Involvement of formyl peptide receptors in the stimulatory effect of crotoxin on macrophages co-cultivated with tumour cells

Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. the present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. the effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 mu g/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. the co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. the production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. the level of secreted IL-1 beta increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA(4) (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA(4) was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect. (C) 2013 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)PAPInstituto Nacional de Ciencia e Tecnologia em ToxinasButantan Inst, Lab Pathophysiol, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Inflammat & Vasc Pharmacol, BR-09913030 Diadema, SP, BrazilUniv São Paulo, Fac Med, BR-01246000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 São Paulo, BrazilButantan Inst, Special Lab Pain & Signaling, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Inflammat & Vasc Pharmacol, BR-09913030 Diadema, SP, BrazilFAPESP: 09/52330-9Instituto Nacional de Ciencia e Tecnologia em Toxinas: INCTTOX 2008/57898-0Web of Scienc

The validity of dementia diagnoses in routinely collected electronic health records in the United Kingdom: A systematic review.

PURPOSE: The purpose of the study is to assess the validity of codes or algorithms used to identify dementia in UK electronic health record (EHR) primary care and hospitalisation databases. METHODS: Relevant studies were identified by searching the MEDLINE/EMBASE databases from inception to June 2018, hand-searching reference lists, and consulting experts. The search strategy included synonyms for "Dementia", "Europe", and "EHR". Studies were included if they validated dementia diagnoses in UK primary care or hospitalisation databases, irrespective of validation method used. The Quality Assessment for Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess risk of bias. RESULTS: From 1469 unique records, 14 relevant studies were included. Thirteen validated individual diagnoses against a reference standard, reporting high estimates of validity. Most reported only the positive predictive value (PPV), with estimates ranging between 0.09 and 1.0 and 0.62 and 0.85 in primary care and hospitalisation databases, respectively. One study performed a rate comparison, indicating good generalisability of dementia diagnoses in The Health Improvement Network (THIN) database to the UK population. Studies were of low methodological quality. As studies were not comparable, no summary validity estimates were produced. CONCLUSION: While heterogenous across studies, reported validity estimates were generally high. However, the credibility of these estimates is limited by the methodological quality of studies, primarily resulting from insufficient blinding of researchers interpreting the reference test. Inadequate reporting, particularly of the specific codes validated, hindered comparison of estimates across studies. Future validation studies should make use of more robust reference tests, follow established reporting guidelines, and calculate all measures of validity

Synthesis and characterizations of zinc oxide nanoparticles and its ability to detect O2 and NH3 gases

In this study, zinc oxide nanoparticles (ZnONPs) were synthesised using royal jelly. The prepared NPs were characterised through transmission electron microscopy, field-emission scanning electron microscopy, X-ray diffraction and Fourier transform infrared analysis. The size of the ZnONPs was 31.75 nm. The produced ZnONPs were evaluated as gas sensors for O2 and NH3 gases at various temperatures and time intervals. The highest sensitivity response to O2 (i.e. 11.1%) was recorded at 100 °C. The highest sensitivity response to NH3 (i.e. 12%) was observed at 25 °C. The sensor exhibited the shortest response and recovery times at different temperatures for O2 and NH3 gases, respectively. At 100 °C, the response time for O2 gas was 18 s, and the recovery time was 23 s. For NH3 gas, the response time was 25 s at 100 °C, and the recovery time was 22 s at 25 °C. These findings demonstrate the unique response and recovery features of the sensor

Frequency of use of the International Classification of Diseases ICD-10 diagnostic categories for mental and behavioural disorders across world regions

Aims.: The study aimed to examine variations in the use of International Classification of Diseases, Tenth Edition (ICD-10) diagnostic categories for mental and behavioural disorders across countries, regions and income levels using data from the online World Psychiatric Association (WPA)-World Health Organization (WHO) Global Survey that examined the attitudes of psychiatrists towards the classification of mental disorders. Methods.: A survey was sent to 46 psychiatric societies which are members of WPA. A total of 4887 psychiatrists participated in the survey, which asked about their use of classification, their preferred system and the categories that were used most frequently. Results.: The majority (70.1%) of participating psychiatrists (out of 4887 psychiatrists) reported using the ICD-10 the most and using at least one diagnostic category once a week. Nine out of 44 diagnostic categories were considerably variable in terms of frequency of use across countries. These were: emotionally unstable personality disorder, borderline type; dissociative (conversion) disorder; somatoform disorders; obsessiveâ\u80\u93compulsive disorder (OCD); mental and behavioural disorders due to the use of alcohol; adjustment disorder; mental and behavioural disorders due to the use of cannabinoids; dementia in Alzheimer's disease; and acute and transient psychotic disorder. The frequency of use for these nine categories was examined across WHO regions and income levels. The most striking differences across WHO regions were found for five out of these nine categories. For dissociative (conversion) disorder, use was highest for the WHO Eastern Mediterranean Region (EMRO) and non-existent for the WHO African Region. For mental and behavioural disorders due to the use of alcohol, use was lowest for EMRO. For mental and behavioural disorders due to the use of cannabinoids, use was lowest for the WHO European Region and the WHO Western Pacific Region. For OCD and somatoform disorders, use was lowest for EMRO and the WHO Southeast Asian Region. Differences in the frequency of use across income levels were statistically significant for all categories except for mental and behavioural disorders due to the use of alcohol. The most striking variations were found for acute and transient psychotic disorder, which was reported to be more commonly used among psychiatrists from countries with lower income levels. Conclusions.: The differences in frequency of use reported in the current study show that cross-cultural variations in psychiatric practice exist. However, whether these differences are due to the variations in prevalence, treatment-seeking behaviour and other factors, such as psychiatrist and patient characteristics as a result of culture, cannot be determined based on the findings of the study. Further research is needed to examine whether these variations are culturally determined and how that would affect the cross-cultural applicability of ICD-10 diagnostic categories

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo