Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Using Human-Centered Design to Adapt Supply Chains and Digital Solutions for Community Health Volunteers in Nomadic Communities of Northern Kenya.

BACKGROUND: Unreliable and nonexistent supply chain procedures and processes are one of the primary barriers to achieving functional community health units in nomadic communities in the arid/semiarid counties of Kenya. METHODS: We used a human-centered design (HCD) approach to engage communities and community health volunteers (CHVs) in redesigning a proven data-centric supply chain approach that included a digital solution, called cStock, for this challenging context. We conducted the HCD process in 4 phases: (1) understanding intent, (2) research and insights, (3) ideation and prototyping, and (4) supply chain design and requirements building. Data collection used qualitative methods and involved a range of stakeholders including CHVs, supervisors, and local beneficiaries. CHVs and their supervisors also participated in cStock usability testing. Drawing on insights and personas generated from the research, stakeholders ideated and codesigned supply chain tools. RESULTS: The research identified critical insights for informing the redesign of cStock for nomadic communities. These insights were categorized into supply chain, information systems, human resources, behaviors, service delivery infrastructure, and connectivity. Four supply chain data solutions were designed, prototyped, tested, and iterated: a stock recording paper-based form, a user-friendly cStock application, a supervisor cStock application, and an unstructured supplementary service data reporting system using feature phones. CONCLUSIONS: Using the HCD process incorporated the perspective of CHVs and their communities and provided key insights to inform the design of the supply chain and adapt cStock. The process helped make cStock to be inclusive and have the potential to have a meaningful impact on strengthening the supply chain for seminomadic and nomadic communities in northern Kenya. A strong supply chain for these CHVs will increase access to essential and reproductive health commodities and contribute to improving the overall health and well-being of these communities, especially women and children.

Factors Associated with Higher Pro-Inflammatory Tumor Necrosis Factor-α Levels in Young Women with Type 1 Diabetes.

AIMS: While cytokines play a role in the etiology of type 1 diabetes, cytokines later in the disease are less understood. We therefore investigated associations of pro-inflammatory tumor necrosis factor-α levels measured at prolonged disease duration with C-peptide at diagnosis, long-term glycemic control, diabetes duration, clinical factors, and health behaviors. METHODS: Data and blood were collected during an ancillary study to the longitudinal Wisconsin Diabetes Registry, a population-based cohort followed since diagnosis of type 1 diabetes. The ancillary study was conducted at 13-18 years diabetes duration, and enrolled premenopausal women age 18-45 years (n=87). RESULTS: Higher tumor necrosis factor-α levels at 13-18 years diabetes duration were independently associated with longer duration (p=0.0004) and worse current renal function (p=0.02). Additionally, diabetes duration modified both of the positive associations of tumor necrosis factor-α levels (both interactions p≤0.01) with mean glycemic control during the previous 10 years (significant only in women with longer durations) and current daily caffeine intake (significant only in women with shorter durations). In women with C-peptide measured at diagnosis (n=50), higher tumor necrosis factor-α levels at 13-18 years duration were associated with lower C-peptide (p=0.01), independent of glycemic control during the previous 10 years. CONCLUSIONS: Lower residual C-peptide at diagnosis and poor long-term glycemic control independently predicted higher pro-inflammatory tumor necrosis factor-α levels years later. The novel relationship with C-peptide needs confirmation in a larger cohort. Given the association between tumor necrosis factor-α and diabetes complications, further longitudinal studies may help clarify the potentially complex associations between glycemic control, inflammatory cytokines, and complications.

Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. METHODS AND RESULTS: We investigated 5079 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) who had food-frequency questionnaires and measurement of pericardial fat and hepatic attenuation at the baseline study visit in MESA, as well as a subgroup with imaging for visceral and subcutaneous fat (N = 1390). A dietary quality score (DietQuality) was constructed to include established food group constituents of a Mediterranean-type diet. Linear models estimated associations of dietary score as well as its constituents with regional adiposity. Baseline mean age was 61 (± 10) years, and approximately half of the participants (47%) were male. Those with a higher DietQuality score were generally older, female, with a lower body mass index, C-reactive protein, and markers of insulin resistance. After adjustment, a higher DietQuality score was associated with lower visceral fat (lowest vs. highest dietary score quartile: 523.6 vs. 460.5 cm(2)/m; P < 0.01 for trend), pericardial fat (47.5 vs. 41.3 cm(3)/m; P < 0.01 for trend), lesser hepatic steatosis (by hepatic attenuation; 58.6 vs. 60.7 Hounsfield units; P < 0.01 for trend), but not subcutaneous fat (P = 0.39). Greater fruits, vegetables, whole grains, seeds/nuts and yogurt intake were associated with decreased adiposity, while red/processed meats were associated with greater regional adiposity. CONCLUSION: A higher quality diet pattern is associated with less regional adiposity, suggesting a potential mechanism of beneficial dietary effects on diabetes, metabolic, and cardiovascular risk.

Systematic analysis of donor and isolation factor's impact on human islet yield and size distribution.

Islet transplantation is a promising therapy for T1DM. Key factors influencing islet yield have been identified with conflicting results. In this study, we analyzed 276 isolations to identify variables for islet yield and, additionally, islet size and size distribution. Pearson correlation analyses demonstrated that BMI had a positive correlation with pancreas size, actual islet count (AIC), and islet equivalent (IEQ)/g (all p ≤ 0.009), while CIT had a negative correlation with AIC and IEQ/g (all p ≤ 0.003). In mixed linear regression, BMI also had a positive correlation with islet size but only for shorter digestion times (≤15 min); there was no association between BMI and islet size for longer digestion times (>15 min). CIT was not associated with islet size. Donor age, sex, and preservation solutions were shown to have no correlation with islet yields or size distribution. Pancreas size had a positive correlation with AIC and a negative association with IEQ/g; it also had positive association with islet size but only for females, not males. Overdigestion was positively associated with islet counts; however, there was also a greater proportion of smaller islets when digestion rate was >74% (p = 0.005). Of the three collagenases analyzed, Sigma V had the lowest digestion rate (mean = 65%), approximately 5% or 10% lower than Roche Liberase HI (p = 0.04) and Serva NB1 (p = 0.0003), respectively; however, the Sigma V group showed better islet size preservation. Yet, the enzymes resulted in similar IEQ/g digested tissue. Of the isolated islets, 70.2% were smaller than 150 µm and contributed only 20.4% to the total IEQ, while 7.4% of the islets were larger than 250 µm but contributed 42.4% to the total IEQ. In summary, BMI, pancreas size, and CIT are useful variables for predicting islet yield, but selection of enzyme and balancing digestion time and rate are also important.

Poor glycemic control is associated with low BMD detected in premenopausal women with type 1 diabetes.

SUMMARY: The etiology of bone fragility in individuals with type 1 diabetes is unknown. This study demonstrated that bone turnover favors resorption and that poor glycemic control is associated with low bone mineral density (BMD) and low bone turnover, in premenopausal women with type 1 diabetes. The results could inform future interventions. INTRODUCTION: Low BMD and fracture may be complications of type 1 diabetes. We sought to determine the roles of bone turnover and glycemic control in the etiology of low BMD. METHODS: Premenopausal women from the Wisconsin Diabetes Registry Study and matched controls were compared (n = 75 pairs). Heel and forearm BMD were measured, and hip and spine BMD were measured in a subset. Markers of bone formation (osteocalcin) and resorption (NTx), and glycemic control (HbA1c) were determined. RESULTS: Age ranged from 18 to 50 years with a mean of 28, and 97% were Non-Hispanic white. Among women with diabetes, mean disease duration was 16 years and current HbA1c was 8%. Compared to controls, women with diabetes had a high prevalence of previous fracture (37% vs. 24%) and low BMD for age (heel or forearm: 49% vs. 31%), low heel and forearm BMD, and low osteocalcin levels. Levels of NTx were similar, suggesting uncoupled turnover favoring resorption. Poor glycemic control was associated with low BMD at all bone sites except the spine, and with low osteocalcin and NTx levels. CONCLUSIONS: Optimal glycemic control may prevent low BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.

A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells.

The utilization of adult stem cells in tissue engineering is a promising solution to the problem of tissue or organ shortage. Adult bone marrow derived mesenchymal stem cells (MSCs) are undifferentiated, multipotential cells which are capable of giving rise to chondrocytes when maintained in a three-dimensional culture and treated with members of the transforming growth factor-beta (TGF-beta) family of growth factors. In this study, we fabricated a nanofibrous scaffold (NFS) made of a synthetic biodegradable polymer, poly(-caprolactone) (PCL), and examined its ability to support in vitro chondrogenesis of MSCs. The electrospun PCL porous scaffold was constructed of uniform, randomly oriented nanofibers with a diameter of 700 nm, and structural integrity of this scaffold was maintained over a 21-day culture period. MSCs cultured in NFSs in the presence of TGF-beta1 differentiated to a chondrocytic phenotype, as evidenced by chondrocyte-specific gene expression and synthesis of cartilage-associated extracellular matrix (ECM) proteins. The level of chondrogenesis observed in MSCs seeded within NFSs was comparable to that observed for MSCs maintained as cell aggregates or pellets, a widely used culture protocol for studying chondrogenesis of MSCs in vitro. Due to the physical nature and improved mechanical properties of NFSs, particularly in comparison to cell pellets, the findings reported here suggest that the PCL NFS is a practical carrier for MSC transplantation, and represents a candidate scaffold for cell-based tissue engineering approaches to cartilage repair.

Multilineage differentiation of adult human bone marrow progenitor cells transduced with human papilloma virus type 16 E6/E7 genes.

We have established a new adult human bone marrow-derived cell line hMPC 32F, stably transduced with human papilloma virus type 16 E6/E7 genes, that displays mesenchymal multilineage differentiation ability in vitro. The hMPC 32F cells exhibited a population doubling time of 22 h and have been maintained in culture for about 20 passages. When cultured in conditions promoting osteogenic, adipogenic, or chondrogenic differentiation, hMPC 32F cells expressed mature differentiated phenotypes. These include (1) osteoblastic phenotype characterized by upregulated alkaline phosphatase (ALP) expression and extracellular matrix mineralization, (2) adipocytic phenotype with the presence of intracellular lipid droplets, and (3) chondrocytic phenotype of round cells surrounded by a sulfated proteoglycan-rich matrix. In addition, the hMPC 32F cells expressed differentiation lineage-specific genes, as detected by RT-PCR. Furthermore, osteogenic and adipogenic cultures responded to regulatory factors such as transforming growth factor-beta1 (TGF-beta1) and 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3). Thus, continuous treatment of osteogenic cultures for 2 weeks with TGF-beta1 decreased ALP activity and mRNA expression and inhibited osteocalcin mRNA expression and matrix mineralization, whereas l,25(OH)2D3 had an additive, stimulatory effect. In adipogenic cultures, treatment with TGF-beta1 for 2 weeks markedly inhibited adipogenesis whereas 1,25(OH)2D3 had no obvious effect. Finally, clonal analysis of hMPC 32F cells revealed a high percentage of multipotent clones, although clones of more restricted differentiation potential were also present. These characteristics of the hMPC 32F cell line suggest their pluripotent, progenitor, and nontransformed nature and indicate their potential application for studying the mechanisms governing developmental potential of adult human bone marrow mesenchymal progenitor cells.

Polymer/alginate amalgam for cartilage-tissue engineering.

Marrow stroma-derived cells (MSC) are highly proliferative, multipotential cells that have been considered as ideal candidate cells for autologous tissue engineering applications. In this study, we have characterized the chondrogenic potential of human MSCs in both a PLA/alginate amalgam and pure PLA macrostructure as model three-dimensional constructs to support both chondrogenic differentiation and proliferation following TGF-beta treatment. MSCs were seeded in experimental groups that consisted of PLA-loaded constructs and PLA/alginate amalgams with and without recombinant human TGF-beta1. Chondrogenesis of the PLA and the PLA/alginate amalgam cultures was assessed at weekly intervals by histology, immunohistochemistry, scanning electron microscopy, sulfate incorporation, and RT-PCR. Chondrogenic differentiation occurs within a polymeric macrostructure with TGF-beta1 treatment as indicated by histological, immunohistochemical, sulfate incorporation, and gene expression profiles. This macrostructure can be further encased in an alginate gel/solution to optimize cell shape and to confine growth factors and cells within the polymer construct, while the polymeric scaffold provides appropriate mechanical/tissue support. The stable three-dimensional PLA/alginate amalgam represents a novel candidate system of mesenchymal chondrogenesis, which is amendable to investigation of mechanical and biological factors that normally modulate cartilage development and formation as well as a potential tissue engineering construct for cartilage repair.

p38 MAP kinase regulation of AP-2 binding in TGF-beta1-stimulated chondrogenesis of human trabecular bone-derived cells.

Collagenase-treated, explanted human trabecular-bone chips are an excellent source of osteoblast-like cells. We have recently shown the multiple differentiation potential of these cells; in addition to osteogenesis and adipogenesis, these cells also undergo chondrogenesis when maintained as high-density pellet cultures (250,000 cells/pellet) in a serum-free, chemically defined medium stimulated with TGF-beta1 (10 ng/mL). In this investigation, we have analyzed how transactivating nuclear transcription factors, specifically AP-2 and SP-1, may interact with common cis-acting elements found in the regulatory region of cartilage-specific genes as part of the signal transduction mechanism of TGF-beta1 and p38 during chondrogenesis of human trabecular bone-derived multipotential cells. Both TGF-beta1 stimulation and p38 MAP kinase activation affect the binding of AP-2 as well as SP-1 to oligonucleotides with sequence similarity to the overlapping AP-2/SP-1 sites found in the putative 52-bp immediate upstream regulatory region and the 5'-untranslated region of the human aggrecan gene. Electrophoretic mobility shift assays show that TGF-beta1 treatment of the bone-derived cells inhibits AP-2 DNA binding but enhances the DNA binding ability of SP-1. Additionally, treatment of these TGF-beta1-stimulated cells with p38 MAP kinase inhibitor, SB203580, rescued the AP-2 DNA binding but did not affect SP-1 DNA binding. These findings indicate that AP-2 DNA binding is the target of both TGF-beta1 and p38 MAP kinase signaling pathways and suggest a possible signal transduction cascade whereby TGF-beta1 induction of chondrogenesis involves the activation of p38 MAP kinase and the subsequent inhibition of DNA binding by AP-2, thereby preventing the transcriptional repression of the aggrecan gene.

Three-dimensional cartilage formation by bone marrow-derived cells seeded in polylactide/alginate amalgam.

Bone marrow-derived cells are considered as candidate cells for cartilage tissue engineering by virtue of their ability to undergo chondrogenesis in vitro when cultured in high density or when embedded within a three-dimensional matrix in the presence of growth factors. This study evaluated the potential of human bone marrow-derived cells for cartilage tissue engineering by examining their chondrogenic properties within a three-dimensional amalgam scaffold consisting of the biodegradable polymer, poly-L-lactic acid (PLA) alone, and with the polysaccharide gel, alginate. Cells were suspended either in alginate or medium and loaded into porous PLA blocks. Alginate was used to improve cell loading and retention within the construct, whereas the PLA polymeric scaffold provided appropriate mechanical support and stability to the composite culture. Cells seeded in the PLA/alginate amalgams and the plain PLA constructs were treated with different concentrations of recombinant human transforming growth factor-beta1 (TGF-beta 1) either continuously (10 ng/mL) or only for the initial 3 days of culture (50 ng/mL). Chondrogenesis was assessed at weekly intervals with cultures maintained for up to 3 weeks. Histological and immunohistochemical analysis of the TGF-beta 1-treated PLA/alginate amalgam and PLA constructs showed development of a cartilaginous phenotype from day 7 to day 21 as demonstrated by colocalization of Alcian blue staining with collagen type II and cartilage proteoglycan link protein. Expression of cartilage specific genes, including collagen types II and IX, and aggrecan, was detected in TGF-beta 1-treated cultures by reverse transcription-polymerase chain reaction analysis. The initiation and progression of chondrogenic differentiation within the polymeric macrostructure occurred with both continuous and the initial 3-day TGF-beta 1 treatment regimens, suggesting that key regulatory events of chondrogenesis take place during the early period of cell growth and proliferation. Scanning electron microscopy revealed abundant cells with a rounded morphology in the PLA/alginate amalgam. These findings suggest that the three-dimensional PLA/alginate amalgam is a potential candidate bioactive scaffold for cartilage tissue engineering applications.

Application of mesenchymal stem cells in the regeneration of musculoskeletal tissues.

Mesenchymal stem cells are a rare population of undifferentiated cells, isolated from adult tissue sources, that have the capacity to differentiate into mesodermal lineages, including bone, fat, muscle, cartilage, tendon, and marrow stroma. These cell populations may be expanded in culture and subsequently permitted to differentiate into the desired lineage. This directed differentiation may be reached by the application of bioactive molecules, specific growth factors, and signaling molecules. Understanding the functional potential of these cells and the signaling mechanisms underlying their differentiation should lead to innovative protocols for clinical orthopaedic interventions. Clinically applicable techniques to isolate, expand, and reimplant these autogenous cells will become part of the repertoire of orthopaedic therapy. In the presence of extrinsic signaling molecules, provided by both the clinician and the local cellular environment, the intrinsic multipotential nature of the stem cells may be realized for applications such as the replacement of bone graft for segmental defects, nonunions, and spinal fusions. Additional applications may include treatment of full-thickness articular defects and articular resurfacing by site-specific delivery of stem cells. The ultimate goal is directed cellular regeneration of damaged or diseased musculoskeletal tissue. Currently, the limitation is our knowledge and ability to direct this differentiation, but with further study molecular orthopaedic interventions should become a reality.

Transcriptional and posttranscriptional regulation of proteoglycan gene expression.

Proteoglycans are among the most complex and sophisticated molecules of mammalian systems in terms of their protein and carbohydrate moieties. These macromolecules are in a continuous interplay with each other and the cell surface signal-transducing pathways, some of which are beginning to be elucidated. Because of their domain structure, catalytic potential, and diversity, these molecules appear to be designed for integrating numerous signaling events. For example, some proteoglycans interact with hyaluronan and lectins, thereby linking cell surfaces and distant matrix molecules. Some interact with collagen during the complex process of fibrillogenesis and regulate this biological process fundamental to animal life. Others interact with growth factors and serve as depot available during growth or tissue remodeling. In this review, we center on the most recent developments of proteoglycan biology, focusing primarily on genomic organization and transcriptional and posttranscriptional control. We discuss only those proteoglycans whose gene and promoter elements have been characterized and proved to be functional. When possible, we correlate the effects of growth factors and cytokines on proteoglycan gene expression with the topology of cis-acting elements in their genomic control regions. The analysis leads to a comprehensive critical appraisal of the principles that underlie the regulation of proteoglycan gene expression and to the delineation of common regulatory mechanisms.

Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene.

Distinct genetic abnormalities (loss-of-function mutations of APC and p53 and oncogenic activation of Ki-ras) are associated with specific stages of the sporadic, most common types of colorectal tumors. However, the inability to maintain primary colon epithelial cells in culture has hindered the analysis of the pathogenetic role of these abnormalities in colorectal tumorigenesis. We have now established primary cultures of epithelial cells from the colon crypts of p53-deficient mice; these cells are nontumorigenic as indicated by their failure to form colonies in soft agar and to grow as tumors in immunodeficient SCID mice and in immunocompetent syngeneic hosts. Upon ectopic expression of an activated Ki-ras gene, p53-deficient colon epithelial cells form colonies in soft agar and highly invasive subcutaneous tumors in both immunodeficient and immunocompetent mice. Ectopic expression of wild-type p53, but not of a DNA-binding-deficient mutant, markedly suppressed the colony-forming ability of the Ki-ras-transformed p53-deficient epithelial cells. Together, these findings establish a functional synergism in colorectal tumorigenesis dependent on the effects of an oncogenic Ki-ras in a p53-deficient background. This model of tumorigenic conversion of colon epithelial cells might be useful to identify genetic changes associated with disease progression and to evaluate the therapeutic response to conventional and novel anticancer drugs.

Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis.

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2-/- mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration.

Comorbidity between abuse of an adult and DSM-III-R mental disorders: evidence from an epidemiological study.

OBJECTIVE: The purpose of this study was to report the prevalence, risk, and implications of comorbidity between partner violence and psychiatric disorders. METHOD: Data were obtained from a representative birth cohort of 941 young adults through use of the Conflict Tactics Scales and Diagnostic Interview Schedule. RESULTS: Half of those involved in partner violence had a psychiatric disorder; one-third of those with a psychiatric disorder were involved in partner violence. Individuals involved in severe partner violence had elevated rates of a wide spectrum of disorders. CONCLUSIONS: The findings support the importance of mental health clinicians screening for partner violence and treating victims and perpetrators before injury occurs.