SliceChip: a benchtop fluidic platform for organotypic culture and serial assessment of human and rodent pancreatic slices.

Enzymatically isolated pancreatic islets are the most commonly used ex vivo testbeds for diabetes research. Recently, precision-cut living slices of human pancreas are emerging as an exciting alternative because they maintain the complex architecture of the endocrine and exocrine tissues, and do not suffer from the mechanical and chemical stress of enzymatic isolation. We report a fluidic pancreatic SliceChip platform with dynamic environmental controls that generates a warm, oxygenated, and bubble-free fluidic pathway across singular immobilized slices with continuous deliver of fresh media and the ability to perform repeat serial perfusion assessments. A degasser ensures the system remains bubble-free while systemic pressurization with compressed oxygen ensures slice medium remains adequately oxygenated. Computational modeling of perfusion and oxygen dynamics within SliceChip guide the system's physiomimetic culture conditions. Maintenance of the physiological glucose dependent insulin secretion profile across repeat perfusion assessments of individual pancreatic slices kept under physiological oxygen levels demonstrated the culture capacity of our platform. Fluorescent images acquired every 4 hours of transgenic murine pancreatic slices were reliably stable and recoverable over a 5 day period due to the inclusion of a 3D-printed bioinert metallic anchor that maintained slice position within the SliceChip. Our slice on a chip platform has the potential to expand the useability of human pancreatic slices for diabetes pathogenesis and the development of new therapeutic approaches, while also enabling organotypic culture and assessment of other tissue slices such as brain and patient tumors.

Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Rehabilitation medicine in palliative care of chronic neurological conditions.

BACKGROUND: People living with long-term neurological conditions (LTNC) often require palliative care. Rehabilitation medicine specialists often coordinate the long-term care of these patients. OBJECTIVE: The aim of the present review was to undertake systematic literature searches to identify the evidence on palliative care for people with LTNC to guide rehabilitation medicine specialists caring for these patients in the UK. METHODS: We searched for evidence for (1) discussion of end of life, (2) planning for end-of-life care, (3) brief specialist palliative care interventions, (4) support for family and carers, (5) training of rehabilitation medicine specialists in palliative care, and (6) commissioning of services. The databases searched were MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database and Health Technology Assessment Database. Evidence was assimilated using a simplified version of the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We identified 2961 records through database searching for neurological conditions and 1261 additional records through database searches for specific symptoms. We removed duplicate records and conference presentations. We screened 3234 titles and identified 330 potentially relevant abstracts. After reading the abstracts we selected 34 studies for inclusion in the evidence synthesis. CONCLUSIONS: From the evidence reviewed we would like to recommend that we move forward by establishing a closer working relationship with specialists in palliative care and rehabilitation medicine and explore the implications for cross-specialty training.

Celiac disease screening in children and adolescents with type 1 diabetes mellitus: What test should be performed?

INTRODUCTION: Children and adolescents with type 1 diabetes mellitus (T1DM) are at high risk for the development of celiac disease (CD) because of the common genetic characteristics of both conditions. The study objectives were to investigate the frequency of the human leukocyte antigen system (HLA) for CD in pediatric T1DM patients and to determine whether HLA testing is suitable for CD screening in that population and is cost-effective as compared to serological screening for CD. PATIENTS AND METHODS: A retrospective, descriptive study was conducted in 296 patients (148 girls; 148 boys) with T1DM aged <18 years who attended a Madrid hospital. Data on the frequency of genotypes DQ2/DQ8 in a subgroup of 92 patients and the additional cost of performing HLA typing for screening CD were collected. Only when the risk HLA haplotype (DQ2/DQ8) is negative no further serological screening for CD is required. RESULTS: Twenty-three patients with T1DM (7.77%) also had CD. Alleles DQ2 or DQ8 were found in 91.3% of patients in whom the HLA haplotype was studied. Thus, only 8.7% with a negative haplotype would have benefited from HLA testing. The additional cost of HLA typing was € 105.2 for each patient with positive DQ2 or DQ8 in our population. CONCLUSIONS: HLA typing is not a cost-effective screening method for CD in T1DM because of the frequent association of T1DM with risk genotypes for CD.

The disparity between regulatory measurements of E. coli in public bathing waters and the public expectation of bathing water quality.

The main objectives of the European Union (EU) Bathing Water Directive (BWD) 2006/7/EC are to safeguard public health and protect designated aquatic environments from microbial pollution. The BWD is implemented through legislation by individual EU Member States and uses faecal indicator organisms (FIOs) as microbial pollution compliance parameters to determine season-end bathing water classifications (either 'Excellent', 'Good', 'Sufficient' or 'Poor'). These classifications are based on epidemiological studies that have linked human exposure to FIOs with the risk of contracting a gastrointestinal illness (GI). However, understanding public attitudes towards bathing water quality, together with perceptions of relative exposure risks, is often overlooked and yet critically important for informing environmental management decisions at the beach and ensuring effective risk communication. Therefore, this study aimed to determine the effectiveness of current regulatory strategies for informing beach users about bathing water quality, and to assess public understanding of the BWD classifications in terms of exposure risk and public health. Two UK designated bathing waters were selected as case studies, and questionnaires were deployed to beach-users. The bathing waters had different classification histories and both had electronic signage in operation for communicating daily water quality predictions. The majority of respondents did not recognise the standardised EU bathing water quality classification signs, and were unaware of information boards or the electronic signs predicting the water quality on that particular day. In general, respondents perceived the bathing water at their respective beach to be either 'good' or 'sufficient', which were also the lowest classifications of water quality they would be willing to accept for bathing. However, the lowest level of risk of contracting a gastrointestinal illness that respondents would be willing to accept suggested a significant misunderstanding of the BWD classification system, with the majority (91%) of respondents finding only a <1% risk level acceptable. The 'Good' classification is much less stringent in terms of likelihood of GI. This study has shown that the current public understanding of the BWD classifications in terms of exposure risk and public health is limited, and an investment in methods for disseminating information to the public is needed in order to allow beach-users to make more informed decisions about using bathing waters.