Stressed and Depressed: Prevalence of Anxiety and/or Depression in Physician Assistant Students.

INTRODUCTION: This research highlights the prevalence of anxiety and/or depression among physician assistant (PA) students compared with the general population. It is believed that the results of this study will encourage graduate programs to place a stronger emphasis on the mental health of students and create a more positive learning environment. METHODS: An original survey was created using questions from Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and several original questions. The survey was distributed using a SurveyMonkey link to directors of all accredited US PA programs. Program directors were asked to distribute the survey to their students. The survey remained open for 6 weeks, after which a cross-sectional statistical analysis was performed to compare the results with national anxiety and depression data in the United States. RESULTS: There is a statistically significant increase in the rate of occurrence of anxiety and/or depression among PA students compared with the general population. According to survey results, 84.4% of respondents experienced feelings of anxiety and 80.9% experienced feelings of depression while enrolled in PA school. Physician assistant students found the greatest need for anxiety and depression treatment during the didactic portion of their program. DISCUSSION: When compared with the national population, the level of anxiety in PA students was found to be 65.3% higher and the levels of depression in PA students to be 72.5% higher. These results should encourage PA programs and health care providers to take action regarding the mental health of future providers.

Physician Assistant Program Accreditation Analysis and Survey of Program Directors.

PURPOSE: To inform physician assistant program directors through citation analysis after implementation of the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) Accreditation Standards, 5th edition. METHODS: This research used descriptive statistics, Pearson correlation, and the coefficient of determination to analyze the citations reported by ARC-PA during January 2021 to February 2023. Concurrent first-time taker Physician Assistant National Certifying Exam (PANCE) results were used to determine whether a correlation exists between pass rates and citations. In addition, a survey was sent to each institution's current program director to investigate leadership concerns and differences between programs placed on a provisional, continued, or probation status by ARC-PA. RESULTS: Of the 98 program submissions for accreditation, 13 submissions resulted in a probation status outcome. For these 13 programs placed on probation, 46.2% and 30.8% were cited for being noncompliant with leadership Standards A2.09 and A1.02, respectively. Pearson correlation analysis indicates a significant negative correlation between ARC-PA citations and first-time taker PANCE pass rates (P = .023, 95% confidence interval [CI] = [-0.49 to -0.04]). This is particularly true for programs with continued accreditation (P = .007, 95% CI = [-0.67 to -0.13]) and programs that performed below the 85% benchmark (P = .013, 95% CI = [-0.94 to -0.22]) for first-time taker PANCE pass rates. Although a negative correlation is observed between the number of levied citations and PANCE pass rates, the coefficient of determination does not indicate that the number of citations can predict PANCE pass rates (R2 = 0.0368). Regarding survey data, 42.86% of programs placed on probation cited institutional support as their biggest program weakness or threat. Conversely, 22.22% of programs with provisional status and 12.5% of programs with continued status reported institutional support as their biggest weakness or threat. CONCLUSION: This research identifies leadership as a deficit of concern associated with programs placed on probation. In addition, a significant negative correlation exists between the number of citations and first-time taker PANCE pass rates-especially for programs with first-time taker PANCE pass rates below 85% or for programs with continued accreditation status.

Substance Use Among Physician Assistant Students: A National Study on the Prevalence of Alcohol, Tobacco, Illicit Substances, and Medication Use.

INTRODUCTION: The purpose of this study was to discover the substance use prevalence among physician assistant students (PA-S) compared with the age-relevant general US population and to examine the frequency of stress, burnout, anxiety, and depression during the didactic and clinical phases, while accounting for the impact of the COVID-19 pandemic. METHODS: A 20-item survey instrument was created. Self-reported data included demographics, anxiety, burnout, tobacco, illicit substances, and prescription medication use. Outcome-based inventories included a modified Perceived Stress Scale, Patient Health Questionnaire-2 (PHQ-2), and Alcohol Use Disorder Identification Test-Concise. The survey was emailed to all US programs (∼270 programs; ∼25,000 students), with 54 programs approving dissemination to their students (n∼4,760). RESULTS: Of the 1432 responses (30% response rate, 96% completion rate), the final validated sample was 1378 students (56.1% didactic, 43.8% clinical). When compared with the national population, PA-S prevalence for tobacco (5.2%) and illicit substance use (9.9%) were notably lower; alcohol (53.5%) was comparable; and prescription medication (7.0%) is only reported for PA students due to the lack of a national comparison. A higher frequency of substance use was observed during the didactic (52.5%) vs clinical (47.5%) phases. Stress was the dominant factor in both phases (93.5% didactic, 86.1% clinical). Respondents reported that the COVID-19 pandemic had minimal impact on reported rates, other than alcohol. DISCUSSION: Although PA-S substance use prevalence is at or below the national population, PA programs are encouraged to review their policies and provide conversations and resources for students who may have one or more risk factors and experience a negative effect from current substance use.

Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities.

Microtubule (MT)-binding centromere protein F (CENP-F) was previously shown to play a role exclusively in chromosome segregation during cellular division. Many cell models of CENP-F depletion show a lag in the cell cycle and aneuploidy. Here, using our novel genetic deletion model, we show that CENP-F also regulates a broader range of cellular functions outside of cell division. We characterized CENP-F(+/+) and CENP-F(-/-) mouse embryonic fibroblasts (MEFs) and found drastic differences in multiple cellular functions during interphase, including cell migration, focal adhesion dynamics, and primary cilia formation. We discovered that CENP-F(-/-) MEFs have severely diminished MT dynamics, which underlies the phenotypes we describe. These data, combined with recent biochemical research demonstrating the strong binding of CENP-F to the MT network, support the conclusion that CENP-F is a powerful regulator of MT dynamics during interphase and affects heterogeneous cell functions.

Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition.

Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protein interaction between blood vessel epicardial substance (Bves) and N-myc downstream regulated gene 4 (NDRG4) is critical for regulation of epicardial cell directional movement, as disruption of this interaction randomizes migratory patterns. Our studies show that Bves/NDRG4 interaction is required for trafficking of internalized fibronectin through the "autocrine extracellular matrix (ECM) deposition" fibronectin recycling pathway. Of importance, we demonstrate that Bves/NDRG4-mediated fibronectin recycling is indeed essential for epicardial cell directional movement, thus linking these two cell processes. Finally, total internal reflectance fluorescence microscopy shows that Bves/NDRG4 interaction is required for fusion of recycling endosomes with the basal cell surface, providing a molecular mechanism of motility substrate delivery that regulates cell directional movement. This is the first evidence of a molecular function for Bves and NDRG4 proteins within broader subcellular trafficking paradigms. These data identify novel regulators of a critical vesicle-docking step required for autocrine ECM deposition and explain how Bves facilitates cell-microenvironment interactions in the regulation of epicardial cell-directed movement.

Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy.

CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs.

Concerted effort of centrosomal and Golgi-derived microtubules is required for proper Golgi complex assembly but not for maintenance.

Assembly of an integral Golgi complex is driven by microtubule (MT)-dependent transport. Conversely, the Golgi itself functions as an unconventional MT-organizing center (MTOC). This raises the question of whether Golgi assembly requires centrosomal MTs or can be self-organized, relying on its own MTOC activity. The computational model presented here predicts that each MT population is capable of gathering Golgi stacks but not of establishing Golgi complex integrity or polarity. In contrast, the concerted effort of two MT populations would assemble an integral, polarized Golgi complex. Indeed, while laser ablation of the centrosome did not alter already-formed Golgi complexes, acentrosomal cells fail to reassemble an integral complex upon nocodazole washout. Moreover, polarity of post-Golgi trafficking was compromised under these conditions, leading to strong deficiency in polarized cell migration. Our data indicate that centrosomal MTs complement Golgi self-organization for proper Golgi assembly and motile-cell polarization.

Murine CENP-F regulates centrosomal microtubule nucleation and interacts with Hook2 at the centrosome.

The microtubule (MT) network is essential in a broad spectrum of cellular functions. Many studies have linked CENP-F to MT-based activities as disruption of this protein leads to major changes in MT structure and function. Still, the basis of CENP-F regulation of the MT network remains elusive. Here, our studies reveal a novel and critical localization and role for CENP-F at the centrosome, the major MT organizing center (MTOC) of the cell. Using a yeast two-hybrid screen, we identify Hook2, a linker protein that is essential for regulation of the MT network at the centrosome, as a binding partner of CENP-F. With recently developed immunochemical reagents, we confirm this interaction and reveal the novel localization of CENP-F at the centrosome. Importantly, in this first report of CENP-F(-/-) cells, we demonstrate that ablation of CENP-F protein function eliminates MT repolymerization after standard nocodazole treatment. This inhibition of MT regrowth is centrosome specific because MT repolymerization is readily observed from the Golgi in CENP-F(-/-) cells. The centrosome-specific function of CENP-F in the regulation of MT growth is confirmed by expression of truncated CENP-F containing only the Hook2-binding domain. Furthermore, analysis of partially reconstituted MTOC asters in cells that escape complete repolymerization block shows that disruption of CENP-F function impacts MT nucleation and anchoring rather than promoting catastrophe. Our study reveals a major new localization and function of CENP-F at the centrosome that is likely to impact a broad array of MT-based actions in the cell.

Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells.

Microtubules are indispensable for Golgi complex assembly and maintenance, which are integral parts of cytoplasm organization during interphase in mammalian cells. Here, we show that two discrete microtubule subsets drive two distinct, yet simultaneous, stages of Golgi assembly. In addition to the radial centrosomal microtubule array, which positions the Golgi in the centre of the cell, we have identified a role for microtubules that form at the Golgi membranes in a manner dependent on the microtubule regulators CLASPs. These Golgi-derived microtubules draw Golgi ministacks together in tangential fashion and are crucial for establishing continuity and proper morphology of the Golgi complex. We propose that specialized functions of these two microtubule arrays arise from their specific geometries. Further, we demonstrate that directional post-Golgi trafficking and cell migration depend on Golgi-associated CLASPs, suggesting that correct organization of the Golgi complex by microtubules is essential for cell polarization and motility.

Microtubule network asymmetry in motile cells: role of Golgi-derived array.

Cell migration requires polarization of the cell into the leading edge and the trailing edge. Microtubules (MTs) are indispensable for polarized cell migration in the majority of cell types. To support cell polarity, MT network has to be functionally and structurally asymmetric. How is this asymmetry achieved? In interphase cells, MTs form a dynamic system radiating from a centrosome-based MT-organizing center (MTOC) to the cell edges. Symmetry of this radial array can be broken according to four general principles. Asymmetry occurs due to differential modulation of MT dynamics, relocation of existing MTs within a cell, adding an asymmetric nucleation site, and/or repositioning of a symmetric nucleation site to one side of a cell. Combinations of these asymmetry regulation principles result in a variety of asymmetric MT networks typical for diverse motile cell types. Importantly, an asymmetric MT array is formed at a non-conventional MT nucleation site, the Golgi. Here, we emphasize the contribution of this array to the asymmetry of MT network.

Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network.

Proper organization of microtubule arrays is essential for intracellular trafficking and cell motility. It is generally assumed that most if not all microtubules in vertebrate somatic cells are formed by the centrosome. Here we demonstrate that a large number of microtubules in untreated human cells originate from the Golgi apparatus in a centrosome-independent manner. Both centrosomal and Golgi-emanating microtubules need gamma-tubulin for nucleation. Additionally, formation of microtubules at the Golgi requires CLASPs, microtubule-binding proteins that selectively coat noncentrosomal microtubule seeds. We show that CLASPs are recruited to the trans-Golgi network (TGN) at the Golgi periphery by the TGN protein GCC185. In sharp contrast to radial centrosomal arrays, microtubules nucleated at the peripheral Golgi compartment are preferentially oriented toward the leading edge in motile cells. We propose that Golgi-emanating microtubules contribute to the asymmetric microtubule networks in polarized cells and support diverse processes including post-Golgi transport to the cell front.

Unsafe sex: do feelings matter?

The purpose of this study was to investigate the relationships among self-efficacy for condom use during distress (SE-Condom Distress), self-efficacy related to general HIV prevention skills (SE-HIV), and HIV risk behaviors, attitudes, and knowledge. Two hundred and twenty two adolescents with psychiatric disorders between 13 and 18 years-old participated. Participants completed measures related to HIV Self-Efficacy, HIV Attitudes, and Sexual Behaviors. Self-efficacy for condom use during distress (SE-Condom Distress) was significantly associated with more HIV protective behaviors. Controlling for observed covariates, SE-Condom Distress was the only variable significantly associated with consistent condom use in a multiple logistic regression (OR=2.43). Self-efficacy regarding condom use during affective arousal is closely associated with HIV-related attitudes and behaviors. Clinicians need to be alert to subtle signs of distress as adolescents contemplate safer sexual behavior.

Repeat rape and multiple offending among undetected rapists.

Pooling data from four samples in which 1,882 men were assessed for acts of interpersonal violence, we report on 120 men whose self-reported acts met legal definitions of rape or attempted rape, but who were never prosecuted by criminal justice authorities. A majority of these undetected rapists were repeat rapists, and a majority also committed other acts of interpersonal violence. The repeat rapists averaged 5.8 rapes each. The 120 rapists were responsible for 1,225 separate acts of interpersonal violence, including rape, battery, and child physical and sexual abuse. These findings mirror those from studies of incarcerated sex offenders (Abel, Becker, Mittelman, Cunningham-Rathner, Rouleau, & Murphy, 1987; Weinrott and Saylor, 1991), indicating high rates of both repeat rape and multiple types of offending. Implications for the investigation and prosecution of this so-called "hidden" rape are discussed.