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For decades, the three-digit United States Medical Licensing Exam Step 1 score has been used to competitively evaluate and compare candidates during the residency application process. Starting in 2022, however, all Step 1 scores will be converted to pass/fail. A different quantitative measure will likely gain importance in its stead, one such being clerkship performance grades. This study aims to determine the consistency of class rank and distribution of clerkship grades reported by medical schools for applicants to a general surgery program.Candidates' Medical Student Performance Evaluation letters from 141 unique US allopathic medical schools were reviewed for student overall class rank, the number of grading tiers in each clerkship, and the percent achieving honors criteria in each clerkship from the 2020 application cycle. Comparative analysis was performed by region and medical school prestige.Most medical schools rank students using a four-tier system (e.g., fail, pass, high pass, and honors). A third of schools do not provide an overall class rank of students (34.7% of schools); this was most prevalent in the Northeast and Western regions. Schools in the Central US more often rank their students in five tiers compared to the South (P 0.01). The percent of students that achieve the highest grading tier varies across the core clerkships (mean 37.1%, range 6.5%-78%); an average of 34.5% of students meet the highest honors tier in their Surgery clerkship. Students at US News and World Report Top 20 medical schools are more likely to receive the highest honors tier, across all core clerkships and overall class rank, than students at schools outside the Top 20 (P 0.05).In the absence of the United States Medical Licensing Exam Step 1 score, the variability in clerkship grading tiers and overall class rank will likely pose a challenge to residency programs' ability to stratify desirable applicants. Further transparency and standardization may be required to compare students objectively and fairly from medical schools across the country. more...

Building on growing research examining lay health professionals delivering postpartum depression preventive interventions, we conducted a hybrid effectiveness-implementation Type 2 trial to examine implementation metrics and determine whether pregnant women receiving Mothers and Babies 1-on-1 delivered by lay home visitors exhibit greater reductions in depressive symptoms and perceived stress than women receiving usual home visiting.1229 (672 control, 557 intervention) pregnant women were enrolled, with intervention participants receiving Mothers and Babies 1-on-1 delivered by a lay home visitor and control participants receiving usual home visiting services. Baseline and six-month follow-up assessments measured client mental health outcomes, with management information system data collected to assess intervention dosage. Surveys were administered nine months post-training to agency managers as well as home visitors who delivered any intervention content.Intent-to-treat analyses indicated a significant reduction in perceived stress among intervention participants compared to controls, while as-treated analyses showed significant reductions in perceived stress and depressive symptoms. Although all study sites adopted the intervention,50 % of eligible women received the intervention. Over two-thirds of home visitors made at least one fidelity-consistent adaptation, with client recruitment and retention in home visiting highlighted as challenges to delivery.Unmeasured historical events may have affected study outcomes and caution should be used generalizing to perinatal women from different racial/ethnic groups and home visiting models.Mothers and Babies 1-on-1 delivered by lay home visitors leads to reductions in perceived stress and depressive symptoms, suggesting task shifting to non-mental health professionals is viable when appropriate training and supervision is provided. more...

Background Deployment-related experiences might be risk factors for soldier suicides, in which case identification of vulnerable soldiers before deployment could inform preventive efforts. We investigated this possibility by using pre-deployment survey and administrative data in a sample of US Army soldiers to develop a risk model for suicide attempt (SA) during and shortly after deployment. Methods Data came from the Army Study to Assess Risk and Resilience in Servicemembers Pre-Post Deployment Survey (PPDS). Soldiers completed a baseline survey shortly before deploying to Afghanistan in 2011–2012. Survey measures were used to predict SAs, defined using administrative and subsequent survey data, through 30 months after deployment. Models were built using penalized regression and ensemble machine learning methods. Results Significant pre-deployment risk factors were history of traumatic brain injury, 9 + mental health treatment visits in the 12 months before deployment, young age, female, previously married, and low relationship quality. Cross-validated AUC of the best penalized and ensemble models were .75–.77. 21.3–40.4% of SAs occurred among the 5–10% of soldiers with highest predicted risk and positive predictive value (PPV) among these high-risk soldiers was 4.4–5.7%. Conclusions SA can be predicted significantly from pre-deployment data, but intervention planning needs to take PPV into consideration. more...

Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized. ARG1 is also expressed by keratinocytes; however, ARG1 function in these critical wound repair cells is not understood. We characterized ARG1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal ARG1 expression was decreased in both human and murine delayed healing wounds. We therefore generated a keratinocyte-specific ARG1-null mouse model (K14-cre;Arg1fl/fl) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration, and differentiation, was significantly delayed in K14-cre;Arg1fl/fl mice. Similarly, using the arginase inhibitor N(omega)-hydroxy-nor-L-arginine, human in vitro and ex vivo models further confirmed this finding, revealing the importance of the downstream polyamine pathway in repair. Indeed, restoring the balance in ARG1 activity through the addition of putrescine proved beneficial in wound closure. In summary, we show that epidermal ARG1 plays, to our knowledge, a previously unreported intrinsic role in cutaneous healing, highlighting epidermal ARG1 and the downstream mediators as potential targets for the therapeutic modulation of wound repair. more...

Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use. more...

Chronic nonhealing wounds in the elderly population are associated with a prolonged and excessive inflammatory response, which is widely hypothesized to impede healing. Previous studies have linked alterations in local L-arginine metabolism, principally mediated by the enzymes arginase (Arg) and inducible nitric oxide synthase (iNOS), to pathological wound healing. Over subsequent years, interest in Arg/iNOS has focused on the classical versus alternatively activated (M1/M2) macrophage paradigm. Although the role of iNOS during healing has been studied, Arg contribution to healing remains unclear. Here, we report that Arg is dynamically regulated during acute wound healing. Pharmacological inhibition of local Arg activity directly perturbed healing, as did Tie2-cre-mediated deletion of Arg1, revealing the importance of Arg1 during healing. Inhibition or depletion of Arg did not alter alternatively activated macrophage numbers but instead was associated with increased inflammation, including increased influx of iNOS(+) cells and defects in matrix deposition. Finally, we reveal that in preclinical murine models reduced Arg expression directly correlates with delayed healing, and as such may represent an important future therapeutic target. more...

Estrogen deprivation is associated with delayed healing, while Hormone Replacement Therapy (HRT) accelerates acute wound healing and protects against development of chronic wounds. Estrogen exerts its effects on healing via numerous cell types by signalling through the receptors ERα and ERβ, which bind to the Estrogen Responsive Element (ERE) and initiate gene transcription. The ERE–luciferase transgenic mouse model has been influential in assessing real-time in vivo estrogen receptor activation across a range of tissues and pathologies. Using this model we demonstrate novel temporally regulated peri-wound activation of estrogen signalling in female mice. Using histological methods we reveal that this signal is specifically localised to keratinocytes of the neoepidermis and wound margin dermal cells. Moreover using pharmacological agonists we reveal that ERβ induces ERE-mediated signal in both epidermal and dermal cells while ERα induces ERE-mediated signal in dermal cells alone. Collectively these novel data demonstrate rapid and regional activation of estrogen signalling in wounded skin. A more complete understanding of local hormonal signalling during repair is essential for the focussed development of new therapies for wound healing. more...

Ineffective emotion regulation and abnormal amygdala activation have each been found in adolescent-onset major depressive disorder. However, amygdala activation during emotion regulation has not been studied in adolescent-onset major depressive disorder.Fourteen unmedicated adolescents diagnosed with current depression without comorbid psychiatric disorders and fourteen well-matched controls ages 13 to 17 years underwent an emotional regulation task during functional magnetic resonance imaging. During this task, participants viewed negatively-valence images and were asked to notice how they were feeling without trying to change it and maintain their emotional reaction ("Maintain") or to interpret the image in such a way as minimize their emotional response ("Reduce").Imaging analyses demonstrated that adolescents with depression showed: (1) greater right amygdala activation during the maintain condition relative to controls, (2) less connectivity during the maintain condition between the amygdala and both the insula and medial prefrontal cortex than controls, and (3) a significant positive correlation between amygdala-seeded connectivities during maintenance of emotion and psychosocial functioning.The current study is a cross-sectional comparison and longitudinal investigations with larger sample sizes are needed to examine the association between amygdala reactivity and emotion regulation over time in adolescent MDD.During the maintain condition, adolescents with depression showed a heightened amygdala response and less reciprocal activation in brain regions that may modulate the amygdala. A poorly modulated, overreactive amygdala may contribute to poor emotion regulation. more...

Previous neuroimaging studies suggest that prefrontal cortex (PFC) modulation of the amygdala and related limbic structures is an underlying neural substrate of effortful emotion regulation. Anxiety-prone individuals experience excessive negative emotions, signaling potential dysfunction of systems supporting down-regulation of negative emotions. We examined the hypothesis that anxious individuals require increased recruitment of lateral and medial PFC to decrease negative emotions. An emotion regulation task that involved viewing moderately negative images was presented during functional magnetic resonance imaging (fMRI). Participants with elevated trait anxiety scores (n = 13) and normal trait anxiety scores (n = 13) were trained to reduce negative emotions using cognitive reappraisal. Blood oxygenation level-dependent (BOLD) changes were contrasted for periods when participants were reducing emotions versus when they were maintaining emotions. Compared to healthy controls, anxious participants showed greater activation of brain regions implicated in effortful (lateral PFC) and automatic (subgenual anterior cingulate cortex) control of emotions during down-regulation of negative emotions. Left ventrolateral PFC activity was associated with greater self-reported reduction of distress in anxious participants, but not in healthy controls. These findings provide evidence of altered functioning of neural substrates of emotion regulation in anxiety-prone individuals. Anxious participants required greater engagement of lateral and medial PFC in order to successfully reduce negative emotions. more...

Genistein has been implicated in the beneficial effects of soy on human health, particularly in the context of ageing. In post-menopausal women reduced systemic estrogen leads to a range of age-associated pathologies, including delayed cutaneous wound healing. We have previously shown that this can be reversed by estrogen replacement. However, the effect of genistein on the skin is poorly understood and crucially the influence of genistein on wound healing has not been assessed. 10-week-old ovariectomised mice were systemically treated with 17beta-estradiol or genistein. Genistein substantially accelerated wound repair, associated with a dampened inflammatory response. Unexpectedly, co-treatment with the ER antagonist ICI had little impact on the anti-inflammatory, healing promoting effects of genistein. Thus genistein's actions are only partially mediated via classical estrogen receptor-dependent signalling pathways. Indeed, we report that alternative (cell-type specific) signalling mechanisms are activated in the skin in response to genistein treatment. more...

The Overall Anxiety Severity and Impairment Scale (OASIS) is a 5-item self-report measure that can be used to assess severity and impairment associated with any anxiety disorder or multiple anxiety disorders. A prior investigation with a nonclinical sample supported the reliability and validity of the OASIS; however, to date it has not been validated for use in clinical samples.The present study assessed the psychometric properties of the OASIS in a large sample (N=1036) of primary care patients whose physicians referred them to an anxiety disorders treatment study. Latent structure, internal consistency, convergent/discriminant validity, and cut-score analyses were conducted.Exploratory and confirmatory factor analyses supported a unidimensional structure. The five OASIS items displayed strong loadings on the single factor and had a high degree of internal consistency. OASIS scores demonstrated robust correlations with global and disorder-specific measures of anxiety, and weak correlations with measures of unrelated constructs. A cut-score of 8 correctly classified 87% of this sample as having an anxiety diagnosis or not.Convergent validity measures consisted solely of other self-report measures of anxiety. Future studies should evaluate the convergence of OASIS scores with clinician-rated and behavioral measures of anxiety severity.Overall, this investigation suggests that the OASIS is a valid instrument for measurement of anxiety severity and impairment in clinical samples. Its brevity and applicability to a wide range of anxiety disorders enhance its utility as a screening and assessment tool. more...

The present investigation compared the subjective and physiological effects of emotional suppression and acceptance in a sample of individuals with anxiety and mood disorders. Sixty participants diagnosed with anxiety and mood disorders were randomly assigned to one of two groups. One group listened to a rationale for suppressing emotions, and the other group listened to a rationale for accepting emotions. Participants then watched an emotion-provoking film and applied the instructions. Subjective distress, heart rate, skin conductance level, and respiratory sinus arrhythmia were measured before, during, and after the film. Although both groups reported similar levels of subjective distress during the film, the acceptance group displayed less negative affect during the post-film recovery period. Furthermore, the suppression group showed increased heart rate and the acceptance group decreased heart rate in response to the film. There were no differences between the two groups in skin conductance or respiratory sinus arrhythmia. These findings are discussed in the context of the existing body of research on emotion regulation and current treatment approaches for anxiety and mood disorders. more...

The present study investigated the relation of compulsive hoarding to other obsessive-compulsive disorder (OCD) symptoms in a sample of 162 patients with OCD. Obsessions and compulsions reported on the Anxiety Disorders Interview Schedule for DSM-IV were submitted to an exploratory factor analysis. Results suggested a four-factor model: "Certainty," "Contamination," "Obsessions," and "Numbers/Ordering." Hoarding did not load on any factor. The sample was divided into three groups: pure hoarding, nonhoarding OCD, and mixed OCD and hoarding. The hoarding group endorsed significantly less anxiety, worry, stress, and negative affect on self-report measures than the mixed and nonhoarding groups. Although hoarding sometimes functions as a compulsion among individuals with OCD, hoarding in the absence of other OCD symptoms may be a clinically distinct syndrome. more...

During protoplast formation by enzymatic digestion of first leaves of oats, A. sativa L. cv. Park and Orbit, the amount of ethylene synthesized was influenced by the type and quantity of enzymes used to digest the tissue, the osmoticum used in the incubation solution, and the age of the tissue at the time of digestion. The amount of ethylene synthesized was not directly related to the number of protoplasts released during tissue digestion. Ethylene synthesis during protoplast formation could be partially blocked by pretreatment of the oat seedlings with 2,5-norbornadiene, an olefinic antiethylene agent. more...