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Handover of patient care is a potential safety risk for the patient due to loss of information which may result in adverse outcome. We hypothesized that a checklist for handover from the operating room (OR) to the intensive care unit (ICU) will lead to an increase of quality regarding information transfer compared with a nonstandardized handover procedure. The study was conducted as a prospective, randomized trial in a university hospital. The quality of handovers with checklist was compared with handovers without checklist. Handovers were recorded by digital voice recorder and analyzed using an individual rating sheet for each patient. This enabled to discriminate between items that “must be handed over” (red items) and items that “should be handed over” (yellow items). A total of 121 patient handovers from OR to ICU were included. Significantly more red items were handed over in the study group compared with the control group (study group: median 87.1%, 25-27 percentile 77.1%-90.0%; control group: median 75.0%, 25-75 percentile 66.7%-88.6%; P < .01). This study gives first evidence that the use of a standardized checklist for patient handover from OR to ICU increases the quantity and quality of transmitted medical information.

BackgroundBreast cancer associated gene 1 (BRCA1) mutant malignancy is an aggressive subtype of breast cancer caused by mutations in the BRCA1 gene. Disease was thought to be caused by an accumulation of genetic damage, but more recently we have evidence showing that there are other factors in the microenvironment such as the immune cells are involved in the initiation of this disease. Many breast tumor subtypes are categorized as cold tumors with low immune infiltration and poor response to immunotherapy. But BRCA1 deficient tumors have been shown to be associated with a more conspicuous immune cell infiltration than other breast cancer subtypes.MethodsWe use a genetically engineered mouse model that lacks BRCA1 and p53 genes for this study. Additionally, we analyzed BRCA1 mutant and tumor tissues from patients. Using a combination of single cell genomics and spatial proteomics we identify changes in the immune microenvironment of the BRCA1 mutant tissues. We also employ methods such as flow cytometry and immunofluorescence to quantify immune cell populations in the BRCA1 mutant tissues.ResultsThrough my analysis of single cell sequencing data and by flow cytometry, there is a substantial increase in pro-inflammatory macrophages within the BRCA1 mutant tissues at the premalignant stage. There is a change in the macrophage phenotype, transitioning from tissue-resident to a more inflammatory type within the microenvironment. Using a powerful spatial proteomics technology, I have also found a substantial accumulation of immune cells in the mutant tissues prior to tumor formation particularly surrounding the epithelial structures. It appears that these immune cells are mostly F4/80+ macrophages. Using in-vitro mammary organoids co-cultured with the mammary gland macrophages from the BRCA1 mutant mice, I found that that there is increased growth and branching of the epithelium. We observe a similar pro-inflammatory microenvironment in human BRCA1 mutation carriers as well.ConclusionsOur data suggests that there is a pro-inflammatory immune microenvironment in the premalignant tissues prior to tumor formation with accumulation of macrophages. Our in-situ analysis suggests that there could be potential interactions between tumor/epithelial cells and macrophages at the premalignant stage. If it is established that the macrophages play a critical role in the initiation of this disease, it would represent a significant paradigm shift in the field. Moreover, it would open the possibility of utilizing immunotherapies as a means of potential strategies for cancer prevention in individuals with BRCA1 mutations.

Current data on the prevalence of overweight and energy-balance behaviors among European children is necessary to inform overweight prevention interventions. A school-based survey among 10-12 year old children was conducted in seven European countries using a standardized protocol. Weight, height, and waist circumference were measured; Engagement in physical activity, sedentary and dietary behaviors, and sleep duration were self-reported. Descriptive analyses were conducted, looking at differences according to country, gender, and parental education. 7234 children (52%girls; 11.6 ± 0.7 years) participated. 25.8% and 5.4% of boys, and 21.8% and 4.1% of girls were overweight (including obese) and obese (according to International Obesity Task Force criteria), respectively. Higher prevalence of overweight/obesity was observed in Greece, Hungary, Slovenia and Spain than in Belgium, Netherlands and Norway. Large differences between countries were found in intakes of sugar-sweetened beverages, breakfast, active transport, TV and computer time. More favorable overweight status and behavior patterns were found in girls than boys and in children of higher educated parents than in children of lower educated parents. High levels and striking differences in overweight status and potential risk behaviors were found among schoolchildren across Europe.

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5′-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5′-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5′polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 5′-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA) n repeat expansions in vivo , implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 5′-flap specificity and catalysis, preventing genomic instability. Flap Endonuclease 1 is a DNA replication and repair enzyme indispensable for maintaining genomic stability. Here the authors provide mechanistic details on how FEN1 selects for 5′-flaps and promotes catalysis to avoid large-scale repeat expansion by a process termed ‘phosphate steering’.

The objective of this scoping review is to explore the systemic barriers that impact health inequities among vulnerable populations (e.g., racial/ethnic and gender groups, people with disabilities, refugees, immigrants, elders, young children, agricultural and fishery workers, and low‐income individuals) when facing climate change stressors. We conducted an extensive review using nine search engines, which yielded 21 publications that focused on the health outcomes and barriers on the topic of climate change among vulnerable populations. Our findings indicated that poverty is the largest challenge preventing people from adequate health access and achieving positive outcomes, particularly for vulnerable populations globally. In addition, institutional and systemic barriers also differ based on regional differences, which suggests that health inequities are context dependent. Our scoping review has implications for (a) enhancing the effectiveness of climate change mitigation strategies and (b) addressing the healthcare barriers of vulnerable populations based on country‐specific challenges. Plain Language Summary This review looked at the challenges that vulnerable groups, such as people from different racial and ethnic backgrounds, women, people with disabilities, refugees, immigrants, the elderly, children, farm and fishery workers, and those with low incomes, face when dealing with the effects of climate change. We wanted to understand how climate change makes health inequalities worse for these groups. We found 21 studies that focused on the health risks and barriers vulnerable populations face because of climate change. We found that the barriers vary by region, meaning that health inequalities depend on where people live. Our review also showed that poverty is the biggest global barrier preventing these groups from getting the healthcare they need. This review suggests two important things: (a) to make climate change solutions more effective, we need to consider how they affect vulnerable groups, and (b) we need to address the specific healthcare challenges that different countries and regions face in order to support those who are most at risk. Key Points A successful and sustainable climate mitigation effort needs to address health inequities when facing climate stressors The reduction of healthcare inequities is dependent on examining country‐specific healthcare barriers that impact vulnerable populations A recommendation is made to explore global healthcare barriers of vulnerable populations to ensure effective climate mitigation strategies

We isolated 77 highly pathogenic avian influenza viruses during routine surveillance in live poultry markets in northern provinces of Vietnam from 2018 to 2021. These viruses are of the H5N6 subtype and belong to HA clades 2.3.4.4g and 2.3.4.4h. Interestingly, we did not detect viruses of clade 2.3.4.4b, which in recent years have dominated in different parts of the world. The viruses isolated in this current study do not encode major determinants of mammalian adaptation (e.g., PB2-E627K or PB1-D701N) but possess amino acid substitutions that may affect viral receptor-binding, replication, or the responses to human antiviral factors. Several of the highly pathogenic H5N6 virus samples contained other influenza viruses, providing an opportunity for reassortment. Collectively, our study demonstrates that the highly pathogenic H5 viruses circulating in Vietnam in 2018–2021 were different from those in other parts of the world, and that the Vietnamese H5 viruses continue to evolve through mutations and reassortment.

Neutrophil-mediated secondary tissue injury underlies acute respiratory distress syndrome (ARDS) and progression to multi-organ-failure (MOF) and death, processes linked to COVID-19-ARDS. This secondary tissue injury arises from dysregulated neutrophils and neutrophil extracellular traps (NETs) intended to kill pathogens, but instead cause cell-injury. Insufficiency of pleiotropic therapeutic approaches delineate the need for inhibitors of dysregulated neutrophil-subset(s) that induce subset-specific apoptosis critical for neutrophil function-shutdown. We hypothesized that neutrophils expressing the pro-survival dual endothelin-1/VEGF-signal peptide receptor, DEspR, are apoptosis-resistant like DEspR+ cancer-cells, hence comprise a consequential pathogenic neutrophil-subset in ARDS and COVID-19-ARDS. Here, we report the significant association of increased peripheral DEspR+CD11b+ neutrophil-counts with severity and mortality in ARDS and COVID-19-ARDS, and intravascular NET-formation, in contrast to DEspR[-] neutrophils. We detect DEspR+ neutrophils and monocytes in lung tissue patients in ARDS and COVID-19-ARDS, and increased neutrophil RNA-levels of DEspR ligands and modulators in COVID-19-ARDS scRNA-seq data-files. Unlike DEspR[-] neutrophils, DEspR+CD11b+ neutrophils exhibit delayed apoptosis, which is blocked by humanized anti-DEspR-IgG4 S228P antibody, hu6g8, in ex vivo assays. Ex vivo live-cell imaging of Rhesus-derived DEspR+CD11b+ neutrophils showed hu6g8 target-engagement, internalization, and induction of apoptosis. Altogether, data identify DEspR+CD11b+ neutrophils as a targetable ‘rogue’ neutrophil-subset associated with severity and mortality in ARDS and COVID-19-ARDS.

While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP–IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.

This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe. We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age. A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex. We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.

The current UK vaccination programme for herpes zoster (HZ) excludes people aged ≥80 years. This study aimed to quantify the number of individuals ≥80 years who missed HZ vaccination and the consequent epidemiological and economic burden of HZ and post-herpetic neuralgia (PHN). Immunocompetent individuals aged ≥80 years between 1st September 2013 and 31st December 2017 in the Clinical Practice Research Datalink were selected and linked to Hospital Episodes Statistics, where available. Rates of HZ and PHN and healthcare resource utilisation were investigated for the overall study population and by age group (80-84, 85-89, ≥90 years old) and the burden of HZ and PHN was projected to the UK population. 4,858 HZ episodes and 464 PHN cases were identified in 255,165 individuals over 576,421 person-years (PY). Rates of HZ and PHN were 8.43 (95% confidence interval [CI] 8.19-8.66) and 0.80 (0.73-0.87) per 1,000 PY respectively and lowest in those aged ≥90 (HZ rate 7.37/1,000 PY; PHN rate 0.56/1,000 PY). Within HZ episodes, 10.27% of GP visits, 5.82% of prescribed medications and 21.65% of hospitalisations were related to HZ/PHN. Median length of hospitalisation increased from 7.0 days for all-cause to 10.5 days for HZ/PHN related hospitalisations. Individuals ≥90 stayed in hospital a median of 3-4 days longer than younger groups. Approximately 2.23 million individuals in the UK missed HZ vaccination since 2013 (1.86 million had never been eligible and 365,000 lost eligibility for HZ vaccination), resulting in an estimated 43,149 HZ episodes. This study highlights the impact of the 80-year upper age limit policy on the health system. Our study estimates that 2.23 million individuals in the UK may have lost the opportunity to be vaccinated and that their burden of HZ and PHN remains high, especially among the very elderly.