Wellspoe0690
IMPORTANCE The impact of food consumption on vaccine responses is unknown. Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, and its polysaccharide capsule is used as a vaccine. We show that capsule type 10A in a pneumococcal vaccine shares an antigenic epitope, βGal(1-6), with pectin, which is in many plant foods and is widely consumed. Immune response to 10A is comparable to that seen with other capsule types, and pectin ingestion may have little impact on vaccine responses. However, antibody to pectin can kill serotype 10A pneumococci and this shared epitope may be considered in pneumococcal vaccine designs. Copyright © 2020 Nahm et al.OBJECTIVES To assess the feasibility and tolerance of NeuroPAP, a new non-invasive ventilation mode which continuously adjusts (during both inspiration and expiration) the pressure support proportionally to the diaphragm electrical activity (Edi), in preterm infants and to evaluate the impact on ventilation pressure and Edi. DESIGN Prospective cross-over single-centre feasibility study. check details SETTING One level 3 neonatal intensive care unit in Canada. PATIENTS Stable preterm infants ventilated with non-invasive positive pressure ventilation (NIPPV). INTERVENTIONS Subjects were successively ventilated in NIPPV with prestudy settings (30 min), in NeuroPAP with minimal pressure similar to NIPPV PEEP (positive end-expiratory pressure) (60 min), in NeuroPAP with minimal pressure reduced by 2 cmH20 (60 min), in continuous positive airway pressure (15 min) and again in NIPPV (30 min). Main outcome measures included tolerance, ventilation pressure, Edi and patient-ventilator synchrony. RESULTS Twenty infants born at 28.0±1.0 weeks were included. NeuroPAP was well tolerated and could be delivered during 100% of planned period. During NeuroPAP, the PEEP was continuously adjusted proportionally to tonic diaphragm Edi, although the average PEEP value was similar to the set minimal pressure. During NeuroPAP, 83 (78-86)% breaths were well synchronised vs 9 (6-12)% breaths during NIPPV (p less then 0.001). CONCLUSIONS NeuroPAP is feasible and well tolerated in stable preterm infants, and it allows transient adaptation in PEEP in response to tonic diaphragm electrical activity changes. Further studies are warranted to determine the impact of these findings on clinical outcomes. TRIAL REGISTRATION NUMBER NCT02480205. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Phototherapy is used on the majority of preterm infants with unconjugated hyperbilirubinaemia. The use of fluorescent tube phototherapy is known to induce oxidative DNA damage in infants and has largely been replaced by blue light-emitting diode phototherapy (BLP). To date, it is unknown whether BLP also induces oxidative DNA damage in preterm infants. OBJECTIVE To determine whether BLP in preterm infants induces oxidative DNA damage as indicated by 8-hydroxy-2'deoxyguanosine (8-OHdG). DESIGN Observational cohort study. METHODS Urine samples (n=481) were collected in a cohort of 40 preterm infants (24-32 weeks' gestational age) during the first week after birth. Urine was analysed for the oxidative marker of DNA damage 8-OHdG and for creatinine, and the 8-OHdG/creatinine ratio was calculated. Durations of phototherapy and levels of irradiance were monitored as well as total serum bilirubin concentrations. RESULTS BLP did not alter urinary 8-OHdG/creatinine ratios (B=0.2, 95% CI -6.2 to 6.6) at either low (10-30 µW/cm2/nm) or high (>30 µW/cm2/nm) irradiance (B=2.3, 95% CI -5.7 to 10.2 and B=-3.0, 95% CI -11.7 to 5.6, respectively). Also, the 8-OHdG/creatinine ratios were independent on phototherapy duration (B=-0.1, 95% CI -0.3 to 0.1). CONCLUSIONS BLP at irradiances up to 35 µW/cm2/nm given to preterm infants ≤32 weeks' gestation does not affect 8-OHdG, an oxidative marker of DNA damage. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Clinical trials have shown the ability of therapeutic vaccines to generate immune responses to tumor-associated antigens (TAAs). What is relatively less known is if this translates into immune-cell (IC) infiltration into the tumor microenvironment. This study examined whether neoadjuvant prostate-specific antigen (PSA)-targeted vaccination with PROSTVAC could induce T-cell immunity, particularly at the tumor site. METHODS An open-label, phase II study of neoadjuvant PROSTVAC vaccine enrolled 27 patients with localized prostate cancer awaiting radical prostatectomy (RP). We evaluated increases in CD4 and CD8 T-cell infiltrates (RP tissue vs baseline biopsies) using a six-color multiplex immunofluorescence Opal method. Antigen-specific responses were assessed by intracellular cytokine staining after in vitro stimulation of peripheral blood mononuclear cells with overlapping 15-mer peptide pools encoding the TAAs PSA, brachyury and MUC-1. RESULTS Of 27 vaccinated patients, 26 had matched prevaccinatio both tumor immune response and peripheral immune response. TRIAL REGISTRATION NUMBER NCT02153918. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND A bidirectional crosstalk between tumor cells and the surrounding microenvironment contributes to tumor progression and response to therapy. Our previous studies have demonstrated that bcl-2 affects melanoma progression and regulates the tumor microenvironment. The aim of this study was to evaluate whether bcl-2 expression in melanoma cells could influence tumor-promoting functions of tumor-associated macrophages, a major constituent of the tumor microenvironment that affects anticancer immunity favoring tumor progression. METHODS THP-1 monocytic cells, monocyte-derived macrophages and melanoma cells expressing different levels of bcl-2 protein were used. ELISA, qRT-PCR and Western blot analyses were used to evaluate macrophage polarization markers and protein expression levels. Chromatin immunoprecipitation assay was performed to evaluate transcription factor recruitment at specific promoters. Boyden chamber was used for migration experiments. Cytofluorimetric and immunohistochemical analyses were carried out to evaluate infiltrating macrophages and T cells in melanoma specimens from patients or mice.