MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Knowledge of emergency dental management among a localized sample of athletic trainers.

BACKGROUND/AIMS: Athletic trainers are often the point person when sports-related traumatic dental injuries (TDIs) occur. The aim of this study was to assess knowledge levels of the management of TDIs among athletic trainers in the Midwest United States, as well as evaluate variables that may influence knowledge levels. MATERIAL AND METHODS: A survey was sent to athletic trainers licensed in Minnesota, Nebraska, and Iowa. The survey included 28 multiple-choice and fill in the blank questions split into three sections. The three sections included background, emergency management of TDIs, and opinion questions. RESULTS: Of the participants, 100% recalled receiving medical first aid training. However, only 71% recalled receiving formal training on emergency management of dental injuries. Although 75% were confident in managing a dental injury, over 63% of participants scored less than 70% in the knowledge score section. Majority of the participants (98.4%) reported that they believe training on the management of TDIs is important. Athletic trainers working with contact sports were more likely to have experienced managing TDIs more recently than those working in noncontact sports. CONCLUSIONS: This study shows the gaps in knowledge among athletic trainers pertaining to management of TDIs and emphasizes the importance of sports community having adequate education on emergency management of such dental injuries.

Weak legs.

A 48 year old lady presented with a 7-week history of progressive generalised myalgia and muscle weakness resulting in recurrent falls. Her past medical history included bipolar affective disorder and a previous stroke. Her medications included clopidogrel 75mg, atorvastatin 80mg, and quetiapine 400mg twice daily.

Studies of multifunctional DNA polymerase I from the extremely radiation resistant Deinococcus radiodurans: Recombinant expression, purification and characterization of the full-length protein and its large fragment.

Deinococcus radiodurans is a bacterium with extreme resistance to desiccation and radiation. Although the origins of this extreme resistance have not been fully elucidated, an efficient DNA repair machinery that includes the enzyme DNA polymerase I, is potentially crucial as part of a protection mechanism. Here we have cloned and performed small, medium, and large-scale expression of full-length D. radiodurans DNA polymerase I (DrPolI) as well as the large/Klenow fragment (DrKlenow). We then carried out functional characterization of 5' exonuclease, DNA strand displacement and polymerase activities of these proteins using gel-based and molecular beacon-based biochemical assays. With the same expression and purification strategy, we got higher yield in the production of DrKlenow than of the full-length protein, approximately 2.5 mg per liter of culture. Moreover, we detected a prominent 5' exonuclease activity of DrPolI in vitro. This activity and, DrKlenow strand displacement and DNA polymerase activities are preferentially stimulated at pH 8.0-8.5 and are reduced by addition of NaCl. Interestingly, both protein variants are more thermostable at pH 6.0-6.5. The characterization of DrPolI's multiple functions provides new insights into the enzyme's role in DNA repair pathways, and how the modulation of these functions is potentially used by D. radiodurans as a survival strategy.

Accuracy of cold sensibility testing on teeth with full-coverage restorations: a clinical study.

AIM: This clinical study evaluated the reliability of the 1,1,1,2-tetrafluoroethane (Endo Ice) cold test to determine the pulpal diagnosis of teeth with full-coverage restorations (FCR). The effect of several variables on its reliability was also investigated. METHODOLOGY: Data collected from 825 patients treated in the Advanced Education Program in Endodontics at the University of Iowa, USA were analysed. The experimental group included 425 teeth with FCR, whilst the control group consisted of 400 teeth with natural crowns (NC). The pulp sensibility test results, tooth type, tooth number, type of crown, age, gender, presence or absence of caries and recent use of analgesics were recorded. Bivariate analyses were performed to assess the variables associated with the accuracy of dental pulp sensibility tests for either teeth with crowns or teeth without crowns using chi-square tests, Fisher's exact tests, Cochran-Mantel-Haenszel tests, and the Wilcoxon rank-sum tests. A P-value of less than 0.05 was used as a criterion for statistical significance, and a P-value in 0.05 < P < 0.10 was used as a criterion for marginal relevance. RESULTS: The sensibility test results for FCR teeth had an accuracy of 0.866; sensitivity of 0.835; specificity of 0.879; a positive predictive value of 0.746; and a negative predictive value of 0.926. The data indicated a significant difference in the accuracy of pulp sensibility test results between the experimental and control groups (P < 0.001). Although the cold test in FCR teeth still had high accuracy, teeth with NC were significantly more likely to have true-positive and true-negative results (91.5% NC vs. 86.6% FCR, P = 0.024). No significant differences between FCR and NC were found concerning gender, tooth type, type of crown, the presence of abutment and recent use of analgesic (P > 0.05). CONCLUSION: Pulp sensibility cold testing with 1,1,1,2-tetrafluoroethane (TFE) on teeth with FCR was less accurate than on teeth without full-coverage crowns. However, the use of TFE cold testing is still a relevant and reliable diagnostic tool, particularly for teeth with a pulpal diagnosis of symptomatic irreversible pulpitis. Clinicians should routinely carry out cold pulp sensibility testing on teeth when making a pulpal diagnosis.

Differentiated thyroid cancer: A retrospective evaluation of the impact of changes to disease management guidelines on patients in South East Scotland.

BACKGROUND: The British Thyroid Association (BTA) updated guidelines for the management of differentiated thyroid cancer (DTC) in 2014. A key update was that patients with unifocal disease >10-≤40 mm in diameter, aged <45 years and with no other risk factors could be considered for lobectomy alone. The aim of this study was to retrospectively evaluate the potential impact of these changes on the management of DTC in South East Scotland, and to analyse the characteristics of lobes now potentially considered for observation rather than resection. METHODS: Consecutive patients were identified through prospectively held regional MDT minutes from 2009 to 13. Data included age, pT, pN, M stage, tumour size, vascular invasion and extra-thyroidal extension. RESULTS: From a cohort of 281 patients, 22 (8%) could now be considered for lobectomy alone. Of these, 4 had disease in the contralateral lobe (18%), all of which were low-risk tumours with no influence on recommendation for radioactive remnant ablation (RRA). Analysis of all patients, regardless of age, with pT1-2N0M0 disease (n = 50) revealed 11 (22%) had contralateral disease. The presence of index multifocal disease was predictive of disease in the contralateral lobe. One patient (2%) had a finding in the contralateral lobe which may potentially influence the recommendation for RRA. In no cases did findings in the contralateral lobe elevate a patient to a group where RRA was routinely recommended by BTA guidelines. DISCUSSION: The updated BTA guidelines are likely to affect only 8% of our cohort. Further analysis questions the role of age in excluding patients from a conservative approach.

The Source of the Problem.

A 58-year-old lady presented to the Emergency Department with a two-day history of shortness of breath and confusion, on a background of one week's history of general malaise, vomiting, fevers and chills. Her past medical history was unremarkable except for a large, benign goitre. Systemic enquiry revealed no symptoms to suggest a focus of infection.

The Source of the Problem.

The portable chest x-ray (Figure 1) shows a widened cardiac silhouette. An endotracheal tube is in situ, indicating the patient is now intubated. The ECG (Figure 2) shows sinus rhythm with widespread mixed convex and concave ST elevation, most notable in V4, V5 and the lateral leads. There is a suggestion of PR depression in the inferior leads.

A national study of the unmet needs of support persons of haematological cancer survivors in rural and urban areas of Australia.

PURPOSE: This study aimed to compare support persons of haematological cancer survivors living in rural and urban areas in regard to the type, prevalence and factors associated with reporting unmet needs. METHODS: One thousand and four (792 urban and 193 rural) support persons of adults diagnosed with haematological cancer were recruited from five Australian state population-based cancer registries. Participants completed the Support Person Unmet Needs Survey (SPUNS) that assessed the level of unmet needs experienced over the past month across six domains. RESULTS: Overall, 66% of support persons had at least one 'moderate, high or very high' unmet need and 24% (n = 182) reported having multiple (i.e. 6 or more) 'high/very high' unmet needs in the past month. There were no significant differences between rural and urban support persons in the prevalence of multiple unmet needs or mean total unmet needs scores. There were however significant differences in the types of 'high/very high' unmet needs with support persons living in rural areas more likely to report finance-related unmet needs. Support persons who indicated they had difficulty paying bills had significantly higher odds of reporting multiple 'high/very high' unmet needs. CONCLUSIONS: This is the first large, population-based study to compare the unmet needs of support persons of haematological cancer survivors living in rural and urban areas. Findings confirm previous evidence that supporting a person diagnosed with haematological cancer correlates with a high level of unmet needs and highlight the importance of developing systemic strategies for assisting support persons, especially in regard to making financial assistance and travel subsidies known and readily accessible to those living in rural areas.

An unusual case of dysphagia.

A 51-year-old lady, with a background of an arachnoid cyst and ventriculo-peritoneal shunt in situ, presented to the Acute Medical Unit with a 2-day history of neck pain. She awoke from sleep with the pain and it persisted since. She had not been involved in any trauma, had no previous history of neck or back pain and her pain was not controlled with simple analgesia. She also complained of new odynophagia and high dysphagia, particularly to solid foods. There was no history of upper respiratory tract infection.

Is there a link between childhood adversity, attachment style and Scotland's excess mortality? Evidence, challenges and potential research.

BACKGROUND: Scotland has a persistently high mortality rate that is not solely due to the effects of socio-economic deprivation. This "excess" mortality is observed across the entire country, but is greatest in and around the post-industrial conurbation of West Central Scotland. Despite systematic investigation, the causes of the excess mortality remain the subject of ongoing debate. DISCUSSION: Attachment processes are a fundamental part of human development, and have a profound influence on adult personality and behaviour, especially in response to stressors. Many studies have also shown that childhood adversity is correlated with adult morbidity and mortality. The interplay between childhood adversity and attachment is complex and not fully elucidated, but will include socio-economic, intergenerational and psychological factors. Importantly, some adverse health outcomes for parents (such as problem substance use or suicide) will simultaneously act as risk factors for their children. Data show that some forms of "household dysfunction" relating to childhood adversity are more prevalent in Scotland: such problems include parental problem substance use, rates of imprisonment, rates of suicide and rates of children being taken into care. However other measures of childhood or family wellbeing have not been found to be substantially different in Scotland compared to England. We suggest in this paper that the role of childhood adversity and attachment experience merits further investigation as a plausible mechanism influencing health in Scotland. A model is proposed which sets out some of the interactions between the factors of interest, and we propose parameters for the types of study which would be required to evaluate the validity of the model.

Unintentional poisoning in young children: does developmental stage predict the type of substance accessed and ingested?

BACKGROUND: When children aged 0-4 years are analysed together as a group for poisoning risk, important differences for smaller age intervals by medicinal and non-medicinal substances are masked. These differences have been attributed to child developmental stages but no studies have been conducted that examine the predictive value of child developmental stage for poisoning by substance type, using 3-month age intervals as a proxy for developmental stage and adjusting for the effect of sex, socio-economic status and remoteness of residence. METHODS: A population-based dataset of unintentional poisoning hospitalizations in children aged 0-4 years was used to predict the type of substance ingested. Associations between the type of substance and age, sex, socio-economic status and remoteness of residence were measured using multivariate logistic regression. RESULTS: Children aged 12-17 months had significantly higher odds of experiencing a non-medicinal poisoning while children aged 24-41 months had significantly higher odds of experiencing a medicinal poisoning. Males and children from more disadvantaged and outer regional areas had higher odds of experiencing a non-medicinal poisoning. CONCLUSIONS: Children aged 0-4 years differ in their stage of development and as a consequence, vary significantly in their ability to access their environment. Our results clearly show that odds of poisoning by medicinal substances compared with non-medicinal substances change as children age. This study provides evidence that child development predicts the type of substance accessed and ingested.

A review of the use of human factors classification frameworks that identify causal factors for adverse events in the hospital setting.

Various human factors classification frameworks have been used to identified causal factors for clinical adverse events. A systematic review was conducted to identify human factors classification frameworks that identified the causal factors (including human error) of adverse events in a hospital setting. Six electronic databases were searched, identifying 1997 articles and 38 of these met inclusion criteria. Most studies included causal contributing factors as well as error and error type, but the nature of coding varied considerably between studies. The ability of human factors classification frameworks to provide information on specific causal factors for an adverse event enables the focus of preventive attention on areas where improvements are most needed. This review highlighted some areas needing considerable improvement in order to meet this need, including better definition of terms, more emphasis on assessing reliability of coding and greater sophistication in analysis of results of the classification. Practitioner Summary: Human factors classification frameworks can be used to identify causal factors of clinical adverse events. However, this review suggests that existing frameworks are diverse, limited in their identification of the context of human error and have poor reliability when used by different individuals.

Public Health England survey of eye lens doses in the UK medical sector.

The ICRP has recently recommended that the occupational exposure limit for the lens of the eye be reduced to 20 mSv in a year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv. There has been concern amongst some groups of individuals, particularly interventional cardiologists and radiologists as well as relevant professional bodies, that implementation of these recommendations into UK law will adversely affect working patterns. However, despite a number of informative European studies, there is currently little UK dosimetry data available upon which judgements can effectively be based. In order to address this knowledge gap, Public Health England has carried out a small, targeted survey of UK lens doses to medical staff undertaking procedures likely to involve the highest levels of radiation exposure. Two out of a total of 61 individuals surveyed had projected annual doses which could be close to 20 mSv, measured outside lead glasses. Use of protective equipment was generally good; however, lead glasses were only used by 9 participants. The results of this survey suggest that compliance with the ICRP recommendations is likely to be possible for most individuals in the UK medical sector.

What Matters to Aboriginal and Torres Strait Islander Youth (WM2Y): a study protocol to develop a national youth well-being measure.

INTRODUCTION: Adolescents face challenges associated with unprecedented environmental, social and technological changes. The impacts of colonisation, intergenerational trauma, racism and socioeconomic disadvantage intensify these challenges for many Aboriginal and Torres Strait Islander adolescents. However, Aboriginal and Torres Strait Islander adolescents also have cultural, spiritual, family and community capital that fosters their well-being.To date, little research has focused on understanding and appropriately measuring the well-being of Aboriginal and Torres Strait Islander adolescents, a pivotal factor in informing and guiding programmes and interventions that support them. This study will identify the domains of well-being and develop a new preference-based well-being measure based on the values and preferences of Aboriginal and Torres Strait Islander youth (aged 12-17 years). METHODS AND ANALYSIS: This project will be conducted across three research phases: (1) qualitative exploration of well-being using PhotoYarning and yarns with adult mentors to develop candidate items; (2) Think Aloud study, quantitative survey, psychometric analysis, validity testing of candidate items and finalisation of the descriptive system; and (3) scoring development using a quantitative preference-based approach. A multinomial (conditional) logit framework will be used to analyse responses and generate a scoring algorithm for the new preference-based well-being measure. ETHICS AND DISSEMINATION: Ethics approvals have been obtained from: the Human Research Ethics Committees for each state and territory where data are being collected, the institutions where the research is being conducted and from the relevant Departments of Education. The new well-being measure will have wide applicability and can be used in assessing the effectiveness of programmes and services. This new national measure will ensure benefit and positive impact through the ability to identify and measure the aspects of well-being important to and valued by Aboriginal and Torres Strait Islander youth. Results will be published in international peer-reviewed journals and presented at conferences, and summaries will be provided to the study partner organisations and other relevant organisations.

Does infection play a role in post-tonsillectomy haemorrhage? A narrative review.

OBJECTIVE: Post-tonsillectomy haemorrhage is an increasingly common cause of morbidity following tonsillectomy. Secondary post-tonsillectomy haemorrhage occurring more than 24 hours after an operation has long been attributed to post-operative infection; however, there is little evidence to support this hypothesis and the associated use of antibiotics in the current literature. METHOD: This study looked at the aetiology and evidence-based management of post-tonsillectomy haemorrhage, and investigated the impact of bacterial infection and antimicrobials on the pathogenesis and clinical course of this complication. RESULTS: A number of peri-operative risk factors for post-tonsillectomy haemorrhage exist, and infective pathologies, including recurrent or chronic tonsillitis and group A streptococcus on blood cultures, may predispose to bleeding. Very few studies have shown a link between post-tonsillectomy haemorrhage and objective markers of infection such as pyrexia, raised inflammatory markers or positive microbiology cultures. The role of antibiotics in secondary post-tonsillectomy haemorrhage remains controversial, and numerous randomised, controlled trials of peri-operative antibiotics have shown no significant difference in bleeding rates between antibiotics and controls. CONCLUSION: Further trials investigating the role of antibiotics and more robust studies investigating the presence of bacterial infection at the time of bleeding may be required to determine the true role of infection in post-tonsillectomy haemorrhage.

A systematic review of the role of penicillin versus penicillin plus metronidazole in the management of peritonsillar abscess.

BACKGROUND: Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in addition to penicillin, but evidence to support this is limited. This review assessed the evidence of benefit of metronidazole for the treatment of peritonsillar abscess. METHODS: A systematic review was conducted of the literature and databases including Ovid Medline, Ovid Embase, PubMed and Cochrane library. Search terms included all variations of peritonsillar abscess, penicillin and metronidazole. RESULTS: Three randomised, control trials were included. All studies assessed the clinical outcomes after treatment for peritonsillar abscess, including recurrence rate, length of hospital stay and symptom improvement. There was no evidence to suggest additional benefit with metronidazole, with studies suggesting increased side effects. CONCLUSION: Evidence does not support the addition of metronidazole in first-line management of peritonsillar abscess. Further trials to establish optimum dose and duration schedules of oral phenoxymethylpenicillin would benefit clinical practice.

CD4 T cell depletion at the cervix during HIV infection is associated with accumulation of terminally differentiated T cells.

In blood, the accumulation of terminally differentiated (TD) T cells during HIV infection is associated with CD4 T cell loss and HIV disease progression. Here, we investigated the maintenance and functional characteristics of memory T cells at the cervix. We found that CD4 T cell depletion at the cervix mirrors CD4 depletion in blood. In all women, depletion of CD4 T cells at the cervix was associated with significant reductions in CD45RA- CCR7+ (central memory [CM]) T cells and the accumulation of CD45RA+ CCR7- (TD T cells). We determined whether inflammation in the genital tract was associated with the local differentiation of T cells at the cervix. In uninfected women, genital tract inflammation was associated with the accumulation of CD45RA- CCR7+ CM CD4 T cells and reduced frequencies of CD45RA+ CCR7- TD cells at the cervix. This finding may reflect the fact that, in the absence of HIV infection, TD T cells may be slowly lost in the presence of genital inflammation, while CD45RA- CCR7+ CM T cells are recruited to replenish the diminishing CD4 T cell pool. Following global stimulation with phorbol myristate acetate (PMA)-ionomycin, we noted a significant interleukin 2 (IL-2) deficit in both cervical and blood CD4 T cells from HIV-infected women compared to uninfected women, while gamma interferon (IFN-γ) production was similar, irrespective of HIV status. Few HIV-infected women had detectable IFN-γ and IL-2 HIV-specific T cell responses at the cervix, and these responses were significantly lower in magnitude than the corresponding responses in blood. These data suggest that CD4 depletion was associated with the accumulation of terminally differentiated T cell phenotypes at the cervical mucosa defective in their ability to produce IL-2. CD4 depletion and compromised immunity at the cervix may be accompanied by progressive decline of central memory-like T cells and development of T cells toward terminally differentiated phenotypes.

Cutting the research pie: a value-weighting approach to explore perceptions about psychosocial research priorities for adults with haematological cancers.

Despite the burden of illness associated with haematological cancers, little research is available about improving psychosocial outcomes for this group. Given scarce research funds, it is important to ensure that resources are used strategically for improving their psychosocial well-being. This study aimed to identify the perceptions of professionals, patients and carers regarding prioritising psychosocial research efforts. First, an expert panel's views on priorities for research were identified. This was followed by a web survey to obtain the perceptions of 117 health professionals, patients and carers. The value-weighting survey used points allocation, allowing respondents to indicate the relative priority of each option. A substantial proportion of resources were allocated to patients who were newly diagnosed or receiving treatment. Less priority was given to other stages of the cancer journey or non-patient populations. There was no indication that any type of psychosocial research was a priority; however, some differences were identified when comparing the priorities of the three respondent groups. To improve psychosocial outcomes for haematological cancer patients, resources should be directed towards patients in the early stages of the cancer journey. There may be a need for research investigating potential interventions to improve psychosocial outcomes for patients with haematological cancers.