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JPMA. the Journal of the Pakistan... May 2024Autoimmune polyendocrine syndromes (APS) encompass m ultiple e ndocrin e gland ins ufficiencies asso ci ated wit h auto immune disease. This c as e report underscores...
Autoimmune polyendocrine syndromes (APS) encompass m ultiple e ndocrin e gland ins ufficiencies asso ci ated wit h auto immune disease. This c as e report underscores the importance of recognising the association between latent auto immune di a betes of ad ults (LADA) and type 3 polyglandular syndrome. A 42-year-old man belonging to R awalpi ndi, Pakistan, p resented to th e out patient department (OPD) of Ali Medi cal Centre, Islamab ad, i n Januar y 2023 with the complaints o f e xtreme thirs t and frequent urination. The patient reported consistently raised app etite an d eating four to five meals a day along with abrupt weight loss, dry mouth, fatigue occasional dizziness, an d dyspnoea. He was diagno s ed with type 3 polygla ndular syndrome w ith associat io n of LADA. Daily administration of 10 units of glargine insulin, along with six units of rapid-acting insulin, was prescribed. The patient's H bA1c level reduce d in a few months afte r succe ssive follow-up. Patients who exhi bit uncontrol led diabe tes despite dietar y and oral hypoglycaemic management should be further investigated for multiple au toimmune endocrine disorders.
Topics: Humans; Adult; Male; Polyendocrinopathies, Autoimmune; Latent Autoimmune Diabetes in Adults
PubMed: 38783454
DOI: 10.47391/JPMA.10108 -
Journal of the American Heart... Jun 2024Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations.
METHODS AND RESULTS
ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, =0.88).
CONCLUSIONS
DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.
Topics: Humans; Atrial Fibrillation; Rivaroxaban; Female; Male; Stroke; Aged; Warfarin; Factor Xa Inhibitors; Anticoagulants; Double-Blind Method; Middle Aged; Time Factors; Treatment Outcome; Morpholines; Thiophenes; Aged, 80 and over
PubMed: 38780169
DOI: 10.1161/JAHA.122.028951 -
GMS Journal For Medical Education 2024The aim of this paper is to present the development of a longitudinal curriculum for medical students that is rooted in the particularity of the medical sciences and...
OBJECTIVES
The aim of this paper is to present the development of a longitudinal curriculum for medical students that is rooted in the particularity of the medical sciences and that aims to build and strengthen medical students' scientific skills and use thereof in clinical practice.
METHODS
The curriculum development was initiated based on students' feedback on the initial curriculum. To improve and expand the curriculum appropriately, a needs assessment, a literature review to define science specific to the medical sciences and practice, and an analysis of national and international curricula were performed. The curriculum development followed the PDCA cycle (Plan-Do-Check-Act).
RESULTS
The curriculum extends across the entire medical study programme from semesters 1 to 10. It consists of the seminar series on basic conduct and the epistemological groundings of science, scientific methods in medical research and health sciences, statistics and the scientific internship. Up to the sixth semester, the focus is on the acquisition of skills and abilities to work on and carry out a concrete research project; starting in semester seven, the critical evaluation and application of research results in everyday clinical practice are introduced. The curriculum is taught by epidemiologists, anthropologists, statisticians and public health scholars. Starting in semester seven, seminars are generally taught together with clinicians as tandem teaching. The curriculum is regularly assessed and adjusted.
CONCLUSIONS
The Brandenburg Scientific Curriculum can be seen as a model of a longitudinal curriculum to teach scientific thinking and acting. One that is at the same time highly integrated in the medical curriculum overall. A central coordination point seems to be necessary to coordinate the teaching content and to ensure that teachers are interconnected. Furthermore, a complex curriculum in scientific methodology requires a set of teachers from a range of disciplinary backgrounds. To ensure equally high-quality education, the variability of research projects and faculty must be taken into account by establishing generally applicable evaluation criteria and fostering faculty development, and providing all students supporting courses throughout the research project.
Topics: Curriculum; Humans; Schools, Medical; Education, Medical, Undergraduate; Program Development; Germany; Science; Students, Medical
PubMed: 38779698
DOI: 10.3205/zma001671 -
BMC Psychology May 2024The objective of this study is to conduct a systematic review regarding the relationship between positive psychological factors, such as psychological well-being and...
OBJECTIVE
The objective of this study is to conduct a systematic review regarding the relationship between positive psychological factors, such as psychological well-being and pleasant emotions, and sports performance.
METHOD
This study, carried out through a systematic review using PRISMA guidelines considering the Web of Science, PsycINFO, PubMed and SPORT Discus databases, seeks to highlight the relationship between other more 'positive' factors, such as well-being, positive emotions and sports performance.
SETTINGS
The keywords will be decided by a Delphi Method in two rounds with sport psychology experts.
PARTICIPANTS
There are no participants in the present research.
ASSESSMENT
The main exclusion criteria were: Non-sport thema, sample younger or older than 20-65 years old, qualitative or other methodology studies, COVID-related, journals not exclusively about Psychology.
MAIN OUTCOMES MEASURES
We obtained a first sample of 238 papers, and finally, this sample was reduced to the final sample of 11 papers.
RESULTS
The results obtained are intended to be a representation of the 'bright side' of sports practice, and as a complement or mediator of the negative variables that have an impact on athletes' and coaches' performance.
CONCLUSIONS
Clear recognition that acting on intrinsic motivation continues to be the best and most effective way to motivate oneself to obtain the highest levels of performance, a good perception of competence and a source of personal satisfaction.
Topics: Humans; Athletic Performance; Athletes; Emotions; Personal Satisfaction; Motivation; Sports
PubMed: 38773650
DOI: 10.1186/s40359-024-01769-8 -
The Journal of Venomous Animals and... 2024Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be...
BACKGROUND
Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB).
METHODS
Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence.
RESULTS
Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery.
CONCLUSION
Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery.
PubMed: 38770186
DOI: 10.1590/1678-9199-JVATITD-2023-0065 -
BioRxiv : the Preprint Server For... May 2024Pseudouridine (psi) is one of the most abundant human mRNA modifications generated from the isomerization of uridine via psi synthases, including and . Nanopore direct...
Pseudouridine (psi) is one of the most abundant human mRNA modifications generated from the isomerization of uridine via psi synthases, including and . Nanopore direct RNA sequencing combined with our recent tool, Mod- ID, enables psi mapping, transcriptome-wide, without chemical derivatization of the input RNA and/or conversion to cDNA. This method is sensitive for detecting changes in positional psi occupancies across cell types, which can inform our understanding of the impact on gene expression. We sequenced, mapped, and compared the positional psi occupancy across six immortalized human cell lines derived from diverse tissue types. We found that lung-derived cells have the highest proportion of psi, while liver-derived cells have the lowest. Further, among a list of highly conserved sites across cell types, most are TRUB1 substrates and fall within the coding sequence. We find that these conserved psi positions correspond to higher levels of protein expression than expected, suggesting translation regulation. Interestingly, we identify cell type-specific sites of psi modification in ubiquitously expressed genes. We validate these sites by ruling out single-nucleotide variants, analyzing current traces, and performing enzymatic knockdowns of psi synthases. Finally, we characterize sites with multiple psi modifications on the same transcript (hypermodification type II) and found that these can be conserved or cell type specific. Among these, we discovered examples of multiple psi modifications within the same k-mer for the first time and analyzed the effect on current distribution. Our data support the hypothesis that motif sequence and the presence of psi synthase are insufficient to drive modifications, that psi modifications contribute to regulating translation and that cell type-specific trans-acting factors play a major role in driving pseudouridylation.
PubMed: 38766185
DOI: 10.1101/2024.05.08.593203 -
Epidemiology and Infection May 2024It is so far unclear how the COVID-19 winter waves started and what should be done to prevent possible future waves. In this study, we deciphered the dynamic course of a...
It is so far unclear how the COVID-19 winter waves started and what should be done to prevent possible future waves. In this study, we deciphered the dynamic course of a winter wave in 2021 in Saxony, a state in Eastern Germany neighbouring the Czech Republic and Poland. The study was carried out through the integration of multiple virus genomic epidemiology approaches to track transmission chains, identify emerging variants and investigate dynamic changes in transmission clusters. For identified local variants of interest, functional evaluations were performed. Multiple long-lasting community transmission clusters have been identified acting as driving force for the winter wave 2021. Analysis of the dynamic courses of two representative clusters indicated a similar transmission pattern. However, the transmission cluster caused by a locally occurring new Delta variant AY.36.1 showed a distinct transmission pattern, and functional analyses revealed a replication advantage of it. This study indicated that long-lasting community transmission clusters starting since early autumn caused by imported or locally occurring variants all contributed to the development of the 2021 winter wave. The information we achieved might help future pandemic prevention.
Topics: COVID-19; Germany; Humans; SARS-CoV-2; Seasons
PubMed: 38751220
DOI: 10.1017/S0950268824000761 -
Global Health, Science and Practice May 2024Understanding trends in contraceptive stock-outs, as well as their structural and demand-side correlates, is critical for policymakers and program managers to identify...
Understanding trends in contraceptive stock-outs, as well as their structural and demand-side correlates, is critical for policymakers and program managers to identify strategies to further anticipate, reduce, and prevent stock-outs. We analyzed trends as well as supply- and demand-side correlates of short-acting contraceptive method stock-outs by using data from multiple rounds of Performance Monitoring for Action Agile surveys. These data longitudinally measured contraceptive availability over 2 years (between November 2017 and January 2020) across 2,134 public and private service delivery points (SDPs) from urban areas of 5 countries (Burkina Faso, Democratic Republic of the Congo [DRC], India, Kenya, and Nigeria). For each country, we analyzed the trends and used multilevel mixed-effect logistic regression to model the odds of short-acting contraceptive stock-outs, adjusting for key structural and demand-side factors of the SDPs. Stock-outs in short-acting contraceptive methods were common in health facilities and varied markedly, ranging from as low as 2.9% (95% confidence interval [CI]=1.7%, 5.1%) in India to 51.0% (95% CIs=46.8%, 56.0%) in Kenya. During the observation period, stock-out rates decreased by 28% in the SDP samples in India (aOR=0.72, <.001) and 8% in Nigeria (aOR=0.92, <.001) but increased by 15% in DRC (aOR=1.15; 036) and 5% in Kenya (aOR=1.05, 003) with each round of data collection. Correlates of stock-out rates included the facility managerial authority (private versus public), whether the facility was rated high quality, whether the facility was at an advanced tier, and whether there was high demand for short-acting contraceptives. In conclusion, stock-outs of short-acting contraceptives are still common in many settings. Measuring and monitoring contraceptive stock-outs is crucial for identifying and addressing issues related to the availability and supply of short-acting contraceptives.
PubMed: 38744488
DOI: 10.9745/GHSP-D-23-00411 -
Frontiers in Plant Science 2024The uridine diphosphate (UDP)-glycosyltransferase (UGT) family is the largest glycosyltransferase family, which is involved in the biosynthesis of natural plant products...
INTRODUCTION
The uridine diphosphate (UDP)-glycosyltransferase (UGT) family is the largest glycosyltransferase family, which is involved in the biosynthesis of natural plant products and response to abiotic stress. UGT has been studied in many medicinal plants, but there are few reports on Platycodon grandiflorus. This study is devoted to genome-wide analysis of UGT family and identification of UGT genes involved in drought stress of Platycodon grandiflorus (PgUGTs).
METHODS
The genome data of Platycodon grandiflorus was used for genome-wide identification of PgUGTs, online website and bioinformatics analysis software was used to conduct bioinformatics analysis of PgUGT genes and the genes highly responsive to drought stress were screened out by qRT-PCR, these genes were cloned and conducted bioinformatics analysis.
RESULTS
A total of 75 PgUGT genes were identified in P.grandiflorus genome and clustered into 14 subgroups. The PgUGTs were distributed on nine chromosomes, containing multiple cis-acting elements and 22 pairs of duplicate genes were identified. Protein-protein interaction analysis was performed to predict the interaction between PgUGT proteins. Additionally, six genes were upregulated after 3d under drought stress and three genes (PGrchr09G0563, PGrchr06G0523, PGrchr06G1266) responded significantly to drought stress, as confirmed by qRT-PCR. This was especially true for PGrchr06G1266, the expression of which increased 16.21-fold after 3d of treatment. We cloned and conducted bioinformatics analysis of three candidate genes, both of which contained conserved motifs and several cis-acting elements related to stress response, PGrchr06G1266 contained the most elements.
DISCUSSION
PgGT1 was confirmed to catalyze the C-3 position of platycodin D and only eight amino acids showed differences between gene PGr008G1527 and PgGT1, which means PGr008G1527 may be able to catalyze the C-3 position of platycodin D in the same manner as PgGT1. Seven genes were highly expressed in the roots, stems, and leaves, these genes may play important roles in the development of the roots, stems, and leaves of P. grandiflorus. Three genes were highly responsive to drought stress, among which the expression of PGrchr06G1266 was increased 16.21-fold after 3d of drought stress treatment, indicating that PGrchr06G1266 plays an important role in drought stress tolerance. To summarize, this study laied the foundation to better understand the molecular bases of responses to drought stress and the biosynthesis of platycodin.
PubMed: 38742211
DOI: 10.3389/fpls.2024.1363251 -
Scandinavian Journal of Trauma,... May 2024Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as...
The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study.
BACKGROUND
Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants.
METHOD
Utilizing comprehensive two-year data from Region Skåne's emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery.
RESULTS
Out of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01-0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department.
CONCLUSION
In patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation.
TRIAL REGISTRATION
This is a retrospective cohort study, does not include any intervention, and has therefore not been registered.
Topics: Humans; Anticoagulants; Female; Retrospective Studies; Male; Aged, 80 and over; Intracranial Hemorrhages; Craniocerebral Trauma; Aged; Prevalence; Administration, Oral; Registries; Tomography, X-Ray Computed; Sweden; Middle Aged; Time Factors; Emergency Service, Hospital
PubMed: 38730480
DOI: 10.1186/s13049-024-01214-0