Adaptations to water stress and pastoralism in the Turkana of northwest Kenya.

The Turkana people inhabit arid regions of east Africa-where temperatures are high and water is scarce-and they practice subsistence pastoralism, such that their diet is primarily composed of animal products. Working with Turkana communities, we sequenced 367 genomes and identified 8 regions putatively involved in adaptation to water stress and pastoralism. One of these regions includes a putative enhancer for STC1-a kidney-expressed gene involved in the response to dehydration and the metabolism of purine-rich foods such as red meat. We show that STC1 is induced by antidiuretic hormone in humans, is associated with urea levels in the Turkana themselves, and is under strong selection in this population (s∼0.041). This work highlights that partnerships with subsistence-level groups can lead to new models of human physiology with biomedical relevance.

Correction: A new potential for methylammonium lead iodide.

Correction for 'A new potential for methylammonium lead iodide' by C. M. Handley et al., Phys. Chem. Chem. Phys., 2017, 19, 2313-2321.

A new potential for methylammonium lead iodide.

We present a new set of interatomic potentials for modelling methylammonium lead iodide. The potential model uses existing potentials for lead iodide and methylammonium, and new functions are fitted to enable these pre-existing potentials to be used together, while still being capable of modelling lead iodide and methylammonium iodide as separate materials. Fitting was performed using a combination of ab initio and experimental reference data. Our simulations are in agreement with experiment and reveal the short and long range ordering of the molecular cations and lead iodide octahedra.

The MMP3 gene in musculoskeletal soft tissue injury risk profiling: A study in two independent sample groups.

Matrix metalloproteinase-3 (MMP3) is a mediator of matrix remodelling and a proposed susceptibility locus in the genetic profile of musculoskeletal soft tissue injuries. Therefore, this study aimed to validate the MMP3 gene as a risk marker for these injuries by conducting a case control genetic association study in two independent samples groups. Three previously investigated MMP3 variants (rs679620, rs591058 and rs650108) in addition to the functional promoter variant (rs3025058) were genotyped in 195 Australian control participants and 79 Australian individuals with chronic Achilles tendinopathy. Similarly, 234 South African individuals with acute anterior cruciate ligament ruptures and 232 matched control participants were also analysed. Based on high linkage with the previously associated MMP3 variant rs679620, rs3025058 was inferred and found to be associated with increased risk for Achilles tendinopathy within the South African group (P = 0.012; OR: 2.88; 95% CI: 1.4 to 6.1). Lastly, the 6A-G-C-G haplotype, constructed from the investigated variants, was significantly associated with reduced risk for Achilles tendinopathy (29% CON vs. 20% TEN, P = 0.037) in the Australian group. In conclusion, a signal surrounding MMP3 is apparent with respect to Achilles tendinopathy. However, whether the investigated variants are contributing to injury susceptibility or whether they are merely linked to the risk conferring variants mapping elsewhere within the MMP gene cluster on chromosome 11, still requires refining.

ELN and FBN2 gene variants as risk factors for two sports-related musculoskeletal injuries.

The proteins ELN and FBN2 are important in extracellular matrix function. The ELN rs2071307 and FBN2 rs331079 gene variants have been associated with soft tissue pathologies. We aimed to determine whether these variants were predisposing factors for both Achilles tendinopathy (AT) and anterior cruciate ligament (ACL) ruptures. For the AT study, 135 cases (TEN group) and 239 asymptomatic controls were recruited. For the ACL rupture study our cohort consisted of 141 cases (ACL group) and 219 controls. Samples were genotyped for both the ELN rs2071307 and FBN2 rs331079 variants using TaqMan assays. Analysis of variance and chi-squared tests were used to determine whether either variant was associated with AT or ACL rupture with significance set at p<0.05. The GG genotype of the FBN2 variant was significantly over-represented within the TEN group (p=0.035; OR=1.83; 95% CI 1.04-3.25) compared to the CON group. We also found that the frequency of the G allele was significantly different between the TEN (p=0.017; OR=1.90; 95% CI 1.11-3.27) and ACL groups (p=0.047; OR=1.76; 95% CI 1.00-3.10) compared to controls. The ELN rs207137 variant was not associated with either AT or ACL rupture. In conclusion, DNA sequence variation within the FBN2 gene is associated with both AT and ACL rupture.

Wolbachia infection and Lepidoptera of conservation concern.

Conservation of at-risk species requires multi-faceted and carefully-considered management approaches to be successful. For arthropods, the presence of endosymbiotic bacteria, such as Wolbachia (Rickettsiales: Rickettsiaceae), may complicate management plans and exacerbate the challenges faced by conservation managers. Wolbachia poses a substantial and underappreciated threat to the conservation of arthropods because infection may induce a number of phenotypic effects, most of which are considered deleterious to the host population. In this study, the prevalence of Wolbachia infection in lepidopteran species of conservation concern was examined. Using standard molecular techniques, 22 species of Lepidoptera were screened, of which 19 were infected with Wolbachia. This rate is comparable to that observed in insects as a whole. However, this is likely an underestimate because geographic sampling was not extensive and may not have included infected segments of the species' ranges. Wolbachia infections may be particularly problematic for conservation management plans that incorporate captive propagation or translocation. Inadvertent introduction of Wolbachia into uninfected populations or introduction of a new strain may put these populations at greater risk for extinction. Further sampling to investigate the geographic extent of Wolbachia infections within species of conservation concern and experiments designed to determine the nature of the infection phenotype(s) are necessary to manage the potential threat of infection.

What does practice development (PD) offer mental health-care contexts? A comparative case study of PD methods and outcomes.

Practice development (PD) in mental health nursing has been progressing over the last decade; however, the level and impact of PD activity in the field of mental health remains poorly understood outside localized project impact. More specific reporting and comparative analysis of PD outcomes will improve this situation. In response, this paper presents three case scenarios from work taking place in Australia and New Zealand, as working examples of how PD methodologies have been applied within mental health practice settings. Using a comparative framework that captures the contributing assumptions, practices, processes and conditions imperative to effective PD work within a mental health-care context, three case vignettes are reviewed. The critical question driving this paper is 'what mental health-care services does PD offer in terms of transformational change approaches and the promotion of effective workplace cultures?' Conditions considered necessary for successful PD initiatives within mental health contexts are explored such as how PD converges and diverges with mental health-related theories, plus where and how PD activity best integrates with the specific elements associated with mental health-care provision. The findings are further reviewed in line with reports of PD outcomes from other fields of health care.

The imaging and classification of severe pelvic ring fractures: Experiences from two level 1 trauma centres.

We describe the routine imaging practices of Level 1 trauma centres for patients with severe pelvic ring fractures, and the interobserver reliability of the classification systems of these fractures using plain radiographs and three-dimensional (3D) CT reconstructions. Clinical and imaging data for 187 adult patients (139 men and 48 women, mean age 43 years (15 to 101)) with a severe pelvic ring fracture managed at two Level 1 trauma centres between July 2007 and June 2010 were extracted. Three experienced orthopaedic surgeons classified the plain radiographs and 3D CT reconstruction images of 100 patients using the Tile/AO and Young-Burgess systems. Reliability was compared using kappa statistics. A total of 115 patients (62%) had plain radiographs as well as two-dimensional (2D) CT and 3D CT reconstructions, 52 patients (28%) had plain films only, 12 (6.4%) had 2D and 3D CT reconstructions images only, and eight patients (4.3%) had no available images. The plain radiograph was limited to an anteroposterior pelvic view. Patients without imaging, or only plain films, were more severely injured. A total of 72 patients (39%) were imaged with a pelvic binder in situ. Interobserver reliability for the Tile/AO (Kappa 0.10 to 0.17) and Young-Burgess (Kappa 0.09 to 0.21) was low, and insufficient for clinical and research purposes. Severe pelvic ring fractures are difficult to classify due to their complexity, the increasing use of early treatment such as with pelvic binders, and the absence of imaging altogether in important patient sub-groups, such as those who die early of their injuries.

Involvement of proteoglycans in tendinopathy.

A major feature of chronic tendinopathy is a change in the nature and organisation of the extracellular matrix of tendon. Increased levels of proteoglycans have been shown in the extracellular matrix of tendinopathic tendons and these appear to influence the increased hydration and swelling of the tissue that is a feature of this condition. There is a paucity of knowledge about proteoglycans in normal and tendinopathic tendons. This review sets out to describe the nature, function and metabolism of proteoglycans present in normal tendon and in tendinopathy and outlines how changes in proteoglycan metabolism may contribute to the development and progression of this disease.

Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations.

OBJECTIVES: A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathy in a South African population. The aim of this case-control genetic association study was to investigate the BstUI and DpnII restriction fragment length polymorphisms (RFLP) in a second population from Australia and to identify a predisposing haplotype for Achilles tendinopathy in both populations. METHODS: 85 Australian and 93 South African patients with tendinopathy, as well as 210 Australian and 132 white South African control subjects were genotyped for the BstUI (rs12722) and DpnII (rs13946) RFLP, as well as markers rs10858286, rs3196378, rs11103544, rs4504708 and rs3128575. RESULTS: The BstUI RFLP (p<0.001) and marker rs3196378 (p = 0.016) were associated with chronic Achilles tendinopathy in Australian subjects. Individuals within both populations with a CC genotype for the BstUI RFLP had a significantly decreased risk of developing tendinopathy versus any other genotypes (Australian odds ratio 0.42, 95% CI 0.20 to 0.86, p = 0.017). The TC inferred haplotype (rs12722, rs3196378) was found to be overrepresented (global p = 0.008) in the South African tendinopathy group compared with all other haplotypes. CONCLUSION: The BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and a region within the COL5A1 3' untranslated region may predispose individuals to an increased risk of developing chronic Achilles tendinopathy.

A summary of the reading comprehension research undertaken with students who are deaf or hard of hearing.

The American Federation of Teachers (1999) has stated that "the most fundamental responsibility of schools is teaching students to read" (p. 7). The central purpose of reading is comprehension--constructing meaning from text. The purpose of the present study was to identify, review, and summarize the research published in professional peer-reviewed journals related to reading comprehension and school-age students who are deaf or hard of hearing between 1963 and 2005. Fifty-two studies were identified and reviewed. The results were summarized in a table and reported descriptively. The most frequently researched reading comprehension teaching strategies were identified and discussed. The need for more research in this critical area was noted.

Effects of glucosamine on proteoglycan loss by tendon, ligament and joint capsule explant cultures.

OBJECTIVE: To investigate the effect of glucosamine on the loss of newly synthesized radiolabeled large and small proteoglycans by bovine tendon, ligament and joint capsule. DESIGN: The kinetics of loss of (35)S-labeled large and small proteoglycans from explant cultures of tendon, ligament and joint capsule treated with 10mM glucosamine was investigated over a 10-day culture period. The kinetics of loss of (35)S-labeled small proteoglycans and the formation of free [(35)S]sulfate were determined for the last 10 days of a 15-day culture period. The proteoglycan core proteins were analyzed by gel electrophoresis followed by fluorography. The metabolism of tendon, ligament and joint capsule explants exposed to 10mM glucosamine was evaluated by incorporation of [(3)H]serine and [(35)S]sulfate into protein and glycosaminoglycans, respectively. RESULTS: Glucosamine at 10mM stimulated the loss of small proteoglycans from ligament explant cultures. This was due to the increased loss of both macromolecular and free [(35)S]sulfate to the medium indicating that glucosamine affected the release of small proteoglycans as well as their intracellular degradation. The degradation pattern of small proteoglycans in ligament was not affected by glucosamine. In contrast, glucosamine did not have an effect on the loss of large or small proteoglycans from tendon and joint capsule or large proteoglycans from ligament explant cultures. The metabolism of cells in tendon, ligament and joint capsule was not impaired by the presence of 10mM glucosamine. CONCLUSIONS: Glucosamine stimulated the loss of small proteoglycans from ligament but did not have an effect on small proteoglycan catabolism in joint capsule and tendon or large proteoglycan catabolism in ligament, tendon or synovial capsule. The consequences of glucosamine therapy at clinically relevant concentrations on proteoglycan catabolism in joint fibrous connective tissues need to be further assessed in an animal model.

Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee.

Expansion of the extracellular matrix is a prominent but poorly characterized feature of tendinosis. The present study aimed to characterize the extent and distribution of the large aggregating proteoglycan versican in patients with patellar tendinosis. We obtained tendon from tendinopathy patients undergoing debridement of the patellar tendon and from controls undergoing intramedullary tibial nailing. Versican content was investigated by Western blotting and immunohistochemistry. Microvessel thickness and density were determined using computer-assisted image analysis. Markers for smooth muscle actin, endothelial cells (CD31) and proliferating cells (Ki67) were examined immunohistochemically. Western blot analysis and immunohistochemical staining revealed elevated versican content in the proximal patellar tendon of tendinosis patients (P=0.042). Versican content was enriched in regions of fibrocartilage metaplasia and fibroblast proliferation, as well as in the perivascular matrix of proliferating microvessels and within the media and intima of arterioles. Microvessel density was higher in tendinosis tissue compared with control tissue. Versican deposition is a prominent feature of patellar tendinosis. Because this molecule is not only a component of normal fibrocartilagenous matrices but also implicated in a variety of soft tissue pathologies, future studies should further detail both pathological and adaptive roles of versican in tendons.

Indomethacin use for the management of patent ductus arteriosus in preterms: a web-based survey of practice attitudes among neonatal fellowship program directors in the United States.

The objective of this study was to determine whether neonatal-perinatal fellowship programs (NFTPs) in the United States vary in indomethacin use for the management of patent ductus arteriosus (PDA) in < or =28 week gestational age infants at birth. A 53-item web-based survey was sent to 84 NFTP directors who received prenotification, followed 2 weeks later by a reminder letter. A total of 56 NFTP directors responded (67% maximum response rate). Wide variation exists in the maximum number of indomethacin courses used to close ductus, use of indomethacin for reopened PDA beyond 14 days, ductal closure definition, contraindications before consideration of indomethacin, interventions for contraindications, and reported ductal closer rate after each indomethacin course. Indomethacin therapy for symptomatic PDA and short course of indomethacin are common practices. Indomethacin use for the management of PDA in premature infants varies among NFTP directors. Practice attitudes may explain variations in ductal closure and ligation rates. Because practice variations may have implications for long-term outcome of vulnerable premature infants, studies relevant to the management of PDA in premature infants are needed.

Behavior change in a student with a dual diagnosis of deafness and pervasive developmental disorder: a case study.

The broad term pervasive developmental disorder (PPD) describes a set of symptoms that occur along a continuum of severity; these symptoms are often referred to as autism spectrum disorders (ASDs). Little is known about the incidence and prevalence of ASDs among students who are deaf or hard of hearing (DHH). Teachers of DHH students, who must work with individuals with dual diagnoses, are at a loss for guidance from the literature. The authors review the literature on ASDs (also referred to as PDD) within the DHH population, provide results of a single-subject study to reduce PDD-type behaviors in a child with hearing loss, and argue that teachers of students who are DHH must learn about practices associated with applied behavior analysis as an tool for intervening therapeutically with children with dual diagnoses of hearing loss plus an ASD.

Effects of long-term exposure to glucosamine and mannosamine on aggrecan degradation in articular cartilage.

OBJECTIVE: To investigate the effect of long-term exposure to glucosamine or mannosamine on the catabolism of aggrecan by explant cultures of bovine articular cartilage maintained in the presence of retinoic acid. DESIGN: The kinetics of loss of 35S-labeled and total aggrecan from explant cultures of bovine articular cartilage maintained in the presence of 1 micro M retinoic acid and exposed to varying concentrations of glucosamine or mannosamine was investigated over a 9-day culture period. In other experiments, the reversibility of the inhibition of aggrecan catabolism by glucosamine or mannosamine was investigated in cultures exposed to these amino sugars for the first 5 days of a 15-day culture period. The metabolism of chondrocytes exposed to these amino sugars was evaluated by measurement of lactate production or 3H-serine and 35S-sulfate incorporation into protein and glycosaminoglycans, respectively. The direct effect of these amino sugars on soluble aggrecanase activity was determined from immunoblots of aggrecan digests. RESULTS: Glucosamine at 5mM concentration and mannosamine at 2mM concentration inhibited degradation of radiolabeled and chemical levels of aggrecan. At concentrations of up to 10mM amino sugars, the metabolism of chondrocytes was not impaired, as determined by lactate production, protein synthesis and the incorporation of 35S-sulfate into proteoglycans. These amino sugars did not inhibit soluble aggrecanase activity. The exposure of articular cartilage explants to 5mM glucosamine or mannosamine for 5 days in culture in the presence or absence of retinoic acid did not provide long-term suppression of stimulated aggrecan loss. CONCLUSIONS: This study indicates that continuous presence of amino sugars is required to protect cartilage from stimulated loss of aggrecan.

Cathepsin D cleaves aggrecan at unique sites within the interglobular domain and chondroitin sulfate attachment regions that are also cleaved when cartilage is maintained at acid pH.

Bovine aggrecan was digested with bovine cathepsin D at pH 5.2 under conditions of partial digestion and the resulting aggrecan core protein fragments were separated by electrophoresis on gradient polyacrylamide gels. The fragments were characterized by their reactivity to specific antibodies and by N-terminal amino acid sequencing. It was also demonstrated that cathepsin D cleaved bovine aggrecan at five sites within the core protein, between residues Phe(342)-Phe(343) in the interglobular domain, Leu(1462)-Val(1463) between the chondroitin sulfate attachment regions 1 and 2 and Leu(1654)-Val(1655), Phe(1754)-Val(1755) and Leu(1854)-Ile(1855) that are located within the chondroitin sulfate attachment region 2 of the core protein. The time course of digestion showed that there was a continued degradation of aggrecan and there was no preferential cleavage of the core protein at any one site. It was shown that cathepsin D digested aggrecan over the pH range 5.2-6.5 resulting in the same products. When bovine cartilage was maintained in explant culture at pH 5.2 there was a rapid loss of both radiolabeled and chemical pools of sulfated glycosaminoglycans into the culture medium and this loss was inhibited by the inclusion in the medium of the aspartic proteinase inhibitor, pepstatin A. The aggrecan core protein fragments appearing in the medium of cultures maintained at pH 5.2 were characterized and it was shown that the fragments had N-terminal sequences starting at Phe(343), Ile(1855), and Val(1755) or Val(1463). This work demonstrates that cathepsin D present within the extracellular matrix of articular cartilage has the potential to contribute to the proteolytic processing of the core protein of aggrecan in this tissue.

The Tasmanian children's project: the needs of children with a parent/carer with a mental illness.

This paper presents some of the key findings and recommendations of the report The Tasmanian Children's Project (TCP): The Needs of Children with a Parent/Carer with a Mental Illness, October, 1999. The TCP, a collaborative venture between the University of Tasmania's School of Nursing and the Mental Health Services - South, Tasmania (Department of Health and Human Services), is the first study in Tasmania to formally examine the needs of children where the parent/carer has a mental illness. The study is a modified replication and extension of the 1993/94 Victorian Children's Project. Extension aspects of the TCP included interviews with children (in addition to parents and service providers), the inclusion of data on both maternal and paternal mental illness and a broad definition of mental illness (beyond psychotic illness and major affective disorder). The report highlights the need to provide a range of programs that encourage the development of personal competency among children, parents, and other family members and those that emphasize interagency collaboration. Implications of this research for mental health nursing education and practice are also addressed.

Expression and activity of ADAMTS-5 in synovium.

ADAMTS proteinases, belonging to the adamalysin subfamily of metalloproteinases, have been implicated in a variety of cellular events such as morphogenesis, cell migration, angiogenesis, ovulation and extracellular matrix breakdown. Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) have been identified in cartilage and are largely responsible for cartilage aggrecan breakdown. We have shown previously that synovium, the membrane lining diarthrodial joints, generates soluble aggrecanase activity. We report here the expression, localization and activity of ADAMTS-5 from human arthritic and bovine synovium. ADAMTS-5 was expressed constitutively in synovium with little or no transcriptional regulation by recombinant human interleukin-1 alpha or all-trans-retinoate, factors previously shown to upregulate aggrecanase activity in cartilage. Aggrecanase activity generated by synovium in vitro and recombinant ADAMTS-5 cleaved aggrecan extensively, resulting in aggrecan fragments similar to those generated by chondrocyte-derived aggrecanases, and the activity was inhibited by heparin. ADAMTS-5 was immunolocalized in human arthritic synovium, where staining was mostly pericellular, particularly in the synovial lining and around blood vessels; some matrix staining was also seen. The possibility that synovium-derived ADAMTS-5 may play a role in cartilage aggrecan breakdown is discussed.

Calcium pentosan polysulfate inhibits the catabolism of aggrecan in articular cartilage explant cultures.

OBJECTIVE: The catabolism of aggrecan and loss of aggrecan fragments from articular cartilage is a key event in the pathogenesis of arthritic diseases such as osteoarthritis. The catabolism of aggrecan is mediated by the specific proteolytic activity termed aggrecanase. The aim of this study was to investigate the effect of the chondroprotective agent calcium pentosan polysulfate (CaPPS) on the aggrecanase-mediated catabolism of aggrecan. METHODS: The catabolism of 35S-labeled aggrecan and loss of tissue glycosaminoglycans (GAGs) were investigated using bovine articular cartilage explant cultures maintained in medium containing varying concentrations of CaPPS (1-100 microg/ml) in the presence or absence of 10(-6)M retinoic acid or 7 ng/ml recombinant human interleukin-1alpha (rHuIL-1alpha). In addition, the effect of CaPPS on the degradation of aggrecan monomers by aggrecanase activity present in conditioned medium from joint capsule explant cultures was investigated. RESULTS: CaPPS inhibited the catabolism of 35S-labeled aggrecan in a dose-dependent manner, particularly when retinoic acid or rHuIL-1alpha was used to stimulate aggrecan catabolism. These effects were reflected in the tissue levels of GAG remaining in these cultures at the end of the experiment. CaPPS inhibited the degradation of aggrecan monomers by soluble aggrecanase activity. CONCLUSION: CaPPS inhibits the catabolism of aggrecan by articular cartilage in a dose-dependent manner, particularly when the processes responsible for aggrecan loss are stimulated. This effect occurs, at least in part, through direct inhibition of aggrecanase activity. CaPPS did not adversely affect overall chondrocyte metabolism, as shown by the incorporation of 35S-sulfate and 3H-leucine into macromolecules and by lactate production in cartilage explant cultures.