To evaluate how the 10-year integration of minimally invasive hysterectomy (MIH) at a safety net hospital impacted surgical approach, perioperative outcomes, and equity of MIH access across racial groups in an underserved patient population. Observational - Retrospective chart review. A single, university-affiliated urban safety-net hospital. The institution serves as a primary teaching site for the one of the largest Obstetrics and Gynecology residency programs in the country and provides care to a predominantly underinsured patient population. 3,004 patients undergoing hysterectomy for benign indications between 2010-2020. Implementation of minimally invasive surgical practices as well as the establishment of a Complex Benign Gynecology fellowship program at an urban safety-net hospital. Over the 10-year implementation period, the proportion of laparoscopic hysterectomies increased from 9% to 46% (p<0.05), while abdominal hysterectomies decreased from 68% to 27% (p<0.05). In this time, the proportion of perioperative complications (Clavien-Dindo grades 1 and 2) decreased from 45.4% in 2010 to 26.8% in 2020 (p<0.05). Grade 3 and 4 complications were consistently rare (< 3%). Operating times did not significantly change over time; however, the median blood loss per surgery decreased from 300 to 200 mL and the median hospital stay was reduced by 50%, from 61 to 30 hours (p<.001). The transition to MIH was associated with significantly increased diagnoses of adenomyosis and endometriosis (p < 0.001). The systematic implementation of MIH in a safety-net setting is feasible and effective, associated with a decrease in complication rates and hospital stays. The shift to minimally invasive techniques additionally improved the often delayed diagnosis of endometriosis and adenomyosis, which are often associated with significant diagnostic delays. These findings demonstrate that increased access to minimally invasive surgery is essential to quality care in safety net populations.
The goat milk industry is expanding, yet the toxic effects of bis(2-ethylhexyl) phthalate (DEHP) on goat mammary glands remain understudied despite extensive in vivo research in mice and humans. This study used mammary epithelial cells to investigate the mechanisms of DEHP-induced damage. Mitochondrial and endoplasmic reticulum damage was observed, accompanied by reactive oxygen species accumulation, indicating oxidative stress. At the transcriptional level, the mitogen-activated protein kinase (MAPK) signalling pathway played a critical role, while protein analysis highlighted the involvement of the ribosome, ferroptosis, and p53 signalling pathways. These findings suggest that DEHP-induced reactive oxygen species (ROS) indirectly activate p53, promoting lipid peroxidation and affecting ferroptosis and ribosome function. Joint analysis identified 22 significantly upregulated and 91 significantly downregulated genes (proteins), with GCLC, SQSTM1, and ATF3 closely related to cell proliferation, apoptosis, and oxidative stress. This study elucidated the health risks to goat mammary epithelial cells caused by DEHP based on cell phenotype and genes (proteins) expression. Our results provide insights for selecting dairy goat breeds resilient to environmental pollutants and ensuring a safer milk supply for human consumption.
Inhalation of silica nanoparticles (SiNPs) triggers progressive pulmonary fibrosis, a pathological process closely associated with macrophage polarization. However, its underlying molecular mechanisms have not been fully elucidated. To elucidate the pathogenic mechanisms, we developed both an mice model of SiNPs-induced pulmonary fibrosis coupled with an indirect co-culture model of RAW264.7 and NIH/3T3 cells. Our findings demonstrated that SiNPs not only promoted macrophage M1 polarization but also led to pulmonary fibrosis. In the indirect co-culture model, M1-polarized RAW264.7 cells induced by SiNPs significantly upregulated collagen I and α-SMA expression in NIH/3T3 cells through enhanced secretion of cytokines IL-6 and TNF-α. Mechanistic investigations uncovered that SiNPs markedly augmented endoplasmic reticulum (ER) stress in RAW264.7 cells, as evidenced by activation of the protein kinase R-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP)/HMG-CoA reductase degradation protein 1 (HRD1) axis. Bioinformatics mining molecular docking and Co-immunoprecipitation (Co-IP) assays demonstrated that HRD1 directly binds STBD1. Pharmacological inhibition of ER stress significantly attenuated M1 polarization in RAW264.7 cells, and subsequent fibrotic markers expression in NIH/3T3 cells via suppression of STBD1-mediated glycophagy activation. Genetic inhibition of glycophagy through STBD1 knockdown effectively reversed both ER stress-driven M1 polarization in RAW264.7 cells and fibrotic markers in NIH/3T3 cells. These findings collectively establish a novel mechanistic paradigm wherein ER stress-mediated glycophagy plays a pivotal role in driving macrophage M1 polarization during SiNPs-induced pulmonary fibrosis.
Palliative and end-of-life care (PEoLC) systems are expanding across services, settings, and stakeholders, increasing their complexity and the need for systemic understanding to support patient outcomes and service delivery. Hospice care is central to the future of PEoLC, as hospices provide holistic services and engage diverse stakeholders. Participatory system mapping offers a way to collectively understand and visualize complex dynamics with those who live and work within these systems. This study aims to capture hospice system dynamics and preliminary leverage points via participatory causal loop diagram (CLD) mapping while evaluating method suitability through 3 research questions: (RQ1) What key variables and causal interrelationships do stakeholders identify in a hospice through participatory system mapping workshops? (RQ2) What preliminary leverage points emerge from the system map? and (RQ3) How effective are participatory system mapping workshops for capturing hospice dynamics? We developed and iteratively refined an innovative hybrid, asynchronous, multimodal design workshop series in a hospice in North West England. Stakeholders were introduced to core concepts in technology, design, systems thinking, and CLDs before engaging in participatory system mapping focused on the hospice experience quality. CLDs generated in workshops and through asynchronous participation were consolidated into a composite hospice system map. Twenty-seven participants, including patients, health care professionals, volunteers, managers, maintenance staff, and chaplaincy, contributed to the mapping process. The resulting map was analyzed using quantitative network analysis (in-degree, out-degree, betweenness, and closeness centrality) alongside qualitative interpretation of key system dynamics. The participatory hospice system map contained 84 variables connected by 175 causal links. Network analysis highlighted patient experience (highest in-degree, 20), advanced care planning (highest out-degree, 8), fundraising (highest betweenness centrality, 0.19), and relationships with community organizations and external stakeholders (highest closeness centrality, 0.23) as central elements in the map. Qualitative analysis illuminated important dynamics, including the impact of hospital admissions and hospice stereotypes, as well as uncertainties around how advanced care planning is shaped and enacted in practice. Participatory system mapping with hospice stakeholders was feasible in a time-pressured setting and generated a nuanced, stakeholder-led representation of hospice system dynamics. The hybrid, multimodal workshop model enhanced access and flexibility, supporting diverse engagement. Network analysis of the CLD suggested preliminary structural and conceptual leverage points and revealed gaps in shared understanding, indicating candidate areas for service development, policy attention, and further research. Future work should examine the replicability of this approach across PEoLC settings and integrate context-specific processes to validate and act on candidate leverage points.
The Imaging and Radiation Oncology Core (IROC) works with the Children's Oncology Group (COG) to provide institutional credentialing and patient radiotherapy plan review for sites that enroll patients on COG clinical trials. COG protocols that include radiotherapy require specific site credentialing activities depending on the treatment technique that is allowed in the protocol. In addition, there are protocol-specific treatment planning guidelines for tumor coverage and normal tissue sparing that define not only protocol acceptable limits, but also variations in limits if deemed clinically necessary, as well as protocol deviations. With many institutions participating in COG protocols, credentialing activities ensure standards for radiotherapy equipment and delivery are met and individual patient case reviews ensure consistency in target delineation, tumor coverage, and normal tissue avoidance for each protocol. The purpose of this work is to provide a descriptive analysis of retrospective credentialing and case review data for COG clinical trials. This work was conducted by representatives of the COG Physics Committee and aimed to characterize protocol deviations of recently closed COG trials. This analysis included closed COG protocols from a 10-year period (2013 to 2023). Phantom credentialing performance of COG institutions was assessed and compared to case review deviations to determine trends. Credentialing phantom irradiation failures were collated and reviewed for common failure modes. From patient case reviews, protocol deviations were categorized, and patterns of protocol deviations are described. This study found that credentialing and case reviews in clinical trial quality assurance (QA) were complementary, identifying unique failure modes, often before they affected enrolled patients. For example, phantom credentialing identified errors in beam modeling or patient setup processes, while case reviews identified errors in anatomical contouring, prescriptions, treatment planning techniques, and dose coverage. While the final rate of protocol deviations was low for COG protocols, many errors were identified through the case review and credentialing processes, highlighting the continued need for quality assurance checks of radiotherapy data in clinical trials.
This study evaluates the effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting as an individualized adjunct to standard treatment on cognitive function in early/mid-stage Alzheimer's patients. This assessor-blinded, randomized controlled trial enrolled 60 Alzheimer's disease (AD) patients (CDR 1-2; aged 55-85), randomized to intervention (n = 30; intervention + standard care) or control (n = 30; standard care). Cognition and brain structure were assessed at baseline and 6 months. Individual cognitive changes were analyzed using Reliable Change Index (RCI). Cognitive change scores differed significantly between groups (p < 0.001). The mean Mini Mental State Examination (MMSE) score increased by +0.9 in the intervention group, while a decrease of -1.5 points was observed in the control group. RCI analysis indicated stability in 93% of intervention and 70% of control participants, with cognitive improvement in 7% and 3.3%, respectively. The intervention method has the potential to stabilize cognitive decline in AD and promote improvement at the individual level. The response to the intervention is closely related to the individual's metabolic phenotype and structural brain integrity. Istanbul Medipol University Non-Interventional Clinical Research Ethics Committee on March 6, 2025, under number 242 and the study was carried out in accordance with the Declaration of Helsinki and its later amendments. gov ID: NCT06898424.
Anti-Müllerian hormone (AMH) is widely used to assess gonadotoxicity related to anti-cancer treatments and to measure ovarian function in cancer survivors. The extent of AMH decline across malignancies and treatment regimens and the degree of subsequent recovery have not been systematically quantified. The primary objective of this review was to quantify the change in AMH following cancer treatment and to model longitudinal AMH trajectories in survivors. The secondary objective was to compare AMH trajectories in cancer survivors with those of age-matched non-cancer controls. Data on long-term ovarian reserve after cancer treatment remain limited. This study integrates recent evidence and age-matched control data to better distinguish treatment-related AMH decline from normal reproductive ageing. A systematic search was performed across CENTRAL, MEDLINE, Google Scholar, Embase, and MedRxiv from inception until 24 January 2024, with an updated search on 19 March 2026. Both MEDLINE and Embase were searched via the Ovid platform, whilst Emtree index terms were used for EMBASE. The search strategy combined both index terms and free-text terms: (gonadotoxicity OR premature menopause OR premature ovarian insufficiency (POI) OR premature ovarian failure (POF)) AND (AMH OR Antimullerian* OR Anti-Mullerian) AND cancer. Studies were included if they involved female cancer patients of any age, including paediatric, adolescent and young adult (AYA), and adult populations, who received chemotherapy and who reported either pre- and post-treatment AMH levels or AMH measurements at defined time points after treatment. Studies were excluded if they did not report quantitative AMH data, involved male patients or non-human subjects, or included studies unrelated to cancer treatment-induced gonadotoxicity. The primary outcome was percentage change in AMH from baseline to 12 and 24 months from the end of treatment. Secondary outcomes included long-term AMH trajectories in adult and paediatric cancer survivors compared to the age-related decline in healthy controls. Risk of bias was assessed using the Joanna Briggs Institute (JBI) study-design-specific critical appraisal tools, and certainty of evidence was evaluated using GRADE. Analyses were performed in GraphPad Prism v10.6. Across all four cohorts (breast, lymphoma, thyroid, and paediatric/AYA mixed cancers), AMH levels were higher at 12 and 24 months compared with 6 months from the end of treatment. With breast cancer (median age 37.8 years, n = 2259), AMH was reduced by 76.4% at 12 months (95% CI: -93.5 to -55.7; 24 studies; GRADE: moderate-certainty evidence). With lymphoma, ABVD treatment regimens (median age 24 years, n = 146) were associated with a smaller reduction in AMH at 12 months (-21.1%; 95% CI: -81.6 to +14.8; four studies; GRADE: low-certainty evidence), whereas non-ABVD regimens (median age 26.3 years, n = 188) were associated with a larger reduction (-90.1%; 95% CI: -96.1 to -68.3; six studies; GRADE: moderate-certainty evidence). With thyroid cancer (median age 32.5 years, n = 181), radioactive iodine treatment was associated with a 57.9% reduction in AMH at 12 months (95% CI: -65.2 to -36.4; 4 studies; GRADE: high-certainty evidence). In the paediatric and AYA mixed cancers cohort (median age 9, n = 176), AMH was reduced by 63.1% at 12 months (95% CI: 64.3-61.9; four studies; GRADE: very low-certainty evidence). Among the adult and paediatric survivors who retained ovarian function, AMH trajectories remained relatively stable and closely aligned with age-matched healthy controls. AMH levels consistently improved between 6 and 12-24 months from the end of cancer treatment. We provide generalizable estimates of AMH trajectories in female survivors of both childhood and young adult cancer, indicating that their long-term AMH declines are similar to those of age-matched controls. PROSPERO registration number: CRD420251000939.
Perilunate injuries are rare high-energy wrist injuries whose open treatment carries a risk of capsular stiffness and carpal devascularisation. Arthroscopically assisted reduction with temporary fixation aims to limit this morbidity, and temporary trans-articular headless compression screws may provide more rigid scapholunate and lunotriquetral control than Kirschner wires. We asked what the mid-term clinical, radiographic and patient-reported outcomes of this technique are, using the contralateral wrist as a paired control, and whether they differ by injury pattern. Retrospective single-centre study of 11 consecutive patients (10 men; mean age 37 years) with a closed perilunate dislocation (n = 7), trans-scaphoid perilunate fracture-dislocation (n = 3) or perilunate injury not dislocated (n = 1) treated between November 2015 and December 2020. All 11 were analysed by intention to treat; injured-versus-contralateral comparisons (Wilcoxon signed-rank test) were restricted to the 10 wrists that retained the index construct. Median follow-up was 47 months. One patient (9%) required four-corner fusion for scapholunate advanced collapse, and radiographic osteoarthritis was seen in 2/11 (18%). The flexion-extension arc (113 ° vs 132 °, p = 0.002) and the scapholunate angle (60 ° vs 50 °, p = 0.018) were significantly worse than the uninjured wrist; grip strength and radiolunate angle did not differ significantly. Median QuickDASH was 4.5 and median PRWE 7. In selected closed, reducible perilunate injuries this technique gave good patient-reported outcomes and maintained carpal alignment in most patients, but flexion-extension and the scapholunate angle remained reduced relative to the uninjured wrist and one in eleven required salvage fusion. Comparative studies are needed before recommending it over open fixation. IV (retrospective case series).
Relaxation techniques, such as the "safe place" imagery exercise, are simple and accessible strategies to cope with the negative effects of stress. While virtual reality (VR) has been applied in relaxation research, it is still unclear whether it enhances the relaxing effect of such exercises or is merely an alternative and similarly effective form of delivery. This study aimed to evaluate whether the use of VR enhances the relaxing effect of the safe place imagery exercise by generating an individualized virtual environment representing each participant's personal safe place with AI. Additionally, the roles of imagery vividness, presence, and satisfaction with the AI-generated safe place were examined. This randomized controlled trial involved a single laboratory session with 4 measurement points followed by a 5-day online follow-up period involving daily self-report questionnaires. A total of 60 adults were randomly assigned to the experimental condition or the control condition. In the experimental condition, participants engaged in the safe place imagery exercise in which they imagined a place where they feel completely safe and comfortable, followed by a stress induction task. Then, participants completed a 3-minute relaxation period within an AI-generated virtual environment representing their personal safe place, which was created based on their individual descriptions. In the control condition, the same procedures were implemented; however, in the 3-minute relaxation period, participants imagined their safe place with their eyes closed. The primary outcome was self-reported relaxation, assessed with the Relaxation State Questionnaire. Secondary outcomes included imagery vividness (assessed with the Vividness of Visual Imagery Questionnaire), presence (assessed with the Igroup Presence Questionnaire), satisfaction with the AI-generated safe place, and use of the safe place in everyday life. The 3-minute relaxation period of both conditions enhanced self-reported relaxation levels with no statistically significant differences between conditions, indicating that relaxation in VR did not outperform traditional mental imagery. Relaxation levels during the 5-day online follow-up period likewise did not differ significantly between conditions, and there were no significant differences in the frequency with which participants used their safe place during the follow-up period. Imagery vividness was positively associated with postintervention relaxation in both conditions, whereas satisfaction with the AI-generated safe place and presence in the virtual environment did not predict outcomes. While relaxation in the AI-generated safe place in VR was effective in promoting relaxation, it did not demonstrate a benefit compared to traditional mental imagery, either immediately after the intervention or during the follow-up period. These findings suggest that VR may represent an effective alternative form of delivery, but not a superior enhancement, for brief relaxation interventions. Future developments might increase the potential of AI and VR as effective tool for promoting relaxation. Open Science Framework 10.17605/OSF.IO/BP53A; https://osf.io/bp53a/overview.
Well-characterized asbestos mineral samples are required for use as analytical standards and in future research projects. Even in areas where asbestos is no longer mined it can still be encountered in mine spoil, when rocks are disturbed by construction projects, and in other mineral products (eg talc and vermiculite), as well as in products made from asbestos and in uncontrolled disposal of those products. While chrysotile was the type of asbestos most commonly mined and used in the United States, amphibole (tremolite and anthophyllite) asbestos is widespread and was also extracted commercially for the manufacture of specific products. Analysts are called upon to recognize the varieties of asbestos when they are encountered. Amphibole asbestos exhibits variation in crystallinity and chemistry, and so it is important that samples where the range of these features is well-described are available. Tremolite and anthophyllite are important constituents of certain rock types, and both can occur in fibrous and nonfibrous crystal habits, and crystallinity and chemistry vary between and within occurrences. Therefore, it is useful to have available a range of samples exhibiting this variation as a reference for analysts and researchers. Tremolite asbestos from an abandoned mine at Cemetery Ridge, Arizona, and anthophyllite asbestos from an abandoned mine near Palm Springs, California, were analyzed using (i) a polarized light microscope with a determination of principal optical properties, (ii) spindle stage analysis using a polarized light microscope to determine whether individual fibers and bundles of the samples were polycrystalline or single-crystal cleavage fragments, (iii) x-ray diffraction, (iv) a transmission electron microscope, including energy dispersive x-ray spectroscopy, and selected area electron diffraction, and (v) electron probe microanalysis. Additional images were acquired with a field-emission scanning electron microscope and transmission electron microscope to show the diversity of appearance. The overall findings of the study indicate that the materials are tremolite asbestos and anthophyllite asbestos. The tremolite asbestos is asbestiform tremolite with some prismatic crystals and cleavage fragments. The following formula was determined from electron probe microanalysis:Na0.01(Ca1.95Fe0.04Mn0.02)∑2.00(Mg4.65Fe0.39Al0.01)∑5.00(Si7.98Al0.02)∑8.00O22(OH)2 The atomic ratio (Mg)/(Mg + Fe) is 0.915, which falls into the compositional range for tremolite, but it is close to the boundary with actinolite (ratio < 0.90), and it is possible that compositional variation between individual grain analyses may report results as actinolite. Accessory quartz was also noted, but in only small quantities (<5%). The anthophyllite asbestos is asbestiform anthophyllite with some prismatic crystals and some accessory minerals. The following formula was determined from electron probe microanalysis:□(Mg1.04Fe0.80Ca0.054Mn0.044)∑1.94(Mg4.98Al0.02)∑5.00Si8.03O22(OH)2Accessory hydrated silicate minerals (talc and chlorite) are also present, but in only small quantities. Materials for research use were prepared by sorting, acid-washing, and mixing for subdivision into vials of approximately 10 g each. The samples can be obtained from Research Triangle Institute (RTI International, Research Triangle Park, NC, United States) on request.
Ankle and knee injuries are common in court sports such as basketball and tennis, where there is an emphasis on cutting maneuvers and cleats are not a viable footwear solution. Such maneuvers generate substantial lateral ground reaction forces with the potential to overcome native anatomic ankle stability. The goal of this study was to develop a simple criterion that could be applied to assess the design of basketball shoes in an effort to enhance ankle stability and subsequently reduce lower extremity injuries. The criterion relates the foot's vertical force (Fv) and mediolateral force (Fml) to the sole and wall thicknesses of the shoe through a critical ratio F v t F ml h , where a critical ratio of is less than 1 denotes shoe instability. To evaluate our proposed criterion, a closed-form analysis combining force data from cutting movements characterized in previously published studies with simple geometric measurements of modern basketball shoes was conducted in nine shoe models. In addition, an experimental evaluation using a custom-built ankle model was carried out to validate the criterion on two of the shoe models. The ankle model included a prosthetic foot, steel shaft, double-U-joint, and load cell readout to acquire force and center of pressure associated with mediolateral ankle tipping. The experimental evaluation supported the validity of the instability envelope. Of the nine currently available shoe models evaluated here, none passed the criterion for all of the previously reported loading conditions and two demonstrated fundamental instabilities at the forefoot or heel.
Ferroptosis links cellular metabolism to immune regulation. Beyond its role as an iron-dependent form of regulated cell death, ferroptosis generates signals, including oxidized lipids, iron metabolites, and damage-associated molecular patterns, that influence inflammatory and immune responses. The pancreas is particularly susceptible to ferroptotic stress because of its high metabolic demand and close integration with immune and stromal networks. In pancreatitis, ferroptosis translates metabolic injury into innate immune activation, contributing to sterile inflammation and tissue damage. In pancreatic cancer, ferroptotic vulnerabilities can be exploited therapeutically, yet ferroptosis-associated signals may also support immune suppression, immune evasion, and treatment resistance. These findings suggest that ferroptosis functions as an immunometabolic checkpoint rather than simply a cell death program. Here, we discuss how ferroptosis shapes immune responses in pancreatitis and pancreatic cancer and examine the factors that determine whether it promotes inflammation, antitumor immunity, or immune tolerance. We also review ferroptosis-targeted therapies and the challenges associated with their clinical application.
Immune checkpoint inhibitors (ICIs), including the programmed cell death protein-1 (PD-1) inhibitor pembrolizumab, have revolutionized metastatic urothelial carcinoma management but are frequently associated with cutaneous immune-related adverse events, including drug-induced bullous pemphigoid (DIBP). We present the case of an 81-year-old man with PD-L1-negative metastatic high-grade papillary urothelial carcinoma with a generalized, pruritic, bullous eruption following treatment with pembrolizumab. Histopathology and direct immunofluorescence confirmed bullous pemphigoid (BP). This case underscores the diagnostic challenges of DIBP. Clinicians must maintain a high index of suspicion and consider early transition to steroid-sparing agents such as rituximab in refractory cases. Timely dermatologic referral and close multidisciplinary coordination are essential.
Early life-history traits of seahorses are closely linked to juvenile survival, dispersal potential and the onset of substrate attachment; however, detailed stage-resolved descriptions remain limited for many Hippocampus species. This study examined reproductive behaviour and early ontogenetic development of the Korean seahorse, Hippocampus haema, during a 40-day laboratory rearing period. Newborns were released in a relatively advanced skeletal condition, particularly in the caudal skeleton. Skeletal staining showed that the caudal bony plates were already ossified and connected at birth, whereas the trunk plates were still only partially connected. Consistent with this condition, newborns bent the prehensile tail and attached to nearby structures immediately after release, indicating functional competence for substrate attachment at birth and suggesting a very short or indistinct planktonic phase under the observed conditions. Coronet morphology changed markedly during juvenile development, with the anterior coronet spine progressively fusing with the coronet. Morphometric model comparison did not strongly support a continuous power function allometry across measured traits. However, segmented regression identified a significant breakpoint in snout depth at 21.3 mm standard length, after which snout depth increased approximately 2.6-fold more steeply. These findings indicate that H. haema is characterised by advanced caudal skeletal development at birth, immediate tail attachment, dynamic coronet development and a discrete ontogenetic shift in snout depth growth. This stage-resolved description provides baseline information for identifying early developmental stages and interpreting early life history variation in this species.
Approximately 15 million people in the UK live with obesity and at least 5 million of these are people with severe obesity (PWSO). Severe obesity significantly compromises health, well-being and quality of life and reduces life expectancy. These adverse outcomes are prevented or ameliorated by weight loss, for which sustained behavioural change is the cornerstone of treatment. Several studies suggest the potential of group-based intervention in Specialist Weight Management Services (SWMS), but PWSO remain underrepresented in research, and evidence on optimal design and outcomes is limited. The success of the PROGROUP feasibility randomised controlled trial (RCT) (ISRCTN22088800) informed the development of this study and additional adjustments have been made in response to the rollout of obesity management medication in the National Health Service (NHS). This study aims to assess the effectiveness and cost-effectiveness of PROGROUP in SWMS and primary care. The RCT will be conducted in SWMS, alongside an implementation study in primary care. The RCT will recruit cohorts of 30 participants to be randomised 1:1 within-cohort to PROGROUP (intervention) or usual care (control). The implementation arm will recruit cohorts of 15 to PROGROUP. The primary objectives for the study are to undertake a process evaluation and economic evaluation of PROGROUP in the RCT and to assess its implementation in primary care. Baseline data and outcome differences at 6 months will be analysed. These will include weight, other clinical measures and patient-reported outcomes, including social and life-satisfaction measures. This study is approved by an NHS Research Ethics Committee (REC reference: 23/WS/0101). Results will be reported in a manuscript that will be submitted to a peer-reviewed medical journal as open access. A lay summary of the findings will be published online, and participants and sites will be signposted to this. ISRCTN13721429.
The pericapsular nerve group (PENG) block was developed to result in local anesthetic (LA) spread in the plane between the iliopubic ramus and the iliacus muscle. We aimed to investigate the anatomical and histological basis of injectate spread following a PENG block. We performed a PENG block in 10 cryopreserved cadavers under ultrasound guidance. A 22-gage, 50 mm needle was inserted using an in-plane approach. After contacting the bone at the target site, 20 mL of the solution mixed with the marker (methylene blue or heparinized erythrocytes) was injected. The dispersion of the injectate was analyzed using anatomical dissection, cryo-cross-sections, and microscopy. Gross anatomical dissection demonstrated methylene blue staining in close proximity to the femoral nerve and its branches, without staining of the obturator nerve. Cryo-cross-sectional and histological analyses showed predominantly subepimysial and intramuscular localization of the injectate within the iliopsoas muscle compartment, without consistent involvement of the hip capsule. Histology identified small nerve branches within adipose-containing connective tissue planes. The injectate following a PENG block was predominantly confined to the iliopsoas muscle compartment. The presence of small intramuscular nerve branches suggests that intramuscular neural blockade may contribute to the analgesic effect. Potential femoral nerve involvement warrants further investigation.
Structural transitions in the energy and industrial sectors are reshaping air quality in the Yangtze River Delta (YRD). Interprovincial NO₂ fluxes over the YRD are quantified using a closed-loop integration method that combines TROPOMI, ERA5, and GEOS-CF datasets. Regional NO₂ column concentrations show a marked decline of (-3.16 ± 1.08) %/yr, with the steepest decreases in Anhui and Jiangsu. Flux analysis reveals weakening trends in both overall and interprovincial NO₂ transport in the YRD. The western segment shows a net influx of 3.29 kg/s, while the eastern segment exhibits a dominant net efflux of 15.25 kg/s. Interprovincial exchanges are also notable, with mean fluxes of 0.68 kg/s, 0.37 kg/s, and 0.20 kg/s for Jiangsu-to-Anhui, Anhui-to-Zhejiang, and Jiangsu-to-Zhejiang, respectively; of which, the Jiangsu-to-Anhui flux shows the fastest decline ((-5.87 ± 1.79 ) %/yr), forming a progressively weakening northwest-to-southeast transport chain. Surface NO₂ concentrations in eight major cities show steady declining trends ((-3.54 ± 0.45) %/yr to (-6.1 ± 0.31) %/yr), with Suzhou and Nanjing exhibiting the steepest declines. The synchronous decline of surface and column NO₂ concentrations, along with transport fluxes, highlights the potential of structural emission mitigation to deliver air-quality benefits across administrative boundaries via regional atmospheric circulation. Our findings underscore that achieving sustainable improvements in air quality in megaregions such as the YRD requires coordinated structural transitions, where the synergy between reforms in the industrial and energy sectors ensures that emission reductions translate into tangible decreases in both local burdens and cross-boundary pollutant fluxes.
Microwave ablation (MWA) efficiency is strongly influenced by impedance mismatch caused by inter-organ dielectric variability, tumor heterogeneity, and temperature-dependent tissue evolution during treatment. This work presents a computational feasibility study of an adaptive impedance matching framework for microwave ablation based on ferroelectric tunable elements and feedback-controlled impedance retuning. The proposed architecture employs voltagecontrolled ferroelectric segments integrated into the matching network to dynamically compensate for dielectric variations under heterogeneous tissue conditions. Full-wave electromagnetic and thermal simulations were performed at 915 MHz across 47 representative scenarios involving liver, lung, kidney, and breast tissues, including variations in tumor size, heterogeneous tumor composition, percolation-driven dielectric transitions, anisotropic tumor geometries, and temperature-dependent dielectric properties. A closed-loop feedback strategy based on reflected-power minimization was computationally modeled to evaluate adaptive tuning behavior. The adaptive matching framework maintained reflection coefficients below -20 dB across all simulated cases, while substantially improving impedance stability relative to conventional fixed matching configurations. Additional frequency-domain analysis demonstrated improved matching behavior across the ISM operating band. The proposed framework also preserved localized SAR distributions and stable thermal coverage under dynamically evolving dielectric conditions. The results support the feasibility of adaptive ferroelectric-based impedance matching as a promising strategy for improving microwave ablation robustness under heterogeneous and thermally evolving tissue environments. Experimental validation and hardware implementation remain subjects of future investigation.
Internal phosphorus (P) loading from sediments remains a major bottleneck for the long-term remediation of eutrophic waters. Although electrochemical strategies for vivianite (Fe3(PO4)2·8H2O) formation show promise for phosphate removal from wastewater, they typically rely on precise pH control, severely limiting their potential for in situ application in complex natural sediments. Here, a low-current-density electrochemical system is reported that directs labile sedimentary P toward crystalline vivianite under bulk aerobic laboratory conditions. Using iron electrodes at 1 mA cm-2, 32% of sedimentary P and 37% of aqueous-system P were converted into vivianite-bound P, within the range reported for authigenic vivianite in Fe-rich, low-sulfidation sediments. Increasing current density accelerated P immobilization but shifted the products toward ferrihydrite-adsorbed P and amorphous Fe-P. XANES and EXAFS showed that low current density preserved Fe(II)-rich products with higher Fe-centered connectivity, whereas higher current densities promoted Fe oxidation and structural disordering. Complementary XRD, XPS, FTIR, Raman, and SEM-EDS supported the formation of layered Fe-P particles with Fe/P ratios close to vivianite stoichiometry at low current density. The low-current condition maintained a favorable pH evolution and sustained Fe2+ supply, thereby favoring Fe(II)-phosphate crystallization over Fe hydroxide/amorphous Fe-P formation. This work demonstrates a charge-quantified, pathway-selective electrochemical mineralization strategy for converting labile sedimentary P into crystalline Fe(II)-phosphate under controlled sediment-water conditions.
Oxidative modification-mediated tau aggregation is believed to contribute to multiple aging-related neurodegenerative diseases. Significant evidences indicate that various aging disease-related aggregates are closely linked to biochemical modification-driven abnormal protein phase separation, a thermodynamic conversion to form biomolecular and functional condensates, which are commonly named membrane-less organelles. However, whether oxidative modification regulates tau phase separation remains elusive. In the present study, we show that oxidative modification of cysteine 291 and cysteine 322 in tau impairs the liquidity of tau condensates in vitro and in cells, and promotes mis-localization of SRRM2 and SRSF2, the pre-mRNA splicing-related nuclear speckle protein, to cytoplasmic tau aggregates to form tau-associated cytoplasmic speckle (TACS). Interestingly and importantly, we found that RING-Bait technology, which has been shown to selectively target and clear protein aggregates, will be helpful for the elimination of TACS upon oxidative stress exposure. Taken together, our study illustrates the role of oxidative modification in tau phase separation and TACS formation, and provides a novel therapeutic strategy for oxidative stress-associated aging-related neurodegenerative diseases.