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The benzophenone (BP) family, including oxybenzone (BP-3), a prevalent sunscreen ingredient and environmental contaminant, has raised concerns since the year 2005. This study investigated oxybenzone toxicity in zebrafish (Danio rerio) eleutheroembryos and brine shrimp (Artemia salina) nauplii, focusing on the LC50 and developmental impacts. Zebrafish embryos (0.100–1.50 mg/L BP-3, 96 h) and A. salina (0.100–5.00 mg/L BP-3, 48 h) were tested with ultrasound-assisted emulsified liquid-phase microextraction (UA-ELPME) used for zebrafish tissue analysis. HPLC-DAD determined BP-3 concentrations (highest: 0.74 ± 0.13 mg/L). Although no significant zebrafish embryo mortality or hatching changes occurred, developmental effects were evident. Lethal concentrations were determined (A. salina LC50 at 24 h = 3.19 ± 2.02 mg/L; D. rerio embryos LC50 at 24 h = 4.19 ± 3.60 mg/L), with malformations indicating potential teratogenic effects. A. salina displayed intestinal tract alterations and D. rerio embryos exhibited pericardial edema and spinal deformities. These findings highlight oxybenzone’s environmental risks, posing threats to species and ecosystem health.

Abstract Background Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. Case presentation We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. Conclusion The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient’s needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Abstract Objective Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population. Methods This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017. Results The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p

Abstract In medicine, abnormalities in quantitative metrics such as the volume reduction of one brain region of an individual versus a control group are often provided as deviations from so-called normal values. These normative reference values are traditionally calculated based on the quantitative values from a control group, which can be adjusted for relevant clinical co-variables, such as age or sex. However, these average normative values do not take into account the globality of the available quantitative information. For example, quantitative analysis of T1-weighted magnetic resonance images based on anatomical structure segmentation frequently includes over 100 cerebral structures in the quantitative reports, and these tend to be analyzed separately. In this study, we propose a global approach to personalized normative values for each brain structure using an unsupervised Artificial Intelligence technique known as generative manifold learning. We test the potential benefit of these personalized normative values in comparison with the more traditional average normative values on a population of patients with drug-resistant epilepsy operated for focal cortical dysplasia, as well as on a supplementary healthy group and on patients with Alzheimer’s disease.

Abstract Background Nasal airway stenosis may lie anterior and/or posterior to the piriform aperture. We intended to compare the nasal airway anterior and posterior to the piriform aperture in patients with and without nasal obstruction. Methods Segmented computed tomography cross-sectional areas of the nasal airway anterior (CT-CSAant) and posterior to the piriform aperture (at the level of the head of the inferior turbinate; CT-CSApost) were compared between patients with nasal obstruction (cases) and trauma controls. CT-CSA were approximately perpendicular to the direction of the nasal airflow. Anterior to the piriform aperture, they were tilted about 30o, 60o and 90o to the nasal floor. Posterior to the piriform aperture, they were tilted about 50o, 80o and 100o to the nasal floor. In cases, we examined the Pearson’s correlation of active anterior rhinomanometry with CT-CSAant and CT-CSApost. Results Narrow and bilateral CT-CSApost were similarly large between 56 cases and 56 controls (all p > 0.2). On the contrary, narrow and bilateral CT-CSAant were significantly smaller in cases than in controls (all p 0.056). Conclusions The nasal airway anterior to the piriform aperture was smaller in patients with nasal obstruction due to skeletal nasal stenosis than that in controls. On the contrary, the nasal airway posterior to the piriform aperture was similarly large between patients with and without nasal obstruction. Furthermore, in patients with nasal obstruction, the anterior nasal airway was narrower compared to that located posterior to it. On the contrary, control patients’ anterior nasal airway was as large as the posterior one.

Se determinó el comportamiento a la fatiga en un tornillo de acero micro aleado AISI 4140 empleado en la culata del motor de combustión interna MAN B&W a través del Método de los Elementos Finitos. A partir de tamaño crítico de grietas de 4,2; 6,2; 8,1 y 21,6 se estableció la metodología de cálculo donde se consideró la carga distribuida de contacto y de rozamiento, las solicitaciones, el esfuerzo normal y el de corte, para determinar el fenómeno de la fractura en el tornillo. Se comprobó que la falla por fatiga del tornillo inicia con tensiones de Von Misses mínimas de 401,8 MPa; las cuales se incrementan hasta un valor máximo de 1 796 MPa; provocando la falla por fractura en los primeros filetes de rosca. La carga aplicada de 2 369 149,4 N; genera un esfuerzo cortante máximo de 104,55 Nm2, siendo este el pico máximo de resistencia antes que se produzca el fallo por fractura y que al ejercer una fuerza de 297 918,52 N; inicia un cambio en el límite elástico de este acero con la propagación de grietas, siendo el valor de 6,2 mm, la zona de transición entre las deformaciones elásticas y plásticas con incremento de la deformación.

Abstract Background Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. Methods A case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search. Results Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases. Conclusions Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations. Key points We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4–7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.

Abstract We present a new event generator for the simulation of both neutral- and charged-current deep inelastic scattering (DIS) at next-to-leading order in QCD matched to parton showers using the POWHEG method. Our implementation builds on the existing POWHEG BOX framework originally designed for hadron-hadron collisions, supplemented by considerable extensions to account for the genuinely different kinematics inherent to lepton-hadron collisions. In particular, we present new momentum mappings that conserve the special kinematics found in DIS, which we use to modify the POWHEG BOX implementation of the Frixione-Kunszt-Signer subtraction mechanism. We compare our predictions to fixed-order and resummed predictions, as well as to data from the HERA ep collider. Finally we study a few representative distributions for the upcoming Electron Ion Collider.

Abstract Background Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case–control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes. Results The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m2). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10–12) and rs2228260 within XBP1 (P = 3.68 × 10–8). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10–6). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10–9) and a gene-based association was identified with ERBB4 (P = 1.59 × 10–6). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata. Conclusions Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

Abstract Background Up to 27% of the German population suffers from recurrent or persistent pain (lasting more than three months). Therefore, prevention of chronic pain is one major object of pain management interventions. The aim of this nationwide, multicentre, randomised controlled trial is to evaluate the efficacy of a 10-week ambulatory (outpatient) interdisciplinary multimodal pain therapy (A-IMPT) for patients with recurrent pain and at risk of developing chronic pain. This project was initiated by the German Pain Society (Deutsche Schmerzgesellschaft e.V.) and the public health insurance provider BARMER. It is currently funded by the German Innovation Fund (01NVF20023). The study PAIN2.0 focuses on reducing pain intensity and pain-related disability and investigates whether this intervention can improve physical activity, psychological well-being, and health literacy. Methods PAIN2.0 is designed as a multicentre 1:1 randomised controlled trial with two parallel groups (randomisation at the patient level, planned N = 1094, duration of study participation 12 months, implemented by 22 health care facilities nationwide). After 6 months, patients within the control group also receive the intervention. The primary outcomes are pain intensity and pain-related impairment, measured as Characteristic Pain Intensity (PI) and Disability Score (DS) (Von Korff), as well as patient-related satisfaction with the intervention. Secondary outcomes are the number of sick leave days, sickness allowance, treatment costs, psychological distress, health-related quality of life, and catastrophizing. The effects of the intervention will be analysed by a parallel-group comparison between the intervention and control groups. In addition, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group before and after the intervention will be performed. Discussion Recurrent or persistent pain is common in the German population and causes high costs for patients and society. The A-IMPT aims to improve pain and pain-related impairments in pain patients at risk of chronification, thereby reducing the risk of developing chronic pain with its high socioeconomic burden. This new therapy could easily be integrated into existing therapy programs if positively evaluated. Trial registration The trial PAIN2.0 has been registered in the German Clinical Trials Register (DRKS) since 21/11/2022 with the ID DRKS00030773 .

The interface formation and chemical and electronic structure of the (Cd,Zn)S:Ga/CuSbS2 thin-film solar cell heterojunction were studied using hard X-ray photoelectron spectroscopy (HAXPES) of the bare absorber and a buffer/absorber sample set for which the buffer thickness was varied between 1 and 50 nm. We find a heavily intermixed interface, involving Cu, Zn, and Cd as well as significant Ga and Cu profiles in the buffer. The valence band (VB) offset at the buffer/absorber interface was derived as (−1.3 ± 0.1) eV, which must be considered an upper bound as the Cu diffused into the buffer might form a Cu-derived VB maximum located closer to the Fermi level. The estimated conduction band minimum was 'cliff'-like; a situation made more severe considering the Cu-deficiency found for the CuSbS2 surface. The complex interface structure's effect on the performance of (Cd,Zn)S:Ga/CuSbS2-based solar cells and its limitation is discussed together with possible mitigation strategies. [ABSTRACT FROM AUTHOR]