Engineered Osteochondral Grafts Using Biphasic Composite Solid Free-Form Fabricated Scaffolds

Tissue engineering has provided an alternative to traditional strategies to repair cartilage damaged by injury or degenerative disease. A successful strategy to engineer osteochondral tissue will mimic the natural contour of the articulating surface, achieve native mechanical properties and functional load-bearing ability, and lead to integration with host cartilage and underlying subchondral bone. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match articular geometry. The objective of this study was to utilize materials and biological factors in an integrated approach to regenerate a multitissue interface. Biphasic composite scaffolds manufactured by IBD and SFF fabrication were used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-L-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein 7 (BMP-7) in the ceramic phase and fully differentiated chondrocytes in the polymeric phase. After subcutaneous implantation into mice, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63145/1/ten.2004.10.1376.pd

Sociocognitive and posttraumatic models of dissociation are not opposed

No Abstracthttp://www.jonmd.comhb201

Institutional abuse and societal silence : an emerging global problem

No abstract available.http://anp.sagepub.com/2015-01-31hb201

Child abuse and the dynamics of silence

Response to Commentary by Haliburn J. Links Between Child Abuse and Major Mental Illness – Psychiatry’s response.http://anp.sagepub.comhb201

The Australian Royal Commission into institutional responses to child sexual abuse

No abstract available.http://anp.sagepub.com/2015-01-31hb201

The role of clinical experience, diagnosis, and theoretical orientation in the treatment of posttraumatic and dissociative disorders : a vignette and survey investigation

Controversy exists regarding the merits of exposure-based treatments for posttraumatic stress disorder (PTSD) versus a phased approach when prominent dissociative symptoms are present. The first aim of this study was to examine the degree to which diagnosing dissociation in two traumatized patients’ vignettes influenced clinicians’ preference for phase-oriented treatment and whether clinicians’ treatment experience contributed to their treatment preference. The second aim was to assess the extent to which participants had observed traumatized patients worsen when treated with exposure therapy or phase-oriented therapy and whether the theoretical orientation and treatment experience of the clinician were related to the observed deterioration. In the tradition of expert and practitioner surveys, 263 clinicians completed a survey of their diagnoses and treatment preferences for two vignettes and their treatment experience, theoretical orientation, and observations of patients’ deterioration. When a marked degree of dissociation was noted in the PTSD vignette, respondents favored phased approaches regardless of the diagnosis given. Reports of having observed patient deterioration during both exposure and phased therapy were predicted by years of experience. Psychodynamic therapists reported more observations of worsening during exposure therapy than cognitive behavior therapy therapists. Clinical experience treating PTSD may heighten awareness of negative therapeutic effects, potentially because experienced clinicians have a lower threshold for detecting such effects and because they are referred more challenging cases.http://www.tandfonline.com/loi/wjtd202018-09-27Psychiatr

Structure-Based Analysis of Five Novel Disease-Causing Mutations in 21-Hydroxylase-Deficient Patients

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients