BACKGROUND: Newborn screening (NBS) and its genetic version, genetic NBS (gNBS), are now used to identify a broad range of conditions, including metabolic, endocrine, and genetic disorders, leading to significant reductions in infant mortality and long-term complications. Advances in genomic technologies, particularly next-generation sequencing, have enhanced the ability to detect rare diseases early, using gNBS, improving long-term outcomes. The availability and scope of gNBS vary across countries, influenced by national policies and technological advancements. This systematic literature review aims to clarify the specific barriers, opportunities, and more general attitudes that stakeholders express about gNBS for rare diseases. MAIN: We extracted articles from 2010 to 2022. We followed the PRISMA guidelines and registered the review via PROSPERO (CRD42022297678). From an initial retrieval of 4519 records, two selection rounds resulted in a final list of 112 articles, which were assessed across different categories exploring various aspects of gNBS. The most important perceived opportunities in gNBS were the benefits of early intervention to reduce the burden of the diagnostic odyssey. The main identified barriers included three key codes: the stress and risk associated with false results and dealing with uncertainty (n = 25), the psychosocial implications (n = 26), and misunderstandings due to lack of education or communication. The majority of respondents expressed positive views, particularly regarding actionability. CONCLUSION: The results indicate a generally favourable attitude toward newborn screening, with subtle variations in viewpoints. Our findings on these themes can specifically inform how final attitudes are shaped based on particular aspects.
This study examines the impact of cognitive load (CL) on lower limb biomechanics during the take-off preparation phase of the platform serve in tennis players of varying skill levels. Fifteen elite and fifteen amateur tennis players performed platform serves before and after completing a 30-minute Stroop task designed to induce CL. Key biomechanical parameters, including joint range of motion (ROM), joint moments, centre of mass (COM) displacement, and ground reaction force (GRF), were assessed using both kinematic and kinetic analysis. After CL, the biomechanical performance of amateur athletes significantly decreased compared to elite athletes. Specifically, amateur athletes showed a 14.19° lower ankle joint range of motion in the sagittal plane (p < 0.001), a 0.04-meter lower COM displacement in the frontal plane (p = 0.017), and a 0.15 Nm/BW lower knee extension moment (p < 0.001). CL adversely affects the lower limb biomechanics of amateur players more than elite players, with elite players demonstrating greater stability. These findings suggest that elite players have developed more efficient motor control mechanisms through extensive training. Tailored training interventions that account for different skill levels could enhance performance stability and mitigate the risk of injury.
Traditional surgical treatment for gynecomastia has multiple complications. Recently, energy-based therapies have gained popularity over conventional surgical treatments, including liposuction using radiofrequency energy, power-assisted liposuction, ultrasound-assisted liposuction, and laser-assisted lipolysis (LAL). This work aims to assess LAL efficacy and glandular tissue treatment using a 1470-nm laser for gynecomastia to correct breast volume, flaccidity, and skin tightening without its removal. This prospective, single-blinded randomized controlled trial was conducted on 30 patients enrolled in the National Institute of Laser Enhanced Sciences outpatient clinic who had gynecomastia classified according to the Simon standard. The participants were randomly allocated to 2 groups: group 1 (n = 15) received conventional liposuction (suction-assisted liposuction), and group 2 received LAL (1470-nm diode laser) treatment. Patients were assessed using the BREAST-Q scale. All patients achieved satisfactory results. The BREAST-Q scores were significantly higher in group 2 compared with group I (P < 0.005). Visual analog scale scores significantly decreased in group 2 (P < 0.001) compared with group 1. Group 2 had significantly improved aesthetic outcomes compared with group 1 (P < 0.001). In group 1, skin retraction and hematoma incidence were significantly greater than in group 2 (P = 0.014, <0.001). The LAL described is safe and reproducible. It showed a higher BREAST-Q value, a significantly better aesthetic outcome, and fewer postoperative complications.
Patients undergoing anterior cruciate ligament reconstruction (ACLR) are at high risk of osteoarthritis or secondary injuries, with abnormal knee contact forces (KCFs) identified as a key factor in joint degeneration. Traditional KCF assessment relies on expensive lab systems while advances in computer vision and AI now enable low-cost alternatives. However, currently available methods oversimplify knee mechanics and neglect compensatory movements, highlighting the urgent need for intelligent, real-time monitoring tools for personalized rehabilitation. Therefore, the aim of this study was to develop and validate an integrated, non-invasive framework for accurate KCFs prediction in ACLR patients during daily activities. We hypothesized that combining enhanced musculoskeletal modeling with a deep learning architecture incorporating spatiotemporal attention would improve the prediction accuracy across multiple movement tasks. This study simultaneously recorded three daily movements of 29 post-ACLR patients using both Vicon and OpenCap. Motion trajectories captured by Vicon were imported into OpenSim for musculoskeletal modeling and KCFs calculation. Dataset comprising OpenCap-derived kinematics and OpenSim-computed KCFs was used to train 3 learning models for the prediction of KCFs in ACLR patients across different movements. Among three models, CNN-BiGRU-Attention model demonstrated the best predictive performance across all three movement tasks (R2walking = 0.973 ± 0.003, R2running = 0.982 ± 0.004, R2descending stairs = 0.951 ± 0.007). CNN and self-attention mechanism collectively enhanced the model's ability to capture key features in ACLR patients' movement data, thereby improving KCF prediction accuracy. Furthermore, for the three daily activities, all models showed superior KCFs prediction performance in running and stair-descent tasks compared to walking. The developed framework successfully achieved high-precision prediction of KCFs. This technological breakthrough not only provides a real-time quantitative tool for rehabilitation monitoring in patients with ACLR, but also facilitates a paradigm shift from static laboratory analysis to dynamic real-time monitoring, with broad application prospects in sports medicine, rehabilitation engineering.
This study evaluates microplastic contamination within critical agricultural infrastructure by examining the Anzaldúas and Rodhe irrigation canals in Reynosa, Mexico. To ensure geographical representativeness while managing analytical throughput, we implemented an in situ composite sampling design, pooling field triplicates across four strategic locations. We processed the resulting matrices through vacuum filtration onto microstructured silicon nitride nanomembranes, followed by hydrophobic staining with Nile Red fluorophore and automated fluorescence imaging under a TRITC optical channel. Image processing utilized a customized digital watershed segmentation macro to isolate, count, and morphologically classify individual synthetic particles. Our findings reveal a pronounced spatial heterogeneity in pollutant loading, establishing a clear decreasing contamination gradient: Rodhe Internal (RI) > Rodhe External (RE) > Anzaldúas Internal (AI) > Anzaldúas External (AE). The Rodhe Canal emerged as the primary vector for microplastic transport; the internal site (RI) exhibited the highest contamination profile (55.73 particles/mL; 2.99 µg), followed by the external site RE (19.64 particles/mL; 1.52 µg). Conversely, the Anzaldúas Canal displayed substantially lower incidence, yielding 2.61 particles/mL (0.48 µg) at the internal site (AI) and a baseline minimum of 1.31 particles/mL (0.09 µg) at the external site (AE). Morphological analysis identified fragments and fibers as the predominant particle types. Crucially, all sites exceeded laboratory blanks by 13.05 to 557.3 times, demonstrating persistent anthropogenic alteration. This work establishes the first regional quantitative baseline within this vital agricultural corridor, validating an efficient, high-throughput diagnostic tool to guide targeted water management policies in northeastern Mexico.
(1) Background: Changes in midsole hardness may affect lower-limb impact loading during forefoot strike (FFS) running in children, yet the biomechanical basis for discriminating elevated VALR-related loading remains unclear. (2) Methods: Fourteen school-aged boys performed FFS running tests in experimental shoes with four midsole hardness levels (37, 42, 47, and 52 Shore C). Lower-limb kinematics and surface electromyography (sEMG) data were collected during the dominant leg stance phase. After preprocessing, VALR was calculated from 336 valid trials, and 28 stance-phase biomechanical features were extracted, yielding a final machine-learning dataset of 324 trials after excluding incomplete feature data. VALR was used to compare loading changes and define trial-level elevated-loading labels based on the median VALR value. Classification models were evaluated under participant-level GroupKFold validation, and XGBoost was retained for exploratory SHAP analysis. (3) Results: VALR showed an upward trend with increasing hardness, but no statistically supported change point was identified. XGBoost achieved an accuracy of 75.93%, precision of 74.14%, recall of 79.63%, F1-value of 0.768, and pooled out-of-fold AUC of 0.738. SHAP analysis indicated that distal and non-sagittal kinematic features contributed most to model classification. (4) Conclusions: Elevated VALR-related loading during children's FFS running may be characterized by a multi-feature model-based pattern rather than a fixed midsole hardness threshold.
This prospective interventional study assessed adolescents' baseline knowledge of the 12 European Code Against Cancer (ECAC) recommendations and evaluated the impact of a school-based multimedia enhanced intervention on knowledge improvement and retention. The intervention comprised six 45-min multimedia lessons promoting knowledge of all 12 ECAC recommendations in German secondary schools. Materials were developed and refined by an interdisciplinary expert panel and underwent pilot testing before implementation. An anonymous single-recall-based, open-ended questionnaire assessed baseline knowledge (t0) and mean knowledge gains immediately post-intervention (t1) and at three months follow-up (t2). Descriptive statistics were computed, with quantitative variables summarized by mean and standard deviation, and qualitative variables by absolute and relative frequencies. A total of 923 pupils participated (51.8% female; 39.0% male; 9.2% diverse/undeclared), with 923 completing baseline (t0), 873 post-intervention (t1), and 779 the follow-up assessments (t2). Notable knowledge gaps regarding the ECAC were present at baseline. Mean (M) knowledge scores increased significantly across all three assessment time points with post-intervention scores (t1, M = 7.63 (Standard deviation (SD) = 2.67); p < 0.0001) significantly higher than at baseline (t0, M = 4.11 (SD = 1.84)). Largest average improvements post intervention (t0-t1) were observed for breastfeeding importance (+ 50%; 1.20% (t0), 51.2% (t1), p < 0.001), vaccination participation (+ 49.6%; 13.9% (t0), 63.5%(t1), p < 0.001) and regular physical activity (+ 39.4%, p < 0.001).The most sustainable recommendation improvements [calculated by (t2-t0)/(t1-t0)] were observed for alcohol abstinence (0.76); healthy dietary pattern (0.72), and physical activity (0.69) respectively. Multimedia enhanced school-based interventions incorporating the ECAC recommendations effectively increase cancer prevention knowledge among adolescents and knowledge retention after three months. While knowledge retention trends indicated a need for reinforcement, our results demonstrate the effectiveness of early, targeted interventions to address baseline knowledge gaps and provide insights that could potentially shape future interventions. Multimedia enhanced school-based interventions incorporating the ECAC recommendations effectively increase cancer prevention knowledge among adolescents and knowledge retention after three months. While knowledge retention trends indicated a need for reinforcement, our results demonstrate the effectiveness of early, targeted interventions to address baseline knowledge gaps and provide insights that could potentially shape future interventions.
Electronic patient-reported outcome tools have the potential to enhance supportive care in oncology and support the timely and accurate identification of patients' needs. This study aimed to develop, implement, and evaluate a user-friendly, web-based digital screening tool at a German Comprehensive Cancer Center that systematically and efficiently assesses the supportive care needs of patients with cancer and enables direct referral to appropriate supportive services through seamless integration with the hospital information system. An interdisciplinary team collaborated with the IT department and the company CANKADO, an electronic patient-reported outcome provider, to create a 14-item digital questionnaire. The tool incorporated validated instruments, such as the Distress Thermometer, the Nutrition Risk Screening, and a short form of the Integrated Palliative Care Outcome Scale, aligned with German Cancer Society certification criteria. Patients accessed the questionnaire via QR codes. Screening results were automatically transferred to the hospital information system, where supportive care requests (SCRs) were generated automatically if indicated. Between June 2024 and May 2025, a total of 8855 QR codes were generated. Of these, 4909 questionnaires were complete and valid for analysis. This information produced 3324 SCRs. Digital screenings resulted in an SCR in 22.4% of cases for psycho-oncology, 18.7% for nutrition, and 27.6% for palliative care. The digital screening maintained or slightly improved screening rates compared to prior methods. The implementation of a digital supportive care screening was feasible and effective within the Comprehensive Cancer Center setting. Future efforts should focus on overcoming barriers for patients with limited digital access or capabilities to ensure the delivery of equitable supportive care.
In this study, we have reported the synthesis of Ni0.4Zn0.6NdxFe2-xO4 with varying concentrations of neodymium (x = 0,0.025,0.05,0.075, 0.1) by sol gel method. The effect of neodymium doping on the structural parameters, magnetic properties, dielectric behavior, AC conductivity, and optical properties has been investigated in detail. Formation of a single phase in all prepared compositions except at x = 0.1 was confirmed by the XRD technique. The EDX analysis has confirmed the compositional uniformity and high purity. The VSM analysis has revealed ferrimagnetic behavior of the doped ferrites. The composition with neodymium content, x = 0.05, is reported to have the lowest coercivity, minimum dielectric loss and reasonably good dielectric constant; therefore can be considered as a potential candidate for high frequency applications. The UV-DRS measurements have revealed a decrease in bandgap thereby indicating possible photocatalytic applications.
Delayed effects of acute radiation exposure (DEARE), including radiation pneumonitis (lung-DEARE), develop weeks to months after radiation exposure. Pathway-targeted biomarkers that capture early oxidative stress and cell death could improve risk stratification and provide objective measures of mitigator efficacy. The objective was to test whether molecular lung imaging predicts long-term survival and mitigator response after irradiation. Rats received 13.5 Gy leg-out partial-body irradiation with a subset treated with the radiation-injury mitigator lisinopril. Rats underwent lung imaging at weeks 2 and 4 post-irradiation with 99mTc-duramycin (cell death) and 99mTc-HMPAO (oxidative stress). Plasma mitochondrial damage-associated molecular patterns (mtDAMPs) were also measured. Irradiation reduced survival with animals evidencing significant pleural effusion as an indication of radiation pneumonitis, which was mitigated with lisinopril as previously shown. Lung uptake of both imaging biomarkers increased in irradiated rats between weeks 2 and 4, consistent with worsening cell death and oxidative stress. Rats that succumbed by day 120 exhibited significantly larger increases in both biomarkers than the survivors. A predictive test was developed that predicted death by day 120 with ~70% sensitivity and specificity. Plasma mtDAMPs (ND1/2 and ATPase 6/8) increased following irradiation, and the D-loop increase from week 2 to 3 separated outcomes (increase in nonsurvivors versus decrease in survivors). Both imaging and mtDAMPs data from lisinopril-treated animals showed blunted responses. Early dual-tracer molecular lung imaging predicted long-term survival after radiation exposure and tracked mitigation with lisinopril. Circulating mtDAMPs may provide complementary systemic information to further strengthen early risk stratification after radiation exposure.
The global prevalence of obesity among children and adolescents is a growing concern, with significant implications for long-term health outcomes. Traditional weight loss programs focusing on diet and physical activity have shown limited efficacy. This study aimed to assess the impact of the FatSecret mobile application, a dietary self-monitoring tool, on BMI z-score (ZBMI) in adolescents with obesity, alongside clinical and metabolic parameters, body composition, dietary intake, binge eating behaviors, and quality of life. Sixty adolescents aged 13-17 years with obesity were randomly assigned to either the application group (balanced energy-restricted diet with daily self-monitoring using the FatSecret app) or the control group (balanced energy-restricted diet with a 3-day food record). Both groups were followed for 6 months with monthly consultations, and 34 patients completed the intervention. Both groups experienced significant improvements in ZBMI, body composition, binge eating scores, and insulin levels. Notably, the FatSecret app demonstrated comparable effectiveness to the validated 3-day food record in supporting weight loss and behavioral improvements. While the control group reported a greater increase in polyunsaturated fat intake, the app group showed significant improvements in pain-related quality of life scores. Adherence to dietary monitoring and dropout rates were similar between groups. The use of a mobile phone application demonstrated effectiveness comparable to the traditional, validated 3-day food record in promoting weight loss and metabolic improvements among adolescents with obesity. These findings support its use as a practical alternative for dietary self-monitoring.
BACKGROUND: Extensive macular atrophy with pseudodrusen-like appearance (EMAP) is a rare retinal disorder characterized by bilateral macular atrophy and subretinal drusenoid deposits (SDDs), typically occurring earlier and progressing faster than age-related macular degeneration. A possible association between EMAP and rheumatic fever (RF) has been proposed, but its prevalence in this population remains unclear. METHODS: In this cross-sectional study, 118 patients (236 eyes) with valvular disease secondary to RF were prospectively screened at a tertiary cardiology clinic. EMAP was defined by vertically predominant macular atrophy with SDDs and exclusion of alternative diagnoses. Multimodal imaging included spectral-domain optical coherence tomography and fundus autofluorescence. Demographic, clinical, and cardiologic parameters were descriptively analyzed between patients with and without EMAP, and compared between those with and without SDDs using appropriate statistical tests. RESULTS: Two patients (1.69%; 95% confidence interval [CI], 0.47–5.97%) met diagnostic criteria for EMAP. Both were women aged 62 and 73 years, with RF onset during childhood and long disease duration (54 and 62 years). SDDs were identified in 12 patients (10.17%; 95% CI, 5.91–16.94%), including both EMAP cases. Patients with SDDs were significantly older (p = 0.007), had longer RF duration (p = 0.032), and received a greater cumulative benzathine penicillin prophylaxis burden (p = 0.029). CONCLUSIONS: EMAP is uncommon among patients with RF-associated valvular disease, suggesting that additional genetic or environmental factors may be necessary for disease manifestation. The prevalence of SDDs highlights potential subclinical retinal involvement associated with chronic systemic inflammation in this patient population.
Pregnancy is accompanied by physiological changes that alter foot structure and loading conditions, which may contribute to foot pain, instability, and an increased risk of falls. Gestational weight gain and pregnancy-related changes in passive soft-tissue compliance occur simultaneously, making it difficult for clinical studies to distinguish their individual contributions to transverse arch deformation. The purpose of this study was to independently quantify the effects of increased body weight and reduced soft tissue stiffness on transverse foot arch geometry during pregnancy and to clarify their potential mechanical relevance. A computed tomography (CT) -based subject-specific finite element (FE) model and a full factorial design were used to independently quantify the effects of body weight (W) and tissue stiffness (K) on the transverse arch. The reference-condition FE prediction was benchmarked against in-shoe plantar pressure measurements from the same participant, showing close agreement for forefoot and heel peak pressures (< 3% difference). A 4 × 4 factorial analysis was then performed across sixteen conditions, including the reference condition and the 1st, 2nd, and 3rd trimester pregnancy states. Under the prescribed W-K schedule, the greatest model-predicted flattening occurred in the second trimester, corresponding to the stage with the largest prescribed reduction in tissue stiffness. Regression analysis showed that increased load was the primary driver of transverse widening of the midfoot, whereas modelled reductions in passive tissue stiffness predominantly governed loss of arch height and curvature. Interaction effects between load and tissue stiffness were minimal, indicating largely independent mechanical pathways. Model-predicted stresses in the medial cuneiform, intermediate cuneiform, and cuboid were highest in the second trimester. Within this single-subject static FE framework, gestational weight gain (W) and modelled reductions in passive tissue stiffness (K) influenced the tarsal transverse arch through distinct mechanical pathways. Increased W was more strongly associated with transverse widening, whereas lower modelled K was more closely related to vertical flattening and loss of arch curvature. Among the simulated conditions, the most pronounced model-predicted flattening occurred in the second trimester, consistent with the prescribed second-trimester minimum in K. These findings provide a mechanical interpretation of pregnancy-related transverse arch deformation and may help guide future studies of supportive exercise and footwear strategies. Not applicable.
This study evaluated tibiofemoral loading and medial meniscal stress distribution in individuals with flexible flatfoot (FFF) during walking under different foot progression angle (FPA) conditions. This study analyzed the gait of 28 FFF patients (16 males, 12 females) under three FPA conditions (neutral, toe-in, toe-out). Kinematic (Vicon) and kinetic (Kistler) data were used to estimate tibiofemoral forces in OpenSim. Subsequently, joint angles and muscle forces at peak tibiofemoral forces were used to drive a finite element (FE) model of the knee, enabling the comparison of meniscal von Mises stress, maximum shear stress, and contact pressure across FPA conditions. Tibiofemoral force increased during early stance (9-11%) in the toe-in condition with this increase reaching statistical significance in males (p = 0.008, mean partial η 2 = 0.70 within the SPM-identified cluster). FE analysis showed that peak stresses and contact pressure were primarily localized in the anterior region of the medial meniscus. A consistent directional response to FPA was observed with the lowest peak values occurring in the toe-in condition and the highest values in the toe-out condition. Adjusting FPA modulates intra-articular knee loading via the kinetic chain. For FFF patients, neutral FPA provides stable loading. The toe-in condition presents a complex mechanism: despite increasing tibiofemoral force (notably in males), it reduces peak stress by altering contact mechanics and stress distribution. Therefore, FFF gait interventions must be individualized based on factors like foot morphology, sex, and functional goals.
Guaiazulene derivatives are of interest due to the low cost of guaiazulene compared to azulene while still retaining many of the same unique electronic properties. Syntheses of guaiazulene-3-carboxylic acid and azulene-1-carboxylic acid derivatives have been described, but they typically rely on uncommon or toxic reagents such as oxalyl bromide or phosgene. We describe a new route to these compounds by functionalization with oxalyl chloride, followed by thermal or bromide-induced decarbonylation and quenching with a nucleophile. Combined experimental and computational studies suggest a concerted 1,2-halide shift mechanism for the decarbonylation.
Employee health is an important factor that influences the productivity and economic success of companies. The goal of health management in companies is to improve employee health by implementing different kinds of interventions, including checkups (voluntary preventive health examinations) that cover a broad set of tests and questions, to give a comprehensive snapshot of the employee's health and uncover priorities for prevention and health promotion. By analyzing health checkup information on a company-wide level, subgroups with increased need for health management interventions may be identified before productivity loss occurs. This study thus analyzed data from a company's health checkup to form an employee health index (EHI) using principal component analysis (PCA) to adequately summarize the data. Additionally, this study investigated whether EHI values were associated with the number of absent workdays on the department level. The study population consisted of employees of a German automotive company. In total, data from 71,054 voluntary health checkups conducted between 2006 and 2016 were analyzed. PCA resulted in five components in three different health aspects (musculoskeletal disorders, mental health, and physiology). Based on these components, departments were categorized as having low, medium, and high needs for health management interventions. Poisson regression was used to analyze differences in absent workdays between departments with low compared to medium or high need for health management interventions. Components describing musculoskeletal disorders and physiology were associated with a change in the rate of absent days per employee. However, results were inconsistent over different time intervals. Therefore, although the presented EHI was to a certain extent associated with future absent workdays, using checkup data to investigate more specific health problems and outcomes related to individual job-related activities or tasks instead of general measures seems to be a more appealing approach.
Treatment for mucopolysaccharidosis II (MPS II; Hunter syndrome) via enzyme replacement therapy with intravenous idursulfase (Elaprase) has been available for over 15 years. This treatment has led to survival of more patients into adulthood and a concomitant rise in the need for transition of care from paediatric to adult care teams; however, implementation of transition pathways is not standardized. This cross-sectional, non-interventional, multi-country qualitative interview study recruited patients with MPS II (n = 13), caregivers of patients with MPS II (n = 23) and healthcare professionals (n = 24) across six countries (Canada, Colombia, Germany, Mexico, the UK and the USA) to investigate approaches to transition of care in MPS II. Data were collected via a sociodemographic questionnaire, a clinical characteristics form and semi-structured interviews. The interviews identified four overarching themes: transition of care approaches and their drivers, components of a successful transition programme, challenges or barriers to transitioning to adult care and suggested improvements to transition of care. Transition pathways showed high variability within and between countries. Participants reported essential items for successful transition, including continuity of care, a key contact person and empowering patients as early as possible in the process. Proposed improvements for transition included additional educational/support resources, psychological support and implementation of protocols to guide a standardized approach. Our study highlights the need for the establishment of common standards for the transition of care from paediatric to adult services for patients with MPS II. Based on the interview responses, we have proposed additional considerations for patients with neuronopathic MPS II. The findings may inform the development of effective transition practices for MPS II and other rare diseases, to optimize the transition of care experience for patients, caregivers and healthcare professionals.
Hyperoxia is both an essential therapy and a contributor to lung injury in acute respiratory distress syndrome. We hypothesized that adult female rats are relatively protected from hyperoxia-induced acute lung injury (HALI) compared with males and that this protection is associated with sex-dependent differences in lung mitochondrial bioenergetics and H2O2 production. Adult rats were exposed to room air (normoxia) or hyperoxia (>95% O2) for up to 60 h. Lung injury was assessed by pleural effusion, lung wet weight, pulmonary vascular filtration coefficient (Kf), histologic injury scores, and cleaved caspase-3 (CC3) staining. Expression of mitochondrial complexes I-V was quantified in lung tissue. Mitochondrial oxygen consumption rates (OCRs) and H2O2 (mtH2O2) production were measured in isolated lung mitochondria, and lung H2O2 release rate was quantified in isolated perfused lungs. Hyperoxia caused systemic and pulmonary injury in both sexes. However, compared with females, males showed greater body weight loss and larger increases in lung wet weight, pleural effusion, Kf, and CC3-positive cells. Hyperoxia decreased complex I expression in males but not females and impaired OCRs in both sexes. For both sexes, complex II was the dominant mtH2O2 source. Hyperoxia nearly doubled mtH2O2 production in female, but not male, mitochondria. Nevertheless, whole lung H2O2 release rate in females did not increase, consistent with enhanced tissue-level scavenging. These findings indicate attenuated severity of HALI in adult females, highlight complex II as a major mtH2O2 source during hyperoxia, and support consideration of sex as a biological variable in mitochondria-targeted therapies for HALI.NEW & NOTEWORTHY We investigated sex-specific responses to hyperoxia-induced acute lung injury (HALI) in rats. Female rats exhibited attenuated severity, with less pleural effusion, pulmonary edema, and apoptosis than males. Studies in isolated mitochondria, lung tissue homogenates, and isolated lungs indicate that this attenuated severity is associated with mitochondrial adaptations and enhanced tissue H2O2 scavenging capacity. These findings underscore the importance of sex as a biological variable and identify mitochondrial complex II as a potential HALI therapeutic target.
The Hunter Outcome Survey (HOS) collected global, real-world data on the natural history of mucopolysaccharidosis II and its treatment with intravenous idursulfase. For eligible patients, home therapy offers a convenient alternative to in-clinic therapy. Using data in HOS as of January 2023, we provide an updated assessment of the safety/tolerability profile of home therapy with idursulfase. The analysis population comprised 333 patients who had received at least one home infusion and 708 patients who had never received home therapy. Median (10th percentile [P10], 90th percentile [P90]) age at home therapy start was 8.9 (2.9, 21.1) years. Median (P10, P90) ages at latest visit were 15.5 (7.7, 29.3) years in the home therapy group and 13.9 (5.2, 29.0) years in the no home therapy group. Patients received a median (P10, P90) of 6.0 (0.8, 12.0) years of home infusions after 1.8 (0.3, 8.7) years of in-clinic therapy, and these timings varied by geographic region. The infusion-related reaction (IRR) rate was 0.11/patient-year during home therapy, 0.13/patient-year for the in-clinic period for the same patients (first 6 months excluded), and 0.05/patient-year for patients who never received home therapy (first 6 months excluded). More than 60% of IRRs were categorized as mild. The adverse event (AE) rate was lower during home therapy (0.59 AEs/patient-year) than during the in-clinic period for the same patients (0.86 AEs/patient-year). Among patients who never received home therapy, the rate was 0.60 AEs/patient-year. Deaths occurred at a rate of 2.17 deaths/100 patient-years of home therapy and 3.60 deaths/100 patient-years among patients never treated with home therapy. No deaths were deemed related to treatment. The rate of missed infusions was 0.52/year during the home therapy period compared with 1.42/year during the in-clinic period for the same patients and 0.57/year for patients who never received home therapy. Our data indicate a similar safety/tolerability profile for intravenous idursulfase administered at home and in clinic in patients with mucopolysaccharidosis II.
Bathing, even in tap water, alters skin physiology. Frequent infant bathing may increase the risk of eczema developing. To undertake a randomised controlled feasibility trial of an intervention to reduce infant bathing frequency and intensity. Randomised controlled trial. 105 pregnant women (≥ 16 years) with family history of atopy, carrying a healthy singleton child (54 male, 51 female) were randomised in a 1:1 ratio during pregnancy, or postnatally prior to the first infant bath. The intervention group were asked to reduce bathing frequency (no more than once a week for the first six months of age) and intensity (keep baths short, not too hot and washing in plain water is usually sufficient). The control group received the routine postnatal infant care advice offered in their maternity unit.The primary feasibility outcome was the proportion of eligible families willing to be randomised to the intervention. The secondary clinical outcome was a blinded assessment of infant eczema at age 6 months, using an adaptation of the UK Working Party Diagnostic Criteria for Atopic Dermatitis. : 261 pregnant women were screened, of whom 21 were ineligible and 105/240 (44%) were randomised to the intervention (52) and control (53) groups. Adherence to the intervention was high with 79.6% (35/44) in the intervention arm bathing their infant once a week or less, compared to 28.6% (14/49) in the control group. In the intervention group 95% (38/40) agreed or strongly agreed that the intervention was acceptable. There was minimal contamination of the control group (1/46). Follow-up was high with 89% (93/105) of families completing the final 6-month questionnaire and 82% (86/105) attended the final visit. Eczema outcomes occurred less frequently in the intervention arm compared to the control arm: visible eczema 15.8% (6/38) vs 29.2% (14/48); parent reported eczema 9.1% (4/44) vs 12.2% (6/49); and doctor diagnosed parent reported eczema 6.8% (3/44) vs 10.2% (5/49). No noteworthy adverse effects of the intervention were reported. These findings support the feasibility of randomising infants during pregnancy to a reduced frequency and intensity bathing intervention for eczema prevention. ISRCTN51491794 (Registered 24/07/2023).