TLR9 Signaling Suppresses the Canonical Plasma Cell Differentiation Program in Follicular B Cells

The relative potency and quality of mouse B cell response to Toll-like receptors (TLRs) signaling varies significantly depending on the B cell subset and on the TLR member being engaged. Although it has been shown that marginal zone cells respond faster than follicular (FO) splenic B cells to TLR4 stimulus, FO B cells retain full capacity to proliferate and generate plasmablasts and plasma cells (PBs/PCs) with 2–3 days delayed kinetics. It is not clear whether this scenario could be extended to other members of the TLR family. Here, using quantitative cell culture conditions optimized for B cell growth and differentiation, we show that TLR9 signaling by CpG, while promoting vigorous proliferation, completely fails to induce differentiation of FO B cells into PBs/PCs. Little or absent Ig secretion following TLR9 stimulus was accompanied by lack of expression of cell surface markers and canonical transcription factors involved in PB/PC differentiation. Moreover, not only TLR9 did not induce plasmocyte differentiation, but it also strongly inhibited the massive PB/PC differentiation of FO B cells triggered by LPS/TLR4. Our study reveals unexpected opposite roles for TLR4 and TLR9 in the control of plasma cell differentiation program and disagrees with previous conclusions obtained in high-density cultures conditions on the generation of plasmocytes by TRL9 signaling. The potential implications of these findings on the role of TLR9 in controlling self-tolerance, clonal sizes and regulation of humoral responses are discussed

Evaluation of Ar, Ar-v7, and P160 Family as Biomarkers for Prostate Cancer: Insights Into the Clinical Significance and Disease Progression

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p \u3c 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p \u3c 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p \u3c 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p \u3c 0.0005), with a shorter time-to-recurrence in the super-expression group (p \u3c 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools

Recommendations for the implementation of a national lung cancer screening program in Portugal—A consensus statement

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Lung Cancer Screening (LCS) programs that use low-dose computed tomography (LDCT) have been shown to reduce LC mortality by up to 25 % and are considered cost-effective. The European Health Union has encouraged its Member States to explore the feasibility of LCS implementation in their respective countries. The task force conducted a comprehensive literature review and engaged in extensive discussions to provide recommendations. These recommendations encompass the essential components required to initiate pilot LCS programs following the guidelines established by the World Health Organization. They were tailored to align with the specific context of the Portuguese healthcare system. The document addresses critical aspects, including the eligible population, methods for issuing invitations, radiological prerequisites, procedures for reporting results, referral processes, diagnostic strategies, program implementation, and ongoing monitoring. Furthermore, the task force emphasized that pairing LCS with evidence-based smoking cessation should be the standard of care for a high-quality screening program. This document also identifies areas for further research. These recommendations aim to guarantee that the implementation of a Portuguese LCS program ensures high-quality standards, consistency, and uniformity across centres. © 2024 Sociedade Portuguesa de Pneumologi

Resting heart rate as a predictor of metabolic dysfunctions in obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>Recent studies have identified that a higher resting heart rate (RHR) is associated with elevated blood pressure, independent of body fatness, age and ethnicity. However, it is still unclear whether RHR can also be applied as a screening for other risk factors, such as hyperglycemia and dyslipidemia. Thus, the purpose of the presented study was to analyze the association between RHR, lipid profile and fasting glucose in obese children and adolescents.</p> <p>Methods</p> <p>The sample was composed of 180 obese children and adolescents, aged between 7-16 years. Whole-body and segmental body composition were estimated by Dual-energy X-ray absorptiometry. Resting heart rate (RHR) was measured by heart rate monitors. The fasting blood samples were analyzed for serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose, using the colorimetric method.</p> <p>Results</p> <p>Fasting glucose, TC, triglycerides, HDL-C, LDL-C and RHR were similar in both genders. The group of obese subjects with a higher RHR presented, at a lower age, higher triglycerides and TC. There was a significant relationship between RHR, triglycerides and TC. In the multivariate model, triglycerides and TC maintained a significant relationship with RHR independent of age, gender, general and trunk adiposity. The ROC curve indicated that RHR has a high potential for screening elevated total cholesterol and triglycerides as well as dyslipidemia.</p> <p>Conclusion</p> <p>Elevated RHR has the potential to identify subjects at an increased risk of atherosclerosis development.</p

The Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A): a study with recently and non-recently divorced adults

Past research has demonstrated that divorced adults show more health problems and psychological distress than married adults. Considering the high prevalence rates of divorce among Western countries, new and robust measures should be developed to measure psychological distress after this specific transition in adulthood. The aim of this study was to adapt and validate a Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A; Sweeper and Halford in J Family Psychol 20(4):632–640, 2006). PAST-A is a self-report measure that assesses two key dimensions of separation adjustment problems: lonely-negativity and former partner attachment. Psychometric properties of the Portuguese version of PAST-A were assessed in terms of factor structure, internal consistency, and convergent and divergent validity, in an online convenience sample with divorced adults (N = 460). The PAST-A two-factor structure was confirmed by exploratory and confirmatory factor analyses, with each factor demonstrating very satisfactory internal consistency and good convergence. In terms of discriminant validity, the Portuguese PAST-A reveals a distinct factor from psychological growth after divorce. The results provided support for the use of the Portuguese PAST-A with divorced adults and also suggested that the explicative factors of the psychological adjustment to divorce may be cross-cultural stable. The non-existence of validated divorce-related well-being measures and its implications for divorce research are also discussed