To Tranexamic Acid or Not to Tranexamic Acid? Accuracy of Antifibrinolytic Administration at Altitude.

Objective: Tranexamic acid (TXA) has demonstrated a reduction in all-cause mortality in trauma patients with hemorrhage. Administering TXA in the prehospital setting presents unique challenges because the identification of bleeding is based on clinical suspicion without advanced imaging or diagnostic tools. The objective of this study was to examine whether prehospital suspicion of bleeding is validated by in-hospital computed tomographic imaging and examination and to determine if patients received TXA in the absence of hemorrhage.

Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study.

The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8676 children, 3-4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1119 children in a nested case-control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter.

Characterization of phenotypic range in DYRK1A haploinsufficiency syndrome using standardized behavioral measures.

DYRK1A haploinsufficiency syndrome is a well-established neurodevelopmental disorder, but detailed information on the range of cognitive and behavioral issues associated with the condition is limited. We studied 24 participants with likely pathogenic or pathogenic variants in DYRK1A through the Simons Searchlight study and systematically assessed their medical history and development using standardized instruments: Vineland Adaptive Behavior Scale II (VABS-II) and Child Behavior Checklists/1.5-5 and 6-18 (CBCL/1.

Alterations in magnetic resonance imaging characteristics of bioabsorbable magnesium screws over time in humans: a retrospective single center study.

Objectives: This study aimed to examine the alterations in magnetic resonance imaging (MRI) characteristics of bioabsorbable magnesium (Mg) screws over time in a single center study in humans.

Methods: Seventeen patients who underwent medial malleolar (MM) fracture or osteotomy fixation using bioabsorbable Mg screws and had at least one postoperative MRI were included in this retrospective study. Six of them had more than one MRI in the postoperative period and were subject of the artifact reduction measurements.

Disrupting circadian rhythms promotes cancer-induced inflammation in mice.

Disruption of circadian rhythms occurs in rotating shift-work, jetlag, and in individuals with irregular sleep schedules. Circadian disruption is known to alter inflammatory responses and impair immune function. However, there is limited understanding of how circadian disruption modulates cancer-induced inflammation.

Cardiovascular disease in the elderly: proceedings of the European Society of Cardiology-Cardiovascular Round Table.

The growing elderly population worldwide represents a major challenge for caregivers, healthcare providers, and society. Older patients have a higher prevalence of cardiovascular (CV) disease, high rates of CV risk factors, and multiple age-related comorbidities. Although prevention and management strategies have been shown to be effective in older people, they continue to be under-used, and under-studied.

Costs of Public Health Screening of Children for Presymptomatic Type 1 Diabetes in Bavaria, Germany.

Objective: We sought to evaluate costs associated with public health screening for presymptomatic type 1 diabetes in 90,632 children as part of the Fr1da study in Bavaria and in forecasts for standard care.

Research Design And Methods: We report on resource use and direct costs for screening-related procedures in the Fr1da study coordination center and laboratory and in participating pediatric practices and local diabetes clinics. Data were obtained from Fr1da study documents, an online survey among pediatricians, and interviews and records of Fr1da staff members.

Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies.

Objective: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations.

Research Design And Methods: To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505).

The Structure of Social Networks and Its Link to Higher Education Students' Socio-Emotional Loneliness During COVID-19.

Lonely students typically underperform academically. According to several studies, the COVID-19 pandemic is an important risk factor for increases in loneliness, as the contact restrictions and the switch to mainly online classes potentially burden the students. The previously familiar academic environment (campus), as well as the exchange with peers and lecturers on site, were no longer made available.

Improving the Affordability of Anticancer Medicines Demands Evidence-Based Policy Solutions.

The high cost of many new anticancer medicines significantly impedes breakthrough discoveries from reaching patients. A commonly heard refrain is that high prices are necessary to compensate for the high costs of research and development (R&D). Yet, there are promising policy proposals aimed at improving affordability without compromising innovation.

Affordable Prices Without Threatening the Oncological R&D Pipeline-An Economic Experiment on Transparency in Price Negotiations.

The high prices of innovative medicines endanger access to care worldwide. Sustainable prices need to be affordable while sufficiently incentivizing research and development (R&D) investments. A proposed solution is increased transparency.

[Precision medicine in pediatric neurology exemplified by the new treatment forms].

Background: In recent years the possibilities for molecular diagnostics and treatment of rare childhood diseases have greatly improved. The first gene-modifying drugs have now been approved, leading to a new era of precision treatment in pediatric neurology.

Objective: This article describes the dynamic developments of precision medicine in pediatric neurology in the areas of prevention, diagnostics and targeted treatment.

Cytotoxicity-Related Gene Expression and Chromatin Accessibility Define a Subset of CD4+ T Cells That Mark Progression to Type 1 Diabetes.

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of children at risk associated with progression to islet autoimmunity.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

Aims: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population.

Methods And Results: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.

Short-term Housing in Metabolic Caging on Measures of Energy and Fluid Balance in Male C57BL/6J Mice ( ).

Metabolic caging is an important tool for quantitative urine and feces collection in rodents, although significant limitations and problems accompany its use. Despite strong opinions among investigators regarding the effects of metabolic caging on energy and fluid homeostasis, careful quantitative analysis of the impact of this caging type-particularly when used for mice-is lacking. The current study assessed the effects of metabolic caging, with or without modifications such as plastic platform inserts, on ingestive behaviors, energy expenditure, accuracy of urine and fecal collection, and ambulatory activities in male C57BL/6J mice.

100 Years of Insulin: Lifesaver, immune target, and potential remedy for prevention.

In this review, we bring our personal experiences to showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as an opportunity to prevent autoimmune diabetes. The work covers the birth of insulin to treat patients, which is now 100 years ago, the development of human insulin, insulin analogues, devices, and the way into automated insulin delivery, the realization that insulin is the primary autoimmune target of type 1 diabetes in children, novel approaches of immunotherapy using insulin for immune tolerance induction, the possible limitations of insulin immunotherapy, and an outlook how modern vaccines could remove the need for another 100 years of insulin therapy.

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency.

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects.

Distribution of RET proto-oncogene variants in children with appendicitis.

Background: In addition to patient-related systemic factors directing the immune response, the pathomechanisms of appendicitis (AP) might also include insufficient drainage leading to inflammation caused by decreased peristalsis. Genetic predisposition accounts for 30%-50% of AP. M.

Age-Dependent Intestinal Repair: Implications for Foals with Severe Colic.

Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes.

A hormone complex of FABP4 and nucleoside kinases regulates islet function.

The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4). Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans, no mechanism of action has yet been described.

Sensitization of the reinforcing value of high energy density foods is associated with increased zBMI gain in adolescents.

Background/objectives: Characterizing behavioral phenotypes that predict increased zBMI gain during adolescence could identify novel intervention targets and prevent the development of obesity. The purpose of this study was to determine if sensitization of the relative reinforcing value (RRV) of high (HED) or low energy density (LED) foods predicts adolescent weight gain trajectories. A secondary aim was to test the hypothesis that relationships between sensitization of the RRV of food and weight change are moderated by delay discounting (DD).

How Mentors Think About the Attainability of Mentoring Goals: The Impact of Mentoring Type and Mentoring Context on the Anticipated Regulatory Network and Regulatory Resources of Potential Mentors for School Mentoring Programs.

Research shows that trained mentors achieve better results than untrained ones. Their training should particularly address their expectations for their future mentoring. Our study involved 190 preservice teachers, potential mentors of ongoing school mentoring for primary and secondary school students of all grades.