time polymerase chain reaction (qPCR) for expression analysis of tenogenic markers and osteochondrogenic marker genes. The expression level of two tenogenic markers, SCX and MKX, was also evaluated by immunocytochemistry. Sirius Red staining was performed to examine the amounts of collagen fibers. Moreover, to investigate the impact of the substrate on tenogenic differentiation, the nanofibrous scaffolds that highly resemble tendon extracellular matrix was employed.Results: Aggregated features formed in spontaneous normal culture conditions followed by up-regulation of tenogenicand osteogenic marker genes, including SCX, MKX, COL1A1, RUNX2, and CTNNB1. TGFB3 treatment exaggeratedmorphological changes and markedly amplified tenogenic differentiation in a shorter period of time. Along with TGFB3 treatment, inhibition of BMPs by GREM2 and SOST delayed migratory events to some extent and dramatically reduced osteo-chondrogenic markers synergistically. Nanofibrous scaffolds increased tenogenic markers while declining the expression of osteo-chondrogenic genes.Conclusion: These findings revealed an appropriate in vitro potential of spontaneous tenogenic differentiation of eq- ASCs that can be improved by simultaneous activation of TGFB and inhibition of osteoinductive signaling pathways.
Glycosylation of Epigallocatechin Gallate by Engineered Glycoside Hydrolases from <i>Talaromyces amestolkiae</i>: Potential Antiproliferative and Neuroprotective Effect of These Molecules
Juan A. Méndez-Líter, Ana Pozo-Rodríguez, Enrique Madruga
et al.
Glycoside hydrolases (GHs) are enzymes that hydrolyze glycosidic bonds, but some of them can also catalyze the synthesis of glycosides by transglycosylation. However, the yields of this reaction are generally low since the glycosides formed end up being hydrolyzed by these same enzymes. For this reason, mutagenic variants with null or drastically reduced hydrolytic activity have been developed, thus enhancing their synthetic ability. Two mutagenic variants, a glycosynthase engineered from a β-glucosidase (BGL-1-E521G) and a thioglycoligase from a β-xylosidase (BxTW1-E495A), both from the ascomycete <i>Talaromyces amestolkiae</i>, were used to synthesize three novel epigallocatechin gallate (EGCG) glycosides. EGCG is a phenolic compound from green tea known for its antioxidant effects and therapeutic benefits, whose glycosylation could increase its bioavailability and improve its bioactive properties. The glycosynthase BGL-1-E521G produced a β-glucoside and a β-sophoroside of EGCG, while the thioglycoligase BxTW1-E495A formed the β-xyloside of EGCG. Glycosylation occurred in the 5″ and 4″ positions of EGCG, respectively. In this work, the reaction conditions for glycosides’ production were optimized, achieving around 90% conversion of EGCG with BGL-1-E521G and 60% with BxTW1-E495A. The glycosylation of EGCG caused a slight loss of its antioxidant capacity but notably increased its solubility (between 23 and 44 times) and, in the case of glucoside, also improved its thermal stability. All three glycosides showed better antiproliferative properties on breast adenocarcinoma cell line MDA-MB-231 than EGCG, and the glucosylated and sophorylated derivatives induced higher neuroprotection, increasing the viability of SH-S5Y5 neurons exposed to okadaic acid.
Therapeutics. Pharmacology
Efficacy of integrative medicine using Yinhua-based herbal granules on herpangina: A Bayesian network meta-analysis of randomized controlled trials
Yongcheng Sheng, Yuhui Zhang, Qin Wang
et al.
Background: Different Traditional Chinese Medicine (TCM) in the format of granules, such as Kanggan Granules (KangGs), Kouyanqing Granules (KouGs), Lianhua Qingwen Granules (LQGs), Qingkailing Granules (QGs) and Xiao'er Qingjie Granules (XQJGs), collectively named Yinhua-based herbal granules (YH-HGs) have been widely used in the management of pediatric outpatients with herpangina. Few head-to-head randomized controlled trials (RCTs) have compared the efficacy of these agents. This network meta-analysis (NMA) was conducted to indirectly compare the efficacy of YH-HGs. Methods: This systematic review and fixed-effect NMA was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for NMA. RCTs assessing the efficacy and safety of YH-HGs in children that were also receiving ribavirin as the conventional therapy were searched from eight databases and two trial registers up to Jan 13, 2022. The primary outcome was total effectiveness rate (TER). The secondary outcomes were total adverse events (TAEs) and the time to symptom improvement of fever, vesicles, pain and salivation. Relative risk (RR) and weighted mean difference with 95% confidence intervals (CIs) were estimated by direct pairwise meta-analysis (MA) and NMA. Results: A total of 10 RCTs, enrolling 1 017 pediatric patients, were included. YH-HGs were better than no medication (NM) in TER (RR = 1.22, 95%CIs, 1.16 – 1.28) by direct pairwise MA, in which KangGs (RR = 1.24, 95%CIs, 1.05 – 1.47), KouGs (RR = 1.17, 95%CIs, 1.08 – 1.27), LQGs (RR = 1.24, 95%CIs, 1.14 – 1.35), QGs (RR = 1.33, 95%CIs, 1.11 – 1.58) and XQJGs (RR = 1.18, 95%CIs, 1.00 – 1.40) were also more efficient than NM. As for secondary outcomes, YH-HGs was associated with a 103% increased risk of TAEs compared to NM, but no significant differences were found. YH-HGs has a more positive symptom improvement effect than NM in fever, vesicles, pain and salivation. The ranking results showed that QGs (79.2%) had the highest probability ranking first in TER and KangGs (63.6%) ranked as the second, followed by LQGs (52.4%), XQJGs (50.3%), KouGs (49.7%), and NM (4.9%) at last. Conclusions: Our findings support the better efficacy of YH-HGs than NM as regards TER. QGs, KangGs, LQGs, XQJGs, KouGs remain superior to NM and their clinical choice should depend on the patient's conditions to improve symptoms better for the different effects. Given the limitations of NMA, head-to-head RCTs with high-quality are needed.
Other systems of medicine
Herpes zoster ophthalmicus infection after kidney transplantation
Abdulmecit Yildiz, Suat Akgür, Alparslan Ersoy
et al.
Herpes zoster causes an acute dermatomal infection with vesicular rash associated with reactivation of the Varicella zoster virus. The infection usually involves the thoracic, cervical, ophthalmic and lumbosacral regions. Herpes zoster infection is common after solid organ transplantation. Herpes zoster ophthalmicus is a rare form of Herpes zoster infection and involves the ophthalmic branch of the trigeminal nerve along the V1-V2 dermatomes. Herein, we reported a kidney recipient who developed Herpes zoster ophthalmicus infection after transplantation.
Accelerometer-assessed outdoor physical activity is associated with meteorological conditions among older adults: Cross-sectional results from the OUTDOOR ACTIVE study.
Birte Marie Albrecht, Imke Stalling, Carina Recke
et al.
BACKGROUND:Meteorological conditions are potential determinants of physical activity (PA). A profound understanding of the determinants of PA behaviour is required for PA promotion. This study examined the association between accelerometer-assessed PA and meteorological conditions among older adults. METHODS:This cross-sectional study included data of 577 adults aged 65-75 years living in Bremen, Germany (52% female; 3278 days). PA was measured with accelerometers for seven consecutive days (10/15-08/16). A threshold of 240 lx was used to differentiate between outdoor physical activity (OPA) and indoor physical activity (IPA). Linear mixed models estimated the association between PA (daily accelerometer counts per minute (CPM)) and meteorological factors (temperature, cloud cover, wind, and no precipitation) derived by principal component analysis. RESULTS:The analyses showed associations between PA in CPM and the meteorological factors temperature (93.7; 95%-CL: 64.9, 122.5) and no precipitation (48.4; 95%-CL: 19.8, 77.0) in women and wind (-40.3; 95%-CL: -59.7, -20.8) and no precipitation (30.1; 95%-CL: 5.6, 54.6) in men. After distinguishing in OPA and IPA for a subsample of 128 participants (473 days), the sex differences were no longer present. OPA in CPM was associated with temperature (women: 174.5; 95%-CL: 81.3, 267.6; men: 183.3; 95%-CL: 81.2, 285.4), cloud cover (women: -153.0; 95%-CL: -200.3, -105.7; men: -123.2; 95%-CL: -174.7, -71.7), and wind (women: -118.6; 95%-CL: -189.6; -47.7; men: -96.9; 95%-CL: -177.0, -16.7). No association between OPA and no precipitation was found (women: 2.9; 95%-CL: -89.0, 94.8; men: -17.1; 95%-CL: -116.7, 82.4). CONCLUSIONS:The results of this study emphasize the importance of meteorological conditions as environmental determinants of PA among older adults. Meteorological conditions should be accounted for in the unbiased assessment of habitual PA and the development of PA promotion programs. Future research should focus on the associations of OPA and IPA with meteorological conditions in different climatic regions.
Coordination compounds in nuclear medicine
S. Jurisson, D. Berning, Wei Jia
et al.
What clinical teachers in medicine need to know
D. Irby