Unmanaged grasslands are a reservoir of Alternaria and other important fungal species with differing emission patterns.

Alternaria is a ubiquitous fungal genus with many allergenic and pathogenic species inhabiting grasslands. We hypothesise that grasslands (natural/man-made) host a diversity of fungal species whose spores have varying emission patterns. Therefore, the purpose of this study was to examine the potential of grasslands for emission, diversity and composition of Alternaria and other fungal species. To test the hypothesis, Hirst-type and multi-vial Cyclone samplers collected air samples from two grassland sites (unmanaged and managed) and a non-grassland site at Lakeside campus of the University of Worcester, United Kingdom for the period May to September 2019. The unmanaged grassland was originally planted with grasses and left uncut for three years. The managed grassland was a roadside verge that was cut once every year, typically after most grasses have flowered. We used optical microscopy and Illumina MiSeq sequencing to investigate the emission, abundance, diversity and composition of the fungal spores from each site alongside meteorological variables. Kruskal-Wallis and Wilcoxon tests examined differences in the bi-hourly Alternaria concentrations between the sites. Shannon's and Simpson's Index determined the diversity of the fungal spores between the unmanaged and non-grassland sites. The results showed that grasslands are a strong source of Alternaria spores with considerably higher numbers of clinically important days compared with the non-grassland site. The managed grassland varied in Alternaria spore emission pattern from the unmanaged, probably due to differences in environmental variables and cutting frequency. The unmanaged grassland and non-grassland sites showed a high diversity of fungi including Alternaria, Cladosporium, Ascochyta, Botrytis and Aureobasidium. Overall, the study shows that grasslands are a strong source of fungal spores with allergenic and pathogenic potential and have varying emission patterns, compared with nearby urban areas where monitoring stations are located. This information is useful for atmospheric modelling of airborne fungal spore sources and has implications for allergy sufferers in particular.

Using qPCR and microscopy to assess the impact of harvesting and weather conditions on the relationship between Alternaria alternata and Alternaria spp. spores in rural and urban atmospheres.

Alternaria is a plant pathogen and human allergen. Alternaria alternata is one of the most abundant fungal spores in the air. The purpose of this study was to examine whether Alternaria spp. spore concentrations can be used to predict the abundance and spatio-temporal pattern of A. alternata spores in the air. This was investigated by testing the hypothesis that A. alternata dominates airborne Alternaria spp. spores and varies spatio-temporally. Secondarily, we aimed at investigating the relationship between airborne Alternaria spp. spores and the DNA profile of A. alternata spores between two proximate (~ 7 km apart) sites. These were examined by sampling Alternaria spp. spores using Burkard 7-day and cyclone samplers for the period 2016-2018 at Worcester and Lakeside campuses of the University of Worcester, UK. Daily Alternaria spp. spores from the Burkard traps were identified using optical microscopy whilst A. alternata from the cyclone samples was detected and quantified using quantitative polymerase chain reaction (qPCR). The results showed that either A. alternata or other Alternaria species spores dominate the airborne Alternaria spore concentrations, generally depending on weather conditions. Furthermore, although Alternaria spp. spore concentrations were similar for the two proximate sites, A. alternata spore concentrations significantly varied for those sites and it is highly likely that the airborne samples contained large amounts of small fragments of A. alternata. Overall, the study shows that there is a higher abundance of airborne Alternaria allergen than reported by aerobiological networks and the majority is likely to be from spore and hyphal fragments.

Adult Vaccination.

Adult vaccination rates are low in the United States, despite clear benefits for reducing morbidity and mortality. Vaccine science is evolving rapidly, and family physicians must maintain familiarity with the most recent guidelines. The recommended adult immunization schedule is updated annually by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. All eligible patients should receive SARS-CoV-2 vaccines according to the current guidelines. Adults without contraindications should also receive an annual influenza vaccine. Hepatitis A vaccine is recommended for adults with specific risk factors. All pregnant patients, adults younger than 60 years, and those 60 years and older who have risk factors should receive a hepatitis B vaccine. A 15- or 20-valent pneumococcal conjugate vaccine is recommended for all patients who are 65 years and older. Patients who receive 15-valent pneumococcal conjugate vaccine should receive a dose of 23-valent pneumococcal polysaccharide vaccine one year later. Adults 19 to 64 years of age should receive a pneumococcal vaccination if they have medical risk factors. A single dose of measles, mumps, and rubella vaccine is recommended for adults without presumptive immunity, and additional doses are recommended for patients with HIV and postdelivery for pregnant patients who are not immune to rubella. A tetanus and diphtheria toxoids booster is recommended every 10 years. For pregnant patients and those in close contact with young infants, a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine should be administered. The human papillomavirus vaccine is recommended for all people through 26 years of age. Herpes zoster vaccine is indicated for all adults 50 years and older. .

Summer pollen flora in rural and urban central England dominated by nettle, ryegrass and other pollen missed by the national aerobiological network.

Abundance and diversity of airborne pollen are important to human health and biodiversity. The UK operational network collects airborne pollen from 8 flowering trees, grasses and three weeds using Hirst traps and microscopic identification from urban areas. Knowledge of total pollen diversity and differences between rural and urban zones is limited. We collect environmental DNA (eDNA) from air during summer and autumn over 3 years with mini cyclones from one urban and one rural site. Data are analysed using next generation sequencing and metabarcoding. We find the most common genus, Urtica (57%), is also identified by the national network. The grasses Lolium (10%), Agrostis (2%) and Holcus (1%) are in the national network grouped at family level, while Brassica (2%), Chenopodium (1%), Impatiens (2%), Plantago (4%) and Tilia (7%) are not part of the UK operational network. DNA from 138 genera was identified, where 2% of the sample could not be associated with specific genera. 40% of the sample was classified better using eDNA methods at the genus level, than by optical methods. We calculate Bray-Curtis dissimilarity for the rural and urban zones and find a systematic difference in biodiversity. Overall, this shows airborne DNA reveals more information than methods based on morphological differences. The results also suggest data from sites located in large urban areas will be less representative for less populated rural areas. This presents a dilemma in balancing a network and the associated costs delivering health relevant information to the most populated areas vs. a nation-wide approach.

Environmental DNA reveals diversity and abundance of Alternaria species in neighbouring heterogeneous landscapes in Worcester, UK.

Alternaria is a pathogenic and allergenic fungus affecting 400 plant species and 334 million people globally. This study aimed at assessing the diversity of Alternaria species in airborne samples collected from closely located (7 km apart) and heterogeneous sites (rural, urban and unmanaged grassland) in Worcester and Lakeside, the UK. A secondary objective was to examine how the ITS1 subregion varies from ITS2 in Alternaria species diversity and composition. Airborne spores were collected using Burkard 7-day and multi-vial Cyclone samplers for the period 5 July 2016-9 October 2019. Air samples from the Cyclone were amplified using the ITS1and ITS2 subregions and sequenced using Illumina MiSeq platform whereas those from the Burkard sampler were identified and quantified using optical microscopy. Optical microscopy and eDNA revealed a high abundance of Alternaria in the rural, urban and unmanaged sites. ITS1 and ITS2 detected five and seven different Alternaria species at the three sampling sites, respectively. A. dactylidicola, A. metachromatica and A. infectoria were the most abundant. The rural, urban and unmanaged grassland sites had similar diversity (PERMANOVA) of the species due to similarity in land use and proximity of the sites. Overall, the study showed that heterogeneous and neighbouring sites with similar land uses can have similar Alternaria species. It also demonstrated that an eDNA approach can complement the classical optical microscopy method in providing more precise information on fungal species diversity in an environment for targeted management. Similar studies can be replicated for other allergenic and pathogenic fungi. Supplementary Information: The online version contains supplementary material available at 10.1007/s10453-022-09760-9.

Analysis of C. difficile infection-related outcomes in European participants in the bezlotoxumab MODIFY I and II trials.

The MODIFY I/II trials demonstrated that bezlotoxumab, a human monoclonal antibody against Clostridioides difficile toxin B, given during antibiotic treatment for Clostridioides difficile infection (CDI) significantly reduced C. difficile recurrence (rCDI) in adults at high risk for rCDI. Efficacy of CDI-directed intervention may depend on ribotype regional epidemiology, and patient characteristics. This post hoc analysis assessed the efficacy of bezlotoxumab in the subgroup of MODIFY I/II trial participants enrolled in Europe. Data from the bezlotoxumab (10 mg/kg single intravenous infusion) and placebo (0.9% saline) groups from MODIFY I/II were compared to assess initial clinical cure (ICC), rCDI, all-cause, and CDI-associated rehospitalizations within 30 days of discharge, and mortality through 12 weeks post-infusion. Of 1554 worldwide participants, 606 were from Europe (bezlotoxumab n = 313, 51%; placebo n = 292; 48%). Baseline characteristics were generally similar across groups, although there were more immunocompromised participants in the bezlotoxumab group (27.2%) compared with placebo (20.1%). Fifty-five percent of participants were female, and 86% were hospitalized at randomization. The rate of ICC was similar between treatment groups. The rate of rCDI in the bezlotoxumab group was lower compared with placebo among European participants overall, and among those with ≥ 1 risk factor for rCDI. Bezlotoxumab reduced 30-day CDI-associated rehospitalizations compared with placebo. These results are consistent with overall results from the MODIFY trials and demonstrate that bezlotoxumab reduces rCDI and CDI-associated rehospitalizations in European patients with CDI. MODIFY I/II (NCT01241552 and NCT01513239).

Tree cover mapping based on Sentinel-2 images demonstrate high thematic accuracy in Europe.

The spatial and temporal distribution of trees has a large impact on human health and the environment through contributions to important climate mechanisms as well as commercial, recreational and social activities in society. A range of tree mapping methodologies has been presented in the literature, but tree cover estimates still differ widely between the individual datasets, and comparisons of the thematic accuracy of the resulting tree maps are rather scarce. The Copernicus Sentinel-2 satellites, which were launched in 2015 and 2017, have a combination of high spatial and temporal resolution. Given that this is a new satellite, a substantial amount of research on development of tree mapping algorithms as well as accuracy assessment of said algorithms have to be done in the years to come. To contribute to this process, a tree map produced through unsupervised classification was created for six Sentinel-2 tiles. The agreement between the tree map and the corresponding national forest inventory, as a function of the band combination chosen, was analysed and the thematic accuracy was assessed for two out of the six tiles. The results show that the highest agreement between the present tree map and the national forest inventory was found for bands 2, 3, 6 and 12. The present tree map has a relative difference in tree cover between 8% and 79% compared to previous estimates, but results are characterised by large scatter. Lastly, it is shown that the overall thematic accuracy of the present map is up to 90%, with the user's accuracy ranging from 34.85% to 92.10%, and the producer's accuracy ranging from 23.80% to 97.60% for the various thematic classes. This demonstrates that tree maps with high thematic accuracy can be produced from Sentinel-2. In the future the thematic accuracy can be increased even more through the use of temporal averaging in the mapping procedure, which will enable an accurate estimate of the European tree cover.

Recurrent Streptococcal Cellulitis: A Case Report and Review.

Cellulitis is an infection of the dermis and subcutaneous layers of the skin. One challenge in treating the disease is that it is often difficult to identify the causative agent; although ß-hemolytic Streptococci and Staphylococcus aureus are the most common causes. In addition, patients who recover from the disease are susceptible to recurrent infections. Here, we briefly review cellulitis and describe a patient's 24-year struggle with recurrent streptococcal cellulitis noting how the patient was negatively affected by changes in care.

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence.

Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Validation of Whole-Genome Sequencing for Identification and Characterization of Shiga Toxin-Producing Escherichia coli To Produce Standardized Data To Enable Data Sharing.

Whole-genome sequencing (WGS) is rapidly becoming the method of choice for outbreak investigations and public health surveillance of microbial pathogens. The combination of improved cluster resolution and prediction of resistance and virulence phenotypes provided by a single tool is extremely advantageous. However, the data produced are complex, and standard bioinformatics pipelines are required to translate the output into easily interpreted epidemiologically relevant information for public health action. The main aim of this study was to validate the implementation of WGS at the Scottish Escherichia coli O157/STEC Reference Laboratory (SERL) using the Public Health England (PHE) bioinformatics pipeline to produce standardized data to enable interlaboratory comparison of results generated at two national reference laboratories. In addition, we evaluated the BioNumerics whole-genome multilocus sequence typing (wgMLST) and E. coli genotyping plug-in tools using the same data set. A panel of 150 well-characterized isolates of Shiga toxin-producing E. coli (STEC) that had been sequenced and analyzed at PHE using the PHE pipeline and database (SnapperDB) was assembled to provide identification and typing data, including serotype (O:H type), sequence type (ST), virulence genes (eae and Shiga toxin [stx] subtype), and a single-nucleotide polymorphism (SNP) address. To validate the implementation of sequencing at the SERL, DNA was reextracted from the isolates and sequenced and analyzed using the PHE pipeline, which had been installed at the SERL; the output was then compared with the PHE data. The results showed a very high correlation between the data, ranging from 93% to 100%, suggesting that the standardization of WGS between our reference laboratories is possible. We also found excellent correlation between the results obtained using the PHE pipeline and BioNumerics, except for the detection of stx2a and stx2c when these subtypes are both carried by strains.

Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection.

Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Predicting the public health benefit of vaccinating cattle against Escherichia coli O157.

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle-human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human-animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases.

Interprofessional Graduate Students' Perspectives on Caring for Vulnerable Populations.

The purpose of this focus group study was to explore graduate students' clinical experiences with vulnerable populations, perceived barriers to care, and ethical issues related to caring for disenfranchised groups. Furthermore, based on their experiences, the students were asked to share suggestions for curricular changes that could enhance care for vulnerable populations through interdisciplinary collaboration and multidisciplinary projects. The responses of the participants add to what is known about the care of vulnerable populations, offering a first-hand description of students' preparation for work with vulnerable populations and the interdisciplinary team.

Utility of Whole-Genome Sequencing of Escherichia coli O157 for Outbreak Detection and Epidemiological Surveillance.

Detailed laboratory characterization of Escherichia coli O157 is essential to inform epidemiological investigations. This study assessed the utility of whole-genome sequencing (WGS) for outbreak detection and epidemiological surveillance of E. coli O157, and the data were used to identify discernible associations between genotypes and clinical outcomes. One hundred five E. coli O157 strains isolated over a 5-year period from human fecal samples in Lothian, Scotland, were sequenced with the Ion Torrent Personal Genome Machine. A total of 8,721 variable sites in the core genome were identified among the 105 isolates; 47% of the single nucleotide polymorphisms (SNPs) were attributable to six "atypical" E. coli O157 strains and included recombinant regions. Phylogenetic analyses showed that WGS correlated well with the epidemiological data. Epidemiological links existed between cases whose isolates differed by three or fewer SNPs. WGS also correlated well with multilocus variable-number tandem repeat analysis (MLVA) typing data, with only three discordant results observed, all among isolates from cases not known to be epidemiologically related. WGS produced a better-supported, higher-resolution phylogeny than MLVA, confirming that the method is more suitable for epidemiological surveillance of E. coli O157. A combination of in silico analyses (VirulenceFinder, ResFinder, and local BLAST searches) were used to determine stx subtypes, multilocus sequence types (15 loci), and the presence of virulence and acquired antimicrobial resistance genes. There was a high level of correlation between the WGS data and our routine typing methods, although some discordant results were observed, mostly related to the limitation of short sequence read assembly. The data were used to identify sublineages and clades of E. coli O157, and when they were correlated with the clinical outcome data, they showed that one clade, Ic3, was significantly associated with severe disease. Together, the results show that WGS data can provide higher resolution of the relationships between E. coli O157 isolates than that provided by MLVA. The method has the potential to streamline the laboratory workflow and provide detailed information for the clinical management of patients and public health interventions.

A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.

BACKGROUND: Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c. RESULTS: Overall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: -0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: -0.47, 0.47]) and fasting plasma glucose (between-treatment differences -4.8 [95% CI: -12.1, 2.1]) were similar in both treatment groups. CONCLUSIONS: These results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01611883 .

E. coli O157 on Scottish cattle farms: evidence of local spread and persistence using repeat cross-sectional data.

BACKGROUND: Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998-2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred. RESULTS: The presence of an E. coli O157 positive local farm (average distance: 5.96 km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p < 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p < 0.001) from the same time frame. CONCLUSIONS: The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources.

Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years.

BACKGROUND: Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years. METHODS: After stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment. RESULTS: Atorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks). CONCLUSIONS: Atorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00418834.

Prevalence of low testosterone in aging men with benign prostatic hyperplasia: data from the Proscar Long-term Efficacy and Safety Study (PLESS).

OBJECTIVES: We examined the prevalence of low testosterone (LT) in the subset of men in the Proscar Long-term Efficacy and Safety Study (PLESS) who had serum total testosterone (TT) measured at baseline. METHODS: PLESS enrolled 3040 men with benign prostatic hyperplasia (BPH). Of these men, 299 had TT and body mass index (BMI) measurements at baseline. Patients were classified as having LT if their baseline TT was <300 ng/dl. RESULTS: Of the 299 PLESS patients with baseline TT and BMI measurements, 65 (21.7%) had LT. The prevalence of LT increased with increasing BMI, occurring in 8/78 (10.3%) normal weight patients (baseline BMI <25 kg/m2), 35/160 (21.9%) overweight patients (baseline BMI ≥25-<30 kg/m2), and 22/61 (36.1%) obese patients (baseline BMI ≥30 kg/m2). CONCLUSIONS: LT was observed in more than one in five PLESS patients with baseline TT and BMI measurements. The prevalence of LT increased with increasing BMI - more than one in three obese PLESS patients with baseline TT measurements had LT.

Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects.

PURPOSE: This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20 mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg in subgroups of obese (BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) diabetic subjects. METHODS: This was a randomized, double-blind, 12-week study of adults 18-79 years with cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. Percent change in LDL-C and other lipids was estimated. RESULTS: In obese subjects (n = 466), percent changes in LDL-C and most other lipids were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin. In non-obese subjects (n = 342), percent changes in LDL-C, total cholesterol, non-HDL-C, Apo B and Apo A-I were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin; and treatment with ezetimibe/simvastatin resulted in greater changes in triglycerides vs rosuvastatin and HDL-C vs doubling the baseline statin dose. The safety profiles were generally similar. CONCLUSIONS: Regardless of baseline obesity status, switching to ezetimibe/simvastatin was more effective at reducing LDL-C, total cholesterol, non-HDL-C, and Apo B vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg.

Microscale pollen release and dispersal patterns in flowering grass populations.

Characterizing pollen release and dispersion processes is fundamental for knowledge advancement in ecological, agricultural and public health disciplines. Understanding pollen dispersion from grass communities is especially relevant due to their high species-specific allergenicity and heterogeneously distributed source areas. Here, we aimed to address questions concerning fine level heterogeneity in grass pollen release and dispersion processes, with a focus on characterizing the taxonomic composition of airborne grass pollen over the grass flowering season using eDNA and molecular ecology methods. High resolution grass pollen concentrations were compared between three microscale sites (<300 m apart) in a rural area in Worcestershire, UK. The grass pollen was modelled with local meteorology in a MANOVA (Multivariate ANOVA) approach to investigate factors relevant to pollen release and dispersion. Simultaneously, airborne pollen was sequenced using Illumina MySeq for metabarcoding, analysed against a reference database with all UK grasses using the R packages DADA2 and phyloseq to calculate Shannon's Diversity Index (α-diversity). The flowering phenology of a local Festuca rubra population was observed. We found that grass pollen concentrations varied on a microscale level, likely attributed to local topography and the dispersion distance of pollen from flowering grasses in local source areas. Six genera (Agrostis, Alopecurus, Arrhenatherum, Holcus, Lolium and Poa) dominated the pollen season, comprising on average 77 % of the relative abundance of grass species reads. Temperature, solar radiation, relative humidity, turbulence and wind speeds were found to be relevant for grass pollen release and dispersion processes. An isolated flowering Festuca rubra population contributed almost 40 % of the relative pollen abundance adjacent to the nearby sampler, but only contributed 1 % to samplers situated 300 m away. This suggests that most emitted grass pollen has limited dispersion distance and our results show substantial variation in airborne grass species composition over short geographical scales.