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Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of −1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p = 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p = 0.166; average supination: 83.5° vs. 85.7°, p = 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p = 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusions: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine adverse perinatal outcomes related to maternal preconception body mass index (BMI). Study Design This is a retrospective observational cohort study at a single institution of 500 consecutive mothers of normal weight with a preconception BMI of 18.5 to less than 25 and 500 additional obese mothers with a preconception BMI more than or equal to 30. Maternal/newborn metrics were stratified by maternal preconception BMI and trend analysis was performed both by simple univariable and multivariable logistic regression analysis. Results The study included 858 mother/baby dyads after 142 were excluded. Trend analysis demonstrated higher preconception BMI was significantly associated with progressively higher rates of cesarean section (p < 0.001), preeclampsia p < 0.001), gestational diabetes (p < 0.001), preterm birth (p = 0.001), lower 1- and 5 minutes Apgar scores (p < 0.001), and neonatal intensive care unit admission (p = 0.002). These associations remained significant in both simple univariable and multivariable logistic regression models. Conclusion We demonstrated obese women are more likely to have maternal complications and neonatal morbidity when compared with normal weight mothers. Maternal and fetal complications increase with increasing obesity with superobese mothers (BMI ≥ 50) having more perinatal adverse outcomes when compared with other classes of obesity. It is reasonable to counsel weight loss prior to conception of women with BMI more than or equal to 30 in an effort to reduce maternal complications and neonatal morbidity related to pregnancy. Key Points Maternal obesity is associated with adverse outcomes. Complications increase with increasing obesity. Superobese mothers have the most adverse outcomes. [ABSTRACT FROM AUTHOR]

Evaluation and mitigation of the potential carcinogenic risks associated with nitrosamines in marketed pharmaceutical products are areas of interest for pharmaceutical companies and health authorities alike. Significant progress has been made to establish acceptable intake (AI) levels for N‐nitrosamine drug substance‐related impurities (NDSRIs) using SAR, however some compounds require experimental data to support derivation of a recommended AI. Many angiotensin‐converting enzyme inhibitors, identified by the suffix "pril," have secondary amines that can potentially react to form nitrosamines. Here we consider a structural assessment and metabolism data, coupled with comprehensive in vitro and in vivo (mouse) genotoxicity testing to evaluate this particular class of nitrosamines. N‐nitroso ramipril and N‐nitroso quinapril, both of which are predicted to have inhibited nitrosamine bioactivation due to steric hinderance and branching at the α‐position were non‐genotoxic in the in vivo liver comet assay and non‐mutagenic in the in vivo Big Blue® mutation and duplex sequencing assays. Predicted metabolism along with in vitro metabolism data and quantum chemical calculations related to DNA interactions offer a molecular basis for the negative results observed in both in vitro and in vivo testing. These nitrosamines are concluded to be non‐mutagenic and non‐carcinogenic; therefore, they should be controlled according to ICH Q3B guidance. Furthermore, these results for N‐nitroso ramipril and N‐nitroso quinapril should be considered when evaluating the appropriate AI and control strategy for other structurally similar "pril" NDSRIs. [ABSTRACT FROM AUTHOR]

To identify factors associated with poor prognoses in newborns with a prenatal diagnosis of gastroschisis in eight hospitals in Bogota, Colombia, from 2011 to 2022. A multi-center retrospective case-control study was conducted on newborns with gastroschisis in eight hospitals in Bogota, Colombia. Poor prognosis was defined as the presence of sepsis, intestinal complications, or death. The study included 101 patients. Preterm newborns under 32 weeks had a poor neonatal prognosis (OR 6.78 95 % CI 0.75–319). Oligohydramnios (OR 4.95 95 % CI 1.15–21.32) and staged closure with silo (OR 3.48; 95 % CI 1.10–10.96) were risk factors for neonatal death, and intra-abdominal bowel dilation of 20–25 mm was a factor for the development of intestinal complications (OR 3.22 95 % CI 1.26–8.23). Intra-abdominal bowel dilation between 20 and 25 mm was associated with intestinal complications, while oligohydramnios was associated with the risk of perinatal death, requiring increased antenatal surveillance of fetal wellbeing. Management with primary reduction when technically feasible is recommended in these infants, considering that the use of silos was associated with higher mortality. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma of the eyelid (MCCE) is a rare yet aggressive neuroendocrine tumour associated with significant morbidity and mortality. This study aimed to investigate survival trends and demographic factors related to MCCE, 2000–2019, using the Surveillance, Epidemiology, and End Results (SEER) Program. Cases were analysed by demographic parameters, disease properties, and survival. Statistical analyses were performed via a dedicated computerized software package. A total 349 cases of MCCE were identified, accounting for 2% of all MCC cases in the United States during that time. Of note, the incidence of MCCE remained stable over the study period (p =.35). Female patients accounted for 56% of the cases, and males for 44%. White patients accounted for 90.8% of the the cases, and Black patients for 2.9%. MCCE incidence increased with age, with the majority of patients age 85+ (p <.05). Incidence was greatest in metropolitan areas and among those with median incomes >$75,000/year. Income correlated with likelihood of MCCE diagnosis (p <.05). Analysis of 5-year survival data showed 20% of the patients died due to MCCE within 5 years of diagnosis. Of these, the majority died within one year of diagnosis. Consistent with previous reports, most patients were white, female, and age 85+.Incidence correlated with metropolitan environments and median income. While most patients did not die from MCCE, majority of recorded deaths occurred within one year of diagnosis. [ABSTRACT FROM AUTHOR]

Objective To investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.Design A prospective observational study.Setting Public healthcare system in Santa Clara County (California, USA).Participants Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021.Outcomes SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.Results Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p

Professional identity development (PID) is a growing focus for higher education researchers interested in graduate employability and workplace readiness. This raises the challenge of how to trace students’ identity shifts. This paper shows how Margaret Archer’s agential morphogenesis can be used to generate understandings of how students’ identities change during professional degree programmes. Archer’s theories of double and triple morphogenesis are applied to data collected through interviews and documentary research. The findings are presented as narratives about two final-year electrical engineering students who participated in employability-development focussed courses at a South African university. These narratives offer in-depth descriptions of the students’ identity shifts as they neared completion of their studies. The richness of the findings, which incorporate the constraints and enablements of the students’ professional identity development, leads to the paper’s argument that agential morphogenesis is a productive analytical tool for researchers wanting to better understand PID in higher education.

Stroke identification is a key step in acute ischemic stroke management. Our objectives were to prospectively examine the agreement between prehospital and hospital Modified National Institutes of Health Stroke Scale (mNIHSS) assessments as well as assess the prehospital performance characteristics of the mNIHSS for identification of large vessel occlusion strokes.Method: In this prospective cohort study conducted over a 20-month period (11/2016–6/2018), we trained 40 prehospital providers (paramedics) in Emergency Neurological Life Support (ENLS) curriculum and in mNIHSS. English-speaking patients aged 18 and above transported for an acute neurological deficit were included. Using unique identifiers, we linked the prehospital assessment records to the hospital record. We calculated the agreement between prehospital and hospital mNIHSS scores using the Bland-Altman analysis and the sensitivity and specificity of the prehospital mNIHSS.Results: Of the 31 patients, the mean difference (prehospital mNIHSS—hospital mNIHSS) was 2.4, 95% limits of agreement (−5.2 to 10.0); 10 patients (32%) met our a priori imaging definition of large vessel occlusion and the sensitivity of mNIHSS ≥ 8 was 6/10 or 0.60 (95% CI: 0.26–0.88) and the specificity was 13/21 or 0.62 (95% CI: 0.38–0.82), respectively.Conclusions: We were able to train prehospital providers to use the prehospital mNIHSS. Prehospital and hospital mNIHSS had a reasonable level of agreement and and the scale was able to predict large vessel occlusions with moderate sensitivity.

ABSTRACT Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6−/−). Micro‐computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6−/− tibias (p 0.01) and osteoid surface (p

The rodent dorsal window chamber is a widely used in vivo model of the microvasculature. The model consists of a 1cm region of exposed microvasculature in the rodent dorsal skin that is immobilized by surgically implanted titanium frames, allowing the skin microvasculature to be visualized. We describe a detailed protocol for surgical implantation of the dorsal window chamber which enables researchers to perform the window chamber implantation surgery. We further describe subsequent wide-field functional imaging of the chamber to obtain hemodynamic information in the form of blood oxygenation and blood flow on a cm size region of interest. Optical imaging techniques, such as intravital microscopy, have been applied extensively to the dorsal window chamber to study microvascular-related disease and conditions. Due to the limited field of view of intravital microscopy, detailed hemodynamic information typically is acquired from small regions of interest, typically on the order of hundreds of μm. The wide-field imaging techniques described herein complement intravital microscopy, allowing researchers to obtain hemodynamic information at both microscopic and macroscopic spatial scales. Compared with intravital microscopy, wide-field functional imaging requires simple instrumentation, is inexpensive, and can give detailed metabolic information over a wide field of view.

Context: Ilizarov method of bone transport is a well-recognized method in treating bone loss; however, soft tissue complications and potential flap compromise associated with the transport process are a major drawback. Aim: We propose the use of a central transport system of cables and pulleys, as introduced by Weber in 1998 to help preserve soft tissue cover, retain flap integrity, and decrease patient discomfort. Design: This was a retrospective study. Patients and Methods: Consecutive series of patients treated for severe bone loss and fragile soft tissue cover, between 2013 and 2018, according to the Weber method of bone transport, were included in the study. In total, six cases were identified. Inclusion criteria were any patient who underwent bone transport using the Weber method due to bone loss caused by trauma or infection. Exclusion criteria were any patient who did not complete the bone distraction process or had a follow-up of < 1 month after bone transport apparatus installation. Results: Five out of six patients completed the bone transport process; one case was excluded from the results since the patient was lost to follow-up before bone distraction was begun. The average follow-up was 13.2 months; no patient had soft tissue complications, the transport process was painless, and the flap integrity was maintained. Bone regenerate was good in all except one case since the patient was lost to follow-up a month after transport was initiated. Conclusion: The Weber method is a reliable technique generating good-quality bone, while maintaining the integrity of the soft tissue envelope, minimizing soft tissue complications associated with the classical method of bone transport. The Weber technique is especially valuable when bone transport is performed in a flap covered area, where the excursion of half pins and K-wires can compromise flap survival.

The intrinsic drivers of glioblastoma (GBM) migration are still poorly understood. Here the authors purify GBM stem cells (GSCs) from patients and profile chromatin accessibility in these cells, identifying TEAD1 as a regulator of migration in human glioblastoma.

Abstract Background Metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (DM2) are all linked to diabetic cardiomyopathy that lead to heart failure. Cardiomyopathy is initially characterized by cardiomyocyte hypertrophy, followed by mitochondrial dysfunction and fibrosis, both of which are aggravated by angiotensin. Caloric restriction (CR) is cardioprotective in animal models of heart disease through its catabolic activity and activation of the expression of adaptive genes. We hypothesized that in the diabetic heart; this effect involves antioxidant defenses and is mediated by SIRT1 and the transcriptional coactivator PGC-1α (Peroxisome proliferator-activated receptor-γ coactivator). Methods Obese Leptin resistant (db/db) mice characterized by DM2 were treated with angiotensin II (AT) for 4 weeks to enhance the development of cardiomyopathy. Mice were concomitantly either on a CR diet or fed ad libitum. Cardiomyocytes were exposed to high levels of glucose and were treated with EX-527 (SIRT1 inhibitor). Cardiac structure and function, gene and protein expression and oxidative stress parameters were analyzed. Results AT treated db/db mice developed cardiomyopathy manifested by elevated levels of serum glucose, cholesterol and cardiac hypertrophy. Leukocyte infiltration, fibrosis and an increase in an inflammatory marker (TNFα) and natriuretic peptides (ANP, BNP) gene expression were also observed. Oxidative stress was manifested by low SOD and PGC-1α levels and an increase in ROS and MDA. DM2 resulted in ERK1/2 activation. CR attenuated all these deleterious perturbations and prevented the development of cardiomyopathy. ERK1/2 phosphorylation was reduced in CR mice (p = 0.008). Concomitantly CR prevented the reduction in SIRT activity and PGC-1α (p

Background. The vulnerability of migrant women, especially those coming from patriarchal societies, leads to the increase of gender violence. This is incremented by a myriad of socio-ecological determinants related to the immigration process and to the nature of male-female relationships. Objectives. The main objective is to conduct a preliminary analysis of recent publications dealing with the relations between gender violence and migrant populations in the European Union, including internally displaced people. Materials and methods. This paper is based on a revision of scientific publications from SCOPUS that relate to migrant women who are victims of gender violence in the European Union. The qualitative thematic analysis was used in order to identify the main issues targeted in the articles. Results. The thematic analysis of the studies reviewed dealing with migration and gender violence highlighted several important themes, including prevalence of violence against migrant women; the forms and contexts of gender violence; the impact of legal, economic environments and socio-cultural barriers; the influence of conflict and war; the impact and consequences of violence, especially on women’s mental health, as well as strategies and suggestions for interventions. Conclusions. Increasing the awareness of migration, regarding the conflicts and problems experienced by migrants (of both genders), could enable health and legal authorities to offer more significant culture and gender sensitive services, thus reducing gender violence.

Objectives. The Far North region of Cameroon has one of the highest neonatal, child mortality and poverty rates in the country. The aim of this study was to understand the gender and culture-related barriers to women’s utilization of RMNCH (reproductive, maternal, neonatal and child health), including HIV services. Material and methods. A participatory qualitative Rapid Assessment Process (RAP) was used and team members included women from the communities involved. Results. Diseases affecting infants are explained by causes ranging from bad nutrition to sorcery and angry ancestors' spirits and traditional treatments are often preferred over medical services. Pregnancy is considered a natural state and a “women's issue”, which is accompanied by cultural and religious norms that protect mother and fetus. Many women give birth at home with traditional birth attendants, who are trusted and follow accepted practices. Pregnant women living with HIV fear disclosing their status since this may lead to stigma and discrimination. Unequal gender power relations - including financial dependency on the husband - pose an additional barrier to service uptake, further enhanced by low male involvement in pregnancy-related health services. Lack of respect and confidentiality by health providers, associated with low-level availability and accessibility of services may also discourage their uptake. Conclusions. The implementation of the RAP findings may enable innovative ways to increase culture and gender sensitivity of RMNCH services, including prevention of vertical transmission of HIV, in communities in Far North of Cameroon