Touro University California

The aim of this project was to predict the skin permeability of compounds in three modified datasets (Steinmetz et al., Stevens et al. as well as Wilschut et al.). We employed Elasticnet, Ridge and Decision Tree Regression algorithms to forecast the skin permeability values of these compounds. When the Ridge regression technique was applied to the modified Wilschut et al dataset, the mean squared error was 0.20, the mean absolute error was 0.33 and the coefficient of determination (R²) was 0.61. The application of the same technique to the modified Stevens et al. dataset resulted in a mean squared error of 1.04, a mean absolute error of 0.5172 and an R-squared value of 0.18. The utilization of the Ridge regression method on the modified Steinmetz et al. dataset resulted in a mean squared error of 0.65, a mean absolute error of 0.67 and an R-squared Score of 0.48. When the Elasticnet regression approach was used on the modified Wilschut et al, the mean squared error was 0.24 and the coefficient of determination (R²) was 0.60. The utilization of the Elasticnet regression technique on the modified Steinmetz et al dataset led to a mean squared error of 0.88 and the coefficient of determination (R²) of 0.30. In comparison, Elasticnet regression technique on the modified Stevens et al dataset led to a mean squared error of 0.32 and the coefficient of determination (R²) of 0.42. The utilization of the Decision Tree(DT) regression on the modified Wilschut et al. dataset, resulted in the mean squared error of 0.28 and the coefficient of determination (R²) of 0.53. Decision Tree regression technique on the modified Stevens et al. dataset yielded a mean squared error: 0.31 and an R-squared Score :of 0.66. When the DT regression method was used on the Steinmetz et al dataset, the mean squared error was 0.89 and the R-squared Score was 0.14. Our comparison analysis utilizing ElasticNet, Ridge, and Decision Tree regression models to forecast skin permeability across three datasets provides significant insights into the relationship between data quality and model efficacy. This finding is consistent with and enhances the advancing field of computer modeling in cutaneous absorption, specifically in medication development, cosmetic safety, and regulatory science.

Purpose Misgendering of transgender and non-binary (TGNB) individuals in healthcare settings can lead to worsened mental and physical health outcomes and decreased utilisation of care. Few studies have investigated the factors that contribute to this phenomenon. The purpose of this study was to apply qualitative methods to explore sources of misgendering, its perceived impact, prevention strategies and clinician responses to accidentally misgendering a patient, as identified by TGNB patients and gender-affirming care clinicians. Methods Between April and June 2022, 20 semi-structured interviews were performed at an academic medical centre in Southern California. Participants were recruited via purposive sampling and included: (1) TGNB patients (n=8) recruited from an interdisciplinary gender-affirming urological practice and (2) gender-affirming care clinicians (n=12) recruited from a regional interdisciplinary Gender Health conference, three of whom identified as TGNB. Interviews were conducted in person or virtually using an open-ended topic guide, audio recorded and transcribed verbatim. Inductive thematic analysis was performed by two independent study personnel who hand-coded the transcripts. Results Four overarching themes were identified: (1) misgendering originates from multiple sources, (2) misgendering discourages individual access to healthcare, creates community hesitation and its perceived impact is modified by setting and intentionality, (3) building a gender-affirming healthcare system requires integration of behaviour, policy and technology and (4) clinicians respond to accidental misgendering by acknowledging, apologising, advancing and acting. Conclusion Our data suggest that misgendering arises from both interpersonal communication and structural factors within healthcare systems, leading to perceived harm and diminished TGNB access to health services. Any potential solution to reduce this phenomenon will require a multifaceted approach integrating behavioural, technological and institutional policy strategies with system-level implementation efforts.

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a growing but often unrecognized medical problem for people with diabetes (particularly type 2 diabetes, especially when associated with obesity). Liver health has not been at the forefront of complications tracked for disease prevention, as traditionally done for diabetic retinopathy, nephropathy, or neuropathy. However, liver steatosis affects approximately two out of three people with type 2 diabetes and places them at an increased risk for metabolic dysfunction–associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma (HCC), and overall liver-related mortality. MASLD is also associated with extrahepatic cancers, atherosclerotic cardiovascular disease, and progression from prediabetes to type 2 diabetes and negatively impacts health-related quality of life. However, most individuals and their health care professionals remain unaware of the severe hepatic or extrahepatic health risks associated with MASLD and the need for early identification. In recognition of this knowledge gap and the rising prevalence of MASLD, this consensus report is a call to action to screen for liver fibrosis and risk stratify people with prediabetes or type 2 diabetes, in particular if obesity is also present. This consensus report explains the rationale for the recent MASLD nomenclature change, how to best risk stratify, current treatment and long-term monitoring options, the value of an interprofessional approach to disease management, and the impact of alcohol intake on liver health. More awareness about the health risks associated with MASLD and broad adoption of screening for liver fibrosis as a new standard of care hold promise for a future without cirrhosis for people with prediabetes and type 2 diabetes.

GLP-1 receptor agonists have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their comparative efficacy and broader applications remain subjects of ongoing research. The aim of the study was to evaluate and compare the efficacy, safety, and clinical applications of three GLP-1 receptor agonists – Semaglutide, Dulaglutide, and Exenatide – through systematic review and meta-analysis. A comprehensive search of PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science (2015–2023) identified 20 randomized controlled trials and observational studies. Primary outcomes included changes in HbA1c and body weight. Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool. Semaglutide demonstrated superior efficacy with mean HbA1c reduction of 1.45% and weight loss of 1.44 kg. Dulaglutide showed consistent reductions in HbA1c (1.1%) and weight (1.2 kg). while Exenatide exhibited moderate effects. Meta-analysis revealed a significant pooled effect estimate favoring GLP-1 receptor agonists. with a mean HbA1c difference of –0.81 (95% CI: –0.92 to –0.70). Gastrointestinal side effects were most common, with Semaglutide showing the highest incidence. This meta-analysis establishes Semaglutide as the most effective GLP-1 receptor agonist for glycemic control and weight reduction, while Dulaglutide and Exenatide offer viable alternatives with fewer side effects. These findings support evidence-based decision-making in T2DM management and highlight the potential broader therapeutic applications of GLP-1 receptor agonists beyond diabetes care.

Biochemical alterations linked to metabolic syndrome (MetS), type 2 diabetes (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) may be brought on by the Western diet. Based on research conducted over the past decade, fructose is one of the main culprits. Over 80% of ingested fructose is metabolized by the liver at first pass, where it stimulates de novo lipogenesis (DNL) to drive hepatic triglyceride (TG) synthesis, which contributes to MASLD, hepatic insulin resistance (IR), and dyslipidemia. Fructose reduction produces quick and significant amelioration in these metabolic disturbances. We hereby propose potential overarching processes that can link these pathways to signaling disruption by the critical metabolic sensor AMP-activated protein kinase (AMPK). We proffer that when large amounts of fructose and glucose enter the liver, triose fluxes may be sufficient to produce transient increases in methylglyoxal (MG), allowing steady-state concentrations between its production and catabolism by glyoxalases to be high enough to modify AMPK-sensitive functional amino acid residues. These reactions would transiently interfere with AMPK activation by both AMP and aldolase. Such a sequence of events would boost the well-documented lipogenic impact of fructose. Given that MG adducts are irreversible, modified AMPK molecules would be less effective in metabolite sensing until they were replaced by synthesis. If proven, this mechanism provides another avenue of possibilities to tackle the problem of fructose in our diet. We additionally discuss potential multimodal treatments and future research avenues for this apparent hepatic AMPK malfunction.

The liver’s crucial role in methylglyoxal (MG) metabolism is frequently overlooked in the literature. We present a perspective that enhances the current understanding of the role of methylglyoxal (MG) and the glyoxalase cycle in the pathogenesis of insulin resistance and obesity, ultimately leading to type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Fructose may be a significant substrate contributing, particularly in contemporary times, to the flux of trioses in the liver, accounting for a substantial portion of MG production. The steady-state concentration of MG—and the subsequent modification of proteins—would then be determined by the flux of trioses, their utilization in lipogenesis, and their decomposition into MG, which is further converted into D-lactate by glyoxalase enzymes GLO1 and GLO2. Consequently, enhancing the activity and/or expression of GLO1 could potentially mitigate the adverse effects of fructose in the liver. Additional research and validation are required to confirm these biological pathways. These arguments are in favor of further research into safe and efficient ways to activate the glyoxalase pathway to lessen the negative effects of fructose metabolism that lead to insulin resistance (IR) and its related repercussions.

Osteopathic family physicians often face time constraints in clinical practice, necessitating the need for efficient, practical, and effective Osteopathic Manipulative Treatment (OMT) techniques. This article presents an overview of practical OMT interventions focusing on autonomics, biomechanics, circulation, and screening—collectively termed the ABCs of OMT. Screening techniques, including (but not limited to) Fluid Wave, Leg Tug, and Zink patterns, help rapidly identify somatic dysfunction. Detailed descriptions and visuals demonstrate efficient myofascial releases for thoracic inlet and thoracoabdominal diaphragm, pelvic region adjustments (supine pelvic gapping and pelvic differential technique), rib raising, and visceral techniques for esophageal and bladder dysfunction. Practical strategies for integrating these brief, high-yield techniques into daily patient care are discussed, facilitating immediate application in clinical practice.

Emerging evidence suggests that experiences of awe benefit health and well-being. The present investigation examined the efficacy of an awe intervention to improve the psychological health—stress, anxiety, depression, and well-being—of patients living with long COVID. The awe intervention, a Randomized-controlled Clinical Trial, was delivered in synchronous online sessions to patients, across the United States (in April 2023), who met the criteria for long COVID. Results revealed significant improvements in psychological health for those in the awe intervention (N = 30), compared to the control group (N = 38): including decreased stress, decreased depression symptoms, and increased well-being. There were no significant differences between groups in anxiety symptoms. Effect sizes ranged from medium to large (d = 0.78–0.96), demonstrating the robustness of these findings. This work is the first to document that awe can have salutary effects on psychological health, such as reducing symptoms of depression. These findings suggest that a brief awe intervention can improve psychological health in people dealing with chronic stress and physical ailments, as in the case of long COVID. Trial registration. The trial is registered at ClinicalTrials.gov (NCT05676008, 09/01/2023).

Background As Ethiopia expands cervical cancer screening services, it urgently needs information to develop appropriate post-screening diagnostic and treatment services for women with abnormal results. Quality cancer care requires extensive coordination among multidisciplinary provider teams. This study explores experiences coordinating care among providers at multiple levels of the cancer-care continuum in Ethiopia. Methods From February 2020 to January 2022, we conducted four focus group discussions (FGDs) and ten key-informant interviews with 34 purposively selected healthcare providers: health extension workers (HEWs) in communities; midwives and nurses at health centers; obstetrician-gynecologists at regional hospitals, and oncology nurses, oncologists, and pathologists at tertiary hospitals. FGDs and interviews were conducted in Amharic and audio-recorded. Audio transcripts were then simultaneously transcribed and translated into English for analysis. Investigators performed thematic analysis using inductive and deductive codes. Results We found four themes: resource scarcity, care centralization, lack of formal coordination mechanisms, and recommendations. Themes were dynamically connected by eight sub-themes. Providers valued teamwork and coordination. However, severe shortages of cancer specialists and high patient loads left little time for communication and hampered the formation of stable care teams. Facilities lacked formal coordination systems, such as patient navigators and case managers. The relative centralization of cancer care specialists and equipment in the capital exacerbated coordination problems. It impeded pre- and post-treatment care communication between tertiary and secondary facilities and caused secondary facilities to unnecessarily refer patients because they lacked the resources to treat them locally. Referral communication was unidirectional, with lower-level providers communicating regularly to higher-level facilities but rarely receiving feedback. The exception was regular, structured feedback from primary facilities to HEWs. Lower-level providers wanted to learn whether their referrals were appropriate or completed, and many used informal channels to gain this information. Respondents recommend decentralizing cancer care services, significantly increasing staff and equipment investments, and adding liaison staff at secondary hospitals to track and communicate patient progress and counsel patients for referral. Conclusions Our findings underscore the need to rapidly increase cancer specialist staff and regional cancer centers in Ethiopia and highlight the importance of developing robust coordination and feedback mechanisms at secondary and tertiary facilities.

The divergence of Homo from gracile australopiths has been described as a trend of decreasing dentognathic size and robusticity, precipitated by stone tool use and/or a shift to softer foods, including meat. Yet, mechanical evidence supporting this narrative is sparse, and isotopic and archaeological data have led to the suggestion that a shift away from a gracile australopith-like diet would not have occurred in the most basal members of Homo but rather only with the appearance of Homo erectus, implying that the origin of our genus is not rooted in dietary change. Here, we provide mechanical evidence that Homo habilis exhibits an australopith-like pattern of facial strain during biting but, unlike most australopiths, was not suited for a diet that required forceful processing by the molar teeth. Homo habilis was at elevated risk of distractive jaw joint forces during those bites, constraining muscle recruitment so as to avoid generating uncomfortable/dangerous levels of tension in the joint. Modern humans have similar limitations. This suggests that selection on skeletal traits favouring forceful postcanine processing was relaxed by the earliest stages in the evolution of our genus, implying that dietary or food processing changes played an important role in the emergence of Homo.

Resumen La declaración de Granada fue el resultado de la necesidad de fortalecer la farmacia práctica clínica, social y administrativa como un área de conocimiento que se materialice en la práctica, la investigación y la política. Para ello, un grupo de editores de revistas de farmacia práctica, clínica y social puso en marcha en el año 2022 en Granada una iniciativa para discutir formas de mejorar la calidad de las publicaciones en esta área, y que culminó en el documento denominado Declaración de Granada. Se desarrollaron dieciocho recomendaciones, agrupadas en seis ámbitos principales: 1) uso apropiado de la terminología; 2) elaborar resúmenes impacto 3) necesidad de las revisiones por pares; 4) limitar la dispersión de revistas; 5) uso más efectivo y adecuado de las métricas de impacto de revistas y artículos; y 6) selección por los autores de la revista de farmacia práctica más apropiada para publicar su trabajo. La declaración de Granada ha sido publicada íntegramente en 14 revistas. Este documento pionero tiene sus antecedentes en otras iniciativas similares desarrolladas por académicos de otros grupos de profesiones de la salud, fomentando el concepto de consenso interdisciplinar y avanzando en el paradigma científico.

In this article, the authors examine the history, development, and current state of K-12 online learning, challenging the assertions that COVID-19-era distance education was unprecedented. Drawing on historical examples, the authors demonstrate how educational systems have repeatedly leveraged various technologies for remote instruction during disruptions, from correspondence courses to radio broadcasts to modern digital platforms. The analysis reveals persistent challenges in implementing effective online learning, including inadequate teacher preparation, inconsistent terminology, and limited theoretical frameworks. While K-12 online learning has shown promise for expanding educational access and flexibility, adoption remains relatively low globally. The article concludes that realizing the potential of K-12 online learning requires addressing fundamental issues in research, practice, and policy while learning from past experiences rather than treating each implementation as novel.

Introduction Pediatric drug-resistant epilepsy (DRE) is defined as epilepsy that is not controlled by two or more appropriately chosen and dosed anti-seizure medications (ASMs). When alternative therapies or surgical intervention is not viable or efficacious, advanced options like deep brain stimulation (DBS) or responsive neurostimulation (RNS) may be considered. Objective Describe the Stanford early institutional experience with DBS and RNS in pediatric DRE patients. Methods Retrospective chart review of seizure characteristics, prior therapies, neurosurgical operative reports, and postoperative outcome data in pediatric DRE patients who underwent DBS or RNS placement. Results Nine patients had DBS at 16.0 ± 0.9 years and 8 had RNS at 15.3 ± 1.7 years (mean ± SE). DBS targets included the centromedian nucleus of the thalamus (78% of DBS patients), anterior nucleus of the thalamus (11%), and pulvinar (11%). RNS placement was guided by stereo-EEG and/or intracranial monitoring in all RNS patients (100%). RNS targets included specific seizure onset zones (63% of RNS patients), bilateral hippocampi (25%) and bilateral temporal lobes (12%). Only DBS patients had prior trials of ketogenic diet (56%) and VNS therapy (67%). Four DBS patients (44%) had prior neurosurgical interventions, including callosotomy (22%) and focal resection (11%). One RNS patient (13%) and one DBS patient (11%) required revision surgery. Two DBS patients (22%) developed postoperative complications. Three RNS patients (38%) underwent additional resections; one RNS patient had electrocorticography recordings for seizure mapping before surgery. For patients with a follow-up of at ≥1 year (n = 7 for DBS and n = 5 for RNS), all patients had reduced seizure burden. Clinical seizure freedom was achieved in 80% of RNS patients and 20% had a >90% reduction in seizure burden. The majority (71%) of DBS patients had a ≥50% reduction in seizures. No patients experienced no change or worsening of seizure frequency. Conclusion In the early Stanford experience, DBS was used as a palliatively for generalized or mixed DRE refractory to other resective or modulatory approaches. RNS was used for multifocal DRE with a clear seizure focus on stereo-EEG and no prior surgical interventions. Both modalities reduced seizure burden across all patients. RNS offers the additional benefit of providing data to guide future surgical planning.

Background While interprofessional education (IPE) has become commonplace, incorporation of motivational interviewing (MI) using standardized patients (SPs) has been rare, particularly use of a multi-pronged strategy of engagement among pharmacy and physician assistant students. Objective The aim of this study was to determine the impact of an IPE MI training intervention that employed students in teams interacting with standardized patients (SPs); specifically, the intervention impact on MI self-efficacy, professional identity formation (PIF) and attitudes toward interprofessional care. Methods First-year PharmD students (PGY1) and second-year physician assistant students (PA-S2) underwent a three-hour didactic class session featuring lecture and video simulations followed by an activity where teams of 6–8 students interacted with 5 different standardized patients (SPs). The educational intervention also featured a group debriefing session and written reflection prompted by answering several questions about how they fared with the SPs. Students' completed pre- and post- intervention surveys featuring standardized instrumentation measuring self-efficacy to engage in MI, professional identity formation, and attitudes toward interprofessional education. Results Students did not achieve substantive gains in MI self-efficacy, yet reported significant improvements in professional identity formation and attitudes toward interprofessional education. Qualitative comments from the post-intervention survey were positive for interprofessional integration and team dynamics (n = 14), though both PGY1 and PA-S2 students commented that academic year concordance, i.e., matching a PGY1 with a PA-S1, in future simulations could improve self-efficacy and confidence. Conclusions An IPE event featuring lecture, interaction with SPs, and an opportunity for mutual self-reflection on one another's roles in patient care might be beneficial to include in pharmacy and PA curriculum, even while such endeavors might be further enhanced using a longitudinal approach.

Background Few studies have evaluated changes in leukocyte telomere length (LTL) over a short time period (e.g. 1 week). LTL shortening is accelerated by exposure to inflammation and reactive oxygen species (ROS) damage. Methods In the context of an isocaloric fructose restriction study that was conducted with 43 Black and Latinx children over a 9-day period, we evaluated the relationship between metabolic health at baseline and metabolic changes and LTL at baseline and %LTL change over the follow-up period. Linear regression models were used to assess associations between metabolic correlates and LTL at baseline and LTL changes over 9 days. Results Overall children lost − 0.05 ± 0.14 T/S units or − 2.98 ± 8.74% total change over the follow-up period. Higher concentrations of HDL-C, APO-AI and a greater % of large HDL-C at baseline were associated with reduced LTL attrition rates at day 10 (p < 0.01; p < 0.01 and p = 0.02 respectively). Increases in APO-AI over the follow-up period were associated with increased LTL attrition over the follow-up period (p = 0.03). Conclusions In this short term isocaloric fructose restriction study, LTL at baseline and changes in LTL over 9 days were associated with HDL-C and APO-AI and not with any other non-HDL-C lipids. Additional, larger studies are necessary to better understand the interplay between short term fructose restriction, LTL changes and HDL-C/APO-AI.

Multilayered epithelia lining our tissue surfaces normally resist traversal by opportunistic bacteria. Previously, we developed a strategy to experimentally perturb this resistance in situ in the corneas of mouse eyes and used it to show that traversal of a multilayered epithelium by Pseudomonas aeruginosa requires ExsA, the transcriptional activator of its type 3 secretion system (T3SS). Here, we developed a novel strategy for quantitatively localizing individual traversing bacteria within the in situ multilayered corneal epithelium and explored the contributions of T3SS components. The results showed that T3SS translocon and T3SS effector mutants had reduced epithelial traversal efficiency. Surprisingly, a ΔpscC mutant unable to assemble the T3SS needle traversed as efficiently as wild-type P. aeruginosa, while a ΔexsD mutant “constitutively on” for T3SS expression was traversal defective. The dispensability of the T3SS needle for effector-mediated traversal was confirmed using a mutant lacking the T3SS operon except for the effector genes (ΔpscU-L mutant). That mutant reacquired the ability to traverse if complemented with rhamnose-inducible exsA, but not if the effector genes were also deleted (ΔpscU-LΔexoSTY). Western immunoblot confirmed ExoS in culture supernatants of rhamnose-induced exsA-complemented ΔpscU-L mutants lacking all T3SS needle protein genes. Together, these results show that epithelial traversal by P. aeruginosa can involve T3SS effectors and translocon proteins independently of the T3SS needle previously thought essential for T3SS function. This advances our understanding of P. aeruginosa pathogenesis and has relevance to the development of therapeutics targeting the T3SS system. IMPORTANCE While the capacity to cross an epithelial barrier can be a critical step in bacterial pathogenesis, our understanding of the mechanisms involved is derived largely from cell culture experimentation. The latter is due to the practical limitations of in vivo/in situ models and the challenge of visualizing individual bacteria in the context of host tissue. Here, factors used by P. aeruginosa to traverse an epithelial multilayer in situ were studied by (i) leveraging the transparent properties and superficial location of the cornea, (ii) using our established method for enabling bacterial traversal susceptibility, and (iii) developing a novel strategy for accurate and quantitative localization of individual traversing bacteria in situ. Outcomes showed that T3SS translocon and T3SS effector proteins synergistically contribute to epithelial traversal efficiency independently of the T3SS needle. These findings challenge the assumption that the T3SS needle is essential for T3SS effectors or translocon proteins to contribute to bacterial pathogenesis.