Mental Health Disclosure Questions on Medical Licensure Applications: Implications for Medical Students, Residents, and Physicians.

Medical trainees and physicians experience high rates of depression, anxiety, suicidal ideation, and burnout. The stigma surrounding mental health may deter help-seeking behaviors and increase informal treatment to maintain anonymity. Invasive health history questions on state medical licensure applications regarding mental health diagnoses and treatment likely increase stigma, reduce help-seeking, and consequently may motivate some applicants to report an inaccurate history to the state medical board. Research on physician mental health, suicide rates, and lack of help-seeking have led to recommendations for changes to licensure questions. In this article, the authors review the language of health history questions, disclosure requirements for applicants, and the potential consequences of disclosing mental health or substance abuse history on state medical licensure applications. They review recent changes to some states' health history questions, using the changes to Florida's licensure application in 2021 as an example, and explore the implications of these changes for reducing stigma and encouraging help-seeking. The authors recommend that state medical boards review and refine licensure applications' health history questions regarding mental health disclosure in ways that strategically address concerns related to stigma, bias, and unwarranted scrutiny. They call for research to examine the impact of such question changes on applicant response accuracy, help-seeking behaviors, and mental health outcomes and stigma. They also recommend that medical schools offer and promote access to mental health services, encourage faculty to normalize help-seeking behaviors, and provide students with information about state licensure processes. Reducing stigma, normalizing trainee and physician experiences, and promoting help-seeking are preliminary steps to promote a culture in academic medicine that prioritizes mental health. In turn, this will encourage trainees and physicians to care for themselves and cultivate physicians who are better equipped to heal and support their patients.

Exceptional continental record of biotic recovery after the Cretaceous-Paleogene mass extinction.

We report a time-calibrated stratigraphic section in Colorado that contains unusually complete fossils of mammals, reptiles, and plants and elucidates the drivers and tempo of biotic recovery during the poorly known first million years after the Cretaceous-Paleogene mass extinction (KPgE). Within ~100 thousand years (ka) post-KPgE, mammalian taxonomic richness doubled, and maximum mammalian body mass increased to near pre-KPgE levels. A threefold increase in maximum mammalian body mass and dietary niche specialization occurred at ~300 ka post-KPgE, concomitant with increased megafloral standing species richness. The appearance of additional large mammals occurred by ~700 ka post-KPgE, coincident with the first appearance of Leguminosae (the bean family). These concurrent plant and mammal originations and body-mass shifts coincide with warming intervals, suggesting that climate influenced post-KPgE biotic recovery.

Author Correction: Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by "normalizing" abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.

Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease. Numerous studies have associated HS with obesity, and recently with metabolic syndrome (MetS). Both obesity and MetS are linked with metabolic changes. Thyroid hormones play a central role in metabolism and exert pleiotropic effects on adipogenesis and the basal metabolism of lipids and glucose. We hypothesized that patients with HS have an altered or dysfunctional metabolism expressed as thyroid function. AIM: To investigate thyroid function in individuals with HS compared with healthy controls (HCs). METHODS: We conducted a retrospective comparative cross-sectional study using blood samples and questionnaire-based self-reported information to assess thyroid function. RESULTS: Our study comprised 430 patients in a population-based HS group, and 20 780 HCs. The age/sex-adjusted analysis showed a significantly lower level (P < 0.001) of thyroid-stimulating hormone (TSH) and a significantly higher level (P < 0.0001) of total triiodothyronine (tT3) for the HS compared with the HC group. The age/sex-adjusted analysis also showed a significant association between clinical hyperthyroidism and HS (an OR = 1.91, 95% CI 1.19-3.07; P = 0.02). When this analysis was adjusted further for the potential confounders of body mass index, smoking and oral contraception, the results remained significant. CONCLUSION: This study suggests that HS is associated with hyperthyroidism. Hyperthyroidism may indicate an altered or dysfunctional metabolism.

Hidradenitis suppurativa and electrocardiographic changes: a cross-sectional population study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease. OBJECTIVES: To investigate the hitherto unknown electrocardiographic (ECG) changes associated with HS, which have recently been associated with significant cardiovascular burden. METHODS: Data were obtained from the cross-sectional Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire; 404 individuals met the HS diagnosis criteria and 19 001 controls without HS were identified. Severity of HS was staged according to a modified Hurley score. The ECG parameters of heart rate (HR), PR interval, QRS duration, JTc interval and QTc interval were obtained from 12-lead resting ECGs. We investigated the difference in means by unpaired t-test or anova. RESULTS: HR was significantly higher [mean difference 2·3 beats per min (bpm), 95% confidence interval (CI) 1·2-3·4; P < 0·01] when adjusting for age and sex, but when adjusting for multivariates, there was no significant difference (0·3 bpm, 95% CI -0·7 to 1·4; P = 0·52). Severe HS was significantly associated with increased HR across all models (2·9 bpm, 95% CI 0·7-5·1; P = 0·01). Mean QRS duration was significantly shorter in the group with mild HS but not in the groups with moderate and severe HS. CONCLUSIONS: Mean resting HR in patients with severe HS was significantly higher compared with controls. Given that resting HR is associated with increased risk of all-cause and cardiovascular mortality, and that patients with HS have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.

Moderate to severe hidradenitis suppurativa patients do not have an altered bacterial composition in peripheral blood compared to healthy controls.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous skin. Patients with HS often report an array of systemic symptoms such as fatigue and malaise. The aetiology of these symptoms remains unclear. Previously, various bacteria have been associated with mature HS lesions, and bacteraemia has been reported in patients with HS using traditional culturing methods. Thus, we hypothesized that a low-grade bacteraemia contributes to the symptomatology in patients with HS. OBJECTIVE: To explore the potential presence of bacteraemia in patients with HS and healthy controls. METHOD: A case-control study. Compositions of bacteria in the blood of 27 moderate to severe HS patients and 26 healthy controls were investigated using next-generation 16S ribosomal RNA gene sequencing (NGS) and routine anaerobic and aerobic blood culturing. None of the participants received any antibiotics (systemic or topical therapy) within 1 month prior to the study. HS patients with a recent flare were randomly selected by consecutive recruitment of eligible patients from the Department of Dermatology, Zealand University Hospital, Denmark. Healthy controls were recruited from the University of Copenhagen as well as from the healthcare staff. RESULTS: The different bacterial compositions were investigated using NGS and traditional anaerobic and aerobic blood culturing. Our NGS analysis provided a previously unreported characterization of the bacterial composition in peripheral blood from patients with HS and healthy controls. Overall, our data demonstrated that patients with HS do not have a different bacterial composition in their peripheral blood than healthy controls. CONCLUSION: The study suggests that the self-reported symptoms in HS such as malaise and fatigue may not be linked to bacteraemia.

Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK).

Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in horses causing intermittent ocular pain, eventually resulting in visual impairment. Affected horses typically respond to immunomodulatory treatment. However, the underlying cause of the disease remains enigmatic. The current study was undertaken to investigate the presence of autoantibodies in horses with immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls screening for serum autoantibodies against the corneal proteome using indirect immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis (2DE) with subsequent western blot analysis was performed followed by mass spectrometric identification of bands or spots of interest. Indirect immunofluorescence did not reveal a difference in immune response towards corneal proteins between healthy horses and those with IMMK. Using western blot analysis some horses affected by IMMK (4/28) showed a single band (1D) or a single spot (2DE) (5/28) not detected in healthy controls. The corresponding spot was identified as maspin (SERPINB5), a protein responsible for the inhibition of corneal vascularisation, cell migration and cell adhesion to the extracellular matrix. Tests with a recombinant human protein commercially available did not verify blot findings, but the human protein may not be fully cross-reactive. Still, maspin might play a role in some cases of equine IMMK. Further research is needed to clarify the etiology of this disease.

Adjunctive yoga v. health education for persistent major depression: a randomized controlled trial.

BACKGROUND: The objective of this study was to determine whether hatha yoga is an efficacious adjunctive intervention for individuals with continued depressive symptoms despite antidepressant treatment. METHOD: We conducted a randomized controlled trial of weekly yoga classes (n = 63) v. health education classes (Healthy Living Workshop; HLW; n = 59) in individuals with elevated depression symptoms and antidepressant medication use. HLW served as an attention-control group. The intervention period was 10 weeks, with follow-up assessments 3 and 6 months afterwards. The primary outcome was depression symptom severity assessed by blind rater at 10 weeks. Secondary outcomes included depression symptoms over the entire intervention and follow-up periods, social and role functioning, general health perceptions, pain, and physical functioning. RESULTS: At 10 weeks, we did not find a statistically significant difference between groups in depression symptoms (b = -0.82, s.e. = 0.88, p = 0.36). However, over the entire intervention and follow-up period, when controlling for baseline, yoga participants showed lower levels of depression than HLW participants (b = -1.38, s.e. = 0.57, p = 0.02). At 6-month follow-up, 51% of yoga participants demonstrated a response (⩾50% reduction in depression symptoms) compared with 31% of HLW participants (odds ratio = 2.31; p = 0.04). Yoga participants showed significantly better social and role functioning and general health perceptions over time. CONCLUSIONS: Although we did not see a difference in depression symptoms at the end of the intervention period, yoga participants showed fewer depression symptoms over the entire follow-up period. Benefits of yoga may accumulate over time.

Prodromal symptoms in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, which presents as recurrent nodules and sinus tracts (tunnels) with subsequent scarring, predominantly involving the intertriginous regions. Although prodromal symptoms (i.e. various symptoms preceding the eruption of the HS lesions) are often mentioned, there have been no formal investigations into this aspect. Insight into prodromal symptoms may enable patients with HS or dermatologists in choosing a more targeted treatment at a much earlier stage, potentially increasing treatment efficacy and quality of life. AIM: To characterize the spectrum of prodromes in patients with HS. METHODS: An extensive questionnaire that explored the frequency, type and time of occurrence of the prodromal symptom(s) and the degree of certainty of the perceived association was administered to 72 patients. RESULTS: The majority of the 72 patients (83.3%; n = 60) confirmed that they experienced one or more symptom(s) prior to the development of inflamed nodules or abscesses. These included: fatigue (32%), malaise (defined as a fever-like sensation) (23%), headache (11%) and nausea (2%). Localized symptoms included skin erythema (75%), paraesthesia (63%) and itching (20%). the majority of the patients stated that the prodromes usually occurred > 24 h (45%) or 12-24 h (20%) before the eruption. CONCLUSION: Our data suggest that the majority of patients with HS experience prodromal symptoms, heralding a flare of their HS. The findings may give rise to important new treatment approaches for the management of HS.

S100A4 (metastasin) positive mesenchymal canine mammary tumour spheroids reduce Tenascin C synthesis under DMSO exposure in vitro.

In breast cancer research S100A4-positive tumour-associated stromal cells are assumed as primary source of Tenascin C (TNC) in the metastatic environment. Aim of the present study was to isolate and characterize S100A4/TNC positive stromal canine mammary tumour (CMT) cells. Cells grown as scaffold-free spheroids were investigated for S100A4, TNC, and proliferative activity under 1.8% DMSO stimulation by means of Western blot and immunohistochemistry. DMSO is a commonly used drug solvent despite well-known side effects on cells including TNC expression. DMSO did not affect proliferation, but TNC was significantly reduced under DMSO exposure for 7 and 14 days, whereby for S100A4 a reducing effect was only observed after 14 days. Without DMSO, cells stably expressed TNC and S100A4 which makes them suitable to be used in experimental approaches requiring S100A4/TNC expressing CMT stromal cells. Results show that 1.8% DMSO should not be used as solvent for experiments concerning TNC/S100A4 expression.

Detection and first characterization of an uncommon haptoglobin in porcine saliva of pigs with rectal prolapse by using boronic acid sample enrichment.

Salivary glycoprotein profiles, obtained after boronic acid enrichment, were studied for the first time in pigs in order to search for specific overall alterations related to acute inflammatory condition. Five healthy pigs and five pigs suffering from rectal prolapse were used, and the levels of acute phase proteins were measured to determine the degree of inflammation of the animals. The enriched glycoprotein profiles, achieved by two-dimensional gel electrophoresis (2DE) were statistically evaluated and spots that appeared differentially regulated between states were subjected to MS analysis for protein identification. Spots from three unique proteins were identified: carbonic anhydrase VI (CA VI), α-1-antichymotrypsin and haptoglobin (Hp). CA VI appeared as two adjacent horizontal spot trains in the glycoprotein profile of healthy animals in its regular isoelectric points (pI). One spot of α-1-antichymotrypsin was found in saliva from pigs with rectal prolapse in an unusual basic pI, and was considered as a breakdown product. Hp was identified as several spot trains in saliva from pigs with rectal prolapse in an unusual alkaline pI and was consequently further investigated. SDS-PAGE and 2DE of paired serum and saliva samples combined with Western blot analysis showed that the unusual Hp position observed in saliva samples was absent in serum. Furthermore, N-glycans from serum and saliva Hp glycopatterns were evaluated from SDS-PAGE Hp bands and showed that the serum N-glycan distribution in Hp ß-chain was comparable in quantity and quality in both groups of animals. In saliva, no Hp ß-chain derived N-glycans could unambiguously be identified from this sample set, thus needing further detailed investigations in the future.

Meta-analyses of the relationship between conformity to masculine norms and mental health-related outcomes.

Despite theoretical postulations that individuals' conformity to masculine norms is differentially related to mental health-related outcomes depending on a variety of contexts, there has not been any systematic synthesis of the empirical research on this topic. Therefore, the authors of this study conducted meta-analyses of the relationships between conformity to masculine norms (as measured by the Conformity to Masculine Norms Inventory-94 and other versions of this scale) and mental health-related outcomes using 78 samples and 19,453 participants. Conformity to masculine norms was modestly and unfavorably associated with mental health as well as moderately and unfavorably related to psychological help seeking. The authors also identified several moderation effects. Conformity to masculine norms was more strongly correlated with negative social functioning than with psychological indicators of negative mental health. Conformity to the specific masculine norms of self-reliance, power over women, and playboy were unfavorably, robustly, and consistently related to mental health-related outcomes, whereas conformity to the masculine norm of primacy of work was not significantly related to any mental health-related outcome. These findings highlight the need for researchers to disaggregate the generic construct of conformity to masculine norms and to focus instead on specific dimensions of masculine norms and their differential associations with other outcomes. (PsycINFO Database Record

Bacterial biofilm in chronic lesions of hidradenitis suppurativa.

BACKGROUND: Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm-driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. OBJECTIVES: To determine and quantify the potential presence of bacterial aggregates in chronic HS lesions. METHODS: In 42 consecutive patients with HS suffering from chronic lesions, biopsies were obtained from lesional as well as from perilesional skin. Samples were investigated using peptide nucleic acid-fluorescence in situ hybridization in combination with confocal laser scanning microscopy. In addition, corresponding histopathological analysis on haematoxylin and eosin slides was performed. RESULTS: Biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The mean diameter of aggregates in lesional skin was significantly greater than in perilesional skin (P = 0·01). Large biofilms (aggregates > 50 µm in diameter) were found in 42% of lesional samples and in only 5% of the perilesional samples (P = 0·009). The majority of the large biofilms were situated in sinus tracts (63%) or in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. CONCLUSIONS: This study suggests that biofilm formation is associated with inflammation of chronic HS lesions. The aggregates most likely occur as a secondary event, possibly due to predisposing local anatomical changes such as sinus tracts (tunnels), keratinous detritus and dilated hair follicles.

Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in "Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)" Miller et al. (2016) [2].

Dataset of liver proteins changed in eu- and hypothyroid female rats upon in vivo exposure to hexabromocyclododecane (HBCD).

Female Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days. Changes in protein patterns obtained by 2D-DIGE were evaluated, and different animal groups compared taking into account their exposure and thyroid status. Proteins significantly altered in abundance in any of these comparisons were identified by mass spectrometry. These data, together with hormone data of the animals, are discussed in "Hexa-bromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1].

Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats.

Hexabromocyclododecane (HBCD) is a brominated flame retardant known for its low acute toxicity as observed in animal experiments. However, HBCD exposure can affect liver functioning and thyroid hormone (TH) status. As exact mechanisms are unknown and only limited toxicological data exists, a gel-based proteomic approach was undertaken. In a eu- and hypothyroid female rat model, rats were exposed to 3 and 30 mg/kg bw/day HBCD for 7 days via their diet, and exposure was related to a range of canonical endpoints (hormone status, body weight) available for these animals. Alterations in the liver proteome under HBCD exposure were determined in comparison with patterns of control animals, for both thyroid states. This revealed significantly changed abundance of proteins involved in metabolic processes (gluconeogenesis/glycolysis, amino acid metabolism, lipid metabolism), but also in oxidative stress responses, in both euthyroid and hypothyroid rats. The results provide a more detailed picture on the mechanisms involved in these alterations, e.g. at the protein level changes of the proposed influence of HBCD on the lipid metabolism. Present results show that proteomic approaches can provide further mechanistic insights in toxicological studies.

Gender specific differences in the liver proteome of rats exposed to short term and low-concentration hexabromocyclododecane (HBCD).

The influence of short term (7-day) exposure of male rats to the brominated flame retardant hexabromocyclododecane (HBCD) was studied by investigation of the liver proteome, both in euthyroid and hypothyroid rats and by comparing results with general data on animal physiology and thyroid hormone, leptin, insulin and gonadotropin concentrations determined in parallel. Proteome analysis of liver tissue by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) revealed that only small protein pattern changes were induced by exposure in males, on just a few proteins with different functions and not involved in pathways in common. This is in contrast to previous findings in similarly exposed eu- and hypothyroid female rats, where general metabolic pathways had been shown to be affected. The largest gender-dependent effects concerned basal concentrations of liver proteins already in control and hypothyroid animals, involving mainly the pathways which were also differently affected by HBCD exposure. Among them were differences in lipid metabolism, which - upon exposure to HBCD - may also be the reason for the considerably higher ratio of γ-HBCD accumulated in white adipose tissue of exposed female rats compared to males. The results further elucidate the already suggested different sensitivity of genders towards HBCD exposure on the protein level, and confirm the need for undertaking toxicological animal experiments in both genders.