Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial.

While statins target many of the pathways to neuroprogression in schizophrenia, the safety and efficacy of statins for treating schizophrenia has never been examined. This is an 8-week randomized double blind controlled clinical trial examining the efficacy and safety of adjunctive lovastatin (20 mg/day) treatment or placebo for people with schizophrenia. The baseline characteristics of the two groups were not different. Endpoint changes in Positive and Negative Syndrome Scale (PANSS) total and subscale scores did not differ between the two groups. However there was a significant difference between the doses of risperidone used in the two groups. The mean dose in the lovastatin and placebo groups were 4.8(1.8) and 3.4(1.4) mg/day, respectively (P<.03). No serious adverse events were reported. Slowness of movements, muscle rigidity, increased appetite, and decreased energy were the most common adverse effects, and these rates did not differ between the two groups. This study failed to demonstrate a benefit of lovastatin on symptoms of schizophrenia. This combination was well tolerated. However, a higher dosage of risperidone was used for treating the disorder in those taking concomitant lovastatin compared to placebo.

The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): study protocol for a randomised control trial.

The aim of the Youth Depression Alleviation-Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support.

Why has the safety and quality movement been slow to improve care?

Buist and Middleton lament that the safety and quality 'agenda' has failed to fundamentally alter the safety of healthcare systems, in part because of the disengagement of doctors from their responsibilities for patient safety . While there have been discernable improvements in the efficiency and effectiveness of care in some settings, patients still experience unacceptable harm and often struggle to have their voices heard; processes are not as efficient as they could be; and costs continue to rise at alarming rates while quality issues remain . Perhaps of most concern, recent public reports into health system failures continue to document a widespread lack of attentiveness to patient concerns, a culture of denial and widespread lack of professionalism . Alarmingly, clinician discontentment, cynicism and burn-out are reflected in antagonistic language by clinicians about the healthcare system and their patients. Taken together with the many dissatisfied and now more vocal patient groups, all point to an unprecedented crisis of faith in our healthcare systems which has been getting worse over past decade . This personal perspective aims to address the fundamental tensions that are keeping much of healthcare reform efforts from successfully transforming the culture and outcomes except at the margins.

Safety applications using Kinect technology

 Microsoft Kinect sensor was introduced with the XBOX gaming console. It features a simple and portable motion capturing system. Kinect nowadays presents a point of interest in many fields of study and areas of research where its affordable price compared to its capabilities. The Kinect sensor has the capability to capture and track detected 3D objects with accuracy comparable to that captured by state of the art commercial systems. Human safety is considered one of the highest concerns, specially nowadays where the existence of machines and robots is widely used. In this paper we present using the Kinect technology for enhancing the safety of equipment and operations in seven different applications. These applications include 1) positioning of child’s car seat to optimise the child’s position in respected to front and side air-bags; 2) board positioning system to improve the teacher’s arm reach posture; 3) gas station safety to prevent children from accessing the gas pump; 4) indoor pool safety to avoid children access to deep pool area; 5) robot safety emergency stop; 6) Workplace safety; and 7) older adults fall prediction.

The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells

Danusertib (Danu) is a pan-inhibitor of Aurora kinases and a third-generation breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (Bcr-Abl) tyrosine kinase inhibitor, but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. This study aimed to investigate the effects of Danu on the growth, apoptosis, autophagy, and epithelial-to-mesenchymal transition (EMT) and the molecular mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. The results demonstrated that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both breast cancer cell lines. Danu arrested MCF7 and MDA-MB-231 cells in G2/M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. Danu significantly decreased the expression of B-cell lymphoma-extra-large (Bcl-xl) and B-cell lymphoma 2 (Bcl-2), but increased the expression of Bcl-2-associated X protein (Bax) and p53-upregulated modulator of apoptosis (PUMA), and promoted the cleavage of caspases 3 and 9. Furthermore, Danu significantly increased the expression levels of the membrane-bound microtubule-associated protein 1A/1B-light chain 3 (LC3-II) and beclin 1 in breast cancer cells, two markers for autophagy. Danu induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (Erk1/2) and inhibited the activation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in breast cancer cells. Treatment with wortmannin (a phosphatidylinositol 3-kinase inhibitor) markedly inhibited Danu-induced activation of p38 MAPK and conversion of cytosolic LC3-I to membrane-bound LC3-II. Pharmacological inhibition and small interfering RNA-mediated knockdown of p38 MAPK suppressed Akt activation, resulting in LC3-II accumulation and enhanced autophagy. Pharmacological inhibition and small interfering RNA-mediated knockdown of Erk1/2 also remarkably increased the level of LC3-II in MCF7 cells. Moreover, Danu inhibited EMT in both MCF7 and MDA-MB-231 cells with upregulated E-cadherin and zona occludens protein 1 (ZO-1) but downregulated N-cadherin, zinc finger E-box-binding homeobox 1 (TCF8/ZEB1), snail, slug, vimentin, and β-catenin. Notably, Danu showed lower cytotoxicity toward normal breast epithelial MCF10A cells. These findings indicate that Danu promotes cellular apoptosis and autophagy but inhibits EMT in human breast cancer cells via modulation of p38 MAPK/Erk1/2/Akt/mTOR signaling pathways. Danu may represent a promising anticancer agent for breast cancer treatment. More studies are warranted to fully delineate the underlying mechanisms, efficacy, and safety of Danu in breast cancer therapy.

Using an evidence-based care bundle to improve initial emergency nursing management of patients with severe traumatic brain injury

AIMS AND OBJECTIVES: To test the feasibility of an evidence-based care bundle in a Thai emergency department. The specific objective of this study was to examine the impact of the implementation of the care bundle on the initial emergency nursing management of patients with severe traumatic brain injury. BACKGROUND: A care bundle approach is one strategy used to improve the consistency, quality and safety of emergency care for different patients groups, however, has not been tested in patients with severe traumatic brain injury. DESIGN: A pretest/post-test design was used. The study intervention was an evidence-based care bundle for initial emergency nursing management of patients with severe traumatic brain injury. METHODS: Nonparticipant observations were conducted between October 2012-June 2013 at an emergency department of a 640 bed regional hospital in Southern Thailand. The initial emergency nursing care was observed in 45 patients with severe traumatic brain injury: 20 patients in the pretest period and 25 patients in the post-test period. RESULTS: There were significant improvements in clinical care of patients with severe traumatic brain injury after implementation of the care bundle: (1) use of end-tidal carbon dioxide monitoring, (2) frequency of respiratory rate assessment, (3) frequency of pulse rate and blood pressure assessment, and (4) patient positioning. CONCLUSION: This study demonstrated that implementation of an evidence-based care bundle improved specific elements of emergency nurses' clinical management of patients with severe traumatic brain injury. RELEVANCE TO CLINICAL PRACTICE: The study suggests that a care bundle approach can be used as a strategy to improve emergency nursing care of patients with severe traumatic brain injury.

What doesn’t kill you makes you fitter: A systematic review of high-intensity interval exercise for patients with cardiovascular and metabolic diseases

High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (≥80% peak power output or ≥85% peak aerobic power, VO2peak). Eleven studies met the inclusion criteria (n = 156; clinically stable, aged 27-66 years), with 13 adverse responses reported (∼8% of individuals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate-intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session.

Toward a standard approach to measurement and reporting of perioperative mortality rate as a global indicator for surgery

INTRODUCTION: The proportion of patients who die during or after surgery, otherwise known as the perioperative mortality rate (POMR), is a credible indicator of the safety and quality of operative care. Its accuracy and usefulness as a metric, however, particularly one that enables valid comparisons over time or between jurisdictions, has been limited by lack of a standardized approach to measurement and calculation, poor understanding of when in relation to surgery it is best measured, and whether risk-adjustment is needed. Our aim was to evaluate the value of POMR as a global surgery metric by addressing these issues using 4, large, mixed, surgical datasets that represent high-, middle-, and low-income countries. METHODS: We obtained data from the New Zealand National Minimum Dataset, the Geelong Hospital patient management system in Australia, and purpose-built surgical databases in Pietermaritzburg, South Africa, and Port Moresby, Papua New Guinea. For each site, we calculated the POMR overall as well as for nonemergency and emergency admissions. We assessed the effect of admission episodes and procedures as the denominator and the difference between in-hospital POMR and POMR, including postdischarge deaths up to 30 days. To determine the need for risk-adjustment for age and admission urgency, we used univariate and multivariate logistic regression to assess the effect on relative POMR for each site. RESULTS: A total of 1,362,635 patient admissions involving 1,514,242 procedures were included. More than 60% of admissions in Pietermaritzburg and Port Moresby were emergencies, compared with less than 30% in New Zealand and Geelong. Also, Pietermaritzburg and Port Moresby had much younger patient populations (P < .001). A total of 8,655 deaths were recorded within 30 days, and 8-20% of in-hospital deaths occurred on the same day as the first operation. In-hospital POMR ranged approximately 9-fold, from 0.38 per 100 admissions in New Zealand to 3.44 per 100 admissions in Pietermaritzburg. In New Zealand, in-hospital 30-day POMR underestimated total 30-day POMR by approximately one third. The difference in POMR if procedures were used instead of admission episodes ranged from 7 to 70%, although this difference was less when central line and pacemaker insertions were excluded. Age older than 65 years and emergency admission had large, independent effects on POMR but relatively little effect in multivariate analysis on the relative odds of in-hospital death at each site. CONCLUSION: It is possible to collect POMR in countries at all level of development. Although age and admission urgency are strong, independent associations with POMR, a substantial amount of its variance is site-specific and may reflect the safety of operative and anesthetic facilities and processes. Risk-adjustment is desirable but not essential for monitoring system performance. POMR varies depending on the choice of denominator, and in-hospital deaths appear to underestimate 30-day mortality by up to one third. Standardized approaches to reporting and analysis will strengthen the validity of POMR as the principal indicator of the safety of surgery and anesthesia care.

N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. OBJECTIVE: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. METHODS: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. RESULTS: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20 %) participants were considered 'responders' (YBOCS ≥35 % reduction at endpoint) versus four (27 %) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). CONCLUSION: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. TRIAL REGISTRATION: ACTRN12613000310763.

Contribuição a inspeção e a avaliação da segurança de estruturas acabadas de concreto armado

Neste trabalho abordam-se as questões relevantes de uma avaliação analítica de estruturas acabadas, apresentando-se os aspectos fundamentais quanto à inspeção e verificação da sua segurança. Primeiramente, apresenta-se os métodos de avaliação, enfatizando-se as vantagens e restrições do emprego de cada método. Quanto à inspeção, são apresentados e discutidos os principais ítens que devem ser verificados nas estruturas acabadas. :t:nfasemaior é dada à inspeção da resistência do concreto, discutindo-se aspectos de sua variação nas ~struturas e apresentando-se os métodos de ensaio empregados. É proposta uma metodologia para a inspeção do concreto, racionalizando-se o emprego dos métodos não-destrutivos. Por fim, destaca-se os aspectos teóricos da verificação da segurança nas estruturas acabadas e as principais diferenças quanto à introdução da segurança nos projetos de novas estruturas.

JCML: A specification language for the runtime verification of Java Card programs

COSTA, Umberto Souza; MOREIRA, Anamaria Martins; MUSICANTE, Matin A.; SOUZA NETO, Plácido A. JCML: A specification language for the runtime verification of Java Card programs. Science of Computer Programming. [S.l]: [s.n], 2010.

Specification and Runtime Verification of Java Card Programs

COSTA, Umberto Souza da; MOREIRA, Anamaria Martins; MUSICANTE, Martin A. Specification and Runtime Verification of Java Card Programs. Electronic Notes in Theoretical Computer Science. [S.l:s.n], 2009.

External Morphology of the Immatures of Polybia paulista (Hymenoptera: Vespidae)

The immatures of Polybia paulista Ihering were described using light and scanning electron microscopy and the results are compared with previous descriptions within the same or related wasps. This study is based on 2 whole nests collected in the municipality of Rio Claro, São Paulo, in Brazil. We have detected the existence of 5 larval instars. The main morphological alterations over development occur in the relative size of structures, yet certain structures appear with subsequent instars and become more evident later in development: increasing density in the number of body spines and papillae; the appearance of body setae in fifth-instar larvae; opening of spiracles upon second-instar larvae; 2 body shapes in fifth-instar larvae; the appearance of a lateral tooth on the mandibles of fourth instar; presence of spines on the maxillae of fifth-instar larvae; altered shape of galea and palps upon third-instar larvae from a cluster of sensilla to a conical elevation; and the appearance of spines on postmentum upon fourth-instar larvae. This way, the present study presents a detailed description of the immatures of P. paulista, and we hope the presented information can be useful to morphological, taxonomic, and phylogenetic studies.

Digestibility and metabolizable energy of maize gluten feed for dogs as measured by two different techniques

Maize gluten feed (MGF) is a co-product of wet milling of maize, and is composed of structures that remain after most starch, gluten and germ has been extracted from the grain. Although currently used in dog foods, its digestibility and energy values have not been documented. Two techniques were used to determine nutrient digestibility of MGF for dog foods. Both techniques used extruded diets fed to Beagle dogs, with six replicates per diet. The first study used a difference method in which 300 g/kg of a reference diet was replaced by MGF. Based on the difference method, the coefficient of total tract apparent digestibility (CTTAD) of MGF was 0.53 for dry matter (DM), 0.69 for crude protein (CP), 0.74 for fat, 0.99 for starch, and 0.55 for gross energy (GE). The calculated metabolizable energy (ME) of MGF was 7.99 MJ/kg (as-fed). The second study used a regression method and included a basal diet and a basal diet with 70, 140 and 210 g MGF/kg of diet (as a substitute for maize starch). Maize gluten feed inclusion resulted in a linear reduction of CTTAD of DM (R(2)=0.99; P<0.001), CP (R(2)=0.95; P=0.002), fat (R(2)=0.87; P=0.009). starch (R(2)=0.81; P<0.001), and GE (R(2)=0.99; P<0.001). Faecal production increased linearly from 56 g to 107 g/dog/d (R(2)=0.99; P<0.001), with a linear reduction of faecal DM (R(2)=0.99: P<0.001) and a linear increase in faecal lactic acid concentration (P<0.02). Both urine (R(2)=0.77; P=0.029) and faeces (R(2)=0.92: P=0.019) showed a linear reduction in pH. Results of ingredient MAD obtained by the regression and difference methods were close (6% or less of variation) for CP, fat, and starch, and also for ME content (1.4% higher for the difference method), but the two methods disagreed on calculated CTTAD of DM and organic matter. The high dietary fiber content of MGF (382 g/kg) may explain the low digestibility of this ingredient. Maize gluten feed could be a useful ingredient for formulations designed to have low energy or reduce the urine pH of dogs. (C) 2011 Elsevier B.V. All rights reserved.

Assessment of informatization for the dispensing of medications at a university hospital

INTRODUCTION: Informatics and automation are important tools for the reduction of work, errors and costs in a hospital pharmacy. OBJECTIVES: To describe the structuring and function of an informatized system for the dispensing of medications and to assess its effect on nursing and pharmacy services during the period from 1997 to 2003. MATERIALS and METHODS: In this descriptive and retrospective study, we performed an analysis of documents addressing the structuring and implementation of the informatized medication dispensing system. In addition, we analyzed the perceptions of nurses, pharmacists and pharmacy assistants who participated in the structuring phase of the system when interviewed about the effect of informatization on administrative aspects (e.g., requisition of medications, presentation of the dispensed medication and system operationalization). RESULTS: The major advantages provided by the new system were 1) the elimination of manual transcripts for prescribed medications, 2) increased speed, 3) better identification of the doses prescribed by physicians, 4) medication labels containing all necessary identification and 5) practicality and safety of optical bar code-based verification of the requested and dispensed medications. CONCLUSIONS: The great majority of the interviewees considered the informatized medication supply system to be of good quality. Analysis of the data provided information that could contribute to the expansion and refinement of the system, provide support for studies regarding the utilization of medications and offer new perspectives for work and productivity.