Feasibility and acceptability of an acceptance and commitment therapy intervention for caregivers of adults with Alzheimer’s disease and related dementias

Background: Caregivers of patients with Alzheimer's disease or a related dementia (ADRD) report high levels of distress, including symptoms of anxiety and depression, caregiving burden, and existential suffering; however, those with support and healthy coping strategies have less stress and burden. Acceptance and Commitment Therapy (ACT) aims to foster greater acceptance of internal events while promoting actions aligned with personal values to increase psychological flexibility in the face of challenges. The objective of this single-arm pilot, Telephone Acceptance and Commitment Therapy Intervention for Caregivers (TACTICs), was to evaluate the feasibility, acceptability, and preliminary effects of an ACT intervention on ADRD caregiver anxiety, depressive symptoms, burden, caregiver suffering, and psychological flexibility. Methods: ADRD caregivers ≥21 years of age with a Generalized Anxiety Disorder Scale (GAD-7) score ≥ 10 indicative of moderate or higher symptoms of anxiety were enrolled (N = 15). Participants received a telephone-based ACT intervention delivered by a non-licensed, bachelor's-prepared trained interventionist over 6 weekly 1-h sessions that included engaging experiential exercises and metaphors designed to increase psychological flexibility. The following outcome measures were administered at baseline (T1), immediately post-intervention (T2), 3 months post-intervention (T3), and 6 months post-intervention (T4): anxiety symptoms (GAD-7; primary outcome); secondary outcomes of depressive symptoms (Patient Health Questionnaire-9), burden (Zarit Burden Interview), suffering (The Experience of Suffering measure), psychological flexibility/experiential avoidance (Acceptance and Action Questionnaire-II), and coping skills (Brief COPE). Results: All 15 participants completed the study and 93.3% rated their overall satisfaction with their TACTICs experience as "completely satisfied." At T2, caregivers showed large reduction in anxiety symptoms (SRM 1.42, 95% CI [0.87, 1.97], p < 0.001) that were maintained at T3 and T4. At T4, psychological suffering (SRM 0.99, 95% CI [0.41, 1.56], p = 0.0027) and caregiver burden (SRM 0.79, 95% CI [0.21, 1.37], p = 0.0113) also decreased. Conclusions: Despite a small sample size, the 6-session manualized TACTICs program was effective in reducing anxiety, suggesting that non-clinically trained staff may be able to provide an effective therapeutic intervention by phone to maximize intervention scalability and reach

Plant Cell-Based Intimin Vaccine Given Orally to Mice Primed with Intimin Reduces Time of \u3ci\u3eEscherichia coli\u3c/i\u3e O157:H7 Shedding in Feces

Intimin is the primary adhesin of Escherichia coli O157:H7, the most common infectious cause of bloody diarrhea in the United States and the leading cause of acute kidney failure in children who develop hemolytic uremic syndrome. Cattle are the primary reservoir of E. coli O157:H7. Indeed, most cases of E. coli O157:H7 infection in the United States occur after ingestion of contaminated undercooked hamburger or produce that had contact with bovine manure. Because intimin is required for persistent colonization of neonatal calves and adult cattle, we hypothesized that an intimin-based vaccination strategy in calves would reduce colonization of cattle with E. coli O157:H7. To test this concept in a small-animal model, we developed transgenic tobacco plant cells that express the carboxy-terminal host cell-binding domain of E. coli O157:H7 intimin. Mice were either immunized intraperitoneally with intimin expressed from the plant cells, fed transgenic plant cells, or both. Here we show that these mice generated an intimin-specific mucosal immune response when primed parenterally and then boosted orally and also exhibited a reduced duration of E. coli O157:H7 fecal shedding after challenge

Plant Cell-Based Intimin Vaccine Given Orally to Mice Primed with Intimin Reduces Time of Escherichia coli O157:H7 Shedding in Feces

Intimin is the primary adhesin of Escherichia coli O157:H7, the most common infectious cause of bloody diarrhea in the United States and the leading cause of acute kidney failure in children who develop hemolytic uremic syndrome. Cattle are the primary reservoir of E. coli O157:H7. Indeed, most cases of E. coli O157:H7 infection in the United States occur after ingestion of contaminated undercooked hamburger or produce that had contact with bovine manure. Because intimin is required for persistent colonization of neonatal calves and adult cattle, we hypothesized that an intimin-based vaccination strategy in calves would reduce colonization of cattle with E. coli O157:H7. To test this concept in a small-animal model, we developed transgenic tobacco plant cells that express the carboxy-terminal host cell-binding domain of E. coli O157:H7 intimin. Mice were either immunized intraperitoneally with intimin expressed from the plant cells, fed transgenic plant cells, or both. Here we show that these mice generated an intimin-specific mucosal immune response when primed parenterally and then boosted orally and also exhibited a reduced duration of E. coli O157:H7 fecal shedding after challenge

Distribution of mef(A) in Gram-Positive Bacteria from Healthy Portuguese Children

We screened 615 gram-positive isolates from 150 healthy children for the presence of the erm(A), erm(B), erm(C), erm(F), and mef(A) genes. The mef(A) genes were found in 20 (9%) of the macrolide-resistant isolates, including Enterococcus spp., Staphylococcus spp., and Streptococcus spp. Sixteen of the 19 gram-positive isolates tested carried the other seven open reading frames (ORFs) described in Tn1207.1, a genetic element carrying mef(A) recently described in Streptococcus pneumoniae. The three Staphylococcus spp. did not carry orf1 to orf3. A gram-negative Acinetobacter junii isolate also carried the other seven ORFs described in Tn1207.1. A Staphylococcus aureus isolate, a Streptococcus intermedius isolate, a Streptococcus sp. isolate, and an Enterococcus sp. isolate had their mef(A) genes completely sequenced and showed 100% identity at the DNA and amino acid levels with the mef(A) gene from S. pneumoniae

A power-based sliding window approach to evaluate the clinical impact of rare genetic variants in the nucleotide sequence or the spatial position of the folded protein

Summary: Systematic determination of novel variant pathogenicity remains a major challenge, even when there is an established association between a gene and phenotype. Here we present Power Window (PW), a sliding window technique that identifies the impactful regions of a gene using population-scale clinico-genomic datasets. By sizing analysis windows on the number of variant carriers, rather than the number of variants or nucleotides, statistical power is held constant, enabling the localization of clinical phenotypes and removal of unassociated gene regions. The windows can be built by sliding across either the nucleotide sequence of the gene (through 1D space) or the positions of the amino acids in the folded protein (through 3D space). Using a training set of 350k exomes from the UK Biobank (UKB), we developed PW models for well-established gene-disease associations and tested their accuracy in two independent cohorts (117k UKB exomes and 65k exomes sequenced at Helix in the Healthy Nevada Project, myGenetics, or In Our DNA SC studies). The significant models retained a median of 49% of the qualifying variant carriers in each gene (range 2%–98%), with quantitative traits showing a median effect size improvement of 66% compared with aggregating variants across the entire gene, and binary traits’ odds ratios improving by a median of 2.2-fold. PW showcases that electronic health record-based statistical analyses can accurately distinguish between novel coding variants in established genes that will have high phenotypic penetrance and those that will not, unlocking new potential for human genomics research, drug development, variant interpretation, and precision medicine

Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia

Background. Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods. Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results. All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9–20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions. The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts