Medical treatment of gastroesophageal reflux in the neonatal intensive care unit: current practice
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Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24 h post IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population.
Management practices and manufacturing firm responses to a randomized energy audit
Increasing the efficiency of industrial energy use is widely considered important for mitigating climate change. We randomize assignment of an energy audit intervention aimed at improving energy efficiency and reducing energy expenditures of small- and medium-sized metal processing firms in Shandong Province, China, and examine impacts on energy outcomes and interactions with firms’ management practices. We find that the intervention reduced firms’ unit cost of electricity by 8% on average. Firms with more developed structured management practices showed higher rates of recommendation adoption. However, the post-intervention electricity unit cost reduction is larger in firms with less developed practices, primarily driven by a single recommendation that corrected managers’ inaccurate reporting of transformer usage at baseline, lowering their electricity costs. By closing management-associated gaps in awareness of energy expenditures, energy audit programmes may reduce a firm’s unit cost of energy but have an ambiguous impact on energy use and climate change.
Exploring dietitians’ experiences caring for patients living with obesity in acute care: a qualitative study
Obesity is a modifiable risk factor associated with hospital-associated complications. Recent studies show there is a high prevalence of patients with obesity presenting to hospital and evidence indicates that people living with obesity should receive diet advice from a dietitian; however, patients often do not receive this care in acute settings.
Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial
First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) and progression-free survival versus chemotherapy for advanced gastroesophageal adenocarcinoma with programmed death ligand 1 combined positive score ≥ 5, meeting both primary end points of the randomized phase 3 CheckMate 649 trial. Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, post hoc exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein–Barr virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.
Foundation dentists’ attitudes and experiences in providing dental care for dependant older adults resident in care home settings
There is a continued increase of older dependant adults in England. Foundation Dentists (FDs) are often the dental workforce being tasked with providing dental care to dependant older adults resident in care home settings. This study explores whether FDs have the experience and confidence to deliver this.
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