Russian intervention in Syria : exploring the nexus between regime consolidation and energy transnationalisation

Interpretations of Russia’s military intervention in Syria overwhelmingly focus on Russia’s political motivations. An alternative view foregrounds Russia’s economic motivations, namely, the construction of a multi-billion-dollar gas pipeline traversing Iran, Iraq and Syria. This article examines the salience of Russia’s economic motivations and considers two related aspects: First, if Russian intervention aims to secure areas of strategic importance for the proposed pipeline. Second, if Russian intervention realises longer term political and commercial interests that include proposed future pipeline projects. The evidence suggests Russian military policies towards Syria are unlikely to be motivated primarily by the prospect of a proposed gas pipeline, but that regime consolidation is a more immediate policy goal. This article then posits that Russian intervention has a distinct ‘dual logic’ aimed at integrating the interests of key regional actors into a transnational energy network, while stabilising Russia’s regional dominance within this network

Validity and reliability of the session RPE method for monitoring exercise training intensity

Objective. The Session Rating of Perceived Extertion (RPE) is a method of measuring exercise intensity that may be useful for the quantitative assessment of exercise training programmes. However, there are inadequate data regarding the validity and reliability of the Session RPE method. This study was designed to evaluate both the validity and reliability of the Session RPE method in comparison to objective measures (%HRpeak, %HRreserve and %VO2peak) of exercise intensity. Methods. Fourteen healthy volunteers (7 male, 7 female) performed 6 randomly ordered 30-minute constant-load exercise bouts at 3 different intensities, with each intensity being repeated. Oxygen consumption (VO2) and heart rate (HR) were measured throughout each exercise bout and normalised to maximal values obtained during a preliminary maximal exercise test. Thirty minutes following the conclusion of each exercise bout, the subject rated the global intensity of the bout using a modification of the Category Ratio (CR) (0 - 10) RPE scale. This rating was compared to the mean value of objectively measured exercise intensity across the duration of the bout. Results. There were significant non-linear relationships between Session RPE and %VO2peak (R2 = 0.76), %HRpeak (R2 = 0.74) and %HRreserve (R2 = 0.71). There were no significant differences between test and retest values of %VO2peak, %HRpeak, %HRreserve and Session RPE during the easy (47 v. 47%, 65 v. 66%, 47 v. 48% and 2.0 v. 1.9), moderate (69 v. 70%, 83 v. 84%, 74 v. 75%, and 4.2 v. 4.3) and hard (81 v. 81%, 94 v. 94%, 91 v. 91% and 7.3 v. 7.4) exercise bouts. Correlations between repeated bouts for %VO2peak (r = 0.98), %HRpeak (r = 0.98), %HRreserve (r = 0.98) and Session RPE (r = 0.88) were significant and strong. Conclusions. The results support the validity and reliability of the Session RPE method of monitoring exercise intensity, although as might be predicted for a subjective method the Session RPE was less precise than the objective measures of exercise training intensity. South African Journal of Sports Medicine Vol. 18 (1) 2006: pp. 14-1

Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis

Structural effects of clinically observed mutations in JAK2 exons 13-15: comparison with V617F and exon 12 mutations

<p>Abstract</p> <p>Background</p> <p>The functional relevance of many of the recently detected JAK2 mutations, except V617F and exon 12 mutants, in patients with chronic myeloproliferative neoplasia (MPN) has been significantly overlooked. To explore atomic-level explanations of the possible mutational effects from those overlooked mutants, we performed a set of molecular dynamics simulations on clinically observed mutants, including newly discovered mutations (K539L, R564L, L579F, H587N, S591L, H606Q, V617I, V617F, C618R, L624P, whole exon 14-deletion) and control mutants (V617C, V617Y, K603Q/N667K).</p> <p>Results</p> <p>Simulation results are consistent with all currently available clinical/experimental evidence. The simulation-derived putative interface, not possibly obtained from static models, between the kinase (JH1) and pseudokinase (JH2) domains of JAK2 provides a platform able to explain the mutational effect for all mutants, including presumably benign control mutants, at the atomic level.</p> <p>Conclusion</p> <p>The results and analysis provide structural bases for mutational mechanisms of JAK2, may advance the understanding of JAK2 auto-regulation, and have the potential to lead to therapeutic approaches. Together with recent mutation profiling results demonstrating the breadth of clinically observed JAK2 mutations, our findings suggest that molecular testing/diagnostics of JAK2 should extend beyond V617F and exon 12 mutations, and perhaps should encompass most of the pseudo-kinase domain-coding region.</p

Multiple molecular markers MAGE-1, MAGE-3 and AFP mRNAs expression nested PCR assay for sensitive and specific detection of circulating hepatoma cells: Enhanced detection of hepatocellular carcinoma

Hepatocellular Carcinoma is a multifactorial, multistep and complex process. Its prognosis is poor and early diagnosis and monitoring of metastasis of HCC is of utmost importance. Circulating alpha-fetoprotien mRNA has been proposed as a marker of HCC cells disseminatedinto the circulation but the specificity of this molecular marker and its correlation with the main HCC clinico-pathological parameters remain controversial. In recent years; several different multi-marker assays have been developed for the detection of hepatoma cells in the peripheral bloodof patients with HCC. In this study 58 patients and 15 matched healthy volunteers were included; the patients were divided into three groups; group A: patients with primary HCC (n =32), group B: patients withcirrhosis with no evidence of HCC (n= 12), group C: patients with metastatic cancer in liver (n= 14). Group D: 15 healthy volunteers age and sex matched. The staging of HCC was carried out according to the Tumor/Node/Metastasis (TNM) classification. Peripheral blood samples were obtained from all subjects; MAGE-1 and MAGE-3 and AFP mRNAs were detected by nested RT-PCR. The positive rates of MAGE-1, MAGE-3 and AFP mRNAs were 18/32 (56.3%), 15/32 (46.9%) and 19/32 (59.4%) respectively in the primary HCC patients. In the cirrhotic group only 4/12 (33.3%) patients were positive for AFP mRNA, whereas in the metastatic group 5/14 (35.7%) and 4/14 (28.6%) were positive to MAGE-1 and MAGE-3 mRNAs respectively. MAGE-1 and MAGE-3 mRNAs were correlated with TNM clinical stages; tumor number and tumor size (p&lt;0.05).Our results indicate that a multi-marker nested RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a hepatocyte-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients. Nested PCR exhibits highersensitivity, stronger specificity and lower false-positive occurrence as compared to single RT

Formulation and in-vitro evaluation of fast dissolving tablets containing a poorly soluble antipsychotic drug

The aim of the present study was to formulate olanzapine fast dissolving tablets (FDT). Olanzapine is a poorly water soluble drug that undergoes first pass metabolism in liver resulted in low oral bioavailability. The water solubility is enhanced by formation of co-amorphous dispersion by solvent evaporation under vacuum method using a polycarboxylic acid (ascorbic acid) as a coformer in two different molar ratios (1:1 and 1:2). The prepared systems were evaluated using differential scanning calorimeter (DSC), Fourier Transform Infra-Red analysis (FTIR), X-ray powder diffraction (XRPD), Scanning electron microscopy (SEM) and saturated solubility. The co-amorphous dispersion system in a molar ratio 1:2 is higher in solubility than 1:1, so it was selected for incorporation into FDT formulation. Compatability study between olanzapine and different tablet excipients including DSC and FTIR showed that the drug is compatible with the selected tablet excipients. Direct compression method was used in FDT formulations using different types and concentrations of superdisintegrants. FDTs were evaluated for weight variation, hardness, friability, wetting time, drug content uniformity, invitro disintegration time and invitro dissolution study. All the prepared FDTs were complied with the compendia standards. F3 and F8 showed lower disintegration time and higher percent of drug dissolved, so they were selected for stability study. After storage for 3 months at 30ºC at 65% relative humidity, both formulations were physically stable regarding color and integrity and had only minor increases in disintegration time, drug content and friability after three months’ storage. The results indicate that olanzapine FDT tablets may serve as a successful strategy for enhancing the bioavailability of olanzapine

Reasons for not Using HIV Pre-Exposure Prophylaxis (PrEP) among Gay and Bisexual Men in Australia: Mixed-Methods Analyses from a National, Online, Observational Study

Although approximately 31,000 Australian gay and bisexual men (GBM) are eligible for HIV pre-exposure prophylaxis (PrEP), only 18,500 people currently use it, indicating a need to investigate why GBM do not use it. This article uses data from a national, online, observational study. It adopts a mixed-methods analysis to responses to survey questions asking about reasons Australian GBM were not using PrEP in 2018, according to their level of HIV risk as delineated by the Australian PrEP prescribing guidelines at the time. Participants responded to check-box questions and had the option to respond to a qualitative free-text question. Results showed that just over one-fifth of men were at higher risk of HIV acquisition. Compared to lower-risk men, higher-risk men were more likely to indicate PrEP was too expensive and more likely to cite embarrassment asking for it. Reasons for not using PrEP included a lack of personal relevance, poor accessibility or knowledge, concerns about PrEP’s inability to protect against STIs, potential side effects, and a preference for condoms. We conclude that health promotion more effectively targeting GBM who may benefit the most from PrEP may be valuable

Time Under the Curve: Assessing the Impact of Regional Lead Treatment Center Home Visit on the Length of Exposure in Lead Poisoned Children

A high proportion of Connecticut residents are at risk of health effects due to lead exposure, especially children under the age of six. The Yale Regional Lead Treatment Center (YRLTC) assists families of children with blood lead levels (BLL) exceeding the Centers for Disease Control and Prevention (CDC) maximum BLL of 5 µg/dL. YRLTC incorporates home visits of lead-exposed children living in Southern Connecticut to mitigate lead poisoning by emphasizing public health initiatives and social work, rather than using a clinic-only approach. This project aimed to evaluate the merits of this new interdisciplinary approach and its tangible effects on health outcomes. Key informant interviews provided perspectives on the value and themes of home visits. Questions focused on physiological measures of lead poisoning and cognitive development, patient interactions during home visits as well as legal, and logistical challenges to lead abatement. The team also shadowed home visits in order to understand the intervention.https://elischolar.library.yale.edu/ysph_pbchrr/1029/thumbnail.jp