Outcomes of the Main Residency Match for Applicants With Disability.

This cohort study assesses match rates of US applicants with and without disability into specialty residence programs.

Anticancer Potential and Safety Profile of ß-Lapachone In Vitro.

Ipê is a plant of the Bignoniaceae family. Among the compounds extracted from this tree, lapachol is notable because its structural modification allows the production of ß-lapachone, which has anticancer properties. The objective of this work was to test this hypothesis at a cellular level in vitro and assess its potential safety for use. The following tests were performed: MTT cell viability assay, apoptotic index determination, comet assay, and micronucleus test. The results showed that ß-lapachone had a high cytotoxic capacity for all cell lines tested: ACP02 (gastric adenocarcinoma cells), MCF7 (breast carcinoma cells), HCT116 (colon cancer cells) and HEPG2 (hepatocellular carcinoma cells). Regarding genotoxicity, the exposure of cells to sublethal doses of ß-lapachone induced DNA damage (assessed by the comet assay) and nuclear abnormalities, such as nucleoplasmic bridges and nuclear buds (assessed by the micronucleus test). All tested cell lines responded similarly to ß-lapachone, except for ACP02 cells, which were relatively resistant to the cytotoxic effects of the compound in the MTT test. Our results collectively indicate that although ß-lapachone showed antiproliferative activity against cancer cell lines, it also caused harmful effects in these cells, suggesting that the use of ß-lapachone in treating cancer should be carried out with caution.

Medical Student Burnout by Race, Ethnicity, and Multiple Disability Status.

This cohort study examines the prevalence of burnout among students underrepresented in medicine by race and ethnicity with multiple disability types.

Variation by Institution in Sexual Harassment Experiences Among US Medical Interns.

This cross-sectional study investigates possible institutional and specialty variations in experiences of sexual harassment among US medical interns.

Innate extracellular Hsp70 inflammatory properties are mediated by the interaction of Siglec-E and LOX-1 receptors.

Innate immune responses to cell damage-associated molecular patterns induce a controlled degree of inflammation, ideally avoiding the promotion of intense unwanted inflammatory adverse events. When released by damaged cells, Hsp70 can stimulate different responses that range from immune activation to immune suppression. The effects of Hsp70 are mediated through innate receptors expressed primarily by myeloid cells, such as dendritic cells (DCs). The regulatory innate receptors that bind to extracellular mouse Hsp70 (mHsp70) are not fully characterized, and neither are their potential interactions with activating innate receptors. Here, we describe that extracellular mHsp70 interacts with a receptor complex formed by inhibitory Siglec-E and activating LOX-1 on DCs. We also find that this interaction takes place within lipid microdomains, and Siglec-E acts as a negative regulator of LOX-1-mediated innate activation upon mHsp70 or oxidized LDL binding. Thus, HSP70 can both bind to and modulate the interaction of inhibitory and activating innate receptors on the cell surface. These findings add another dimension of regulatory mechanism to how self-molecules contribute to dampening of exacerbated inflammatory responses.

The synthetic dye malachite green found in food induces cytotoxicity and genotoxicity in four different mammalian cell lines from distinct tissuesw.

Malachite green (MG) is a synthetic dye that uses ranges from its application as a tissue dye to that as an antiparasitic in aquaculture. Several studies have reported the presence of this compound in food dyes and in the meat of fish raised in captivity for human consumption, suggesting risks both for the end user and for as those who handle these products because of MG toxic properties described in the literature. Here we evaluated the cytotoxic and genotoxic profiles of MG in four different cell lines (ACP02, L929, MNP01, and MRC-5). Two of these cell lines are stomach cells (normal and cancer lineages) and the potential ingestion of MG makes this a relevant cell type. Cells were treated with MG at concentrations ranging from 0.1 µM to 100 µM, and tested by MTT assay, a differential apoptosis/necrosis assay (EB/OA), the micronucleus test (MN), and the comet assay. MG exhibits dose-dependent cytotoxicity toward all of the tested cell types; higher concentrations of MG cause cell necrosis, while lower concentrations induce apoptosis. MG has a genotoxic profile increasing the rates of micronuclei, nucleoplasmic bridges, nuclear buds, and DNA fragmentation; L929 and MRC-5 showed more sensibility than ACP02 and MNP01.

Posttraumatic Stress Disorder Symptoms Among First-Year Resident Physicians Working Before and During the COVID-19 Pandemic.

This cohort study investigates differences in posttraumatic stress disorder (PTSD) symptoms among first-year resident physicians training before and during the first wave of the COVID-19 pandemic (March to June 2020).

Inhibitory innate receptors and their potential role in transplantation.

The regulatory arm of the immune system plays a crucial role in maintaining immune tolerance and preventing excessive immune responses. Immune regulation comprises various regulatory cells and molecules that work together to suppress or regulate immune responses. The programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) are examples of inhibitory receptors that counteract activating signals and fine-tune immune responses. While most of the discoveries of immune regulation have been related to T cells and the adaptive immune system, the innate arm of the immune system also has a range of inhibitory receptors that can counteract activating signals and suppress the effector immune responses. Targeting these innate inhibitory receptors may provide a complementary therapeutic approach in several immune-related conditions, including transplantation. In this review, we will explore the potential role of innate inhibitory receptors in controlling alloimmunity during solid organ transplantation.

Prevalence of Disability and Use of Accommodation Among US Allopathic Medical School Students Before and During the COVID-19 Pandemic.

This survey study assesses self-disclosures of disability, disability types, and accommodation needs reported by US allopathic medical schools in 2021 vs 2015 and 2019.

Barriers to Disclosure of Disability and Request for Accommodations Among First-Year Resident Physicians in the US.

Importance: Ensuring access to accommodations is critical for resident physicians and their patients. Studies show that a large proportion of medical trainees with disabilities do not request needed accommodations; however, drivers of nonrequests are unknown. Objective: To assess the frequency of accommodation requests among first-year resident physicians (ie, interns) with disabilities and to identify possible drivers of nonrequest for needed accommodations. Design, Setting, and Participants: As part of the Intern Health Study, a longitudinal cohort study of first-year resident physicians, residents at 86 surgical and nonsurgical residency programs in 64 US institutions provided demographic and training characteristics 2 months prior to matriculation (April-May 2021). At the end of their intern year (June 2022), participants completed a new survey with questions about disability-related information, including disability status, disability type, whether they received accommodations, and if not, reasons for nonaccommodation. Poststratification and attrition weights were used to estimate the frequency of accommodation requests and reasons for not requesting accommodations. Interns reporting at least 1 disability were included in the analysis. Main Outcomes and Measures: Prevalence of reported disabilities, residency specialties distribution, frequency of accommodation requests, and reasons for nonaccommodation among resident physicians with disabilities. Results: Among the 1486 resident physicians who completed the baseline survey, 799 (53.8%) replied to the disability questions. Of those, 94 interns (11.8%; weighted number, 173 [11.9%]) reported at least 1 disability and were included in the present study (weighted numbers, 91 [52.6%] men, 82 [47.4%] women, mean [SD] age, 28.6 [3.0] years). Among interns with reported disability and need for accommodations (83 of 173 [48.0%]), more than half (42 [50.6%]) did not request them. The most frequently reported reasons for not requesting needed accommodations were fear of stigma or bias (25 [59.5%]), lack of a clear institutional process for requesting accommodations (10 [23.8%]), and lack of documentation (5 [11.9%]). Conclusions and Relevance: Program directors should investigate cultural and structural factors within their programs that contribute to an environment where residents do not feel safe or supported in disclosing disability and requesting accommodation and review their disability policies for clarity.

Mental health trajectories of Brazilian health workers during two waves of the COVID-19 pandemic (2020-2021).

This study aimed to: (a) monitor the progression of symptoms of mental health burden among frontline workers caring for COVID-19 patients in Brazil during the two waves of the pandemic, considering the number of new cases and deaths, and; (b) to verify the different mental health outcomes and potential associations with current burnout symptoms. A non-probabilistic sample of health professionals was assessed as the pandemic progressed in Brazil (May/2020 August/2021). Standardized instruments focusing on anxiety, depression, insomnia, post-traumatic stress, and burnout symptoms were applied online. The results indicate a decrease in anxiety levels, what was related to when the number of new cases declined (end 1th-wave); symptoms returned to higher levels later. Emotional exhaustion increased when there was a higher incidence of cases, returning to the baseline levels at the end of the second wave. Depersonalization symptoms increased in this phase, characterized by a further decrease in new cases, while professional accomplishment decreased during the follow-up. The highest number of new cases was associated with a higher frequency of anxiety (OR = 1.467;95%CI = 1.109-1.941; p = 0.007) and professional accomplishment (OR = 1.490;95%CI = 1.098-2.023; p = 0.011). The subjects with trajectory of resilience against anxiety presented the lowest level of emotional exhaustion and depersonalization (p < 0.05). The conclusion is that the pressure experienced by healthcare professionals throughout the pandemic caused different impacts on their mental health, emphasizing the dynamic nature of this condition and the need for constant monitoring and care. This finding directly affects mental health prevention and intervention measures, which remain a priority and require continuous reinforcement, especially among the most vulnerable groups.

A high CMV-specific T cell response associates with SARS-CoV-2-specific IL-17 T cell production.

Human cytomegalovirus (CMV) is a widespread persistent herpes virus requiring lifelong immune surveillance to maintain latency. Such long-term interactions with the immune system may be associated with deleterious effects including immune exhaustion and senescence. Regarding the COVID-19 pandemic, we asked whether CMV-specific cellular and humoral activity could influence immune responses toward SARS-CoV-2 and/or disease severity. All adults with mild (n = 15) and severe (n = 14) COVID-19 were seropositive for anti-CMV IgG, but negative for IgM antibodies. Antibody titers did not correlate with COVID-19 severity. Six patients presented elevated frequencies of CMV-specific CD4 + and CD8 + T cells producing IFNγ, IL-17, and TNFα, designated as CMV high responders (hiT CMV). In comparison to low CMV responders, hiT CMV individuals exhibited higher frequencies of SARS-CoV-2-specific CD4 + IL-17 + and CD8 + IFNγ + , IL-17 + or TNFα + T cells. These results indicate that high frequencies of CMV-specific T cells may be associated with a SARS-CoV-2-reactive profile skewed toward Th17-dominated immunity.

Disability, program access, empathy and burnout in US medical students: A national study.

OBJECTIVE: The objective of this study is to investigate whether self-disclosed disability and self-reported program access are associated with measures of empathy and burnout in a national sample of US medical students. METHODS: The authors obtained data from students who responded to the Association of Medical Colleges (AAMC) Year 2 Questionnaire (Y2Q) in 2019 and 2020. Data included demographic characteristics, personal variables, learning environment indicators, measures of burnout (Oldenburg Burnout Inventory for Medical Students), empathy (Interpersonal Reactivity Index) and disability-related questions, including self-reported disability, disability category and program access. Associations between disability status, program access, empathy and burnout were assessed using multivariable logistic regression models accounting for YQ2 demographic, personal-related and learning environment measures. RESULTS: Overall, 23 898 (54.2%) provided disability data and were included. Of those, 2438 (10.2%) self-reported a disability. Most medical students with disabilities (SWD) self-reported having program access through accommodations (1215 [49.8%]) or that accommodations were not required for access (824 [33.8%]). Multivariable models identified that compared with students without disabilities, SWD with and without program access presented higher odds of high exhaustion (1.50 [95% CI, 1.34-1.69] and 2.59 [95% CI, 1.93-3.49], respectively) and lower odds of low empathy (0.75 [95% CI, 0.67-.85] and 0.68 [95% CI, 0.52-0.90], respectively). In contrast, multivariable models for disengagement identified that SWD reporting lack of program access presented higher odds of high disengagement compared to students without disabilities (1.43 [95% CI, 1.09-1.87], whereas SWD with program access did not (1.09 [95% CI, 0.97-1.22]). CONCLUSIONS: Despite higher odds of high exhaustion, SWD were less likely to present low empathy regardless of program access, and SWD with program access did not differ from students without disabilities in terms of disengagement. These findings add to our understanding of the characteristics and experiences of SWD including their contributions as empathic future physicians.

SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.

New derivative of trans-dehydrocrotonin isolated from Croton cajucara shows reduced cytotoxic and genotoxic effects in hepatocellular carcinoma (HepG2) cell line.

The Croton cajucara (Euphorbiales, Euphorbiaceae) plant occurs widely in the Amazon region, where its leaves and stem bark are consumed by the population to treat several diseases. The secondary metabolite trans-dehydrocrotonin (DCTN) is mainly accountable for the biological activities of this plant. However, prolonged consumption is associated with hepatotoxic effects due to the furan ring present in the molecule. This group is responsible for toxicity reactions in other drugs. In this work, we inserted a COOH group into the molecule to prevent the formation of toxic intermediates. We assessed the cytotoxicity and genotoxicity of both molecules on HepG2 cells. Results showed that the new derivative (CCTN) is less cytotoxic and did not reduce cell viability at any concentration tested. Genotoxicity was also reduced as assessed by the comet and micronucleus assay. Therefore, the new derivative appears to be promising and additional tests should be performed to evaluate its therapeutic activities.

Study on the zoonotic cycle of tegumentary leishmaniasis in an endemic area of a metropolitan region in the Northeastern region of Brazil.

This study was conducted to characterize the transmission cycle of the tegumentary leishmaniasis (TL) in an old colonization area at Pernambuco State, Brazil. The aims were to identify autochthonous cases, sandflies fauna, domestic animals as possible reservoir hosts and the Leishmania species involved in this endemic area. A total of 168 suspected human cases of TL and 272 domestic animals (canine, feline, equine, goat, and sheep) were included. The sandflies were captured and identified by species. Patients were predominantly male and the average age was 37+18.1 years old. Of 85 patients who had skin lesions, 25.6% of them had direct positive smears for TL and 34 isolates were identified as Leishmania (Viannia) braziliensis. The confirmation for TL diagnosed by molecular detection (PCR) was almost three times more sensitive than the direct test [p < 0.001; PR = 2.72] associated with clinical examination. The Kappa test on PCR between two different specimens, biopsy, and skin lesion swab was 60.8% (p < 0.001). More than 200 specimens of sandflies (80 males and 159 females) were captured and identified as Lutzomyia whitmani (99.6%) and Lu. evandroi (0.4%). The detection of L. (V.) braziliensis by Real-Time PCR in the blood of a captured fed female was positive in 59.3% of Lu. whitmani. Of the 272 domestic animals included, 61.76% were male (n = 168). Thirty-six animals (13.2%) had lesions compatible with TL (34 dogs, 1 cat and 1 sheep) and 3 of them, all dogs, had lesions on the snout, showing destruction of cartilage and mucosa. The study suggests the participation of domestic animals as possible reservoirs. However, further studies are necessary to better understand the transmission cycle and take recommended measures in order to control the disease.

Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic.

Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation. Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12. Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F1-125 = 7.67; p = 0.006; ηp 2 = 0.06; F1-125 = 6.58; p = 0.01; ηp 2 = 0.05; F1-125 = 4.28; p = 0.04; ηp 2 = 0.03, respectively) after the end of the treatment. Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.

Leishmania V. braziliensis infection in asymptomatic domestic animals within an endemic region in the Northeast of Brazil.

BACKGROUND: American cutaneous leishmaniasis is a commonly neglected, vector-borne tropical parasitic disease that is a major public health concern in Brazil. Leishmania (Viannia) braziliensis is the main species associated with the disease. Accurate diagnosis is based on epidemiological surveillance, clinical assessment, and laboratory testing. Leishmania (V.) braziliensis has been detected in several wild and synanthropic mammals. Their epidemiological role has not been entirely elucidated. This study aimed to assess potential L. braziliensis infections in asymptomatic domestic animals, by molecular and serological testing in endemic areas, in the metropolitan region of Recife. METHODS: Blood samples and conjunctival fluids were collected from 232 animals (canids, felids, equines, and caprines) for the detection of L. braziliensis using molecular tests (conventional and real-time polymerase chain reaction [PCR and qPCR]). For immunological detection, blood samples from 115 dogs were assessed using enzyme-linked immunosorbent assay. RESULTS: Real-time quantitative PCR showed positive results for blood and conjunctival samples in all investigated species. The results of the blood and conjunctival samples were 68.2% and 26.9% in Canis familiaris, 100% and 41.7% in Felis catus, 77.3% and 30.8% in Equus caballus/Equus asinus, and 50% and 33.3% in Capra hircus samples, respectively. CONCLUSIONS: Results from this study adds valuable information to our understanding of the role of asymptomatic domestic animals, L. braziliensis life cycle, and American cutaneous leishmaniasis in Northeast Brazil.

Workplace Protections and Burnout Among Brazilian Frontline Health Care Professionals During the COVID-19 Pandemic.

Health care workers from low- and middle-income countries have been playing a critical role in overcoming the challenges related to the COVID-19 pandemic; yet little is known about the relationship between workplace protections and wellbeing of Brazilian health care workers during the pandemic. This study aimed to evaluate whether Brazilian health care workers were satisfied with their workplace measures to protect their physical and mental health during the pandemic, and to assess the associations of such levels of satisfaction with indicators of burnout. Licensed Brazilian health care professionals were recruited via popular media between 5/19/2020 and 8/23/2020 to complete an online survey including questions about their demographic/professional characteristics, satisfaction with their workplace protective measures during the pandemic, and validated questionnaires assessing neuroticism, resilient coping, and symptoms of burnout. Most participants reported being dissatisfied with their workplace measures to protect their physical (516, 56.3%) and mental health (756, 82.5%). In multivariable analysis adjusted for personal and environmental factors, dissatisfaction with workplace physical health protections was significantly associated with higher levels of emotional exhaustion (B = 1.08, 95% CI = 0.47-1.69) and depersonalization (B = 0.61, 95% CI = 0.10-1.12), and dissatisfaction with workplace mental health protections significantly associated with higher levels emotional exhaustion (B = 1.17, 95% CI = 0.40-1.95). Efforts to improve both physical and mental health protective measures are critical to guarantee that health care workers continue to provide care at their maximum capacity.