The acceptability of alcohol screening and brief intervention for older adults in community venues.

Background: Evidence supports the effectiveness of alcohol brief interventions (ABI) in health-care settings but the acceptability of conducting ABIs in wider community venues such as supermarkets, hospital atriums and train stations remains unclear. This study examines the acceptability of conducting ABIs for older adults in community settings.

Method: ABIs were conducted in community venues in five sites across the United Kingdom as part of the Drink Wise, Age Well program.

Defining and modeling dynamic spatial heterogeneity within tumor microenvironments.

Many solid tumors exhibit significant genetic, cellular, and biophysical heterogeneity which dynamically evolves during disease progression and after treatment. This constant flux in cell composition, phenotype, spatial relationships, and tissue properties poses significant challenges in accurately diagnosing and treating patients. Much of the complexity lies in unraveling the molecular changes in different tumor compartments, how they influence one another in space and time and where vulnerabilities exist that might be appropriate to target therapeutically.

The Effectiveness of Preventative Interventions to Reduce Mental Health Problems in at-risk Children and Young People: A Systematic Review of Reviews.

Mental health problems are the leading cause of childhood disability worldwide, resulting in poor outcomes for children and young people that persist into adulthood. It is essential that those young people most at risk of developing mental health problems receive effective preventative interventions. Whilst there have been a number of systematic reviews which have examined the effectiveness of secondary prevention interventions for specific groups of children and young people, or to address identified mental health concerns, no review has engaged with the breadth of this literature.

Barriers to Accessing Primary Dental Care in Adults with Alcohol Dependence: A Qualitative Study.

Background: People with alcohol dependence (AD) frequently experience oral health problems, but their dental attendance is poor, with limited evidence to the reasons why from their perspective.

Objective: To explore perceived barriers, motivators, and facilitators to accessing primary dental care in people with AD.

Methods: Qualitative study consisting of remote one-to-one and group semistructured interviews with a convenience sample of adults with lived experience of AD in northern England.

Factors affecting primary care practitioners' alcohol-related discussions with older adults: a qualitative study.

Background: Risk of harm from drinking is heightened in later life, owing to age-related sensitivities to alcohol. Primary care services have a key role in supporting older people (aged ≥50 years) to make healthier decisions about alcohol.

Aim: To examine primary care practitioners' perceptions of factors that promote and challenge their work to support older people in alcohol risk-reduction.

Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies.

Despite the significant contributions of immunocompetent mouse models to the development and assessment of cancer immunotherapies, they inadequately represent the genetic and biological complexity of corresponding human cancers. Immunocompromised mice reconstituted with a human immune system (HIS) and engrafted with patient-derived tumor xenografts are a promising novel preclinical model for the study of human tumor-immune interactions. Whilst overcoming limitations of immunocompetent models, HIS-tumor models often rely on reconstitution with allogeneic immune cells, making it difficult to distinguish between anti-tumor and alloantigen responses.

Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy-induced cytokine release syndrome.

Objectives: Humanised mice have emerged as valuable models for pre-clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft--host disease (GvHD).

Managing older people's perceptions of alcohol-related risk: a qualitative exploration in Northern English primary care.

Background: Risk of harm from drinking increases with age as alcohol affects health conditions and medications that are common in later life. Different types of information and experiences affect older people's perceptions of alcohol's effects, which must be navigated when supporting healthier decisions on alcohol consumption.

Aim: To explore how older people understand the effects of alcohol on their health; and how these perspectives are navigated in supportive discussions in primary care to promote healthier alcohol use.

Extensive heterogeneity in somatic mutation and selection in the human bladder.

The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted ( = 1914 microbiopsies), whole-exome ( = 655), and whole-genome ( = 88) sequencing. We found widespread positive selection in 17 genes.

Health and social care providers' perspectives of older people's drinking: A systematic review and thematic synthesis of qualitative studies.

Background: alcohol may increase risks to late-life health, due to its impact on conditions or medication. Older adults must weigh up the potential risks of drinking against perceived benefits associated with positive roles of alcohol in their social lives. Health and social care workers are in a key position to support older people's decisions about their alcohol use.

Distinct microbial and immune niches of the human colon.

Gastrointestinal microbiota and immune cells interact closely and display regional specificity; however, little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterization of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady state. We describe distinct helper T cell activation and migration profiles along the colon and characterize the transcriptional adaptation trajectory of regulatory T cells between lymphoid tissue and colon.

Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology.

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors.

Drinking in later life: a systematic review and thematic synthesis of qualitative studies exploring older people's perceptions and experiences.

Background: alcohol presents risks to the health of older adults at levels that may have been 'safer' earlier in life. Moderate drinking is associated with some health benefits, and can play a positive role in older people's social lives. To support healthy ageing, we must understand older people's views with regards to their drinking.

In vitro hypoxic cytotoxicity of nitroimidazoles: uptake and cell cycle phase specificity.

The hypoxic cytotoxicity of four different 2-nitroimidazoles of similar electron affinities but different lipophilicities was compared using EMT6/Ro mouse mammary tumor cells in exponential growth phase in severely (less than 20 ppm) hypoxic conditions. The relative cytotoxicities were misonidazole (MISO) = desmethylmisonidazole (9963) greater than SR-2508 much greater than SR-2555 indicating that the compounds with the lowest lipophilicity were less cytotoxic. The rates of uptake of these compounds were MISO greater than 9963 greater than SR-2508 = SR-2555.

Cytotoxicity of hypoxic cell sensitizers in multicell spheroids.

Multicell tumor spheroids of EMT6/Ro cells were used to evaluate the cytotoxicity of several hypoxic cell sensitizers. The number of clonogenic cells per spheroid was determined after different exposure periods and concentrations of misonidazole, Ro-05-9963, and SR 2508 which have similar electron affinities. The kinetics of cytotoxicity were similar for each drug and the clonogenic fraction was reduced by about 0.

Evidence for the presence of secondary calcium phosphate in bone and its stabilization by acid production.

Calvaria from three 4-day-old chicks were incubated in a variety of buffers to study the parameters controlling the equilibration of bone with its supporting fluid environment. Strong inferential chemical evidence was obtained for the presence in viable bone of some calcium phosphate phase of high solubility apparently governed by the Ksp of CaHPO4-2H2O. In dead bone, this phase underwent spontaneous conversion to a higher Ca/P ratio.

Further studies on the nature of fluid compartmentalization in chick calvaria.

Labeled mannitol and polyethylene glycol (mol. wt. 4000), PEG, were used as space markers to estimate the fluid compartmentalization of calvaria taken from 3-5-day-old chicks.