Anxious arousal predicts within-person changes in hippocampal volume in adults with a history of childhood maltreatment: A CAN-BIND4 report.

Childhood maltreatment (CM) is a strong transdiagnostic risk factor for future psychopathology. This risk is theorized to emerge partly because of glucocorticoid-mediated atrophy in the hippocampus, which leaves this area sensitive to further volume loss even through adulthood in the face of future stress and the emergence of psychopathology. This proof-of-principle study examines which specific dimensions of internalizing psychopathology in the context of a CM history are associated with decreases in hippocampal volume over a 6-month period. This study included 80 community-recruited adults (ages 18-66 years, 61.3% women) oversampled for a lifetime history of internalizing psychopathology. At baseline and a naturalistic 6-month follow-up, the symptom dimensions of the tripartite model (anxious arousal, anhedonic depression, and general distress) were assessed by self-report. Hippocampal volume was derived through T1-weighted magnetic resonance imaging scanning segmented via the volBrain HIPS pipeline. CM severity was determined via a semistructured, contextual interview with independent ratings. We found that higher levels of anxious arousal predicted decreases in hippocampal volume over time in those with greater severity of CM but were associated at a trend with increases in hippocampal volume over time in those with lower severity of maltreatment. Findings were specific to anxious arousal and the CA1 subregion of the hippocampus. These novel results suggest that for individuals with a history of CM, transdiagnostic interventions that target and reduce psychological and physiological arousal may result in the preservation of hippocampal structure and, thus, improvements in cognitive and emotional regulation in the face of stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sexual, Physical, and Emotional Maltreatment in Childhood Are Differentially Associated With Sexual and Physical Revictimization in Adulthood.

Childhood maltreatment increases risk for sexual and physical revictimization in adulthood. The goal of the current study was to examine whether this risk is associated with specific maltreatment types (i.e., sexual vs. physical vs. emotional maltreatment vs. neglect) and perpetrators (i.e., mother vs. father). Participants included 720 adult women from North America and the United Kingdom, recruited through the online platform Prolific Academic. The severity of childhood maltreatment and adult physical and sexual victimization were assessed in two separate sessions through self-report questionnaires. All maltreatment types were modeled together to account for their co-occurrence. Greater severity of sexual maltreatment was significantly and independently associated with greater risk for sexual, physical, and sexual + physical revictimization. Further, in the full sample, risk of revictimization was predicted by greater severity of father-perpetrated emotional and physical maltreatment. In contrast, in subgroup analyses focusing on plurisexual (i.e., bi/pansexual) women, risk of revictimization was predicted by greater severity of mother-perpetrated emotional and physical maltreatment. These results suggest that girls with sexual and emotional maltreatment histories are at highest risk for revictimization. Future research identifying the biological, psychological, and social sequelae of these specific exposures may enable the development of specific intervention programs that have the potential for maximum efficacy in preventing further violence against women most at risk.

Demographics and Clinical Characteristics of Adult Patients Hospitalized due to COVID-19 in a Rural/Suburban Integrated Health System in Southcentral Pennsylvania, March Through May 2020.

Existing characterizations of coronavirus disease 2019 (COVID-19) admissions have occurred primarily in urban settings. This report describes demographic and clinical characteristics of the first COVID-19 patients presenting to a 6-hospital integrated health care system in rural/suburban southcentral Pennsylvania. Medical records of adult patients admitted with COVID-19 between March and May of 2020 were retrospectively reviewed for demographics, symptomatology, imaging, and lab values. Results were largely consistent with previous studies, although gastrointestinal manifestations were more prevalent, with diarrhea reported in 25.4% of patients hospitalized due to COVID-19. Nursing home patients represented 10.1% of admissions but accounted for 35.5% of total deaths in our sample. Patients self-identifying as Hispanic were disproportionately affected. Although Hispanic ethnicity was self-reported in only 9% of the community population, Hispanic patients accounted for 34% of admissions. Our data provide a unique focused review of hospitalized COVID-19 patients in a rural/suburban setting.

Staff Perceptions of Preimplementation Barriers and Facilitators to a Mobile Health Antiretroviral Therapy Adherence Counseling Intervention in South Africa: Qualitative Study.

BACKGROUND: South Africa adopted a universal test and treatment program for HIV infection in 2015. The standard of care that people living with HIV receive consists of 3 sessions of readiness counseling delivered by lay counselors (LCs). In the largest antiretroviral therapy (ART) program worldwide, effective and early HIV and ART education and support are key for ensuring ART adoption, adherence, and retention in care. Having LCs to deliver readiness counseling allows for the wide task-sharing of this critical activity but carries the risks of loss of standardization, incomplete content delivery, and inadequate monitoring and supervision. Systems for ensuring that a minimum standard of readiness counseling is delivered to the growing number of people living with HIV are essential in the care cascade. In resource-constrained, high-burden settings, mobile health (mHealth) apps may potentially offer solutions to these treatment gaps by providing content structure and delivery records. OBJECTIVE: This study aims to explore, at a large Cape Town-based nonprofit HIV care organization, the staff's perceived preimplementation barriers and facilitators of an mHealth intervention (Masivukeni) developed as a structured app for ART readiness counseling. METHODS: Masivukeni is a laptop-based app that incorporates written content, graphics, short video materials, and participant activities. In total, 20 participants were included in this study. To explore how an mHealth intervention might be adopted across different staff levels within the organization, we conducted 7 semistructured interviews (participants: 7/20, 35%) and 3 focus groups (participants in 2 focus groups: 4/20, 20%; participants in 1 focus group: 3/20, 15%) among LCs, supervisors, and their managers. In total, 20 participants were included in this study. Interviews lasted approximately 60 minutes, and focus groups ranged from 90 to 120 minutes. The Consolidated Framework for Implementation Research was used to explore the perceived implementation barriers and facilitators of the Masivukeni mHealth intervention. RESULTS: Several potential facilitators of Masivukeni were identified. Multimedia and visual elements were generally regarded as aids in content delivery. The interactive learning components were notably helpful, whereas facilitated updates to the adherence curriculum were important to facilitators and managers. The potential to capture administrative information regarding LC delivery and client logging was regarded as an attractive feature. Barriers to implementation included security risks and equipment costs, the high volume of clients to be counseled, and variable computer literacy among LCs. There was uncertainty about the app's appeal to older clients. CONCLUSIONS: mHealth apps, such as Masivukeni, were perceived as being well placed to address some of the needs of those who deliver ART adherence counseling in South Africa. However, the successful implementation of mHealth apps appeared to be dependent on overcoming certain barriers in this setting.

The effectiveness of a group-based computerized HIV/STI prevention intervention for black women who use drugs in the criminal justice system: study protocol for E-WORTH (Empowering African-American Women on the Road to Health), a Hybrid Type 1 randomized controlled trial.

BACKGROUND: This paper describes the study protocol of a hybrid type I randomized controlled trial that evaluates the effectiveness and cost-effectiveness of implementing Empowering African-American Women on the Road to Health (E-WORTH), an Afrocentric, group-based, computerized human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention intervention for controlled substance-using black women in community corrections settings in New York City. METHODS/DESIGN: We provide an overview of E-WORTH's hybrid type I design, which is guided by the Consolidated Framework for Implementation Research (CFIR). E-WORTH combines HIV/STI and intimate partner violence (IPV) prevention components and tests the comparative effectiveness of E-WORTH and streamlined HIV testing versus streamlined HIV testing alone in decreasing biologically confirmed HIV and STI incidence, sexual risk, and IPV, as well as in improving access to HIV and STI prevention services and care. DISCUSSION: This paper provides an overview of E-WORTH's intervention protocol and serves as a framework for using hybrid type I designs, guided by the CFIR conceptual framework, to evaluate HIV/STI and IPV prevention interventions in community corrections settings. We discuss how E-WORTH's hybrid type I design advances implementation science through its effectiveness and cost-effectiveness aims as well as through a mixed-methods study that evaluates multilevel theory-driven factors (structural, organizational, staffing, and client) guided by the CFIR that influences the implementation of E-WORTH in a criminal justice setting. This study also addresses the novel challenges and opportunities of implementing an intervention that targets specific racial subgroup(s) in a community corrections setting that services all populations, implementing a group-based intervention with technological components in such settings, and employing community-based participatory research strategies to guide recruitment and retention efforts. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02391233 . Registered on 17 March 2015.

Efficacy of a Computerized Intervention on HIV and Intimate Partner Violence Among Substance-Using Women in Community Corrections: A Randomized Controlled Trial.

OBJECTIVES: To test the efficacy of a computerized, group-based HIV and intimate partner violence (IPV) intervention on reducing IPV victimization among substance-using women mandated to community corrections. METHODS: Between November 2009 and January 2012, we randomly allocated 306 women from community corrections in New York City to 3 study arms of a computerized HIV and IPV prevention trial: (1) 4 group sessions intervention with computerized self-paced IPV prevention modules (Computerized Women on the Road to Health [WORTH]), (2) traditional HIV and IPV prevention intervention group covering the same HIV and IPV content as Computerized WORTH without computers (Traditional WORTH), and (3) a Wellness Promotion control group. Primary outcomes were physical, injurious, and sexual IPV victimization in the previous 6 months at 12-month follow-up. RESULTS: Computerized WORTH participants reported significantly lower risk of physical IPV victimization, severe injurious IPV victimization, and severe sexual IPV victimization at 12-month follow-up when compared with control participants. No significant differences were seen between Traditional WORTH and control participants for any IPV outcomes. CONCLUSIONS: The efficacy of Computerized WORTH across multiple IPV outcomes highlights the promise of integrating computerized, self-paced IPV prevention modules in HIV prevention groups.

Project WINGS (Women Initiating New Goals of Safety): A randomised controlled trial of a screening, brief intervention and referral to treatment (SBIRT) service to identify and address intimate partner violence victimisation among substance-using women receiving community supervision.

BACKGROUND: The high rate of intimate partner violence (IPV) victimisation found among substance-using women receiving community supervision underscores the need for effective IPV victimisation screening, brief intervention and referral to treatment services (SBIRT) for this population. AIMS: This randomised controlled trial (RCT) aims to assess the feasibility, safety and efficacy of a single-session computerised self-paced IPV SBIRT (Computerised WINGS) in identifying IPV victimisation among women under community supervision and increasing access to IPV services, compared to the same IPV SBIRT service delivered by a case manager (Case Manager WINGS). METHODS: This RCT was conducted with 191 substance-using women in probation and community court sites in New York City. RESULTS: No significant differences were found between Computerised and Case Manager WINGS arms on any outcomes. Both arms reported identical high rates of any physical, sexual or psychological IPV victimisation in the past year (77% for both arms) during the intervention. Both arms experienced significant increases from baseline to the 3-month follow-up in receipt of IPV services, social support, IPV self-efficacy and abstinence from drug use. CONCLUSIONS: Findings suggest that both modalities of WINGS show promise in identifying and addressing IPV victimisation among substance-using women receiving community supervision.

Enhancing Lay Counselor Capacity to Improve Patient Outcomes with Multimedia Technology.

Multimedia technologies offer powerful tools to increase capacity of health workers to deliver standardized, effective, and engaging antiretroviral medication adherence counseling. Masivukeni-is an innovative multimedia-based, computer-driven, lay counselor-delivered intervention designed to help people living with HIV in resource-limited settings achieve optimal adherence. This pilot study examined medication adherence and key psychosocial outcomes among 55 non-adherent South African HIV+ patients, on antiretroviral therapy (ART) for at least 6 months, who were randomized to receive either Masivukeni or standard of care (SOC) counseling for ART non-adherence. At baseline, there were no significant differences between the SOC and Masivukeni groups on any outcome variables. At post-intervention (approximately 5-6 weeks after baseline), -clinic-based pill count adherence data available for 20 participants (10 per intervention arm) showed a 10 % improvement for-participants and a decrease of 8 % for SOC participants. Masivukeni participants reported significantly more positive attitudes towards disclosure and medication social support, less social rejection, and better clinic-patient relationships than did SOC participants. Masivukeni shows promise to promote optimal adherence and provides preliminary evidence that multimedia, computer-based technology can help lay counselors offer better adherence counseling than standard approaches.

Efficacy of a group-based multimedia HIV prevention intervention for drug-involved women under community supervision: project WORTH.

IMPORTANCE: This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision. OBJECTIVE: We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to Health) among drug-involved women under community supervision. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention (traditional WORTH); (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH. MAIN OUTCOMES AND MEASURES: Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners. RESULTS: Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts (ß = 0.10; 95% CI = 0.02-0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI = 0.57-0.90). CONCLUSION AND RELEVANCE: The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system. TRIAL REGISTRATION: ClinicalTrials.gov NCT01784809.

Implementation of a couple-based HIV prevention program: a cluster randomized trial comparing manual versus Web-based approaches.

BACKGROUND: Despite great need, the number of HIV prevention implementation studies remains limited. The challenge for researchers, in this time of limited HIV services agency resources, is to conceptualize and test how to disseminate efficacious, practical, and sustainable prevention programs more rapidly, and to understand how to do so in the absence of additional agency resources. We tested whether training and technical assistance (TA) in a couple-based HIV prevention program using a Web-based modality would yield greater program adoption of the program compared to training and TA in the same program in a manual-based modality among facilitators who delivered the interventions at 80 agencies in New York State. METHODS: This study used a cluster randomized controlled design. Participants were HIV services agencies (N = 80) and up to 6 staff members at each agency (N = 253). Agencies were recruited, matched on key variables, and randomly assigned to two conditions. Staff members participated in a four-day, face-to-face training session, followed by TA calls at two and four months, and follow-up assessments at 6, 12, and 18 months post- training and TA. The primary outcomes examined number of couples with whom staff implemented the program, mean number of sessions implemented, whether staff implemented at least one session or whether staff implemented a complete intervention (all six sessions) of the program. Outcomes were measured at both the agency and participant level. RESULTS: Over 18 months following training and TA, at least one participant from 13 (33%) Web-based assigned agencies and 19 (48%) traditional agencies reported program use. Longitudinal multilevel analysis found no differences between groups on any outcomes at the agency or participant level with one exception: Web-based agencies implemented the program with 35% fewer couples compared with staff at manual-based agencies (IRR 0.35, CI, 0.13-0.94). CONCLUSION: Greater implementation of a Web-based program may require more resources and staff exposure, especially when paired with a couple-based modality. Manual-based and traditional programs may hold some advantage or ease for implementation, particularly at a time of low economic resources. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01863537.

Masivukeni: development of a multimedia based antiretroviral therapy adherence intervention for counselors and patients in South Africa.

Effective medical treatment for HIV/AIDS requires patients' optimal adherence to antiretroviral therapy (ART). In resource-constrained settings, lack of adequate standardized counseling for patients on ART remains a significant barrier to adherence. Masivukeni ("Let's Wake Up" in Xhosa) is an innovative multimedia-based intervention designed to help people living with HIV in resource-limited settings achieve and maintain high levels of ART adherence. Adapted from a couples-based intervention tested in the United States (US), Masivukeni was developed through community-based participatory research with US and South African partners and informed by Ewart's Social Action Theory. Innovative computer-based multimedia strategies were used to translate a labor- and training-intensive intervention into one that could be readily and widely used by lay counselors with relatively little training with low-literacy patients. In this paper, we describe the foundations of this new intervention, the process of its development, and the evidence of its high acceptability and feasibility.

Identification of Ni-(L-His)2 as a substrate for NikABCDE-dependent nickel uptake in Escherichia coli.

Nickel is an important cofactor for several microbial enzymes. The ATP-dependent NikABCDE transporter is one of several types of uptake pathways known to be important for nickel acquisition in microbes. The Escherichia coli NikA periplasmic binding protein is structurally homologous to the di- and oligopeptide binding proteins, DppA and OppA. This structural similarity raises interesting questions regarding the evolutionary relationships between the recognition of nickel ions and short peptides. We find that in defined minimal growth medium NikABCDE transports nickel ions in the presence of exogenously added L-histidine (L-His), but not D-histidine. Both nickel uptake in cells and nickel binding to purified NikA showed an L-His concentration dependence consistent with recognition of a Ni-(L-His)2 complex. This discovery reveals parallels to the transport of other metal complexes, notably iron, and suggests the structural diversity of nickel transporters may arise from the need to recognize extracellular nickel complexed with different organic ligands, whether they be exogenously or endogenously produced. Further, these results suggest that experiments examining the physiology and ecology of nickel-requiring microbes should account for the possibility that the growth medium may not support nickel uptake.

Guiding epithelial cell phenotypes with engineered integrin-specific recombinant fibronectin fragments.

The extracellular matrix (ECM) provides important cues for directing cell phenotype. Cells interact with underlying ECM through cell-surface receptors known as integrins, which bind to specific sequences on their ligands. During tissue development, repair, and regeneration of epithelial tissues, cells must interact with an interstitial fibronectin (Fn)-rich matrix, which has been shown to direct a more migratory/repair phenotype, presumably through interaction with Fn's cell binding domain comprised of both synergy Pro-His-Ser-Arg-Asn (PHSRN) and Arg-Gly-Asp (RGD) sequences. We hypothesized that the Fn synergy site is critical to the regulation of epithelial cell phenotype by directing integrin specificity. Epithelial cells were cultured on Fn fragments displaying stabilized synergy and RGD (FnIII9'10), or RGD alone (FnIII10) and cell phenotype analyzed by cytoskeleton changes, epithelial cell-cell contacts, changes in gene expression of epithelial and mesenchymal markers, and wound healing assay. Data indicate that epithelial cells engage RGD only with αv integrins and display a significant shift toward a mesenchymal phenotype due, in part, to enhanced transforming growth factor-ß activation and/or signaling compared with cells on the synergy containing FnIII9'10. These studies demonstrate the importance of synergy in regulating epithelial cell phenotype relevant to tissue engineering as well as the utility of engineered integrin-specific ECM fragments in guiding cell phenotype.

Nickel-specific response in the transcriptional regulator, Escherichia coli NikR.

Studies of the transcriptional repression of the Ni-specific permease encoded by the Pnik operon by Escherichia coli NikR using a LacZ reporter assay establish that the NikR response is specific to nickel in vivo. Toward understanding this metal ion-specific response, X-ray absorption spectroscopy (XAS) analysis of various M-NikR complexes (M = Co(II), Ni(II), Cu(II), Cu(I), and Zn(II)) was used to show that each high-affinity binding site metal adopts a unique structure, with Ni(II) and Cu(II) being the only two metal ions to feature planar four-coordinate complexes. The results are consistent with an allosteric mechanism whereby the geometry and ligand selection of the metal present in the high-affinity site induce a unique conformation in NikR that subsequently influences DNA binding. The influence of the high-affinity metal on protein structure was examined using hydrogen/deuterium (H/D) exchange detected by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). Each NikR complex gives rise to differing amounts of H/D exchange; Zn(II)- and Co(II)-NikR are most like apo-NikR, while the exchange time course is substantially different for Ni(II) and to a lesser extent for Cu(II). In addition to the high-affinity metal binding site, E. coli NikR has a low-affinity metal-binding site that affects DNA binding affinity. We have characterized this low-affinity site using XAS in heterobimetallic complexes of NikR. When Cu(II) occupies the high-affinity site and Ni(II) occupies the low-affinity site, the Ni K-edge XAS spectra show that the Ni site is composed of six N/O-donors. A similar low-affinity site structure is found for the NikR complex when Co(II) occupies the low-affinity site and Ni(II) occupies the high-affinity site, except that one of the Co(II) ligands is a chloride derived from the buffer.

Nickel homeostasis in Escherichia coli - the rcnR-rcnA efflux pathway and its linkage to NikR function.

The nickel physiology of Escherichia coli is dominated by its Ni-Fe hydrogenase isozymes, which are expressed under anaerobic growth conditions. Hydrogenase activity in E. coli requires the NikABCDE nickel transporter, which is transcriptionally repressed by NikR in the presence of excess nickel. Recently, a nickel and cobalt-efflux protein, RcnA, was identified in E. coli. This study examines the effect of RcnA on nickel homeostasis in E. coli. Under nickel-limiting conditions, deletion of rcnA increased NikR activity in vivo. Nickel and cobalt-dependent regulation of rcnA expression required the newly identified transcriptional repressor RcnR (formerly YohL). Deletion of rcnR results in constitutive rcnA expression and a corresponding decrease in NikR activity. Purified RcnR binds directly to the rcnA promoter DNA fragment and this interaction is inhibited by nickel and cobalt. Nickel accumulation is affected differently among deletion strains with impaired nickel homeostasis. Surprisingly, in low nickel growth conditions rcnA expression is required for nickel import via NikABCDE. The data support a model with two distinct pools of nickel ions in E. coli. NikR bridges these two pools by controlling the levels of the hydrogenase-associated pool based on the nickel levels in the second pool.

Complex transcriptional control links NikABCDE-dependent nickel transport with hydrogenase expression in Escherichia coli.

Escherichia coli requires nickel under anaerobic growth conditions for the synthesis of catalytically active NiFe hydrogenases. Transcription of the NikABCDE nickel transporter, which is required for NiFe hydrogenase synthesis, was previously shown to be upregulated by FNR (fumarate-nit rate regulator) in the absence of oxygen and repressed by the NikR repressor in the presence of high extracellular nickel levels. We present here a detailed analysis of nikABCDE transcriptional regulation and show that it closely correlates with hydrogenase expression levels. We identify a nitrate-dependent mechanism for nikABCDE repression that is linked to the NarLX two-component system. NikR is functional under all nickel conditions tested, but its activity is modulated by the total nickel concentration present as well as by one or more components of the hydrogenase assembly pathway. Unexpectedly, NikR function is independent of NikABCDE function, suggesting that NikABCDE is a hydrogenase-specific nickel transporter, consistent with its original identification as a hydrogenase (hyd) mutant. Further, the results suggest that the hydrogenase assembly pathway is sequestered within the cell. A second nickel import pathway in E. coli is implicated in NikR function.