Contribution of Piezo2 to endothelium-dependent pain.

BackgroundWe evaluated the role of a mechanically-gated ion channel, Piezo2, in mechanical stimulation-induced enhancement of hyperalgesia produced by the pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell dependent. We also evaluated its role in a preclinical model of a vascular endothelial cell dependent painful peripheral neuropathy.ResultsThe local administration of oligodeoxynucleotides antisense to Piezo2 mRNA, at the site of nociceptive testing in the rat's hind paw, but not intrathecally at the central terminal of the nociceptor, prevented innocuous stimulus-induced enhancement of hyperalgesia produced by endothelin-1 (100 ng). The mechanical hyperalgesia induced by oxaliplatin (2 mg/kg. i.v.), which was inhibited by impairing endothelial cell function, was similarly attenuated by local injection of the Piezo2 antisense. Polymerase chain reaction analysis demonstrated for the first time the presence of Piezo2 mRNA in endothelial cells.ConclusionsThese results support the hypothesis that Piezo2 is a mechano-transducer in the endothelial cell where it contributes to stimulus-dependent hyperalgesia, and a model of chemotherapy-induced painful peripheral neuropathy

Hurricane Intensity, Sea Surface Temperature, and Stochastic Variation

Abstract not provide

Extended family caring for children orphaned by AIDS: balancing essential work and caregiving in a high HIV prevalence nations.

While over 90 per cent of the 15 million children who have been orphaned by HIV/AIDS are cared for by family members, there is little information about whether adults can meet orphans' essential caregiving needs while working to economically survive. Using a survey we conducted in Botswana of 1033 working adults, we analyse the experience of adults who are caring for orphans. Over one-third of working adults were caring for orphans and many with few financial resources: 82% were living on household incomes below US$10 purchasing power parity adjusted per person per day. Because of their caregiving responsibilities, they were less able to supplement income with overtime, weekend, evening, or night work. At the same time caregiving responsibilities meant orphan caregivers spent fewer hours caring for their own children and other family members. Nearly half of orphan caregivers had difficulties meeting their children's needs, and nearly 75% weren't able to meet with children's teachers. Pay loss at work compounded the problems: One-quarter of orphan caregivers reported having to take unpaid leave to meet sick childcare needs and nearly half reported being absent from work for children's routine health care. This paper makes clear that if families are to provide adequate care for orphans while economically surviving there needs to be increases in social supports and improvements in working conditions

Measuring Patient Experience During the Covid-19 Pandemic And Beyond

Traditional patient experience measures may not fully capture the changes quickly transpiring in patient care due to COVID-19. This paper presents a questionnaire that could be a helpful starting point. The questionnaire addresses topics such as telehealth and non-visit-based care; care by non-physicians; discussion about end-of-life preferences, domestic violence, social health needs; and primary care follow-up after acute carehttps://deepblue.lib.umich.edu/bitstream/2027.42/155624/1/Patient survey development_AFM submission.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155624/2/2019 CPC+ Beneficiary Survey (English).pdfDescription of Patient survey development_AFM submission.pdf : Main ArticleDescription of 2019 CPC+ Beneficiary Survey (English).pdf : Surve

Biomedical service - towards the 10th year anniversary

Version of RecordPublishe

Risks of Mortality and Morbidity from Worldwide Terrorism: 1968-2004

Worldwide data on terrorist incidents between 1968 and 2004 gathered by the RAND corporation and the Oklahoma City National Memorial Institute for the Prevention of Terrorism (MIPT) were assessed for patterns and trends in morbidity/mortality. Adjusted data analyzed involve a total of 19,828 events, 7,401 ''adverse'' events (each causing {ge}1 victim), and 86,568 ''casualties'' (injuries) of which 25,408 were fatal. Most terror-related adverse events, casualties and deaths involved bombs and guns. Weapon-specific patterns and terror-related risk levels in Israel (IS) have differed markedly from those of all other regions combined (OR). IS had a fatal fraction of casualties about half that of OR, but has experienced relatively constant lifetime terror-related casualty risks on the order of 0.5%--a level 2 to 3 orders of magnitude more than those experienced in OR that increased {approx}100-fold over the same period. Individual event fatality has increased steadily, the median increasing from 14 to 50%. Lorenz curves obtained indicate substantial dispersion among victim/event rates: about half of all victims were caused by the top 2.5% (or 10%) of harm-ranked events in OR (or IS). Extreme values of victim/event rates were approximated fairly well by generalized Pareto models (typically used to fit to data on forest fires, sea levels, earthquakes, etc.). These results were in turn used to forecast maximum OR- and IS-specific victims/event rates through 2080, illustrating empirically based methods that could be applied to improve strategies to assess, prevent and manage terror-related risks and consequences