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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.

To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD).73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo.The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms.There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state.Clinicaltrials.gov NCT00490542.

Rosa damascena, or Damask rose, is a rose hybrid commonly harvested for rose oil used in perfumery and for rose water used to flavor food. The petal extract of R. damascena was recently found to decrease Drosophila melanogaster mortality without impairing reproductive fitness or metabolic rate. Here, we report that R. damascena extended both mean and maximum lifespan of the fly. The extract also protected against oxidative stress in flies, predominantly in females. However, it did not alter mitochondrial respiration or content, superoxide production, or the major antioxidant defenses, superoxide dismutase and catalase. The extract increased survival in both sexes when exposed to reduced iron, though surprisingly, it sensitized both sexes to heat stress (survival at 37°C), and appeared to down-regulate the major heat shock protein HSP70 and the small mitochondrial heat shock protein HSP22, at 25°C and after heat shock (4 h at 37°C). We hypothesize that R. damascena extends lifespan by protecting against iron, which concomitantly leads to decreased HSP expression and compromising heat tolerance.

Abstract Background Educational innovation in health professional education is needed to keep up with rapidly changing healthcare systems and societal needs. This study evaluates the implementation of PACE, an innovative curriculum designed by the physiotherapy department of the HAN University of Applied Sciences in The Netherlands. The PACE concept features an integrated approach to learning and assessment based on pre-set learning outcomes, personalized learning goals, flexible learning routes, and programmatic assessment. PACE distinguishes itself from traditional education because of the flexible learning routes, vertical organization in learning communities, absence of pre-defined learning activities and class schedules, and a culture of continuous learning and development. PACE is based on three guiding principles: 1) flexible and varied, 2) self-directed and collaborative, 3) future-oriented. PACE was implemented in 2021 for first-year students. This study evaluates the implementation to inform future curriculum development. Methods A sequential explanatory mixed methods design was used to evaluate the implementation of PACE using a questionnaire, focus groups, in-depth interviews, and a national progress test allowing for benchmarking results. Participants were undergraduate physiotherapy students of cohort 2021–2022, the first group who experienced PACE and teachers involved with this cohort. Questionnaire data were analyzed using descriptive statistics. To compare mean total scores of the national progress test between four different universities a one-way ANOVA was conducted including a post-hoc analysis. Reflexive thematic analysis guidelines were applied to analyze the interview data. Results In total 82 first year students (44,6%) of cohort 2021–2022 and 36 teachers (60%) completed the questionnaire. Results show that the guiding principles were implemented as intended. Results of the national progress test on knowledge and clinical reasoning showed that students of the HAN University performed well compared to other universities. Thematic analysis of interviews and focus groups resulted in three themes and nine subthemes: 1) navigating a personalized curriculum, 2) caring and sharing, and 3) shaping professional identity. PACE contributed positively to students' intrinsic motivation, learning joy, identity development, and life-long learning skills. Areas for improvement were self-directed learning support, and teaching strategies to prompt deep learning. Conclusion The evaluation showed that the guiding principles of PACE were implemented as intended and that the innovation positively contributed to student learning,

Abstract Addressing health inequities in health professions education is essential for preparing healthcare workers to meet the demands of diverse communities. While simulation has become a widely recognized and effective method for providing safe and authentic clinical learning experiences, there has been limited attention towards the power of simulation in preparing health practitioners to work with groups who experience health disparities due to systems of inequality. Balancing technical proficiency with educational approaches that foster critical reflection and inform action oriented towards social accountability is essential. Transformational learning promotes the development of critical consciousness through critical reflection. Debriefing plays a crucial role in fostering learning in this direction by providing a structured opportunity to critically reflect on taken for granted assumptions, examine power and privilege embedded within systems and structures, and empower learners to take action toward changing those conditions. Building on the Promoting Excellence and Reflective Learning in Simulation (PEARLS) Healthcare Debriefing Tool, we propose a PEARLS Debriefing for Social Justice and Equity (DSJE) Tool that specifically directs attention to systems of inequality that contribute to health disparities for vulnerable groups across a range of simulation scenarios. This approach has two aims: (a) to transform debriefings into a critically reflective space by engaging learners in dialogue about social and structural determinants of health that may create or perpetuate inequities and (b) to foster critical reflection on what actions can be taken to improve the health and well-being of identified at risk and vulnerable groups. From this perspective, we can use the adapted PEARLS Tool to incorporate conversations about systems of inequality, equity, diversity, and inclusion (EDI) into our existing educational practices, and make concentrated efforts towards community-driven and socially conscious simulation-based education (SBE).

Abstract There is growing recognition that preparing health professionals to work with complex social issues in the delivery of healthcare requires distinct theoretical and pedagogical approaches. Recent literature highlights the significance of employing simulated environments which aim to immerse learners in the experiences of diverse populations and bridge the gap between academic learning and lived realities across a diverse society. Virtual Reality (VR) is gaining traction as a promising pedagogical approach in this context. VR has been argued to offer distinct advantages over traditional educational methods by allowing learners to see the world through the eyes of diverse populations, and to learn about social injustices while immersed in a mediated environment. It also has practical benefits in its capacity to expose large number of students to these topics with relatively modest resources compared to other approaches. This debate article explores VR as an innovative pedagogical approach for facilitating critical reflection, dialogue and transformative learning about social issues in health professions education (HPE). It examines the potential affordances as well as risks and dangers of integrating VR into educational programs and highlights key pedagogical, practical, and ethical considerations. Emphasis is placed on the importance of these considerations in efforts toward ethical, safe, and respectful use of VR in educational settings. This paper contributes to the ongoing dialogue on VR simulation as an innovative approach to HPE and highlights the importance of creating conditions that maximize its educational benefits and minimize potential harms.

Abstract We investigate the possible production of a MeV-scale sterile fermion through the up-scattering of neutrinos on nuclei and atomic electrons at different facilities. We consider a phenomenological model that adds a new fermion to the particle content of the Standard Model and we allow for all possible Lorentz-invariant non-derivative interactions (scalar, pseudoscalar, vector, axial-vector and tensor) of neutrinos with electrons and first-generation quarks. We first explore the sensitivity of the DUNE experiment to this scenario, by simulating elastic neutrino-electron scattering events in the near detector. We consider both options of a standard and a tau-optimized neutrino beams, and investigate the impact of a mobile detector that can be moved off-axis with respect to the beam. Next, we infer constraints on the typical coupling, new fermion and mediator masses from elastic neutrino-electron scattering events induced by solar neutrinos in two current dark matter direct detection experiments, XENONnT and LZ. Under the assumption that the new mediators couple also to first-generation quarks, we further set constraints on the up-scattering production of the sterile fermion using coherent elastic neutrino-nucleus scattering data from the COHERENT experiment. Moreover, we set additional constraints assuming that the sterile fermion may decay within the detector. We finally compare our results and discuss how these facilities are sensitive to different regions of the relevant parameter space due to kinematics arguments and can hence provide complementary information on the up-scattering production of a sterile fermion.

Focusing on elastic neutrino–electron scattering events, we explore the prospect of constraining new physics beyond the Standard Model at the DUNE Near Detector (ND). Specifically, we extract the attainable sensitivities for motivated scenarios such as neutrino generalized interactions (NGIs), the sterile neutrino dipole portal and unitarity violation. We furthermore examine the impact of the τ-optimized flux at the DUNE-ND and compare our results with those obtained using the standard CP-optimized flux. We find that our present analysis is probing a previously unexplored region of the parameter space, complementing existing results from cosmological observations and terrestrial experiments.

BackgroundSuicide remains a leading cause of death among veterans in the United States, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation (SI) and suicide attempts (SAs). mTBI worsens impulsivity and contributes to poor social and occupational functioning, which further increases the risk of SI and SAs. Repetitive transcranial magnetic stimulation is a neuromodulatory treatment approach that induces neuroplasticity, potentially repairing neurodamage. Intermittent theta burst stimulation (iTBS) is a second-generation form of transcranial magnetic stimulation that is safe, shorter in duration, displays a minimal side effect profile and is a promising treatment approach for impulsivity in mTBI. Our novel proposed treatment protocol uses frontal pole iTBS to target the ventromedial prefrontal cortex, which may reduce impulsivity by strengthening functional connectivity between the limbic system and frontal cortex, allowing for improved top-down control of impulsive reactions, including SI and SAs. ObjectiveThe objectives of this study are to (1) develop an iTBS intervention for veterans with mTBI, impulsivity, and SI; (2) assess the feasibility and tolerability of the intervention; and (3) gather preliminary clinical outcome data on SI, impulsivity, and functions that will guide future studies. MethodsThis is a pilot, double-blinded, randomized controlled trial. In developing this protocol, we referenced the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. We will enroll 56 participants (28 active iTBS and 28 sham iTBS). The iTBS intervention will be performed daily, 5 days a week, for 2 weeks. We will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention. Measures included will assess functioning, impulsivity, suicidality, posttraumatic stress disorder, and depressive symptoms. We will collect qualitative data through semistructured interviews to elicit feedback on the participants’ experiences and symptoms. We will perform quantitative and qualitative analyses to (1) assess the feasibility, tolerability, and acceptability of the treatment; (2) gather advanced neuroimaging data to assess neural changes elicited by treatment; and (3) assess improvements in outcome measures of impulsivity and suicidality in veterans with mTBI. ResultsThis study protocol was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 14-003). This novel treatment is a 5-year research project (April 1, 2023, to March 31, 2028) funded by the Veterans Administration Rehabilitation Research and Development service (CDA2 award IK2 RX002938). Study results will be disseminated at or before the project’s end date in March 2028. ConclusionsWe will provide preliminary evidence of the safety, feasibility, and acceptability of a novel frontal pole iTBS treatment for mTBI, impulsivity, SI and SAs, and functional deficits. Trial RegistrationClinicalTrials.gov NCT05647044; https://clinicaltrials.gov/study/NCT05647044 International Registered Report Identifier (IRRID)PRR1-10.2196/58206

Abstract Background Both memory clinic professionals and patients see value in digital tools, yet these hardly find their way to clinical practice. We explored the usability of a digital tool to support the diagnostic work-up in daily memory clinic practice. We evaluated four modules that integrate multi-modal patient data (1.cognitive test; cCOG, and 2. MRI quantification; cMRI) into useful diagnostic information for clinicians (3. cDSI) and understandable and personalized information for patients (4. patient report). Methods We conducted a mixed-methods study in five Dutch memory clinics. Fourteen clinicians (11 geriatric specialists/residents, two neurologists, one nurse practitioner) were invited to integrate the tool into routine care with 43 new memory clinic patients. We evaluated usability and user experiences through quantitative data from questionnaires (patients, care partners, clinicians), enriched with thematically analyzed qualitative data from interviews (clinicians). Results We observed wide variation in tool use among clinicians. Our core findings were that clinicians: 1) were mainly positive about the patient report, since it contributes to patient-centered and personalized communication. This was endorsed by patients and care partners, who indicated that the patient report was useful and understandable and helped them to better understand their diagnosis, 2) considered the tool acceptable in addition to their own clinical competence, 3) indicated that the usefulness of the tool depended on the patient population and purpose of the diagnostic process, 4) addressed facilitators (ease of use, practice makes perfect) and barriers (high workload, lack of experience, data unavailability). Conclusion This multicenter usability study revealed a willingness to adopt a digital tool to support the diagnostic process in memory clinics. Clinicians, patients, and care partners appreciated the personalized diagnostic report. More attention to education and training of clinicians is needed to utilize the full functionality of the tool and foster implementation in actual daily practice. These findings provide an important step towards a lasting adoption of digital tools in memory clinic practice.