Holocene paleoecology and paleoceanography of the southwestern Black Sea shelf revealed by ostracod assemblages

The Holocene replacement of Ponto-Caspian ostracod assemblages by Mediterranean species is studied in two long composite cores, M02-45 (a composite of cores M02-45P, M02-45 T and M05-03P) and M05-50 (a composite of cores M05-50P and M05-51G), acquired at sites −69 m and −91 m deep on the southwestern Black Sea shelf. Composite core M02-45 was collected from the middle shelf and composite core M05-50 was acquired on the distal fringe of the eastern levée of a saline underflow channel emanating from the Strait of Bosphorus. Sixteen radiocarbon dates in M02-45 and nine in M05-50 are used to construct age models, which show recovery of sediments as old as 12,915 cal yr BP (M02-45 site) and 12,010 cal yr BP (M05-50 site). A total of 45 ostracod species are identified in the two cores. From ~12,000 to ~7425 cal yr BP, the ostracod assemblage is dominated by Ponto-Caspian species, mainly Loxoconcha sublepida, L. lepida and Tyrrhenocythere amnicola donetziensis. From ~7425 to ~6315 cal yr BP the assemblage consists of nearly equal abundances of Mediterranean species (Cytheroma variabilis in M02-45; Sagmatocythere littoralis in M05-50) and the Ponto-Caspian species. After ~6315 cal yr BP to the tops of the cores, the assemblage is dominated by Mediterranean species, including Palmoconcha agilis, Carinocythereis carinata, Hiltermannicythere rubra and Pterygocythereis jonesii. Cluster analysis further subdivides the stratigraphic succession into six bioecozones with different ostracod assemblages. The changes in the ostracod assemblages from one bioecozone to the next indicate that progressive environmental changes took place on the southwestern Black Sea shelf from at least 7500 cal yr BP to the present. The first hint of changing conditions at ~7500 cal yr BP lags the initial reconnection to the Mediterranean Sea through the Strait of Bosphorus by ~2000 yr, demonstrating that Black Sea salinity increased slowly and took that long to reach values tolerable to marine ostracod immigrants. Widespread colonization by Mediterranean species took even longer, ~3000 years from the time of the initial reconnection

Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia

The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA

Plasmodium vivax but not Plasmodium falciparum blood-stage infection in humans is associated with the expansion of a CD8+ T cell population with cytotoxic potential

P. vivax and P. falciparum parasites display different tropism for host cells and induce very different clinical symptoms and pathology, suggesting that the immune responses required for protection may differ between these two species. However, no study has qualitatively compared the immune responses to P. falciparum or P. vivax in humans following primary exposure and infection. Here, we show that the two species differ in terms of the cellular immune responses elicited following primary infection. Specifically, P. vivax induced the expansion of a subset of CD8+ T cells expressing the activation marker CD38, whereas P. falciparum induced the expansion of CD38+ CD4+ T cells. The CD38+ CD8+ T cell population that expanded following P. vivax infection displayed greater cytotoxic potential compared to CD38- CD8+ T cells, and compared to CD38+ CD8+ T cells circulating during P. falciparum infection. We hypothesize that P. vivax infection leads to a stronger CD38+ CD8+ T cell activation because of its preferred tropism for MHC-I-expressing reticulocytes that, unlike mature red blood cells, can present antigen directly to CD8+ T cells. This study provides the first line of evidence to suggest an effector role for CD8+ T cells in P. vivax blood-stage immunity. It is also the first report of species-specific differences in the subset of T cells that are expanded following primary Plasmodium infection, suggesting that malaria vaccine development may require optimization according to the target parasite

The global distribution of the Duffy blood group

Blood group variants are characteristic of population groups, and can show conspicuous geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*BES variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite

Vancomycin Heteroresistance Is Associated with Reduced Mortality in ST239 Methicillin-Resistant Staphylococcus aureus Blood Stream Infections

Background: Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI)

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care.</p> <p>Methods/Design</p> <p>This is a multicentre parallel arm block randomized controlled trial (RCT) of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change.</p> <p>Discussion</p> <p>The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent variables allows us to assess the broader impact on the intervention including both hard end points as well as patient reported outcomes. This program, if found to be effective, has the potential to be implemented within the existing renal services delivery model in Singapore, particularly as this is being delivered by health care professionals already working with hemodialysis patients in these settings who are specifically trained in facilitating self management in renal patients.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRTN31434033">ISRTN31434033</a></p

Fluorescence-Tracking of Activation Gating in Human ERG Channels Reveals Rapid S4 Movement and Slow Pore Opening

Background: hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening. Methods and Findings: Tetramethylrhodamine-5-maleimide (TMRM) fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449) in the S1–S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the VK of activation to 227.562.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1–S2 linker cysteines with valines allowed unobstructed recording of S3–S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-VON, with VK,1 = 237.861.7 mV, and VK,2 = 43.567.9 mV. The first phase, VK,1, was,20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-VK = 218.361.2 mV), and relatively unchanged in a non-inactivating E519C:S620T mutant (V K = 234.461.5 mV), suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarizatio

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

Effects of Terrestrial Buffer Zones on Amphibians on Golf Courses

A major cause of amphibian declines worldwide is habitat destruction or alteration. Public green spaces, such as golf courses and parks, could serve as safe havens to curb the effects of habitat loss if managed in ways to bolster local amphibian communities. We reared larval Blanchard's cricket frogs (Acris blanchardi) and green frogs (Rana clamitans) in golf course ponds with and without 1 m terrestrial buffer zones, and released marked cricket frog metamorphs at the golf course ponds they were reared in. Larval survival of both species was affected by the presence of a buffer zone, with increased survival for cricket frogs and decreased survival for green frogs when reared in ponds with buffer zones. No marked cricket frog juveniles were recovered at any golf course pond in the following year, suggesting that most animals died or migrated. In a separate study, we released cricket frogs in a terrestrial pen and allowed them to choose between mown and unmown grass. Cricket frogs had a greater probability of using unmown versus mown grass. Our results suggest that incorporating buffer zones around ponds can offer suitable habitat for some amphibian species and can improve the quality of the aquatic environment for some sensitive local amphibians