Critical appraisal of the clinical practice guideline for the management of dyslipidaemia and prevention of cardiovascular disease: AACE 2017 guidelines.

Objective: This study aims to appraise 2017 AACE Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease by using Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Method: A total of seven investigators who have obtained a postgraduate Doctor of Pharmacy or Masters of Clinical Pharmacy, appraised the dyslipidaemia guidelines independently, by using AGREE II tool. Key findings: Among all the domains, the highest-scoring domain was the clarity of presentation (87%), and the lowest was the applicability (26%). The assessors gave the top ranking for both ‘scope and purpose’ (78%) and ‘Editorial independence’ (79%). The overall guideline assessment was 61%. Most of the investigators (four out of seven) recommended using the guidelines in clinical practice with modifications. Conclusion: The appraisal obtained in this article can be utilized by guideline developers to improve the quality of their upcoming guidelines. Healthcare professionals can be aware of guideline limitations and the importance of quality assessment of the guideline before applying their recommendations whenever possible by using Agree II tool

Insights into the structure-function relationships of dimeric C3d fragments

Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future

Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell–cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with “Pitt-Hopkins-like syndrome-1” (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype–phenotype correlation. Patients (M:F 14:8) were aged between 3 and 19 years and affected by global developmental delay (GDD) (n = 21), moderate to profound intellectual disability (n = 17) and epilepsy (n = 21). Seizures mainly started in the first two years of life (median 22.5 months). Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. Autism spectrum disorder (ASD) and/or other neuropsychiatric comorbidities were present in nine patients (40.9%). Nonspecific midline brain anomalies were noted in most patients while focal signal abnormalities in the temporal lobes were noted in three subjects. Genotype–phenotype correlation was performed by also including 50 previously published patients (15 mono- and 35 bi-allelic variants). Overall, GDD (p < 0.0001), epilepsy (p < 0.0001), hyporeflexia (p = 0.012), ASD (p = 0.009), language impairment (p = 0.020) and severe cognitive impairment (p = 0.031) were significantly associated with the presence of biallelic versus monoallelic variants. We have defined the main features associated with biallelic CNTNAP2 variants, as severe cognitive impairment, epilepsy and behavioral abnormalities. We propose CASPR2-deficiency neurodevelopmental disorder as an exclusively recessive disease while the contribution of heterozygous variants is less likely to follow an autosomal dominant inheritance pattern

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Multinational prospective cohort study of rates and risk factors for ventilator-associated pneumonia over 24 years in 42 countries of Asia, Africa, Eastern Europe, Latin America, and the Middle East: Findings of the International Nosocomial Infection Control Consortium (INICC)

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P <.0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P <.0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P <.0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P <.0001)Revisión por pare

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function

International Nosocomial Infection Control Consortium report, datasummary of 50 countries for 2010-2015 : Device-associated module

Q3Artículo original1495-1504Background: We report the results of International Nosocomial Infection Control Consortium (INICC) sur-veillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America,Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific.Methods:During the 6-year study period, using Centers for Disease Control and Prevention National Health-care Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregateof 3,506,562 days.Results:Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAIrates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associatedpneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples,frequencies of resistance ofPseudomonasisolates to amikacin (29.87% vs 10%) and to imipenem (44.3%vs 26.1%), and ofKlebsiella pneumoniaeisolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27%vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs.Conclusions:Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported inCDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the re-duction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC’s main goal tocontinue facilitating education, training, and basic and cost-effective tools and resources, such as stan-dardized forms and an online platform, to tackle this problem effectively and systematically

Credit risk management : a comparative study between islamic and conventional banks in Turkey

06.03.2018 tarihli ve 30352 sayılı Resmi Gazetede yayımlanan “Yükseköğretim Kanunu İle Bazı Kanun Ve Kanun Hükmünde Kararnamelerde Değişiklik Yapılması Hakkında Kanun” ile 18.06.2018 tarihli “Lisansüstü Tezlerin Elektronik Ortamda Toplanması, Düzenlenmesi ve Erişime Açılmasına İlişkin Yönerge” gereğince tam metin erişime açılmıştır.Bu araştırmada, katılım bankaları ve konvansiyonel bankalarda kredi riskini belirleyen değişkenler belirlenmek amaçlanmaktadır. İslami ve Konvansiyonel Bankalar arasında bir karşılaştırma vurgulanmıştır. Araştırmacı, panel verinin sabit etkiler modelini kullanarak, Türkiye'de üç Katılım Bankasına ait üç aylık verileri 2008 Ç1- 2017 Ç4 arasındaki dönemleri analiz etmek için kullandı. Geleneksel bankalar için, Türkiye'deki önceki araştırmalar, İslami bankaları geleneksel bankalarla karşılaştırmak için kullanılmıştır. Takipteki krediler oranı kredi riski mümesseli olarak kullanılmıştır. Ampirik sonuçlara göre, Katılım bankalarındaki takipteki krediler, özel karşılıklar ve kredi / mevduat oranlarından olumlu yönde etkilenmekte ve ölçekten olumsuz yönde etkilenmektedir. Geleneksel bankalarda ise net faiz marjı, özel karşılıklar, sermaye yeterlilik oranlarından olumlu yönde etkilenmekte ve kredi / mevduat oranı, kredi / aktif oranı ve hacminden olumsuz yönde etkilenmektedir. İslami bankalar ile geleneksel bankalar arasında, kredi zararları ve Alacaklar / Aktifler oranları haricinde, tüm çalışma değişkenleri bakımından belirgin farklılıklar vardı.In this research, we aimed to identify variables determining credit risk in Islamic and conventional banks. A comparison between Islamic and Conventional Banks is highlighted. The researcher employed a panel data fixed effect model to analyze quarterly data belong to three Islamic Banks in Turkey for the period 2008 Q1 to 2017 Q4. While for conventional banks, previous studies conducted in Turkey are used to compare Islamic banks to conventional banks. Non-performing Loans (NPL) ratio was used as a proxy for credit risk. According to Empirical result, NPL in Islamic Banks is positively affected by Loan Loss Provision, and Proportion of Loans to Deposits, and negatively affected by Assets Size. While in conventional banks it is positively affected by Net Interest Margin, Loan Loss Provision, and Capital Adequacy Ratio and negatively affected by Proportion of Loan to Deposits, Proportion of Loans to Assts and SIZE. There were clear differences between both Islamic and Conventional banks related to all variables of study except Loan Loss Provision and Proportion of Loan to Assets ratios

Fluoroquinolones’ Biological Activities against Laboratory Microbes and Cancer Cell Lines

Development of novel derivatives to rein in and fight bacteria have never been more demanding, as microbial resistance strains are alarmingly increasing. A multitude of new fluoroquinolones derivatives with an improved spectrum of activity and/or enhanced pharmacokinetics parameters have been widely explored. Reporting novel antimicrobial agents entails comparing their potential activity to their parent drugs; hence, parent fluoroquinolones have been used in research as positive controls. Given that these fluoroquinolones possess variable activities according to their generation, it is necessary to include parent compounds and market available antibiotics of the same class when investigating antimicrobial activity. Herein, we provide a detailed guide on the in vitro biological activity of fluoroquinolones based on experimental results published in the last years. This work permits researchers to compare and analyze potential fluoroquinolones as positive control agents and to evaluate changes occurring in their activities. More importantly, the selection of fluoroquinolones as positive controls by medicinal chemists when investigating novel FQs analogs must be correlated to the laboratory pathogen inquest for reliable results