Relationships of Basal Level of Serum 17-Hydroxyprogesterone with that of Serum Androstenedione and Their Stimulated Responses to a Low Dose of ACTH in Young Adult Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

A single measurement of serum 17α-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R2 = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Inhibition of N1-Src kinase by a specific SH3 peptide ligand reveals a role for N1-Src in neurite elongation by L1-CAM

In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells. In cultured neurons, PDN1 fused to a fluorescent protein inhibited neurite outgrowth, an effect that was mimicked by shRNA targeting the N1-Src microexon. PDN1 also inhibited L1-CAM-dependent neurite elongation in cerebellar granule neurons, a pathway previously shown to be disrupted in Src(−/−) mice. PDN1 therefore represents a novel tool for distinguishing the functions of N1-Src and C-Src in neurons and is a starting point for the development of a small molecule inhibitor of N1-Src

The Fitness Cost of Antibiotic Resistance in Streptococcus pneumoniae: Insight from the Field

Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates.We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone.Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2- dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods: Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤ 300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results: 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (Azm(R)) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (Azm(R) 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of Azm(R) and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008

Evidence for Female-Biased Dispersal in the Protandrous Hermaphroditic Asian Seabass, Lates calcarifer

Movement of individuals influences individual reproductive success, fitness, genetic diversity and relationships among individuals within populations and gene exchange among populations. Competition between males or females for mating opportunities and/or local resources predicts a female bias in taxa with monogamous mating systems and a male-biased dispersal in polygynous species. In birds and mammals, the patterns of dispersal between sexes are well explored, while dispersal patterns in protandrous hermaphroditic fish species have not been studied. We collected 549 adult individuals of Asian seabass (Lates calcarifer) from four locations in the South China Sea. To assess the difference in patterns of dispersal between sexes, we genotyped all individuals with 18 microsatellites. Significant genetic differentiation was detected among and within sampling locations. The parameters of population structure (FST), relatedness (r) and the mean assignment index (mAIC), in combination with data on tagging-recapture, supplied strong evidences for female-biased dispersal in the Asian seabass. This result contradicts our initial hypothesis of no sex difference in dispersal. We suggest that inbreeding avoidance of females, female mate choice under the condition of low mate competition among males, and male resource competition create a female-biased dispersal. The bigger body size of females may be a cause of the female-biased movement. Studies of dispersal using data from DNA markers and tagging-recapture in hermaphroditic fish species could enhance our understanding of patterns of dispersal in fish

A reporting format for leaf-level gas exchange data and metadata

Leaf-level gas exchange data support the mechanistic understanding of plant fluxes of carbon and water. These fluxes inform our understanding of ecosystem function, are an important constraint on parameterization of terrestrial biosphere models, are necessary to understand the response of plants to global environmental change, and are integral to efforts to improve crop production. Collection of these data using gas analyzers can be both technically challenging and time consuming, and individual studies generally focus on a small range of species, restricted time periods, or limited geographic regions. The high value of these data is exemplified by the many publications that reuse and synthesize gas exchange data, however the lack of metadata and data reporting conventions make full and efficient use of these data difficult. Here we propose a reporting format for leaf-level gas exchange data and metadata to provide guidance to data contributors on how to store data in repositories to maximize their discoverability, facilitate their efficient reuse, and add value to individual datasets. For data users, the reporting format will better allow data repositories to optimize data search and extraction, and more readily integrate similar data into harmonized synthesis products. The reporting format specifies data table variable naming and unit conventions, as well as metadata characterizing experimental conditions and protocols. For common data types that were the focus of this initial version of the reporting format, i.e., survey measurements, dark respiration, carbon dioxide and light response curves, and parameters derived from those measurements, we took a further step of defining required additional data and metadata that would maximize the potential reuse of those data types. To aid data contributors and the development of data ingest tools by data repositories we provided a translation table comparing the outputs of common gas exchange instruments. Extensive consultation with data collectors, data users, instrument manufacturers, and data scientists was undertaken in order to ensure that the reporting format met community needs. The reporting format presented here is intended to form a foundation for future development that will incorporate additional data types and variables as gas exchange systems and measurement approaches advance in the future. The reporting format is published in the U.S. Department of Energy's ESS-DIVE data repository, with documentation and future development efforts being maintained in a version control system