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Objective: This article examined possible ways of classifying eating disorders not otherwise specified (EDNOS) using latent profile analysis (LPA). Method: Of 687 patients being seen for an evaluation for an eating disorder, 284 were classified as having anorexia nervosa (AN) or bulimia nervosa (BN). LPA was performed on the remaining 403 cases (EDNOS). Results: Five clusters were identified that characterized individuals who appeared to be: (1) subsyndromal restrictor AN patients that denied a great deal of eating disorder (ED) psychopathology; (2) subsyndromal ED patients, some but not all of whom were low weight; (3) subsyndromal BN with higher rates of vomiting than binge-eating; (4) primarily overweight individuals with low levels of ED pathology; or (5) overweight patients who most resembled binge eating disorder (BED). Conclusion: Most EDNOS cases resembled AN, BN, or BED cases and can be conceptualized several ways, one of which is to see them as existing on a continuum with the DSM-IV ED. Int J Eat Disord 2007 © 2007 by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims: The first metatarsal pronation deformity of hallux valgus feet is widely recognized. However, its assessment relies mostly on 3D standing CT scans. Two radiological signs, the first metatarsal round head (RH) and inferior tuberosity position (ITP), have been described, but are seldom used to aid in diagnosis. This study was undertaken to determine the reliability and validity of these two signs for a more convenient and affordable preoperative assessment and postoperative comparison., Methods: A total of 200 feet were randomly selected from the radiograph archives of a foot and ankle clinic. An anteroposterior view of both feet was taken while standing on the same x-ray platform. The intermetatarsal angle (IMA), metatarsophalangeal angle (MPA), medial sesamoid position, RH, and ITP signs were assessed for statistical analysis., Results: There were 127 feet with an IMA > 9°. Both RH and ITP severities correlated significantly with IMA severity. RH and ITP were also significantly associated with each other, and the pronation deformities of these feet are probably related to extrinsic factors. There were also feet with discrepancies between their RH and ITP severities, possibly due to intrinsic torsion of the first metatarsal., Conclusion: Both RH and ITP are reliable first metatarsal pronation signs correlating to the metatarsus primus varus deformity of hallux valgus feet. They should be used more for preoperative and postoperative assessment., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 Wu and Lam.)

Talipes equinovarus, also called clubfoot, is a relatively common congenital defect affecting approximately one in every 1000 live births. Most cases of clubfoot are expected to be idiopathic and unrelated to an underlying genetic syndrome. In approximately 20% of cases, a clear genetic etiology is identified. Here we present two cases of bilateral clubfoot identified via fetal ultrasound in the first trimester associated with osteogenesis imperfecta diagnosed in the second trimester. Both fetuses presented with multiple fractures and were identified to have loss-of-function variants in COL1A1. An association between clubfeet in the first trimester and osteogenesis imperfecta has not been previously reported to the best of our knowledge, which leads to unique opportunities for prompt diagnosis, genetic counseling and testing, and appropriate management., (© 2024 Wiley Periodicals LLC.)

Melanoma is the most aggressive type of skin cancer and is responsible for the majority of deaths from skin cancer. Therapeutic advances in the last few decades, notably the development of novel targeted therapies and immunotherapies have significantly improved patient outcomes; nonetheless, these options remain limited due to the onset of resistance to treatment modalities and relapse. In this review, we focus on the available therapeutic options, their benefits, and limitations., (© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Melanoma is the most aggressive and deadly form of skin cancer due to its high propensity to metastasize to distant organs. Significant progress has been made in the last few decades in melanoma therapeutics, most notably in targeted therapy and immunotherapy. These approaches have greatly improved treatment response outcomes; however, they remain limited in their abilities to hinder disease progression due, in part, to the onset of acquired resistance. In parallel, intrinsic resistance to therapy remains an issue to be resolved. In this review, we summarize currently available therapeutic options for melanoma treatment and focus on possible mechanisms that drive therapeutic resistance. A better understanding of therapy resistance will provide improved rational strategies to overcome these obstacles., Competing Interests: The authors declare no conflicts of interest.

Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice. The greatest reduction in tumor progression was observed in male mice treated with single-agent troriluzole and anti-PD-1. Furthermore, a randomly selected group of mice was removed from treatment after 18 weeks and maintained for up to an additional 48 weeks demonstrating the utility of the TGS mouse model to perform a ≥1-year preclinical therapeutic study in a physiologically relevant tumor-host environment. Digital spatial imaging analyses were performed in tumors and tumor microenvironments across treatment modalities using antibody panels for immune cell types and immune cell activation. The results suggest that immune cell populations and cytotoxic activities of T cells play critical roles in treatment responses in these mice. Examination of a group of molecular protein markers based on the proposed mechanisms of action of inhibitors of glutamatergic signaling and immune checkpoint showed that alterations in expression levels of xCT, γ-H2AX, EAAT2, PD-L1, and PD-1 are likely associated with the loss of treatment responses. These results suggest the importance of tracking changes in molecular markers associated with the mechanism of action of therapeutics over the course of a longitudinal preclinical therapeutic study in spatial and temporal manners., (© 2024 The Authors.)

Mouse models that reflect human disorders provide invaluable tools for the translation of basic science discoveries to clinical therapies. However, many of these in vivo therapeutic studies are short term and do not accurately mimic patient conditions. In this study, we used a fully immunocompetent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, mGluR1, as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, which is a prodrug of riluzole, plus an antibody against PD-1, an immune checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to improved survival in troriluzole and/or anti-PD-1-treated male mice that correlated with differential CD8 + T cells and CD11b + myeloid cell populations in the tumor-stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immunocompetent setting., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO's latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women's experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: (1) develop and optimise a strategy for implementing the LCG (formative phase); and (2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase)., Methods: In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women's experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness., Discussion: Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally., Trial Registration: CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022)., (© 2023. The Author(s).)

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Cancer is the second leading cause of death, and incidences are increasing globally. Simply defined, cancer is the uncontrolled proliferation of a cell, and depending on the tissue of origin, the cancer etiology, biology, progression, prognosis, and treatment will differ. Carcinogenesis and its progression are associated with genetic factors that can either be inherited and/or acquired and are classified as an oncogene or tumor suppressor. Many of these genetic factors converge on common signaling pathway(s), such as the MAPK and PI3K/AKT pathways. In this review, we will focus on the metabotropic glutamate receptor (mGluR) family, an upstream protein that transmits extracellular signals into the cell and has been shown to regulate many aspects of tumor development and progression. We explore the involvement of members of this receptor family in various cancers that include breast cancer, colorectal cancer, glioma, kidney cancer, melanoma, oral cancer, osteosarcoma, pancreatic cancer, prostate cancer, and T-cell cancers. Intriguingly, depending on the member, mGluRs can either be classified as oncogenes or tumor suppressors, although in general most act as an oncogene. The extensive work done to elucidate the role of mGluRs in various cancers suggests that it might be a viable strategy to therapeutically target glutamatergic signaling.

Background: Hypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO 4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO 4 remains underused, particularly in low- and middle-income countries (LMICs)., Objective: This qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO 4 to prevent or treat pre-eclampsia/eclampsia., Search Strategy: We searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021., Selection Criteria: Primary qualitative and mixed-methods studies on factors affecting use of MgSO 4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion., Data Collection and Analysis: We applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO 4 ., Main Results: We included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO 4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO 4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation., Conclusions: These findings can inform policy and guideline development and improve implementation of MgSO 4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used., Tweetable Abstract: Global qualitative review identifies factors affecting underutilisation of MgSO 4 for pre-eclampsia and eclampsia., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Globally, there is growing awareness of the important contributions men can make as key stakeholders in maternal and newborn health (MNH), and increased investment in interventions designed to influence men's engagement to improve MNH outcomes. Interventions typically target men, women, couples or health providers, yet how these stakeholders perceive and experience interventions is not well understood and the fact that women may experience these interventions as disempowering has been identified as a major concern. This review aims to synthesise how women, men, and providers perceive and experience interventions designed to influence men's engagement in MNH, in order to identify perceived benefits and risks of participating in interventions, and other key factors affecting uptake of and adherence to interventions. We conducted a qualitative evidence synthesis based on a systematic search of the literature, analysing a purposive sample of 66 out of 144 included studies to enable rich synthesis. Women, men and providers report that interventions enable more and better care for women, newborns and men, and strengthen family relationships between the newborn, father and mother. At the same time, stakeholders report that poorly designed or implemented interventions carry risks of harm, including constraining some women's access to MNH services and compounding negative impacts of existing gender inequalities. Limited health system capacity to deliver men-friendly MNH services, and pervasive gender inequality, can limit the accessibility and acceptability of interventions. Sociodemographic factors, household needs, and peer networks can influence how men choose to support MNH, and may affect demand for and adherence to interventions. Overall, perceived benefits of interventions designed to influence men's engagement in MNH are compelling, reported risks of harm are likely manageable through careful implementation, and there is clear evidence of demand from women and men, and some providers, for increased opportunities and support for men to engage in MNH., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mutant isocitrate-dehydrogenase 1 ( mIDH1 ) synthesizes the oncometabolite 2-hydroxyglutarate (2HG), which elicits epigenetic reprogramming of the glioma cells’ transcriptome by inhibiting DNA and histone demethylases. We show that the efficacy of immune-stimulatory gene therapy (TK/Flt3L) is enhanced in mIDH1 gliomas, due to the reprogramming of the myeloid cells’ compartment infiltrating the tumor microenvironment (TME). We uncovered that the immature myeloid cells infiltrating the mIDH1 TME are mainly nonsuppressive neutrophils and preneutrophils. Myeloid cell reprogramming was triggered by granulocyte colony-stimulating factor (G-CSF) secreted by mIDH1 glioma stem/progenitor-like cells. Blocking G-CSF in mIDH1 glioma–bearing mice restores the inhibitory potential of the tumor-infiltrating myeloid cells, accelerating tumor progression. We demonstrate that G-CSF reprograms bone marrow granulopoiesis, resulting in noninhibitory myeloid cells within mIDH1 glioma TME and enhancing the efficacy of immune-stimulatory gene therapy.

Background: The spread of the novel coronavirus (COVID-19) was declared a pandemic by the World Health Organization on 11th March 2020. Since then there has been a rapid rise in development of maternal and perinatal health guidelines related to COVID-19. The aim of this project was to develop a database of Australian and international recommendations relating to antenatal, intrapartum and postpartum care of women during the COVID-19 pandemic, in order to identify inconsistencies in clinical guidance., Methods: We conducted weekly web searches from 30th March to 15th May 2020 to identify recommendations pertaining to the care of women during pregnancy, labour and postpartum period from national or international professional societies, specialist colleges, Ministries of Health, Australian state and territory governments, and international guideline development organisations. Individual recommendations were extracted and classified according to intervention type, time period, and patient population. Findings were reported using descriptive analysis, with areas of consensus and non-consensus identified., Results: We identified 81 guidelines from 48 different organisations. Generally, there was high consensus across guidelines for specific interventions. However, variable guidance was identified on the use of nitrous oxide during labour, administration of antenatal corticosteroids, neonatal isolation after birth, labour and birth companions, and the use of disease modifying agents for treating COVID-19., Conclusion: Discrepancies between different guideline development organisations creates challenges for maternity care clinicians during the COVID-19 pandemic. Collating recommendations and keeping up-to-date with the latest guidance can help clinicians provide the best possible care to pregnant women and their babies., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Like other cancers, melanomas are associated with the hyperactivation of two major cell signaling cascades, the MAPK and PI3K/AKT pathways. Both pathways are activated by numerous genes implicated in the development and progression of melanomas such as mutated BRAF , RAS , and NF1 . Our lab was the first to identify yet another driver of melanoma, Metabotropic Glutamate Receptor 1 (protein: mGluR1, mouse gene: Grm1 , human gene: GRM1 ), upstream of the MAPK and PI3K/AKT pathways. Binding of glutamate, the natural ligand of mGluR1, activates MAPK and PI3K/AKT pathways and sets in motion the deregulated cellular responses in cell growth, cell survival, and cell metastasis. In this review, we will assess the proposed modes of action that mediate the oncogenic properties of mGluR1 in melanoma and possible application of anti-glutamatergic signaling modulator(s) as therapeutic strategy for the treatment of melanomas.

Melanoma, a cancer of the skin, arises from transformed melanocytes. Melanoma has the highest mutational burden of any cancer partially attributed to UV induced DNA damage. Localized melanoma is "curable" by surgical resection and is followed by radiation therapy to eliminate any remaining cancer cells. Targeted therapies against components of the MAPK signaling cascade and immunotherapies which block immune checkpoints have shown remarkable clinical responses, however with the onset of resistance in most patients, and, disease relapse, these patients eventually become refractory to treatments. Although great advances have been made in our understanding of the metastatic process in cancers including melanoma, therapy failure suggests that much remains to be learned and understood about the multi-step process of tumor metastasis. In this review we provide an overview of melanocytic transformation into malignant melanoma and key molecular events that occur during this evolution. A better understanding of the complex processes entailing cancer cell dissemination will improve the mechanistic driven design of therapies that target specific steps involved in cancer metastasis to improve clinical response rates and overall survival in all cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Eddy, Shah and Chen.)

Background: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect. We hypothesized that intraoperative stimulated Raman histology (SRH) and deep neural networks can be used to improve the intraoperative detection of glioma recurrence., Methods: We used fiber laser-based SRH, a label-free, nonconsumptive, high-resolution microscopy method (<60 sec per 1 × 1 mm2) to image a cohort of patients (n = 35) with suspected recurrent gliomas who underwent biopsy or resection. The SRH images were then used to train a convolutional neural network (CNN) and develop an inference algorithm to detect viable recurrent glioma. Following network training, the performance of the CNN was tested for diagnostic accuracy in a retrospective cohort (n = 48)., Results: Using patch-level CNN predictions, the inference algorithm returns a single Bernoulli distribution for the probability of tumor recurrence for each surgical specimen or patient. The external SRH validation dataset consisted of 48 patients (recurrent, 30; pseudoprogression, 18), and we achieved a diagnostic accuracy of 95.8%., Conclusion: SRH with CNN-based diagnosis can be used to improve the intraoperative detection of glioma recurrence in near-real time. Our results provide insight into how optical imaging and computer vision can be combined to augment conventional diagnostic methods and improve the quality of specimen sampling at glioma recurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nephrotic syndrome (NS) is a leading cause of chronic kidney disease. We found recessive NOS1AP variants in two families with early-onset NS by exome sequencing. Overexpression of wild-type (WT) NOS1AP , but not cDNA constructs bearing patient variants, increased active CDC42 and promoted filopodia and podosome formation. Pharmacologic inhibition of CDC42 or its effectors, formin proteins, reduced NOS1AP-induced filopodia formation. NOS1AP knockdown reduced podocyte migration rate (PMR), which was rescued by overexpression of WT Nos1ap but not by constructs bearing patient variants. PMR in NOS1AP knockdown podocytes was also rescued by constitutively active CDC42 Q61L or the formin DIAPH3 Modeling a NOS1AP patient variant in knock-in human kidney organoids revealed malformed glomeruli with increased apoptosis. Nos1ap Ex3-/Ex3- mice recapitulated the human phenotype, exhibiting proteinuria, foot process effacement, and glomerulosclerosis. These findings demonstrate that recessive NOS1AP variants impair CDC42/DIAPH-dependent actin remodeling, cause aberrant organoid glomerulogenesis, and lead to a glomerulopathy in humans and mice., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Melanoma is the most aggressive and dangerous form of skin cancer that develops from transformed melanocytes. It is crucial to identify melanoma at its early stages, in situ, as it is "curable" at this stage. However, after metastasis, it is difficult to treat and the five-year survival is only 25%. In recent years, a better understanding of the etiology of melanoma and its progression has made it possible for the development of targeted therapeutics, such as vemurafenib and immunotherapies, to treat advanced melanomas. In this review, we focus on the molecular mechanisms that mediate melanoma development and progression, with a special focus on the immune evasion strategies utilized by melanomas, to evade host immune surveillances. The proposed mechanism of action and the roles of immunotherapeutic agents, ipilimumab, nivolumab, pembrolizumab, and atezolizumab, adoptive T- cell therapy plus T-VEC in the treatment of advanced melanoma are discussed. In this review, we implore that a better understanding of the steps that mediate melanoma onset and progression, immune evasion strategies exploited by these tumor cells, and the identification of biomarkers to predict treatment response are critical in the design of improved strategies to improve clinical outcomes for patients with this deadly disease.

OBJECTIVE. The purposes of this study were to assess the feasibility and safety of perfusion CT of patients with severe traumatic brain injury (TBI) at hospital admission and to examine whether early in-hospital mortality could be characterized with perfusion CT (PCT). The hypothesis was that PCT can be used to characterize brain death, when present, in patients with severe TBI at hospital admission. SUBJECTS AND METHODS. In this prospective cohort pilot study, PCT was performed on patients with severe TBI at first imaging workup at hospital admission. PCT images were processed at the end of the study and assessed for features of brain death. The PCT features were then compared with the clinical outcome of in-hospital mortality. RESULTS. A total of 19 patients (13 men [68.4%]; six women [31.6%]; mean age, 36.4 years; median, 27.5 years) had a mean hospital stay longer than 1 month. No complications of PCT were found. In the first 48 hours after admission, four patients (21%) died. Admission PCT changes suggesting brainstem death were sensitive (75%) and specific (100%) and had high positive (100%) and negative (93.75%) predictive value for correct classification early in-hospital mortality. CONCLUSION. Admission PCT of patients with severe TBI was feasible and safe. Admission PCT findings helped in correctly classifying early in-hospital mortality in the first 48 hours of hospital admission.

Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation, low body weight, and elevated levels of bone marrow adipose tissue (BMAT). BMAT is negatively associated with BMD in AN and more than 85% of women with AN have low bone mass and an increased risk of fracture. Although a majority of women with AN are amenorrheic, which is associated with low BMD, oral contraceptive pills, containing supraphysiologic doses of estrogen, are not effective in increasing bone mass. We performed a 6-month, open-label study of transdermal estradiol (0.045 mg/day) + levonorgestrel (0.015 mg/day) in 11 women with AN (mean age ± SEM: 37.2 ± 2.3 years) to investigate the effects of transdermal, physiologic doses of estrogen on BMD and BMAT in women with AN. We measured change in BMD by DXA, change in BMAT at the spine/hip by 1 H-magnetic resonance spectroscopy, and change in C-terminal collagen cross-links (CTX), P1NP, osteocalcin, IGF-1, and sclerostin after 3 and 6 months of transdermal estrogen. Lumbar spine (2.0% ± 0.8%; p = 0.033) and lateral spine (3.2% ± 1.1%; p = 0.015) BMD increased after 6 months of transdermal estrogen. Lumbar spine BMAT decreased significantly after 3 months (-13.9 ± 6.0%; p = 0.046). Increases in lateral spine BMD were associated with decreases in CTX ( p = 0.047). In conclusion, short-term treatment with transdermal, physiologic estrogen increases spine BMD in women with AN. Future studies are needed to assess the long-term efficacy of this treatment. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research., (© 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.)

There have been steep falls in rates of child stunting in much of Sub-Saharan Africa (SSA). Using Demographic and Health Survey data, we document significant reductions in stunting in seven SSA countries in the period 2005-2014. For each country, we distinguish potential determinants that move in a direction consistent with having contributed to the reduction in stunting from those that do not. We then decompose the change in stunting and in proximal determinants into a part that can be explained by changes in distal determinants and a residual part that captures the impact of unmeasured factors, such as vertical nutrition programs. We show that increases in coverage of child immunization, deworming medication and maternal iron supplementation often coincide with a fall in stunting. The magnitudes and directions of changes in two other proximal determinants -- age-appropriate feeding and diarrhea prevalence -- suggest that these have not been strong contributors to the fall in stunting. Utilization of maternity care emerges from the decomposition analysis as the most important distal determinant associated with reduced stunting, and also with increased coverage of iron supplementation, and, to a lesser extent, with child immunization and deworming medication. This circumstantial evidence is strong enough to warrant more detailed investigation of the extent to which maternity care is an effective channel through which to target further attacks on the blight of undernourished children.

Recently, recessive mutations of MAGI2 were identified as a cause of steroid-resistant nephrotic syndrome (SRNS) in humans and mice. To further delineate the pathogenesis of MAGI2 loss of function, we generated stable knockout lines for the two zebrafish orthologues magi2a and magi2b by CRISPR/Cas9. We also developed a novel assay for the direct detection of proteinuria in zebrafish independent of transgenic background. Whereas knockout of magi2b did not yield a nephrotic syndrome phenotype, magi2a -/- larvae developed ascites, periorbital edema, and proteinuria, as indicated by increased excretion of low molecular weight protein. Electron microscopy demonstrated extensive podocyte foot process effacement. As in human SRNS, we observed genotype/phenotype correlation, with edema onset occurring earlier in zebrafish with truncating alleles (5-6 days post fertilization) versus hypomorphic alleles (19-20 days post fertilization). Paradoxically, corticosteroid treatment exacerbated the phenotype, with earlier onset of edema. In contrast, treatment with cyclosporine A or tacrolimus had no significant effect. Although RhoA signaling has been implicated as a downstream mediator of MAGI2 activity, targeting of the RhoA pathway did not modify the nephrotic syndrome phenotype. In the first CRISPR/Cas9 zebrafish knockout model of SRNS, we found that corticosteroids may have a paradoxical effect in the setting of specific genetic mutations., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Aberrant glutamatergic signaling has been implicated in altered metabolic activity in many cancer types, including malignant melanoma. Previously, we have illustrated the role of metabotropic glutamate receptor 1 (GRM1) in neoplastic transformation of melanocytes in vitro and spontaneous metastatic melanoma in vivo . In this study, we showed that autocrine stimulation constitutively activates the GRM1 receptor and its downstream mitogenic signaling. GRM1-activated (GRM1 + ) melanomas exhibited significantly increased expression of glutaminase (GLS), which catalyzes the first step in the conversion of glutamine to glutamate. In cultured GRM1 + melanoma cell lines, CB-839, a potent, selective, and orally bioavailable inhibitor of GLS, suppressed cell proliferation, while riluzole, an inhibitor of glutamate release, promoted apoptotic cell death in vitro and in vivo . Combined treatment with CB-839 and riluzole treatment proved to be superior to single-agent treatment, restricting glutamate bioavailability and leading to effective suppression of tumor cell proliferation in vitro and tumor progression in vivo . Hyperactivation of GRM1 in malignant melanoma is an oncogenic driver, which acts independently of canonical melanoma proto-oncogenes, BRAF or NRAS. Overall, these results indicate that expression of GRM1 promotes a metabolic phenotype that supports increased glutamate production and autocrine glutamatergic signaling, which can be pharmacologically targeted by decreasing glutamate bioavailability and the GLS-dependent glutamine to glutamate conversion. SIGNIFICANCE: These findings demonstrate that targeting glutaminolytic glutamate bioavailability is an effective therapeutic strategy for GRM1-activated tumors., (©2019 American Association for Cancer Research.)

Background: Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults., Objective: Evaluate differences in bone accrual over 12 months in OA, eumenorrheic athletes (EA) and non-athletes (NA). We hypothesized that bone accrual would be lower in OA than EA and NA, with differences most pronounced at non-weight bearing trabecular sites., Methods: 27 OA, 29 EA, and 22 NA, 14-25 years old, completed 12-months of the prospective study. Athletes were weight-bearing endurance athletes. Subjects were assessed for areal BMD and bone mineral content (BMC) using DXA at the femoral neck, total hip, lumbar spine and whole body (WB). Failure load (a strength estimate) at the distal radius and tibia was assessed using microfinite element analysis of data obtained via high resolution peripheral quantitative computed tomography (HRpQCT). The primary analysis was a comparison of changes in areal BMD, BMC, and failure load across groups over 12-months at the respective sites., Results: Groups did not differ for baseline age, height or BMI. Percent body fat was lower in both OA and EA compared to NA. OA attained menarche later than EA and NA. Over the follow-up period, OA gained 1.9 ± 2.7 kg of weight compared to 0.5 ± 2.4 kg and 0.8 ± 2.3 kg in EA and NA respectively (p = 0.09); 39% of OA resumed menses. Changes in BMD, BMD Z-scores, and tibial failure load over 12-months did not differ among groups. At follow up, EA had higher femoral neck, hip and WB BMD Z-scores than NA, and higher hip BMD Z-scores than OA (p < 0.05) after adjusting for covariates. At follow-up, radial failure load was lower in OA vs. NA, and tibial failure load lower in OA and NA vs. EA (p ≤ 0.04 for all). Change in weight and fat mass were associated with changes in BMD measures at multiple sites., Conclusion: Despite weight gain and menses recovery in many OA during follow-up, residual deficits persist without catch-up raising concerns for suboptimal peak bone mass acquisition., (Copyright © 2018. Published by Elsevier Inc.)

Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained. Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS. Here, we describe mutations in genes encoding 4 components of the outer rings of the NPC, namely NUP107, NUP85, NUP133, and NUP160, in 13 families with SRNS. Using coimmunoprecipitation experiments, we showed that certain pathogenic alleles weakened the interaction between neighboring NPC subunits. We demonstrated that morpholino knockdown of nup107, nup85, or nup133 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP107, NUP85, or NUP133 in podocytes activated Cdc42, an important effector of SRNS pathogenesis. CRISPR/Cas9 knockout of nup107 or nup85 in zebrafish caused developmental anomalies and early lethality. In contrast, an in-frame mutation of nup107 did not affect survival, thus mimicking the allelic effects seen in humans. In conclusion, we discovered here that mutations in 4 genes encoding components of the outer ring subunits of the NPC cause SRNS and thereby provide further evidence that specific hypomorphic mutations in these essential genes cause a distinct, organ-specific phenotype.

Objective: We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in participants with anorexia nervosa (AN) and normal-weight oligoamenorrheic athletes (OAs). However, data directly comparing compartment-specific bone parameters in participants with AN, OAs, and controls are lacking., Design: A total of 468 female participants 14 to 21.9 years old were included: 269 with AN, 104 OAs, and 95 normal-weight eumenorrheic controls. Dual-energy x-ray absorptiometry was used to assess areal BMD (aBMD) of the whole body less head (WBLH), spine, and hip. High-resolution peripheral quantitative computed tomography was used to assess volumetric BMD (vBMD), bone geometry, and structure at the non-weight-bearing distal radius and weight-bearing distal tibia., Results: Participants with AN had lower WBLH and hip aBMD z scores than OAs and controls (P < 0.0001). Participants with AN and OAs had lower spine aBMD z scores than controls (P < 0.01). At the radius, total and cortical vBMD, percentage cortical area, and thickness were lower in the AN and OA groups than in controls (P ≤ 0.04); trabecular vBMD was lower in participants with AN than controls. At the tibia, participants with AN had lower measures for most parameters compared with OAs and controls (P < 0.05); OAs had lower cortical vBMD than controls (P = 0.002). Participants with AN and OAs had higher fracture rates than controls. Stress fracture prevalence was highest in OAs (P < 0.0001); nonstress fracture prevalence was highest in participants with AN (P < 0.05)., Conclusion: AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OAs, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.

Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.

Exosomes are naturally occurring membrane-bound nanovesicles generated constitutively and released by various cell types, and often in higher quantities by tumor cells. Exosomes may facilitate communication between the primary tumor and its local microenvironment, supporting cell invasion and other early events in metastasis. A neuronal receptor, metabotropic glutamate receptor 1 (GRM1), when ectopically expressed in melanocytes, induces in vitro melanocytic transformation and spontaneous malignant melanoma development in vivo in a transgenic mouse model. Our earlier studies showed that genetic modulation in GRM1 expression by siRNA or disruption of GRM1-mediated glutamate signaling interfere with downstream effectors resulting in a decrease in both cell proliferation in vitro and tumor progression in vivo . In this study, we sought to determine whether exosome formation might play a role in GRM1 mediated melanoma development and progression. To test this, we utilized in vitro cultured cells in which GRM1 expression and function could be modulated by pharmacological and genetic means and determined effects on exosome production. We also tested the effects of exosomes from GRM1 expressing melanoma cells on growth, migration and invasion of GRM1 negative cells. Our results show that although GRM1 expression has no influence on exosome quantity, exosomes produced by GRM1-positive cells modulate the ability of the recipient cell to migrate, invade and exhibit anchorage-independent cell growth., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Purpose: This study aimed to update our liver computed tomography (CT) protocol according to published guidelines, and to quantitatively evaluate the effect of these modifications., Methods: The modified liver CT protocol employed a faster injection rate (5 vs 3 mL/s), later arterial phase (20-second vs 10-second postbolus trigger), and weight-based dosing of iodinated contrast (1.7 mL/kg vs 100 mL fixed dose). Liver and vascular attenuation values were measured on CTs of patients with cirrhosis from January to September 2015 (old protocol, n = 49) and from October to December 2015 (modified protocol, n = 31). CTs were considered adequate if liver enhancement exceeded 50 Hounsfield units (HU) in portal venous phase, or when the unenhanced phase was unavailable, if a minimum iodine concentration of 500 mg I/kg was achieved. Attenuations and iodine concentrations were compared using the t test and the number of suboptimal studies was compared with Fisher's exact test., Results: CTs acquired with the modified protocol demonstrated higher aortic (P = .001) and portal vein (P < .0001) attenuations in the arterial phase as well as greater hepatic attenuation on all postcontrast phases (P = .0006, .002, and .003 for arterial, venous, and equilibrium phases, respectively). Hepatic enhancement in the portal venous phase (61 ± 15 HU vs 51 ± 16 HU; P = .0282) and iodine concentrations (595 ± 88 mg I/kg vs 456 ± 112 mg I/kg; P < .0001) were improved, and the number of suboptimal studies was reduced from 57% to 23% (P = .01)., Conclusions: A liver CT protocol with later arterial phase, faster injection rate, and weight-based dosing of intravenous contrast significantly improves liver enhancement and iodine concentrations in patients with cirrhosis, resulting in significantly fewer suboptimal studies., (Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: Both estrogen and exercise may have cognition enhancing benefits; however, young oligomenorrheic/amenorrheic athletes (OA) with estrogen deficiency have not been evaluated for cognitive deficits. Our objective was to determine whether 6 months of estrogen replacement will impact cognitive domains in OA. We hypothesized that estrogen replacement would improve verbal memory and executive control in OA., Methods: We performed cognitive assessments at baseline and after 6 months in 48 OA (14-25 years) randomized to estrogen (EST+) (oral 30 µg ethinyl estradiol [n = 16] or transdermal 100 µg 17-β-estradiol patch [n = 13]) or no estrogen (EST-) (n = 19) in an ongoing clinical trial. Neurocognitive testing included California Verbal Learning Test-Second Edition (CVLT-II) (for verbal memory) and Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS-CWIT) (executive control)., Results: On average, subjects (mean ± SEM age: 19.9 ± 3.1 years, body mass index: 20.6 ± 2.3 kg/m²) participated in 10.3 ± 5.9 hours per week of weight-bearing activities of their lower limbs. The EST+ group performed better for CVLT-II verbal memory scores for immediate recall over 6 months of therapy compared to EST- (P < .05) even after controlling for baseline scores and age. Changes in D-KEFS-CWIT scores over 6 months did not differ between the groups. However, the EST+ group had greater improvements in inhibition-switching completion time over 6 months compared with the EST- group after controlling for baseline scores and age (P = .01)., Conclusions: OA show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies exploring cognition in OA., Trial Registration: ClinicalTrials.gov identifier: NCT00946192., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity., Competing Interests: Compliance with ethical standards Financial support The UK Medical Research Council and the Wellcome Trust (Grant Ref: 092731) and the University of Bristol provide core support for ALSPAC.This research was funded by a National Institute of Health Research (NIHR) clinician scientist award to Dr N Micali and by a grant from NIMH to Drs Field and Micali (R01 MH087786). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Conflict of interest They authors declare that they have no conflict of interest.

Cancer is the second leading cause of death in the United States, and about 6% of the estimated cancer diagnoses this year will be melanoma cases. Melanomas are derived from transformation of the pigment producing cells of the skin, melanocytes. Early stage melanoma is usually curable by surgical resection, but late stage or subsequent secondary metastatic tumors are treated with some success with chemotherapies, radiation and/or immunotherapies. Most cancer patients die from metastatic disease, which is especially the case in melanoma. A better understanding of tumor metastasis will provide insights and guide rational therapeutic designs. Recently, the importance of melanoma-derived exosomes in the progression of that cancer has become more apparent, namely, their role in various stages of metastasis, including the induction of migration, invasion, primary niche manipulation, immune modulation and pre-metastatic niche formation. This review focuses on the critical roles that melanoma exosomes play in the progression of this deadly disease., Competing Interests: The authors declare no conflict of interest.

Background: Teamwork is seen as an important element of patient care in acute hospital settings. The complexity of the journey of care for patients highlights the need for health professionals to collaborate and communicate clearly with each other. Health organizations in western countries are committed to improving patient safety through education of staff and teamwork education programs have been integral to this focus. There are no current systematic reviews of the experience of health professionals who participate in teamwork education in acute hospital settings., Objectives: The objective of this systematic review was to search for the best available evidence on the experiences of health professionals who participate in teamwork education in acute hospital settings., Inclusion Criteria Types of Participants: This review considered studies reporting on experiences of registered health professionals who work in acute hospitals. This included medical, nursing and midwifery and allied health professionals., Phenomena of Interest: The focus of the meta-synthesis was the experiences and reflections of health professionals who were involved in teamwork education in acute hospital settings., Context: The geographical context for this review was acute hospitals in rural or metropolitan settings in Australia and overseas countries. The review focused on the experiences of health professionals who work in acute hospitals and participated in teamwork education programs., Types of Studies: This review considered studies that focused on qualitative data including, but not limited to, designs such as phenomenology, grounded theory, ethnography, action research and feminist research.In the absence of research studies, other text such as opinion papers, discussion papers and reports were considered. Studies published in English and from 1990 to 2013 were included in this review., Search Strategy: The literature search for relevant papers occurred between 13 September and 26 October 2013. A three-step search strategy was utilized in this review. The databases searched were PubMed, CINAHL, Embase and Scopus., Methodological Quality: The standardized critical appraisal tool the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to assess the methodological quality of included papers., Data Extraction: Data that included statements and text of interest was extracted from papers included in the study using the standardized data extraction tool from JBI-QARI., Data Synthesis: Qualitative research findings were pooled using JBI-QARI. This involved the aggregation and synthesis of findings to generate a set of statements that represented that aggregation., Results: In total, 116 papers were selected for analysis of full text, 11 papers were selected for critical appraisal and seven papers were selected for data synthesis. This resulted in 44 findings. The findings were assigned to 16 categories based on identified similarities across the papers. The categories were integrated into six meta-syntheses. These were: Meta-synthesis One: It is important to recognize that organizational culture and expectations have an impact on health professionals' participation and experience of teamwork education. Meta-synthesis Two: Understanding how successful teams function is central to the development of teamwork education programs and the experience of participants. Meta-synthesis Three: A health professional's experience of teamwork education will be influenced by his/her starting point of learning. Meta-synthesis Four: Participants highly value teamwork education programs that are implemented by facilitators who create practical authentic learning opportunities and foster reflection and debriefing for participants. Meta-synthesis Five: High fidelity simulation used with specific communication strategies provides a powerful learning opportunity for health professions to practice teamwork skills. Meta-synthesis Six: Participants have increased confidence and are motivated to apply their newly learnt teamwork skills into their daily practice., Conclusions: The review identified qualitative evidence that can guide organizations and education facilitators in the development and implementation of teamwork education in acute hospital settings. Although the quality of the specific teamwork education programs was an important factor, there were a number of issues that also impacted on the experiences of health professionals who participated in teamwork education programs. These included the context that the program was delivered in, the diversity of health care teams, starting points of individual learners, the type of tools utilized in education programs, the levels of confidence and motivation of learners post training and the opportunity to transfer into practice new learning., Implications for Practice: Drawing from the synthesized findings of the review, recommendations for practice have been devised in order to guide the development and implementation of teamwork education in acute hospital settings and to improve the experience of participating health professionals. The Joanna Briggs Institute utilizes Grades of Recommendation to rate a health management strategy in terms of its desirable effects, evidence of adequate quality supporting its use, benefits of use, and the inclusion of patient experience, values and preferences. A strong recommendation has a Grade A and a weak recommendation has a Grade B. The FAME (Feasibility, Appropriateness, Meaningfulness and Effectiveness) scale was used to inform the strength of the following six recommendations for practice from the review: RECOMMENDATION ONE: All members of a team should be encouraged by their organization/managers to participate in teamwork education programs in order to foster a positive culture of learning and teamwork within the team.JBI Recommendation: Grade A. This recommendation is appropriate and applicable to all health professionals in acute hospital settings, is associated with positive experiences for participants of teamwork education programs and has a beneficial effect on participants., Recommendation Two: Facilitators of teamwork education programs should understand how successful teams function and consider these factors when planning or delivering training.JBI Recommendation: Grade A. This recommendation is associated with positive experiences for participants and creates a beneficial effect to the quality of a teamwork education program., Recommendation Three: Facilitators of teamwork education programs need to explore participant learning needs and their prior experiences of working in teams before implementing teamwork education programs.JBI Recommendation: Grade A. This recommendation creates a beneficial effect to the participants of teamwork education programs and to the quality of education provided by facilitators., Recommendation Four: Facilitators of teamwork education programs should provide learning opportunities that are practical, authentic to participants and foster constructive debriefing and reflection.JBI Recommendation: Grade A. This recommendation is applicable to all health professionals and circumstances in which teamwork education occurs, is associated with positive experiences and has a beneficial effect on participants., Recommendation Five: High fidelity simulation should be considered in acute hospitals for the training of teamwork skills in addition to clinical skills. Scenarios provide realistic opportunities for participants to practice communication strategies that enhance teamwork.JBI Recommendation: Grade A. This recommendation is applicable to all health professionals and circumstances in which teamwork education occurs and has a beneficial effect on participants of education programs., Recommendation Six: Team managers should harness the new confidence and motivation of staff around teamwork skills following participation in teamwork education programs and ensure that there are opportunities in the workplace to apply new skills and knowledge into daily practice.JBI Recommendation: Grade A. This recommendation is applicable to all health professionals and circumstances in which teamwork education occurs, is adaptable to a variety of circumstances and has a beneficial effect on health professional's daily practice of teamwork skills., Implications for Research: In order to strengthen the evidence base about teamwork education in acute hospital settings there needs to be quantitative and qualitative research into:How organizations that have successfully embedded a culture of collaboration and safety in health teams have planned, implemented and evaluated teamwork education programs in acute hospital settings?What are the characteristics of teams that have led to successful participation in teamwork education and positive outcomes for team performance?What are the experiences, training and support provided to education facilitators who successfully implement teamwork education programs in acute hospitals?

Purpose. The goal of this study was to investigate the effects of arm weight support training using the ArmeoSpring for subacute patients after stroke with different levels of hemiplegic arm impairments. Methods. 48 inpatients with subacute stroke, stratified into 3 groups from mild to severe upper extremity impairment, were engaged in ArmeoSpring training for 45 minutes daily, 5 days per week for 3 weeks, in addition to conventional rehabilitation. Evaluations were conducted at three measurement occasions: immediately before training (T1); immediately after training (T2); and at a 3-week follow-up (T3) by a blind rater. Results. Shoulder flexion active range of motion, Upper Extremity Scores in the Fugl-Meyer Assessment (FMA), and Vertical Catch had the greatest differences in gain scores for patients between severe and moderate impairments, whereas FMA Hand Scores had significant differences in gain scores between moderate and mild impairments. There was no significant change in muscle tone or hand-path ratios between T1, T2, and T3 within the groups. Conclusion. Arm weight support training is beneficial for subacute stroke patients with moderate to severe arm impairments, especially to improve vertical control such as shoulder flexion, and there were no adverse effects in muscle tone.

Background: Overvaluation of body shape/weight is thought to be the core psychopathology underlying eating disorders, which propels engagement in non-compensatory weight-control behaviors. In turn, these behaviors lead to binge eating and/or maintenance of low weight thereby reinforcing overvaluation. The present study investigated the reciprocal relationship between overvaluation and engagement in non-compensatory weight-control behaviors (defined in two ways: restrictive eating and compulsive exercise) among women diagnosed with anorexia nervosa or bulimia nervosa (N = 237)., Method: Participants completed clinical interviews in which weekly eating disorder symptoms and behaviors were assessed over 2 years., Results: Overvaluation on a given week was associated with greater engagement in non-compensatory weight-control behaviors during the following week. Further, engagement in non-compensatory weight-control behaviors on a given week was associated with greater overvaluation during the following week. These findings held true regardless of participants' shape/weight concerns (feelings of fatness and fat phobia), and eating disorder diagnosis., Conclusions: Our data provide empirical support for key aspects of the transdiagnostic cognitive-behavioral model of eating disorders and suggest that targeting non-compensatory weight-control behaviors in treatment may help alleviate overvaluation and shape/weight concerns.

Purpose: A study was performed to evaluate the ACR Select software in determining the level of appropriateness of computed tomography (CT) and magnetic resonance imaging (MRI) in Island Health in British Columbia., Methods: A total of 1228 consecutive CT and MRI studies performed in a 3-day period were entered into a software program provided by the National Decision Support Company based on the ACR Appropriateness Criteria. The program was able to analyze 93% (1141) of these studies. A subset of these requisitions was manually reviewed., Results: The software program demonstrated a very low 2.5% inappropriate rate and manual review showed an even lower number of 0.6%. In a sample of studies deemed to be appropriate by the software, manual review agreed with this ranking in all cases. In addition, in 20% of cases where CT was done, the software program suggested that MRI would be a more appropriate choice., Conclusions: First, the ACR Select software is a useful tool to assess appropriateness of CT and MRI, although it may underestimate the level of appropriateness of studies labeled as inappropriate. Second, CT and MRI are being ordered appropriately in Island Health in British Columbia. The software recommendation of MRI as more appropriate in 20% of cases where CT was done suggests a lack of MRI resources in Island Health., (Copyright © 2015 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

Context: Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk., Objective: The objective of the study was to investigate hip fracture risk in AN and overweight/obese women., Design: This was a cross-sectional study., Setting: The study was conducted at a Clinical Research Center., Patients: PATIENTS included 368 women (aged 19-45 y): 246 AN, 53 overweight/obese, and 69 lean controls., Main Outcome Measures: HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φ(attenuated)) were measured., Results: Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φ(attenuated) was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φ(attenuated) (P < .05). Mean φ(attenuated) (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures., Conclusions: Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD.

Objectives: The current standards for classifying eating disorders were primarily informed by adult, clinical study populations, while it is unknown whether an empirically based classification system can be supported across preadolescence through young adulthood. Using latent class analyses, we sought to empirically classify disordered eating in females from preadolescence to young adulthood, and assess the association between classes and adverse outcomes., Method: Latent class models were fit using observations from the 9,039 girls participating in the growing up today study, an on-going cohort following participants annually or biennially since 1996 when they were ages 9-14 years. Associations between classes and drug use, binge drinking, and depressive symptoms were assessed using generalized estimating equations., Results: Across age groups, there was evidence of six classes: a large asymptomatic class, a class characterized by shape/weight concerns, a class characterized by overeating without loss of control, and three resembling full and subthreshold binge eating disorder, purging disorder, and bulimia nervosa. Relative prevalences of classes varied across developmental stages, with symptomatic classes increasing in prevalence with increasing age. Symptomatic classes were associated with concurrent and incident drug use, binge drinking, and high depressive symptoms., Discussion: A classification system resembling broader definitions of DSM-5 diagnoses along with two further subclinical symptomatic classes may be a useful framework for studying disordered eating among adolescent and young adult females., (© 2014 Wiley Periodicals, Inc.)

Irisin and FGF21 are novel hormones implicated in the "browning" of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.