Safety and efficacy of fixed-dose combination rilpivirine-tenofovir-emtricitabine (RPV/TDF/FTC) in treatment-experienced patients infected with HIV-1

Purpose of the study: Rilpivirine (RPV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non-inferiority to efavirenz (EFV) in terms of efficacy and safety profiles. The vast majority of clinical data has been performed in the treatment naïve population and has not been studied in depth in treatment-experienced patients. We sought to explore the safety and efficacy of RPV/TDF/FTC in treatment-experienced patients attending our clinics. Methods: HIV-infected individuals commenced on RPV/TDF/FTC from December 2011 to June 2012 were retrospectively identified from a patient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated. At baseline, 1 month and 3 month time points the following laboratory results were compared using the Kruskal-Wallis test: CD4 count, HIV viral load, amino transferase (ALT), cholesterol, triglyceride and HDL/cholesterol ratio. Summary of results: Sixty-five patients (4 female) were identified. Median age was 38 years (range: 25–73). Fifty-six patients were treatment experienced (2 re-start); 39 on NNRTI-based (33 on EFV), 10 on PI-based and 4 on other regimens. 9 patients were naïve to treatment. The reasons for switch are illustrated in Fig. 1. Fifty-four patients had HIV-RNA-1<40 copies/mL at the time of switch and all remained undetectable at 3 months. At baseline, the median CD4 count was 555 cells/mm3 (range: 209–1586) in the switch group, which increased significantly to 638 cells/mm3 (p<0.005) 3 months after switch. Switch to RPV/TDF/FTC had a favorable effect on lipid profile. At baseline the median cholesterol, triglyceride and HDL/cholesterol ratio levels were 4.8 mmol/L, 1.78 mmol/L and 4.37 respectively. At 1 month post-switch this decreased to 4.5 mmol/L, 1.65 mmol/L and 4.24 and at 3 months post-switch decreased to 4.1 mmol/L, 1.44 mmol/L and 4.04. Median HIV-RNA-1 in treatment-naïve patients (n=9) at baseline was 50298 copies/mL, at 1 month four patients had HIV-RNA-1<40 copies/mL and at 3 months eight patients had HIV-RNA-1<40 copies/mL. RPV/TDF/FTC had no favourable effect on lipid profile in treatment-naïve group and had no effect on ALT levels in either the switch or the treatment-naïve group. Conclusion: In this cohort, RPV/TDF/FTC has been shown to have a safe virological efficacy and safety profile as a switch therapy for patients suppressed on their current standard of care and are experiencing adverse events

Optimal motion control and vibration suppression of flexible systems with inaccessible outputs

This work addresses the optimal control problem of dynamical systems with inaccessible outputs. A case in which dynamical system outputs cannot be measured or inaccessible. This contradicts with the nature of the optimal controllers which can be considered without any loss of generality as state feedback control laws for systems with linear dynamics. Therefore, this work attempts to estimate dynamical system states through a novel state observer that does not require injecting the dynamical system outputs onto the observer structure during its design. A linear quadratic optimal control law is then realized based on the estimated states which allows controlling motion along with active vibration suppression of this class of dynamical systems with inaccessible outputs. Validity of the proposed control framework is evaluated experimentally

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Long-term treadmill exercise upregulated hippocampal learning-related genes without improving cognitive behaviour in socially isolated rats

Background: Some environment enrichments such as exercise has been reported to improve the diminished cognitive functions and related gene expression. Therefore, we aimed to investigate the effects of prolonged treadmill exercise on long-term learning and hippocampal gene expression, which involves learning and plasticity. Materials and methods: Male Wistar rats (n = 32) randomly assigned into four groups: control (C), social isolation (SI), exercised (E), social isolation + exercise (SE) during postnatal days (PNDs) 21–34. Social isolation protocol was applied during 14 days by placing the rat alone in a cage. Rats were exercised daily, 5 days per week, for overall 4 weeks. Finally, learning performance was evaluated by the novel object recognition test. At the end of learning test, the rats were decapitated to isolate hippocampus tissues for learning related gene expression such as N-methyl-d-aspartate receptor (NMDAR) subunit genes (Grin1, Grin2a, Grin2b) and cyclin dependent kinase 5 (Cdk5), Cdk5 regulatory subunit p35 (Cdk5r), activity-regulated, cytoskeletal-associated protein (Arc), the immediate early gene (c-Fos, a marker of neuronal activation), doublecortin (DCX), achaetescute homolog 1 (ASCL1), brain-derived neurotrophic factor (BDNF) by real-time polymerase chain reaction (RT-PCR). Results: Grin1, NMDAR subunit gene expression was increased significantly in E group compared to other groups. Grin2b, NMDAR subunit gene expression was increased in E group compared to the SI group. Cdk5 level increased in E group compared to the SE group. The ASCL1 gene expression increased in E group compare to the SE group. The DCX gene expression increasing in C group compared to SI and SE groups. Conclusions: Taken together these findings may point out that long-term social isolation down-regulated learning-related genes. However, treadmill exercise together with social isolation did not restore this down-regulation although treadmill exercise increased learning-related genes without improving cognitive behaviour

Soft power and exchange rate volatility

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordStandard models—based exclusively on macro-financial variables—have made little progress in explaining the behaviour of exchange rates. In this paper, we introduce a neglected set of ‘soft power’ factors capturing a country's demographic, institutional, political, and social underpinnings to shed some light on the ‘missing’ determinants of exchange rate volatility over time and across countries. Based on a balanced panel dataset comprising 115 countries during the period 1996–2015, the empirical results are generally robust across different estimation methodologies and show a high degree of persistence in exchange rate volatility. After controlling for standard macroeconomic factors, we find that the ‘soft power’ variables—such as an index of voice and accountability, life expectancy, educational attainments, fragility of the banking sector, financial openness, and the share of agriculture relative to services—have a statistically significant influence on the level of exchange rate volatility across countries. In other words, countries with greater ‘soft power’ (i.e. better institutional quality) tend to experience a lower degree of exchange rate volatility

How scientists and physicians use Twitter during a medical congress

OBJECTIVES: During medical congresses Twitter allows discussions to disseminate beyond the congress hall and reach a wider audience. Insights into the dynamics of social media interactions during congresses, dissemination of scientific information and the determinants of a successful tweet may allow us to better understand social media's role in science communication. METHODS: We retrospectively extracted social media data during the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017 and 2018 using NodeXL. We compared social media activity during these two congresses. Subsequently, we conducted in-depth analyses to identify the components of a successful tweet and multivariable analysis to assess independent factors associated with retweet activity. RESULTS: In 2018, approximately 13,000 delegates attended ECCMID, but only 591 Twitter accounts actively tweeted about the congress. Although fewer tweets were posted in 2018 compared to 2017 (4,213 vs 4,657, respectively), ECCMID2018 generated a 63% increase in the total number of retweets (p <0.001). According to multivariable logistic regression analysis, using multimedia, URL or hashtags and mentioning other Twitter account(s) were independently associated with retweet success. Mentioning of other users and use of multimedia were the only consistent predictors of retweets irrespective of the number of followers. CONCLUSIONS: A substantial increase in retweet activity and a modest increase in the number of influential Twitter accounts were observed between two successive congresses. Dissemination of scientific messages is more successful when connected accounts are actively involved in social media activity, and social media posts constitute the right combination of components.PostprintPeer reviewe

Understanding TERT promoter mutations: a common path to immortality

Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients.Support was provided from a generous gift from the Dabbiere family(RJB,AM,JFC), the Hana Jabsheh Research Initiative (RJB,AM,JFC), and NIH grants NCI P50CA097257 (RJB,AM,JFC), P01CA118816-06 (RJB,AM,JFC), R01HG003008 (HTR), and R01CA163336 (JSS). Additional support was provided from the Sontag Foundation Distinguished Scientist Award (JSS), Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (AXM), IF/00601/2012 (BMC), Programa Operacional Regional do Norte (ON.2—O Novo Norte) (BMC), Quadro de Referência Estratégico Nacional (BMC), and Fundo Europeu de Desenvolvimento Regional (BMC).info:eu-repo/semantics/publishedVersio

Leek yellow stripe virus newly reported in Turkey

[Anstract Not Available

Effect of harvest time on physicochemical quality parameters, oxidation stability, and volatile compounds of extra virgin olive oil

The aim of this study was to determine the changes in some physicochemical properties of olives (fruit weight, water content and oil content) and olive oils (total chlorophyll, carotenoid, pheophytin a, peroxide value and free acidity), and in the chemical properties (fatty acids, tocopherols, phenolics, oxidation stability and volatile profiles) of oils during ripening.Ripening indices (RI) of olive samples were 1.93 (unripe), 4.28 (ripe) and 5.89 (overripe). Most of the mentioned features changed with ripening. During ripening there was a sharp decrease in total chlorophyll, carotenoid and pheophytin a contents. An increase in oleic and linoleic acids and a decrease in palmitic acid were found in the fatty acid composition. Olive oils showed strong relations among oxidation stability, tocopherol content, total phenols content, and antiradical actvity of phenol extracts and these parameters decreased with maturation. Nevertheless, higher amounts of trans-2-hexenal were found in the oil from ripe olives than from unripe and overripe olives. On the other hand, the highest concentration of hexanal was found in the oil from overripe olives.In general, significant differences were observed in fruit weight, pigments, free acidity, fatty acid, tocopherol, and total phenolics contents, radical scavenger activity, oxidation stability, phenolic profile and volatile profile between the olive oils from the Gemlik cultivar at different stages of maturation