Are human V\u3b42pos T cells really resistant to aging and Human Cytomegalovirus infection?

In their recent paper, Weili Xu et al. [1] described the different behaviors of V\u3b41pos and V\u3b42pos T cell subsets in response to lifelong stress and claimed that V\u3b42pos T cells are not affected by aging and Human Cytomegalovirus (HCMV) infection. While we agree that these two \u3b3\u3b4 T cell subsets diverge both in phenotype/function and in tissue distribution, we are somewhat surprised that authors did not take into account the several previously published and contradictory experimental evidence in regards to senescence of V\u3b42pos T cells [2,3]. These latter studies reported that HCMV infection not only induces a clonal expansion of a distinct V\u3b39neg/V\u3b42pos T cell subset, but also determines a concomitant adaptive differentiation from CD27high na\uefve cells to CD27low/neg terminal-effectors. However, Weili Xu et al. argued that the expression and kinetics of both CD27 and CD45RA surface markers do not change and follow the homeostatic changes of V\u3b42pos T cells. This statement goes in the opposite direction to previously reported findings as the CD27/CD45RA phenotype has been shown to mark the maturation and differentiation (TNa\uefve, TCentral-Memory, Teffector-Memory and TEffectory-Memory RA) of V\u3b42pos T cells. Indeed, the different surface expression of both CD27 and CD45 parallel the progressive decrease of telomere length, the proliferative capacity as well as the different effector-functions and resistance to death of V\u3b42+ T cells in response to antigens and homeostatic cytokines [4,5]. Hence, we believe that these controversial issues require further discussion beyond the unilateral conclusion given by the study of Weili Xu et al

Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer.

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2pos T cells showing a relative increase of terminally-differentiated CD27neg/CD45RApos (TEMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on TEMRA Vδ2pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57pos and TEMRA Vδ2pos T cells. Similar results were found for tumor infiltrating Vδ2pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2pos T cells by inducing higher frequencies of circulating CD57pos TEMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57pos TEMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2pos T cells

Characterisation of the immune-related transcriptome in resected biliary tract cancers

Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906

Use of biological drugs in patients with psoriasis and psoriatic arthritis in italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of differentanti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsApatients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 wasanalyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug sur-vival rate and probability of maintaining PASI response were evaluated. The impact of dependentvariables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients wereincluded, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumabfollowed by etanercept and infliximab in PsO and PsA patients. The probability of maintainingPASI response was significantly higher for adalimumab followed by infliximab. For PsO patients,the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2–15.6,p<.001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3,p<.001) vs. adalimumab. Likewise, for PsApatients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI:1.4–3.8,p5.01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1,p5.018) vs. adalimumab. Adalimumabcould be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsApatients

Can nurses remain relevant in a technologically advanced future?

Technological breakthroughs occur at an ever-increasing rate thereby revolutionizing human health and wellness care. Technological advancements have drastically changed the structure and organization of the healthcare industry. McKinsey Global Institute estimates that 800 million workers worldwide could be replaced by robots by the year 2030. There is already a robotic revolution happening in healthcare wherein robots have made tasks and procedures more efficient and safer. Locsin and Ito has addressed the threat to nursing practice with human nurses being replaced by humanoid robots. Routine nursing care dictated solely by prescribed procedures and accomplishment of nursing tasks would be best performed by machines. With the future practice of nursing in a technologically advanced future transcending the implementation of nursing actions to achieve predictable outcomes, how can human nurses remain relevant as practitioners of nursing? Nurses should be involved in deciding which aspects of their practice can be delegated to technology. Nurses should oversee the introduction of automated technology and artificial intelligence ensuring their practice to be more about the universal aspects of human care continuing under a novel system. Nursing education and nursing research will change to encompass a differentiated demand for professional nursing practice with, and not for, robots in healthcare

The Lived Experience of Discontinuing Hormonal Contraception Among Women in Rural Uganda

The purpose of the study was to describe the experience of discontinuing hormonal contraceptive use among women in rural Uganda. A significant number of women in Uganda discontinue hormonal contraception even though such method has been effective. Consequently, these women have unprotected sex, although not wanting to conceive. Narrative descriptions of the experiences by eight women were analyzed using content analysis. The findings describe the experience as Frustration and Helplessness, Living in Fear of Uncertainty, Ingenuity of using other methods of contraception, thus fostering the Accomplishments of being a wife, mother, and woman. Implications for nursing practice, research, and education are described

Autoimmunity and otolaryngology diseases

Many systemic autoimmune diseases have otolaryngology manifestations that could represent a diagnostic challenge for clinicians, as they often constitute an early sign of an otherwise asymptomatic autoimmune condition and may lead to delayed diagnosis and treatment. In other cases, otolaryngology manifestations can be overlooked in patients with previously diagnosed autoimmune diseases. The pres- ence of concomitant conditions, the heterogeneity of studies available in the literature, and the lack of randomized trials are factors that may limit the prompt diagnosis of otolaryn- gology manifestations in systemic autoimmune diseases, with underestimation of the problem and undertreatment of the related condition