Integrating the social determinants of health into curriculum: AMEE Guide No. 162.

The World Health Organization (WHO) defines the Social Determinants of Health (SDOH) as the non-medical factors influencing health outcomes. SDOH is associated with conditions in which people are born, grow, work, and live. Medical schools and licensing bodies are increasingly recognizing the need for doctors and healthcare professionals to be aware of their patient's social context and how it impacts their states of health and disease. However, there is considerable variation in the approaches of different institutions and countries to incorporating SDOH into their curricula. In order to allow clinicians to adopt a holistic approach to patient health, equipping them with extensive knowledge of SDOH would give learners the confidence, skills, knowledge, and attitudes needed to effectively engage with patients and their families. This approach aids health professionals with knowledge of the influence of the social context and cultural factors that affect patients' behaviors in relation to health. Incorporating the SDOH in medical and health professional school curricula would contribute towards adequately preparing future healthcare practitioners to provide effective, comprehensive, and equitable care, especially to marginalized and underserved populations. The Guide will take an evidence-based approach grounded in the available contemporary literature and case studies. The focus will be on integrating SDOH into undergraduate and postgraduate medical curricula to promote an understanding of the social factors that influence patients' and communities' health. Ultimately, this guide seeks to contribute to the reduction of inequalities in health.

The Neurophysiological Lesion: A Scoping Review.

Objective: The purpose of this study was to examine the extent of the literature on the neurophysiological lesion as referenced in functional neurology. Methods: A literature search was performed within the period from 2010 to March 2021. Search terms included central sensitization, central sensitivity syndrome, nociplastic pain, cold hyperalgesia, heat hyperalgesia, mechanical hyperalgesia, dynamic mechanical allodynia, temporal summation, spatial summation, and descending inhibition. A qualitative synthesis summarized the research findings, including clinical conditions and effect of spinal manipulation. Results: There were 30 studies, which included 7 high-level studies (meta-analysis or systematic reviews), 22 randomized controlled studies, and 1 scoping review. The findings suggest the existence of the changes in the central integrated state of a population of neurons with various disorders, experimentally induced stimulation, and treatment. The current literature suggests plasticity of the central integrative state (CIS) with the onset of pathologies and the changes in the CIS with different conservative nonpharmacologic treatments. Conclusions: This review suggests changes in the resting state of the CIS of a population of neurons that exist in the physiologic lesion may change in response to various therapies, including manipulative therapy. The findings from this review provide support of the hypothesis that nonpharmacologic conservative care may affect the neurophysiological lesion. However, studies were heterogeneous and evidence was lacking in the translation of targeting the therapies to distinct neuronal areas for clinical outcomes to treat specific disease states.

Metabolic Control Analysis of triacylglycerol accumulation in oilseed rape.

The increasing global demand for vegetable oils will only be met if there are significant improvements in the productivity of the major oil crops, such as oilseed rape. Metabolic engineering offers the prospect of further gains in yield beyond that already achieved by breeding and selection but requires guidance as to the changes that need to be made. Metabolic Control Analysis, through measurement and estimation of flux control coefficients, can indicate which enzymes have the most influence on a desired flux. Some experiments have previously reported flux control coefficients for oil accumulation in the seeds of oilseed rape, and others have measured control coefficient distributions for multi-enzyme segments of oil synthesis in seed embryo metabolism measured in vitro. In addition, other reported manipulations of oil accumulation contain results that are exploited further here to calculate previously unknown flux control coefficients. These results are then assembled within a framework that allows an integrated interpretation of the controls on oil accumulation from the assimilation of CO2 to deposition of oil in the seed. The analysis shows that the control is distributed to an extent that the gains from amplifying any single target are necessarily limited, but there are candidates for joint amplification that are likely to act synergistically to produce much more significant gains.

Bioengineering of Soybean Oil and Its Impact on Agronomic Traits.

Soybean is a major oil crop and is also a dominant source of nutritional protein. The 20% seed oil content (SOC) of soybean is much lower than that in most oil crops and the fatty acid composition of its native oil cannot meet the specifications for some applications in the food and industrial sectors. Considerable effort has been expended on soybean bioengineering to tailor fatty acid profiles and improve SOC. Although significant advancements have been made, such as the creation of high-oleic acid soybean oil and high-SOC soybean, those genetic modifications have some negative impacts on soybean production, for instance, impaired germination or low protein content. In this review, we focus on recent advances in the bioengineering of soybean oil and its effects on agronomic traits.

An investigation into chiropractic intern adherence to radiographic guidelines in clinical decisions with a descriptive comparison to clinical practitioners.

OBJECTIVE: The purpose of this study was to assess chiropractic interns' knowledge and adherence to radiographic clinical practice guidelines (CPGs) and compare their clinical decisions to previous surveys of established practitioners in Canada and Australia. METHODS: A clinical decision-making survey was administered to 88 interns. The survey contained clinical scenarios and vignettes with inquiries regarding indications for radiographic referral, the likelihood of referral, and the application of CPGs. RESULTS: Forty-four percent (43.75%) of the interns were aware of CPGs, 38.75% were unsure, and 17.5% were not aware. When asked specific questions about the appropriateness of diagnostic imaging, the interns' responses were similar to those of practitioners in Canada and Australia. When interns evaluated a clinical vignette, there was lower compliance with CPGs. CONCLUSION: The interns' clinical decisions regarding the use of diagnostic radiography did not significantly differ from those of practitioners who were surveyed in other related studies. Interns were inconsistent in applying their decision making in clinical cases. Notwithstanding the similarities with practitioners, some deviation from the guidelines indicates the need for further intern education to improve the implementation of CPGs for optimal cost-effective and clinically appropriate care.

Supervising the senior medical resident: Entrusting the role, supporting the tasks.

INTRODUCTION: Postgraduate competency-based medical education has been implemented with programmatic assessment that relies on entrustment-based ratings. Yet, in less procedurally oriented specialties such as internal medicine, the relationship between entrustment and supervision remains unclear. We undertook the current study to address how internal medicine supervisors conceptualise entrusting senior medical residents while supervising them on the acute care wards. METHODS: Guided by constructivist grounded theory, we interviewed 19 physicians who regularly supervised senior internal medicine residents on inpatient wards at three Canadian universities. We developed a theoretical model through iterative cycles of data collection and analysis using a constant comparative process. RESULTS: On the internal medicine ward, the senior resident role is viewed as a fundamentally managerial and rudimentary version of the supervisor's role. Supervisors come to trust their residents in the senior role through an early 'hands-on' period of assessment followed by a gradual withdrawal of support to promote independence. When considering entrustment, supervisors focused on entrusting a particular scope of the senior resident role as opposed to entrustment of individual tasks. Irrespective of the scope of the role that was entrusted, supervisors at times stepped in and stepped back to support specific tasks. CONCLUSION: Supervisors' stepping in and stepping back to support individual tasks on the acute care ward has an inconsistent relationship to their entrustment of the resident with a particular scope of the senior resident role. In this context, entrustment-based assessment would need to capture more of the holistic perspective of the supervisor's entrustment of the senior resident role. Understanding the dance of supervision, from relatively static overall support of the resident in their role, to fluidly stepping in and out for specific patient care tasks, allows us insight into the affordances of the supervisory relationship and how it may be leveraged for assessment.

Best Practices for Chiropractic Management of Adult Patients With Mechanical Low Back Pain: A Clinical Practice Guideline for Chiropractors in the United States.

OBJECTIVE: The purpose of this paper was to update the previously published 2016 best-practice recommendations for chiropractic management of adults with mechanical low back pain (LBP) in the United States. METHODS: Two experienced health librarians conducted the literature searches for clinical practice guidelines and other relevant literature, and the investigators performed quality assessment of included studies. PubMed was searched from March 2015 to September 2021. A steering committee of 10 experts in chiropractic research, education, and practice used the most current relevant guidelines and publications to update care recommendations. A panel of 69 experts used a modified Delphi process to rate the recommendations. RESULTS: The literature search yielded 14 clinical practice guidelines, 10 systematic reviews, and 5 randomized controlled trials (all high quality). Sixty-nine members of the panel rated 38 recommendations. All but 1 statement achieved consensus in the first round, and the final statement reached consensus in the second round. Recommendations covered the clinical encounter from history, physical examination, and diagnostic considerations through informed consent, co-management, and treatment considerations for patients with mechanical LBP. CONCLUSION: This paper updates a previously published best-practice document for chiropractic management of adults with mechanical LBP.

Effect of Vitamin D Supplementation on Outcomes in People With Early Psychosis: The DFEND Randomized Clinical Trial.

Importance: People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes. Objective: To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP. Design, Setting, and Participants: This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019. Interventions: Monthly augmentation with 120 000 IU of cholecalciferol or placebo. Main Outcomes and Measures: The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline. Results: A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 to 4.94); Global Assessment of Function disability score (mean difference, -0.01; 95% CI, -5.25 to 5.23), or Calgary Depression Scale score (mean difference, -0.39; 95% CI, -2.05 to 1.26) at 6 months. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. Conclusions and Relevance: In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies. Trial Registration: isrctn.org Identifier: ISRCTN12424842.

The Role of Chiropractic Care in Providing Health Promotion and Clinical Preventive Services for Adult Patients with Musculoskeletal Pain: A Clinical Practice Guideline.

Objective: To develop evidence-based recommendations on best practices for delivery of clinical preventive services by chiropractors and to offer practical resources to empower provider applications in practice. Design: Clinical practice guideline based on evidence-based recommendations of a panel of practitioners and experts on clinical preventive services. Methods: Synthesizing the results of a literature search for relevant clinical practice guidelines and systematic reviews, a multidisciplinary steering committee with training and experience in health promotion, clinical prevention, and/or evidence-based chiropractic practice drafted a set of recommendations. A Delphi panel of experienced practitioners and faculty, primarily but not exclusively chiropractors, rated the recommendations by using the formal consensus methodology established by the RAND Corporation/University of California. Results: The Delphi consensus process was conducted during January-February 2021. The 65-member Delphi panel reached a high level of consensus on appropriate application of clinical preventive services for screening and health promotion counseling within the chiropractic scope of practice. Interprofessional collaboration for the successful delivery of clinical preventive services was emphasized. Recommendations were made on primary, secondary, tertiary, and quaternary prevention of musculoskeletal pain. Conclusions: Application of this guideline in chiropractic practice may facilitate consistent and appropriate use of screening and preventive services and foster interprofessional collaboration to promote clinical preventive services and contribute to improved public health.

Vitamin D in the time of the coronavirus (COVID-19) pandemic - a clinical review from a public health and public mental health perspective.

Individuals with serious mental disorders (SMD) may have a higher risk of vitamin D (VIT-D) deficiency. They also experience higher mortality because of coronavirus disease 2019 (COVID-19) infection. Therefore, we have conducted a comprehensive review to examine the significance of VIT-D for public health and public mental health during the ongoing COVID-19 pandemic. This review had three specific aims, from a global perspective to (a) create a profile of VIT-D and review the epidemiology of VIT-D deficiency, (b) explore VIT-D deficiency as risk factor for SMD and COVID-19 infections and (c) examine the effectiveness of VIT-D supplementation for both conditions. We found that, in terms of SMD, the evidence from laboratory and observational studies points towards some association between VIT-D deficiency and depression or schizophrenia. Mendelian randomisation studies, however, suggest no, or reverse, causality. The evidence from intervention studies is conflicting. Concerning COVID-19 infection, on proof of principle, VIT-D could provide a plausible defence against the infection itself and against an adverse clinical course. But data from observational studies and the first preliminary intervention studies remain conflicting, with stronger evidence that VIT-D may mitigate the clinical course of COVID-19 infection rather than the risk of infection in the first place. From a public health and public mental health point of view, based on the currently limited knowledge, for individuals with SMD, the benefits of VIT-D optimisation through supplementation seem to outweigh the risks. VIT-D supplementation, however, should not substitute for vaccination or medical care for COVID-19 infection.

Low-Level Laser Light Therapy Dosage Variables vs Treatment Efficacy of Neuromusculoskeletal Conditions: A Scoping Review.

OBJECTIVE: The purpose of this scoping review was to identify and synthesize literature on dosage variables on the efficacy of low-level laser therapy (LLLT) for neuromusculoskeletal conditions. METHODS: A scoping literature review was conducted by searching the following databases: the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, Medline, the Physiotherapy Evidence Database, the Index to Chiropractic Literature, manufacturer websites, and online guidelines. The search was modeled after STARLITE criteria. The reporting used Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR). Articles were included if LLLT was used in any treatment group for a neuromusculoskeletal complaint with dosage and effectiveness reported. This was tabulated by source, dosage variables, conditions, outcome measures, and conclusions. Data were charted in Excel format. Frequency counts were performed on ordinal data. Descriptive statistics were computed for the continuous data. RESULTS: A total of 86 articles were included in the review. They revealed a broad range of musculoskeletal conditions and diverse dosage parameters. Seven individual parameters were found that would alter the dosage. Although duration of application is an independent clinical factor, the negative-outcome studies were inconsistent in duration. There was lack of statistical difference between the studies with improved vs unimproved outcomes. No statistical differences were noted between the dosage parameters and efficacy. CONCLUSION: Although many articles were found on LLLT for neuromusculoskeletal conditions, the studies had amorphous parameters. A heterogeneity of reported doses precluded the synthesis of sufficient evidence to correlate dosage variables with improved or unimproved outcomes. Therefore, based on the current literature, dosage variables for the efficacy of LLLT for neuromusculoskeletal conditions are uncertain at this time.

Best Practices for Chiropractic Management of Patients with Chronic Musculoskeletal Pain: A Clinical Practice Guideline.

Objective: To develop an evidence-based clinical practice guideline (CPG) through a broad-based consensus process on best practices for chiropractic management of patients with chronic musculoskeletal (MSK) pain. Design: CPG based on evidence-based recommendations of a panel of experts in chronic MSK pain management. Methods: Using systematic reviews identified in an initial literature search, a steering committee of experts in research and management of patients with chronic MSK pain drafted a set of recommendations. Additional supportive literature was identified to supplement gaps in the evidence base. A multidisciplinary panel of experienced practitioners and educators rated the recommendations through a formal Delphi consensus process using the RAND Corporation/University of California, Los Angeles, methodology. Results: The Delphi process was conducted January-February 2020. The 62-member Delphi panel reached consensus on chiropractic management of five common chronic MSK pain conditions: low-back pain (LBP), neck pain, tension headache, osteoarthritis (knee and hip), and fibromyalgia. Recommendations were made for nonpharmacological treatments, including acupuncture, spinal manipulation/mobilization, and other manual therapy; modalities such as low-level laser and interferential current; exercise, including yoga; mind-body interventions, including mindfulness meditation and cognitive behavior therapy; and lifestyle modifications such as diet and tobacco cessation. Recommendations covered many aspects of the clinical encounter, from informed consent through diagnosis, assessment, treatment planning and implementation, and concurrent management and referral. Appropriate referral and comanagement were emphasized. Conclusions: These evidence-based recommendations for a variety of conservative treatment approaches to the management of common chronic MSK pain conditions may advance consistency of care, foster collaboration between provider groups, and thereby improve patient outcomes.

Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.

BACKGROUND: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness. METHODS: We will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity. DISCUSSION: This review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118808.

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. METHODS/DESIGN: The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. DISCUSSION: The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. TRIAL REGISTRATION: ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Wastewater input reductions reverse historic hypereutrophication of Boston Harbor, USA.

This paper documents the changes that followed large nutrient (N and P) and organic matter input reductions to a major metropolitan marine bay, Boston Harbor (USA). Before input reduction, its N and P inputs fell in the upper range of the < 1-> 300 gN m-2 year-1 and < 0.1-> 40 gP m-2 year-1 for coastal systems. Elevated nutrient and organic matter inputs are recognized causes of coastal eutrophication. Treatment upgrades and then diversion of its wastewater discharges offshore, lowered its N, P, and organic C inputs by 80-90%. The input decreases lowered its trophic status from hypereutrophic to eutrophic-mesotrophic. With the reversal of hypereutrophication, pelagic production and phytoplankton biomass decreased, and the nitrogen limitation relative to phosphorus limitation increased. Benthic metabolism and dissolved inorganic N fluxes decreased, and benthic-pelagic coupling was altered. Bottom-water dissolved oxygen, already at healthy levels, increased, and seagrass expanded. Coastal management requires that the changes, following the nutrient and organic matter input reductions implemented to address eutrophication, be understood. Boston Harbor's recovery, because its water column was vertically well mixed and marine, was more pronounced than in many other systems.

Risk variables associated with abnormal calcium, magnesium and phosphate levels among emergency department patients.

OBJECTIVE: The utility of calcium, magnesium and phosphate measurement in the ED is limited. We aimed to determine clinical risk variables for abnormal levels of these electrolytes in order to inform the development of an ordering guideline. METHODS: We performed a retrospective, observational study of patients who presented to a tertiary referral ED between January and June 2017. Adult patients who had serum calcium, magnesium or phosphate tests completed during their ED stay were included. Presenting symptoms and signs, comorbidities, medication use and laboratory values were extracted from the medical record. Patients with missing data items were excluded. Logistic regression models determined clinical risk variables associated with low and high levels of each electrolyte. RESULTS: A total of 33 120 adults presented during the study period. Of the 1679 calcium, 1576 magnesium and 1511 phosphate tests, 228 (13.6%), 158 (10.0%) and 387 (25.6%) were abnormal, respectively. Significant risk variables (P < 0.05) for abnormal levels were: hypocalcaemia - vomiting, perioral numbness, hand/foot spasm, calcium and phosphate supplements and chemotherapy (odds ratio [OR] range 5.9-17.3); hypercalcaemia - female sex, vomiting, polyuria, confusion, hyperparathyroidism, cancer and type 1 diabetes (OR range 2.3-9.7); hypomagnesemia - female sex, proton pump inhibitor use, tacrolimus use, alcohol abuse and type 2 diabetes (OR range 2.2-13.1); hypermagnesemia - lethargy, thiazide use and chronic kidney disease (OR range 4.3-4.5); hypophosphatemia - nausea, seizure and glucocorticoid use (OR range 1.7-2.1); and hyperphosphataemia - polyuria, diuretics and chronic kidney disease (OR range 1.9-5.0). CONCLUSION: A range of demographic, comorbid, medication and clinical variables are associated with abnormal calcium, magnesium and phosphate levels. These findings will inform the development of clinical guidelines to rationalise calcium, magnesium and phosphate testing. Justification may be required for testing patients with no risk variables.

A Pilot Study of the Effects of Chair Yoga and Chair-Based Exercise on Biopsychosocial Outcomes in Older Adults With Lower Extremity Osteoarthritis.

This pilot study examined whether chair yoga and chair-based exercise are effective in managing biopsychosocial outcomes for older adults with lower extremity osteoarthritis. Both interventions improved physical function and mobility over time, although no significant differences between the 2 interventions were identified.

Benzothiazole-based compounds as potent endothelial lipase inhibitors.

A series of benzothiazoles with a cyano group was synthesized and evaluated as endothelial lipase (EL) inhibitors for the potential treatment of cardiovascular diseases. Efforts to reduce molecular weight and polarity in the series led to improved physicochemical properties of these compounds, as well as selectivity for EL over hepatic lipase (HL). As a benchmark compound, 8i demonstrated potent EL activity, an acceptable absorption, distribution, metabolism and elimination (ADME) profile and pharmacokinetic (PK) exposure which allowed further evaluation in preclinical animal efficacy studies.

Increase in lysophosphatidate acyltransferase activity in oilseed rape (Brassica napus) increases seed triacylglycerol content despite its low intrinsic flux control coefficient.

Lysophosphatidate acyltransferase (LPAAT) catalyses the second step of the Kennedy pathway for triacylglycerol (TAG) synthesis. In this study we expressed Trapaeolum majus LPAAT in Brassica napus (B. napus) cv 12075 to evaluate the effects on lipid synthesis and estimate the flux control coefficient for LPAAT. We estimated the flux control coefficient of LPAAT in a whole plant context by deriving a relationship between it and overall lipid accumulation, given that this process is a exponential. Increasing LPAAT activity resulted in greater TAG accumulation in seeds of between 25% and 29%; altered fatty acid distributions in seed lipids (particularly those of the Kennedy pathway); and a redistribution of label from 14 C-glycerol between phosphoglycerides. Greater LPAAT activity in seeds led to an increase in TAG content despite its low intrinsic flux control coefficient on account of the exponential nature of lipid accumulation that amplifies the effect of the small flux increment achieved by increasing its activity. We have also developed a novel application of metabolic control analysis likely to have broad application as it determines the in planta flux control that a single component has upon accumulation of storage products.

Neurochemical effects of oxytocin in people at clinical high risk for psychosis.

Alterations in neurochemical metabolites are thought to play a role in the pathophysiology of psychosis onset. Oxytocin, a neuropeptide with prosocial and anxiolytic properties, modulates glutamate neurotransmission in preclinical models but its neurochemical effects in people at high risk for psychosis are unknown. We used proton magnetic resonance spectroscopy (1H-MRS) to examine the effects of intranasal oxytocin on glutamate and other metabolites in people at Clinical High Risk for Psychosis (CHR-P) in a double-blind, placebo-controlled, crossover design. 30 CHR-P males were studied on two occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on the concentration of glutamate, glutamate+glutamine and other metabolites (choline, N-acetylaspartate, myo-inositol) scaled to creatine were examined in the left thalamus, anterior cingulate cortex (ACC) and left hippocampus, starting approximately 75, 84 and 93 min post-dosing, respectively. Relative to placebo, administration of oxytocin was associated with an increase in choline levels in the ACC (p=.008, Cohen's d = 0.54). There were no other significant effects on metabolite concentrations (all p>.05). Our findings suggest that, at ∼75-99 min post-dosing, a single dose of intranasal oxytocin does not alter levels of neurochemical metabolites in the thalamus, ACC, or hippocampus in those at CHR-P, aside from potential effects on choline in the ACC.