Islet transplantation can provide insulin independence in patients with type 1 diabetes, but islets derived from two or more donors are often required. A significant fraction of the functional islet mass is lost to apoptosis in the immediate posttransplant period. The caspase inhibitor N-benzyloxycabonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-FMK) has been used therapeutically to prevent apoptosis in experimental animal models of ischemic injury, autoimmunity, and degenerative disease. In the current study, zVAD-FMK therapy was examined in a syngeneic islet transplant model to determine whether caspase inhibition could improve survival of transplanted islets. zVAD-FMK therapy significantly improved marginal islet mass function in renal subcapsular transplantation, where 90% of zVAD-FMK-treated mice became euglycemic with 250 islets, versus 27% of the control animals (P < 0.001). The benefit of zVAD-FMK therapy was further demonstrated after intraportal transplantation, where 75% of zVAD-FMK-treated animals established euglycemia with only 500 islets, and all of the controls remained severely diabetic (P < 0.001). zVAD-FMK pretreatment of isolated islets in the absence of systemic therapy resulted in no significant benefit compared with controls. Long-term follow-up of transplanted animals beyond 1 year posttransplant using glucose tolerance tests confirmed that a short course of zVAD-FMK therapy could prevent metabolic dysfunction of islet grafts over time. In addition, short-term zVAD-FMK treatment significantly reduced posttransplant apoptosis in islet grafts and resulted in preservation of graft insulin reserve over time. Our data suggest that caspase inhibitor therapy will reduce the islet mass required in clinical islet transplantation, perhaps to a level that would routinely allow for insulin independence after single-donor infusion. Diabetes 56:1289-1298, 2007 T he introduction of the Edmonton Protocol in 2000 led to substantial improvements in 1-year insulin independence rates in clinical islet transplantation (1,2). However, recent long-term follow-up indicates marked reduction in graft function, with only 15% of islet recipients maintaining insulin independence at 5 years (3). Although single-donor islet transplant success has been reported in Minnesota in a limited number of patients, most centers still require at least two donors (4,5). The decline in insulin independence rates seen in clinical islet transplantation is currently not fully characterized, but it is likely to be complex. Detrimental factors include recurrent ␤-cell autoimmunity, subclinical allograft rejection, metabolic exhaustion, chronic islet toxicity of immunosuppressive drugs, and limitations from the intraportal site of islet delivery (2). Strategies designed to maximize survival and minimize immune reactivity of the initial islet mass are likely to have a major impact in enhancing long-term clinical outcomes.A variety of approaches have been explored to prevent apoptotic destruction of islets in the experimental setting, and alth...

In nursing homes, aggression is seen in almost 32% of residents. Often, there are medical causes associated with delirium to account for such aggressive behaviors. This chapter discusses the incidence of and issues related to resident-to-staff and resident-to-resident aggression involving patients with major neurocognitive disorders in long-term care settings. Often such aggression results in physical injuries to staff. Resident-to-staff aggression most commonly occurs during direct caregiving. Resident-to-resident assault is not uncommon and has been categorized into 13 major subtypes. Use of physical restraint and pharmacological interventions in response to agitation and aggression in nursing homes carries liability due to risk of injury. The chapter also addresses sexuality of elderly nursing home residents, federal regulations mandating the allowance of expression of sexual needs of residents, and barriers that can impede expression of sexuality by residents. The chapter concludes with a discussion of elder-to-caregiver aggression in the community, including violent behavior toward family and caregivers employed by home healthcare agencies.

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Introduction Healthcare workers in long-term care settings and group homes for the disabled are at signi?cant risk of contracting COVID-19 and subsequently infecting the residents, fellow co-workers, and their family. In addition, lower paying long-term care healthcare workers maybe working multiple jobs which increases the risk of exposure. In April 2020, 27% of all deaths in the population was among residents in long-term care. The elderly population has the greatest risk for mortality from COVID-19 (Liu et al. 2020) and are disproportionality a?ected by social distance and self-isolation. Most long-term care settings have implemented lockdowns preventing families from visiting and limiting interactions among residents. Social isolation of the elderly is considered a serious public health concern. Social disconnection is a risk factor for increased depression and anxiety among the elderly. It is hypothesized that elderly persons are at high risk for poor mental health outcomes from the COVID-19 pandemic. The Alzheimer's Disease International suggest that those with dementia “may become more anxious, angry, stressed, agitated, and withdrawn during the outbreak”. These factors potentially may increase stress on healthcare workers in long-term care settings beyond the fears of exposure and transmitting COVID-19 to their families. There are few studies to date that examine the mental health impact of COVID-19 on healthcare workers in long-term care. The United Nations has highlighted the mental health risk to workers in long-term care. “First responders and front line workers, particularly workers in health and long-term care play a crucial role in ?ghting the outbreak and saving lives. However, they are under exceptional stress, being faced with extreme workloads, di?cult decisions, risks of becoming infected and spreading infection to families and communities, and witnessing deaths of patients.” Methods Healthcare workers in long-term care facilities, and assisted living facilities in Rhode Island were given questionnaires to complete that examined mental health and risk factors associated with COVID-19. The questionnaire includes items on the healthcare worker's experience with COVID-19. Resilience is measured using The Brief Resilience Scale assessing the individual's ability to bounce back or recover from stress. Subjective incompetence is de?ned as the perceived incapacity to perform tasks and express feelings deemed appropriate in a stressful situation. Increasing distress and subjective incompetence may convert a normal reaction to stress into mental disorder requiring intervention. Demoralization is measured using the Demoralization Scale-II. Depression and anxiety is measured using two of the most commonly used screens in clinical care, the PHQ-9 for depression and the GAD-7 for generalized anxiety. Family functioning during and before the COVID-19 pandemic is measured using the three-item Brief Assessment of Family Functioning. Social support is measured d...