Spatial variability of precipitation regimes over Turkey

Turkish annual precipitation regimes are analysed to provide large-scale perspective and redefine precipitation regions. Monthly total precipitation data are employed for 107 stations (1963–2002). Precipitation regime shape (seasonality) and magnitude (size) are classified using a novel multivariate methodology. Six shape and five magnitude classes are identified, which exhibit clear spatial structure. A composite (shape and magnitude) regime classification reveals dominant controls on spatial variability of precipitation. Intra-annual timing and magnitude of precipitation is highly variable due to seasonal shifts in Polar and Subtropical zones and physiographic factors. Nonetheless, the classification methodology is shown to be a powerful tool that identifies physically-interpretable precipitation regions: (1) coastal regimes for Marmara, coastal Aegean, Mediterranean and Black Sea; (2) transitional regimes in continental Aegean and Southeast Anatolia; and (3) inland regimes across central and Eastern Anatolia. This research has practical implications for understanding water resources, which are under ever growing pressure in Turkey

Efficacy of tadalafil in Egyptian and Turkish men with erectile dysfunction

A randomised, double-blind, parallel, placebo-controlled, 12-week study was carried out to evaluate the efficacy and safety of 20-mg tadalafil taken ‘as needed’ in a population of men with erectile dysfunction (ED) from Egypt and Turkey. One hundred and thirty-two patients were randomised in this study. Tadalafil was superior to placebo on all three co-primary efficacy end points. The mean change from baseline for the erectile function domain of the International Index of Erectile Function was 9.3 ± 0.8 for the tadalafil group and 2.3 ± 1.6 for the placebo group. Tadalafil-treated patients reported a significantly greater improvement in the mean percentage of successful penetrations (tadalafil: 34.5 ± 4.1; placebo: −4.6 ± 8.1) and successful intercourse attempts (tadalafil: 52.2 ± 3.8; placebo: 16.8 ± 7.8) than placebo-treated patients as measured by the Sexual Encounter Profile. Tadalafil was generally well tolerated with 82% of adverse events being mild in severity. Tadalafil 20-mg taken ‘as needed’ significantly improved the erectile function in Egyptian and Turkish men with ED

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4

Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Panel

The authors acknowledge the participants for their cooperation Conflict of Interest: None of the authors declare any interest. Formatting of funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin

Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism : A systematic review by the EAU Sexual and Reproductive Health Guidelines panel

Peer reviewedPostprin

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD- 2457 (Community of Madrid to JAH and FG).Peer Reviewe

Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans