Simultaneous Identification of Functional Antigen-Specific CD8+ and CD4+ Cells after In Vitro Expansion Using Elongated Peptides.

Elongated peptides (EPs), containing possibly one or multiple epitope/s, are increasingly used for the screening of antigen-specific CD8+ and CD4+ cell responses. Here, we present an in vitro protocol that allows the amplification of antigen-specific cells and the subsequent functional analysis of both T cell types using EPs. Known viral-derived epitopes were elongated to 20 mer EPs on the N-, C-, and both termini for HLA class I binders, or on the N- and C- termini for HLA class II binders. With EP stimulation only, the percentage of responding CD8+ T cells was dependent on the elongation site of the EP, whereas CD4+ T cell responses were completely lost in 22% of the tests performed ex vivo. A short-term amplification step plus the addition of a TLR3 agonist (Poly-ICLC) together with an increased EP concentration improved markedly the detection of CD8+ and CD4+ T cell reactivities.

Midwifery centers as enabled environments for midwifery: A quasi experimental design assessing women's birth experiences in three models of care in Bangladesh, before and during covid.

BACKGROUND: The midwifery model of care is a human rights-based approach (HRBA) that is unique and appropriate for the majority of healthy pregnant women, yet full expression may be limited within the medical model. Midwifery centers are facilities designed specifically to enable the practice of midwifery. In high resource countries, they have been shown to be cost effective, evidence-based, avoid over medicalization, and provide safe, efficient and satisfying care. METHODS: A quasi-experimental design was used to assess the impact of three models of care on women's experiences of respect, and trust in maternity care provision, both before and during the pandemic in Bangladesh, as well as their fear and knowledge around COVID-19, during the pandemic. The models were: "fully enabled midwifery" ("FEM") in freestanding midwifery centers; "midwifery and medicine" ("MAM") in medical facilities with midwives working alongside nurses and doctors; and "no midwifery" ("NoM") in medical facilities without midwives. Phone survey data were collected and analyzed from all women (n = 1,191) who delivered from Jan 2020-June 2020 at seven health care facilities in Bangladesh. Comparison of means, ANOVA, post hoc Tukey, and effect size were used to explore the differences in outcomes across time periods. FINDINGS: Pre-pandemic, women served by the FEM model reported significantly higher rates of trust and respect (p<0·001) compared to the NoM model, and significantly higher rates of trust (p<0·001) compared to MAM. During the pandemic, in the FEM model, the experiences of respect and trust did not change significantly from the pre-pandemic rates, and were significantly higher than both the MAM and NoM models (p < 0·001). Additionally, during the pandemic, women served by the FEM model had the lowest experience of COVID fear (p<0·001). INTERPRETATION: Fully enabled midwifery in midwifery centers had a significantly positive effect on woman's experience of respect and trust in care compared to the other models, even in the context of a pandemic.

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial.

BACKGROUND: Peptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells. METHODS: Twenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination. RESULTS: Most patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed. CONCLUSION: Targeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation. TRIAL REGISTRATION NUMBER: NCT03199872.

Chromosome 1 blood pressure QTL region influences renal function curve and salt sensitivity in SHR.

One or more quantitative trait locus (QTL) for blood pressure (BP) exists on rat chromosome 1, in the vicinity of the Sa gene. The present work examined whether this QTL region: 1) alters pressure-natriuresis relationship and 2) affects the BP response to salt load. Male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, and rats from an SHR congenic strain that contains a WKY chromosome 1 segment spanning the BP QTL region (SHR. WKY-Sa) were used. In an acute study in anesthetized animals, renal function was measured at several levels of renal perfusion pressure. In a chronic study, BP was measured in freely moving rats using telemetry during normal and high sodium intake (2% NaCl as drinking water for 2 wk). WKY rats showed a significantly higher glomerular filtration rate and increased pressure-natriuresis compared with SHR. SHR.WKY-Sa also demonstrated an increased glomerular filtration rate and enhanced pressure-natriuresis, associated with a lower tubular sodium reabsorption, compared with SHR. These modifications were accompanied by a lower basal BP in SHR.WKY-Sa compared with SHR and a markedly reduced BP response to salt load. These findings suggest that the BP QTL(s) present in this region of chromosome 1 influences BP and salt sensitivity, at least partly, by modulating pressure-natriuresis.

Dental hygienists' opinions about loupes in education.

PURPOSE: The present study was conducted in order to explore dental Hygienists' perceptions of the advantages and disadvantages of loupes, and the extent to which dental hygienists believe loupes should be utilized in the educational setting. METHODS: Dental hygienists were contacted through a popular dental hygiene website and were asked to participate in a survey regarding the use of loupes. Eight hundred sixty-eight valid surveys were completed. Participants were asked to indicate the extent to which they use loupes, the environments in which they have used loupes, when they think loupes should be introduced to students in dental hygiene school, and the advantages and disadvantages of using loupes. RESULTS: Results indicated approximately 60.5% of practicing dental hygienists surveyed for the study always or sometimes use loupes, however only 21% had actually used loupes as a student. A number of differences were found between those respondents who use loupes and those who do not use loupes in regards to how they believe loupes should be used in education. Alleged advantages of using loupes received much greater support than alleged disadvantages. Members of the American Dental Hygienists' Association (ADHA) were much more likely to always use loupes than non-ADHA respondents. CONCLUSION: Dental hygienists participating in the survey believe that loupes should be introduced to dental hygiene students, although many believe using loupes should be an option while in school. Wide agreement exists among dental hygienists in regards to the advantages of using loupes. The authors contend that loupes are a vital tool that students should learn how to use, but the use of loupes should be optional once a student has learned how to use them properly.

Conducting needs assessment using the comprehensive participatory planning and evaluation model to develop nutrition and physical activity interventions in a rural community in the Mississippi delta.

BACKGROUND: Members of a Lower Mississippi Delta community and university partners used the Comprehensive Participatory Planning and Evaluation (CPPE) model to assess nutrition and health problems and develop a menu of interventions. OBJECTIVES: We sought to identify and prioritize nutrition and physical activity problems in the community and to identify interventions to address the problems. METHODS: Community members and university partners used the CPPE process to identify and prioritize nutrition and physical activity problems. The participants developed causal models to break down the identified problems to their root causes. They then developed a menu of interventions and criteria to rank the interventions. RESULTS: The identified problems were intake of unhealthy foods, lack of nutrition education, and lack of adequate physical activity. The menu of interventions consisted of seven objectives to address poor nutrition and physical activity as well as a total of 19 interventions to meet these objectives. CONCLUSION: Directly involving community members in identifying health problems and solutions results in the development of interventions that are likely to have greater acceptability with the community.