Unequivocal identification of brown adipose tissue in a human infant

We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.     

Prioritising health in anti-doping: What Australians think

ObjectivesThere is debate concerning whether the guiding paradigm for anti-doping policy should be the current legalistic approach or a “harm minimisation” approach prioritising athlete health. This study sought to determine whether a representative sample of Australians prioritises health above other concerns using the World Anti-Doping Code's Spirit of Sport statement which lists the 11 attributes that define the moral basis for anti-doping.DesignA Best–Worst Scaling (BWS) Balanced Incomplete Block Design experiment using 11 choice sets of five Spirit attributes from the set of 11, with the attributes within each choice set in a random order.MethodsA representative sample of n = 168 Australians responded to an on-line survey. The BWS scores defined the relative ranking of each attribute to define an aggregate model and demographically defined models (gender, education, sports participation and sports following).ResultsHealth was ranked as 7/11 in the aggregate model. Only those who did not follow sport prioritised health (2/11), with other demographic models failing to show a meaningful departure from the aggregate model.ConclusionsAustralians ranked health below other attributes in the Spirit of Sport, appearing to prioritise “rule following” consistent with the legalistic approach. This challenges the harm minimisation approach to managing the role of drugs in sport and suggests that rule-following and legalistic approaches to drug use should take precedence over health messages.     

Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia

The aim of the present study was to investigate the relationship between circulating PCSK9 (proprotein convertase subtilisin kexin type?9) and FCHL (familial combined hyperlipidaemia) and, when positive, to determine the strength of its heritability. Plasma PCSK9 levels were measured in FCHL patients (n=45), NL (normolipidaemic) relatives (n=139) and their spouses (n=72). In addition, 11 FCHL patients were treated with atorvastatin to study the response in PCSK9 levels. PCSK9 levels were higher in FCHL patients compared with NL relatives and spouses: 96.1 compared with 78.7 and 82.0?ng/ml (P=0.004 and P=0.002 respectively). PCSK9 was significantly associated with both TAG (triacylglycerol) and apolipoprotein B levels (P<0.001). The latter relationship was accounted for by LDL (low-density lipoprotein)-apolipoprotein B (r=0.31, P=0.02), not by VLDL (very-low-density lipoprotein)-apolipoprotein B (r=0.09, P=0.49) in a subgroup of subjects (n=59). Heritability calculations for PCSK9 using SOLAR and FCOR software yielded estimates of 67-84% respectively (P<0.0001). PCSK9 increased from 122 to 150?ng/ml in 11 FCHL patients treated with atorvastatin (40?mg) once daily for 8?weeks (P=0.018). In conclusion, plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results, combined with the significant rise in PCSK9 levels after statin therapy, warrant further studies in order to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidaemia.     

Imaging presentation of complicated diabetic ketoacidosis: a case report

Spontaneous pneumomediastinum is a fairly uncommon complication of diabetic ketoacidosis. Knowledge of the clinical and radiographic manifestation is important for the proper management of patients since the disease usually follows a benign evolution. We report a case of a 20-year-old soldier who presented with a pneumomediastinum that was initially falsely attributed to a motor vehicular crash.     

The information sources used by community nurse prescribers

A purposive sample of 22 community nurse prescribers and five prescribing leads were interviewed to determine how nurses both access and assess the reliability of pharmacological information. Prescribers used both printed material and other professionals to obtain pharmacological information. The most commonly mentioned sources of printed material were journals and the British National Formulary. Other people that nurses obtained information from included pharmaceutical company representatives, community pharmacists, nurse specialists, colleagues, and GPs. Nurses described the attributes that they associated with reliable information (previous vetting, up-to-date and used by other healthcare professionals) and unreliable information (produced by those with a vested interest). Much of the pharmacological information supporting prescribers is aimed at doctors and may not be accessible for nurse prescribers. Organizations seeking to influence evidence-based practice should consider the method of communication in addition to the message.     

Potential role for psychological skills training in emergency medicine: Part 1 ‐ Introduction and background

Psychological skills training (PST) is the systematic acquisition and practice of different psychological techniques to improve cognitive and technical performance. This training consists of three phases: education, skills acquisition and practice. Some of the psychological skills developed in this training include relaxation techniques, focusing and concentration skills, positive ‘self‐suggestion’ and visualisation exercises. Since the middle of the 20th century, PST has been successfully applied by athletes, performing artists, business executives, military personnel and other professionals in high‐risk occupations. Research in these areas has demonstrated the breadth and depth of the training's effectiveness. Despite the benefits realised in other professions, medicine has only recently begun to explore certain elements of PST. The present paper reviews the history and evidence behind the concept of PST. In addition, it presents some aspects of PST that have already been incorporated into medical training as well as implications for developing more comprehensive programmes to improve delivery of emergency medical care.     

Longitudinal invariance and construct validity of the abbreviated late-life function and disability instrument in healthy older adults

Szabo AN, Mullen SP, White SM, Wojcicki TR, Mailey EL, Gothe N, Olson EA, Fanning J, Kramer AF, McAuley E. Longitudinal invariance and construct validity of the abbreviated Late-Life Function and Disability Instrument in healthy older adults.

Objective

To cross-validate the psychometric properties of the abbreviated Late-Life Function and Disability Instrument (LL-FDI), a measure of perceived functional limitations and disability.

Design

Baseline and 12-month follow-up assessments conducted across the course of a 12-month exercise program.

Setting

University research community.

Participants

Older healthy adults (N=179; mean ± SD age, 66.43±5.67y) at baseline; 145 were retained at follow-up.

Interventions

Not applicable.

Main Outcome Measures

LL-FDI and functional performance measures.

Results

Factor analyses confirmed the factor structure of the abbreviated LL-FDI, and all subscales met minimal criteria for temporal invariance. Significant correlations also were found between functional limitations subscales and an array of physical function performance measures, supporting the scale's construct validity.

Conclusions

The abbreviated LL-FDI with some modifications appears to be temporally invariant in community-dwelling older adults. Additionally, moderate relationships between functional limitations and functional performance provide further support for these being conceptually distinct constructs.     

Protective variant for hippocampal atrophy identified by whole exome sequencing

We used whole‐exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in‐silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole‐brain analysis and meta‐analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next‐generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. Ann Neurol 2015;77:547–552     

Attenuated psychosis syndrome: benefits of explicit recognition

概述

符合轻微精神病综合征（attenuated psychosis syndrome ，APS）标准的个体具有独有的特征，越来越多的文献认为对符合APS标准的个体提供服务在临床上能获益，因而APS的诊断在精神病学中有着重要作用，但过去却被忽视了。推行这一诊断将有助于减少对具有前驱期精神病性状态个体的过度诊断和治疗。因为青少年是被诊断为APS的主要群体，所以也应鼓励那些主要为青少年服务的医生接受关于轻微精神病综合征的全面培训。虽然只有一部分APS个体最终会发展为精神病，但是临床上所有的APS个体都需要得到帮助——无论他们的转归如何。DSM-5正式列出APS，这将有利于开展如何识别这类个体的临床需求以及如何满足这些需求的研究。

中文全文

本文全文中文版从2015年4月8日起在http://dx.doi.org/10.11919/j.issn.1002-0829.215015可供免费阅览下载Prevention of psychotic illness – which can be a devastating condition-has become a growing priority of mental health clinicians and researchers. Advances in the identification of people with attenuated psychotic symptoms, a group generally at increased risk for psychosis, have allowed for the development of novel intervention strategies. These interventions have had promising results, including symptom improvement, better functioning, delayed onset of psychosis, and reduced rates of transition from attenuated to full-threshold psychosis.[1],[2] Moreover, identifying and potentially treating individuals with attenuated psychosis will shorten or completely eliminate the period during which individuals destined to develop psychosis experience psychotic symptoms without treatment (i.e., the ‘duration of untreated psychosis’ or DUP), a change that is related to several positive outcomes, including better response to treatment, higher quality of life, and reduced mortality after the onset of psychotic illness.[3],[4] Given this tremendous potential benefit of early intervention, the importance of a reliable category to identify people with attenuated psychosis is hard to overstate. The field has created a variety of related labels to represent an attenuated, at-risk state, including ‘clinical high-risk,’ ‘ultra high-risk,’ ‘the prodrome,’ and ‘psychosis-risk syndrome.’ The term ‘Attenuated Psychosis Syndrome’ (APS), a construct characterized by attenuated psychotic symptoms that overlap with an at-risk status, has been added to the DSM-5 both as a condition for future study and as one of the possible presentations of Other Specified Schizophrenia Spectrum and Other Psychotic Disorders, 298.8 (F28).[5] Thus, the DSM-5 currently acknowledges APS as a potential disorder and provides clinicians and researchers a mechanism to recognize a clinically meaningful attenuated form of psychosis that is associated with risk for progression to full psychosis. Despite ongoing debate about the inclusion of APS in the DSM-5,[6],[7] including the Forum commentary by Dr. Xu and colleagues[8], there has been substantial validating evidence for the construct.[9],[10] Approximately 64% of persons meeting criteria for APS do not develop a psychotic disorder within three years of the onset of APS.[11] They are, nevertheless, at risk for a variety of mental health problems that merit clinical monitoring and management including, but not limited to, subthreshold psychotic symptoms, depression, anxiety, attention-deficit and hyperactivity disorder (ADHD), cognitive deficits, impaired social functioning, family stress, substance abuse, exposure to trauma, and lower quality of life. Moreover, the pattern of distress and symptomatology experienced by individuals with APS is distinct both from that seen in community members who do not seek treatment and from non-APS treatment seekers. Thus the clinical identification of APS is not only important as a method for identifying persons at high-risk of subsequent psychosis; it is also a broad marker for identifying individuals who merit active treatment to address a variety of psychological symptoms.[11],[12],[13] Much more high-quality research among individuals with APS is needed to characterize the level of morbidity and to identify the predictors of outcome. DSM-5 already provides a diagnostic label that includes APS (Other Specified Schizophrenia Spectrum and Other Psychotic Disorders), but the subsequent definition of a specific APS diagnostic category (currently under discussion for the forthcoming DSM-5.1) could greatly facilitate research on APS by promoting improved communication and integration of knowledge between the increasing number of expert centers conducting research on APS or other high-risk syndromes. For instance, prior to the publication of the DSM-5, characteristic symptoms of ‘clinical high-risk’ (CHR) were not well captured under any existing DSM category, indicating the need and potential utility of defining such a category. Using vignette methodology in a study of community-based mental health providers, we found that when given a list of DSM-IV-TR diagnoses the majority of providers diagnosed our validated APS vignette as having a full psychotic illness and 69% of them recommended treatment with antipsychotic medication, a treatment that is explicitly not recommended for this population.[14],[15] This work suggests that over-diagnosis and consequent over-treatment is likely common for patients with APS; having a specific APS category in DSM-5 should facilitate more accurate classification and, hopefully, more appropriate treatment for this important population. Another important advantage of the recognition of APS in the DSM-5 involves workforce development. Despite the fact that at least 50% of people who ultimately develop schizophrenia report attenuated psychotic symptoms in adolescence, psychosis tends to be considered an “adult” disorder. In a recent pilot poll of mental health providers, we found that providers who self-label as child or adolescent-focused providers reported being relatively unfamiliar with psychosis, while those who self-label as adult-focused providers (who were less comfortable working with youth) report more familiarity with psychosis.[16] These findings suggest that the current mental health workforce is not effectively trained to both be sensitive to early signs of psychosis, and to be aware of the developmental needs of adolescents. The APS diagnosis, which primarily occurs among adolescents and young adults, has the potential to shift attention to psychotic and pre-psychotic symptoms in a younger age range and, thus, lead to increased training and sensitivity to risk for psychosis among youth-oriented mental health providers. We have found that even brief training sessions can increase the understanding and awareness of risk signs for psychosis among youth-focused providers.[17] A potential strategy that may help improve the reliability of the APS diagnosis is the use of pre-screening measures. Our research has shown that a variety of methods designed to assess APS symptoms, including both self-report measures and family member-reported measures, are effective for improving diagnostic reliability in real-world clinical settings.[18],[19],[20],[21] Further, when these measures are used to determine whether or not to refer an individual to a specialized clinic for early psychosis, the positive predictive values for future psychosis have ranged from 39 to 53%. Although untested at this point, these results suggest that pre-screened individuals who then meet APS criteria are a subgroup of persons with APS who are at elevated risk of subsequent psychosis. Screening may identify more individuals in need of APS-tailored care, both among those who do and do not subsequently transition to full psychosis.[22]. The inclusion of APS in DSM-5’s Section 3 (for conditions meriting further study) and under the Other Specified Schizophrenia Spectrum and Other Psychotic Disorders diagnosis is an important advance for the field of psychiatry. Given the unique characteristics of people who meet criteria for APS and the growing literature on the clinical benefits of providing services to individuals who meet these criteria, the APS diagnosis serves an important, and previously missing, role in psychiatry. Use of the APS category has the potential to identify, diagnose, and appropriately treat individuals who were likely misclassified and mismanaged in the past. Furthermore, recognition of APS as a common condition among adolescents should promote expanded training about psychosis and attenuated psychosis among clinicians who primarily provide services to children and youth. Only some of the individuals with APS subsequently develop psychosis (i.e., there are many ‘false positives’), but all of them have existing clinical needs – regardless of subsequent conversion. The formal recognition of APS in DSM-5 will facilitate the research needed to identify and meet those needs.