Changes in Nursing Home Populations Challenge Practice and Policy.

U.S. nursing homes (NH) have a growing prevalence of individuals with severe mental illness (SMI) and substance use disorders (SUD), and an associated increasing proportion of people under 65. We explored how Directors of Nursing (DONs) perceive challenges and strategies in caring for these populations. We conducted semi-structured telephone interviews with 32 DONs from diverse facilities around the U.S. Participants reported that people with SUD and SMI often present behavioral challenges requiring resource intensive responses, while regulations constrain optimal medication treatment. Younger individuals are considered more demanding of staff and impatient with traditional NH activities designed for older people. Some NHs report they screen out people with behavioral health disorders; they tend to be concentrated in NHs in economically disadvantaged communities. Individuals may remain in NHs because suitable settings for discharge are unavailable. These developments constitute a back door "re-institutionalization" of people with behavioral health disorders, and a growing crisis.

Identification of epsilon toxin-producing Clostridium perfringens strains in American retail food.

Food samples (n = 216) from New York city were tested for the presence of C. perfringens via PCR for specific toxin genes. Thirty-four (16%) samples were positive for C. perfringens. Of these 34, 31 (91.2%) were type A or E, one (2.9%) was type B, and two (5.9%) were type D.

Implementing Montessori approaches after training: A mixed methods study to examine staff understanding and movement toward action.

Background: This paper uses Normalization Process Theory (NPT) to examine staff impressions of Montessori-based program training and implementation at Veterans Affairs Community Living Centers (VA CLCs; nursing homes). Methods: We conducted a mixed-methods evaluation of Montessori Approaches to Person-Centered Care (MAP-VA) at eight VA CLCs. Trainings were conducted as either a live virtual course or a pre-recorded asynchronous class. Two NPT constructs, coherence building and cognitive participation, informed qualitative interview questions, surveys, and analyses focused on staff movement from knowledge to action during initial implementation. Data collection included staff-completed standardized post-training exams (N = 906), post-training evaluations (N = 761), and optional validated surveys on perceptions of Montessori training (N = 307). Champions (peer-leaders) from each CLC completed semi-structured qualitative interviews post-training (N = 22). Findings: The majority of staff (83%-90%) passed all courses. Staff evaluated the training highly (80%+ agreement) on learning relevant new knowledge and confidence applying new skills. On average, staff felt MAP-VA would become a normal part of their work (7.68/10 scale), and reported increased familiarity with Montessori approaches after training (p = .002). Qualitative interview data from staff trained in Montessori supported three themes concordant with the NPT dimensions of coherence building and cognitive participation. (1) Coherence regarding Montessori: staff demonstrated an understanding of the program and mentioned the benefits of Montessori compared to their previous usual routines. Cognitive participation or engagement with Montessori: (2) staff had positive feelings about Montessori principles/applications and demonstrated a willingness to try the Montessori approach, and (3) staff made sense of the new intervention through early rehearsal of Montessori principles/practices and recognized opportunities for using Montessori in future interactions. Conclusions: Montessori virtual training resulted in high levels of coherence and cognitive participation among multidisciplinary staff, evidenced by high knowledge, self-efficacy, and readiness to act. The asynchronous and synchronous trainings were accessible, relevant, and supported diverse learners.

Clostridium perfringens Epsilon Toxin Binds to and Kills Primary Human Lymphocytes.

Clostridium perfringens epsilon toxin (ETX) is the third most lethal bacterial toxin and has been suggested to be an environmental trigger of multiple sclerosis, an immune-mediated disease of the human central nervous system. However, ETX cytotoxicity on primary human cells has not been investigated. In this article, we demonstrate that ETX preferentially binds to and kills human lymphocytes expressing increased levels of the myelin and lymphocyte protein MAL. Using flow cytometry, ETX binding was determined to be time and dose dependent and was highest for CD4+ cells, followed by CD8+ and then CD19+ cells. Similar results were seen with ETX-induced cytotoxicity. To determine if ETX preference for CD4+ cells was related to MAL expression, MAL gene expression was determined by RT-qPCR. CD4+ cells had the highest amount of Mal gene expression followed by CD8+ and CD19+ cells. These data indicate that primary human cells are susceptible to ETX and support the hypothesis that MAL is a main receptor for ETX. Interestingly, ETX bindings to human lymphocytes suggest that ETX may influence immune response in multiple sclerosis.

Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.

Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin-producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

A Novel Panel of Rabbit Monoclonal Antibodies and Their Diverse Applications Including Inhibition of Clostridium perfringens Epsilon Toxin Oligomerization.

The pore-forming epsilon toxin (ETX) produced by Clostridium perfringens is among the most lethal bacterial toxins known. Sensitive antibody-based reagents are needed to detect toxin, distinguish mechanisms of cell death, and prevent ETX toxicity. Using B-cell immuno-panning and cloning techniques, seven ETX-specific monoclonal antibodies were generated from immunized rabbits. ETX specificity and sensitivity were evaluated via western blot, ELISA, immunocytochemistry (ICC), and flow cytometry. ETX-neutralizing function was evaluated both in vitro and in vivo. All antibodies recognized both purified ETX and epsilon protoxin via western blot with two capable of detecting the ETX-oligomer complex. Four antibodies detected ETX via ELISA and three detected ETX bound to cells via ICC or flow cytometry. Several antibodies prevented ETX-induced cell death by either preventing ETX binding or by blocking ETX oligomerization. Antibodies that blocked ETX oligomerization inhibited ETX endocytosis and cellular vacuolation. Importantly, one of the oligomerization-blocking antibodies was able to protect against ETX-induced death post-ETX exposure in vitro and in vivo. Here we describe the production of a panel of rabbit monoclonal anti-ETX antibodies and their use in various biological assays. Antibodies possessing differential specificity to ETX in particular conformations will aid in the mechanistic studies of ETX cytotoxicity, while those with ETX-neutralizing function may be useful in preventing ETX-mediated mortality.