Environmental contamination and transmission of Ascaris suum in Danish organic pig farms

BACKGROUND: Although Ascaris suum is the most common pig nematode, the on-farm transmission dynamics are not well described. METHODS: We performed a 1-year field study on five organic pig farms, mapping egg contamination levels in pens and pasture soil as well as faecal egg counts in starter pigs, finisher pigs, dry and lactating sows. The uppermost bedding material was sampled from three pen areas (resting, intermediate and latrine) of shallow and deep litter pens. RESULTS: Ascaris suum was found on all farms. Averaged across farm and season, the prevalence of A. suum was 48, 64, 28 and 15 % in starters, finishers, dry and lactating sows, respectively. For starters and finishers, the prevalence varied with season increasing towards the end of the year when 83–96 % of finishing pigs from each farm had fresh liver white spots. Farrowing pastures were contaminated with a mean of 78–171 larvated eggs/kg dry soil depending on farm, while pastures for starter pigs contained 290–5397 larvated eggs/kg dry soil. The concentration of eggs in soil was highest in the autumn. Indoors, all pen areas were contaminated with A. suum eggs at comparable levels for shallow and deep litter. Overall there were 106, 445 and 1331 eggs/g dry straw in the resting, intermediate and latrine areas, respectively. However, more eggs were undergoing development in resting areas (44 %) compared to intermediate (33 %) and latrine areas (13 %). Irrespective of area, more eggs were undergoing development in the autumn, but overall there were very few fully developed (i.e., infective) eggs in the bedding material. Laboratory embryonation of eggs from the bedding material nevertheless revealed that an overall mean of 79 % of the eggs were viable. CONCLUSION: The organic pigs of all ages were continuously exposed to A. suum, but mainly younger animals were infected. Deep litter appeared to be a less important source of A. suum eggs than previously believed compared to shallow litter. Long-term pasture rotation to eliminate pasture contamination was not possible, and control programs should therefore include thorough cleaning indoors and composting/long-term storage of bedding material and manure to inactivate eggs and reduce transmission to pigs

A Longitudinal Study of Pediatricians Early in their Careers: PLACES

The American Academy of Pediatrics (AAP) launched the Pediatrician Life and Career Experience Study (PLACES), a longitudinal study that tracks the personal and professional experiences of early career pediatricians, in 2012. We used a multipronged approach to develop the study methodology and survey domains and items, including review of existing literature and qualitative research with the target population. We chose to include 2 cohorts of US pediatricians on the basis of residency graduation dates, including 1 group who were several years out of residency (2002–2004 Residency Graduates Cohort) and a second group who recently graduated from residency at study launch (2009–2011 Residency Graduates Cohort). Recruitment into PLACES was a 2-stage process: (1) random sample recruitment from the target population and completion of an initial intake survey and (2) completion of the first Annual Survey by pediatricians who responded positively to stage 1. Overall, 41.2% of pediatricians randomly selected to participate in PLACES indicated positive interest in the study by completing intake surveys; of this group, 1804 (93.7%) completed the first Annual Survey and were considered enrolled in PLACES. Participants were more likely to be female, AAP members, and graduates of US medical schools compared with the target sample; weights were calculated to adjust for these differences. We will survey PLACES pediatricians 2 times per year. PLACES data will allow the AAP to examine career and life choices and transitions experienced by early-career pediatricians

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation.

Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation

Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. / Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. / Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. / Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted

Bacterial contamination of Saudi Arabian paper currency: A report from Al-Kharj

Background: Currency is a public support tool for exchange of commodity and services. It’s prevalent practice for acquiring bread to broast and bath to bed has connected all human being together irrespective of race and occupation. Currency notes along with their denomination values also carry pathogens if contaminated and will act as an agent for infection transference. Therefore the objective of this cross-sectional study was to assess the load microbial pathogens of paper currency collected in selected public places of Al-Kharj, Saudi Arabia.Methods: Currency notes under study were assessed through microbiological culture, microscopic and biochemical visualization techniques.Results: The results from this cross-sectional study suggested that lower the currency denominations higher was the microbial contaminations, frequency percentage was lower with higher isolations. Small eateries were the biggest source of contaminated currency from the ten selected centres. Percentage microorganism occurrence for Bacillus sp., Staphylococcus sp., Klebsiella sp. and E. coli was 56.84%, 25.03%, 13.40% and 04.71% respectively in all currency notes under study.Conclusions: The outcomes of this study revealed that currency notes can be a source for microbe transmission causing infectious diseases represent public health hazards to the community and individuals

Enantiomeric separation and determination of stereospecific drug release from marketed racemic omeprazole products by chiral HPLC

The objective of carrying out this research work was to investigate the effect of chirality on stereospecific dissolution of omeprazole enantiomers from various marketed racemic omeprazole products. Omeprazole is used for the treatment of gastro-duodenal ulcers and symptomatic gastro-oesophageal reflux. Dissolution of various marketed products was performed using USP type I apparatus in 0.1 N HCl for 2 h and in pH 6.8 phosphate buffer for 1 h at 100 rpm. The separation of enantiomers was done using a chiral HPLC method on CHIRAL AGP column (100 x 4.6 mm i.d.). The wavelength for UV detection was set at 210 nm. The mobile phase was 10 mM phosphate buffer with 5 % acetonitrile adjusted to pH 6.5 at a flow rate of 0.9 ml min-1 with an injector valve fitted to a 50 μL volume sample loop. The retention times for R and S enantiomers of omeprazole were 5 and 7.5 min, respectively. The dissolution of S enantiomer of Ocid-20 and Omee was found to be significantly more compared to their R enantiomer at 5 and 10 min dissolution time points after which there was no stereospecific discrimination in the dissolution. From the S/R ratios of different racemic omeprazole marketed products it was concluded that at 5 and 10 min dissolution time points there was a stereospecific drug release between the S and R enantiomers with the brands Ocid-20 and Omee (p 0.05).Colegio de Farmacéuticos de la Provincia de Buenos Aire

The MDM2 antagonist idasanutlin in patients with polycythemia vera:results from a single-arm phase 2 study

Idasanutlin, an MDM2 antagonist, showed clinical activity and a rapid reduction in JAK2 V617F allele burden in patients with polycythemia vera (PV) in a phase 1 study. This open-label phase 2 study evaluated idasanutlin in patients with hydroxyurea (HU)-resistant/-intolerant PV, per the European LeukemiaNet criteria, and phlebotomy dependence; prior ruxolitinib exposure was permitted. Idasanutlin was administered once daily on days 1 through 5 of each 28-day cycle. The primary end point was composite response (hematocrit control and spleen volume reduction > 35%) in patients with splenomegaly and hematocrit control in patients without splenomegaly at week 32. Key secondary end points included safety, complete hematologic response (CHR), patient-reported outcomes, and molecular responses. All patients (n = 27) received idasanutlin; 16 had response assessment (week 32). Among responders with baseline splenomegaly (n = 13), 9 (69%) attained any spleen volume reduction, and 1 achieved composite response. Nine patients (56%) achieved hematocrit control, and 8 patients (50%) achieved CHR. Overall, 43% of evaluable patients (6/14) showed a ≥50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (week 32). Nausea (93%), diarrhea (78%), and vomiting (41%) were the most common adverse events, with grade ≥ 3 nausea or vomiting experienced by 3 patients (11%) and 1 patient (4%), respectively. Reduced JAK2 V617F allele burden occurred early (after 3 cycles), with a median reduction of 76%, and was associated with achieving CHR and hematocrit control. Overall, the idasanutlin dosing regimen showed clinical activity and rapidly reduced JAK2 allele burden in patients with HU-resistant/- intolerant PV but was associated with low-grade gastrointestinal toxicity, leading to poor long-term tolerability. This trial was registered at www.clinincaltrials.gov as #NCT03287245

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells. </p