Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked.

OBJECTIVE—Within the context of a large, nationwide outcomes research program in type 2 diabetes, we assess the prevalence of self-reported erectile dysfunction and evaluate its impact on quality of life. RESEARCH DESIGN AND METHODS—The study involved 1,460 patients enrolled by 114 diabetes outpatient clinics and 112 general practitioners. Patients were asked to complete a questionnaire investigating their ability to achieve and maintain an erection. Various aspects of quality of life were also assessed depressive using the following instruments: SF-36 Health Survey, diabetes health distress, psychological adaptation to diabetes, depressive symptoms (CES-D scale), and quality of sexual life. RESULTS—Overall, 34% of the patients reported frequent erectile problems, 24% reported occasional problems, and 42% reported no erectile problems. After adjusting for patient characteristics, erectile dysfunction was associated with higher levels of diabetes-specific health distress and worse psychological adaptation to diabetes, which were, in turn, related to worse metabolic control. Erectile problems were also associated with a dramatic increase in the prevalence of severe depressive symptoms, lower scores in the mental components of the SF-36, and a less satisfactory sexual life. A total of 63% of the patients reported that their physicians had never investigated their sexual problems. CONCLUSIONS—Erectile dysfunction is extremely common among type 2 diabetic patients and is associated with poorer quality of life, as measured with generic and diabetes-specific instruments. Despite their relevance, sexual problems are seldom investigated by general practitioners and specialists

Quality of Care and Outcomes in Type 2 Diabetic Patients A comparison between general practice and diabetes clinics

OBJECTIVE—The role of general practice and diabetes clinics in the management of diabetes is still a matter of debate. Methodological flaws in previous studies may have led to inaccurate conclusions when comparing the care provided in these different settings. We compared the care provided to type 2 diabetic patients attending diabetes outpatient clinics (DOCs) or being treated by a general practitioner (GP) using appropriate statistical methods to adjust for patient case mix and physician-level clustering. RESEARCH DESIGN AND METHODS—We prospectively evaluated the process and intermediate outcome measures over 2 years in a sample of 3,437 patients recruited by 212 physicians with different specialties practicing in 125 DOCs and 103 general practice offices. Process measures included frequency of HbA1c, lipids, microalbuminuria, and serum creatinine measurements and frequency of foot and eye examinations. Outcome measures included HbA1c, blood pressure, and total and LDL cholesterol levels. RESULTS—Differences for most process measures were statistically significantly in favor of DOCs. The differences were more marked for patients who were always treated by the same physician within a DOC and if that physician had a specialty in diabetology. Less consistent differences in process measures were detected when patients followed by GPs were compared with those followed by physicians with a specialty other than diabetology. As for the outcomes considered, patients attending DOCs attained better total cholesterol levels, whereas no major differences emerged in terms of metabolic control and blood pressure levels between DOCs and GPs. Physicians' specialties were not independently related to patient outcomes. CONCLUSIONS—Being followed always by the same physician in a DOC, particularly if the physician had a specialty in diabetes, ensured better quality of care in terms of process measures. In the short term, care provided by DOCs was also associated with better intermediate outcome measures, such as total cholesterol levels

A continuous infusion of a minor histocompatibility antigen-immunodominant peptide induces a delay of male skin graft rejection.

We previously reported that an inhibition of antigen-specific Interferon-gamma release and cytotoxicity occurs after a continuous infusion of an HY immunodominant peptide although this treatment is not able to cause a significant delay of male skin grafts rejection. In vivo administration of high doses of an HY peptide, through mini-osmotic pumps, in naïve female mice was used to study the effects on the male skin grafts rejection. A continuous infusion of 1mg of an HY peptide induces a significant delay of male skin graft rejection. In vitro HY-specific Interferon-gamma release was inhibited adding peptide-specific suppressor cells: the ability to inhibit Interferon-gamma release was evident when two HY peptides were present on the same dendritic cells indicating that the suppressor cells exert "linked-suppression". The phenotype of the suppressor cells is CD8(+)CD28(-) and these cells express more CD62 ligand and FOXP3 than controls. Suppressor cells were able to cause a significant delay of rejection of male skin grafts when injected in naive female mice. The inhibitory effects of these suppressor cells seem to be due to the impairment of antigen presentation; down-regulation of B7 molecules on dendritic cells occurred. Taken all together, our data demonstrate that a continuous infusion of an immunodominant HY peptide induces a T CD8 suppressor subset able to inhibit immune responses to male tissues and cells

Deciphering the genome repertoire of Pseudomonas sp. M1 toward β-Myrcene biotransformation

Pseudomonas sp. M1 is able to mineralize several unusual substrates of natural and xenobiotic origin, contributing to its competence to thrive in different ecological niches. In this work, the genome of M1 strain was resequenced by Illumina MiSeq to refine the quality of a published draft by resolving the majority of repeat-rich regions. In silico genome analysis led to the prediction of metabolic pathways involved in biotransformation of several unusual substrates (e.g., plant-derived volatiles), providing clues on the genomic complement required for such biodegrading/biotransformation functionalities. Pseudomonas sp. M1 exhibits a particular sensory and biotransformation/biocatalysis potential toward β-myrcene, a terpene vastly used in industries worldwide. Therefore, the genomic responsiveness of M1 strain toward β-myrcene was investigated, using an RNA sequencing approach. M1 cells challenged with β-myrcene(compared with cells grown in lactate) undergo an extensive alteration of the transcriptome expression profile, including 1,873 genes evidencing at least 1.5-fold of altered expression (627 upregulated and 1,246 downregulated), toward β-myrcene-imposed molecular adaptation and cellular specialization. A thorough data analysis identified a novel 28-kb genomic island, whose expression was strongly stimulated in β-myrcene-supplemented medium, that is essential for β-myrcene catabolism. This island includes β-myrcene-induced genes whose products are putatively involved in 1) substrate sensing, 2) gene expression regulation, and 3) β-myrcene oxidation and bioconversion of β-myrcene derivatives into central metabolism intermediates. In general, this locus does not show high homology with sequences available in databases and seems to have evolved through the assembly of several functional blocks acquired from different bacteria, probably, at different evolutionary stages.Acknowledgments This work was supported by FEDER through POFC— COMPETE and by national funds from Foundation for Science and Technology (Portugal) through the projects PEst-C/BIA/UI4050/2011, PTDC/EBB-BIO/104980/2008 and PTDC/BIA-MIC/113733/09, and through a PhD grant (grant number SFRH/BD/76894/2011) to P.S.-C.info:eu-repo/semantics/publishedVersio

Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study

OBJECTIVES: VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses. METHODS: A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients). RESULTS: In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)\u2089\u2085(%) 0.51-0.74; intention to treat (ITT) P=0.031, CI\u2089\u2085(%) 0.47-0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4%; PP P=0.017, CI\u2089\u2085(%) 0.51-0.74; ITT P=0.046, CI\u2089\u2085(%) 0.47-0.69) and in rectal bleeding (PP P=0.014, CI\u2089\u2085(%) 0.46-0.70; ITT P=0.036, CI\u2089\u2085(%) 0.41-0.65), whereas stool frequency (PP P=0.202, CI\u2089\u2085(%) 0.39-0.63; ITT P=0.229, CI\u2089\u2085(%) 0.35-0.57), physician's rate of disease activity (PP P=0.088, CI\u2089\u2085(%) 0.34-0.58; ITT P=0.168, CI\u2089\u2085(%) 0.31-0.53), and endoscopic scores (PP P=0.086, CI\u2089\u2085(%) 0.74-0.92; ITT P=0.366, CI\u2089\u2085(%) 0.66-0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4%; PP P=0.069, CI\u2089\u2085(%) 0.36-0.60; ITT P=0.132, CI\u2089\u2085(%) 0.33-0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects. CONCLUSIONS: VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance

Electrically Induced Mixed Valence Increases the Conductivity of Copper Helical Metallopolymers

Abstract: Controlling the flow of electrical current at the nanoscale typically requires complex top‐down approaches. Here, a bottom‐up approach is employed to demonstrate resistive switching within molecular wires that consist of double‐helical metallopolymers and are constructed by self‐assembly. When the material is exposed to an electric field, it is determined that ≈25% of the copper atoms oxidize from CuI to CuII, without rupture of the polymer chain. The ability to sustain such a high level of oxidation is unprecedented in a copper‐based molecule: it is made possible here by the double helix compressing in order to satisfy the new coordination geometry required by CuII. This mixed‐valence structure exhibits a 104‐fold increase in conductivity, which is projected to last on the order of years. The increase in conductivity is explained as being promoted by the creation, upon oxidation, of partly filled d z 2 orbitals aligned along the mixed‐valence copper array; the long‐lasting nature of the change in conductivity is due to the structural rearrangement of the double‐helix, which poses an energetic barrier to re‐reduction. This work establishes helical metallopolymers as a new platform for controlling currents at the nanoscale

Underwater Application of Quantitative PCR on an Ocean Mooring

The Environmental Sample Processor (ESP) is a device that allows for the underwater, autonomous application of DNA and protein probe array technologies as a means to remotely identify and quantify, in situ, marine microorganisms and substances they produce. Here, we added functionality to the ESP through the development and incorporation of a module capable of solid-phase nucleic acid extraction and quantitative PCR (qPCR). Samples collected by the instrument were homogenized in a chaotropic buffer compatible with direct detection of ribosomal RNA (rRNA) and nucleic acid purification. From a single sample, both an rRNA community profile and select gene abundances were ascertained. To illustrate this functionality, we focused on bacterioplankton commonly found along the central coast of California and that are known to vary in accordance with different oceanic conditions. DNA probe arrays targeting rRNA revealed the presence of 16S rRNA indicative of marine crenarchaea, SAR11 and marine cyanobacteria; in parallel, qPCR was used to detect 16S rRNA genes from the former two groups and the large subunit RuBisCo gene (rbcL) from Synecchococcus. The PCR-enabled ESP was deployed on a coastal mooring in Monterey Bay for 28 days during the spring-summer upwelling season. The distributions of the targeted bacterioplankon groups were as expected, with the exception of an increase in abundance of marine crenarchaea in anomalous nitrate-rich, low-salinity waters. The unexpected co-occurrence demonstrated the utility of the ESP in detecting novel events relative to previously described distributions of particular bacterioplankton groups. The ESP can easily be configured to detect and enumerate genes and gene products from a wide range of organisms. This study demonstrated for the first time that gene abundances could be assessed autonomously, underwater in near real-time and referenced against prevailing chemical, physical and bulk biological conditions

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Proteome changes driven by phosphorus deficiency and recovery in the brown tide-forming alga Aureococcus anophagefferens

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e28949, doi:10.1371/journal.pone.0028949.Shotgun mass spectrometry was used to detect proteins in the harmful alga, Aureococcus anophagefferens, and monitor their relative abundance across nutrient replete (control), phosphate-deficient (−P) and −P refed with phosphate (P-refed) conditions. Spectral counting techniques identified differentially abundant proteins and demonstrated that under phosphate deficiency, A. anophagefferens increases proteins involved in both inorganic and organic phosphorus (P) scavenging, including a phosphate transporter, 5′-nucleotidase, and alkaline phosphatase. Additionally, an increase in abundance of a sulfolipid biosynthesis protein was detected in −P and P-refed conditions. Analysis of the polar membrane lipids showed that cellular concentrations of the sulfolipid sulphoquinovosyldiacylglycerol (SQDG) were nearly two-fold greater in the −P condition versus the control condition, while cellular phospholipids were approximately 8-fold less. Transcript and protein abundances were more tightly coupled for gene products involved in P metabolism compared to those involved in a range of other metabolic functions. Comparison of protein abundances between the −P and P-refed conditions identified differences in the timing of protein degradation and turnover. This suggests that culture studies examining nutrient starvation responses will be valuable in interpreting protein abundance patterns for cellular nutritional status and history in metaproteomic datasets.Research for this work was supported by a National Oceanic and Atmospheric Administration ECOHAB grant (#NA09NOS4780206) and National Science Foundation grant (#OCE-0723667) and a STAR Research Assistance Agreement No. R-83041501-0 awarded by the U.S. Environmental Protection Agency. Further support came from the Woods Hole Coastal Ocean Institute. LLW was supported by a Environmental Protection Agency STAR Fellowship (#FP916901). EMB was supported by a National Science Foundation (NSF) Graduate Research Fellowship (#2007037200) and an Environmental Protection Agency STAR Fellowship (#F6E20324)

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal