THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

BACKGROUND: PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. METHODS: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. RESULTS: Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. CONCLUSION: These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31

Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant; Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.).Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant;Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.)

Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study

BACKGROUND: Spices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an experimental study was conducted in normal male mice. METHODS: The extracts (50% ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate). RESULTS: The extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity. CONCLUSION: The extracts (50% ethanolic) of nutmeg and clove enhanced the sexual behaviour of male mice

Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (coronavirus disease 2019 [COVID-19]) pandemic revealed the vulnerability of specific population groups in relation to susceptibility to acute deterioration in their health, including hospital admission and mortality. There is less data on outcomes for people with type 1 diabetes (T1D) following SARS-CoV-2 infection than for those with type 2 diabetes (T2D). In this study we set out to determine the relative likelihood of hospital admission following SARS-CoV-2 infection in people with T1D when compared to those without T1D. Methods: This study was conducted as a retrospective cohort study and utilised an all-England dataset. Electronic health record data relating to people in a national England database (NHS England’s Secure Data Environment, accessed via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium) were analysed. The cohort consisted of patients with a confirmed SARS-CoV-2 infection, and the exposure was whether or not an individual had T1D prior to infection (77,392 patients with T1D). The patients without T1D were matched for sex, age and approximate date of the positive COVID-19 test, with three SARS-CoV-2-infected people living without diabetes (n = 223,995). Potential factors influencing the relative likelihood of the outcome of hospital admission within 28 days were ascertained using univariable and multivariable logistic regression. Results: Median age of the people living with T1D was 37 (interquartile range 25–52) years, 47.4% were female and 89.6% were of white ethnicity. Mean body mass index was 27 (standard error [SE] 0.022) kg/m2, and mean glycated haemoglobin (HbA1c) was 67.3 (SE 0.069) mmol/mol (8.3%). A significantly higher proportion of people with T1D (10.7%) versus matched non-diabetes individuals (3.9%) were admitted to hospital. In combined analysis including individuals with T1D and matched controls, multiple regression modelling indicated that the factors independently relating to a higher likelihood of hospital admission were: T1D (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.62–1.80]), age (OR 1.02, 95% CI 1.02–1.03), social deprivation (higher Townsend deprivation score: OR 1.07, 95% CI 1.06–1.08), lower estimated glomerular filtration rate (eGFR) value (OR 0.975, 95% CI 0.974–0.976), non-white ethnicity (OR black 1.19, 95% CI 1.06–1.33/OR Asian 1.21, 95% CI 1.05–1.39) and having asthma (OR 1.27, 95% CI 1.19–1.35]), chronic obstructive pulmonary disease (OR 2.10, 95% CI 1.89–2.32), severe mental illness (OR 1.83, 95% CI 1.57–2.12) or hypertension (OR 1.44, 95% CI 1.37–1.52). Conclusion: In this all-England study, we describe that, following confirmed infection with SARS-CoV-2, the risk factors for hospital admission for people living with T1D are similar to people without diabetes following confirmed SARS-CoV-2 infection, although the former were more likely to be admitted to hospital. The younger age of individuals with T1D in relation to risk stratification must be taken into account in any ongoing risk reduction strategies regarding COVID-19/future viral pandemics

Correction to: Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England

The article “Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England”, written by Adrian H. Heald, David A. Jenkins, Richard Williams, Rajshekhar N. Mudaliar, Amber Khan, Akheel Syed, Naveed Sattar, Kamlesh Khunti, Asma Naseem, Kelly A. Bowden-Davies, J. Martin Gibson, William Ollier, on behalf of the CVD-COVID-UK/COVID-IMPACT Consortium was originally published electronically on the publisher’s Internet portal (currently SpringerLink) on August 25, 2023, without open access. Now, the article is updated with open access as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The original article has been corrected

Quality Of Antenatal Care In Rural Southern Tanzania: A Reality Check.

Counselling on the danger signs of unpredictable obstetric complications and the appropriate management of such complications are crucial in reducing maternal mortality. The objectives of this study were to identify gaps in the provision of ANC services and knowledge of danger signs as well as the quality of care women receive in case of complications. The study took place in the Rufiji District of Tanzania in 2008 and was conducted in seven health facilities. The study used (1) observations from 63 antenatal care (ANC) sessions evaluated with an ANC checklist, (2) self-assessments of 11 Health workers, (3) interviews with 28 pregnant women and (4) follow-up of 12 women hospitalized for pregnancy-related conditions.Blood pressure measurements and abdominal examinations were common during ANC visits while urine testing for albumin or sugar or haemoglobin levels was rare which was often explained as due to a lack of supplies. The reasons for measuring blood pressure or abdominal examinations were usually not explained to the women. Only 15/28 (54%) women were able to mention at least one obstetric danger sign requiring medical attention. The outcomes of ten complicated cases were five stillbirths and three maternal complications. There was a considerable delay in first contact with a health professional or the start of timely interventions including checking vital signs, using a partograph, and detailed record keeping. Linking danger signs to clinical and laboratory examination results during ANC with the appropriate follow up and avoiding delays in emergency obstetric care are crucial to the delivery of coordinated, effective care interventions

Development of a validated search filter for Ovid Embase for degenerative cervical myelopathy.

Funder: Royal College of Surgeons of England; Id: http://dx.doi.org/10.13039/501100000297BACKGROUND: Degenerative cervical myelopathy (DCM) is a recently proposed umbrella term for symptomatic cervical spinal cord compression secondary to degeneration of the spine. Currently literature searching for DCM is challenged by the inconsistent uptake of the term 'DCM' with many overlapping keywords and numerous synonyms. OBJECTIVES: Here, we adapt our previous Ovid medline search filter for the Ovid embase database, to support comprehensive literature searching. Both embase and medline are recommended as a minimum for systematic reviews. METHODS: References contained within embase identified in our prior study formed a 'development gold standard' reference database (N = 220). The search filter was adapted for embase and checked against the reference database. The filter was then validated against the 'validation gold standard'. RESULTS: A direct translation was not possible, as medline indexing for DCM and the keywords search field were not available in embase. We also used the 'focus' function to improve precision. The resulting search filter has 100% sensitivity in testing. DISCUSSION AND CONCLUSION: We have developed a validated search filter capable of retrieving DCM references in embase with high sensitivity. In the absence of consistent terminology and indexing, this will support more efficient and robust evidence synthesis in the field

Measuring co-authorship and networking-adjusted scientific impact

Appraisal of the scientific impact of researchers, teams and institutions with productivity and citation metrics has major repercussions. Funding and promotion of individuals and survival of teams and institutions depend on publications and citations. In this competitive environment, the number of authors per paper is increasing and apparently some co-authors don't satisfy authorship criteria. Listing of individual contributions is still sporadic and also open to manipulation. Metrics are needed to measure the networking intensity for a single scientist or group of scientists accounting for patterns of co-authorship. Here, I define I1 for a single scientist as the number of authors who appear in at least I1 papers of the specific scientist. For a group of scientists or institution, In is defined as the number of authors who appear in at least In papers that bear the affiliation of the group or institution. I1 depends on the number of papers authored Np. The power exponent R of the relationship between I1 and Np categorizes scientists as solitary (R>2.5), nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or collaborators (R<1.75). R may be used to adjust for co-authorship networking the citation impact of a scientist. In similarly provides a simple measure of the effective networking size to adjust the citation impact of groups or institutions. Empirical data are provided for single scientists and institutions for the proposed metrics. Cautious adoption of adjustments for co-authorship and networking in scientific appraisals may offer incentives for more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure

Role of F-18-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease

BACKGROUND: 18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has recently attracted interest for the measurement of disease activity in Crohn's disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activity and its response to treatment in patients with CD. METHODS: Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used to assess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity (Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component and underwent scanning before and 12 weeks after the initiation of anti–tumor necrosis factor alpha therapy. Patients were subcategorized on the basis of a clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took part in the test–retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures. RESULTS: The sensitivity and specificity of 18F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measures correlated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEAN demonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt >0.80 and % variability <20%) compared with volume-dependent FDG-PET measures. A proportion of the FDG signal (10%–30%) was found to originate from the lumen of diseased segments. CONCLUSIONS: 18F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD