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Initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is part of National Comprehensive Cancer Network guidelines for head and neck squamous cell carcinoma (HNSCC), yet more than 50% of patients experience a delay. In a randomized clinical trial of patients with locally advanced HNSCC undergoing surgery, Navigation for Disparities and Untimely Radiation Therapy (NDURE), an enhanced navigation-based intervention that targets PORT-related care steps, improved timely PORT relative to usual care (UC) navigation. To examine the mechanisms by which NDURE improved timely PORT relative to UC navigation among patients with HNSCC. This randomized clinical trial was conducted at a single US academic medical center and enrolled adults with locally advanced HNSCC undergoing surgery and PORT. Data were collected from May 2020 to January 2024, and data were analyzed from May 2025 to January 2026. The primary end point was initiation of PORT within 6 weeks of surgery. Five PORT-related care steps were evaluated as mediators: (1) preoperative radiation oncology consultation, (2) preoperative dental evaluation, (3) timely postoperative radiation oncology evaluation (within 21 days of surgery), (4) timely computed tomography (CT) simulation (within 7 days after the radiation oncology appointment), and (5) timely radiation planning (CT simulation to PORT start within 14 days). Causal mediation analysis was performed to determine the effect of the PORT-related care steps, individually and as a group, on timely PORT. Of 145 included patients, 51 (35.2%) were female and 94 (64.8%) were male; 30 (20.7%) were Black and 115 (79.3%) were White; and the median (IQR) age was 63.0 (54.0-69.0) years. A total of 67 patients were randomized to NDURE and 78 to UC. NDURE improved preoperative radiation oncology consultation (odds ratio [OR], 4.9; 95% CI, 2.3-10.3), preoperative dental evaluation and extractions (OR, 27.6; 95% CI, 3.6-213.0), timely postoperative radiation oncology evaluation (OR, 5.0; 95% CI, 2.4-10.7), and timely radiation planning (OR, 2.1; 95% CI, 1.1-4.2). Timely postoperative radiation oncology evaluation mediated 24% (95% CI, 8-65) and completion of more than half of the PORT-related care steps mediated 53% (95% CI, 28-95) of the effect of NDURE on improving timely PORT relative to UC. In this secondary analysis of a randomized clinical trial, NDURE improved timely PORT relative to UC primarily by enhancing early postoperative evaluation by radiation oncology and completion of a greater number of PORT-related care steps. PORT-related care steps, including preoperative evaluation by radiation oncology, preoperative dental evaluation, timely postoperative radiation oncology evaluation, timely CT simulation, and timely radiation planning, are important intervention targets to improve timely PORT. ClinicalTrials.gov Identifier: NCT04030130.

Remote therapeutic monitoring uses technology to track physical activity and exercise. This study evaluates the implementation outcomes and effects of remote therapeutic monitoring on steps and exercise over 6 months. Mixed-methods were used in this hybrid type 2 effectiveness implementation report in outpatients with Parkinson's disease, multiple sclerosis, stroke, concussion, post-COVID-fatigue, or musculoskeletal pain. Participants wore activity trackers synced to a mobile application. Clinicians evaluated activity, tailored goals, and performed clinical measures as part of their physical therapy. Effects were measured using daily steps and weekly aerobic exercise minutes. Implementation outcomes synthesized data from medical records, surveys, exit interviews, and meeting notes. Forty-two patient participants (mean age 56 ± 16 years; 55% female) enrolled in this study; 81% (n = 34) completed 6 months of monitoring. Fidelity to participant tracker use and clinician goal setting were high. Daily steps increased from 4892 ± 3694 to 5958 ± 4385, and weekly exercise from 44 ± 66 to 83 ± 85 minutes. Mixed effects models showed significant but decelerating improvements (steps: β = 87.5, P = 0.002; β2 = -2.4, P = 0.01; exercise: β = 3.6, P = 0.002; β2 = -0.1, P = 0.006). Participant interviews showed motivation and accountability drove engagement, while health and technology issues were barriers. This first study of remote therapeutic monitoring of steps and exercise in physical therapy suggests therapist-supported monitoring is implementable and may enhance long-term physical activity and exercise participation.

Human 3D in vitro models are increasingly adopted in preclinical drug discovery, as they better recapitulate tissue-like architecture, cell-cell interactions, and organ-specific functions compared with conventional 2D cultures. In parallel, initiatives such as the FDA Modernization Act 2.0 and the proposed 3.0 encourage the use of human-relevant in vitro systems as New Approach Methodologies (NAMs) alongside animal models. However, most 3D cell-based workflows rely on manual protocols that are difficult to standardize, producing variable spheroid morphology and fragmented culture steps that impair assay robustness and cross-study comparability. To address these challenges, we present the MO:BOT, a modular benchtop platform designed to standardize and automate complex 3D cell-based workflows. The MO:BOT integrates critical steps of 3D cell culture, including accurate cell seeding, precise medium exchange, on-deck image-based quality control, scalable compound dosing, and downstream assays. Here, we describe a proof-of-concept automated protocol to generate HepG2 liver spheroids and perform acetaminophen (APAP) drug-response testing. Compared with a manual workflow, the MO:BOT not only reduces hands-on time but also minimizes well-to-well variability in liver spheroid size and improves overall spheroid viability. We demonstrate that standardized, well-tuned pipetting routines can maintain the integrity of delicate 3D structures. An MO:BOT-automated APAP dose-exposure experiment with seven concentrations yields a clear sigmoidal cell-toxicity profile with matching changes in viability, LDH release, and ALT activity, demonstrating that improved spheroid uniformity enhances the sensitivity and robustness of downstream assays. The MO:BOT advances the standardization, scalability, and reproducibility of 3D in vitro models, supporting their broader adoption in preclinical research.

Both electron transfer (ET) and proton transfer (PT) are common steps in energy conversion across chemistry and biology. Coupling of these two transfer events reduces the energy demand relative to either individual process, but introduces a fundamentally new process-proton-coupled electron transfer (PCET)-with its own demands for a suitable theoretical description. Conceptualization of PCET usually involves a square scheme representing ET, PT, and PCET steps, each generating states with different energies. While intuitive, these square schemes do not offer structural insights such as the identities and contributions of nuclear motions to PCET. Herein, we present a computational approach that maps these square schemes onto real space coordinates (Å), from which ground and excited-state potential energy surfaces can be generated. This mapping involves the identification of PT and ET coordinates and reconstruction of the potential energy surfaces in orthogonalized coordinates. We find qualitative differences in key features of the surfaces for two distinct processes within PCET, namely concerted proton-electron transfer and hydrogen atom transfer, which may help to distinguish different PCET scenarios.

The microbiota has impact on virtually every aspect of poultry production, including performance, health, and food safety. It is therefore not surprising that considerable promise exists for the application of microbiota science in addressing current and future challenges faced across the poultry industry. Yet, methodological variation among poultry microbiota studies has had negative impact on reproducibility of findings, thereby slowing the application of effective microbiota-based solutions in a production setting. The experimental workflow in microbiota research involves many steps, ranging from sample collection to bioinformatic processing. Likewise, at each experimental stage there exists a vast methodological toolbox available to poultry microbiota researchers. As the technical decisions made at each experimental stage have demonstrable impact on each downstream step, outcomes in microbiota research are largely dependent on the methodologies employed. In order to improve translatability and reproducibility between different methodological pipelines, it is essential that a best practice framework be adopted in poultry science regarding microbiota research. The present review seeks to briefly encapsulate our symposium on microbiome methodology in poultry research. This symposium discussed the need for a robust set of evidence-based guidelines that streamline microbiota research in poultry. Attention was given to each major stage of a typical poultry microbiota study, including sample collection, storage, extraction, library preparation, sequencing, bioinformatic and data analyses, as well as data reporting and repositories. The use of positive and negative controls, improved reporting of raw data, and other tangible aspects that improve consistency and reproducibility across poultry microbiota study designs were highlighted. Ultimately, it was the goal of this symposium not to advocate a single methodology, but instead to demonstrate the need for robust practices at each experimental stage that enable cross-study comparisons of findings in poultry microbiota research.

Emergence of Wnt/β-catenin signaling was a major metazoan innovation, yet how its core molecular interactions evolved remains unresolved. Here, we investigated evolution of the Wnt/β-catenin destruction complex (BDC), a conserved regulatory module that represses Wnt/β-catenin signaling by targeting cytoplasmic β-catenin for degradation. In bilaterians, BDC activity depends on interactions between Axin, APC, and β-catenin. However, bioinformatic analyses suggested that early-diverging metazoans lack the canonical β-catenin-binding motifs required for these interactions raising questions about the origin of BDC function. Using functional assays in Nematostella vectensis, a representative of the Cnidaria, the outgroup to bilaterians, we demonstrate that both NvAxin and NvAPC regulate Wnt/β-catenin signaling, indicating the presence of a BDC despite the lack of canonical bilaterian binding motifs. In vitro experiments revealed that NvAxin binds Nvβ-catenin through previously unrecognized low-affinity interactions. Guided by AlphaFold3 predictions, we identified two β-catenin-binding motif-like sequences in cnidarian Axin including one within the Axin-RGS domain, and a single motif in the Axin-RGS domain of placozoans, sponges, and ctenophores. Functional analyses showed that a conserved residue within these motifs is required for Axin-β-catenin interaction. Our results support a model where an ancestral β-catenin-binding motif-like sequence in Axin-RGS acquired weak β-catenin-binding capacity in early-emerging metazoans followed by motif duplication in the cnidarian-bilaterian last common ancestor. In bilaterians, the duplicated β-catenin-binding motif evolved higher-affinity for β-catenin, while the ancestral sequence was lost. By integrating phylogenetics, AI-based structural prediction, and experimental validation we have revealed for the first time the molecular steps underlying functional evolution of a complex signaling pathway.

Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) for focal congenital hyperinsulinism (CHI) poses a specific intraoperative challenge: reliable, continuous identification of the intrapancreatic common bile duct (CBD) in an anatomically diminutive, tactile-feedback-free operative field. We describe a standardized indocyanine green (ICG) fluorescence-guided biliary visualization workflow for pediatric LDPPHR and report its initial implementation experience. In this retrospective case series, we summarized the application of this standardized workflow in seven consecutive children with focal CHI who underwent ICG fluorescence-guided LDPPHR at Beijing Children's Hospital from February 2025 to March 2026. The workflow comprised seven sequential steps: exposure and preparation, first-dose ICG administration, initial biliary mapping, boundary-guided pancreatic head dissection, repeated fluorescence assessment and reinjection when required, post-resection perfusion assessment, and reconstruction with final intraoperative checking. The workflow was completed as planned in all seven cases, with full workflow adherence in 7/7 procedures. Continuous visualization of the intrapancreatic CBD under near-infrared (NIR) illumination was achieved in 7/7 procedures. Repeated white-light/NIR correlation was feasible throughout dissection in all cases. The fluorescence-guided workflow was implemented without intraoperative abandonment. No bile leak, clinically relevant postoperative pancreatic fistula (ISGPS 2016 criteria), or duodenal ischemia was observed. Median operative time was 310 min (range 229-570 min). This stepwise ICG biliary visualization workflow was technically feasible and was implemented without biliary adverse events in this initial retrospective case series. As a workflow description with feasibility observations rather than an efficacy study, this report suggests that repeated real-time delineation of the intrapancreatic CBD may facilitate duct-sparing dissection; whether it reduces bile duct injury requires validation in larger comparative studies.

Differentiating bacterial from viral infections in febrile young infants is challenging, particularly in dengue-hyperendemic regions. We developed and internally validated a clinical machine-learning model to enhance diagnostic accuracy in this risk population in Colombia. We retrospectively analyzed a pediatric infectious admission cohort (<18&#x2009;years) at a reference hospital in southern Colombia from 2007 to 2019. 4671 admissions (2251 bacterial and 2420 viral) were included. Nine clinical and laboratory variables were used to train an eXtreme Gradient Boosting (XGBoost) classifier. We divided the data into development (70%) and test (30%) sets, with Youden's J statistics defining the optimal threshold. Penalized logistic regression (LR) and single-marker rules [leukocytosis, C-reactive protein (CRP)] served as comparators. The young-infant XGBoost achieved an area under the receiver-operating characteristic curve (AUC) of 0.896, outperforming LR (0.790) and single markers (0.746-0.706). Sensitivity was 93.5%, specificity 76.1%, positive predictive value 87.9%, and negative predictive value 86.4% in the temporal validation cohort. Discrimination was highest in children aged 6-10&#x2009;years (AUC 0.967). CRP positivity, leukocytosis >16&#x2009;&#xd7;&#x2009;10&#xb3; &#xb5;l-1, and thrombocytopenia <150&#x2009;&#xd7;&#x2009;10&#xb3; &#xb5;l-1 were the most informative features. A nine-variable XGBoost model using routine clinical and hematologic variables accurately differentiated bacterial from viral infections in children from a low-resource dengue-endemic setting. Performance remained stable during temporal validation. Improved specificity with preserved sensitivity supports earlier targeted therapy and antibiotic stewardship. Multicenter studies and exploration of clinical challenges are the next steps for this kind of tool.

Relative energy deficiency in sport (REDs) is a syndrome that impairs physiological function because of low energy availability. Awareness and knowledge of REDs among athletes and health professionals are essential for early identification and prevention. To translate into Brazilian Portuguese and culturally adapt a questionnaire that assesses knowledge of the signs, symptoms, and consequences of REDs, originally created by Pai et al., and to obtain evidence of content and face validity. Translation, cultural adaptation, and validation study conducted remotely using online tools and digital data collection. The translation and cultural adaptation consisted of the following steps: two independent translations, synthesis of the translations by a committee of health professionals, two back-translations, and review by a committee of experts to determine the best version for testing. For content validity, the content validity coefficient (CVC) was calculated based on the evaluation of the experts committee on the practical pertinence, theoretical relevance, and linguistic clarity of the items of the pretest version. For face validity, the pretest version was applied to 30 individuals who assessed the items for linguistic clarity, adequacy, and comprehensibility. The CVC for the scale was 0.97. The CVC values for clarity, pertinence, and relevance were 0.97, 1 and 0.99, respectively. All items had a CVC > 0.8, confirming acceptable content validity. The pretest version was tested on 12 female runners, eight coaches, and 10 dietitians. Items were clear and comprehensible to 93% and adequate to 96% of respondents. No changes were needed, and the pretest version was defined as the Brazilian version of the questionnaire to assess REDs knowledge (QC-REDs). The QC-REDs obtained strong content and face validity. It provides a rigorously adapted tool for Brazil, supported by positive feedback from the target population, demonstrating its applicability and usability. This instrument fills a crucial gap and offers a valuable resource for researchers and professionals working with athletes at risk of REDs. Future research should focus on psychometric validation to further solidify its effectiveness in the Brazilian context.

We develop a method for simulating colloidal suspensions using multiparticle collision dynamics (MPCD) with a discrete particle model represented as a rigid body. The key steps for incorporating the rigid-body constraints are to thermalize the velocities of the discrete sites before they participate in the MPCD collision step, then transfer momentum from the sites to the rigid body. We demonstrate that the rigid-body model produces the expected statistics for a single spherical particle and the same transport properties for a hard-sphere colloidal suspension as an equivalent model using harmonic bonds to maintain the site geometry. Importantly, the rigid-body model has less computational overhead and may permit a larger simulation time step than the harmonic-bond model, leading to a nearly order of magnitude speedup in benchmark simulations of hard-sphere colloidal suspensions. Our method is compatible with arbitrary discretization, so it enables more efficient MPCD simulations of suspensions of colloidal particles with complex shapes.

Deuterium incorporation is a powerful strategy for modulating metabolic stability and probing reaction mechanisms. However, existing approaches based on defunctionalization or hydrogen-deuterium exchange are typically limited to mono-deuteration or suffer from poor site selectivity, restricting access to multi-deuterated carbon centers. Herein, we report a cost-effective strategy for decarbonylative multi-deuteration of aldehydes by integrating polar &#x3b1;-deuteration, thiyl radical-mediated hydrogen atom transfer (HAT), and decarbonylative deuteration. A key feature of this approach is an equilibrium-controlled radical-polar process, in which multiple reversible steps are directed toward productive pathways through irreversible trapping of alkyl radicals. The method employs inexpensive, commercially available reagents and exhibits a broad substrate scope encompassing primary, secondary, and tertiary aldehydes, including structurally complex substrates. This strategy provides a practical platform for the synthesis of highly deuterated carbon frameworks, offering new opportunities for isotopic labeling and medicinal chemistry.

The systematic conversion of adverse drug reactions (ADRs) into new therapeutic indications represents one of the oldest and most productive sources of repositioned drugs; however, it has not been subjected to formal mechanistic analysis. This study aims to propose a mechanistic taxonomy of convertible ADRs and a structured workflow for translating documented adverse effects into testable repositioning hypotheses. In this narrative review, historical cases of ADR-driven repositioning spanning five decades-from sildenafil and minoxidil to semaglutide-were analyzed and classified within a four-dimensional framework organized along the axes of: (1) target identity (on-target versus off-target conversion); (2) dose, route of administration, and reformulation; (3) patient population and clinical context; and (4) pharmacogenomic variability. Each historical case was successfully classified within the proposed taxonomy. A five-step theoretical workflow-comprising signal identification, taxonomic classification, mechanistic verification, feasibility assessment, and preliminary evidence search-was developed to operationalize the framework for prospective hypothesis generation. Computational tools including side-effect similarity networks, network pharmacology, and transcriptomic signature reversal were identified as means to support specific workflow steps. The proposed taxonomy and workflow provide a replicable, mechanism-informed approach to ADR-driven drug repositioning, while also delineating the pharmacological, regulatory, and methodological challenges that separate a repositioning signal from an approved therapeutic indication.

The neonatal intensive care unit employs advanced technologies to manage critical conditions. Electrical impedance tomography is a noninvasive, radiation-free imaging technique that provides real-time monitoring of pulmonary ventilation. The literature on electrical impedance tomography in the neonatal population is scattered and heterogeneous, justifying a scoping review. To map and synthesize the available evidence on the applicability of electrical impedance tomography in neonates receiving respiratory support in the neonatal intensive care unit. This protocol follows the steps described by Arksey and O'Malley as well as the recommendations of PRISMA-ScR and the Joanna Briggs Institute Manual for scoping reviews. The following databases will be used to guide searches: PubMed&#xae;, Embase, CINAHL, Web of Science, and Cochrane, with no date restrictions, in English, Spanish, and Portuguese. Two independent reviewers will screen, extract data, and assess the quality of eligible studies. Ethics approval is not required for this protocol and scoping review, as the study will rely exclusively on data from previously published research that has already obtained ethical approval. The results will be disseminated in a peer-reviewed scientific journal.

This three-group RCT investigated the comparative effectiveness of mobile application-based performance feedback (MABPF) interventions, with and without hourly reminders, on cardiovascular risk factors (CVRF) among university staff in Nigeria in the context of Mobile health technology offering promising opportunities to promote physical activity (PA), but evidence on its effectiveness in reducing CVRF, which are causes of major non-communicable diseases (NCDs), is limited. Participants were randomised to: (1) MABPF with hourly reminders, (2) MABPF without reminders, or (3) education-only control. The primary outcome was objectively measured step counts; secondary outcomes included blood pressure, adiposity indices, lipid profile, and blood sugar. The Google Fit application is MABPF, with a daily physical activity target set at 10,000 steps and 150 heart points. Pedometer step counts showed significant between-group differences, with Intervention Group 1 recording a higher median weekly step count compared to Intervention Group 2 (U&#x2009;=&#x2009;721.500, p&#x2009;=&#x2009;0.002) and the control group (U&#x2009;=&#x2009;482, p&#x2009;<&#x2009;0.001) at 12 weeks. The MABPF with reminders group showed greater improvements in systolic BP (F&#x2009;=&#x2009;5.818, p&#x2009;=&#x2009;0.004) and total cholesterol (F&#x2009;=&#x2009;4.976, p&#x2009;=&#x2009;0.008), while MABPF without reminders was more effective for blood sugar reduction (F&#x2009;=&#x2009;3.308, p&#x2009;=&#x2009;0.038) and HDL increase (F&#x2009;=&#x2009;3.357, p&#x2009;=&#x2009;0.039). Although within the control, statistically significant reductions in stress levels, increases in HDL cholesterol, and decreases in blood glucose levels were noted; however, compared to the control group, both MABPF intervention groups demonstrated superior improvements in the above stated variable as well as systolic blood pressure, total cholesterol, LDL cholesterol, and step counts. These results supports the potential of low-cost digital technology for workplace cardiovascular prevention in resource-limited settings. These findings contribute to One Health NCDs prevention by the effective CVRF reduction reported in this study using a low-cost digital technology. Furthermore, the intervention could work in other workplace settings and communities worldwide. Trial registration: Trial number PACTR202405808298188 (24 May 2024).

Acute T-cell-mediated rejection (ACR) remains an important complication after liver transplantation. Polymorphisms in the factor H gene (CFH) and factor H-related protein genes (CFHRs) affect the risk of multiple complement-related diseases. Given the complement system's key role in alloimmunity, we hypothesized that variants in CFH and CFHRs associate with ACR risk after liver transplantation. In 689 donor-recipient pairs, the deletion of CFHR1 and CFHR3 (CFHR3,1&#x394;), a low-expression variant of CFHR2, and CFH haplotypes were extracted from both donor and recipient genotypes following appropriate imputation and quality control steps. Kaplan-Meier survival curves and multivariable Cox regression analysis showed increased ACR incidence after transplantation of donor livers carrying 2 copies of the CFHR3,1&#x394; (log-rank p=0.03, HR: 2.76, 95% CI: 1.18-6.45) or the related CFH-H4a haplotype (log-rank p=0.03, HR: 1.65, 95% CI: 1.04-2.63). In contrast, a lower ACR incidence was observed after transplanting donor livers with a low-expressing CFHR2 variant (log-rank p=0.04, HR: 0.66, 95% CI: 0.45-0.96) or the related CFH-H2 haplotype (log-rank p=0.01, HR: 0.58, 95% CI: 0.37-0.92). When analyzing recipient genotypes, only CFHR3,1&#x394; was associated with ACR (log-rank: p=0.01, HR: 2.55, 95% CI: 1.15-5.65). Common functional variants in the CFH-CFHR region are associated with rejection risk after liver transplantation, highlighting a previously overlooked relevance of the complement system in liver transplantation.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose activation, clustering, and endocytic trafficking together regulate the duration and strength of downstream signaling. In non-small cell lung cancer (NSCLC), activating mutations such as exon 19 deletions (ex19del) and L858R drive oncogenesis, yet how these mutations alter receptor clustering and engagement with the endocytic machinery at the plasma membrane remains poorly understood. Here, we combined pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) with quantitative live-cell total internal reflection fluorescence microscopy (TIRFM) to determine how EGFR variants differ in dimerization, adaptor recruitment, and internalization. PIE-FCCS measurements revealed mutation-specific differences in receptor clustering: EGFRWT displayed ligand-induced multimerization, EGFRL858R exhibited strong ligand-independent dimerization with additional ligand-driven clustering, whereas the exon 19 deletion variants showed weaker ligand-dependent dimerization and limited higher-order multimerization. Live-cell imaging of EGFR and the clathrin adaptor AP-2 during the first 30 minutes after EGF stimulation revealed distinct alterations in clathrin-mediated endocytosis (CME). The EGFRE746-A750del mutant showed minimal AP-2 engagement, indicating impaired adaptor recruitment, whereas EGFRL747-A750>P exhibited high basal AP-2 engagement that persisted after stimulation, suggesting altered clathrin assembly dynamics with sustained membrane association. In contrast, EGFRL858R showed ligand-dependent AP-2 recruitment similar to wild type but with reduced net internalization. Together, these results demonstrate that oncogenic EGFR mutations produce distinct combinations of receptor clustering and adaptor engagement that differentially perturb early steps of CME. These findings provide mechanistic insight into how altered receptor dynamics at the plasma membrane may contribute to sustained signaling in RTK-driven cancers.

Implant design in total knee arthroplasty (TKA) may influence knee stability and muscle demand during stair descent. However, comparative clinical data remain limited. This study compared postoperative stair-descent ability between medial-pivot (MP) TKA and conventional cruciate-retaining (CR) and posterior-stabilized (PS) TKA. Female patients who underwent unilateral MP (EVOLUTION, MicroPort Orthopedics) or conventional CR/PS TKA (ATTUNE, DePuy Synthes) were retrospectively reviewed and propensity score-matched (1:1) for age, body mass index, and preoperative handgrip strength. At 1 year postoperatively, bilateral knee range of motion (ROM) and isometric quadriceps strength (normalized to body weight) were measured. Stair descent over three 20-cm steps was evaluated for gait pattern (step-over-step or step-to-step) and perceived difficulty. A total of 164 patients were included (82 MP and 82 conventional TKA). Postoperative ROM in both knees was comparable between groups. Significantly fewer patients in the MP group reported difficulty during stair descent than in the conventional group (27% vs. 45%, p = 0.015). The proportion of patients who used a step-over-step pattern was similar between groups (82% vs. 71%, p = 0.12). In the conventional group, patients who descended using a step-over-step pattern demonstrated significantly greater preoperative handgrip strength and higher postoperative quadriceps strength than those who descended using a step-to-step pattern; however, no such differences were observed in the MP group. Among patients using the step-over-step pattern, the quadriceps strength of the operated limb was significantly lower in the MP group than in the conventional group (0.345 vs. 0.385 kgf/kg; p = 0.04). MP TKA was associated with less difficulty during stair descent than conventional CR/PS TKA. Although the frequencies of step-over-step descent were similar, MP TKA enabled effective stair descent despite lower quadriceps strength, suggesting reduced muscular demand during weight-bearing flexion.

The development of effective treatment strategies for human immunodeficiency virus (HIV) infection is a major achievement.&#xa0;Antiretroviral drugs inhibit key steps in the viral replication cycle and consist of six mechanistic classes:&#xa0;HIV entry inhibitors, reverse-transcriptase inhibitors (both nucleosides and nonnucleosides), capsid inhibitors, integrase inhibitors, and protease inhibitors.&#xa0;Antiretroviral therapy (ART) suppresses viral replication, thereby enhancing immune function, decreasing morbidity and mortality, and preventing viral transmission.&#xa0;Consequently, ART is recommended for all persons with HIV infection. On the basis of randomized clinical trials, the Food and Drug Administration has approved 36 antiretroviral drugs for the treatment of HIV infection since 1987;&#xa0;of these, 28 are currently available in the United States, and combination ART regimens are used.&#xa0;Initial preferred ART regimens are potent, convenient, and unlikely to cause side effects and consist of an HIV integrase inhibitor with a high barrier to resistance combined with one or two nucleoside reverse-transcriptase inhibitors. In the majority of patients using current ART regimens, viral replication is durably suppressed below detectable levels.&#xa0;Patients receiving ART are monitored for virologic response over time, and if virologic failure occurs, the next regimen is selected on the basis of treatment history and the results of drug-resistance testing; often, antiretroviral drugs from new classes are administered.&#xa0;Today, the life expectancy of someone with HIV infection who consistently takes ART approaches that of the general population.

Both type II (consumer/client-on-worker) and type III (worker-on-worker) workplace violence and mistreatment exist within the sign language interpreting field, however type III (also known as horizontal violence or lateral aggression) is more commonly reported. Between 22 to 90% of sign language interpreters have witnessed and/or experienced forms of horizontal violence or behaviors associated with it and 0 to 8% have knowingly perpetrated horizontal violence against another interpreter. This perspective article aims to provide a cross-industry approach by sharing general practices and previous strategies used within the mental and general healthcare settings. We describe how these tools have been adapted to other industries and model how to apply them to the sign language interpreting field. Available regulatory guidance emphasizes employer responsibility for identifying workplace violence hazards and implementing evidence-informed prevention strategies. Safety and Violence Education (SAVE) was designed for front-line healthcare professionals who are exposed to multiple, well-documented risk factors for workplace violence. The original SAVE curriculum primarily emphasized the perceived predominance of consumer/client-on-worker violence in community mental health settings. Critical steps in adapting SAVE for sign language interpreters involved organizational/administrative exposure control strategies, like cultivating awareness of how organizational culture intersects with emotional and psychological safety and emphasized behavioral/interpersonal approaches by recognizing, preventing, and mitigating worker-on-worker aggression, bullying, and relational-based conflict. The adapted SAVE sought to "break the cycle" of horizontal violence and establish a sustainable culture of safety, respect, and professional resilience among sign language interpreters.