Surface CD1d, involved in immune cell interactions, was assessed for effects on hematopoiesis. Mouse bone marrow (BM) hematopoietic stem (HSCs) and progenitor (HPCs) cells expressed CD1d. Numbers and cycling status of HPCs in BM and spleen of different strains of CD1d-/- mice were significantly enhanced, suggesting CD1d as a negative regulator of HPCs. In support of this, CD1d was required for stem cell factor (SCF) and Flt3-ligand (FL) synergistic enhancement of colony stimulating factor (CSF)-induction of HPC colony formation, and for HPC response to myelosuppressive chemokines. Colony formation by immature subsets of HPCs was greatly enhanced when normal, but not CD1d -/-, BM cells were pretreated with CD1d antibodies in vitro. These effects required the full CD1d cytoplasmic tail. In contrast, long-, but not short-, term repopulating HSC engraftment was significantly impaired, effects minimally influenced by the presence of a truncated CD1d cytoplasmic tail. Pretreatment of normal BM cells with CD1d antibodies greatly enhanced their engraftment of HSCs. These results implicate CD1d in a previously unrecognized regulatory role of normal and stressed hematopoiesis.

OBJECTIVE:To identify the most useful clinical and histologic markers that facilitate early diagnosis in LMNA-related muscular dystrophy and to assess the usefulness of Western blotting (WB) for lamin A/C. METHODS:We analyzed the clinical and histologic features and WB results of all patients with laminopathies diagnosed in a research-based diagnostic service over 8 years. RESULTS:Although patients with congenital muscular dystrophy (MDCL)(n = 5) and Emery-Dreifuss muscular dystrophy (EDMD)(n = 5) had distinctive early clinical features, the lack of a suggestive clinical phenotype significantly delayed diagnosis in 2 of 3 patients with limb-girdle muscular dystrophy (LGMD)(n = 3). In addition, 6 of 20 muscle biopsy samples were considered nondystrophic, which contributed to delays in diagnosis in some patients. Neck extensor involvement (weakness or contractures) was the most consistent clinical sign, present in all patients. Reduced lamin A/C levels on WB were seen in 5 of 9 patients with laminopathies. CONCLUSION:Clinical features provide the best clues for diagnosing MDCL and EDMD early in the disease, and we urge clinicians to become familiar with those phenotypes. WB for lamin A/C may contribute to diagnosis but requires technical expertise, and results are normal in many individuals with LMNA mutations. Because of the survival benefit of early diagnosis and treatment, we recommend that LMNA gene sequencing be performed in all patients with undiagnosed congenital muscular dystrophy and neck extensor weakness, all patients with genetically undiagnosed LGMD, and those with suggestive clinical signs and nonspecific histologic abnormalities.

This overview of psychology in South Africa presents a concise and historical account of its science and practice, from its early origins in the late nineteenth century to the present, and traces seminal influences on the discipline. It is a review of how psychology in South Africa developed over more than a century to become one of the most popular subjects in universities and an established and recognized profession, whose members play a variety of roles in the South African polity and larger society. The impact that apartheid racism had on key aspects of psychology's development is traversed, and the influences that previous ruling party politics had on professional psychological organizations are delineated. The unification of psychology under the Psychological Society of South Africa, a few months before the advent of democracy in South Africa, is explicated. The protection of the title of psychologist in law and certain other changes in the legislative environment, enabling a greater role for psychologists, are reported. The primary research sites for psychology and its funding and the main university psychology programs are described, as are the requirements for registration and licensure. The genesis and the importance of the work of internationally acclaimed South African psychologists, such as J. Wolpe and A. A. Lazarus, are contextualized. With the increased participation of progressive black psychologists in leadership and research in the past two decades, a transformed psychology has the potential to play a significant role in addressing human issues confronting South Africa.

Research-generated information about mental disorders is crucial in order to establish the health needs in a given setting, to propose culturally apt and cost-effective individual and collective interventions, to investigate their implementation, and to explore the obstacles that prevent recommended strategies from being implemented. Yet the capacity to undertake such research in low- and middle-income countries is extremely limited. This article describes two methods that have proved successful in strengthening, or that have the potential to strengthen, mental health research capacity in low-resource settings. We identify the central challenges to be faced, review current programs offering training and mentorship, and summarize the key lessons learned. A structured approach is proposed for the career development of research staff at every career stage, to be accompanied by performance monitoring and support. A case example from the Mental Health and Poverty Project in sub-Saharan Africa illustrates how this approach can be put into practice-in particular, by focusing upon training in core transferrable research skills.

Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.

PURPOSE: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). METHODS AND MATERIALS: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS)(including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. RESULTS: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79%(p = 0.138) and the 5-year OS rate was 87% vs. 80%(p = 0.159). On multivariate analysis, percent positive cores (PPC)(p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50%(p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. CONCLUSIONS: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.

A cohort study was carried out on 112 breeding pig farms in England to investigate the impact of type of farrowing accommodation on preweaning mortality in piglets. Four types of farrowing accommodation were studied; farrowing crates, indoor loose pens, crate/loose systems (where the sow was restrained in a crate during birth and the first days of lactation before being moved to a loose pen) and outdoor farrowing in arcs in paddocks. Four estimates of preweaning mortality were collected: an oral estimate from the farmer before the visit, an estimate from the 6-month rolling average from computer records, records from 20 litters observed when the farm was visited and prospective records collected from 20 farrowings after the visit. These four estimates were significantly correlated. The prospective records also included a farmer reported date and cause of death. From the prospective data there were 25,031 piglets from 2143 litters from 112 farms, 6.5% of piglets were stillborn while live born preweaning mortality was 12%. Mixed effect discrete time survival, binomial and competing risk, models were used to investigate the association between preweaning mortality and farrowing accommodation, controlling for sow parity, litter size and number of piglets stillborn and fostered. There was a reduced risk of stillbirths in outdoor farrowing systems compared with crated systems. Farmers reported that crushing of healthy piglets was the most frequent cause of death accounting for 55% of live born preweaning mortality. There was no significant difference in mortality in live born piglets by farrowing system. There was a significantly higher risk of farmer reported crushing of healthy live born piglets in outdoor arcs compared with piglets reared with sows in farrowing crates and a significantly reduced risk of death from causes other than crushing in piglets reared outdoors or in crate/loose systems compared with piglets reared in crated systems. We conclude that, in the farms in this study, farrowing crates reduced the risk of preweaning live born mortality attributable to crushing but piglets in this system were at increased risk of death from other causes. Consequently crates had no significant effect on overall preweaning mortality percentage. In all four commercial production systems; outdoor, farrowing crates, crate/loose farrowing systems and indoor loose housed systems, there were similar levels of mortality.

PURPOSE: Studies exploring the relationship between poverty and mental health in low and middle income countries (LMICs) have produced somewhat conflicting results. This has partly been attributed to poorly operationalized and oversimplified poverty measures. This paper has two aims:(1) to review how socio-economic outcomes in psychiatric epidemiology in LMICs are measured;(2) based on this review, to provide a set of generic recommendations for measuring poverty in psychiatric epidemiology in LMIC. This is relevant for mental health researchers, and for practitioners and policy makers who use mental health research findings. METHODS: This review was part of a broader systematic review examining the association between poverty and mental illness. An analytic framework was developed to examine the definition and measurement of poverty in these studies. RESULTS: The majority of studies provided no definition for the concept of poverty being used, and very few measured poverty through standardized or validated methods. Many poverty indicators were broken down into extremely open-ended and vague categories, with no details on how the parameters were defined or derived, and no documentation of the time period and unit of analysis for which the poverty variable was measured. CONCLUSIONS: This review revealed that using poverty as an indicator in mental health research in LMIC is still in its infancy, with much room for improvement. The implications of poor measurement of poverty in psychiatric epidemiology are discussed. The recommendations provided will hopefully help researchers in psychiatric epidemiology use the concept of poverty in a much more critical, systematic and appropriate manner.