Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T‐cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1^hi) develop normally in immunocompetent and Rag2^?/?thymi, their differentiation is partially blocked in Rag2^?/?Il2rg^?/? counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross‐talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)⁺ mTEC subtypes expressing intermediate CCRL1 levels (CCRL1^int) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2^?/? thymi, CCRL1^int mTECs are restored in Rag2^?/?Marilyn TCR‐Tg mice, indicating that the appearance of postnatal‐restricted mTECs is closely linked with T‐cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.     

Patient Safety in Dental Practice: Lessons to Learn About the Risks and Limits of Professional Liability

IntroductionHealth professionals should work with the notion of risk involved in the health care process. Dental practice risk is of particular interest because it encompasses both aesthetic and functional components. Focusing on guidelines suggested by the World Health Organization and objectives on patient safety, this study has 2 objectives: to present Portuguese medicolegal data on corporal damage evaluation related to iatrogenic sequelae during dental practice and to present updated evidence on patient safety.Materials and methodsA retrospective study was performed by analysing data from the database of the Laboratory of Forensic Dentistry of the Faculty of Medicine, University of Coimbra, Portugal, from 2013 to 2018.ResultsOne hundred seven medicolegal files were selected according to the inclusion and exclusion criteria. Iatrogenic sequelae (73.8%, 79 out of 107) were categorised as risks (60 out of 79) and malpractice (19 out of 79). The risk was associated mostly with mandibular dysfunction and orthodontic treatment (62.2%). Malpractice was mostly associated with neurological deficit and implant rehabilitation (47.4%).Discussion and conclusionGreater attention to these data by professionals was emphasised, especially when considering patient safety and health care quality. This article presents the Portuguese data on professional liability in the field of dental practice, categorising iatrogenic sequelae into risks and malpractice, as well as the oral rehabilitation procedure and timeline.     

Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".     

Effects of the Ketogenic Diet in the Treatment of Gliomas: A Systematic Review

The ketogenic diet (KD) is a restrictive therapeutic diet, distinguished by being hyperlipidic, normoproteic, and hypoglucidic. This diet simulates biochemical changes related to fasting periods to achieve systemic ketosis. The metabolic particularities of glioma tumors motivated the rise in investigations and nutritional strategies, such as KD, to modulate the glycemic response as a treatment. This systematic review followed the PRISMA recommendations and was published in PROSPERO, with the identification CRD42021264173. The databases used were EMBASE, PubMed/Medline, Scopus, and Web of Science, and the studies were analyzed using the web-based application Rayyan. To analyze the risk of bias, Cochrane RevMan 5 software was used. For the analysis and treatment of statistical data, Microsoft® Excel® was used. A total of nine original articles were included. Data on survival, symptomology, and quality of life were collected. Mean overall survival was 15.9 months. Constipation and fatigue were the most reported symptoms. In 44.4% of the studies, an improvement in the quality of life was found. The KD is supported by most published studies as an effective therapy in the treatment of malignant gliomas due to its positive effects on patient survival. It was not possible to conclude the effectiveness of KD on quality of life.     

Prevalence and Persistence of Anxiety and Depression over Five Years since Breast Cancer Diagnosis—The NEON-BC Prospective Study

Anxiety and depression are frequent among patients with breast cancer (BCa). Evidence of the persistence and recovery from these conditions and their determinants is scarce. We describe the occurrence of clinically significant anxiety and depression symptoms and their associated factors among BCa patients. A total of 506 women admitted in 2012 at the Portuguese Institute of Oncology of Porto were evaluated before treatment and after one, three, and five years (7.9% attrition rate). The five-year prevalence of anxiety and/or depression (Hospital Anxiety and Depression Scale, subscores ≥ 11) was 55.4%. The peak prevalence for anxiety was before treatment (38.0%), and after one year for depression (13.1%). One in five patients with anxiety/depression at baseline had persistent anxiety/depression over time, while only 11% and 22% recovered permanently from anxiety and depression, respectively, during the first year. Higher education, higher income, practicing physical activity, and adequate fruit and vegetable intake were protective factors against anxiety and/or depression. Loss of job and income, anxiolytics and antidepressants, cancer-related neuropathic pain, and mastectomy were associated with higher odds of anxiety and/or depression. These results highlight the importance of monitoring anxiety/depression during the first five years after cancer diagnosis and identify factors associated with these conditions.     

Dietary Supplements and the Skin: Focus on Photoprotection and Antioxidant Activity—A Review

Skin health is not only significantly affected by ageing, but also by other lifestyle-related factors, such as sun exposure, exercise and eating habits, smoking or alcohol intake. It is known that the cutaneous tissue can exhibit visible signs of senescence, in the form of, for example, dull complexion, loss of firmness, or changes in pigmentation. Consumers attempt to improve skin health and appearance not only by cosmetic products, but also with the consumption of food supplements. Recently, there has been an increase in the amount of food supplements with claims that are related to skin and hair health. Nevertheless, the literature is still scarce in evidence of the efficacy of this type of products. Considering this scenario, we aim in this review to assemble studies and methodologies that are directed at the substantiation of the cutaneous health claims of food supplements. For example, we reviewed those that were indicative of antioxidant properties, improvement in pigmentation disorders, increased hydration or protection against the damages caused by ultraviolet radiation.     

Synergistic interaction effect between job control and social support at work on general psychological distress

Purpose  

Little is known about the interaction between job control and social support at work on common mental disorders. To examine whether there is a synergistic interaction effect between job control and social support at work on general psychological distress and whether it differs by the level of job demands.     

The Importance of Measuring Competency-Based Outcomes: Standard Evaluation Measures Are Not Surrogates for Clinical Performance of Internal Medicine Residents

Background: Despite recent emphasis on educational outcomes, program directors still rely on standard evaluation techniques such as tests of knowledge and subjective ratings. Purposes: To assess the correlation of standard internal medicine (IM) residency evaluation scores (attending global evaluations, In-Training examination, and Mini-Clinical Examination Exercise) with documented performance of preventive measures for continuity clinic patients. Methods: Cross-sectional study of 132 IM residents attending an IM teaching clinic, July 2000 to June 2003, comparing standard evaluations with chart audit. Results: Mean resident performance ranged from 53% (SD = 24) through 89% (SD = 20) across the 6 preventive measures abstracted from 1,102 patient charts. We found weak and mostly not significant correlations between standard measures and performance of preventive services. Conclusions: Standard measures are not adequate surrogates for measuring clinical outcomes. This supports the Accreditation Council for Graduate Medical Education's recommendations to incorporate novel Toolbox measures, like chart audit, into residency evaluations.