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Although patients with Alzheimer's disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status.To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing.Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses.Observational cohort study.146 participants in the Framingham Heart Study.Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions.Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90.The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.

The Gram-negative, opportunistic pathogen

Purpose: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. Methods: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. Results: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. Conclusion: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.

Pseudomonas aeruginosa is an opportunistic, Gram-negative pathogen and an important cause of hospital acquired infections, especially in immunocompromised patients. Highly virulent P. aeruginosa strains use a type III secretion system (T3SS) to inject exoenzyme effectors directly into the cytoplasm of a target host cell. P. aeruginosa strains that express the T3SS effector, ExoU, associate with adverse outcomes in critically ill patients with pneumonia, owing to the ability of ExoU to rapidly damage host cell membranes and subvert the innate immune response to infection. Herein, we review the structure, function, regulation, and virulence characteristics of the T3SS effector ExoU, a highly cytotoxic phospholipase A2 enzyme.

The role of tissue specific metabolism of endogenous glucocorticoids (GCs) in the pathogenesis of human disease has been a field of intense interest over the last 20 years, fuelling clinical trials of metabolism inhibitors in the treatment of an array of metabolic diseases. Localised pre-receptor metabolism of endogenous and therapeutic GCs by the 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes (which interconvert endogenous GCs between their inactive and active forms) are increasingly recognised as being critical in mediating both their positive and negative actions on bone homeostasis. In this review we explore the roles of endogenous and therapeutic GC metabolism by the 11β-HSD enzymes in the context of bone metabolism and bone cell function, and consider future strategies aimed at modulating this system in order to manage and treat various bone diseases.

Gender variations in health literacy have implications for engagement in preventive behaviours and the uptake of health services, especially in areas such as the Caribbean where there are marked disparities in life expectancy and health service utilization. A self-reported questionnaire was used to examine men’s concepts of health, their help-seeking behaviours and their functional and interactive health literacy. Two hundred and forty-eight men across the life course participated at three sites in Trinidad. Data were analysed using descriptive statistics, with free-text responses analysed thematically. Men were concerned about, and accepted responsibility for their own health but social norms concerning sickness and masculinity were barriers to accessing health services. Almost one-third (31.5%) sought advice from a healthcare service when they were last sick because they were prompted to do so by their wife/partner or family. Levels of functional and interactive health literacy were not high among older men, who were reliant on healthcare professionals to communicate health messages. There was an age divide in e-health literacy. There is little published evidence on men’s health literacy, particularly from Caribbean countries such as Trinidad and Tobago. This study highlights the importance of the design and implementation of specific policies focusing on men’s health. A major challenge is to engage with men who do not access health services.

Objectives Bruxism is a commonly reported oral parafunctional activity characterised by excessive tooth grinding or clenching outside normal functional activity. The present systematic review aims to examine the available literature to determine the effectiveness of occlusal splints in the treatment of bruxism compared to no treatment and alternative treatment modalities. Data Data extraction was undertaken in conjunction with quality of evidence assessment. Sources A literature search of the following databases was undertaken: MEDLINE via OVID, Pubmed (Medline), Cochrane Oral Health Group’s Trials, The Cochrane Central Register of Controlled Trials and EMBASE. Study selection Randomised Controlled Trials (RCT) and quasi-RCTs which met the inclusion criteria were selected for analysis. These included studies comparing occlusal splints to no treatment or other interventions. Results Twenty-two studies were identified for review with fourteen meeting the inclusion criteria. Only a small number of studies were available in each comparison (one or two for some) all of which had a medium to high risk of bias. Conclusions There is insufficient evidence to determine whether occlusal splint therapy for the treatment of bruxism provides a benefit over no treatment, other oral appliances, TENS, behavioural or pharmacological therapy. Furthermore, there is a lack of studies in each comparison with many suffering from a high risk of bias. There is a need for further research in this area and improvement in trial quality. Clinical significance statement This systematic review aimed to determine the effectiveness of occlusal splints in the treatment of bruxism. It found there was insufficient evidence to recommend occlusal splint therapy over no treatment or other treatment modalities. This is relevant to dental clinicians who may provide such appliances and cautions them in treatment provision.

Background: The opioid epidemic has spurred investigations for nonopioid options, yet limited research persists on medical marijuana's (MMJ) efficacy in managing cancer-related symptoms. Objective:...

Background Rheumatoid arthritis is a chronic and common inflammatory autoimmune disease. This primarily involves the synovia of the joints, but can cause many extra-articular manifestations as well, including peripheral ulcerative keratitis (PUK) and necrotising scleritis. These are often a threat to vision; they significantly compromise not only the eyeʼs structural integrity but are also important for prognosis and need urgent management. History and signs Three cases of peripheral ulcerative keratitis associated with rheumatoid arthritis were recorded in the electronic databank of the Jules Gonin Uveitis Clinic, two with necrotising scleritis and peripheral ulcerative keratitis and one with only peripheral ulcerative keratitis. They were all followed at Jules Gonin Eye Hospital (Lausanne, Switzerland), conjointly with the Department of Rheumatology at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). Therapy and Outcome Good initial therapeutic response was observed in the two patients who received rituximab therapy. The patient who received only high dose corticosteroid developed massive colon perforation as well as acute renal insufficiency a few days after her ocular event. Conclusion From our limited number of patients, we found that the two patients who received the induction therapy with rituximab were stabilised from an ocular standpoint; however, rituximab had to be switched to other molecules, either due to other systemic symptoms from the disease itself or due to adverse effect of this treatment. This contributes to the increasing number of reports that rituximab can be an effective treatment for refractory ocular complications of rheumatoid arthritis (RA), at least as an induction therapy.

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

The aim of the present study was to determine the best anthropometric discriminators of type 2 diabetes mellitus (T2DM) among White and Black males and females in a large US sample.We used Atherosclerosis Risk in Communities study baseline data (1987-89) from 15 242 participants (1827 with T2DM) aged 45-65 years. Anthropometric measures included a body shape index (ABSI), body adiposity index (BAI), body mass index, waist circumference (WC), waist: height ratio (WHtR), and waist: hip ratio (WHR). All anthropometric measures were standardized to Z-scores. Using logistic regression, odds ratios for T2DM were adjusted for age, physical activity, and family history of T2DM. The Akaike information criterion and receiver operating characteristic C-statistic were used to select the best-fit models.Body mass index, WC, WHtR, and WHR were comparable discriminators of T2DM among White and Black males, and were superior to ABSI and BAI in predicting T2DM (P 0.0001). Waist circumference, WHtR, and WHR were the best discriminators among White females, whereas WHR was the best discriminator among Black females. The ABSI was the poorest discriminator of T2DM for all race-gender groups except Black females. Anthropometric values distinguishing T2DM cases from non-cases were lower for Black than White adults.Anthropometric measures that included WC, either alone or relative to height (WHtR) or hip circumference (WHR), were the strongest discriminators of T2DM across race-gender groups. Body mass index was a comparable discriminator to WC, WHtR, and WHR among males, but not females.

Hypertrophic osteoarthropathy is sometimes the paraneoplasic manifestation of cancer of pulmonary origin. It is rarely present in case of breast cancer, even at a metastatic stage. In its complete form, this entity includes periostitis (predominantly bilateral and affecting upper and lower limbs), digital clubbing and, rarely, arthritis. We report the case of a female patient with metastatic breast cancer and an incomplete form of hypertrophic osteoarthropathy, clearly asymetric and without digital clubbing.

Objectives . To explore what it is like to be a pregnant smoker in Sunderland and to inform the development of a Smoking Cessation Programme; to use qualitative techniques to develop a cessation programme tailored to pregnant smokers. Study design . The intervention follows years of social marketing research and development in Sunderland, Wearside, UK. Methods . Information derived from nine focus groups (mainly with women from deprived areas, social class C2D and E) provided insights into the issues facing smoking pregnant women. This information was then used to overcome barriers to smoking cessation using the principles of social marketing. The number of women recruited into a specially designed smoking cessation support initiative was compared with women recruited into comparable groups in the North East. Results . Recruitment of pregnant (and non-pregnant) smokers to the new NHS smoking cessation programme in Sunderland has increased during the intervention phase compared with neighbouring Primary Care Trust areas (in which different smoking cessation interventions targeted at pregnant women were being undertaken). Conclusions . This innovative intervention has been successful in generating ideas, guiding development of a customer-friendly service and encouraging women to come forward for smoking cessation support during their pregnancy. The target population have welcomed the approach, and health professionals have enjoyed and benefited from the role play with professional actors.

Gun-safety programs frequently warn children not to touch guns with little consideration that the messages may enhance the allure of the guns. In the current study, boys rated and ranked their preference for a gun in comparison with other desirable objects. One week later, when left alone in the room with the objects, they were forbidden to touch either the gun or some other object. Observations of their behavior and reevaluation of their attitudes followed. Although the boys forbidden to touch the gun did not report an increased preference for it, all participants were significantly more likely to touch the forbidden gun than to touch other forbidden objects. Age, parent- and coach-reported simulated gun-play, and coach-reported risky behavior predicted gun-touching behavior. The results of the current study indicate that guns hold a unique allure and cast further doubt on the ability of gun admonitions to keep children safe around guns.

The present study investigated the effectiveness of a skills-based firearm safety program on reducing children's play with firearms. In a randomized control study, 34 children aged 4 to 7 years participated in a week-long firearm safety program; the Control Group was composed of 36 children. After the program, pairs of children were observed playing in a structured setting in which they had access to a semiautomatic pistol. A total of 53% of the pairs played with the gun, and there was no difference in gun-play behavior between those children who did and did not receive the intervention. Interview data revealed significant discrepancies in parent and child reports of parental gun ownership and inaccurate parental predictions of their children's interest in guns. The results of the current study cast doubt on the potential effectiveness of skills-based gun safety programs for children.

Endogenous glucocorticoids are implicated in the development and resolution of inflammation. Until recently it was thought that these glucocorticoids arose primarily from the adrenal gland. However, it is now known that several cell types can generate active glucocorticoids within their cytoplasm through expression of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. In a more limited range of cell types, glucocorticoids can be inactivated by the related 11β-HSD2 enzyme. Both enzymes are regulated by inflammation in various settings. In rheumatoid arthritis, 11β-HSD activity is present in the inflamed synovium and appears to influence articular and extraarticular disease processes. The generation of active glucocorticoids in the synovium is strongly linked to the level of inflammation. This local production of glucocorticoids is likely to have paracrine consequences and could underpin inflammation-associated bone loss. The role of 11β-HSD enzymes in the severity and persistence of inflammatory arthritis in a clinical setting is currently being explored.

Practice development (PD) in mental health nursing has been progressing over the last decade; however, the level and impact of PD activity in the field of mental health remains poorly understood outside localized project impact. More specific reporting and comparative analysis of PD outcomes will improve this situation. In response, this paper presents three case scenarios from work taking place in Australia and New Zealand, as working examples of how PD methodologies have been applied within mental health practice settings. Using a comparative framework that captures the contributing assumptions, practices, processes and conditions imperative to effective PD work within a mental health-care context, three case vignettes are reviewed. The critical question driving this paper is 'what mental health-care services does PD offer in terms of transformational change approaches and the promotion of effective workplace cultures?' Conditions considered necessary for successful PD initiatives within mental health contexts are explored such as how PD converges and diverges with mental health-related theories, plus where and how PD activity best integrates with the specific elements associated with mental health-care provision. The findings are further reviewed in line with reports of PD outcomes from other fields of health care.

Two barriers prevent adenovirus-based vectors from having wide application. One is the difficulty of making new adenoviruses, and the second is the strong immunological reaction to viral proteins. Here we describe uses of Cre-lox recombination to overcome these problems. First, we demonstrate a simple method for constructing E1-substituted adenoviruses. Second, we demonstrate a method to construct adenovirus vectors carrying recombinant genes in place of all of the viral genes, so-called gutless adenovirus vectors. The pivotal feature in each method is the use of a negatively selected adenovirus named psi5. We engineered a cis-acting selection into psi5 by flanking its packaging site with loxP sites. When psi5 was grown in cells making a high level of Cre recombinase, the packaging site was deleted by recombination and the yield of psi5 was reduced to 5% of the wild-type level. To make a new E1-substituted virus, we used psi5 as a donor virus and recombined it with a shuttle vector via a loxP site. The resulting recombinant virus has a single loxP site next to the packaging site and therefore outgrows psi5 in the presence of Cre recombinase. To make a gutless virus, we used psi5 as a helper virus. The only viral sequences included in the gutless vector are those needed in cis for its replication and packaging. We found that a loxP site next to the packaging site of the gutless virus was necessary to neutralize homologous recombination between psi5 and the gutless viruses within their packaging domains.

Fatty acids with more than 22 carbon atoms (very-long-chain fatty acids; VLCFAs) are normal cellular components that have been implicated in the pathophysiology of a number of peroxisomal disorders. To date, however, essentially nothing is known regarding their biological activities. Ca2+ mobilization is an important intracellular signalling system for a variety of agonists and cell types. Given that several polyunsaturated long-chain fatty acids mobilize intracellular Ca2+ and that we have postulated that the VLCFAs may be involved in signal transduction, we examined whether the tetraenoic VLCFA induced Ca2+ mobilization in human neutrophils. We report that fatty acid-induced intracellular Ca2+ mobilization declined for fatty acid species of more than 20 carbon atoms, but increased again as the carbon chain length approached 30. This Ca2+ mobilization occurred independently of inositol 1,4,5-triphosphate production and protein kinase C translocation and involved both the release of Ca2+ from the intracellular stores and changes to the influx or efflux of the ion. We further observed that triacontatetraenoic acid [30:4(n-6)] mobilized Ca2+ from a thapsigargin-insensitive intracellular pool distinct from the thapsigargin-sensitive pools affected by arachidonic acid [20:4(n - 6)] or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). 20:4 (n - 6) induced strong superoxide production (chemiluminescence) which was inhibited by thapsigargin pretreatment. In contrast, fatty acid-induced superoxide production progressively declined as the carbon chain length increased beyond 20-22 carbon atoms. Further studies suggested that the thapsigargin-insensitive Ca2+ mobilization elicited by 30:4 (n - 6) was not related to oxyradical formation, while the thapsigargin-sensitive Ca2+ mobilization induced by 20:4 (n - 6) may be involved in the initiation but not necessarily the maintenance of superoxide production. In conclusion, this is the first report to demonstrate a biological activity for the VLCFA and indicates that 30:4 (n - 6) influences second messenger systems in intact cells that differ from those affected by long-chain fatty acids such as 20:4 (n - 6).

We compared interpersonal distance and coping among two groups of pre-school pediatric patients diagnosed with either HIV or cancer and a third group of healthy children. In comparison to the children with cancer, children with HIV indicated greater mother-child interpersonal distance--a finding that correlated with mothers' reports of social withdrawal. Other notable findings included increased father-child distance in the HIV population and mother-child discrepancies of perceived interpersonal distance. In addition, seven of the children with HIV indicated that the adults turn away--a finding that correlated with the children's knowledge of their illness. We also explored the possible role of protective communication in the pediatric HIV population.

Since the International Agency for Research on Cancer labeled crystalline silica a probable carcinogen in 1988, government regulations have required sand and other products to contain warning labels and researchers have attempted to quantitatively assess low-exposure risks. The uncertainties are unlikely to diminish any time soon, and little value exists in calculating such risks, as low exposures to this ubiquitous mineral are commonplace in both urban and rural areas due to many uncontrollable activities. What is certain is that regulatory resources targeted at continuing high-level occupational exposures would be much more likely to have beneficial public health consequences than continued attempts to assess low-exposure risks quantitatively. Images p152-a

The objective was to consider the feasibility of food diaries as a method of understanding the dietary behaviour of people with schizophrenia. Examination of the food diaries completed in 1 week by eight patients with schizophrenia. All the patients were successful in completing the task. Examination of the food diaries revealed that: eating fruit and vegetables was largely absent; there was very little variety in most of the patients' diets; patients relied heavily on convenience food and ready meals for their main meal; as a rule patients followed an ordered mealtime routine; generally patients did not drink enough fluid; they were not big treat eaters; only one patient recorded drinking any alcohol; overall there appeared to be poor diet literacy in our small sample. The results show that on the whole, people with schizophrenia have a poor diet. This could be due to a combination of financial difficulty, lack of skills in food preparation, lack of motivation to prepare food or ignorance of what constitutes a healthy diet. The fact that they all managed to complete the task is perhaps evidence of motivation to improve their health and demonstrates the utility of food diaries in educating this population.

There is extensive international evidence that people with severe mental illness have a lower standard of physical health than the general population. This leads to higher morbidity and mortality rates. Many of the causes for this poor physical health are modifiable. Yet the physical needs of this consumer group are neglected by healthcare systems in Australia, and elsewhere. While medical specialists are clearly integral to remedying this, nurses are well placed to play a key role in focused prevention and early intervention in the physical well-being of consumers with mental health problems. This paper outlines the specifics on how mental health nurses can be sensitized, prepared and empowered to help turn this serious health issue around. In particular, mental health nurses could be trained in and then utilize a new physical health check and response system in the UK (called the Health Improvement Profile) if adapted for use within Australia. This profile will be briefly introduced, and then its value to improving health care discussed.

Healthcare professionals in primary and secondary care should monitor the physical health of people with serious mental illness, yet in practice this does not appear to be a routine intervention. Our objective is to develop evidence-based training for healthcare professionals to enable them all to offer better physical care to this population. We performed a systematic search with the aim of evaluating the current evidence of the efficacy of education interventions. Search terms covered Severe Mental Illness, Physical Health and Education. The search yielded 147 papers, of which none were eligible for inclusion. A number of studies were excluded from this review as although there was an implicit education package provided to healthcare professionals, no information was reported on the outcomes of this education with regard to healthcare professionals' knowledge, attitudes and behaviours. The only information that these studies provided was patient-specific outcomes. It is vital that researchers start to publish details of healthcare professional education and their outcomes in physical health and serious mental illness research.

Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed in people with ID and to audit clinical practice against the standards.Data were collected from the clinical records of individuals with ID who were under the care of mental health services in the UK, and prescribed an antipsychotic drug.The sample comprised 2319 patients from 39 clinical services. Twenty-seven per cent of the patients had a diagnosis of a psychotic illness (ICD-10 F20-29) and 27% an affective illness (ICD-10 F30-39). The proportion who did not have a psychiatric diagnosis ranged from 6% of those with borderline/mild ID to 21% of those with severe/profound ID. Overall, the most common indications for prescribing an antipsychotic drug were comorbid psychotic illness, anxiety and agitation, and a range of behavioural disturbances. The prevalence of use of antipsychotic drugs to manage challenging behaviour in the absence of concomitant mental illness increased with the severity of ID and accounted for almost half of prescriptions in those with severe/profound ID. Adherence to the audit standards related to documentation of clinical indications and review of efficacy was high. Side effect monitoring was less assiduous.In clinical practice, most prescriptions for antipsychotic drugs in people with ID are consistent with the evidence base and the overall quality of prescribing practice, as measured against recognised standards, is good, although in some patients potentially remedial side effects may not be detected and treated.

1. The rate of transfusion decreased from 64% in 1992 to 36% in 2000. This need for transfusions continued despite the introduction of erythropoetin. Females were transfused more frequently than males. SLE patients were transfused more often than those with other diseases. 2. Transfusions no longer had a beneficial effect on the outcome of transplantation, but rather with more transfusions, the graft outcome became lower, as might be expected. 3. Rejection of a kidney transplant had the strongest effect on sensitization, followed by transfusion and then pregnancies. Females were more susceptible to sensitization than males. Although non-transfused males should not have been sensitized, as many as 13% were reported to have antibodies. As many as 20% of nulliparous females without transfusions also were reported to have antibodies. 4. SLE patients were most often sensitized among patients with various diseases. Females of all diseases were more sensitized than males. 5. Unsensitized regraft patients had a 3% lower 3-year graft survival than unsensitized first graft patients. Among sensitized patients, regraft patients had a 4% lower graft survival than sensitized first graft patients. 6. Patients with polycystic kidney disease had the highest 3-year graft survival in both the sensitized and non-sensitized patients. Sensitization to a PRA level of less than 50% was not detrimental to patients with all the various diseases. 7. For cadaver donor regraft patients, HLA-DR mismatch had a greater effect than AB mismatch. There was a 10 percentage point lower 3-year graft survival in cadaver donor regraft patients mismatched for 2 DR antigens than mismatched for 0 DR antigens. 8. For living donor transplants, regrafts from 0 AB or 0 DR mismatched transplants had the same graft survival as first transplants.

Advocacy groups on both sides of the guns issue frequently point to changing personal behavior--of both parents and children--as a key element in reducing gun violence among youth. Efforts to bring about these changes range from community-based campaigns, to laws and programs that encourage parents to store their guns safely, to educational initiatives that focus on keeping young children away from guns and encouraging youth to resolve disputes without violence. Unfortunately, these behavior-oriented programs have not shown great success in reducing youth gun violence. This article reviews the research surrounding behavioral approaches to gun violence prevention and highlights obstacles that hamper the effectiveness of these programs. Supportive communities can play a key role in protecting youth from violence in general, but the few community-based violence prevention programs that focus on youth have not been shown to decrease youth access to or use of guns. By and large, behavioral programs and legal interventions aimed at parents have not been proven to reduce youth gun violence. This may be due in part to parental misperceptions about children's risk of injury and ability to protect themselves. Children and youth are particularly difficult targets for behavioral change programs. Cognitive immaturity among younger children and perceptions of invulnerability among adolescents may be part of the reason. Most programs that seek to persuade youth to stay away from guns have not been proven effective. The author concludes that, although behavioral programs could be improved, overall they hold only limited promise for reducing youth gun violence.

Epidemiological studies and experiments using animal models and cultured breast cancer cells have suggested that a high intake of dietary fat could increase breast cancer risk. Little is known about the biochemical pathways by which various free fatty acids (FFAs) influence breast cancer cell proliferation and apoptosis. The present study was designed to investigate the effects of the two most abundant circulating FFAs, oleate and palmitate, on established human breast cancer cell lines after a short period of serum starvation. The unsaturated FFA oleate (C:18:1) stimulated cell proliferation, whereas the saturated FFA palmitate (C:16) dose dependently inhibited it. The half maximal effective concentrations of oleate and palmitate in the presence of albumin were 5 and 25 microM, respectively. The growth-inhibitory effect of palmitate in MDA-MB-231 cells was related to the induction of apoptosis as indicated by morphological and biochemical criteria. Moreover, oleate protected cells against the proapoptotic action of palmitate. Oleate and palmitate increased and decreased phophatidylinositol 3-kinase (PI3-K) activity, respectively, and the actions of the two FFAs on the enzyme were antagonistic. The PI3-K inhibitors wortmannin and LY294002 completely blocked the proliferative action of oleate. 2-Bromopalmitate, a nonmetabolizable analogue, did not affect MDA-MB-231 cell proliferation, suggesting that palmitate must be metabolized to exert its effect. Thus, various types of fatty acids are not equivalent with respect to their actions on breast cancer cell proliferation and apoptosis. The results support the concept that PI3-K is implicated in the control of breast cancer cell growth by FFAs and that PI3-K may provide a link between fat and cancer. The data are also consistent with the view that the type of FFA and their ratios in the diet in addition to the total amount of fat influence mammary carcinogenesis.

In order to contextualize Altschul's interest in group dynamics we present a brief history of staff group work approaches in the UK and USA. Using case examples, the work of staff group sensitivity and group supervision is described. The difficulties of working in staff groups are highlighted and the antipathy towards group practice is discussed. It is argued that learning about conflict resolution in staff groups prepares nurses for dealing with conflicts in clinical practice. The case for re-invigorating interest in group theory and practice is presented. In presenting our reflections on staff group work, we hope not only to re-kindle the type of interest in groups that inspired Altschul but also to represent the case that it is ill conceived to attempt the work of mental health nursing without recourse to the supervisory resources of group theory, practice and support. It is through group feedback that mental health nurses and other health professionals can extend their learning about interpersonal relations, achieve quality standardization through peer feedback and reflect on practice in truly collaborative ways (Schon 1983).

PURPOSE this study examined predictors of macrosomia in a multiethnic sample of 213 low-income women diagnosed with gestational diabetes mellitus (GDM) after week 24 of their pregnancy. METHODS Medical records were reviewed retrospectively. Variables examined were mother's height, weight history, educational level, age at diagnosis, weeks at diagnosis and delivery, type of diabetes, mean fasting blood glucose (FBG), and infant's weight, sex, and Apgar scores. RESULTS Fifty-one percent of babies were macrosomic. Weight gain, nonpregnant weight, weight at delivery, FBG, and Apgar scores at 1 minute were associated with macrosomia, especially in Hispanic women. Logistic regression revealed that nonpregnant weight was the strongest predictor of macrosomia. CONCLUSIONS Nonobese GDM mothers with optimal weight gain but with high FBG levels >90 mg/dL may be at risk for macrosomia. The major concerns with obese GDM mothers are nonpregnant weight and high blood glucose levels, in this order. Education for women with GDM should target these risk factors to decrease macrosomia.

The therapeutic approach to cerebral arteriovenous malformations has been modified with the availability of stereotactic radiosurgery, initially, the main indications of radiosurgery were limited, non surgical arteriovenous malformations. Indications are now much more diverse. Imaging plays an important role in the radiosurgical management of arteriovenous malformations and its evaluation. In this review, the different roles of neuroimaging are discussed; characterization of malformations, choice of the best indications, role of embolization, delimitation of the target, evaluation of results and complications of radiosurgery.

The purpose of this study was to compare children's play and aggressive behavior with firearms before and after an information-based intervention. Correlates of aggression and gun play were also analyzed. Subjects were 24 pairs of preschool children videotaped for 10 minutes in a structured play setting, in which they had access to a variety of toys and to real and toy guns. One child from each dyad was then exposed to an information-based intervention and told not to play with guns. The children were again videotaped in the same setting approximately 1 week later. Results indicated that the intervention was ineffective in modifying the behavior of the children. Regression analyses revealed that access to a parent's firearm was correlated with gun play and that gun play and handling of firearms in the home were correlated with aggressive behavior. The findings in this study represent the first systematic attempt to decrease gun play in children and suggest that information provision alone is an insufficient intervention.

Value analysis and shared governance are two management concepts relatively new to the health care industry. Operating together, they complement each other and can result in a comprehensive "quality management" plan. An example of this model in a purchasing decision illustrates the benefits that can result from use of this collaborative, multidisciplinary approach.

Coping strategies and communication of three groups of 20 preschool children and their parents were compared. One group was composed of children infected with the human immunodeficiency virus (HIV) who displayed clinical symptoms of the disease; the second group was composed of children diagnosed with cancer; and the third group was composed of healthy children. Results indicated that the parents of children with life-threatening illnesses reported greater degrees of wishful thinking than did control subjects. Furthermore, parents of children with HIV reported more wishful thinking than did parents of children with cancer. Finally, significantly more children with cancer were aware of their diagnosis than were children with HIV. The findings in this study suggest coping and communication difficulties for parents and children with HIV.

MRF4 is a member of the muscle-specific basic helix-loop-helix transcription factor family that also includes MyoD, myogenin, and Myf-5. Each of these proteins, when overexpressed in fibroblasts, converts the cells to differentiated muscle fibers that express several skeletal muscle genes, such as those for alpha-actin, muscle creatine kinase, and troponin I. Despite the fact that MRF4 functions as a positive transcriptional regulator, the MRF4 protein is subject to negative regulation by a variety of agents, most notably by exposure of cells to purified growth factors, such as basic fibroblast growth factor (bFGF). In an effort to establish whether bFGF inhibits MRF4 activity through specific posttranslational modifications, we examined whether MRF4 exists in vivo as a phosphoprotein and whether the phosphorylation status of the protein regulates its activity. Our results indicate that MRF4 is phosphorylated predominantly on serine residues, with weak phosphorylation occurring on threonine residues. Both cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) phosphorylate MRF4 in vitro as well as in vivo, and the overexpression of each kinase inhibits MRF4 activity and thus blocks terminal differentiation. PKC-directed phosphorylation of a conserved threonine residue (T-99) situated within the DNA-binding domain inhibits MRF4 from binding in vitro to specific DNA targets. However, although T-99 itself is essential for myogenic activity, our studies demonstrate that the phosphorylation status of T-99 does not play a major role in regulating MRF4 activity in vivo, since PKA, PKC, and bFGF inhibit the activity of MRF4 proteins in which the identified PKA and PKC sites have been mutated. We suggest that the negative regulation of MRF4 imposed by bFGF does not involve a direct modification of the protein at the identified PKA and PKC sites but instead may involve the modification of specific coregulators that interact with this muscle regulatory factor.

Our aim was to determine the population frequencies of the major slow acetylator alleles of the polymorphic N-acetyltransferase (NAT2) gene, whose locus maps to chromosome 8. We used allele-specific PCR amplification on 786 dried blood spots obtained from Hong Kong Chinese, U.S. Koreans, U.S. blacks, U.S. Hispanics, Germans, and U.S. whites. Our results show that four slow acetylator alleles can be detected as mutations at positions 481, 590, and 857 in the NAT2 gene. Recognized base substitutions at positions 341 and 803 need not be determined, because they were almost always associated with the 481T mutation. The known mutation at position 282 was strongly associated with the 590A mutation. The 481T, 590A, and 857A mutations accounted for virtually all of the slow acetylator alleles in Asian and white populations. The 857A mutation proved to be an Asiatic allele. The results will be useful in large-scale epidemiologic studies of cancer and other conditions potentially associated with the acetylator polymorphism.

E2F is a sequence-specific DNA-binding factor which binds to sites that occur in pairs upstream of the adenovirus E1A and E2 early transcriptional start sites. Substantial quantities of E2F activity were found in uninfected-cell extracts, and there was a modest increase in E2F activity during an adenovirus type 5 (Ad5) infection. In uninfected cells, E2F was found to exist in multiple forms that could be separated chromatographically. Extracts prepared at 24 h after Ad5 infection contained a new form of E2F. This infection-specific form may have been a modified version of one of the forms present in uninfected cells. The infection-specific E2F was shown to bind cooperatively to a pair of E2F sites found upstream of the Ad2 early region 2 mRNA cap site. This binding was sensitive to the spacing between the sites and their relative orientation. In contrast, E2F binding in uninfected-cell extracts was unaffected by changes in orientation and spacing, consistent with very low cooperativity or independent binding.

In this randomized double-blind study, 51 patients with uncomplicated anal or pharyngeal Neisseria gonorrhoeae infection were evaluated to determine the efficacy and safety of 200- or 400-mg of enoxacin twice a day for two days. Enoxacin cured all anal infections and 12 out of 13 pharyngeal infections. All 82 isolates of N. gonorrhoeae tested were inhibited by 1 microgram of enoxacin/ml.