Mental health trends among medical students.

Student mental health concerns can manifest in several forms. Medical students juggling a multitude of trials (i.e., intense academic rigor, financial debt, sleep deprivation, lack of control, continual exposure to sickness and death, and training mistreatment) can help explain the higher prevalence of psychological disorders within this population. Furthermore, these mental health difficulties are not static; certain challenges move into the forefront as students face key transition points in schooling. Primary examples include the entry year of medical school, the shift from preclinical curriculum to clinical training, and the final moments prior to beginning residency. Given the existing mental health trends among medical students at baseline, it can be concluded that the COVID-19 pandemic has exacerbated the stress, anxiety, and depression associated with medical education. Solutions do indeed exist to address the moral injury medical students face, from expanded crisis management training and implementation of peer support networks to destigmatization of and improved access to professional mental health resources. It is up to the curators of the medical education system to make these solutions the new status quo.

Telehealth reform post-public health emergency: crucial next steps.

As the pandemic made it unsafe for providers and patients to meet in person, the US government implemented key temporary telehealth waivers in March 2020 that expanded Medicare telehealth coverage dramatically. Some of the most significant changes included the removal of location restrictions so that patients and providers could engage in telehealth from their homes, full provider reimbursement for telehealth visits, coverage for more medical specialties and types of practitioners such as occupational and physical therapists, and the allowance of telehealth prescription of controlled substances. The waivers will end when the government removes the federal status of a public health emergency, which is expected to occur in 2023. Nearly 64 million Medicare patients are at risk of losing most modalities of telehealth access. We present current legislation that could combat this "telehealth cliff" and defend the position that Medicare telehealth access should remain permanently expanded.

Revisão sistemática do benefício cosmético da aplicação tópica do filtrado de fermentação / Systematic review of cosmetic benefit of topical application of ferment filtrate

O filtrado de fermentação, (FF), um subproduto de leveduras rico em nutrientes, é usado cosmeticamente no leste da Ásia desde a década de 1970. Revisamos sistematicamente os efeitos deste ativo tópico na saúde da pele e determinamos as limitações nos estudos disponíveis. A literatura recente mostrou evidências na redução do tamanho dos poros, e tambem da aspereza, hiperpigmentação e vermelhidão. No entanto, esses estudos são limitados em eficácia devido ao pequeno tamanho da amostra, muitas variáveis e capacidade limitada de validação externa. Devido ao aumento de produtos cosméticos contendo esse ingrediente, é necessária uma análise crítica da literatura disponível e futura para evitar a desinformação do consumidor

Ferment filtrate (FF), a by-product of nutrient-rich yeast, is believed to be used cosmetically in East Asia since the 1970s. We systematically reviewed the topical effects of ferment filtrate on skin health and determined limitations in the available studies. Recent literature has shown evidence in reducing the baseline fluctuation of pore size, roughness, hyperpigmentation, and redness. However, these studies are limited in efficacy due to their small sample size, their confounding variables, and their limited generalizability. Because of the increase of cosmetic products containing this ingredient, critical analysis of the available and future literature is necessary to prevent consumer misinformation.

Dexamethasone preconditioning improves the response of collagen-induced arthritis to treatment with short-term lipopolysaccharide-stimulated collagen-loaded dendritic cells.

Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course. Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs). Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN- γ levels than those from CIA group. Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells.

A short protocol using dexamethasone and monophosphoryl lipid A generates tolerogenic dendritic cells that display a potent migratory capacity to lymphoid chemokines.

BACKGROUND: Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. METHODS: TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. RESULTS: After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. CONCLUSION: We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection.

Blocking of p38 and transforming growth factor ß receptor pathways impairs the ability of tolerogenic dendritic cells to suppress murine arthritis.

OBJECTIVE: Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able to reduce inflammation when therapeutically administered into mice with collagen-induced arthritis (CIA). The aim of this study was to uncover the mechanisms that define the tolerogenic effect of short-term LPS-modulated DCs on CIA. METHODS: Bone marrow-derived DCs were stimulated for 4 hours with LPS and characterized for their expression of maturation markers and their cytokine secretion profiles. Stimulated cells were treated with SB203580 or SB431542 to inhibit the p38 or transforming growth factor ß (TGFß) receptor pathway, respectively, or were left unmodified and, on day 35 after CIA induction, were used to inoculate mice. Disease severity was evaluated clinically. CD4+ T cell populations were counted in the spleen and lymph nodes from inoculated or untreated mice with CIA. CD4+ splenic T cells were transferred from mice with CIA treated with LPS-stimulated DCs or from untreated mice with CIA into other mice with CIA on day 35 of arthritis. RESULTS: Treatment with LPS-stimulated DCs increased the numbers of interleukin-10 (IL-10)-secreting and TGFß-secreting CD4+ T cells, but decreased the numbers of Th17 cells. Adoptive transfer of CD4+ T cells from treated mice with CIA reproduced the inhibition of active CIA accomplished with LPS-stimulated DCs. The therapeutic effect of LPS-stimulated DCs and their influence on T cell populations were abolished when the p38 and the TGFß receptor pathways were inhibited. CONCLUSION: DCs modulated short-term (4 hours) with LPS are able to confer a sustained cure in mice with established arthritis by re-educating the CD4+ T cell populations. This effect is dependent on the p38 and the TGFß receptor signaling pathways, which suggests the participation of IL-10 and TGFß in the recovery of tolerance.