Objective Reducing sedentary behavior in youth is a global health priority, with classroom-based interventions, such as standing desks, offering potential benefits. This study used community-engaged research (CEnR) methods to inform the development of a standing desk intervention by assessing teacher perspectives on implementation barriers and relevant study outcomes in K-12 schools. Methods An electronic survey was administered on February 7-8, 2024, to Pennsylvania teachers via the Penn State PRO Wellness Healthy Champions program, which provides online wellness resources to schools, along with the publication of a monthly newsletter. Eligible respondents taught K-12 students in brick-and-mortar schools. The 48-item survey assessed demographics, use of activity-permissive learning environments (APLE) including standing desks, willingness to trial APLE, and acceptability of study outcomes. Results Of 81 initial respondents, 48 met the inclusion criteria. Teachers were predominantly white (44/48, 91.7%), female (34/48, 70.8%), and > 40 years old (26/48, 54.2%). Most (45/48, 93.8%) used traditional desks; only (14/48, 29.2%) currently use APLE. A majority (30/48, 62.5%) expressed willingness to trial standing desks. Barriers included cost, space limitations, and lack of administrative support. Teachers prioritized improvements in student concentration (22/48, 45.8%) over health-related outcomes. Questionnaire-based outcome measures were most acceptable, while biometric measures (e.g., BMI, blood pressure) and finger-prick blood collection were viewed less favorably. Logistic regression found no demographic predictors of willingness to trial standing desks. Conclusion Teachers' interest in classroom standing desks centers on potential benefits for student focus and behavior, with hesitancy around health data collection and logistical constraints. These findings guided the research team's CEnR approach to school partnerships, resulting in the inclusion of concentration-related outcomes and planning for barriers in the study design. Engaging educators early in the research process supported alignment between research goals and community priorities, enhancing the feasibility of a school-based standing desk intervention.
Detached Mindfulness (DM) is a central, transdiagnostic technique within Metacognitive Therapy (MCT). It involves increasing meta-awareness of intrusions while decentring from and disengaging with them, and is used to reduce the Cognitive Attentional Syndrome and dysfunctional metacognitive beliefs-key components of the metacognitive model of psychological disorders. Although DM is typically delivered within a full MCT protocol, recent research has begun to evaluate DM as a stand-alone intervention. The current study aimed to systematically review and meta-analyse its effects. Studies were included in the systematic review if they examined DM delivered as a stand-alone intervention in clinical or non-clinical samples. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar in May 2025. Methodological quality and risk of bias were assessed using an adapted quality appraisal checklist. Random-effects meta-analyses were conducted for clinical trials, and narrative synthesis for experimental studies. Fourteen studies met inclusion criteria, representing twelve independent samples exposed to DM (N = 256; all aged ≥17). Three samples evaluated DM as a stand-alone treatment in clinical trials (two in obsessive-compulsive disorder and one in panic disorder). Of the remaining nine samples, seven (one clinical, six non-clinical) examined the effects of DM on experimentally induced psychological symptoms, and two (non-clinical) on pre-existing symptoms. Across the three clinical trials, DM was associated with large symptom reductions (pooled Hedges' g for primary outcomes = -1.80, 95% CI [-2.84, -0.76]; pooled g for depressive symptoms measured as a secondary outcome = -1.15, 95% CI [-2.23, -0.08]. Of the remaining nine samples, eight reported beneficial effects of DM on at least one outcome, with significant effects typically in the medium-to-large range. These findings provide converging, but still limited, evidence that DM as a stand-alone intervention is associated with improvements in psychological symptoms and related processes. The results have implications for future component analyses of MCT and for the development of brief, transdiagnostic metacognitive interventions. However, there are significant limitations to the current research base including the small number of studies, methodological shortcomings, and lack of long-term follow-up; these are discussed as well as suggestions for future studies.
Lateral Lumbar Interbody Fusion (LLIF) is a useful minimally invasive technique for arthrodesis, yet subsidence is still a significant postoperative concern. This study aims to evaluate the impact of the number of operative levels on subsidence rates following LLIF. Patients who underwent LLIF procedures between 2014 and 2022 at two quaternary referral centers were reviewed. Collected variables included age, sex, BMI, smoking status, number of operative levels, cage material, average operative level bone density (Hounsfield units), and length of imaging follow-up. Two independent spine surgeons graded postoperative implant subsidence on postoperative imaging according to the Marchi criteria. 144 patients (218 surgical levels) met the inclusion criteria. Lateral plate fixation was utilized at 110 (50%) levels. Median imaging follow-up was 13 months [IQR: 11-29 months]. On univariate analysis, only PEEK cage material (p = 0.033) and the presence of lateral plating (p = 0.012) were significantly different between patients with and without subsidence; however, on multiple logistic regression, both lateral plating (p = 0.03) and increased number of operative levels (p = 0.047) were associated with decreased odds of subsidence, while age (p = 0.013) and PEEK cage material (p = 0.036) were associated with increased odds of subsidence. Multilevel stand-alone LLIF may reduce the rate of subsidence independent of other surgical factors such as lateral plating. Future biomechanical studies should be conducted to further determine the protective mechanism of multilevel LLIF.
This study aimed to (1) determine whether active three-dimensional (3D) self-correction induces immediate changes in spinal alignment compared with passive standing, (2) examine associations between anthropometric variables and spinal alignment parameters, and (3) identify coupled predictive relationships among alignment parameters during self-correction in adolescents with idiopathic scoliosis (AIS). Fifty-four adolescents with AIS (mean age 16.96 ± 2.61 years) were assessed using the DIERS Formetric 4D surface topography system under two conditions: passive standing and active self-correction following a standardized 30-minute training session. Measured variables included trunk inclination, lateral deviation, surface rotation, thoracic kyphosis, and lumbar lordosis. Between-condition differences were analyzed using the Wilcoxon signed-rank test. Associations with anthropometric variables were examined using Spearman's correlation. Multiple linear regression models were applied to identify predictors of correction magnitude based on baseline alignment parameters. Significant improvements were observed during active self-correction in trunk inclination, lateral deviation, surface rotation, thoracic kyphosis, and trunk length (p < 0.05), with no significant changes in lumbar lordosis or pelvic tilt. Anthropometric variables showed no meaningful associations with alignment parameters (p > 0.05), except for a weak correlation between trunk inclination and body weight (r = -0.233). Regression analyses demonstrated that correction magnitude was strongly associated with baseline alignment parameters, with substantial explanatory power (R² up to 0.720). Significant cross-planar relationships indicated interdependence among coronal, sagittal, and transverse parameters. Active 3D self-correction produces immediate, measurable improvements in spinal alignment in AIS. Correction responses are primarily determined by baseline biomechanical alignment rather than anthropometric factors and exhibit coupled, multi-planar interactions, supporting integrated PSSE approaches targeting coordinated control across all planes.
To test whether the Stand Up for Healthy Aging intervention improved eating-related habits/behaviors of office-based workers and to explore associations between changes in sedentary behaviors and eating indicators. Participants (n = 38; 76.3%women) were randomized to a 6-month intervention (sit-stand desks + motivational nudges) vs waitlist control. Eating-related habits/behaviors were assessed with the MedDietScore and other indicators. Group differences were examined using t tests/Mann-Whitney U-tests. Intervention effects were assessed with repeated measures analysis of covariances, adjusting for clustering, sex, age, and body mass index. Associations were examined with Pearson correlations. A time × group interaction was observed for vegetable consumption (P = 0.04), with a moderate effect size (ηp2 = 0.114), increasing in the intervention and decreasing in the control group. At the end of the intervention, participants in the intervention group also reported higher adherence to the Mediterranean diet compared with the control group (P = 0.01). Prolonged (≥ 30 minutes) sitting was negatively associated with reliance on hunger and satiety cues (r = -0.39, P = 0.02). The Stand Up for Healthy Aging intervention, designed to reduce and break up sedentary behavior, promoted changes in some eating habits/behaviors, underscoring the potential of such approaches to foster healthier eating.
This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of fermented oyster extract (FGO) as a functional food ingredient for promoting growth in children with idiopathic short stature (ISS). In total, 80 children aged 6-9 years with height below the 25th percentile for age and gender per the Korean National Growth Charts, 2017, were included. They were randomly assigned to receive either 500 mg/d FGO or a matched placebo for 24 weeks. The primary outcome was a change in height while standing; secondary outcomes included growth rate, height standard deviation score (height-SDS), bone age (BA), and levels of growth-related hormones and bone metabolism markers. In the intention-to-treat analysis, mean height gain at 24 weeks was 3.22±0.71 and 2.38±0.74 cm in the FGO and placebo groups (P<0.001). Growth rate, height-SDS, BA, serum insulin-like growth factor-1, and urinary deoxypyridinoline increased significantly in the FGO group compared with the placebo group (P<0.05). In contrast, growth hormone and insulin-like growth factor-binding protein-3 levels did not vary between groups. No serious adverse events or clinically meaningful laboratory abnormalities were observed; however, two events of mild rash, possibly related to FGO, led to one drop-out. These findings suggest that standardized FGO may safely augment linear growth and bone metabolism in children with ISS. This product could be developed as a marine-derived functional food for pediatric growth support, although more long-term and multicenter studies are warranted to confirm the generalizability of these effects and FGO durability.
Agricultural systems vary worldwide due to location, socioeconomic conditions, and management practices. Understanding the patterns and key factors that lead to differences between farms is crucial to providing the best support for their development. In our study, we interviewed farmers who operate small-scale dairy farms (with 1-5 cows) in a major agricultural region of Poland specifically, the voivodships Małopolskie and Podkarpackie, to understand how socioeconomic factors and farm management practices shape the diversity of farm profiles, and we evaluated our results using cluster analysis. Our findings confirmed the diversity among small-scale farming systems, allowing the identification of three distinct farm profiles. One of these clusters reflects part-time farmers characterized by low agricultural incomes, another long-standing peasant or hobby farms, while the smallest cluster referred to more professionalized agricultural systems. The key factors that characterized the different farm profiles were related to animal production (i.e. grazing time), infrastructure (i.e. manure storage facilities), farm size (i.e. land area), farming practices (i.e. mineral fertiliser use) and farmer's experience. The analysis also identified various socioeconomic factors that influenced the prospects for the continuity of different farm profiles, pointing out the need to devise support policies very specifically addressing the respective needs.
Malus 'Praire Rose' (MPR) stands out for its unique rose-like appearance and floral scent (FS) with potential applications in the fragrance industry. Despite limited exploration at the molecular level, this study investigated the FSs production mechanism in MPR across four flower developmental stages using metabolomics and transcriptomics. Results revealed that the predominant FSs in MPR flowers were terpenoids (à-Ionone, trans-á-Ionone, geranylacetone, and alpha-farnesene, etc.) and phenolic compounds (phenylethyl alcohol, 2-(4-Methoxyphenyl)ethanol, etc.). The highest concentration and diversity of these compounds were observed during the S4 developmental stage. 34 key differentiators (VIP ≥ 1&P<0.05) were identified, including linalool, geranylacetone, trans-á-Ionone, 2-ethyl-6-methyl-phenol, 2-(4-methoxyphenyl)ethanol and phenylethyl alcohol. Transcriptomic analysis pinpointed 16 genes and 25 transcription factors highly correlated with the six volatile organic compounds above. The hypothesis posits a heightened reliance on the MEP pathway for the terpene synthesis pathway, emphasizing phenylethyl alcohol as a pivotal compound for distinguishing crabapple species. An intriguing observation suggests a potential inconsistency between compound synthesis rates and volatilization in MPR. The findings above deepen our understanding of FS, providing valuable perspectives for future research in the aromatic breeding of crabapples.
This study investigated the middle (MCAv) and posterior (PCAv) cerebral artery blood velocity and end-tidal carbon dioxide (PETCO2) responses during sprint interval exercise (SIE). We also examined the relationships between MCAv, PCAv and blood pressure during the 60 min post SIE. Fourteen healthy adults completed four 30 s maximal cycle sprints, each separated by 4 min of unloaded cycling. MCAv and PCAv demonstrated a rapid increase followed by a return towards the initial baseline values during each sprint. The increase during the first sprint (MCAv: +31.9% ± 19.9%, PCAv: +32.5% ± 30.6%) was always greater than subsequent sprints (p ≤ 0.039). Each sprint was followed by a transient increase in MCAv and PCAv, which mirrored PETCO2. SIE was followed by 60 min of hypocapnia, and blood pressure was significantly lowered 10-20 and 40-55 min post SIE. However, resting MCAv was not altered, and PCAv was only lower 5 min post SIE. Resting MCAv phase and gain, and PCAv phase were largely unaltered apart from the first 5 min post SIE. The ability to buffer changes in blood pressure during repeated squat-stand maneuvers remained intact 60 min post SIE, although a greater fall in MCAv and PCAv was noted during a single sit-to-stand transition at this time.
Poor physical function has been associated with higher cardiovascular disease (CVD) risk. However, the association between physical function and atrial fibrillation (AF) remains understudied. The comprehensive investigation of the association between physical function and incident AF risk could highlight a novel target for AF prevention. A total of 4,803 participants without diagnosed AF from the Atherosclerosis Risk in Communities (ARIC) Study cohort with physical function assessed in 2011-2013 were studied. Physical function was measured using Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength. Hospital discharge codes and death certificates were used to ascertain incident AF through 2022, and through 2020 for participants from Jackson. Cox regression was used to assess the association between physical function and incident AF risk, adjusting for multiple covariates. Z-score transformations were performed to identify the physical function measure most strongly associated with incident AF risk, and SPPB component analysis was performed to identify the most influential SPPB component. Mean age of the study participants was 75.1 ± 5.0 years, with 41.2% being male participants and 22.2% being black participants. During a median follow-up of 9.2 years, there were 809 incident AF events. SPPB (HR: 0.93, 95% CI: 0.90-0.96, per 1-point increase) and grip strength (HR: 0.87, 95% CI: 0.78-0.96, per 10kg increase) were inversely associated with incident AF risk, while 4-meter walk time (HR: 1.08, 95% CI: 1.03-1.13, per 1-second increase) was positively associated with incident AF risk. SPPB had the strongest association with incident AF risk. Within SPPB, only the chair stand component was significantly associated with incident AF risk. The findings suggest that better physical function is associated with reduced incident AF risk, with higher SPPB having the strongest association. Given the modifiable nature of physical function, these findings highlight a potential novel target for AF prevention in aging populations. Physical function has been associated with cardiovascular diseases, however, the relationship between physical function and incident atrial fibrillation (AF) remains understudied. This study found that better Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength were all independently associated with reduced risk of incident AF.In this study, higher SPPB was most strongly associated with reduced risk of incident AF, implying the importance of multi-domain measures of physical function.This study found that within SPPB, higher chair stand component score was the only component significantly associated with reduced risk of incident AF, highlighting the critical role of muscle strength in the association between physical function and risk of incident AF.The results suggest that physical function may be a novel modifiable target for AF prevention.
A simple suspension method has been widely used in Japan, however, chemical interactions among drugs in co-suspensions have not been fully clarified. Magnesium oxide (MgO), which is frequently prescribed as a laxative, can interact with various drugs. Eplerenone and spironolactone, potassium-sparing diuretics, are sometimes co-prescribed with MgO to older patients. In this study, we investigated the chemical stability of eplerenone and spironolactone in a co-suspension with MgO and characterized the structures of the degradation products that were formed under the conditions. An eplerenone or spironolactone tablet was soaked with or without an MgO tablet in warm water in a tube according to a standard simple suspension method. The contents in the tube were mixed by inversion after 10 min, 1 h or 5 h to prepare a simple suspension. In separate experiments, the suspension prepared after 10 min soaking was allowed to stand for 50 min or 4.8 h at room temperature. The suspensions were immediately analyzed by high-performance liquid chromatography. The recovery rates of the diuretics from the suspensions were calculated relative to the labeled amounts. The degradation products were isolated and the structures analyzed by high-resolution mass spectrometry. The high-performance liquid chromatographic analysis showed that the diuretics were stable in their simple suspensions without MgO under any of the conditions. When co-suspended with MgO, a slight degradation was observed for eplerenone after just 10 min soaking and the degradation was statistically significant after 5 h soaking, whereas spironolactone was stable even after 5 h soaking. On the other hand, when the co-suspensions with MgO were left alone after mixing, eplerenone significantly degraded in 50 min, and spironolactone slightly degraded in the same period. Based on the mass spectra from the degradation products, hydrolysis of the lactone ring was shown to have occurred in both diuretics co-suspended with MgO. For spironolactone, hydrolysis and elimination of the thioester were also shown to have occurred in the co-suspensions. Eplerenone is more unstable than spironolactone in the simple co-suspension with MgO. As such, the simple co-suspensions of eplerenone are preferably prepared immediately before administration.
Humanity has developed a wide range of physical machines engineered to perform work for specific purposes while emphasizing controllability and upscaling. Recently, a growing aspiration has emerged to construct minuscule mechanical systems, often enabled by a microscopic, bottom-up understanding of nature. As biological systems inherently function at sub-micrometer scales, artificial nanoscale machines have attracted increasing attention as a route to achieve nature-like synthetic and functional precision. Among the possible strategies to activate and drive such systems, light stands out as a highly efficient and versatile energy source that can interact strongly with plasmonic nanomaterials. Owing to strong optical responses, efficient photothermal conversion, and catalytic activity, plasmonic nanostructures can transduce light energy into spatially confined optical, thermal, and chemical gradients, which in turn generate nanoscale mechanical motions. This Perspective highlights the designing principles for these plasmonic nanomachines and fundamental physics behind plasmonically driven force generation and motion, while focusing on approaches that localize energy inputs via material integration. We further explore how energetic and geometric asymmetries provide directional forces that enable translational and rotational motions, guiding movement along targeted trajectories. This framework lays a foundation for advancing autonomous, optically addressable plasmonic nanomachines, overcoming key challenges and opening avenues for nanomachinery and nanorobotics.
Over the past several decades, the management of nonmetastatic nonsmall cell lung cancer (NSCLC) has centered on identifying patients eligible for upfront surgical treatment. This selection has traditionally relied on multidisciplinary assessments of clinical operability and oncologic resectability, with the latter depending primarily on mediastinal lymph node evaluation, a key prognostic factor in determining whether patients should be directed toward upfront surgery or definitive chemoradiotherapy. The recent incorporation of immune checkpoint inhibitors (ICIs) into standard neoadjuvant therapy has transformed this paradigm. By significantly enhancing pathologic response and improving survival across the full spectrum of N2 disease, neoadjuvant ICI therapy is reshaping the prognostic weight traditionally assigned to mediastinal nodal involvement, challenging long-standing staging practices. Rather than serving primarily to exclude patients from surgery, mediastinal assessment in the immunotherapy era may play a more selective role in baseline risk stratification while also potentially gaining new roles, such as in the evaluation of treatment response and nodal downstaging, which could support broader refinements in clinical decision-making. This update synthesizes emerging evidence and evolving clinical concepts to re-examine mediastinal assessment in the immunotherapy era, with implications for clinical decision-making and future trial design in nonmetastatic NSCLC.
Screening and diagnosing sarcopenia is crucial in dialysis patients since sarcopenia has been associated with adverse outcomes in this population. However, the sarcopenia diagnosis may be different according to the strength or physical performance tests used for its diagnosis. Therefore, this study aimed to evaluate the agreement and reliability between different measures of muscle strength and physical performance in dialysis patients. Cross-sectional analysis by which patients on hemodialysis and peritoneal dialysis were enrolled. The sit-to-stand test and handgrip strength (HGS) were performed to evaluate muscle strength. The 4m-gait speed test and Short Physical Performance Battery (SPPB) were performed to evaluate physical performance. Low muscle strength and low physical performance were defined according to consensus from the European Working Group on Sarcopenia in Older People (EWGSOP2). One-hundred ninety patients were enrolled, median age 58.5 (49.5-68.0), 57.4% male. HGS was negatively correlated with sit-to-stand test (r = -0.263; P = 0.001). Cohen kappa coefficient (κ) shows fair reliability between the classification of HGS (κ = 0.258; P < 0.001), and there was 60.0% of agreement. Gait speed was negatively correlated with SPPB score (r = -0.824; P < 0.001). There was moderate reliability between the classification of these tests (κ = 0.702; P < 0.001), with 85.3% of agreement. There were differences in the classification of parameters of muscle strength and physical performance for sarcopenia diagnosis according to EWGSOP2 in maintenance dialysis patients, leading to variations in the prevalence of sarcopenia within the same criteria.
Spoilage microorganisms and pathogenic bacteria can negatively impact food safety and stability, leading to potential health risks and economic losses. Predictive microbiology is a crucial tool for forecasting microbial behavior in food matrices, and supervised machine learning stands out as an effective solution for handling complex datasets (e.g., multiple variables and non-linear relationships). This work aims to develop a growth prediction model for Listeria monocytogenes, Listeria innocua and aerobic spoilage bacteria in food and culture media using artificial neural networks. The model development involved the implementation of the Multilayer Perceptron algorithm applied to datasets obtained from the ComBase platform. We evaluated different models to understand the impact of dataset size, additional input variables, food matrix data, and microorganism data on model performance. Experimental data were also used for model validation. Results demonstrate favorable statistical metrics for all models (R2 = [0.847-0.929], RMSE = [0.55-0.852], Bf = [1.002-1.011] and Af = [1.071-1.108]), indicating the efficacy of the proposed approach for the intended application. Furthermore, validation of the model using experimental data on the growth of total aerobic spoilage bacteria in beef demonstrated its ability to accurately describe the kinetics of microbial growth. These findings underscore the potential of Multilayer Perceptron models to predict microbial growth in various food matrices and culture media, exhibiting robust performance and generalization capability.
Despite the long-standing recognition of the impact of trypanosomiasis on brain functions, efforts to link the associated disease pathology to neuroinflammation and cognitive deficits have been largely unsuccessful, with trypanocidal drugs often proven ineffective. In this study, using novel object recognition task for recognition memory, we compared interleukin-4 receptor alpha-inhibited mice with trypanosome infection. Furthermore, we treated with Iloprost, a prostacyclin analogue, and the standard drug Diminazene aceturate subsequently for changes in transcriptional expressions of IL-4 and IL-13. Given the role of IL-4 in cognitive learning and the established anti-inflammatory effects of Iloprost, we hypothesized that Iloprost treatment could enhance IL-4/IL-13 signalling via IL-4Rα, thereby mitigating cognitive deficits associated with CNS trypanosome infection. This study revealed that Iloprost modulates the neuroimmune response of IL-4Rα, thereby influencing the IL-4 and IL-13 mRNA expressions. This study suggests that Iloprost plays a role in suppressing the neurocognitive response of Trypanosomiasis in mice. Our findings indicate that the prostacyclin analogue (Iloprost) potentiates the IL-4Rα pathway through the upregulation of IL-13 and IL-4 signalling. These activated signalling pathways might contribute to the protective effects of Iloprost on cognitive impairment in trypanosomiasis.
Semen nano purification represents an innovative advancement in livestock reproductive biotechnology, offering a targeted, non-invasive approach to sperm selection. Traditional semen processing techniques, such as centrifugation, swim-up, and density gradient methods, primarily rely on physical characteristics like motility and morphology, which often fail to eliminate apoptotic, acrosome damaged or functionally impaired spermatozoa. In contrast, magnetic nano-purification enables selective removal of defective sperm based on molecular surface markers, including phosphatidylserine, ubiquitin, acrosomal glycans and other membrane proteins associated with specific conditions. This review explores how understanding sperm subpopulation diversity and surface biomarker expression provides a foundation for advanced, fertility-driven sperm selection strategies. It further discusses the principles of magnetic nanoparticle synthesis, surface functionalization, and the practical workflow of semen purification. Comparative studies demonstrate that nano-purified spermatozoa exhibit superior membrane integrity, motility, mitochondrial activity, and DNA quality while reducing oxidative stress. Notably, field trials have shown enhanced conception rates with nano-purified semen at half the conventional sperm dose. The method's low cost, safety, and ease of use in field settings make it a practical option for its utility in artificial breeding programs. Future perspectives highlight its potential for multiplexed selection and non-invasive sex-sorting through sperm surface biomarker-specific conjugation. Collectively, magnetic nano purification stands as a transformative strategy to improve sperm quality, enhance reproductive outcomes, and support genetic advancement in livestock production systems.
Burnout and clinical depression are often experienced by medical students in the United States, which impacts individual wellbeing as well as professionalism, empathy, and patient care. This study aimed to evaluate stress and wellbeing among first-year medical students at one accredited M.D. institution by administering the Medical Student Stress Scale (MSSS), a context-specific measure designed to capture multidimensional sources of medical student stress. The MSSS, a 22-item questionnaire, was administered to first-year medical students during the 2024-2025 academic calendar, in the fall and spring, alongside a Brief Resilience Scale (BRS) and demographic questionnaire. According to the MSSS, stress was measured by calculating a summative score, ranging from 0 to 88, with higher scores indicative of greater levels of stress. The BRS measures resilience with a total score determined as a summation of the six item responses, categorized as low (1-2.99), normal (3-4.3), or high (4.31-5). The overall response rate was 61% (107/175) in the fall and 47% (87/175) in the spring. Average student stress scores in the fall and spring were 34.3 and 38.8, respectively. The resilience score in the fall and spring was 3.6 and 3.5, respectively. Multivariable linear regression showed that student stress decreased by 10 and 13 points with every 1-point increase on the BRS in the fall and spring, respectively (p < 0.001). This correlates with a 11-15% reduction in stress. Additionally, at both time points, males displayed a significantly lower estimated stress score than females (p = 0.044 and p = 0.016). In the spring, compared to students of Christian faith, Jewish students displayed an estimated 10-point increase in stress (p = 0.024), and Muslim students displayed an estimated 17-point increase in stress (p = 0.005). Additionally, students that reported they were low-income displayed an estimated 8-point increase in stress compared to non-low-income students (p = 0.009). To identify trends in both stress and resilience, the MSSS and BRS are feasible surveys to implement in medical schools. Understanding how stress and resilience are affecting medical students provides an opportunity to create tangible interventions to better support student wellness and create resilient physicians.
Efficient cytosolic delivery of nucleic acids is critically limited by poor endosomal escape. While the cationic surface of nanocarriers can enhance endosomal destabilization, these systems suffer from rapid clearance and protein corona formation, a long-standing challenge known as the polycation dilemma. Charge-converting nanocarriers can mitigate this issue by masking positive charges during circulation; however, they remain constrained by inefficient endosomal escape. To overcome this limiting step, we designed enzyme-responsive, charge-converting fusogenic liposomes that combine polyphosphate coatings with DOPE/DOTAP-based fusogenic liposomes. The polyphosphate suppresses cationic charge during circulation, while alkaline-phosphatase-mediated dephosphorylation restores the cationic charge required for membrane fusion. Liposomes were systematically characterized for size, zeta-potential, and phosphate-release-induced charge conversion. Their interaction with Caco-2 cells was mechanistically investigated using confocal microscopy, flow cytometry, and Förster resonance energy transfer, demonstrating the existence of a fusion-driven uptake. Upon loading with plasmid DNA, the most fusogenic formulations enabled a rapid onset of GFP expression consistent with direct cytosolic access. Overall, this work provides a mechanistic investigation of polyphosphate-coated fusogenic liposomes and demonstrates that enzyme-triggered charge conversion can be coupled to membrane fusion to facilitate cytosolic delivery.
Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disorder of the central nervous system, typically presenting after infection or vaccination. Rarely, ADEM may involve the peripheral nervous system, presenting with pure motor axonal neuropathy, which poses a diagnostic and therapeutic challenge. We report a 22-year-old Asian male with no prior medical history who initially experienced a mild upper respiratory infection followed by headache and a single generalized tonic-clonic seizure. He subsequently developed altered consciousness and flaccid paraplegia. Brain magnetic resonance imaging demonstrated asymmetric, poorly marginated supratentorial white-matter hyperintensities on T2-weighted and fluid-attenuated inversion recovery sequences. Cerebrospinal fluid analysis revealed mild lymphocytic pleocytosis and elevated protein, while autoimmune encephalitis panels and infectious studies were negative. Nerve conduction studies revealed predominantly motor axonal neuropathy affecting the lower limbs, with sensory sparing. The patient received high-dose intravenous methylprednisolone followed by therapeutic plasma exchange due to incomplete motor recovery. After 2 weeks, he regained the ability to stand and ambulate with support, and repeat magnetic resonance imaging at 3 months demonstrated complete resolution of the lesions. This case highlights a rare presentation of ADEM with peripheral nervous system involvement in a young adult, distinguished by predominant motor axonal neuropathy and a favorable response to plasma exchange. Recognition of peripheral involvement in ADEM is essential, particularly in younger patients with persistent weakness despite corticosteroid therapy, as timely diagnosis and intervention can significantly improve functional outcomes.