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This qualitative study explores the resilience of a community of 108 English-speaking immigrants in Israel facing the stress of the COVID-19 pandemic. It features the social constructivist approach to resilience as a negotiation of adversities using coping strategies understood within the framework of control, coherence, and connectedness. We discuss data in an articulated perspective of themes comprised of language barriers, transnationality, and the us/them divide, which constitute a common thread in the negotiation of resilience. The pathways to resilience, geared to help individuals in the meaning-making process, build distress tolerance, increase social support, embrace a view of a deep human interconnectedness, and take goal-directed value-driven actions, constituting a basis for interventions. Counseling practice should offer English-speaking immigrants to Israel specific resources that encourage acceptance-based coping, culturally relevant practices of mindfulness, as well as tools that promote social interactions and build resilience by cultivating positive emotions and social connection.

Transgender women are among the populations at highest risk for HIV in the USA and have elevated risk for intimate partner violence (IPV). There is an urgent need for integrated HIV-IPV prevention interventions for transgender women. Using qualitative methods, we explored transgender women's lived experiences of IPV and the relationship between IPV and HIV risk. Using thematic analysis, we identified four key concepts that warrant inclusion in the development of models for IPV and HIV interventions: (1) considering the boundaries of IPV; (2) normalising expectations of chronic violence; (3) relationship safety; (4) calls for trans-affirming and empowering services.

OBJECTIVE The primary objective of this hybrid I clinical trial of Date SMART (Date Skills to Manage Aggression in Relationships for Teens) was to reduce adolescent dating violence (ADV) among juvenile-justice involved females over 1 year. Secondary objectives were to determine if the intervention reduced sexual risk behavior and delinquency. Last, we evaluate system buy-in vis à vis mandated referrals to the program. METHODS Participants were females, ages 14 to 18 (N = 240), involved in a family court in the Northeast United States. The Date SMART group intervention consisted of cognitive-behavioral skill building, and the knowledge-only comparison group consisted of psychoeducation regarding sexual health, ADV, mental health and substance use. RESULTS Court mandates to intervention were common (41%). Among those with ADV exposure, Date SMART participants reported fewer acts of physical and/or sexual ADV (rate ratio, 0.57; 95% confidence interval [CI], 0.33–0.99) and cyber ADV (rate ratio, 0.75; 95% CI, 0.58–0.96) at follow-up, relative to control. There were significant reductions in the number of vaginal and/or anal sex acts reported by Date SMART participants relative to control (rate ratio, 0.81; 95% CI 0.74–0.89). In the overall sample, within group reductions in some ADV behaviors and delinquency were observed in both conditions. CONCLUSIONS Date SMART was seamlessly integrated into the family court setting and received stakeholder buy-in. Although not superior to control as a primary prevention tool, Date SMART was effective in reducing physical and/or sexual ADV, and cyber ADV, as well as vaginal and/or anal sex acts, among females with ADV exposure over 1 year.

The developmental period of late adolescence/young adulthood is characterized by transitioning to an independent individual with a self-identity, established health habits and the components of resilience: (1) confidence in one’s abilities (personal competence) and (2) the ability to adapt to changes (acceptance of self and life). This two-wave, prospective study examines the associations among self-identity, health habits and resilience in 18 year olds (n = 149) before military service and six months afterward. The questionnaire included validated scales of resilience and self-identity, as well as instruments measuring health habits, family environment and demographic characteristics. Cross-sectional findings indicated that resilience at baseline was associated with gender-male (p

Individuals with Panic Disorder (PD) often have impaired insight, which can impede their willingness to seek treatment. Cognitive processes, including metacognitive beliefs, cognitive flexibility, and jumping to conclusions (JTC) may influence the degree of insight. By understanding the relationship between insight and these cognitive factors in PD, we can better identify individuals with such vulnerabilities to improve their insight. The aim of this study is to examine the relationships between metacognition, cognitive flexibility, and JTC with clinical and cognitive insight at pretreatment. We investigate the association among those factors changes and changes in insight over treatment. Eighty-three patients diagnosed with PD received internet-based cognitive behavior therapy. Analyses revealed that metacognition was related to both clinical and cognitive insight, and cognitive flexibility was related to clinical insight at pre-treatment. Greater changes in metacognition were correlated with greater changes in clinical insight. Also, greater changes in cognitive flexibility were related to greater changes in cognitive insight. The current study extends previous studies suggesting potential relationships among insight, metacognition, and cognitive flexibility in PD. Determining the role of cognitive concepts in relation to insight may lead to new avenues for improving insight and can have implications for engagement and treatment-seeking behaviors. Funding Agencies|Israel National Institute for Health Policy Research [2015/181]

We consider entanglement-assisted communication over the qubit depolarizing channel under the security requirement of covert communication, where not only the information is kept secret, but the transmission itself must be concealed from detection by an adversary. Previous work showed that $O(\sqrt{n})$ information bits can be reliably and covertly transmitted in $n$ channel uses without entanglement assistance. However, Gagatsos et al. (2020) showed that entanglement assistance can increase this scaling to $O(\sqrt{n}\log(n))$ for continuous-variable bosonic channels. Here, we present a finite-dimensional parallel, and show that $O(\sqrt{n}\log(n))$ covert bits can be transmitted reliably over $n$ uses of a qubit depolarizing channel.

Virus assembly and disassembly are critical steps in the virus lifecycle; however, virus disassembly is much less well understood than assembly. For hepatitis B virus (HBV) capsids, disassembly of the virus capsid in the presence of guanidine hydrochloride (GuHCl) exhibits strong hysteresis that requires additional chemical energy to initiate disassembly and disrupt the capsid structure. To study disassembly of HBV capsids, we mixed T = 4 HBV capsids with 1.0 to 3.0 M GuHCl, monitored the reaction over time by randomly selecting particles, and measured their size with resistive-pulse sensing. Particles were cycled forward and backward multiple times to increase the observation time and likelihood of observing a disassembly event. The four-pore device used for resistive-pulse sensing produces four current pulses for each particle during translocation that improves tracking and identification of single particles and increases the precision of the particle-size measurements when the pulses are averaged. We studied disassembly at GuHCl concentrations below and above denaturing conditions of the dimer, the fundamental unit of HBV capsid assembly. As expected, capsids showed little disassembly at low GuHCl concentrations (e.g., 1.0 M GuHCl), whereas at higher GuHCl concentrations (≥ 1.5 M), capsids exhibited disassembly, sometimes as a complex series of events. In all cases, disassembly was an accelerating process, where capsids catastrophically disassembled within a few 100 ms of reaching critical stability; disassembly rates reached tens of dimers per second just before capsids fell apart. Some disassembly events exhibited metastable intermediates that appeared to lose one or more trimers of dimers in a stepwise fashion.

Acute mesenteric ischemia (AMI) is a medical condition with high levels of morbidity and mortality. However, most patients suspected of AMI will eventually have a different diagnosis. Nevertheless, these patients have a high risk for co-morbidities.To analyze patients with suspected AMI with an alternative final diagnosis, and to evaluate a machine learning algorithm for prognosis prediction in this population.In a retrospective search, we retrieved patient charts of those who underwent computed tomography angiography (CTA) for suspected AMI between January 2012 and December 2015. Non-AMI patients were defined as patients with negative CTA and a final clinical diagnosis other than AMI. Correlation of past medical history, laboratory values, and mortality rates were evaluated. We evaluated gradient boosting (XGBoost) model for mortality prediction.The non-AMI group comprised 325 patients. The two most common groups of diseases included gastrointestinal (33%) and biliary-pancreatic diseases (27%). Mortality rate was 24.6% for the entire cohort. Medical history of chronic kidney disease (CKD) had higher risk for mortality (odds ratio 2.2). Laboratory studies revealed that lactate dehydrogenase (LDH) had the highest diagnostic ability for predicting mortality in the entire cohort (AUC 0.70). The gradient boosting model showed an area under the curve of 0.82 for predicting mortality.Patients with suspected AMI with an alternative final diagnosis showed a 25% mortality rate. A past medical history of CKD and elevated LDH were associated with increased mortality. Non-linear machine learning algorithms can augment single variable inputs for predicting mortality.

Description, Single-molecule fluorescence optical tweezers studies combined with high-speed AFM reveal early events in the HBV life cycle., Self-assembly of supramolecular complexes such as viral capsids occurs prominently in nature. Nonetheless, the mechanisms underlying these processes remain poorly understood. Here, we uncover the assembly pathway of hepatitis B virus (HBV), applying fluorescence optical tweezers and high-speed atomic force microscopy. This allows tracking the assembly process in real time with single-molecule resolution. Our results identify a specific, contact-rich pentameric arrangement of HBV capsid proteins as a key on-path assembly intermediate and reveal the energy balance of the self-assembly process. Real-time nucleic acid packaging experiments show that a free energy change of ~1.4 kBT per condensed nucleotide is used to drive protein oligomerization. The finding that HBV assembly occurs via contact-rich energy minima has implications for our understanding of the assembly of HBV and other viruses and also for the development of new antiviral strategies and the rational design of self-assembling nanomaterials.

Community mental health centers (CMHCs) provide the majority of mental health services for low-income individuals in the United States. Exposure and response prevention (ERP), the psychotherapy of choice for obsessive-compulsive disorder (OCD), is rarely delivered in CMHCs. This study aimed to establish the acceptability and feasibility of testing a behavioral therapy team (BTT) intervention to deliver ERP in CMHCs. BTT consisted of individual information-gathering sessions followed by 12 weeks of group ERP and concurrent home-based coaching sessions. The sample consisted of 47 low-income individuals with OCD who were randomized to receive BTT or treatment as usual (TAU). Symptom severity and quality-of-life measures were assessed at pretreatment, posttreatment, and 3- and 6-month posttreatment. Feasibility of training CMHC staff was partially successful. CMHC therapists successfully completed rigorous training and delivered ERP with high fidelity. However, training paraprofessionals as ERP coaches was more challenging. ERP was feasible and acceptable to patients. BTT participants were more likely than TAU participants to attend their first therapy session and attended significantly more treatment sessions. A large between-group effect size was observed for reduction in OCD symptoms at posttreatment but differences were not maintained across 3- and 6-month follow-ups. For BTT participants, within-group effect sizes reflecting change from baseline to posttreatment were large. For TAU participants, depression scores did not change during the active treatment phase but gradually improved during follow-up. Results support feasibility and acceptability of ERP for this patient population. Findings also underscore the importance of implementation frameworks to help understand factors that impact training professionals.

Objective: This study examined whether personal characteristics of consumers with serious mental illness (SMI), including being an immigrant, explained the lack of concordance in quality-of-life (QOL) ratings reported by consumers versus those reported by staff caring for consumers. Method: In a sample of consumers with SMI (n = 4,956), including nonimmigrants and immigrants from Ethiopia and countries comprising the former Soviet Union (FSU), we examined consumer-reported and staff-reported QOL ratings. Regression models measured the contributions of covariates to QOL ratings made by both groups. Results: Staff-reported QOL ratings were consistently lower than consumer-reported QOL ratings. Consumer-reported QOL ratings made by FSU immigrants were lower than consumer-reported QOL ratings made by Ethiopian immigrants or by nonimmigrants (p < .01). Conversely, staff-reported QOL ratings on Ethiopian immigrants were lower than staff-reported QOL ratings on FSU immigrants or nonimmigrants (p < .05). While consumer-reported QOL ratings were associated with the covariates of gender (p < .01), disability level (p < .001), and health status (p < .001), staff-reported QOL ratings were associated with the covariates of single marital status (p < .05), education (p < .001), and disability level (p < .001). Conclusions and Implications for Practice: Among consumers with SMI, FSU immigrants reported the lowest QOL ratings, yet staff rated the QOL of Ethiopian immigrants as the lowest. Bias is a potential explanation for this discrepancy. An educational program focusing on cultural awareness, sensitivity, and competency might help staff better understand consumers' needs, thereby contributing to better service and potentially improving staff's ability to make assessments of consumers' functioning and QOL. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Global gradients in species biodiversity are expected to reflect tighter packing of species closer to the equator. Yet, empirical validation of these patterns has so far focused on less diverse taxa, with comparable assessments of mega-diverse groups historically constrained by the taxonomic impediment. Here we assess the temporal and spatial turnover dynamics of arthropod communities sampled across 129 globally distributed monitoring sites. Overall, we encountered more than 150,000 unique BINs (i.e., species proxies). We show that global differences in community compositional change are linked to latitudinal, spatial, and temporal gradients, which are largely consistent across biogeographic regions. This general latitudinal imprint on community composition provides a mechanistic underpinning for global biodiversity gradients.

Conventional treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus (AF), resulting in a high incidence of recurrent herniation and persistent disfunction. The lack of repair and the acute inflammation that arise after injury further compromises the disc and can result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annular repair and the local delivery of bioactive anti-inflammatory factors. TARPs transmit physiologic strains to mechanically-activated microcapsules (MAMCs) embedded within, which activate and release encapsulated biomolecules in response to physiologic loading. Here, we demonstrate that the TARP design modulates implant biomechanical properties and regulates MAMC mechano-activation. Next, the FDA-approved anti-inflammatory molecule, interleukin 1 receptor antagonist, Anakinra, was loaded in TARPs and the effects of TARP-mediated annular repair and Anakinra delivery was evaluated in a model of annular injury in the goat cervical spine. TARPs showed robust integration with the native tissue and provided structural reinforcement at the injury site that prevented disc-wide aberrant remodeling resulting from AF detensioning. The delivery of Anakinra via TARP implantation improved the retention of disc biochemical composition through increased matrix deposition and retention at the site of annular injury. Anakinra delivery additionally attenuated the inflammatory response associated by scaffold implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the AF. These results demonstrate the translational and therapeutic potential of this novel TARP system for the treatment of intervertebral disc herniations.One Sentence SummaryTension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

Gender rules, patriarchy, and cultural taboos on sexual issues in traditional societies may compel adolescents to seek sexual information from informal and inadequate sources. The aim of this cross-sectional study was to determine whether the level and sources of sexual knowledge differed by gender in the traditional community comprising Palestinian-Israeli high school students. Guided by the Human Ecological Systems Model and informed by a community-based participatory research approach, a convenience sample of high school students (n = 558) was recruited. Although findings indicated that both boys and girls had low levels of sexual knowledge, the areas of knowledge deficits varied by gender. The model demonstrated good fit for boys but not for girls. Post hoc analyses indicated that girls obtained sexual knowledge solely from close family members, while boys obtained sexual knowledge from multiple sources. Very few students of either gender obtained sexual knowledge from doctors or nurses, but with community input on cultural issues, nurses can play a pivotal role in creating comprehensive, school-based sex education for adolescents living in traditional societies.

Hepatitis B virus (HBV) core protein-targeting compounds are in or entering clinical development without a standardized nomenclature. We propose a naming convention for these core-targeting antiviral products to provide clarity and accelerate HBV drug development.

Given its complex shape and relatively small size, the trapezium surface at the trapeziometacarpal (TMC) joint is a particularly attractive target for anatomic biologic joint resurfacing, especially given its propensity to develop osteoarthritis, and the limited and sub-optimal treatment options available. For this to advance to clinical translation, however, an appropriate large animal model is required. In this study, we explored the porcine accessory carpal bone (ACB) as a model for the human trapezium. We characterized ACB anatomy, geometry, joint and tissue-scale mechanics, and composition across multiple donors. We showed that the ACB is similar both in size, and in the saddle shape of the main articulating surface to the human trapezium, and that loads experienced across each joint are similar. Using this information, we then devised a fabrication method and workflow to produce patient-specific tissue-engineered replicas based on CT scans, and showed that when such replicas are implanted orthotopically in an ex vivo model, normal loading is restored. Data from this study establish the porcine ACB as a model system in which to evaluate function of engineered living joint resurfacing strategies. STATEMENT OF SIGNIFICANCE: Biologic joint resurfacing, or the replacement of a joint with living tissue as opposed to metal and plastic, is the holy grail of orthopaedic tissue engineering. However, despite marked advances in engineering native-like osteochondral tissues and in matching patient-specific anatomy, these technologies have not yet reached clinical translation. Given its propensity for developing osteoarthritis, as well as its small size and complex shape, the trapezial surface of the trapeziometacarpal joint at the base of the thumb presents a unique opportunity for pursuing a biologic joint resurfacing strategy. This work establishes the porcine accessory carpal bone as an animal model for the human trapezium and presents a viable test-bed for evaluating the function of engineered living joint resurfacing strategies.

Background: Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor–functionalized self-assembling KLD hydrogel (“functionalized hydrogel”) has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Hypothesis: Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Study Design: Controlled laboratory study. Methods: Bilateral cartilage defects (15-mm diameter) were created on the medial trochlear ridge of the femoropatellar joints in 8 adult horses (16 defects total). One defect was randomly selected to receive the treatment, and the contralateral defect served as the control (microfracture only). Treatment consisted of 2-minute trypsin pretreatment of the surrounding cartilage, subchondral bone microfracture, and functionalized hydrogel premixed with growth factors (platelet-derived growth factor and heparin-binding insulin-like growth factor 1). After surgery, all horses were subjected to standardized controlled exercise on a high-speed treadmill. Clinical evaluation was conducted monthly, and radiographic examinations were performed at 2, 16, 24, 32, 40, and 52 weeks after defect creation. After 12 months, all animals were euthanized. Magnetic resonance imaging, arthroscopy, gross pathologic evaluation of the joint, histology, immunohistochemistry, and biomechanical analyses were performed. Generalized linear mixed models (with horse as random effect) were utilized to assess outcome parameters. When P values were Results: Improved functional outcome parameters were observed for the treatment group, even though mildly increased joint effusion and subchondral bone sclerosis were noted on imaging. Microscopically, treatment resulted in improvement of several histologic parameters and overall quality of repaired tissue. Proteoglycan content based on safranin O–fast green staining was also significantly higher in the treated defects. Conclusion: Trypsin treatment combined with functionalized hydrogel resulted in improved microfracture augmentation. Clinical Relevance: Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes, especially in more active patients.

Objective: This integrative study reviewed quantitative community-based participatory research (CBPR) studies on adult migrant populations and examined CBPR partnerships with community repr...

ניסוי ראשון בקורס פסיכולוגיה ניסויית סמסטר קיץ תשע"ז

Pre registration for minno timing study.

Standard assessment of cartilage repair progression by visual arthroscopy can be subjective and may result in suboptimal evaluation. Visible–near infrared (Vis-NIR) fiber optic spectroscopy of joint tissues, including articular cartilage and subchondral bone, provides an objective approach for quantitative assessment of tissue composition. Here, we applied this technique in the 350–2,500 nm spectral region to identify spectral markers of osteochondral tissue during repair with the overarching goal of developing a new approach to monitor repair of cartilage defects in vivo. Full thickness chondral defects were created in Yucatan minipigs using a 5-mm biopsy punch, and microfracture (MFx) was performed as a standard technique to facilitate repair. Tissues were evaluated at 1 month (in adult pigs) and 3 months (in juvenile pigs) post-surgery by spectroscopy and histology. After euthanasia, Vis-NIR spectra were collected in situ from the defect region. Additional spectroscopy experiments were carried out in vitro to aid in spectral interpretation. Osteochondral tissues were dissected from the joint and evaluated using the conventional International Cartilage Repair Society (ICRS) II histological scoring system, which showed lower scores for the 1-month than the 3-month repair tissues. In the visible spectral region, hemoglobin absorbances at 540 and 570 nm were significantly higher in spectra from 1-month repair tissue than 3-month repair tissue, indicating a reduction of blood in the more mature repair tissue. In the NIR region, we observed qualitative differences between the two groups in spectra taken from the defect, but differences did not reach significance. Furthermore, spectral data also indicated that the hydrated environment of the joint tissue may interfere with evaluation of tissue water absorbances in the NIR region. Together, these data provide support for further investigation of the visible spectral region for assessment of longitudinal repair of cartilage defects, which would enable assessment during routine arthroscopy, particularly in a hydrated environment.

Interventions targeting traditional barriers to antihypertensive medication adherence have been developed and evaluated, with evidence of modest improvements in adherence. Translation of these interventions into population-level improvements in adherence and clinical outcomes among older adults remains suboptimal. From the Cohort Study of Medication Adherence among Older adults (CoSMO), we evaluated traditional barriers to antihypertensive medication adherence among older adults with established hypertension (N = 1,544; mean age = 76.2 years, 59.5% women, 27.9% Black, 24.1% and 38.9% low adherence by proportion of days covered (i.e., PDC

Background Intimate Partner Violence (IPV) is a significant public health problem often associated with serious mental health and physical health implications. Substance use disorders (SUDs) are one of the most common comorbidities among women with IPV, increasing risk of subsequent IPV. Methods The current study examined the feasibility, acceptability, and preliminary effectiveness of a brief computerized intervention to reduce alcohol and drug use among women with IPV. Fifty women with recent IPV and alcohol and drug use risk were recruited from domestic violence shelters and randomized to the experimental computerized intervention or to an attention and time control condition. The primary outcome was percent heavy drinking or drug using days in 3 month increments over the 6 months after leaving the shelter. Receipt of substance use services and IPV severity were evaluated as secondary outcomes. Results The computerized intervention was feasible and acceptable, with high (n = 20, 80%) completion rates, engagement with the intervention, and satisfaction scores. As expected in this pilot trial, there were no significant differences between conditions in percent heavy drinking/drug using days or receipt of substance use services and large individual differences in outcomes. For example, receipt of substance use services decreased by a mean of 0.05 times/day from the baseline to the 6-month time period in the control condition (range -1.00 to +0.55) and increased by a mean of 0.06 times/day in the intervention condition (range -0.13 to +0.89). There were large decreases in IPV severity over time in both conditions, but directions of differences favored the control condition for IPV severity. Conclusion A computerized intervention to reduce the risk of alcohol/drug use and subsequent IPV is feasible and acceptable among residents of a domestic violence shelter. A fully powered trial is needed to conclusively evaluate outcomes.

Introduction Understanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice. Methods TCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan–Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability. Results Among 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score. Conclusions Median durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA. Trial Registration ClinicalTrials.gov identifier, NCT01402661

Articular cartilage injury can lead to joint-wide erosion and the early onset of osteoarthritis. To address this, we recently developed a rapid fabrication method to produce patient-specific engineered cartilage tissues to replace an entire articular surface. Here, we extended that work by coupling a mesenchymal stromal cell-laden hydrogel (methacrylated hyaluronic acid) with the porous polycaprolactone (PCL) bone integrating phase and assessed the composition and mechanical performance of these constructs over time. To improve initial construct stability, PCL/hydrogel interface parameters were first optimized by varying PCL pretreatment (with sodium hydroxide before ethanol) before hydrogel infusion. Next, cylindrical osteochondral constructs were formed and cultured in media containing transforming growth factor β3 for up to 8 weeks, with constructs evaluated for viability, histological features, and biochemical content. Mechanical properties were also assessed in axial compression and via an interface shear strength assay. Results showed that the fabrication process was compatible with cell viability, and that construct biochemical content and mechanical properties increased with time. Interestingly, compressive properties peaked at 5 weeks, while interfacial shear properties continued to improve beyond this time point. Finally, these fabrication methods were combined with a custom mold developed from limb-specific computed tomography imaging data to create an anatomic implantable cell-seeded biologic joint surface, which showedmaturation similar to the osteochondral cylinders. Future work will apply these advances in large animal models of critically sized osteochondral defects to study repair and whole joint resurfacing.

Objective: The goal of this project was to develop a systematic framework through which interventions promoting intergenerational solidarity in 11 countries could be assessed. Background: Although intergenerational solidarity—the exchange of material, social, and emotional support and care between family generations—benefits both the country's economic well-being (macro-level) and the individual's physical, mental, and social well-being (micro-level), decreasing intergenerational solidarity is evident in many industrialized countries. Interventions promoting intergenerational solidarity are increasingly being developed, but few are described in the literature. Moreover, no unifying framework describing them exists. Method: Representatives from 11 countries convened to identify interventions promoting intergenerational solidarity. After several meetings, a unifying framework was created. Representatives selected a convenience sample of programs and abstracted information based on the framework. Results: The outcome of social well-being was virtually ubiquitous in most programs. Countries appeared to take a broad view of intergenerational solidarity, focusing on interactions among generations, rather than interactions within families. Discussion and Implications: The framework enabled the systematic abstraction and assessment of programs. Most programs had no standard method of evaluating their outcomes. Longitudinal evaluations would be optimal if we want to identify the best practices in intergenerational solidarity programs.

Author(s): Mariani, Christopher L; Zlotnick, Joshua A; Harrysson, Ola; Marcellin-Little, Denis J; Malinak, Kristen; Gavitt, Ashley; Guevar, Julien | Abstract: ObjectiveTo assess the accuracy of three-dimensionally (3-D) printed drill guides in constraining the trajectory of drill tracts for implants in canine thoracic vertebrae.Study designExperimental ex vivo study.Sample populationFive canine thoracic vertebral column specimens.MethodsGuides to constrain drill trajectories were designed on the basis of computed tomographic (CT) imaging of six thoracic vertebrae (T8-T13) and were 3-D printed. The guides were used to create drill tracts in these vertebrae by both an experienced and a novice surgeon, and CT imaging was repeated. The entry point and angulation of actual and planned drill tracts were compared for both surgeons. Unintended cortical violations were also assessed by using a modified Zdichavsky classification.ResultsFifty-eight drill tracts were created in 30 vertebrae. Mean entry point deviation was 1.4 mm (range, 0.4-3.4), and mean angular deviation was 5.1° (range, 1.5°-10.8°). There were no differences between surgeons in entry point deviation (P = .07) or angular deviation (P = .22). There were no unintended cortical bone violations, and all drill tracts were classified as modified Zdichavsky grade I.ConclusionThe 3-D printed guides used in the current study yielded drill tracts with small linear and angular errors from intended paths and 100% accuracy for placement within vertebral pedicles and bodies. This technique was conveniently used by both an experienced and a novice surgeon.Clinical significanceThis technique might be immediately applicable to clinical cases requiring thoracic vertebral stabilization and may allow safe and accurate implant placement for surgeons with varying experience levels.

Resistive-pulse sensing with solid-state nanopores is a sensitive, label-free technique for analyzing single molecules in solution. To add functionality to resistive-pulse measurements, direct coupling of the nanopores to other pores and nanoscale fluidic elements, e.g., reactors, separators, and filters, in the same device is an important next step. One approach is monolithic fabrication of the fluidic elements in the plane of the substrate, but methods to generate pores with circular cross sections are needed to improve sensing performance with in-plane devices. Here, we report a fabrication method that directly patterns nanopores with circular cross sections in series and in plane with the substrate. A focused ion beam (FIB) instrument is used to mill a lamella in a nanochannel and, subsequently, bore a nanopore through the lamella. The diameter and geometry of the nanopore are controlled by the current and dose of the ion beam and by the tilt angle and thickness of the lamella. We fabricated devices with vertical and tilted lamellae and nanopores with diameters from 40 to 90 nm in cylindrical and conical geometries. To test device performance, we conducted resistive-pulse measurements of hepatitis B virus (HBV) capsids. Current pulses from T = 3 capsid (~31 nm diameter) and T = 4 capsid (~35 nm diameter) were well resolved and exhibited relative pulse amplitudes (Δi/i) up to 5 times higher than data obtained on nanopores with rectangular cross sections. For smaller pore diameters (≤ 45 nm), which approach the diameters of the capsids, a dramatic increase in the pulse amplitude was observed for both T = 3 and T = 4 capsids. Two and three pores fabricated in series further improved the resolution between the relative pulse amplitude distributions for the T = 3 and T = 4 capsids by up to 2-fold.

IntroductionThis protocol describes a study testing the efficacy of interpersonal psychotherapy (IPT) for major depressive disorder following perinatal loss (early and late fetal death and early neonatal death). Perinatal loss is associated with elevated risk of major depressive disorder and post-traumatic stress disorder (PTSD). Perinatal loss conveys specific treatment needs. The trial will be the first fully powered randomised trial of treatment for any psychiatric disorder following perinatal loss.Methods and analysisA sample of 274 women in Flint and Detroit areas in Michigan who experience a major depressive episode following a perinatal loss will be randomised to group IPT for perinatal loss or to group coping with depression. We anticipate that 50% of the sample will have co-occurring PTSD. Assessments occur at baseline, mid-treatment (8 weeks), post-treatment (16 weeks) and follow-up (28 weeks). Clinical outcomes include time to recovery from major depressive episode (primary), depressive symptoms, PTSD symptoms and time to recovery from PTSD. Additional outcomes include social support, social role functioning (including parental functioning for those with living children), well-being, grief (including complicated grief and fault beliefs) and fear of subsequent pregnancies. Social support and grief are hypothesised mediators of IPT effects on time to recovery from major depressive episode.Ethics and disseminationThe trial was approved by Michigan State University’s Biomedical Institutional Review Board. It has a data and safety monitoring board and has been submitted to the community-based organisation partners community ethics review board. Written operating procedures outline methods for protecting confidentiality, monitoring and recording adverse events, and safeguarding participants. We will share study results with research and clinical communities, community organisations through which we recruited, and will offer results to study participants. Deidentified datasets will be available through the National Institute of Mental Health Data Archive and to qualified investigators on request.Trial registration numberNCT04629599.

BackgroundPregnancy and motherhood increase the risk for long-term exposure to physical, psychological and sexual intimate partner violence (IPV; sexual or physical violence by current or former partners). Pregnant women and mothers with children under 5 who have experienced IPV exhibit poor physical and mental health and obstetric outcomes. Depression and posttraumatic stress disorder (PTSD) are the two most common mental health consequences of IPV. There is good evidence that women with good social support have better mental health and IPV outcomes.MethodsThis study will develop MOthers’ AdvocateS In the Community (MOSAIC) Plus intervention for pregnant women and mothers with children under the age of 5. MOSAIC uses trained mentor mothers and has been found to reduce subsequent IPV. This study will blend the original MOSAIC intervention with principles of interpersonal psychotherapy (IPT) to address symptoms of depression, PTSD, and prevent subsequent risk of IPV. We will conduct a pilot randomized trial of the MOSAIC Plus intervention compared to the traditional MOSAIC intervention to determine its feasibility and acceptability. Study samples include focus groups (n=36), open trial (n=15), and a randomized pilot trial including 40 pregnant women and mothers with children under 5 who report current/recent of IPV and elevated symptoms of maternal depression and/or PTSD. The study’s primary outcome will be changes in maternal depressive and PTSD symptoms. Secondary outcomes will include reduction in subsequent IPV, improvement in functioning, changes in social support and effectiveness in obtaining resources.DiscussionThis is a formative study evaluating the feasibility and acceptability of a mentor mother intervention for pregnant women and mothers with children under 5. Promising results of this study will be used for a larger, fully-powered randomized trial evaluating the effectiveness of a mentor mother intervention in preventing subsequent IPV and reducing depressive and PTSD symptoms in this population.Strengths and limitations of this studyThe study is informed by a robust qualitative approach to intervention development that involves a series of focus group discussions.This study aims to develop an intervention that reduces future intimate partner violence, while also addressing related maternal mental health outcomes.A rigorous and reproducible design includes randomization, clear inclusion criteria, manualized treatment protocols and fidelity assessments.The study will use reliable and validated measures.Given the small sample size, results from the pilot randomized trial are underpowered to draw firm conclusions about effectiveness.

Aims and objectives: This study examines the relationship between social status and postpartum depression by migrant generation and determines whether social support moderates the relationship between migrant generations and postpartum depression. Background: Postpartum depression (PPD) afflicts more than 1 in 10 childbearing women worldwide; and this mental health problem may be higher among vulnerable populations of women such as migrants, an increasingly prevalent group in many countries. Social support and migrant generation (1st generation—mother and her parents born outside the host country; 2nd generation—mother born in the host country but not her parents; 2.5 generation—mother and one parent born in the host country) may contribute to the conflicting findings on migrant mothers and postpartum depression. Design: This study used a cross-sectional design. Methods: Sample recruitment of migrant and non-migrant first-time mothers (n=515) was implemented through an online platform. A STROBE checklist guided the reporting of this study. Results: PPD was lower among mothers with social support. While social support was negatively associated with PPD for all mothers, PPD was not associated with migrant generation nor was a moderation effect found. Conclusions: Social support is negatively associated with PPD for all mothers, but levels of PPD for migrant mothers may be linked to country-specific healthcare resources and immigration policies. Immigrant policies influence migrant mothers’ healthcare access; thus, immigration policies may influence PPD among first-time migrant mothers and the manner in which nurses can provide formal support. This study finds that social support, including the formal social support provided by nurses, decreases the likelihood of PPD. Demands on nurses’ technical and assessment skills are high, but nurses also need to remember that their skills of providing social support are equally important, and for first-time mothers, may contribute to decreasing PPD.

Hepatitis B Virus (HBV) must release its contents to initiate infection, making capsid disassembly critical to the viral life cycle. Capsid assembly proceeds through a cascade of weak interactions to yield uniform particles. However, there is a hysteresis to capsid dissociation that allows capsids to persist under conditions where they could not assemble. In this study we have sought to define the basis of hysteresis by examining urea induced dissociation of in vitro assembled HBV capsids. In general, capsid samples show a mixture of two pools, differentiated by stability. Labile capsid dissociation corresponds to a ~5 μM pseudo-critical concentration of assembly (pcc), the same as observed in assembly reactions. Dissociation of the stable pool corresponds to a sub-femtomolar pcc, indicative of hysteresis. The fraction of stable capsids in an assembly reaction increases with the integrity of the Cp preparation and when association is performed in higher ionic strength, which modifies Cp conformation. Labile complexes are more prevalent when assembly conditions yield many kinetically trapped (incomplete and overgrown) products. Cp isolated from stable capsids reassembles into a mixture of stable and labile capsids. These results suggest that hysteresis arises from an ideal capsid lattice, even when some of the substituents in that lattice have defects. Consistent with structural studies that show a subtle difference between Cp dimers and Cp in capsid, we propose that hysteresis arises when HBV capsids undergo a lattice-dependent structural transition.

BACKGROUND: Thumb carpometacarpal (CMC) osteoarthritis (OA), a degenerative condition affecting hand use, is typically evaluated through radiographs and clinical examination. Although this can determine treatment, it is difficult to evaluate functional limitations. Shear wave elastography (SWE) is a quantitative ultrasound technique that characterizes tissue stiffness. QUESTIONS/PURPOSES: This pilot study aimed to establish data of the SWE findings in the thenar eminence muscles in patients with first CMC OA and correlate these findings with the clinical tests of hand function. METHODS: This cross-sectional study correlated the SWE stiffness of thenar eminence muscles to clinical tests of hand function in patients with first CMC OA and in asymptomatic control subjects, using Spearman’s correlation coefficient. Mean SWE values of the thenar eminence muscles in patients were compared with those in control subjects. The study was performed in a non-profit tertiary care hospital setting. Patients and control subjects were recruited on a volunteer basis. RESULTS: SWE values in the abductor pollicis brevis and flexor pollicis brevis muscles showed moderate to very strong correlation with multiple measures of hand function. Mean SWE values of the thenar eminence muscles in first CMC OA patients were lower than those in asymptomatic control subjects. CONCLUSIONS: Correlations between mean SWE values in the thenar eminence muscles and clinical measures of hand function suggest decreased function in subjects with less stiff thenar eminence muscles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-020-09795-z) contains supplementary material, which is available to authorized users.

Increasingly evidence suggests that the self-reported health status (SRH) of 2nd generation immigrant youth (native-born youth with at least one parent who was born abroad) may be lower than non-immigrant youth. This cross-sectional study compared the SRH of 2nd generation immigrant to non-immigrant youth ( n = 291), accounting for confounders including a clinical measure (i.e., body mass index), internal resources (i.e., diet, exercise, smoking), and external resources (i.e., socioeconomic status, family social support). Regressions showed SRH was associated with socioeconomic status ( p

Objective To estimate the effect of an interpersonal therapy-based intervention on reducing the risk of postpartum depression in adolescents. Methods A randomized controlled trial enrolled 250 pregnant adolescents who were aged 18 years or younger at conception. The initial sample size calculation estimated 276 participants (324 with attrition) were needed to detect a 50% reduction in risk of the primary outcome, postpartum major depressive episode, with an alpha of 0.05% and 80% power. An interim analysis by the Data Safety and Monitoring Committee informed a revision in the sample size target to 250. Participants were randomized to the intervention (n=129) or a time-matched control group (n=121) who attended sessions about pregnancy topics. Each group received five prenatal sessions and a postpartum booster session. A structured diagnostic interview was administered at baseline and specific time points through 12-months postpartum to assess for major depressive episode onset. Results Participants were recruited from December 2011 to May 2016 through urban prenatal care sites in the state of Rhode Island. Of the 250 participants, 58% identified as Hispanic and 20% as black or African American. The rate of major depressive episode by 12 months postpartum was 7.0% (95% CI 2.3-11.7%) in the control group and 7.6% (95% CI 2.5-12.7%) in the intervention group, with no significant difference between groups at any time point (P=.88 by log-rank test). Conclusion No benefit was shown between the intervention and control groups in the rates of major depressive episode, which is likely related to a lower than predicted rate of this outcome in the control group (7.6% actual vs 25% predicted). Enhanced local community resources available to pregnant and parenting adolescents during the study period may be an explanation for this result. Clinical trial registration ClinicalTrials.gov, NCT01482832.

While there is an effective vaccine for Human Hepatitis B Virus (HBV), 257 million people have chronic infections for which there is no cure. The assembly process for the viral capsid is a potential therapeutic target. In order to understand the capsid assembly process, we investigated the dimeric building blocks of the capsid. To understand what blocks assembly, we took advantage of an assembly incompetent mutant dimer, Cp149-Y132A, located in the interdimer interface. This mutation leads to changes in protein dynamics throughout the structure of the dimer as measured by hydrogen-deuterium exchange mass spectrometry (HDX-MS). To further understand how the HBV capsid assembles, the homologue woodchuck HBV (WHV) capsid protein dimer (Cp) was used. WHV is more stable than HBV in HDX-MS and native mass spectrometry experiments. Because the WHV Cp assembles more rapidly into viral capsids than HBV, it was suspected that an increase in stability of the intradimer interface and/or in the contact region leads to increased assembly rates. The differences in dynamics when comparing HBV and human Cp149-Y132A as well as the differences in dynamics when comparing the HBV and WHV Cps allowed us to map an allosteric network within the HBV dimer. Through a careful comparison of structure, stability, and dynamics using four different capsid protein dimers, we conclude that protein subunit dynamics regulate HBV capsid assembly.

Adolescent girls in low-resource settings account for over 7.3 million births annually (generally unplanned). Unplanned teen pregnancies are increasing in low-resource settings. As part of a funded Round 20 Grand Challenges Exploration project (Healthy Minds for Adolescent Mothers), we investigated unplanned teen pregnancies in Haiti’s Cité Soleil shantytown, teens’ biopsychosocial challenges, and desirable interventions. Key stakeholders (N = 23): pregnant teens (13-17-year-olds, n = 8; 18-19-year-olds, n = 8) and health providers (18 or older, n = 7), participated by age group and role in focus groups (FGs). ATLAS.ti facilitated the analysis of transcribed FG audio recordings. Ninety-four percent (n = 15) of teens reported “Banm prèv,” translated “Give me proof,” as a cause of their unplanned pregnancies. Banm prèv describes when teens are propositioned by men who demand proof of their unpretentiousness or virginity. A subtle, covert, locally unchallenged phenomenon that is supported by damaging gender norms, Banm prèv constitutes an illusionary choice between teens’ yielding non-consensual control of their bodies and the tacit alternative of gang rape. Banm prèv underscores teens’ difficulty discerning consensual from coerced sex. Associated unplanned pregnancies occasion guilt, shame, stigma, depression, anxiety, and trauma in teens. Cité Soleil teens need contextually relevant, community-supported, age-appropriate interventions that challenge existing norms, build on cultural strengths, and include comprehensive sexuality education, including knowledge of reproductive rights. A traditional, contextually familiar, engaging, and humorous story-telling tradition, i.e., krik-krak, packaged in video format, is a useful framework for interventions to reduce depressive symptoms, stress, and anxiety for Cité Soleil teens experiencing unplanned pregnancies.

Introduction Similar outcomes have been observed between patients with rheumatoid arthritis (RA) responding to tocilizumab (TCZ) with methotrexate (MTX) who discontinued vs. continued MTX and between patients receiving MTX who added TCZ vs. switched to TCZ monotherapy. This study examined MTX discontinuation and dose decreases in patients with RA initiating TCZ in a real-world setting. Methods TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ in combination with MTX and had a 6-month follow-up visit without TCZ discontinuation were included. Patients were grouped by MTX dose at the time of TCZ initiation (≤ 10 mg, > 10 to ≤ 15 mg, > 15 to ≤ 20 mg, > 20 mg). The primary outcome was the proportion of patients with changes in MTX use at 6 months, with a secondary analysis at 12 months. Changes in disease activity [Clinical Disease Activity Index (CDAI)] and patient-reported outcomes (PROs) at 6 and 12 months were summarized descriptively. Results Of 444 included patients, 82.7% were female and 83.7% white, with mean (SD) disease duration of 11.6 (9.3) years, baseline CDAI score of 24.0 (15.4), and baseline MTX dose of 17.7 (5.8) mg. At 6 months, 139 patients (31.3%) discontinued or decreased their MTX dose. All MTX dose groups and patients who discontinued, decreased, maintained, or increased their MTX dose displayed improvements in CDAI scores and PROs at 6 months. Similar patterns and results were observed at 12 months. Conclusions A considerable proportion of patients initiating TCZ discontinued or decreased their MTX dose after TCZ initiation. Improvements in disease activity and functionality were observed in patients who decreased or stopped MTX. This real-world study confirmed prior observations that discontinuing or decreasing MTX may be a treatment strategy for patients initiating TCZ combination therapy. Trial Registration ClinicalTrials.gov identifier, NCT01402661., Plain Language Summary Rheumatoid arthritis (RA) is a long-term disease that causes joint swelling, stiffness, and pain. Unless RA is treated quickly, patients can experience joint damage and disability. Patients with RA often take methotrexate (MTX) as their first treatment, but many patients do not have sufficient improvement with MTX alone. For these patients, doctors often add another medicine called a biologic to their existing treatment. However, taking more medications is associated with toxic effects and can make it harder for patients to stay on their therapy. Tocilizumab (TCZ) is a biologic that is used to treat RA. In one clinical trial, reported by Kremer et al., patients whose RA improved when they were taking TCZ plus MTX were subsequently able to stop taking MTX and their RA remained well controlled (Arthritis Rheumatol 70(8):1200–1218, 2018). However, researchers had not looked at whether patients outside of a clinical trial (in the “real world”) can stop taking MTX or take less MTX after they start taking TCZ. This study used real-world data to examine if patients who start taking TCZ subsequently stop taking or take less MTX. This study showed that many patients were able to stop taking or take less MTX during the year after they started taking TCZ. Patients who stopped or decreased their MTX dose had less-active RA and reported that they felt better and had fewer symptoms. These results suggest that it is common for patients in the real world to stop taking or take less MTX after they start taking TCZ.