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The hippocampus and medial entorhinal cortex (MEC) form a cognitive map that facilitates spatial navigation. As part of this map, MEC grid cells fire in a repeating hexagonal pattern across an environment. This grid pattern relies on inputs from the medial septum (MS). The MS, and specifically GABAergic neurons, are essential for theta rhythm oscillations in the entorhinal-hippocampal network; however, the role of this population in grid cell function is unclear. To investigate this, we use optogenetics to inhibit MS-GABAergic neurons and observe that MS-GABAergic inhibition disrupts grid cell spatial periodicity. Grid cell spatial periodicity is disrupted during both optogenetic inhibition periods and short inter-stimulus intervals. In contrast, longer inter-stimulus intervals allow for the recovery of grid cell spatial firing. In addition, grid cell phase precession is also disrupted. These findings highlight the critical role of MS-GABAergic neurons in maintaining grid cell spatial and temporal coding in the MEC.
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Córtex Entorrinal , Neurônios GABAérgicos , Células de Grade , Optogenética , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Animais , Córtex Entorrinal/fisiologia , Córtex Entorrinal/metabolismo , Córtex Entorrinal/citologia , Células de Grade/fisiologia , Camundongos , Masculino , Ritmo Teta/fisiologia , Núcleos Septais/fisiologia , Núcleos Septais/metabolismoRESUMO
Earlier laboratory-based evidence has suggested that polyphenol-rich, decaffeinated whole coffee cherry extract (CCE) supports improvements in acute and long-term cognitive performance. To better understand CCE's potential to promote cognitive processing, we conducted a first-of-its-kind remote clinical trial. Participants were randomized into one of two intervention arms: placebo or 200 mg CCE. At the beginning of the study, participants were asked to complete a set of acute cognitive challenges as part of the baseline assessment. Tasks were nearly identical to those used in previous, laboratory-based research. Acute results support that CCE outperformed placebo, reducing omissions and improving accuracy, during working memory and inhibitory control tasks. Long-term results indicate that CCE outperformed placebo on a measure of accuracy. This contributes to the literature in three ways: (1) results improve upon previously reported robust and consistent findings in a real-world setting that a single-dose of CCE acutely improved cognitive performance; (2) results replicate previous laboratory findings but in a real-world setting that long-term CCE supplementation outperformed placebo on measures of accuracy in a working memory task; and (3) it serves as proof of concept of a novel remote clinical trial model that may provide real-world evidence of efficacy while increasing accessibility and cohort diversity.
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Cognição , Memória de Curto Prazo , Extratos Vegetais , Humanos , Memória de Curto Prazo/efeitos dos fármacos , Método Duplo-Cego , Extratos Vegetais/farmacologia , Masculino , Feminino , Adulto , Cognição/efeitos dos fármacos , Adulto Jovem , Prunus avium/química , Suplementos Nutricionais , Estudos Longitudinais , Inibição PsicológicaRESUMO
BACKGROUND: Geroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes. METHODS: This study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts. RESULTS: Distinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways. CONCLUSIONS: This study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05297825.
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Envelhecimento , Metilação de DNA , Dieta Vegana , Epigênese Genética , Humanos , Feminino , Masculino , Envelhecimento/genética , Pessoa de Meia-Idade , Idoso , Dieta , Gêmeos/genética , Dieta VegetarianaRESUMO
OBJECTIVE: To pilot a situational judgment test (SJT) developed to assess empathy, integrity, and teamwork and explore differences in performance between first-year (P1) and fourth-year (P4) student pharmacists based on gender, race or ethnicity, and geographical region. METHODS: An SJT was developed to assess empathy, integrity, and teamwork, using best practices. The SJT was piloted tested with P1 and P4 student pharmacists at 5 institutions. Scores were adjusted for elevation and scatter to minimize the subgroup differences in response styles. RESULTS: The unadjusted mean SJT scores for P1 and P4 student pharmacists were 79.7 % and 80.7 %, respectively. The adjusted scores for P1 and P4 student pharmacists were 86.3 % and 87.2 %, respectively. Small differences were observed across institutions which can likely explained by multiple factors. The mean scores were higher among students who were older, female, identified as White, and spoke English as their first language. The subgroup differences persisted even after adjusting scores for elevation and scatter. CONCLUSION: Performance on an SJT designed to assess empathy, integrity, and teamwork was similar to others in the literature; however, differences in performance were observed across subgroups. Additional research is needed to determine whether these differences reflect test bias or other possible factors.
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Educação em Farmácia , Empatia , Julgamento , Estudantes de Farmácia , Humanos , Feminino , Masculino , Estudantes de Farmácia/psicologia , Educação em Farmácia/métodos , Avaliação Educacional/métodos , Projetos Piloto , Adulto , Adulto JovemRESUMO
OBJECTIVE: Sufficient evidence within the past two decades have shown that osteoarthritis (OA) has a sex-specific component. However, efforts to reveal the biological causes of this disparity have emerged more gradually. In this narrative review, we discuss anatomical differences within the knee, incidence of injuries in youth sports, and metabolic factors that present early in life (childhood and early adulthood) that can contribute to a higher risk of OA in females. DESIGN: We compiled clinical data from multiple tissues within the knee joint-since OA is a whole joint disorder-aiming to reveal relevant factors behind the sex differences from different perspectives. RESULTS: The data gathered in this review indicate that sex differences in articular cartilage, meniscus, and anterior cruciate ligament are detected as early as childhood and are not only explained by sex hormones. Aiming to unveil the biological causes of the uneven sex-specific risks for knee OA, we review the current knowledge of sex differences mostly in young, but also including old populations, from the perspective of (i) human anatomy in both healthy and pathological conditions, (ii) physical activity and response to injury, and (iii) metabolic signatures. CONCLUSIONS: We propose that to close the gap in health disparities, and specifically regarding OA, we should address sex-specific anatomic, biologic, and metabolic factors at early stages in life, as a way to prevent the higher severity and incidence of OA in women later in life.
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Cartilagem Articular , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/epidemiologia , Feminino , Masculino , Fatores Sexuais , Cartilagem Articular/metabolismo , Fatores de Risco , Articulação do Joelho , Caracteres Sexuais , Fatores Etários , Traumatismos em Atletas , CriançaRESUMO
Evidence suggests that both pharmacy students and preceptors are struggling in the experiential setting. Underlying this phenomenon is a potential interconnected and cyclic set of behaviors being reinforced between students and preceptors. These behaviors can contribute to or are the result of higher levels of burnout and a decrease in the development of student clinical skills and subsequent performance on rotation. In this review, the authors investigate various challenges commonly encountered in the experiential environment. These challenges can range from an observed decrease in student engagement, motivation, and critical thinking skills to an increase in preceptor burnout and culture shifts in the clinical practice environments. These factors all ultimately impact patient care and overall student performance. For each challenge identified, strategies will be presented that can be implemented by students, preceptors, and pharmacy programs to break the cyclic pattern identified.
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Educação em Farmácia , Motivação , Preceptoria , Estudantes de Farmácia , Humanos , Estudantes de Farmácia/psicologia , Educação em Farmácia/métodos , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/psicologia , Aprendizagem Baseada em Problemas/métodos , Competência ClínicaRESUMO
The development of a congenital heart defect (CHD) is multifactorial, with many cases having an unknown etiology. This study explored whether maternal race and lived environment were associated with an infant being born with a critical CHD. A cross-sectional, case-control design was conducted utilizing secondary data analysis. The CHD group (N = 199) consisted of infants diagnosed with a critical CHD within the first year of life identified from hospital databases. The non-CHD group (N = 548) was a random sample of infants selected from the state's vital statistics database. The primary outcome was a critical CHD diagnosis. Maternal race, residential rurality, and the Social Vulnerability Index (SVI) were assessed for associations with a critical CHD using bivariate and multilevel regression models. Bivariate findings reported significance among residential rurality (p < 0.001), SVI ranking overall (p = 0.017), and SVI by theme (theme 1 p = 0.004, theme 2 p < 0.001, theme 3 p = 0.007, and theme 4 p = 0.049) when comparing infants with and without a critical CHD diagnosis. Results of multilevel logistic regression analyses further identified living in a rural residential area compared to urban areas (OR = 7.32; p < 0.001) as a predictor for a critical CHD diagnosis. The findings of lived environmental level associations provides information needed for continued investigation as the burden of a critical CHD continues to impact families, suggesting further research efforts are needed to improve health disparities.
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INTRODUCTION: Post-operative pelvic & acetabular fixation patients are conventionally imaged using 3-view radiographs (AP, inlet and outlet). The efficacy of such radiographs is inconsistent due to technical difficulties capturing an adequate view, often necessitating repeat radiographs and therefore increasing radiation exposure. Radiographs can be difficult to interpret, limiting the assessment of fracture reduction and fixation, especially with respect to metalwork positioning around articular surfaces. Traditionally, post-operative pelvic & acetabular fixation patients undergo repeat 3-view radiographs post-operatively, at 6 weeks, followed by at 3, 6, 12, 18 and 24 months. We propose a new pathway, in which patients have one low-dose pelvic CT immediately post-operatively, followed by one radiograph (AP pelvis) at the same time points. METHODS: A new pelvic CT protocol was created to provide high quality 3D imaging whilst delivering a 5 times lower radiation dose (compared to normal pelvic CT). Data for all pelvic radiographs and CTs between January 2021 and March 2022 was exported. Using dose area product values, effective radiation dose and attributable lifetime cancer risk were calculated. RESULTS: There were 42 patients included in the analysis (age range 15 to 87).The average effective dose for the 3-view pelvic X-rays was 0.6mSv (range 0.2 to 2.8mSv), and 1.1mSv (range 0.5 to 2.2mSv) for the low-dose pelvic CT. Traditional 7 × 3-view post-operative radiographs: 7 × 0.6mSv = 4.2mSv (corresponding to 1 in 11,000 cancer risk) Low dose post-operative CT and 6 × 1-view radiographs: 1.1mSv + (6 × 0.6mSv / 3) = 2.3mSv (corresponding to 1 in 20,000 cancer risk) CONCLUSION: Low-dose CT scanning (in conjunction with 1-view radiographs) is an effective and safe imaging modality in the post-operative assessment of pelvic & acetabular fracture fixation, conferring a lower radiation burden, easier logistics, and higher quality images when compared to the traditional pathway of 3-view radiographs.
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Acetábulo , Fixação Interna de Fraturas , Fraturas Ósseas , Ossos Pélvicos , Doses de Radiação , Tomografia Computadorizada por Raios X , Humanos , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/lesões , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Idoso , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Adolescente , Idoso de 80 Anos ou mais , Fixação Interna de Fraturas/métodos , Adulto Jovem , Imageamento Tridimensional , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos , Período Pós-Operatório , Exposição à RadiaçãoRESUMO
Fiber-reinforcement approaches have been used to replace aligned tissues with engineered constructs after injury or surgical resection, strengthening soft biomaterial scaffolds and replicating anisotropic, load-bearing properties. However, most studies focus on the macroscale aspects of these scaffolds, rarely considering the cell-biomaterial interactions that govern remodeling and extracellular matrix organization toward aligned neo-tissues. As initial cell-biomaterial responses within fiber-reinforced microenvironments likely influence the long-term efficacy of repair and regeneration strategies, here we elucidate the roles of spatial orientation, substrate stiffness, and matrix remodeling on early cell-fiber interactions. Bovine mesenchymal stromal cells (MSCs) were cultured in soft fibrin gels reinforced with a stiff 100 µm polyglycolide-co-caprolactone fiber. Gel stiffness and remodeling capacity were modulated by fibrinogen concentration and aprotinin treatment, respectively. MSCs were imaged at 3 days and evaluated for morphology, mechanoresponsiveness (nuclear Yes-associated protein [YAP] localization), and spatial features including distance and angle deviation from fiber. Within these constructs, morphological conformity decreased as a function of distance from fiber. However, these correlations were weak (R2 = 0.01043 for conformity and R2 = 0.05542 for nuclear YAP localization), illustrating cellular heterogeneity within fiber-enforced microenvironments. To better assess cell-fiber interactions, we applied machine-learning strategies to our heterogeneous dataset of cell-shape and mechanoresponsive parameters. Principal component analysis (PCA) was used to project 23 input parameters (not including distance) onto 5 principal components (PCs), followed by agglomerative hierarchical clustering to classify cells into 3 groups. These clusters exhibited distinct levels of morpho-mechanoresponse (combination of morphological conformity and YAP signaling) and were classified as high response (HR), medium response (MR), and low response (LR) clusters. Cluster distribution varied spatially, with most cells (61%) closest to the fiber (0-75 µm) belonging to the HR cluster, and most cells (55%) furthest from the fiber (225-300 µm) belonging to the LR cluster. Modulation of gel stiffness and fibrin remodeling showed differential effects for HR cells, with stiffness influencing the level of mechanoresponse and remodeling capacity influencing the location of responding cells. Together, these novel findings demonstrate early trends in cellular patterning of the fiber-reinforced microenvironment, showing how spatial orientation, substrate biophysical properties, and matrix remodeling may guide the amplitude and localization of cellular mechanoresponses. These trends may guide approaches to optimize the design of microscale scaffold architecture and substrate properties for enhancing organized tissue assembly at the macroscale.
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INTRODUCTION: Tenofovir-based oral pre-exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user-controlled long-acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90-day TFV ring. METHODS: Between January and June 2019, Microbicide Trials Network (MTN)-038 enrolled 49 HIV-negative participants into a phase 1, randomized (2:1) trial comparing a 90-day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV-diphosphate (TFV-DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self-report. RESULTS: Mean age was 29.5; 46 identified as cisgender-female and three gender non-conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV-DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low (<0.1 g) residual TFV. Residual TFV did not differ by socio-demographics, sexual activity, Nugent Score or vaginal microbiota. Most participants reported being fully adherent to ring use: 85% and 81% in the TFV and placebo arms, respectively (p = 1.00). A majority of participants reported liking the ring (median 8 on a 10-point Likert scale) and reported a high likelihood of using the ring in the future, if effective (median 9). CONCLUSIONS: The 90-day TFV ring was well-tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use.
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Infecções por HIV , Tenofovir , Adulto , Feminino , Humanos , Adenina , Herpesvirus Humano 2 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Microbiota , Tenofovir/efeitos adversos , Tenofovir/farmacocinética , Estados UnidosRESUMO
Current understanding of the physiological underpinnings of normative pain processing is incomplete. Enhanced knowledge of these systems is necessary to advance our understanding of pain processes as well as to develop effective therapeutic interventions. Previous neuroimaging research suggests a network of interrelated brain regions that seem to be implicated in the processing and experience of pain. Among these, the dorsal anterior cingulate cortex (dACC) plays an important role in the affective aspects of pain signals. The current study leveraged functional MRS to investigate the underlying dynamic shifts in the neurometabolic signature of the human dACC at rest and during acute pain. Results provide support for increased glutamate levels following acute pain administration. Specifically, a 4.6% increase in glutamate was observed during moderate pressure pain compared with baseline. Exploratory analysis also revealed meaningful changes in dACC gamma aminobutyric acid in response to pain stimulation. These data contribute toward the characterization of neurometabolic shifts, which lend insight into the role of the dACC in the pain network. Further research in this area with larger sample sizes could contribute to the development of novel therapeutics or other advances in pain-related outcomes.
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Dor Aguda , Humanos , Feminino , Dor Aguda/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Giro do Cíngulo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Ácido GlutâmicoRESUMO
OBJECTIVE: Conduct a multisite, survey-based study assessing rates of self-reported depressive symptoms among student pharmacists enrolled in the first 3 years (P1-P3) of 4-year Doctor of Pharmacy (PharmD) curricula. METHODS: This study followed a cross-sectional observational design conducted at Washington State University, College of Pharmacy and Pharmaceutical Sciences, and the University of Arkansas for Medical Sciences, College of Pharmacy. Student pharmacists in the first 3 years of pharmacy school (P1-P3) of the PharmD curricula were invited to voluntarily complete the Center for Epidemiologic Studies Depression Scale (CES-D) to collect self-reported measures of depression. The CES-D is a validated 20-item instrument using a 4-point Likert scale. RESULTS: A total of 1795 surveys were evaluated from P1-P3 students at Washington State University, College of Pharmacy and Pharmaceutical Sciences and University of Arkansas for Medical Sciences, College of Pharmacy over a 4-year period (2019-2022). Overall, 1150 (64.1%) surveys indicated the presence of depressive symptoms on CES-D. The highest rate of reported depressive symptoms was recorded in 2021 (71.4%), notably during the coronavirus disease 2019 pandemic, whereas the lowest rate was prepandemic in 2019 (57.8%). The P1 cohort had the highest depression rate in 2020 and 2021, whereas the P2 cohort was highest in 2019 and 2022. The P3 cohort screening positive for depression increased from 52.6% to 69.3% over the 4-year period. CONCLUSION: This multisite, longitudinal study confirms that self-reported depressive symptoms in student pharmacists are significantly higher than what is reported in undergraduate students. Opportunities exist for pharmacy educators and university wellness services to better identify and serve student pharmacists experiencing depression or depressive episodes.
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Depressão , Estudantes de Farmácia , Humanos , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Educação em Farmácia , Estudos Longitudinais , PrevalênciaRESUMO
OBJECTIVE: The primary objective of this study was to examine the levels of agreement and reliability of a situational judgment test (SJT) using a diverse pool of pharmacy practice faculty as subject matter experts. Secondary aims included analyses to build support for test validity and fairness. METHODS: An SJT containing 18 scenarios and 118 responses assessing empathy, integrity, and teamwork was developed and delivered to pharmacy practice faculty at 5 schools of pharmacy across the United States. Reliability was assessed by examining internal consistency, inter-rater reliability, and split-half reliability. Only responses which attained an inter-rater agreement>0.7 were included in the final version of the SJT. All responses were scored using a near-miss system, allowing higher scores for answers more closely aligned with the key, which was determined by the faculty who completed the SJT. Test fairness was reported using descriptive statistics. RESULTS: Thirty-nine faculty across the 5 participating institutions completed the SJT. The final version of the SJT included 105 responses, achieving an inter-rater agreement of>0.7 (inter-rater reliability of 0.98). Split-half reliability was 0.72. The average score was 85.7%, and no differences in performance were observed based on demographic characteristics. CONCLUSION: An SJT designed to assess empathy, integrity, and teamwork achieved reasonable levels of reliability among pharmacy practice faculty across the United States, and the results provided initial support for test validity and fairness. These results support a pilot to assess this SJT among students representing multiple institutions.
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Educação em Farmácia , Julgamento , Humanos , Julgamento/fisiologia , Reprodutibilidade dos Testes , Educação em Farmácia/métodos , Empatia , EstudantesRESUMO
The hippocampus and medial entorhinal cortex (MEC) form a cognitive map that facilitates spatial navigation. As part of this map, MEC grid cells fire in a repeating hexagonal pattern across an environment. This grid pattern relies on inputs from the medial septum (MS). The MS, and specifically its GABAergic neurons, are essential for theta rhythm oscillations in the entorhinal-hippocampal network, however, it is unknown if this subpopulation is also essential for grid cell function. To investigate this, we used optogenetics to inhibit MS-GABAergic neurons during grid cell recordings. We found that MS-GABAergic inhibition disrupted grid cell spatial periodicity both during optogenetic inhibition and during short 30-second recovery periods. Longer recovery periods of 60 seconds between the optogenetic inhibition periods allowed for the recovery of grid cell spatial firing. Grid cell temporal coding was also disrupted, as observed by a significant attenuation of theta phase precession. Together, these results demonstrate that MS-GABAergic neurons are critical for grid cell spatial and temporal coding in the MEC.
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Importance: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds). Objective: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention. Design, Setting, and Participants: This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data. Intervention: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks. Main Outcomes and Measures: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being. Results: A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] µIU/mL; 95% CI, -5.3 to -0.4 µIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg). Conclusions and Relevance: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients. Trial Registration: ClinicalTrials.gov Identifier: NCT05297825.
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Doenças Cardiovasculares , Dieta Vegana , Adulto , Feminino , Humanos , Masculino , Peso Corporal , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Insulinas , Gêmeos Monozigóticos , Verduras , Pessoa de Meia-Idade , Dieta SaudávelRESUMO
A small but growing body of research has suggested the potential for cannabis substitution to support Managed Alcohol Program (MAP) service users to reduce acute and chronic alcohol-related harms. In 2022, researchers from the Canadian Managed Alcohol Program Study (CMAPS) noted a dearth of accessible, alcohol-specific educational resources to support service users and program staff to implement cannabis substitution pilots at several MAP sites in Canada. In this essay, we draw on over 10-years of collaboration between CMAPS, and organizations of people with lived experience (the Eastside Illicit Drinkers Group for Education (EIDGE) and SOLID Victoria) to describe our experiences co-creating cannabis education resources where none existed to support MAP sites interested in beginning to provide cannabis to participants. The research team relied on the unique lived experiences and informal cannabis-related harm reduction strategies described by EIDGE and SOLID members to create cannabis education resources that were accurate and relevant to MAP sites. EIDGE was familiar with creating peer-oriented educational resources and convened meetings and focus groups to engage peers. CMAPS research team members created standard cannabis unit equivalencies to support program delivery, and clinical advisors ensured that the stated risks and benefits of cannabis substitution, as well as tapering guidance for withdrawal management, were safe and feasible. The collaboration ultimately produced tailored client-facing and provider-facing resources. Our experience demonstrates that the lived expertise of drinkers can play an integral role in creating alcohol harm reduction informational materials, specifically those related to cannabis substitution, when combined with data from rigorous, community-based programs of research like CMAPS. We close by listing additional considerations for cannabis substitution program design for MAP settings emerging from this process of collaboration between illicit drinkers, service providers, clinicians, and researchers for consideration by other programs.
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Cannabis , Humanos , Canadá , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Redução do Dano , Grupos FocaisRESUMO
Objective: To identify gaps among Australian Long COVID support services and guidelines alongside recommendations for future health programs. Methods: Electronic databases and seven government health websites were searched for Long COVID-specific programs or clinics available in Australia as well as international and Australian management guidelines. Results: Five Long COVID specific guidelines and sixteen Australian services were reviewed. The majority of Australian services provided multidisciplinary rehabilitation programs with service models generally consistent with international and national guidelines. Most services included physiotherapists and psychologists. While early investigation at week 4 after contraction of COVID-19 is recommended by the Australian, UK and US guidelines, this was not consistently implemented. Conclusion: Besides Long COVID clinics, future solutions should focus on early identification that can be delivered by General Practitioners and all credentialed allied health professions. Study findings highlight an urgent need for innovative care models that address individual patient needs at an affordable cost. We propose a model that focuses on patient-led self-care with further enhancement via multi-disciplinary care tools.
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Hernias occur when part of an organ, typically the intestines, protrudes through a disruption of the fascia in the abdominal wall, leading to patient pain, discomfort, and surgical intervention. Over one million hernia repair surgeries occur annually in the USA, but globally, hernia surgeries can exceed 20 million. Standard practice includes hernia repair mesh to help hold the compromised tissue together, depending on where the fascial disruption is located and the patient's condition. However, the recurrence rate for hernias after using the most common type of hernia mesh, synthetic, is currently high. Physiological-level electrical stimulation (ES) has shown beneficial effects in improving healing in soft tissue regeneration. Piezoelectric materials can produce low-level electrical signals from mechanical loading to help speed healing. Combining the novelty of piezo elements to create an electrically active hernia repair mesh for faster healing prospects is explored in this study through simulated transcutaneous mechanical loading of the piezo element with therapeutic ultrasound. A tissue phantom was developed using Gelatin #0 and Metamucil® to better simulate a clinical application of the therapeutic ultrasound loading modality. The cellular viability of varying ultrasound intensities and temporal effects was analyzed. Overall, minimal cytotoxicity was observed across all experimental groups during the ultrasound intensity and temporal viability studies.
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Parede Abdominal , Telas Cirúrgicas , Animais , Camundongos , Humanos , Parede Abdominal/cirurgia , Herniorrafia , Hérnia , FibroblastosRESUMO
Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD's neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their "real world" drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.