Design of a randomized superiority trial of a brief couple treatment for PTSD.

Interpersonal difficulties are common among veterans with posttraumatic stress disorder (PTSD) and are associated with poorer treatment response. Treatment outcomes for PTSD, including relationship functioning, improve when partners are included and engaged in the therapy process. Cognitive-behavioral conjoint therapy for PTSD (CBCT) is a manualized 15-session intervention designed for couples in which one partner has PTSD. CBCT was developed specifically to treat PTSD, engage a partner in treatment, and improve interpersonal functioning. However, recent research suggests that an abbreviated CBCT protocol may lead to sufficient gains in PTSD and relationship functioning, and yield lower dropout rates. Likewise, many veterans report a preference for receiving psychological treatments through clinical videoteleconferencing (CVT) rather than traditional face-to-face modalities that require travel to VA clinics. This manuscript describes the development and implementation of a novel randomized controlled trial (RCT) that examines the efficacy of an abbreviated 8-session version of CBCT ("brief CBCT," or B-CBCT), and compares the efficacy of this intervention delivered via CVT to traditional in-person platforms. Veterans and their partners were randomized to receive B-CBCT in a traditional Veterans Affairs office-based setting (B-CBCT-Office), CBCT through CVT with the veteran and partner at home (B-CBCT-Home), or an in office-delivered, couple-based psychoeducation control condition (PTSD Family Education). This study is the first RCT designed to investigate the delivery of B-CBCT specifically to veterans with PTSD and their partners, as well as to examine the delivery of B-CBCT over a CVT modality; findings could increase access to care to veterans with PTSD and their partners

Student wellness during curriculum implementation of a lifestyle medicine approach within the Social-Ecological Model: a longitudinal study

Purpose The student-life experience is an ideal time to implement lifelong wellness behaviors needed for the professional role. The ongoing effects of the COVID pandemic have amplified the need for Doctor of Physical Therapy (DPT) educational programs to train an emerging workforce that can, through personal wellness, withstand the stressors of personal and professional lives. The study purpose is to: a) evaluate the change in student wellness from matriculation to mid-program to completion after implementation of a curriculum based on a lifestyle medicine approach within the Social-Ecological Model, and b) compare student wellness between cohorts that matriculated before and during the COVID pandemic. Methods/Description We implemented curricular interventions to promote student wellness and professional formation in the fall of 2019. Students first study healthy behaviors for themselves, followed by learning experiences around the professional formation as a healthy clinician, and finally health promotion for patients and communities. We also modified program policies (e.g., holistic admissions, attendance, tutoring, faculty advising) to be student-centered. Three student cohorts in the DPT program at a Midwest academic medical center agreed to participate. Cohort19 (C19, n = 66) matriculated in 2019, Cohort20 (C20, n=66) in 2020, and Cohort21 (C21, n=64) in 2021. Participants completed the Five Factor Wellness Inventory (FFW) at matriculation into the 32-month program. C19 and C20 completed the FFW midway through the program as planned. Remaining assessments will occur as scheduled at program midpoint and completion. The FFW inventory is the gold standard for identifying central factors for healthy living. The wellness score is composed of 5 “Selfs” (Essential, Social, Creative, Physical, and Coping) made up of 17 domains where the acceptance of personal responsibility and choice have positive effects on well-being. A one-way ANOVA was used to compare FFW scores of all 3 cohorts at matriculation. Paired sample t-tests were used to compare results of C19 and C20 at mid-program and over time (matriculation and mid-program). Results/Outcomes The curriculum revisions and policy modifications were implemented in fall 2019. There were unexpected COVID-directed health measures beginning in March 2020 resulting in a move to more virtual activities that were not planned in our curriculum and new pressures related to student wellness. Three cohorts of DPT students (C19, C20, C21) completed the FFW at matriculation. Additionally, C19 and C20 completed the FFW at mid-program. The response rate for the FFW across all cohorts and time points was 100%. Comparison across cohorts: At matriculation, one of 17 FFW domain scores was found to be significantly different across cohorts. The score for the exercise domain (physical self) was significantly higher (p=.046) for C19 (pre-COVID) compared to C21. However, at mid-program for C19 and C20 (both during COVID), scores were significantly lower in C19 compared to C20 in five domains: culture (p=.004) and gender identification (p=.005) (essential self), nutrition (p=.037) (physical self), leisure (p=.020) and self-worth (p=.035) (coping self). Comparison over time: A comparison of FFW scores between matriculation and mid-program for C19 showed a significant increase in self-care scores (p\u3c.001 ) (essential self). For C20 scores significantly increased at mid-program in the coping self domains of leisure (p=.001) and stress management (p=.025), friendship (p=.018) (social self), and nutrition (p=.001) (physical self) leading to a significant improvement in overall FFW score (p=.037). Conclusions To optimally train a health workforce, faculty are studying methods to promote student wellness as part of student professional formation along with the curriculum for the PT of the future. Our study shows higher wellness scores in several domains in cohorts matriculating after COVID compared to before. This finding is interesting as it could indicate students entering professional school were potentially more prepared in terms of healthy behaviors due to the public health news surrounding COVID . Our study shows that components of student wellness may be improving due, in part , to the curriculum interventions and policies supporting wellness. These are important findings especially given the intended curriculum delivery was interrupted by directed health measures beginning in March 2020. The future direction is to continue to assess outcome measures through the end-of-program. In addition, we are analyzing additional measures of wellness such as psychological capital of hope, confidence, resilience and optimism, and social capital measuring connections with others for a sense of belonging. Our curriculum and supportive policies could be a model to demonstrate how student wellness can be aligned with a lifestyle medicine approach within the individual, relationship, community and society components of the Social-Ecological Model. REFERENCES Bezner JR. Promoting Health and Wellness: Implications for Physical Therapist Practice. Phys Ther. 2015; 95(10):1433-1444. Brooke, T., Brown, M., Orr, R., & Gough, S. (2020). Stress and burnout: exploring postgraduate physiotherapy students’ experiences and coping strategies. BMC Medical Education, 20(1), 1-11. Centers for Disease Control.Social Ecological Model. https://www.cdc.gov/violenceprevention/about/social-ecologicalmodel.html; Materials developed by Dahlberg LL, Krug EG. Violence: a global public health problem. In: Krug E, Dahlberg LL, Mercy JA, Zwi AB, Lozano R, eds. World Report on Violence and Health.Geneva, Switzerland: World Health Organization; 2002:1-21. Coffey DS, Eliot K, Goldblatt E, et al. A multifaceted systems approach to addressing stress within health professions education and beyond [discussion paper]. National Academy of Medicine website. https://nam.edu/wp-content/uploads/2017/01/Multifacted-Systems-Approach-to-Addressing-Stress-Within-Health-Professions-Education-and-Beyond.pdf Published January 30, 2017. Dean D. (2009) Physical therapy in the 21st century (Part II): Evidence-based practice within the context of evidence-informed practice, Physiotherapy Theory and Practice, 25:5-6, 354-368. Douris, P. C., D\u27Agostino, N. A., Mathew, S. K., Anderson, R. P., Bauman, K. M., Tiangtham, S. A., ... & Hall, C. A. (2020). The physiological and psychological effects of the first year of an entry-level physical therapist education program on students. Journal of Physical Therapy Education, 34(3), 186-191. Myers JE, Sweeny TJ. Five Factor Wellness Inventory. Mindgarden https://www.mindgarden.com/99-five-factor-wellness-inventory. Accessed 3.15.202

APOLIPOPROTEIN E (epsilon) genotype has a greater impact on apoB-48 than apoB-100 responses to dietary fat manipulation- insights from the SATgenε study

SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat (LF); high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Sf >400, Sf 60-400 and Sf 20-60) by specific ELISA. A genotype*meal/diet interaction for the Sf >400 fraction apoB-48 response (P400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident. CONCLUSION: Our study revealed marked effects of dietary fat composition on the Sf >400 apoB-48 response and particle TAG content in E4 carriers relative to the 'wild-type' E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis. This article is protected by copyright. All rights reserved

High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon

Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA(2mob), present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA(2mob) operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA(2mob) operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA(2mob) operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex-vivo cytokine production – insights from the SATgenε study

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgene study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgene participants (n = 52/88), prospectively recruited according to APOE genotype (n = 26 E3/E3 and n = 26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45 g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24 h with either 0.05 or 1 lg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-a and IL-10 production; TNF-a concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P < 0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P < 0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-a and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects

Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching

BACKGROUND: Acetylation of lysine residues in histone tails plays an important role in the regulation of gene transcription. Bromdomains are the readers of acetylated histone marks, and, consequently, bromodomain-containing proteins have a variety of chromatin-related functions. Moreover, they are increasingly being recognised as important mediators of a wide range of diseases. The first potent and selective bromodomain inhibitors are beginning to be described, but the diverse or unknown functions of bromodomain-containing proteins present challenges to systematically demonstrating cellular efficacy and selectivity for these inhibitors. Here we assess the viability of fluorescence recovery after photobleaching (FRAP) assays as a target agnostic method for the direct visualisation of an on-target effect of bromodomain inhibitors in living cells. RESULTS: Mutation of a conserved asparagine crucial for binding to acetylated lysines in the bromodomains of BRD3, BRD4 and TRIM24 all resulted in reduction of FRAP recovery times, indicating loss of or significantly reduced binding to acetylated chromatin, as did the addition of known inhibitors. Significant differences between wild type and bromodomain mutants for ATAD2, BAZ2A, BRD1, BRD7, GCN5L2, SMARCA2 and ZMYND11 required the addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) to amplify the binding contribution of the bromodomain. Under these conditions, known inhibitors decreased FRAP recovery times back to mutant control levels. Mutation of the bromodomain did not alter FRAP recovery times for full-length CREBBP, even in the presence of SAHA, indicating that other domains are primarily responsible for anchoring CREBBP to chromatin. However, FRAP assays with multimerised CREBBP bromodomains resulted in a good assay to assess the efficacy of bromodomain inhibitors to this target. The bromodomain and extraterminal protein inhibitor PFI-1 was inactive against other bromodomain targets, demonstrating the specificity of the method. CONCLUSIONS: Viable FRAP assays were established for 11 representative bromodomain-containing proteins that broadly cover the bromodomain phylogenetic tree. Addition of SAHA can overcome weak binding to chromatin, and the use of tandem bromodomain constructs can eliminate masking effects of other chromatin binding domains. Together, these results demonstrate that FRAP assays offer a potentially pan-bromodomain method for generating cell-based assays, allowing the testing of compounds with respect to cell permeability, on-target efficacy and selectivity

Draft Genome Sequences of Four Bacillus thermoamylovorans Strains Isolated from Milk and Acacia Gum, a Food Ingredient

The thermophilic bacterium Bacillus thermoamylovorans produces highly heat-resistant spores that can contaminate food products, leading to their spoilage. Here, we present the whole-genome sequences of four B. thermoamylovorans strains, isolated from milk and acacia gum

Calorimetric Investigation of Copper Binding in the N-Terminal Region of the Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event

Although the Cu²⁺-binding sites of the prion protein have been well studied when the protein is fully saturated by Cu²⁺, the Cu²⁺-loading mechanism is just beginning to come into view. Because the Cu²⁺-binding modes at low and intermediate Cu²⁺ occupancy necessarily represent the highest-affinity binding modes, these are very likely populated under physiological conditions, and it is thus essential to characterize them in order to understand better the biological function of copper–prion interactions. Besides binding-affinity data, almost no other thermodynamic parameters (e.g., Δ<i>H</i> and Δ<i>S</i>) have been measured, thus leaving undetermined the enthalpic and entropic factors that govern the free energy of Cu²⁺ binding to the prion protein. In this study, isothermal titration calorimetry (ITC) was used to quantify the thermodynamic parameters (<i>K</i>, Δ<i>G</i>, Δ<i>H</i>, and <i>T</i>Δ<i>S</i>) of Cu²⁺ binding to a peptide, PrP­(23–28, 57–98), that encompasses the majority of the residues implicated in Cu²⁺ binding by full-length PrP. Use of the buffer <i>N</i>-(2-acetomido)-aminoethanesulfonic acid (ACES), which is also a well-characterized Cu²⁺ chelator, allowed for the isolation of the two highest affinity binding events. Circular dichroism spectroscopy was used to characterize the different binding modes as a function of added Cu²⁺. The <i>K</i>_d values determined by ITC, 7 and 380 nM, are well in line with those reported by others. The first binding event benefits significantly from a positive entropy, whereas the second binding event is enthalpically driven. The thermodynamic values associated with Cu²⁺ binding by the Aβ peptide, which is implicated in Alzheimer’s disease, bear striking parallels to those found here for the prion protein

Draft Genome Sequences of 10 Bacillus subtilis Strains That Form Spores with High or Low Heat Resistance

Here, we report the draft genome sequences of 10 isolates of Bacillus subtilis, a spore forming Gram-positive bacterium. The strains were selected from food products and produced spores with either high or low heat resistance