Search

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.

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.

© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. The objective of this study was to improve cartilage repair and integration using self-assembling KLD hydrogel functionalized with platelet-derived growth factor-BB and heparin-binding insulin-like growth factor-1 with associated enzymatic trypsin pre-treatment of the native cartilage. Bilateral osteochondral defects were created at the central portion of the femoral trochlear groove of 48 skeletally mature, white New Zealand rabbits. One limb received a randomly assigned treatment and the contralateral limb served as the control. Treated defects were exposed to trypsin for 2 min and filled with self-assembling KLD hydrogel only, or associated to growth factors. All control limbs received KLD hydrogel alone or received only trypsin but not hydrogel. Ninety days post-defect creation, the rabbits were euthanized and magnetic resonance imaging, radiography, macroscopic evaluation, histology, and immunohistochemistry of the joint and repaired tissue were performed. Mixed model analyses of variance were utilized to assess the outcome parameters and individual comparisons were performed using Least Square Means procedure and differences with p-value ' 0.05 were considered significant. Trypsin enzymatic pre-treatment improved cellular morphology, cluster formation and subchondral bone reconstitution. Platelet-derived growth factor-BB improved subchondral bone healing and basal integration. Heparin-binding insulin-like growth factor-1 associated with platelet-derived growth factor improved tissue and cell morphology. The authors conclude that self-assembling KLD hydrogel functionalized with platelet-derived growth factor and heparin-binding insulin-like growth factor-1 with associated enzymatic pre-treatment of the native cartilage with trypsin resulted in an improvement on the cartilage repair process. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2307–2315, 2019.

Aim Using the case of Israel, we examine the confluence of current philosophies of health care along with the historical trends of health promotion/disease prevention services to consider strategies for increasing inclusiveness and for updating and improving their service delivery. Background Health services in Israel are at a crossroads. Plans to integrate the historic, nurse-operated, nationwide programme, providing health promotion/disease prevention services to pregnant women and young children for all residents (Tipat Halav) into the National Health Service System's existing Sickness Funds are under discussion. Sources of evidence Using a discourse approach, this paper examines the current and historical context of health promotion/disease prevention services. Our history shows an increasingly treatment-based perspective and dwindling support for inclusive services. In the current health system, Tipat Halav nurses solely provide inclusive health promotion/disease prevention services to pregnant women and young children. Informed by the World Health Organization, a reorientation to health promotion/disease prevention is essential in an ageing society where chronic rather than infectious diseases are the reigning health problems. Conclusion Israel needs to reorganize the health system using a public health approach that both incorporates existing structures and establishes new ones, such as creating a network to elicit community input, and instituting nurse-operated clinics designed to provide health promotion/disease prevention services for all ages and all residents. Implications for health and nursing policy The newly created health system framework demands activism among all health professionals to legislate for an inclusive, holistic orientation. Master's level clinical programmes in community health nursing are vital to ensure the provision of optimal health promotion/disease prevention services.

Hepatitis B virus (HBV) core protein is a model system for studying assembly and disassembly of icosahedral structures. Controlling disassembly will allow re-engineering the 120 subunit HBV capsid, making it a molecular breadboard. We examined removal of subunits from partially crosslinked capsids to form stable incomplete particles. To characterize incomplete capsids, we used two single molecule techniques, resistive-pulse sensing and charge detection mass spectrometry. We expected to find a binomial distribution of capsid fragments. Instead, we found a preponderance of 3 MDa complexes (90 subunits) and no fragments smaller than 3 MDa. We also found 90-mers in the disassembly of uncrosslinked HBV capsids. 90-mers seem to be a common pause point in disassembly reactions. Partly explaining this result, graph theory simulations have showed a threshold for capsid stability between 80 and 90 subunits. To test a molecular breadboard concept, we showed that missing subunits could be refilled resulting in chimeric, 120 subunit particles. This result may be a means of assembling unique capsids with functional decorations. This article is protected by copyright. All rights reserved.

This study explored the acceptability, feasibility, and initial efficacy of an expanded version of a PTSD treatment developed for residents of battered women's shelters, Helping to Overcome PTSD through Empowerment (HOPE) in women who received standard shelter services (SSSs). A Phase I randomized clinical trial comparing HOPE + SSSs (n = 30) to SSSs (n = 30) was conducted. Primary outcome measures included the Clinician-Administered PTSD Scale (Blake et al., 1995) and the Revised Conflict Tactic Scales (Straus, Hamby, Boney-McCoy, & Sugarman, ). Participants were followed at 1-week, and 3- and 6-months posttreatment. Only 2 women dropped out of HOPE + SSS treatment. Latent growth curve analyses found significant treatment effects for PTSD from intimate partner violence (IPV) (β = -.007, p = .021), but not for future IPV (β = .002, p = .709) across follow-up points. Significant effects were also found for secondary outcomes of depression severity (β = -.006, p = .052), empowerment (β = .155, p = .022), and resource gain (β = .158, p = .036). Additionally, more women in HOPE + SSSs were employed at 3- and 6-month follow-up compared to those in SSSs only. Results showed the acceptability and feasibility of adding IPV-related treatment to standard services. They also suggested that HOPE may be a promising treatment for residents of battered women's shelters. Further research with a larger sample, utilizing more diverse shelter settings and a more rigorous control condition, is needed to confirm these findings.

Introduction and Aims The multiple risk model postulates that accumulating risk factors increase adolescent drunkenness and smoking. The normalisation theory adds to this by arguing that the relation between accumulative risk and drunkenness and smoking is dependent on the distribution of these behaviours in the larger population. More concretely, normalisation theory predicts that: (i) when population level use increases, low risk adolescents will be more likely to use alcohol and cigarettes; and (ii) adolescents facing multiple risk factors will be equally likely to use alcohol and cigarettes, regardless of trends in population level use. The current study empirically tests these assumptions on five waves of nationally representative samples of Israeli Jewish youth. Design and Methods Five cross-sectional waves of data from the Israeli Health Behaviour in School-aged Children survey for Jewish 10th graders were used. Logistic regression models measured the impact of changes in population level use across waves on drunkenness and smoking, and their association with differing levels of risk factors. Results Between zero and two risk factors, the risk of drunkenness and smoking increases for each additional risk factor. When reaching two risk factors, added risk does not significantly increase the likelihood of smoking and drunkenness. Changes in population level drunkenness and smoking did not systematically relate to changes in the individual level relationship between risk factors and smoking and drunkenness. Discussion and Conclusions The pattern of results in this study provides strong evidence for the multiple risk factor model and inconsistent evidence for the normalisation theory. [Sznitman SR, Zlotnick C, Harel-Fisch Y. Normalisation theory: Does it accurately describe temporal changes in adolescent drunkenness and smoking? Drug Alcohol Rev 2015]

Around hospitalization, older adults often experience functional decline which can be a reflection of their need for nursing care. Given a shortage of nurses, determining the relationship between functional change and patients' satisfaction with nursing care can help to gauge the need for care. We assessed this relationship in a mixed prospective-correlational cohort study with 393 patients, 70 years or older. The art, tangible aspects and general satisfaction with nursing care were measured through interviews conducted at discharge. Patients' functional status was assessed at admission and discharge. Decline in functioning during hospitalization was the most powerful predictor of higher satisfaction with art and tangible aspects of nursing care in multivariate regression (β = 0.17-0.19, P < 0.01). This finding suggests that patients whose functioning deteriorates during hospitalization, have a greater need for and more contact with professional nursing care, and therefore report higher satisfaction with specific aspects of nursing care.

Intimate partner violence (IPV) is a significant public health problem associated with high rates of posttraumatic stress disorder (PTSD). Few longitudinal studies have investigated IPV-related PTSD and we know of only 1 longitudinal study to date that has explored IPV-related PTSD in residents of battered women's shelters. The current report describes a prospective study of IPV-related PTSD in an initial sample of 147 residents of battered women's shelters. Baseline correlates of remission of IPV-related PTSD (i.e., PTSD and IPV severity, loss of personal and social resources, cessation of abuse, reunion with abuser, and length of shelter stay) over a 6-month follow-up period were investigated. Although findings are consistent with prior research suggesting a natural recovery of PTSD in IPV-victims, they also show that a significant number (46.8%) of women exhibit chronic PTSD. Participants whose PTSD remitted over follow-up had at baseline less severe IPV-related PTSD (partial η(2) = .104) and fewer loss of personal and social resources (partial η(2) = .095), and were less likely to reunite with their abuser after leaving the shelter than participants with chronic PTSD (3.3% and 22.4%, respectively). Clinical implications and limitations of findings are discussed. Language: en

This article focuses on how the ability to speak and read English affects Latino citizens' participation in U.S. elections, and evaluates the extent to which this language barrier might be overcome by living in a community with a relatively large Latino population and having access to registration materials and ballots in Spanish. Using data primarily from the Pew Hispanic Center, we find that the inability to speak and read English hinders registration and turnout among Latino citizens. While the language barrier to turnout is mitigated by several factors, the barrier to registration is more intractable. These results have implications for researchers and practitioners interested in the political participation of this increasingly prominent group. In particular, understanding the role of English proficiency is a critical first step in thinking about policy prescriptions that will bring into the political process a growing number of Latino citizens, particularly those with limited English skills. Este estudio se enfoca en como las habilidades de hablar y leer el ingles afectan la participacion de ciudadanos latinos en las elecciones estadounidenses, y evalua la medida en que esta barrera del idioma podria ser superada viviendo en una comunidad con una poblacion latina relativamente grande y teniendo acceso a materiales de registro electoral y boletas en espanol. Usando datos principalmente del Pew Hispanic Center, encontramos que la baja habilidad para hablar y leer en ingles obstaculiza el registro y participacion entre ciudadanos de origen latino. Mientras que la barrera del lenguaje para ejercer el derecho al voto es mitigada al vivir en una comunidad con una poblacion latina relativamente grande y con acceso a boletas bilingues, la barrera para inscribirse en el registro de electores es mas restrictiva. Estos resultados tienen implicaciones para investigadores, practicantes, y legisladores interesados en la participacion politica de este grupo cada vez mas prominente de electores. Entender el papel del dominio de el ingles es, particularmente, un primer paso critico para pensar recetas de politicas que incorporen en el proceso politico un creciente numero de ciudadanos latinos, especialmente aquellos con un limitado dominio del idioma ingles.

This study examined gender differences in a range of lifetime psychiatric disorders in a sample of 272 offenders newly admitted to a prison substance abuse program. Although these men and women did not differ in severity of substance use in the six months prior to incarceration, women were significantly more likely than men to report a lifetime psychiatric disorder and a lifetime severe disorder. Furthermore, gender differences emerged in the pattern of lifetime psychiatric comorbidity. Women reported greater lifetime major depression, posttraumatic stress disorder, eating disorder, and borderline personality disorder; men were more likely than women to meet criteria for antisocial personality disorder. Additionally, female offenders were found to have a higher degree of internalizing disorders than male offenders, but there were no gender differences in degree of externalizing disorders. The study concluded that women offenders newly admitted to a prison substance abuse program present with a greater psychiatric vulnerability and a different pattern of psychiatric comorbidity than their male counterparts.

Research has shown both childhood physical and sexual abuse to be associated with later suicide attempts, although some studies have not supported these findings. However, few studies have investigated differences in physical and sexual abuse histories among single and multiple suicide attempters. The goals of the current study were two-fold: (a) to replicate previous findings of associations between childhood sexual and physical abuse and suicide attempts, and (b) to explore differences in reports of childhood physical and sexual abuse among single and multiple suicide attempters. While our results supported the findings that individuals with a history of suicide attempts are more likely to report histories of childhood physical and sexual abuse, we did not find a difference in reported abuse between single and multiple suicide attempters. Implications of these findings, as well as implications for future research, are discussed.

Here we report the effect of a heteroaryldihydropyrimidine (HAP) antiviral compound, BAY 41-4109, on Hepatitis B virus (HBV) capsid assembly and on preformed HBV capsids. The HBV capsid is an icosahedral complex of 120 capsid protein dimers. BAY41-4109 inhibits virus production in vivo by a mechanism that targets the viral capsid. We found that BAY 41-4109 was able to both accelerate and misdirect capsid assembly in vitro. As little as one HAP molecule for every five HBV dimers was sufficient to induce formation of non-capsid polymers. Unlike the related molecule HAP-1 (Stray et al., Proc. Natl. Acad. Sci. USA 102:8138-43, 2005), no stable assembly intermediates were observed in assembly reactions with BAY 41-4109, indicating that accelerated assembly by BAY 41-4109 was still kinetically regulated by the nucleation rate. Preformed capsids were stabilized by BAY 41-4109, up to a ratio of one inhibitor molecule per two dimers. However, at BAY 41-4109:dimer ratios of 1:1 and greater, capsids were destabilized to yield very large non-capsid polymers. These data suggest the existence of two functionally distinguishable classes of drug-binding sites on HBV capsids. Occupation of the first class of site stabilizes capsid, while binding at the second class requires or induces structural changes that cannot be tolerated without destabilizing the capsid. Our data suggest that HAP compounds may inhibit virus replication by inducing assembly inappropriately and, when in excess, by misdirecting assembly decreasing the stability of normal capsids.

Despite the high rates of posttraumatic stress disorder (PTSD) among battered women in shelters, virtually no treatments for these women have been developed or tested. This study evaluated the initial feasibility and efficacy of an individual, cognitive-behavioral treatment for battered women with PTSD or subthreshold PTSD in shelters. Eighteen women participated in an open-trial where they received a new treatment, Helping to Overcome PTSD with Empowerment (HOPE). Intent-to-treat analyses indicate that participants experienced significant decreases in PTSD symptoms, depressive symptoms, in their loss of resources and degree of social impairment; and significant increases in their effective use of community resources. These gains were maintained over time. Results should be interpreted with caution due to the small sample size and lack of a control group.

A virus capsid is constructed from many copies of the same protein(s). Molecular recognition is central to capsid assembly. The capsid protein must polymerize in order to create a three-dimensional protein polymer. More than structure is required to understand this self-assembly reaction: one must understand how the pieces come together in solution.

Using an in vitro assay for CD80 promoter activity, the transcriptional response of primary cultured human keratinocytes from different donors in response to allergens and irritants was studied. The CD80 promoter activity was increased reproducibly after exposure to certain chemicals. The epithelial cell lines HeLa and HaCaT also increased CD80 transcriptional activity in response to exposure to a panel of different allergens and irritants. Normal or immortalized keratinocytes responded reproducibly with a unique pattern to a panel of chemicals in which the culture increases CD80 transcription after exposure to certain chemicals and has no increase in CD80 transcription after exposure to other chemicals. Some keratinocyte cultures responded positively to certain chemicals whereas others did not respond to the same chemicals. Cultured keratinocytes from 16 of 20 adult donors (80%) responded to nitrochlorobenzene in vitro by increasing CD80 transcriptional activity, thus predicting subsequent sensitization to this same hapten (χ2 = 7.2, P < 0.0073). Thus, a keratinocyte CD80 gene expression assay exhibits good sensitivity in predicting allergic contact dermatitis for sensitizers such as dinitrochlorobenzene. These data suggest that there is a rationale for developing the use of gene-transcription-based predictive assays to identify individual susceptibility to cutaneous reactivity after exposure to allergens and irritants. Copyright © 2004 John Wiley & Sons, Ltd.

Haemophilus influenzae lipoprotein e (P4) is a member of the DDDD phosphohydrolase superfamily and mediates heme transport. Each of the aspartate residues of the signature motif is required for phosphomonoesterase activity, as none of the e (P4) single D mutants (D64A, D66A, D181N, and D185A) possessed detectable phosphomonoesterase activity. These results suggest that the signature motif is essential to the phosphomonoesterase activity of lipoprotein e (P4). When assessed for phosphomonoesterase-dependent heme transport activity in Escherichia coli hemA strains, plasmids containing D181N and D185A retained heme transport as indicated by aerobic growth while D64A and D66A did not. We conclude that phosphomonoesterase activity is not required for heme transport.

One aim of this study was to examine the strength of association between posttraumatic stress disorder (PTSD) and alexithymia relative to other psychiatric disorders in a sample of 252 treatment-seeking psychiatric patients. The other aim of this study was to explore which type of childhood trauma was associated with a greater level of adult alexithymia. The study found that PTSD and borderline personality disorder (BPD) were the two disorders among selected psychiatric disorders to contribute independently to a higher degree of alexithymia. Another finding was that a greater severity of emotional neglect and physical neglect, rather than abuse, was significantly related to higher levels of alexithymia. In addition, the study found that among these variables, BPD had the strongest relationship to alexithymia.

Affect dysregulation is pervasive among women with histories of childhood sexual abuse. It is an important aspect of the clinical presentation of posttraumatic stress disorder (PTSD), a disorder that frequently characterizes survivors of childhood abuse. Based on distinctions between approach and avoidance orientations to coping, there is controversy regarding whether initial treatment for trauma survivors should employ an exposure-based approach to increase affect or an affect-management approach to reduce it. In this article, we review theoretical and empirical literature regarding affect dysregulation and its relations with childhood sexual abuse and PTSD. We then describe a new affect-management group for adult survivors of childhood sexual abuse that is based on a stage approach to the treatment of trauma. This group emphasizes skill acquisition, symptom reduction, and patient stabilization. Affect-management strategies such as mindfulness, crisis planning, and challenging distorted thinking are presented to patients. Preliminary research findings support the use of this treatment.

Based on a 15-month prospective study, the following variables demonstrated an association with residential stability in a countywide probability sample of 397 homeless adults: female gender, a history of less than 1-year homelessness, absence of a health problem that limited work ability, entitlement-benefit income, and use of subsidized housing. Multivariate analyses show that two forms of public support—entitlement income and subsidized housing—were the most important variables associated with exits from homelessness into stable housing. Homeless adults with substance use disorders were more likely than other homeless adults to obtain unstable, but not stable housing. Homeless adults with mental disorders were no less likely than other homeless adults to report stable housing. Stable housing is necessary to break the cycle of homelessness, and economic resources such as entitlement income and subsidized housing are associated with stable housing for homeless adults.© 1999 John Wiley & Sons, Inc.

The purpose of this study was to examine the course of comorbid posttraumatic stress disorder (PTSD) in 54 patients with another anxiety disorder. Using a prospective longitudinal design, the present study found that during the first 5 years of follow-up the probability of full remission from a chronic episode of PTSD was .18. Findings from this and other research confirm clinical impressions that a substantial number of people never fully remit from their PTSD even after many years. Variables associated with a longer time to remit from an episode of chronic PTSD were a history of alcohol abuse and a history of childhood trauma.

Systematic research on effective treatment for survivors of childhood sexual abuse with posttraumatic stress disorder (PTSD) is virtually non-existent. The aim of the present study was to compare the effectiveness of an affect-management treatment (AM) group to a wait list control condition for female survivors of childhood sexual abuse with PTSD. Forty-eight female survivors of childhood sexual abuse with PTSD were randomly assigned to either a 15-week affect-management treatment group or to a wait list control condition. All subjects received individual psychotherapy and pharmacotherapy for the duration of the study, and for at least 1-month prior to the study. Controlling for pretreatment scores, subjects who completed the affect-management treatment group (n = 17) reported significantly fewer posttreatment symptoms of PTSD and dissociation than subjects in the wait list control condition (n = 16). Our findings suggest that an affect-management group treatment is beneficial as an adjunct to individual psychotherapy and pharmacotherapy for survivors of childhood sexual abuse with PTSD.