BackgroundThe Parkinson's Disease (PD) Home Diary (HD) is a common clinical outcome measure, but studies show only fair agreement between clinical observer and patient assessments, with no significant improvement after patient training.ObjectivesTo investigate the agreement between a clinical observer and relatives of PD patients when assessing the patient's motor status in the HD. Agreement was also assessed for relative-patient and patient-observer pairs.MethodsThis observational study included 28 PD patients with motor fluctuations and their relatives. It involved a screening visit with structured training on motor fluctuations and one day of motor ratings, where the observer, relative, and patient independently assessed the patient's motor state in the HD half-hourly.ResultsObserver, patient, and relative triads completed 445 HD assessment sets. Temporal agreement was fair for observer-relatives (Cohen's κ = 0.250) and relatives-patients (κ = 0.230), but slight for patients-observer (κ = 0.120). For observer-relatives, agreement was highest for "On without dyskinesia" (71%), and lowest for "Off" (26%). Daily time distributions differed significantly between relatives and the clinical observer for "Off" (p = 0.006) and "On without dyskinesia" (p = 0.012), but not for "On with dyskinesia" (p = 1.000).ConclusionsThis study reports fair temporal agreement of motor state assessments between relatives-observer and relatives-patients, with slight agreement between patients-observer. Relatives' assessments of daily time in different motor states showed significant differences from the clinical observer assessments. This further highlights the challenges in obtaining reliable motor status data and the need for further research into objective assessment methods. Comparing how relatives of Parkinson patients and doctors rate Parkinson's motor statesPurpose?Parkinson's disease patients often develop motor fluctuations, switching between feeling well (“On”), feeling worse (“Off”), and having involuntary movements (“On with dyskinesia”). To track these fluctuations, patients often use a Home Diary to record their motor state every 30 min. The diary is widely used both in clinical care and in research. However, previous studies show that patients and healthcare professionals often disagree when simultaneously assessing the patients motor state in the diary. This can lead to incorrect treatment decisions or misleading study results. Since relatives of Parkinson patients may notice the patients’ symptoms differently, involving them might give a more accurate view of the patient's condition.The study aimed to find out how well clinicians and relatives agree when rating the patient's motor state using the Home Diary. It also investigated how patients agree with clinicians and relatives.How?The study included 28 Parkinson's patients and their relatives. First, they attended a screening visit where they also participated in an education about motor fluctuations. Next, they spent a full day (8:30 AM–4:00 PM) at the clinic. During this time, the patient, their relative, and the clinician independently recorded the patient's motor state every 30 min using the Home Diary.Findings?Clinicians and relatives agreed on the patient's motor state 52% of the assessments. Agreement was highest for “On without dyskinesia” (71%), followed by “On with dyskinesia” (52%). However, they only agreed on the “Off” state in 26% of cases. Relatives and patients agreed 56% of the time, while patients and clinicians agreed 44% of the time.Meaning?The study shows that agreement on motor state ratings is low between clinician, patients, and relatives. This highlights the difficulty of obtaining reliable information about Parkinson patients’ motor fluctuations and the need for more reliable ways to assess them.
To examine the prevalence in Australia of stigmatising attitudes towards people with six different mental health conditions: depression, early and long-term/untreated forms of schizophrenia, bipolar disorder, borderline personality disorder and attention-deficit/hyperactivity disorder (ADHD). Cross-sectional population-based survey using the probability-based online panel Life in Australia. Participants responded to one of six vignettes describing a person with a mental health condition. Australia, 11-25 November 2024. Representative sample of 6032 adult residents of Australia. Proportions of participants who agreed or strongly agreed with 13 stigmatising attitudes and proportions who were definitely or probably unwilling to interact in five different social situations with the person in the vignette. Stigmatising attitudes were generally lowest for depression and highest for long-term schizophrenia and borderline personality disorder. Beliefs about unpredictability had the highest endorsement: 61.9% (95% confidence interval [CI], 58.2%-65.5%) for long-term schizophrenia; 56.3% (95% CI, 52.5%-59.9%) for borderline personality disorder; 52.8% (95% CI, 49.0%-56.6%) for early schizophrenia; 50.7% (95% CI, 47.0%-54.4%) for bipolar disorder; 29.2% (95% CI, 25.9%-32.7%) for ADHD and 23.3% (95% CI, 20.2%-26.7%) for depression. Forcing treatment was endorsed by 25.9% (95% CI, 22.6%-29.5%) for early schizophrenia and 24.1% (95% CI, 21.0%-27.6%) for long-term schizophrenia. For all conditions, at least 20% of participants did not agree that the person in the vignette was a person of worth, with agreement ranging from 78.5% (95% CI, 75.1%-81.6%) for early schizophrenia to 67.4% (95% CI, 63.8%-70.9%) for long-term schizophrenia. There were high levels of unwillingness for the person in the vignette to marry into the family: ranging from 29.7% (95% CI, 26.4%-33.2%) for ADHD to 64.4% (95% CI, 60.7%-67.9%) for long-term schizophrenia. Stigma related to mental health conditions remains prevalent in Australia and contributes to social and economic exclusion among those affected. Sustained action is needed across multiple sectors to address stigma, particularly towards conditions such as schizophrenia and borderline personality disorder, which are poorly understood within the community. The Known: Stigma related to mental health can have profound negative impacts, leading to reluctance to seek help or disclose mental health problems, discrimination in personal relationships, healthcare and the workplace and poorer recovery outcomes. The New: Stigmatising attitudes in the Australian population are prevalent, particularly towards people with schizophrenia and borderline personality disorder. Depression and attention‐deficit/hyperactivity disorder are relatively less stigmatised, with bipolar disorder associated with moderate levels of stigma. The Implications: There is a need for continued action to reduce stigma within the Australian population so that people with mental health conditions can live full and meaningful lives.
Femoroacetabular Impingement Syndrome (FAIS) is a prominent source of non-arthritic hip pain and is highly prevalent in young active populations. Decisions to undergo surgery are significant in nature and require proper understanding of potential benefits and risks. To develop and user-test a patient decision aid comparing non-surgical management and hip arthroscopy for FAIS with an additional military-related section. Mixed-methods. The initial draft of the decision aid was developed by a multidisciplinary steering group. An iterative process of semi-structured interviews, re-drafting and further interviews provided feedback on the decision aid. The interviews were analysed reflexively using thematic analysis for qualitative findings. Acceptability questionnaires were analysed using descriptive statistics for quantitative findings. We interviewed 27-participants; 13 clinicians (6 physiotherapists, 3 orthopaedic surgeons, 2 general practitioners, 1 sports medicine doctor, 1 anaesthesia pain physician) and 14 patients. Most participants rated the decision aid's acceptability as good-to-excellent. Participants agreed on most aspects of the decision aid including the introduction, treatment options, comparison of outcomes and questions to consider asking a health professional. Participants agreed on including more information on the treatment options and provide more long-term outcomes comparing the options. Our decision aid met all 6 of the International Patient Decision Aid Standards qualifying criteria. Our decision aid was considered a useful tool that may help patients choose an appropriate treatment option for the management of FAIS. A clinical trial evaluating the impact of the decision aid on decision making for patients considering surgery for FAIS is needed.
Hospital falls can be reduced through patient and staff education, yet limited evidence exists about how staff can systematically implement patient falls prevention education. Planning implementation with staff may enhance their acceptance, engagement, and delivery of falls education to hospital patients. The objective of the study was to design an implementation plan with hospital staff to guide the successful delivery of patient falls education. Three participatory workshops using a world café methodology were conducted in 1 Western Australian and 2 Victorian hospitals. Participants were presented with information about a patient falls education program called "Safe Recovery" and discussed program implementation strategies. Conversation topics were staff education and training needs, ward support, and organizational requirements. Table discussions were captured on paper and analyzed iteratively at the forum. Subsequently, workshop field notes were analyzed using inductive content analysis. Sixty-two hospital staff (n = 42 nurses, n = 12 allied health, n = 8 other) participated in the workshops. Participants considered the implementation process would be enabled at: (1) individual level, by providing accessible and flexible training to optimize staff engagement; (2) ward level, by establishing clear implementation protocols, engaging and supporting team leaders, and (3) ensuring clear communication between staff, patients, and families; and (4) organizational level, by leadership supporting sustained implementation. Group consensus was that it was important to have a single, agreed vision to implement the Safe Recovery Program. Staff engagement facilitated the development of a shared vision and structured plan to implement a patient falls prevention education program on hospital wards.
To systematically evaluate the effectiveness and safety of brivaracetam (BRV) as adjunctive therapy for focal epilepsy. Electronic databases (PubMed, Proquest, Web of Science, Clinical Trials, and Cochrane Library) were searched without date restriction. RCTs and observational studies of patients with focal epilepsy receiving adjunctive BRV that reported responder rates were included. Title, abstract and the full text were checked independently and in duplicate by two reviewers. Disagreements were resolved through discussion. One author extracted data which was verified by a second author using identified common standard in advance, including using a risk of bias tool we agreed on to evaluate study quality. Twenty-two studies (7 RCTs, 15 observational studies; 8150 patients) were included. The pooled responder rate was 44.0% (95% CI: 36.0%-51.0%). Subgroup differences were significant for study design and duration of epilepsy (P < 0.05), but not for male proportion, age, or sample size (P > 0.05). Treatment-emergent adverse events were common (53.9%-79.3% in RCTs), predominantly somnolence, dizziness, fatigue, and headache. Serious adverse events and discontinuation due to adverse events were both infrequent (<10%), with no novel safety signals. Adjunctive BRV achieves a pooled responder rate of 44.0%, with results stable on sensitivity analysis. Longer duration of epilepsy may be associated with reduced effectiveness. BRV exhibits an acceptable safety profile, supporting its use as an adjunctive option for focal epilepsy.
Positron emission tomography (PET) without usable or accompanying magnetic resonance imaging (MRI) is typically excluded in quantitative analyses of Alzheimer's disease, potentially limiting study generalizability. We investigated participant features predicting data exclusion in magnetic resonance (MR)-dependent analyses and evaluated an existing MR-free PET pipeline to quantify these missing data. Imaging, clinical, cognitive, and sociodemographic data were analyzed for 2119 individuals in a multi-site cohort. Agreement between MR-dependent and MR-free Centiloids (CL) assessed using intra-class correlations and features predicting data exclusion were examined using logistic regressions. MR-free and MR-dependent CLs generally agreed, but MR-free CLs underestimated MR-dependent cross-sectionally and longitudinally. Approximately 19.5% (n = 405) of our cohort would have been excluded in MR-dependent analyses. Age and cerebrovascular comorbidities were consistent exclusion features across multiple sites. Data exclusion in imaging studies is not entirely random. Flexible quantification methods like MR-free PET could supplement traditional methods to improve generalizability in large, multi-site studies.
Emergency department (ED) overcrowding is a routine challenge for most hub hospitals, reported by more than 90% of ED medical directors several times each week. Alternate treatment locations are permissible within the Emergency Medical Treatment and Labor Act (EMTALA) regulations (with patient consent) as long as hospitals screen and stabilize any patient presenting to an ED. This pilot study explored the feasibility and patient acceptability of offering financial compensation to low-acuity patients who agreed to transfer from an overcrowded ED to critical access hospitals. Four eligible patients requiring medical-surgical admission participated. Transfers included travel vouchers of $300-$500. All transfers were completed safely without retransfer or complications, and all patients were discharged home. The aggregate Net Promoter Score was +75, indicating strong satisfaction. Findings suggest that modest financial incentives may support patient-approved interfacility transfers, ease ED overcrowding, and enhance utilization of underused hospitals while complying with EMTALA. Further study of this model is warranted.
W. Yang, X. Yang, X. Wang, J. Gu, D. Zhou, Y. Wang, B. Yin, J. Guo and M. Zhou, "Silencing CDR1as Enhances the Sensitivity of Breast Cancer Cells to Drug Resistance by Acting as a miR-7 Sponge to Down-Regulate REGγ," Journal of Cellular and Molecular Medicine 23, no. 8 (2019): 4921-4932, https://doi.org/10.1111/jcmm.14305. The above article, published online on 27 June 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley & Sons Ltd. The retraction has been agreed following concerns raised by a third party. An investigation identified multiple instances of duplication within Figures 2B, 5B and 6B as well as duplication between Figures 2B and 5B. The authors were contacted and invited to comment on the concerns and to provide supporting data, but no response was received. The editors no longer have confidence in the reliability of the findings reported in the article. The authors did not respond to our notice of retraction.
Vital signs are objective measurements of the body's most basic, essential functions, indicating overall health status. However, such assessments are time-consuming and so are not always prioritized. Measuring vital signs before doctor visits may, therefore, be an effective and efficient strategy. We piloted a preclinic vital signs assessment (PCVSA) procedure within a primary care center to determine its feasibility and acceptability. A mixed methods cross-sectional design was used for piloting the PCVSA procedure. Study participants included adult patients and practice staff. Patients had vital signs assessed by a primary care assistant before general practitioner (GP) visits. Collected data concerned participants' study engagement, the timings of PCVSA/GP visits, and surveys/interviews investigating participants' experiences. A total of 16 patients and 4 staff participated. The mean duration for PCVSAs was 2 minutes and 23 seconds (SD 38.8 s), and the mean duration for GP visits was 9 minutes and 21 seconds (SD 252.4 s). Patients said the PCVSA was a "Positive experience" (n=14, 88%), "Helpful" (n=13, 81%), "Valuable" (n=7, 44%), and "Interesting" (n=6, 38%). The GP said the PCVSAs were either "Helpful" (8/15, 53%) or "Extremely Helpful" (7/15, 47%) in each of their consultations and that the PCVSAs improved engagement with patients (12/15, 80%), allowed them to spend more time gaining an understanding of the conditions of patients (14/15, 93%), and enhanced productivity during consultations (11/15, 73%). The GP strongly agreed that collecting PCVSA data before appointments would benefit patients over time. Qualitative interviews with practice staff yielded three themes: (1) improved patient engagement and efficient consultation, (2) time-saving potential, and (3) practicing in general practice and associated challenges. The PCVSA pilot showed good feasibility and acceptability as indicated by high participant engagement, short PCVSA and GP visit times (albeit GP visit times did not measure non-patient-facing clinical activity), and positive feedback from patients and staff. Introducing PCVSAs in health care settings may have potential in terms of improving the standard and efficiency of care.
The aim of this consensus statement was to develop evidence-based recommendations on perioperative fasting, taking the growing global awareness of the negative effects of prolonged fasting before surgery into account, particularly with respect to clear liquids. A systematic literature search was conducted, including assessments of the risk of bias and the overall level of evidence using GRADE methodology to develop 13 preliminary recommendations on perioperative fasting. This was followed by a 3-stage Delphi process involving an international, multidisciplinary panel of 68 experts and nonexperts. Experts on perioperative fasting were selected via a focused literature search, while nonexperts were selected via relevant organizations. The panel comprised anesthetists, surgeons, nurses, cardiologists, gastroenterologists, other physicians, patient representatives and members of international organizations related to the topic, including patient safety organizations and enhanced recovery after surgery (ERAS) societies. The panel of 68 stakeholders subsequently agreed on 8 recommendations. These recommendations are intended for all healthcare professionals as guidance for perioperative fasting in adults undergoing sedation or anesthesia. The consensus statement supports current preoperative fasting practices for solid food and non-clear liquids, reflecting the lack of meaningful new evidence. Patients should fast for 6h with respect to non-clear liquids, including milk, milk products, meal replacement drinks and enteral feeding formulas. They should fast for at least 6h with respect to solid food; for large fatty meals fasting for 8h or longer may be necessary; however, with respect to clear liquids it reflects a fundamental shift towards more liberal liquid regimens. It is recommended that institutional protocols should be implemented to reduce liquid fasting times. These protocols can either encourage patients to drink clear liquids until 2 h before the start of anesthesia or sedation or permit the intake of clear liquids less than 2 h before the start of anesthesia or sedation within institutional protocols. Clear liquids include water, tea or coffee with sugar or honey (including a small amount of milk, up to one fifth of the total volume), clear juices, lemonade and clear carbohydrate drinks. The consensus statement further recommends that oral intake should be resumed as soon as clinically feasible and that preprocedural gastric ultrasound performed by a trained provider can be used to guide clinical decisions when additional information is required. These consensus-based recommendations are not an official guideline issued by any national or international professional society. Nevertheless, they are currently regarded as the most comprehensive and up-to-date review of the available evidence, based on robust methodology. The broad international consensus suggests that the recommendations published in Die Anaesthesiologie provide a reliable basis to improve the quality of patient care by minimizing periprocedural fasting times, within safe margins. To achieve this, preoperative liberal clear liquid regimens can be implemented with institutional protocols. EINLEITUNG: Ziel des vorgestellten Konsensus-Statements war es, evidenzbasierte Empfehlungen zur perioperativen Nüchternheit zu entwickeln, die dem weltweit wachsenden Bewusstsein für die negativen Auswirkungen verlängerter präoperativer Karenzzeiten – insbesondere für klare Flüssigkeiten – Rechnung tragen. Auf Grundlage einer systematischen Literaturrecherche wurden 13 vorläufige Empfehlungen zur perioperativen Nüchternheit entwickelt. Von diesen wurden nach Überarbeitung in einem dreistufigen Delphi-Prozess durch ein internationales, multidisziplinäres Gremium 8 Empfehlungen konsentiert. Insgesamt nahmen 68 Vertreter:innen verschiedener Interessengruppen – darunter Patient:innen, Anästhesist:innen, Chirurg:innen, Ärzt:innen weiterer Fachrichtungen, Pflegekräfte sowie Mitglieder:innen relevanter internationaler Organisationen – aus 5 Kontinenten teil. Das Konsensus-Statement bestätigt im Wesentlichen die Empfehlungen früherer Leitlinien zu nichtklaren Flüssigkeiten, fester Nahrung, Kaugummi und postoperativer oraler Nahrungsaufnahme. Hinsichtlich klarer Flüssigkeiten spiegelt es jedoch ein grundlegendes Umdenken hin zu liberaleren Flüssigkeitsregimen wider. Es wird empfohlen, institutionelle Protokolle zur Verkürzung der Flüssigkeitskarenzzeiten zu implementieren. Diese können entweder eine feste Mindestkarenzzeit von 2 h vor dem Eingriff vorsehen oder das Trinken klarer Flüssigkeiten bis zum Abruf in den OP erlauben. Diese internationale, multidisziplinäre Konsenserklärung zielt darauf ab, die Qualität der Patientenversorgung zu verbessern, indem präoperative Nüchternheitszeiten innerhalb sicherer Grenzen minimiert werden. Die Umsetzung liberalisierter präoperativer Flüssigkeitsempfehlungen durch klar definierte institutionelle Protokolle stellt hierfür einen zentralen Ansatz dar.
Many adolescent cancer patients experience emotional and psychological distress following a cancer diagnosis. Here, we describe development of a question prompt list (QPL) designed to empower adolescent surgical oncology patients to ask questions that are important to them during surgical discussions. Adult cancer survivors diagnosed and treated for cancer between the ages of nine and eighteen and Family Advisory Council parent members at an academic children's hospital participated in focus groups to evaluate our novel QPL. Focus groups were recorded and transcribed verbatim. At the end of the focus groups, participants were surveyed about QPL acceptability, appropriateness, and feasibility. Thematic content analysis of transcripts was performed, and data were used to guide QPL optimization. Eleven adult cancer survivors and two parents participated. Ten key themes were identified: (1) emotional toll of a cancer diagnosis impacts the ability to ask questions; (2) QPL as a tool of empowerment; (3) provide QPL prior to surgical consultation; (4) provide QPL multiple times; (5) provide QPL in both print and digital formats; (6) QPLs can impact discussion quality; (7) QPLs can impact perception of surgeons; (8) QPL barriers; (9) using QPL with parents or caregivers; and (10) expansion of QPL to other disciplines. Nearly 100% of participants agreed that the QPL was acceptable, appropriate, and feasible. Our novel QPL was acceptable, appropriate, and feasible to all participants. Participants felt that the QPL would reduce the emotional and psychological difficulty of discussing a cancer diagnosis and surgery for cancer.
Patient-generated health data (PGHD) can enhance patient-centered care by improving disease awareness and preparedness for clinical encounters. However, automated incorporation of PGHD into electronic medical records (EMRs), which is a prerequisite for broader clinical implementation, remains technically and administratively challenging. This study describes the development of Miri-Alimi, a PGHD collection platform that delivers mobile social networking service-based previsit questionnaires with automated transfer of structured patient responses into the EMR, and evaluates patient participation, EMR documentation quality, and user satisfaction in a cardiology outpatient clinic. This single-center observational study was conducted between August and November 2024 and included 751 consecutive cardiology outpatients, comprising 282 first-visit patients and 469 patients attending follow-up visits for heart failure. All eligible patients received a previsit electronic questionnaire link via KakaoTalk or multimedia messaging service prior to their scheduled visit. The primary outcomes were the overall survey response rate among all enrolled patients and EMR documentation completeness among follow-up patients with heart failure. Documentation quality was evaluated based on 3 prespecified parameters relevant to routine heart failure care-dyspnea, peripheral edema, and medication adherence status-and was quantified using an EMR completeness score ranging from 0 to 3. Secondary outcomes included patient and provider satisfaction assessed using postvisit 5-point Likert-scale surveys. Firth penalized logistic regression was used to evaluate the association between survey response status and EMR completeness, with adjustment for age and sex. The response rate was 38.5% (289/751), including 48.9% (138/282) of new patients and 32.2% (151/469) of follow-up patients with heart failure. Responders were younger than nonresponders (mean 62.0, SD 15.7 years vs mean 69.8, SD 12.5 years; P<.001). Among the follow-up patients with heart failure, EMR completeness was higher among responders (median score 3, IQR 3-3) than among nonresponders (median score 0, IQR 0-1; P<.001). Patient satisfaction was high: 82.9% (63/76) to 92.1% (70/76) agreed that the system was appropriate, easy to use, and helpful, and 78.9% (60/76) completed the survey in <10 minutes. Both cardiologists and 7 of the 8 participating nurses supported continued use of the system, citing workflow efficiency gains. Miri-Alimi enabled patient-friendly PGHD collection without requiring log-ins or a dedicated app and demonstrated direct transfer of patient responses into the EMR. Its use was associated with effective transfer and structured integration of PGHD into the EMR, as well as high satisfaction among survey respondents and participating staff. Further studies should evaluate sustainability and associations with long-term clinical outcomes across diverse care settings.
The United Kingdom (UK) and Dutch governments have recently implemented mandatory financial risk (affordability) assessments for online gambling as a harm prevention measure. Assessments should trigger at a level of gambling expenditure that strikes a balance between harm prevention (most at-risk consumers should surpass the threshold) and liberty preservation (most no-/lower-risk consumers should gamble below it), yet little empirical research exists to guide threshold setting. We aimed to demonstrate how research can inform the harm-prevention, liberty-preservation trade-off in this context and evaluate the UK's proposed implementation of financial risk assessments. We reanalysed a dataset that combines self-reported Problem Gambling Severity Index (PGSI) scores and open banking data from consumers who gamble (n = 424) to (1) simulate the impact of the UK's rolling 30-day £150 net-deposit (deposits minus withdrawals) threshold for financial risk assessments, and (2) identify optimal threshold values for these assessments under different circumstances. Participants were UK residents who had gambled in the past year, recruited via Prolific in April 2024. Participants completed a survey containing the PGSI and agreed to provide their past 12 months' banking records. Over 12 months, two-thirds of at-risk (PGSI ≥1) and nearly half of no-/lower-risk participants crossed the UK's £150 threshold [area under the curve = 0.66, 95% confidence intervals (CIs) = 0.62-0.71], demonstrating a greater emphasis on harm prevention over liberty preservation. Increasing the value to £186.9 (95% CIs = £69.5-£401.7) slightly improved this balance, although £150 remained within the range of appropriate values. Optimising for harm prevention in our sample required lowering the threshold to £39.0 (95% CIs = £29.6-£58.8), while emphasising liberty preservation increased it to £716.5 (95% CIs = £508.5-£990.9). We found that using a more conservative definition of risk (≥2 PGSI harms) resulted in higher thresholds, and lower thresholds may be appropriate for younger adults (<30 years). Finally, our findings suggest that thresholds based on spending with all operators-rather than single operators as implemented in the UK-may be better able to differentiate at-risk from no-/lower-risk consumers, although the added benefit of this approach in our sample was marginal and further research is needed to confirm its value. The United Kingdom's £150 net-deposit threshold for financial risk assessments for online gambling may place more emphasis on harm prevention than liberty preservation. This study provides a methodological template for guiding the implementation of financial risk assessments for online gambling. Because our sample is not representative of the broader UK gambling population, our specific threshold estimates should be treated as provisional.
Ion transport across membranes plays a vital role in both the central nervous system and the maintenance of normal human physiological activities. Classical Poisson-Nernst-Planck (PNP) model fails to accurately capture the non-Coulombic interactions, such as short-range repulsion and long-range attraction, and thus cannot discriminate between ion species like Na+ and K+ based on their inherent properties. Here, we proposed a three-dimensional computable PNP model modified with the Lennard-Jones (LJ) potential, which incorporates the influence of different LJ parameters on ion concentration distributions. The estimated Na+/K+ selectivity ratio of the sodium ion channel protein using this model agreed well with molecular dynamics simulations. Furthermore, the effects of various nanochannel and ionic parameters on transmembrane transport are systematically elucidated. Analysis using an axisymmetric model reveals that the LJ effect, set by its energy and distance parameters (ϵ,δ), dictates the sign (enhancement or suppression) of its influence on ion current, while the channel geometry determines its amplitude. We present a phase diagram that directly correlates these (ϵ,δ) parameters with the resultant current modulation. This structure-property relationship may provide valuable insights for designing selective nanopores.
Parity has been reached among French residents in the intensive care medicine (ICM) specialty; however, concerns about underrepresentation of women in leadership position and gender discriminations remain. We hypothesised that perception of gender inequity differs between female and male ICM residents and increases along the ICM training. This nationwide observational closed-survey investigated how ICM residents experienced their medical curriculum, how they perceived the ICM specialty, and the potential reasons for women to be underrepresented in leadership position. Among 113 residents who responded to the survey, 63 (55.6%) were females, and 85 (75.2%) were beginners. Twenty-nine (25.7%) answered to be always or often self-confident, and this number was lower in female than in male residents (14.3% versus 40.8%, p = 0.003). Women had less often than men the feeling to keep up with the situation along their medical training (39.7% versus 70.8%, p = 0.004). Societal injunctions to prioritise family over professional responsibilities were more often considered as barriers to leadership position by women than by men (75.8% versus 51.1%, p = 0.015). Fully trained residents agreed more frequently than beginners with the 2 following reasons associated with gender gap in ICM leadership position: men being more ambitious (31.1% versus 9.4%, p = 0.024) and professional environment discriminating against women (64% versus 46.2%, p = 0.017). Experience of non-physical sexual harassment was very common in female residents, with 74.6% of them reporting to have been directly subjected to jokes of a sexual nature (versus 28.6% of men, p = 0.001) and 49.2% of them to have been victims of allegations with humiliating connotation (versus 22.4% of men, p = 0.007). Female ICM residents reported more often the feeling of not coping with their medical training, the lack of self-confidence, and non-physical sexual harassment than men. Reported awareness of a less supportive institutional environment to women academic career and of difference in assertiveness between men and women increased along advancement in ICM training suggesting room for interventions.
Physical activity among college students is a complex phenomenon influenced by many factors. This study aimed to examine the associations among psychological resilience, physical self-efficacy, and physical activity among college students and to analyze the statistically mediating role of physical self-efficacy in this relationship. A cross-sectional study design was employed, involving 650 college students selected from a university in Zhuhai. Measurements were conducted using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Connor-Davidson Resilience Scale (CD-RISC), and the College Students' Physical Self-Efficacy Scale. A total of 600 valid questionnaires were retrieved. The statistical analysis was performed using SPSS 29.0 and Process 4.2 software and included mainly correlation, regression, mediation, and moderation analyses. The results of this study revealed that psychological resilience, physical activity, and physical self-efficacy were correlated significantly positively with each other. The statistical results indicated an indirect statistical association from psychological resilience to physical activity via physical self-efficacy, with an indirect coefficient of 0.133 (95% confidence interval: 0.080-0.194). In this model, the indirect path coefficient accounted for approximately 50.19% of the total path coefficient. In addition, gender moderated the strength of the association significantly between physical self-efficacy and physical activity. Psychological resilience was correlated not only directly positively with college students' physical activity levels but also indirectly significantly with physical self-efficacy. Therefore, while considering gender differences, focusing on student levels of psychological resilience and physical self-efficacy can aid in the understanding of the psychological factors associated with college students' active participation in physical activity.
Acute myeloid leukemia (AML) has a poor prognosis and is associated with aberrant NF-κB activation, providing a tumor-selective therapeutic window. Therefore, a combination therapy involving FDA-approved ferumoxytol (Feraheme, FeNPs) and NF-κB-responsive GBA interference was developed in this study. GBA is a key enzyme that maintains lysosomal lipid metabolism and membrane composition homeostasis. Its inhibition causes lysosomal storage disorders and functional impairment, leading to the release of labile iron that contributes mainly to ferroptosis in AML. Using a miR30-based shRNA system, we constructed and screened an AML-specific GBA-knockdown plasmid, pNM6-miGBA (miGBA). Low-dose FeNPs promote the Fenton reaction and amplify an NF-κB positive feedback loop, markedly enhancing miGBA-mediated cytotoxicity without activating NF-κB in normal cells. Detection of ferroptosis biomarkers, transmission electron microscopy, and RNA-seq confirmed that the synergistic mechanism of FeNPs and miGBA involves ferroptosis. The combination significantly prolonged survival in AML-bearing mice and produced no notable toxicity to major organs, hematologic parameters, or liver and kidney function tests. In summary, combination therapy with FeNPs and miGBA achieves potent anti-AML efficacy with favorable in vivo safety, and has potential for clinical development.
Left atrial remodeling (LAR) critically contributes to the progression of heart failure (HF) and the development of atrial fibrillation (AF) following myocardial infarction (MI). The protein α2δ1, primarily known for its role in neuropathic pain, is abundantly expressed in atrial tissue, but its involvement in post-MI LAR remains unclear. Here, LAR models were established in rats post-MI, and atrial hypertrophy was induced in HL-1 cells using angiotensin II (AngII). The role of α2δ1 in atrial hypertrophy was examined through treatment with either the α2δ1 inhibitor gabapentin or a C-terminal interfering peptide (α2δ1 CT-pep). A significant upregulation of α2δ1 expression was observed in the left atrium (LA) of MI rats and in AngII-treated HL-1 cells. Western blot analysis revealed increased α2δ1 levels in membrane fractions and decreased levels in the cytoplasmic fractions compared to controls. Both gabapentin and α2δ1 CT-pep treatment significantly reduced HL-1 cell hypertrophy and inhibited CAMKII and HDAC4 phosphorylation. Co-immunoprecipitation assays demonstrated an interaction between α2δ1 and GluN1, which was enhanced by AngII stimulation. Inhibition of α2δ1 attenuated the α2δ1-GluN1 interaction and reduced GluN1 translocation to the plasma membrane. In MI-induced HF rats, gabapentin treatment diminished atrial hypertrophy, suppressed AF inducibility and duration, and decreased membrane-associated α2δ1 and GluN1 levels. These findings suggest that the C-terminal domain of α2δ1 may contribute to left atrial hypertrophy in chronic ischemic heart failure and is associated with altered membrane GluN1 abundance and p-CAMKII/p-HDAC4 signaling. α2δ1 may therefore represent a potential therapeutic target for left atrial remodeling in ischemic heart failure.
To investigate the possible clinical application of niacin-induced skin flush response for diagnosing psychiatric disorders in adolescents and its potential correlation with blood test -indicators. This is a cross-sectional study that included 51 adolescents with psychiatric disorders and 18 healthy controls (control group) matched for age and gender. Demographic and clinical data and blood test results were collected. The response to niacin-induced skin flush was tested in all participants using an integrated detection platform for skin testing with niacin developed by the Chunling Wan research team at Shanghai Jiao Tong University. The differences in niacin responses between the disease and control groups were compared using the Mann-Whitney U test. The correlation between niacin responses and clinical indicators was analyzed using Spearman's correlation analysis. Compared to the control group, the disease group exhibited lower sensitivity and weaker response intensity to niacin-induced skin flush, particularly for depression and bipolar disorder. The niacin responses showed potential as an auxiliary tool for diagnosing psychiatric disorders in adolescents. The area under the curve values of 0.891, 0.838, and 0.784 clearly distinguished between depression, bipolar disorder, and behavioral and emotional disorders, respectively. The niacin response in adolescents with psychiatric disorders was associated with thyroid hormone levels (T3, p = 0.030; free T3, p = 0.023), uric acid (p = 0.002) levels, red blood cell count (p = 0.056), and standard deviation in red blood cell distribution width (p = 0.023). The niacin-induced skin flush response is significantly abnormal in adolescents with psychiatric disorders and can aid in clinical diagnosis. It also significantly correlates with thyroid function, antioxidant capacity, and red blood cell morphology and count.
Ibrexafungerp (IBX) is the first approved triterpenoid antifungal indicated for the treatment of vulvovaginal candidiasis, particularly in cases resistant to azole and echinocandin therapies. In this study, a sensitive, simple, and environmentally sustainable spectrofluorimetric method was developed for the quantitative determination of IBX in pharmaceutical tablets. The method is based on chemical derivatization of IBX with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl), forming a highly fluorescent adduct measured at an emission wavelength of 554 nm following excitation at 472 nm. The reaction proceeds via nucleophilic substitution between the primary amine group of IBX and NBD-Cl. Experimental conditions affecting derivatization and fluorescence intensity were systematically optimized. The method exhibited excellent linearity over the concentration range of 150-2000 ng/mL (r² = 0.9996), with limits of detection and quantification of 39.196 and 118.774 ng/mL, respectively. Validation according to ICH guidelines confirmed satisfactory accuracy, precision, and robustness. The method was successfully applied without interference from excipients. Greenness assessment using Analytical Eco-Scale, AGREE, and GAPI tools confirmed the environmentally friendly nature of the proposed method, supporting its suitability for routine quality control applications.