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Genetics contributes susceptibility to most psychiatric conditions and the under-standing of these genetic factors is increasing rapidly. Because of such breakthroughs and their implications for patient care, professional nursing organizations support the incorporation of genetics into nursing curricula and the attainment of a working knowledge of genetics by all nurses. In this article, the basics of psychiatric genetics are presented to provide a foundation for the understanding of current and future findings in the field as well as information about family history assessment and appropriate references that the practitioner may find helpful. [ABSTRACT FROM AUTHOR]

Objective: To describe a multidisciplinary approach for delivery room management of congenital epulis. Study Design: Case reports. Methods: Reporting of two cases of congenital epulis and review of the literature. Results: Antepartum ultrasonography demonstrated massive intraoral masses in two fetuses whereby concerns regarding the patency of the airway at birth necessitated development of a multidisciplinary team of maternal-fetal medicine, neonatal-perinatal medicine, anesthesiology, and otolaryngology. Surgical excision was performed before delivery in one infant and after complete delivery in the other without a need for endotracheal intubation and general anesthesia. Feeding was started early, and both infants were discharged after brief hospital stays. Pathological findings were consistent with congenital epulis. Differential diagnosis and options for surgical intervention are discussed, including ex utero intrapartum treatment. Conclusions: A multidisciplinary approach to antenatally identified congenital intraoral masses facilitates care at birth. Surgical treatment in this milieu may be simple and complete at the time of delivery. [ABSTRACT FROM AUTHOR]

Vaginal swabs were examined for sexually transmissible organisms in 238 girls seen over a 36 month period from July 1989 to June 1992 inclusive. Three groups were seen (age range 1.5-16.1 years), 165 in group 1 in whom there had been a disclosure of sexual abuse, 35 in group 2 where there was a strong suspicion of sexual abuse, and 38 with vulvovaginitis who formed group 3. The isolation of recognised sexually transmitted organisms was low; however, of group 1 19% were colonised with Gardnerella vaginalis compared with 3% of group 2 and 3% of group 3. These figures show significant differences in the proportion of children in each group isolating only from children over the age of 8 years and in five of the six girls with Candida spp there was concern about sexual abuse. Vulvovaginitis in young children was not associated with vaginal candidiasis. The relation of findings to age is discussed and recommendations are made for testing procedures. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is poorly addressed in G8 screening. The aim of the present study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores. Methods: Seventy-four consecutive urogeriatric patients aged 75 and above were evaluated. All patients underwent G8 and Mini-Cog © screening. Patients with a G8 score above 14 were considered geriatric "healthy or fit". A Mini-Cog© from four to five points was considered inconspicuous in screening for cognitive impairment. The additional information of a Mini-Cog© screening during G8 screening was evaluated by looking at G8 "fit and healthy" patients who had conspicuous Mini-Cog© tests and vice versa. Additionally, the results of the neuropsychological subitem "E" of the G8 score were compared with the results of the Mini-Cog© screening. Results: The mean age of the patients was 83 y (min. 75-max. 102). Sixty-one of the patients were males, and 13 were females. Twenty-nine of the patients had a normal G8 score and were considered "healthy or fit", and 45 were not. Forty-three of the patients had an inconspicuous Mini-Cog©, and 31 had a conspicuous Mini-Cog© of less than four points. The majority of G8 "healthy or fit" patients ( n = 24/29) had an inconspicuous Mini-Cog© test. However, of them, five patients had a Mini-Cog© of less than four points, which is suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 subscore in item "E" of two points, 6 patients had a conspicuous Mini-Cog© of less than four points. Conclusions: As shown by the present study, the Mini-Cog© might extend the G8 screening with regard to the detection of cognitive functional impairments that are not detected by the G8 screening alone. It can be easily added to G8 screening.

The goal of this manuscript is to provide a comprehensive and multi-disciplinary review of the best nursing practices of caring for mechanically ventilated patients. By reviewing human medicine literature, the authors will extrapolate procedures that have been found to be most effective in reducing the risk of mechanical ventilation (MV) complications. Paired with review of the current standards in veterinary medicine, the authors will compile the best practice information on mechanically ventilated patient care, which will serve as a detailed resource for the veterinary nursing staff. Written from a nursing standpoint, this manuscript aims to consolidate the nursing assessment of a mechanically ventilated patient, addressing both systemic and physical changes that may be encountered during hospitalization. The goal of this review article is to present information that encourages a proactive approach to nursing care by focusing on understanding the effects of polypharmacy, hemodynamic changes associated with MV, complications of recumbent patient care, and sources of hospital acquired infections. When applied in conjunction with the more technical aspects of MV, this manuscript will allow veterinary technicians involved in these cases to understand the dynamic challenges that mechanically ventilated patients present, provide guidance to mitigate risk, address issues quickly and effectively, and create an up-to date standard of practice that can be implemented., 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 © 2023 Meitner, Feuerstein and Steele.)

This work leverages a custom implementation of a deep neural network-based object detection algorithm to detect people and a set of assistive devices relevant to clinical environments. The object detections form the basis for the quantification of different ambulatory activities and related behaviors. Using features extracted from detected people and objects as input to machine learning models, we quantify how a person ambulates and the mode of ambulation being used.Clinical relevance- This system provides the data required for clinicians and hospitalized patients to work together in the creation, monitoring, and adjustment of ambulatory goals.

Introduction/background: The G8 score is a widespread screening tool for geriatric frailty in oncology. The aim of this study was to evaluate the scores and relevance of G8 items in a standard screening of geriatric patients with uro-oncologic diseases to better understand the results of the assessment., Methods: Eighty-two consecutive uro-oncologic geriatric patients aged 75 years and older were evaluated. All patients underwent a G8 screening that consisted of 8 items. Patients with a G8 score above 14 were considered geriatric "fit", while others were considered to be "frail". Overall results and single item scores were evaluated. Clinical data were gathered from patients' charts., Results: The mean age of the patients was 82 years (min. 75-max. 102). In 36 of the patients, the G8 score indicated "no-frailty", and in 46 patients, the G8 score indicated "frailty". The mean G8 score was 12.9 (min 4-max 17 pts). Item analysis revealed that points were most often lost in items H (polypharmacy), P (comparison of health status to peers) and Age. Fifty-nine, 56 and 52 patients lost points on item Age, item H and item P, respectively. In contrast, the majority of patients reached the maximum score for nutritional items [i.e., items A (food intake), B (weight loss) and F (body mass index (BMI))]. For item A, 73 patients reached the maximum score; for item B, 62 patients reached the maximum score; and for item F, 72 patients reached the maximum score. There were no differences in this distribution pattern when comparing tumour entities, sex, and patients with local vs. metastatic disease., Conclusion: The present study revealed a high percentage of suspicious test results. Potential reasons for these findings include the low threshold of the G8 overall score and the fact that in some items, points were easily lost. Modifications of the test should be considered., (© 2023. The Author(s).)

Objective: Nurses are immersed in stories, and nurses who participate in flight transfers have stories to tell that may hold interest and offer insight for air medical professionals around the world., Methods: Using a narrative inquiry methodology, 5 nurses working for a children's transport service in England were invited to tell stories from their experiences of air medical transfers. The aim of this article was to describe the meanings the nurses assigned to their experiences of flight transfers and to develop an interpretation of the narrative accounts, investigating the implications of the stories., Results: This study provides a record of nurses' flight experiences within a predominately road-based children's transport service. The analysis considered the following topics: humor, parental presence on transport, and the joy and fear associated with the work. Implications for the training of nurses who fly were identified; it is recommended that the design of training should place the technical challenges of the work in the context of the emotional challenges., Conclusion: This article is a timely reflection on the social context of this new nursing experience for any situation around the world, which is seeing expansion of children's air medical transport provision., (Copyright © 2021. Published by Elsevier Inc.)

Our work identifies subjects based on their height and the distance between their joints. Using a depth sensing camera, we obtained the position of a person's joints in 3D space relative to each other. The distances between adjacent joints and height of a subject's head are used to create a vector of eight features for an individual to use for identification. Using modified KNN, full and partial feature sets were used to identify subjects. Additionally, our classifier can be utilized to assess ambulation (such as walking's velocity and distance) of subject, when identified.

Objective: Discovering how transport nurses around the world are prepared and supported for a flight role may illuminate areas of best practice. This article reviews the flight nursing research, exploring what the international literature tells us about the role of flight nurses and discovering lessons from their experiences that may have particular relevance for the UK context., Methods: The results of a literature search and thematic synthesis for flight nursing research are described., Results: Thirteen research articles were obtained covering a broad range of countries. The scope of practice encompasses primary and secondary transport services and both civilian and military personnel. In an attempt to distill the role, work, and purpose of a flight nurse, a list of all the themes and categories that could be identified within the literature was assembled. These were inductively refined into 8 cluster themes, seeking to capture a broad description of the role of a nurse who flies. The definition of a "flight nurse" in the international context is debated. Thoughts related to training and education and, in particular, the nontechnical challenges of the role are discussed., Conclusion: This reflection provides insights that will influence the ongoing conversation around future air medical service development., (Copyright © 2019 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Objectives: To outline the challenges and provide practical recommendations for recruiting inactive, statin-free older adults to facilitate feasible study designs. Data was obtained from a double-blind randomised-controlled clinical trial investigating the effects of acipimox versus placebo on muscle function and metabolism in older (65-75 years), inactive, statin-free males. The initial recruitment target was 20 volunteers within 12 months (November 2016-November 2017)., Results: Recruitment occurred via the Exeter 10,000 database containing 236 'eligible' males, a Facebook campaign reaching > 8000 ≥ 65 years old males, 400 directly-addressed letters to ≥ 66 year old males, > 1500 flyers distributed within the community, > 40 emails to local community groups, 4 recruitment talks, 2 magazine adverts and 1 radio advert. Widespread recruitment efforts reaching > 120,000 people led to the recruitment of 20 volunteers (18 completed the clinical trial) within a 25-month timeframe, highlighting the challenge of the timely recruitment of inactive, statin-free older adults for clinical trials. We recommend recruitment for future clinical trials should take a multi-pronged approach from the outset, prioritising the use of volunteer databases, Facebook campaigns and delivering recruitment talks.

Background and Objective: Prevention of exacerbations in chronic obstructive pulmonary disease (COPD) is important to decrease overall declines in functioning and improve quality of life. The present study sought to develop a psychometrically valid measure of perceived triggers of exacerbations in COPD patients, the COPD Exacerbation Trigger Inventory (CETI)., Methods: Participants (n = 192) were recruited through local clinics and online to complete surveys of the CETI, demographic information, disease-specific information and the COPD Assessment Test (CAT). The CETI included a free response section on patients' individual top triggers, combined with ratings of their controllability., Results: Exploratory principal component analyses identified a stable 5-factor structure (33 items), from which trigger subscales for weather/climate, air pollution/irritants, exercise, infection/illness and psychological factors were formed (internal consistency Cronbach's α = 0.90-0.94). Trigger factors were associated with COPD functional status, exacerbation frequency and healthcare utilization. Participants found personal triggers related to dust, air pollution, smoking and physical activity to be the most easily controlled, whereas those related to psychological factors, climate, infection, respiratory symptoms and sleep to be more difficult to control. Greater perceived controllability of triggers was associated with lower CAT scores, indicating better health status and less impact of the disease on functioning., Conclusion: The CETI is a psychometrically valid measure of perceived exacerbation triggers in patients with COPD. Perceived triggers are associated with clinical outcomes. Assessment of trigger classes and their controllability may prove useful in both research and clinical settings with COPD patients and to further our knowledge in prevention and disease management., (© 2018 Asian Pacific Society of Respirology.)

Emerging research indicates that individuals with asthma have an increased risk of cognitive impairment, yet the associations of asthma with neural correlates of memory remain relatively unknown. The hippocampus is the predominant neural structure involved in memory, and alterations in the hippocampal metabolic profile are observed in individuals with mild cognitive impairment. We therefore hypothesized that individuals with asthma may have altered hippocampal metabolites compared to healthy controls. Structural magnetic resonance imaging (sMRI) and proton magnetic resonance spectroscopy ( 1 H-MRS) were used to compare hippocampal volume and metabolites of otherwise healthy adults with and without asthma (N = 40), and to study the association of these measures with cognitive function and asthma-related variables. Participants underwent 3-Tesla sMRI and 1 H-MRS, with the volume of interest placed in the left hippocampus to measure levels of N -acetylaspartate (NAA), glutamate (Glu), creatine (Cr), and myo-inositol (MI), as indicators of neuronal viability, cellular activity, cellular energy reserve, as well as glial activation. Individuals with asthma had lower hippocampal NAA compared to healthy controls. For all participants, poorer cognitive function was associated with reduced NAA and Glu. For individuals with asthma, poorer cognitive function was associated with reduced disease control. Additionally, short-acting rescue bronchodilator use was associated with significantly lower NAA, and Glu, whereas inhaled corticosteroid use was related to significantly higher Cr and in tendency higher NAA and Glu. All findings controlled for left hippocampal volume, which was not different between groups. These findings highlight that asthma and/or its treatment may affect hippocampal chemistry. It is possible that the observed reductions in hippocampal metabolites in younger individuals with asthma may precede cognitive and hippocampal structural deficits observed in older individuals with asthma.

Objective: Bisphenol A (BPA) has been associated with adverse human health outcomes and exposure to this compound is near-ubiquitous in the Western world. We aimed to examine whether self-moderation of BPA exposure is possible by altering diet in a real-world setting., Design: An Engaged Research dietary intervention study designed, implemented and analysed by healthy teenagers from six schools and undertaken in their own homes., Participants: A total of 94 students aged between 17 and 19 years from schools in the South West of the UK provided diet diaries and urine samples for analysis., Intervention: Researcher participants designed a set of literature-informed guidelines for the reduction of dietary BPA to be followed for 7 days., Main Outcome Measures: Creatinine-adjusted urinary BPA levels were taken before and after the intervention. Information on packaging and food/drink ingested was used to calculate a BPA risk score for anticipated exposure. A qualitative analysis was carried out to identify themes addressing long-term sustainability of the diet., Results: BPA was detected in urine of 86% of participants at baseline at a median value of 1.22 ng/mL (IQR 1.99). No effect of the intervention diet on BPA levels was identified overall (P=0.25), but there was a positive association in those participants who showed a drop in urinary BPA concentration postintervention and their initial BPA level (P=0.003). Qualitative analysis identified themes around feelings of lifestyle restriction and the inadequacy of current labelling practices., Conclusions: We found no evidence in this self-administered intervention study that it was possible to moderate BPA exposure by diet in a real-world setting. Furthermore, our study participants indicated that they would be unlikely to sustain such a diet long term, due to the difficulty in identifying BPA-free foods., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Current animal models of sepsis often incorporate antibiotics to be consistent with clinical standards for treatment of patients in the intensive care unit. However, such experimental intervention is commonly initiated very early after infectious insult, which likely blunts the progression of systemic inflammation and downstream pathology. The objective of this study was to establish an animal model of sepsis with delayed therapeutic intervention, allowing a longer disease course and downstream pathology, but still resulting in a high survival rate. Severe lethal abdominal infection was initiated in young adult (17-18-week-old) C57BL/6 mice by cecal slurry (CS) injection. When initiated early (1- or 6-h post-CS injection), antibiotic treatment (imipenem, 1.5 mg/mouse i.p., twice/day for 5 days) rescued the majority of mice; however, few of these mice showed evidence of bacteremia, cytokinemia, or organ injury. When antibiotic treatment was delayed until late time-points (12- or 24-h post-CS injection) the majority of animals did not survive beyond 48 h. When fluid resuscitation (physiological saline, s.c.) was performed in combination with antibiotic treatment (twice daily) beginning at these late time-points, the majority of mice survived (75%) and showed bacteremia, cytokinemia, organ dysfunction, and prolonged body weight loss (<90% for 4 weeks). We recommend that this new repeated combination treatment with antibiotics and fluids resuscitation be initiated at a late time point after bacteremia becomes evident because this model more closely mimics the downstream pathological characteristics of severe clinical sepsis yet maintains a high survival rate. This model would be advantageous for studies on severe sepsis and postintensive care illness.

Emotional stimuli elicit airway constriction in individuals with asthma and in healthy individuals, but little is known about effects of repeated stimulation. We therefore explored the effect of repeated emotion induction on respiratory resistance (R rs ) using unpleasant, high-arousal surgery films and investigated effects of respiration and emotional reactivity. Twenty-six participants (13 with asthma) watched a series of 12 short, 45-s surgery films followed by 2-min recovery periods. R rs assessed with impulse oscillometry was significantly elevated during films in both groups compared to baseline and recovered quickly after that. No habituation of airway responses occurred. R rs was higher in participants who felt more aroused and less in control when watching the films. Changes in R rs remained significant when controlling for changes in respiration or emotional experience. Thus, although unpleasant stimuli lead to elevated R rs , airway obstruction is not exacerbated with repeated stimulation due to a fast return to baseline after stimulation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1.

The molecular mechanisms and genetic architecture that facilitate adaptive radiation of lineages remain elusive. Polymorphic chromosomal inversions, due to their recombination-reducing effect, are proposed instruments of ecotypic differentiation. Here, we study an ecologically diversifying lineage of Anopheles gambiae, known as the Bamako chromosomal form based on its unique complement of three chromosomal inversions, to explore the impact of these inversions on ecotypic differentiation. We used pooled and individual genome sequencing of Bamako, typical (non-Bamako) An. gambiae and the sister species Anopheles coluzzii to investigate evolutionary relationships and genomewide patterns of nucleotide diversity and differentiation among lineages. Despite extensive shared polymorphism and limited differentiation from the other taxa, Bamako clusters apart from the other taxa, and forms a maximally supported clade in neighbour-joining trees based on whole-genome data (including inversions) or solely on collinear regions. Nevertheless, F ST outlier analysis reveals that the majority of differentiated regions between Bamako and typical An. gambiae are located inside chromosomal inversions, consistent with their role in the ecological isolation of Bamako. Exceptionally differentiated genomic regions were enriched for genes implicated in nervous system development and signalling. Candidate genes associated with a selective sweep unique to Bamako contain substitutions not observed in sympatric samples of the other taxa, and several insecticide resistance gene alleles shared between Bamako and other taxa segregate at sharply different frequencies in these samples. Bamako represents a useful window into the initial stages of ecological and genomic differentiation from sympatric populations in this important group of malaria vectors., (© 2016 John Wiley & Sons Ltd.)

Objectives: Visceral adipose tissue is a major site for expression of proinflammatory and procoagulant genes during acute systemic inflammation. In this study, we tested whether the loss of fat mass by dietary restriction would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia., Design: Prospective, laboratory controlled experiments., Setting: Aging and critical care research laboratory in a university hospital., Subjects: Middle-aged (12-month old) male C57BL/6 mice., Interventions: Mice were subjected to 40% dietary restriction for 3 weeks followed by induction of abdominal sepsis or endotoxemia by intraperitoneal injection with cecal slurry or lipopolysaccharide, respectively., Measurements and Main Results: Compared with freely fed mice, dietary restricted mice exhibited dramatically improved survival (80% vs 0% after sepsis; p < 0.001 and 86% vs 12% after endotoxemia; p = 0.013) and significantly reduced visceral fat-derived messenger RNA expression of interleukin-6, thrombospondin-1, plasminogen activator inhibitor-1, and tissue factor, which positively correlated with fat mass. Plasma levels of interleukin-6 were significantly reduced by dietary restriction and correlated with adipose interleukin-6 messenger RNA levels and fat mass (p < 0.001; R = 0.64 and 0.89). In vitro culture of visceral fat explants from naive dietary restricted mice showed significantly reduced interleukin-6 secretion compared with that from freely fed mice in response to lipopolysaccharide. Analysis of major adipose immune cell populations by flow cytometry demonstrated that macrophages were the only cell population reduced by dietary restriction and that CD11c/CD206 (M2-type) and CD11c/CD206 (double negative) macrophages, in addition to T cells, are the major immune cell populations that produce interleukin-6 in middle-aged mice during systemic inflammation., Conclusions: Short-term dietary restriction drastically improved the survival outcome of middle-aged mice during both polymicrobial sepsis and sterile endotoxemia. Improved survival was accompanied by a significantly attenuated inflammatory response in adipose tissue, which is likely due to alterations of both fat mass quantity and qualitative changes, including a reduction in macrophage populations.

Objective: Perception of personal identity cannot be separated from the perception of the social context and one's social identity. Full involvement in group psychotherapy may require not only the awareness of personal impairment, but also social identification. The aim of the current study was to examine the association between social identification and symptom improvement in group-based psychotherapy., Method: 169 participants received 12 sessions of group-based cognitive behavioral therapy for social anxiety disorder. Social identification, the extent to which a person identifies with those who suffer from the same psychological problem as themselves and/or with those lacking psychopathology (non-sufferers), and clinical outcome were assessed at baseline, mid-and posttreatment, and 1, 3, and 6-months follow-up., Results: At baseline, patients aspired for closeness with non-sufferers, and viewed themselves as distant from fellow sufferers and non-sufferers. After treatment, participants viewed not only themselves, but also other individuals with social anxiety, as closer to both non-sufferers and fellow sufferers. These ratings were related to clinical outcomes., Conclusions: The increase in closeness to both sufferers and non-sufferers across treatment may reflect a movement towards a more tolerant, less dichotomous and rigid, separation of ill and healthy that occurs with successful social anxiety treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Glucokinase-maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10-60%): persistent incidental childhood hyperglycemia (10-60%) and gestational diabetes mellitus (1-2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Self-directed disgust, a component of self-criticism, may present an important, yet unexplored emotion in the context of nonsuicidal self-injury (NSSI). The aim of this study was to examine the role of self-disgust in NSSI, specifically as a potential mediator in the relations between depression and NSSI as well as sexual abuse and NSSI, and to also better understand characteristics that might differentiate recent and past self-injurers. A total of 549 college students completed measures assessing NSSI, self-disgust, depression, anxiety sensitivity, and physical and sexual abuse. Results indicated self-disgust fully mediated the relation between depressive symptoms and NSSI status and partially mediated the relation between sexual abuse and NSSI status. Additionally, compared to past self-injurers (4.6%; n = 25), recent self-injurers (6.4%; n = 35) endorsed significantly higher self-disgust and depressive symptoms. Self-disgust may be an important component in NSSI and should be addressed in treatment.

Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) is considered the gold standard model for sepsis research, it may not be preferable for experiments comparing animals of different size or under different dietary regimens. By comparing cecum size, shape, and cecal content characteristics in mice under different experimental conditions (aging, diabetes, pancreatitis), we show that cecum variability could be problematic for some CLP experiments. The cecal slurry (CS) injection model, in which the cecal contents of a laboratory animal are injected intraperitoneally to other animals, is an alternative method for inducing polymicrobial sepsis; however, the CS must be freshly prepared under conventional protocols, which is a major disadvantage with respect to reproducibility and convenience. The objective of this study was to develop an improved CS preparation protocol that allows for long-term storage of CS with reproducible results. Using our new CS preparation protocol we found that bacterial viability is maintained for at least 6 months when the CS is prepared in 15% glycerol-PBS and stored at -80°C. To test sepsis-inducing efficacy of stored CS stocks, various amounts of CS were injected to young (4-6 months old), middle-aged (12-14 months old), and aged (24-26 months old) male C57BL/6 mice. Dose- and age-dependent mortality was observed with high reproducibility. Circulating bacteria levels strongly correlated with mortality suggesting an infection-mediated death. Further, injection with heat-inactivated CS resulted in acute hypothermia without mortality, indicating that CS-mediated death is not due to endotoxic shock. This new CS preparation protocol results in CS stocks which are durable for freezing preservation without loss of bacterial viability, allowing experiments to be performed more conveniently and with higher reproducibility than before.

Background: Hyperventilation has been associated with adverse effects on lung function, symptoms, and well-being in asthma. We examined whether raising end-tidal CO2 levels (ie, Pco2) compared with slow breathing is associated with improvements in asthma control, including peak flow variability., Methods: One hundred twenty patients with asthma were randomly assigned to capnometry-assisted respiratory training (CART) for raising Pco2 or slow breathing and awareness training (SLOW) for slowing respiratory rate. Patients received five weekly sessions and completed bid homework exercises over 4 weeks. Blinded assessments at baseline, posttreatment, 1- and 6-month follow-up of asthma control, Pco2, and diurnal peak flow variability were primary outcome measures. Additionally, we measured pulmonary function (spirometry, forced oscillation, exhaled nitric oxide, and methacholine challenge), symptoms, quality of life, and bronchodilator use. Because the control group received active treatment, we expected improvements in asthma control in both groups but more pronounced benefits from CART., Results: Improvements were seen in 17 of 21 clinical indexes (81.0%) in both interventions, including the primary outcome variables asthma control (d = 0.81), peak flow variability (d = 0.54), quality of life, bronchodilator use, lung function, and airway hyperreactivity. Most improvements were sustained across the 6-month follow-up. Compared with slow breathing, CART showed greater increases in Pco2 (d = 1.45 vs 0.64 for CART vs SLOW, respectively) and greater reductions in respiratory impedance during treatment, less distress during methacholine challenge, and greater reduction in asthma symptoms at follow-up (P < .05)., Conclusions: Brief interventions aimed at raising Pco2 or slowing respiratory rate provide significant, sustained, and clinically meaningful improvements in asthma control. Raising Pco2 was associated with greater benefits in aspects of lung function and long-term symptoms., Trial Registry: ClinicalTrials.gov; No.: NCT00975273; URL: www.clinicaltrials.gov.

Objective: Differences in blood pressure between arms are associated with vascular disease and increased mortality; this has not been reported in diabetes. We explored these associations, and assessed reference standard and pragmatic measurement techniques, in people with diabetes and in nondiabetic controls., Research Design and Methods: A prospective cohort study in Devon, England, recruited 727 people with type 1 or type 2 diabetes and 285 nondiabetic controls. Simultaneous repeated measurements of bilateral blood pressure were made at recruitment. Data were used to inform a pragmatic measurement strategy. Interarm differences were examined for cross-sectional associations with target organ disease and prospective mortality associations (median follow-up 52 months)., Results: We found 8.6% of participants with diabetes and 2.9% of controls had systolic interarm differences ≥10 mmHg. Single pairs of blood pressure measurements had high negative predictive values (97-99%) for excluding interarm differences. Systolic interarm differences ≥10 mmHg in diabetes were associated with peripheral arterial disease (odds ratio [OR] 3.4 [95% CI 1.2-9.3]). Differences ≥15 mmHg were associated with diabetic retinopathy (OR 5.7 [1.5-21.6]) and chronic kidney disease (OR 7.0 [1.7-29.8]). Systolic interarm differences were associated prospectively with increased cardiovascular mortality: hazard ratios 3.5 (1.0-13.0) for ≥10 mmHg and 9.0 (2.0-41.0) for ≥15 mmHg., Conclusions: Blood pressure should be measured in both arms during initial assessment in diabetes. Systolic interarm differences can be excluded with a single pair of measurements. In the population with diabetes, systolic differences may be associated with an increased risk of morbidity and mortality., (© 2014 by the American Diabetes Association.)

Importance: Glycemic targets in diabetes have been developed to minimize complication risk. Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for type 1 and type 2 diabetes., Objective: To assess the association between chronic, mild hyperglycemia and complication prevalence and severity in patients with GCK mutations., Design, Setting, and Participants: Cross-sectional study in the United Kingdom between August 2008 and December 2010. Assessment of microvascular and macrovascular complications in participants 35 years or older was conducted in 99 GCK mutation carriers (median age, 48.6 years), 91 nondiabetic, familial, nonmutation carriers (control) (median age, 52.2 years), and 83 individuals with young-onset type 2 diabetes (YT2D), diagnosed at age 45 years or younger (median age, 54.7 years)., Main Outcomes and Measures: Prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease., Results: Median HbA1c was 6.9% in patients with the GCK mutation, 5.8% in controls, and 7.8% in patients with YT2D. Patients with GCK had a low prevalence of clinically significant microvascular complications (1% [95% CI, 0%-5%]) that was not significantly different from controls (2% [95% CI, 0.3%-8%], P=.52) and lower than in patients with YT2D (36% [95% CI, 25%-47%], P<.001). Thirty percent of patients with GCK had retinopathy (95% CI, 21%-41%) compared with 14% of controls (95% CI, 7%-23%, P=.007) and 63% of patients with YT2D (95% CI, 51%-73%, P<.001). Neither patients with GCK nor controls required laser therapy for retinopathy compared with 28% (95% CI, 18%-39%) of patients with YT2D (P<.001). Neither patients with GCK patients nor controls had proteinuria and microalbuminuria was rare (GCK, 1% [95% CI, 0.2%-6%]; controls, 2% [95% CI, 0.2%-8%]), whereas 10% (95% CI, 4%-19%) of YT2D patients had proteinuria (P<.001 vs GCK) and 21% (95% CI, 13%-32%) had microalbuminuria (P<.001). Neuropathy was rare in patients with GCK (2% [95% CI, 0.3%-8%]) and controls (95% CI, 0% [0%-4%]) but present in 29% (95% CI, 20%-50%) of YT2D patients (P<.001). Patients with GCK had a low prevalence of clinically significant macrovascular complications (4% [95% CI, 1%-10%]) that was not significantly different from controls (11% [95% CI, 5%-19%]; P=.09), and lower in prevalence than patients with YT2D (30% [95% CI, 21%-41%], P<.001)., Conclusions and Relevance: Despite a median duration of 48.6 years of hyperglycemia, patients with a GCK mutation had low prevalence of microvascular and macrovascular complications. These findings may provide insights into the risks associated with isolated, mild hyperglycemia.

Schedules of intermittent food delivery induce excessive fluid intake, termed schedule-induced polydipsia (SIP), and hypothalamic-pituitary-adrenal (HPA) axis activation is important for the expression and maintenance of this adjunctive behavior. Previous work has focused on examining the relationship between water intake and plasma corticosterone (CORT) in rats at a single or a limited range of fixed time (FT) intervals. However, little remains known regarding SIP and the corresponding stress response (1) across the bitonic function that epitomizes adjunctive behavior, (2) when ethanol is the available fluid, and (3) when a species other than rat or multiple strains are studied. Here we report the findings from ethanol-preferring C57BL/6J (B6) and non-preferring DBA/2J (D2) mice serially exposed to progressively larger FT intervals (0 → 60 min) and given access to either water or a 5% (v/v) ethanol solution. Following 2 weeks of experience with each schedule, blood samples were collected at the conclusion of the last 60-min session to evaluate CORT and the blood ethanol concentration (BEC) achieved. While both strains exhibited a bitonic function of ethanol intake and BEC that peaked at or near a 5-min interval, only D2 mice showed a similar response with water. In contrast, CORT levels rose monotonically with incremental increases in the FT interval regardless of the strain examined or fluid type offered, indicating that glucocorticoid release likely reflects the aversive aspects of increasing intervals between reinforcement rather than engagement in adjunctive behavior. These findings also caution against the use of a single intensity stressor to evaluate the relationship between stress and ethanol intake, as the magnitude of stress appears to affect ethanol consumption in a non-linear fashion., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aims: HaemoglobinA1c (HbA1c) is recommended for diabetes diagnosis but fasting plasma glucose (FPG) has been useful for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting hyperglycaemia. We aimed to derive age-related HbA1c reference ranges for these patients to determine how well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-onset type 1 (T1D) and type 2 diabetes (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1c and/or FPG diagnostic criteria., Methods: Individuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1D (n = 278) and T2D (n = 319) aged ≥18years were recruited. Receiver Operating Characteristic (ROC) analysis determined effectiveness of HbA1c and FPG to discriminate between groups., Results: HbA1c reference ranges in subjects with GCK mutations were: 38-56 mmol/mol (5.6-7.3%) if aged ≤40years; 41-60 mmol/mol (5.9-7.6%) if >40years. All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age-appropriate reference ranges. 69% (31/99) of controls were below these lower limits. HbA1c was also effective in discriminating those with a GCK mutation from those with T1D/T2D. Using the upper limit of the age-appropriate reference ranges to discriminate those with a mutation from those with T1D/T2D correctly identified 97% of subjects with a mutation. The majority (438/597 (73%)) with other types of young-onset diabetes had an HbA1c above the upper limit of the age-appropriate GCK reference range. HbA1c ≥48 mmol/mol classified more people with GCK mutations as having diabetes than FPG ≥7 mmol/l (68% vs. 48%, p = 0.0009)., Conclusions: Current HbA1c diagnostic criteria increase diabetes diagnosis in patients with a GCK mutation. We have derived age-related HbA1c reference ranges that can be used for discriminating hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and family members for genetic testing.

Understanding asthma symptom perception is necessary for reducing unnecessary costs both for asthma sufferers and society and will contribute to improving asthma management. The primary aim of this study was to develop and test a standardized method for classification of asthma perceiver categories into under-, normal, and overperceiver groups based on the comparison between self-report and lung function components of asthma control. Additionally, the degree to which demographic variables and anxiety contributed to the classification of patients into perceiver groups was examined. Patients underwent methacholine or reversibility testing to confirm asthma diagnosis. Next, participants completed lung function testing over 3 days before their next appointment. Finally, patients filled out demographic and self-report measures including the Asthma Control Test (ACT). Each self-report category of control assessed by the ACT (interference, shortness of breath, nighttime awakenings, rescue inhaler usage, and a composite total score) was compared with lung function measurements using a modified version of the asthma risk grid. Using the modified asthma risk grid to determine perceiver categorization, this sample included 14 underperceivers, 29 normal perceivers, and 36 overperceivers. A discriminant analysis was performed that indicated that a majority of underperceivers were characterized by being African American and having low asthma-specific anxiety. Normal perceivers in this sample tended to be older. Overperceivers tended to be female. Our findings encourage further research using the reported method of classifying asthma patients into perceiver categories.

Objective: To demonstrate the importance of using a combined genetic and functional approach to correctly interpret a genetic test for monogenic diabetes., Research Design and Methods: We identified three probands with a phenotype consistent with maturity-onset diabetes of the young (MODY) subtype GCK-MODY, in whom two potential pathogenic mutations were identified: [R43H/G68D], [E248 K/I225M], or [G261R/D217N]. Allele-specific PCR and cosegregation were used to determine phase. Single and double mutations were kinetically characterized., Results: The mutations occurred in cis (double mutants) in two probands and in trans in one proband. Functional studies of all double mutants revealed inactivating kinetics. The previously reported GCK-MODY mutations R43H and G68D were inherited from an affected father and unaffected mother, respectively. Both our functional and genetic studies support R43H as the cause of GCK-MODY and G68D as a neutral rare variant., Conclusions: These data highlight the need for family/functional studies, even for previously reported pathogenic mutations.

Aims: To investigate all-cause and cardiovascular mortality in subjects with diabetes caused by a mutation in the hepatocyte nuclear factor 1alpha gene (HNF1A)., Methods: We identified 39 British families with HNF1A mutations. Consenting individuals were asked details of age and cause of death of parents and siblings. Copies of death certificates were requested from the family or were obtained via the Offices for National Statistics., Results: Data were collated on 241 control subjects and 153 mutation carriers. Of those who died, 66% of mutation carriers died from a cardiovascular-related illness compared with 43% of control subjects (P = 0.02). Family members with HNF1A mutations died at a younger age than familial control subjects [all-cause hazard ratio, adjusting for sex and smoking status: 1.9 (95% confidence interval 1.2, 2.9, P = 0.006; cardiovascular hazard ratio: 2.3, confidence interval 1.3, 4.2, P = 0.006)]., Conclusions: We have shown that individuals known to have diabetes caused by a mutation in the HNF1A gene have an increased risk of cardiovascular mortality compared with their unaffected family members. As with other forms of diabetes, consideration should be given to early statin therapy despite a seemingly protective lipid profile.

We know less about positive mental imagery than we do about negative mental imagery in depression. This study examined the relationship between depressed mood and the subjective experience of emotion in imagined events; specifically, prospective imagery, and imagery in response to emotionally ambiguous stimuli. One hundred and twenty-six undergraduates completed measures of depression, imagery vividness for future events, and a homograph interpretation task in which they generated images and subsequently rated image pleasantness and vividness. As predicted, compared to low dysphoria, high dysphoria was associated with poorer ability to vividly imagine positive (but not negative) future events. These findings were augmented by the observation that high dysphorics provided lower pleasantness ratings of images generated in response to homographs they interpreted as positive. We suggest that an imbalance in the inability to vividly imagine positive but not negative future events may curtail the ability of high dysphorics to be optimistic. High dysphoric individuals are further disadvantaged: even when they interpret ambiguity positively, the resulting images they generate are associated with less positive affect. Therapeutic strategies that address both such positive-specific imagery biases hold promise for depression treatment innovation.

Nasal continuous-positive-airway-pressure (NCPAP) is popular for infant respiratory support. We compared delivered to intended intra-prong, proximal-airway, and distal-airway pressures using ventilator (V-NCPAP) and bubble (B-NCPAP) devices. Measurements were repeated at five flows (4, 6, 8, 10, and 12 L/min) and three NCPAP (4, 6, and 8 cm H2O) under no, small, and large nares-prong interface leak conditions. With no-leak, delivered B-NCPAP was systematically greater than intended levels at all pressure sites. The corresponding V-NCPAP flow-dependence was none-to-minimal. Prong and intra-airway B-NCPAP overshoots were also observed with small-leak, while only prong B-NCPAP showed a flow-dependent overshoot for large-leak. Leaks did not affect intra-prong V-NCPAP but resulted in progressively lower than desired, flow-independent intra-airway V-NCPAP. We conclude that the self-adjusting capability of ventilators allows closely matched actual versus intended V-NCPAP. Alternatively, for the range of flows used clinically, intra-prong and intra-airway B-NCPAP are systematically higher at increasing flows than operator-intended levels, even when appreciable nares-prong leak is present. Additionally, the oscillations (noise) characterizing B-NCPAP are substantially attenuated between the proximal and distal airways; therefore, it is unlikely that B-NCPAP engenders ventilation or lung recruitment via this phenomenon. Tubing submersion depth for setting the level of B-NCPAP is highly inaccurate, and operators should instead rely on intra-prong pressure measurement.

Background: Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4alpha) and HNF1A/TCF1 (encoding HNF-1alpha), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice., Methods and Findings: We examined birthweight and hypoglycaemia in 108 patients from families with diabetes due to HNF4A mutations, and 134 patients from families with HNF1A mutations. Birthweight was increased by a median of 790 g in HNF4A-mutation carriers compared to non-mutation family members (p < 0.001); 56% (30/54) of HNF4A-mutation carriers were macrosomic compared with 13% (7/54) of non-mutation family members (p < 0.001). Transient hypoglycaemia was reported in 8/54 infants with heterozygous HNF4A mutations, but was reported in none of 54 non-mutation carriers (p = 0.003). There was documented hyperinsulinaemia in three cases. Birthweight and prevalence of neonatal hypoglycaemia were not increased in HNF1A-mutation carriers. Mice with pancreatic beta-cell deletion of Hnf4a had hyperinsulinaemia in utero and hyperinsulinaemic hypoglycaemia at birth., Conclusions: HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia. This study establishes a key role for HNF4A in determining foetal birthweight, and uncovers an unanticipated feature of the natural history of HNF4A-deficient diabetes, with hyperinsulinaemia at birth evolving to decreased insulin secretion and diabetes later in life.

Premature infants with respiratory distress oxygenate better and have improved breathing synchrony when they are nursed in the prone position. We investigated whether work of breathing (WOB) is decreased in the prone position in healthy premature infants nearing discharge from the neonatal intensive care unit. Nineteen convalescing premature infants in room air were studied in both supine and prone position. Positioning order was randomized. Mean birth weight was 1358 +/- 332 (SD) g, gestational age 29.7 +/- 2.1 weeks, weight at study 1757 +/- 248 g, and age at study 33.6 +/- 1.4 days. Calibrated respiratory inductance plethysmography (RIP) was used to measure tidal volume; an esophageal catheter estimated pleural pressure. Inspiratory, elastic, and resistive WOB were calculated and were unaffected by prone versus supine positioning (P = 0.46, 0.36, and 0.87, respectively). Similarly, respiratory rate, tidal volume, minute ventilation, and lung compliance did not differ between positions. These data suggest that sleep position recommendations for healthy premature infants discharged home without oxygen should be no different than for term infants.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with a 3.2 to 6.8-fold increased risk of severe hypoglycemia in type 1 diabetes. This relationship has not been assessed in type 2 diabetes. We aimed to test for association of the ACE I/D polymorphism with severe hypoglycemia in type 2 diabetes. Patients with type 2 diabetes (n = 308), treated with insulin (n = 124) or sulphonylureas (n = 184), were classified according to whether or not they had previously experienced severe hypoglycemia. Samples of DNA were genotyped for the ACE I/D polymorphism using two alternative polymerase chain reactions to prevent mistyping due to preferential amplification of the D allele. Overall, 12% of patients had previously experienced one or more episodes of severe hypoglycemia. This proportion did not differ between genotype groups (odds ratio (95% confidence limits) for carriers of D allele relative to II homozygotes: 0.79 (0.35-1.78)). This study found no evidence for association of the ACE I/D polymorphism with severe hypoglycemia frequency in patients with type 2 diabetes. However, we cannot rule out a smaller effect (odds ratio

Measurement of lung volume may be useful in determining the degree of lung disease and for optimizing an infant's mechanical ventilator settings. A chest radiograph (CXR) is often used to estimate lung volume, because direct measurement, e.g., functional residual capacity (FRC), is neither practical nor possible in the neonatal intensive care unit. In supinely positioned infants, good correlation was found between lung area determined by CXR and lung volume, e.g., functional residual capacity (FRC). Whether this is true for the prone position is unknown. Since positioning may affect oxygenation and pulmonary function, we studied the relationship between lung area measured from CXR and FRC during both supine and prone positioning in 14 mechanically ventilated preterm infants. Lung area was determined from CXRs using computed radiography and FRCs obtained by helium dilution at end-expiration in both supine and prone positions. Reproducibility of lung area measurements was demonstrated by high correlations between two observers (R2 = 0.92 and 0.99 for supine and prone, respectively). When supine, lung area was 15.4 +/- 3.1 cm2, and FRC was 19.5 +/- 7.3 ml. In prone position, lung area was 16.7 +/- 4.2 cm2, and FRC 23.0 +/- 9.4 ml. There was a moderate to strong positive correlation between lung area and FRC for both positions (supine: r = 0.57, P < 0.03; prone: r = 0.63, P < 0.02). Lung area measured by computed radiography is a reproducible and practical method for estimating lung volume from routine chest X-rays in both supine and prone positions in mechanically ventilated preterm infants., (Copyright 2005 Wiley-Liss, Inc.)

Objective: To compare work of breathing and breathing asynchrony during bubble nasal continuous positive airway pressure (NCPAP) vs variable-flow (VF)-NCPAP in premature infants., Study Design: We studied 18 premature infants of birth weight <1500 g who required NCPAP for mild respiratory distress. Each infant was studied on bubble and VF-NCPAP at 8, 6, 4, and 0 cm H2O. Tidal volumes were obtained by calibrated respiratory inductance plethysmography. Esophageal pressure estimated intrapleural pressure. Inspiratory and resistive work of breathing were calculated from pressure-volume data. Breathing asynchrony was assessed with phase angle. The results at all NCPAP levels were referenced to VF-NCPAP values at 8 cm H2O., Results: Provision of NCPAP with either device decreased inspiratory work of breathing, tidal volume, and minute ventilation relative to NCPAP of 0 cm H2O. Bubble NCPAP did not decrease resistive work of breathing relative to 0 cm H2O. Resistive work of breathing (p=0.01), respiratory rate (p<0.03), and phase angle (p=0.002) were all greater with bubble compared to VF-NCPAP., Conclusion: The more labored and asynchronous breathing seen with bubble NCPAP may lead to higher failure rates over the long term than with VF-NCPAP.

Glucokinase (GCK) serves as the pancreatic glucose sensor. Heterozygous inactivating GCK mutations cause hyperglycemia, whereas activating mutations cause hypoglycemia. We studied the GCK V62M mutation identified in two families and co-segregating with hyperglycemia to understand how this mutation resulted in reduced function. Structural modeling locates the mutation close to five naturally occurring activating mutations in the allosteric activator site of the enzyme. Recombinant glutathionyl S-transferase-V62M GCK is paradoxically activated rather than inactivated due to a decreased S0.5 for glucose compared with wild type (4.88 versus 7.55 mM). The recently described pharmacological activator (RO0281675) interacts with GCK at this site. V62M GCK does not respond to RO0281675, nor does it respond to the hepatic glucokinase regulatory protein (GKRP). The enzyme is also thermally unstable, but this lability is apparently less pronounced than in the proven instability mutant E300K. Functional and structural analysis of seven amino acid substitutions at residue Val62 has identified a non-linear relationship between activation by the pharmacological activator and the van der Waals interactions energies. Smaller energies allow a hydrophobic interaction between the activator and glucokinase, whereas larger energies prohibit the ligand from fitting into the binding pocket. We conclude that V62M may cause hyperglycemia by a complex defect of GCK regulation involving instability in combination with loss of control by a putative endogenous activator and/or GKRP. This study illustrates that mutations that cause hyperglycemia are not necessarily kinetically inactivating but may exert their effects by other complex mechanisms. Elucidating such mechanisms leads to a deeper understanding of the GCK glucose sensor and the biochemistry of beta-cells and hepatocytes.

Background: The evidence for postnatal debriefing generally lacks clarification of what postnatal debriefing constitutes. This is true of the recommendation in the United Kingdom for midwives to undertake 'active postnatal debriefing' (Department of Health 1999)., Aim: The study aimed to explore current practice and describe the provision of postnatal debriefing in two health regions of England., Methods: A descriptive survey using cohort sampling was undertaken using a self-report questionnaire which was sent to each maternity unit in the two regions (n = 46). A response rate of 93% (n = 43) was obtained. The questionnaire collected information about the maternity units and their provision of 'postnatal debriefing'. A list of debriefing descriptors formed the basis of the questionnaire, and comprised activities that various authors had included in their definitions of debriefing., Results: Responses indicated that 38 (88%) of maternity units offered women an opportunity to 'debrief' by discussing their experiences of maternity care. The provision of this service fell into three distinct sub-groups: firstly, those who provided a service which is in keeping with debriefing, however not all the maternity units actually called their service debriefing; secondly, those who provided a service which is fundamental postnatal care, usually called routine postnatal care; thirdly, those who provided a service which was inconsistent and neither debriefing nor postnatal care. This inconsistency was also reflected in the names chosen for the service., Conclusions: The findings of this study support previous claims that confusion about postnatal debriefing continues. Recommendations for practice are made with the intention of promoting a consistent approach; this would also enable further research and evaluation to be conducted.

The Exeter Research Alliance for Diabetes is a research project recently implemented at the Royal Devon and Exeter Hospital. The project investigates the genetic and environmental influences on the development of diabetes and its associated complications. This article describes the process of instigating the study from an initial research idea through to the implementation of the project.

The tidal breathing flow volume loop (TBFVL) may provide objective assessments of infant airway function. We examined whether infant biologic variability and technical limitations of commercial equipment might affect tidal breathing indices. TBFVLs were obtained in 79 sleeping, healthy, 1-5-day-old infants, divided into two groups: 1) TBFVLs were obtained immediately after face mask placement, i.e., within 5-20 sec (Group A), or 2) after a delay of 2-3 min following face mask placement (Group B). Both tidal volume (VT) and respiratory rates (RR) were significantly lower (25% and 20%, respectively) in Group A than in Group B. VT mean (SD) was 4.45 (0.93) ml/kg for Group A and 6.09 (1.11) ml/kg for Group B (P < 0.0001); RR was 48.4 (12.2) min-1 and 60.0 (15.60) min-1 for Groups A and B, respectively (P < 0.0003). The time to peak expiratory flow as a ratio of total expiratory time (tPTEF:tE), purported to be a useful index of airway obstruction, was also significantly (P < 0.0001) attenuated in TBFVLs obtained immediately after face mask placement; tPTEF:tE was 0.26 (0.09) and 0.37 (0.05) in Groups A and B, respectively. Reproducibility of tPTEF:tE was affected by the timing of recordings. Intraindividual coefficients of variation were greater in Group A (36.53%) than Group B (18.82%). Similarly, significant differences were observed in mean value and variability of other indices of airway function between Groups A and B. Although they are easy to perform, we conclude that tidal breathing analyses may be significantly complicated by simple differences in measurement conditions.

The aim was to study the outcome of criminal investigation into allegations of sexual abuse made by 160 children assessed over a two year period in a specialist paediatric unit in the North of England. In all, 141 of the 160 children (88%) were female, and 99 (62%) were aged under 12 years. There were 145 males and nine females named by children in allegations of sexual abuse. Fathers formed the largest single group of alleged male perpetrators (56/176). None of the nine alleged female abusers was prosecuted. Of the 145 males, 57 reached trial; 49 were convicted, an 86% conviction rate of those sent to trial and a rate of proven sexual offence (including cautions) of 44% (54/124) among men originally interviewed by the police. Twenty five per cent of children (17/68) who could have testified did so, most giving evidence against someone who was known to them. Pragmatic selection of cases for prosecution resulted in an outcome highly vindicating of the decision to prosecute. The possible effects of this process are discussed.