Community Outbreak of Pseudomonas aeruginosa Infections Associated with Contaminated Piercing Aftercare Solution, Australia, 2021.

In April 2021, the South Eastern Sydney Local Health District Public Health Unit (Sydney, New South Wales, Australia) was notified of 3 patients with Pseudomonas aeruginosa infections secondary to skin piercings performed at the same salon. Active case finding through laboratories, clinician alerts, and monitoring hospital visits for piercing-related infections identified additional cases across New South Wales, and consumers were alerted. We identified 13 confirmed and 40 probable case-patients and linked clinical isolates by genomic sequencing. Ten confirmed case-patients had used the same brand and batch of aftercare solution. We isolated P. aeruginosa from opened and unopened bottles of this solution batch that matched the outbreak strain identified by genomic sequencing. Piercing-related infections returned to baseline levels after this solution batch was recalled. Early outbreak detection and source attribution via genomic sequencing are crucial for controlling outbreaks linked to contaminated products. Manufacturing standards for nonsterile cosmetic products and guidance for piercing aftercare warrant review.

Patterns of infection following transrectal ultrasound-guided biopsy of the prostate in a regional New South Wales Centre.

OBJECTIVE: To determine the rates, severity and patterns of resistance in patients presenting with post-transrectal ultrasound infection in a regional centre in New South Wales, Australia. DESIGN: A single-centre retrospective review from August 2013 until August 2017. SETTING: Murrumbidgee Local Health District, New South Wales. PARTICIPANTS: All patients who underwent transrectal ultrasonography biopsy of the prostate in the public health system. MAIN OUTCOME MEASURES: Rate of infection and sepsis following biopsy of the prostate requiring readmission to hospital within 30 days from the procedure. RESULTS: A total of 317 men underwent transrectal ultrasound-guided biopsy of the prostate over the study period. Nineteen (6%) patients presented with clinical signs of post-transrectal ultrasound infection, of which 18 (5.7%) required readmission for intravenous antibiotics. Median time to readmission was 2 days (0-7), and the average length of hospital stay was 5 days (1-15). Three (0.3%) patients required admission to intensive care for inotropic support. Thirteen patients (68%) had positive blood cultures, and all were positive for Escherichia coli. Four of these patients (21%) had extended spectrum beta-lactamase producing isolates resistant to their preoperative antibiotics. CONCLUSION: Prostate cancer is common in the elderly community with worse outcomes in regional settings. Infective complications from transrectal ultrasound biopsy were 6% in this regional setting with high rates of multi-resistant organisms. Awareness of this is important for rural health practitioners who are likely to be exposed to this patient population.

Shopping on the Public and Private Health Insurance Marketplaces: Consumer Decision Aids and Plan Presentation.

BACKGROUND: The design of the Affordable Care Act's (ACA) health insurance marketplaces influences complex health plan choices. OBJECTIVE: To compare the choice environments of the public health insurance exchanges in the fourth (OEP4) versus third (OEP3) open enrollment period and to examine online marketplace run by private companies, including a total cost estimate comparison. DESIGN: In November-December 2016, we examined the public and private online health insurance exchanges. We navigated each site for "real-shopping" (personal information required) and "window-shopping" (no required personal information). PARTICIPANTS: Public (n = 13; 12 state-based marketplaces and HealthCare.gov ) and private (n = 23) online health insurance exchanges. MAIN MEASURES: Features included consumer decision aids (e.g., total cost estimators, provider lookups) and plan display (e.g., order of plans). We examined private health insurance exchanges for notable features (i.e., those not found on public exchanges) and compared the total cost estimates on public versus private exchanges for a standardized consumer. RESULTS: Nearly all studied consumer decision aids saw increased deployment in the public marketplaces in OEP4 compared to OEP3. Over half of the public exchanges (n = 7 of 13) had total cost estimators (versus 5 of 14 in OEP3) in window-shopping and integrated provider lookups (window-shopping: 7; real-shopping: 8). The most common default plan orders were by premium or total cost estimate. Notable features on private health insurance exchanges were unique data presentation (e.g., infographics) and further personalized shopping (e.g., recommended plan flags). Health plan total cost estimates varied substantially between the public and private exchanges (average difference $1526). CONCLUSIONS: The ACA's public health insurance exchanges offered more tools in OEP4 to help consumers select a plan. While private health insurance exchanges presented notable features, the total cost estimates for a standardized consumer varied widely on public versus private exchanges.

Sexually Transmitted Diseases of Bulls.

Reproduction is essential for successful cow-calf and dairy production and the most important economic trait for cow-calf producers. For efficient reproduction to occur in beef herds, cows or heifers must conceive early during the breeding season, maintain the pregnancy, calve unassisted or with very little assistance, rebred in a timely manner and wean a calf every year. In the case of dairy cattle, cows or heifers are expected to become pregnant, maintain the pregnancy, and calve every 12 to 15 months to produce milk. Interruption of that process leads to delay or total loss of production. Although fertile bulls are required to achieve reproduction, they come with potential risk of transmitting disease during breeding.

Managing Beef Bulls During the Off-Season.

As approximately 94% of beef cow-calf operations use only natural service for breeding their cows and heifers, replacement bulls are a significant, necessary cost of producing beef calves. The value realized from beef bulls includes number and quality of calves sired, weight of calves sold, production value of daughters retained, and the bull's salvage value. Considering the importance of maintaining and recouping the cost of this significant investment, there is little information in peer reviewed literature about maintaining bulls in the off-season to prepare the bull for optimum performance in subsequent breeding seasons.

Reduced Cochlear MRI Signal and Hearing Outcomes in Conservatively Managed Vestibular Schwannoma Patients.

OBJECTIVE: This study aimed to determine if hypointense cochlear magnetic resonance imaging (MRI) constructive interference in steady-state (CISS) signal correlates with hearing outcomes in conservatively managed vestibular schwannoma (VS) patients. STUDY DESIGN: Retrospective review of 657 cases from 1992 to 2020. SETTING: Tertiary academic referral center. PATIENTS: A retrospective review was performed to identify conservatively managed VS patients with appropriate baseline MRI, audiology, and at least 12-month audiological follow-up. Patients were excluded if they progressed to surgery or radiotherapy in less than 12 months, bilateral tumors, or surgery on the contralateral ear. INTERVENTION: Conservatively managed patients with CISS imaging studies and audiology testing. MAIN OUTCOME MEASURES: Primary outcome measure change in pure-tone average (PTA) and word recognition score (WRS). Secondary outcome measures tumor size, presence of lateral fluid cap, or cystic changes. RESULTS: A total of 92 individuals (47% male, 58 ± 11.6 yr) met the inclusion criteria, with 36 (39%) of patients demonstrating abnormal cochlear CISS signal. At baseline, abnormal cochlear CISS signal was associated with higher intracanalicular (IC) length (7.9 versus 6.6 mm, p = 0.0177) and lower WRS (55.7 versus 78.8 dBHL, p = 0.0054). During follow-up, individuals with abnormal cochlear CISS signal had significantly higher PTA (62.4 versus 46.4 dBHL, p = 0.0010). After adjusting for baseline covariates, abnormal cochlear CISS signal was consistently associated with a greater increase in PTA of 8.3 dBHL (95% confidence interval, 2.9-13.7; p = 0.0032) from baseline when compared with the normal group. CONCLUSIONS: Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients.

In situ analyses of genome instability in breast cancer.

Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer. We modeled this process in vitro by measuring these same features in human mammary epithelial cell cultures during ZNF217-mediated transition through telomere crisis and immortalization. Taken together, the data suggest that transition through telomere crisis and immortalization in breast cancer occurs during progression from usual ductal hyperplasia to ductal carcinoma in situ.

Physical traits, performance data, and reproductive tract maturity score can be used to predict fertility and likelihood of early conception in beef replacement heifers consigned to a heifer development program in the southeastern United States.

OBJECTIVE: To identify growth and reproductive measurements that can be used to select heifers with the potential to be more reproductively efficient. SAMPLE: A total of 2,843 heifers consigned to the Georgia Heifer Evaluation and Reproductive Development program between 2012 and 2021 with a mean (min, max) age of heifers at delivery of 347 days (275, 404). PROCEDURES: Reproductive tract maturity score (RTMS), weight at delivery as a percentage of target breeding weight, hip height 3 to 4 weeks after delivery, and average daily gain during the first 3 to 4 weeks after delivery were evaluated as potential predictors of the variables of interest. RESULTS: The model-adjusted odds of pregnancy were 1.40 to 1.67 times higher for heifers with an RTMS of 3, 4, or 5 when compared to heifers with an RTMS of 1 or 2. For every 2.5-cm increase in hip height and every 1-month increase in age at the beginning of the breeding period the model-adjusted odds of pregnancy were 1.10 and 1.16 times higher, respectively. The model-adjusted pregnancy hazard rate for heifers with an RTMS of 3, 4, or 5 was 1.19 to 1.25 times higher than that of heifers with an RTMS of 1 or 2. For every 2.5-cm increase in hip height, the model-adjusted hazard rate for pregnancy was 1.04 times greater. CLINICAL RELEVANCE: Physical traits related to animal maturity and attainment of early puberty can be used to select heifers that are more likely to become pregnant early in their first breeding season.

Airway clearance techniques for chronic obstructive pulmonary disease.

BACKGROUND: Cough and sputum production are common in chronic obstructive pulmonary disease (COPD) and are associated with adverse clinical outcomes. Airway clearance techniques (ACTs) aim to remove sputum from the lungs, however evidence of their efficacy during acute exacerbations of COPD (AECOPD) or stable disease is unclear. OBJECTIVES: To assess the safety and efficacy of ACTs for individuals with AECOPD and stable COPD. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials from inception to October 2011, and PEDro in October 2009. SELECTION CRITERIA: We included randomised parallel trials and randomised cross-over trials which compared an ACT to no treatment, cough or sham ACT in participants with investigator-defined COPD, emphysema or chronic bronchitis. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and assessed the risk of bias. We analysed data from studies of AECOPD separately from stable COPD, and classified the effects of ACTs as 'immediate' (less than 24 hours), 'short-term' (24 hours to eight weeks) or 'long-term' (greater than eight weeks). One subgroup analysis compared the effects of ACTs that use positive expiratory pressure (PEP) to those that do not. MAIN RESULTS: Twenty-eight studies on 907 participants were included in the review. Study sample size was generally small (range 5 to 96 people) and overall quality was generally poor due to inadequate blinding and allocation procedures. Meta-analyses were limited by heterogeneity of outcome measurement and inadequate reporting of data.In people experiencing AECOPD, ACT use was associated with small but significant short-term reductions in the need for increased ventilatory assistance (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.05 to 0.85; data from four studies on 171 people), the duration of ventilatory assistance (mean difference (MD) -2.05 days, 95% CI -2.60 to -1.51; mean duration for control groups seven days; data from two studies on 54 people) and hospital length of stay (MD -0.75 days, 95% CI -1.38 to -0.11; mean duration for control groups nine days; one study on 35 people). Data from a limited number of studies revealed no significant long-term benefits of ACTs on the number of exacerbations or hospitalisations, nor any short-term beneficial effect on health-related quality of life (HRQoL) as measured by the St. George's Respiratory Questionnaire (SGRQ) total score (MD -2.30, 95% CI -11.80 to 7.20; one study on 59 people).In people with stable COPD, data from single studies revealed no significant short-term benefit of ACTs on the number of people with exacerbations (OR 3.21, 95% CI 0.12 to 85.20; one study on 30 people), significant short-term improvements in HRQoL as measured by the SGRQ total score (MD -6.10, 95% CI -8.93 to -3.27; one study on 15 people) and a reduced long-term need for respiratory-related hospitalisation (OR 0.27, 95% CI 0.08 to 0.95; one study on 35 participants).The magnitude of effect of PEP-based ACTs on the need for increased ventilatory assistance and hospital length of stay was greater than for non-PEP ACTs, however we found no statistically significant subgroup differences. There was one report of vomiting during treatment with postural drainage and head-down tilt. AUTHORS' CONCLUSIONS: Evidence from this review indicates that airway clearance techniques are safe for individuals with COPD and confer small beneficial effects on some clinical outcomes. Consideration may be given to the use of airway clearance techniques for patients with COPD in both acute and stable disease, however current studies suggest that the benefits achieved may be small.

Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma.

BACKGROUND: Inhaled beta-agonist therapy is central to the management of acute asthma. This review evaluates the benefit of an additional use of intravenous beta(2)-agonist agents. OBJECTIVES: To determine the benefit of adding intravenous (IV) beta(2)-agonists to inhaled beta(2)-agonist therapy for acute asthma treated in the emergency department. SEARCH METHODS: Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register which is a compilation of systematic searches of MEDLINE, EMBASE, CINAHL, and CENTRAL as well as handsearching of 20 respiratory journals. Bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. The search was performed in September 2012. SELECTION CRITERIA: Only RCTs were considered for inclusion. Studies were included if patients presented to the emergency department with acute asthma and were treated with IV beta(2)-agonists with inhaled beta(2)-agonist therapy and existing standard treatments versus inhaled beta(2)-agonists and existing standard treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and confirmed their findings with corresponding authors of trials. We obtained missing data from authors or calculated from data present in the papers. We used fixed-effect model for odds ratios (OR) and for mean differences (MD) we used both fixed-effect and random-effects models and reported 95% confidence intervals (CI). MAIN RESULTS: From 109 potentially relevant studies only three (104 patients) met our inclusion criteria: Bogie 2007 (46 children), Browne 1997 (29 children) and Nowak 2010 (29 adults). Bogie 2007 investigated the addition of intravenous terbutaline to high dose nebulised albuterol in children with acute severe asthma, requiring intensive care unit (ICU) admission. Browne 1997 investigated the benefit of adding intravenous salbutamol to inhaled salbutamol in children with acute severe asthma in the emergency department. Nowak 2010 investigated addition of IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) among adults, and was reported as a conference abstract only.There was no significant advantage (OR 0.29; 95%CI 0.06 to 1.38, one trial, 29 adults) for adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) with regard to hospitalisation rates.Various outcome indicators for the length of stay were reported among the trials. Browne 1997 reported a significantly shorter recovery time (in terms of cessation of 30 minute salbutamol) for children in the IV salbutamol with inhaled salbutamol group (four hours) versus the 11.1 hours for the inhaled salbutamol group (P = 0.03). Time to cessation of hourly nebuliser was also significantly shorter (P = 0.02) for the IV plus inhaled salbutamol group (11.5 hours versus 21.2 hours), and they were ready for emergency patient discharge on average 9.7 hours earlier than the inhaled salbutamol group (P < 0.05). In a paediatric ICU study Bogie 2007 reported no significant advantage in length of paediatric ICU admission (hours) for adding IV terbutaline to nebulised albuterol (MD -12.95, 95% CI: -38.74, 12.84).Browne 1997 reported there were only six out of 14 children with a pulmonary index score above six in the IV plus inhaled salbutamol group at two hours compared with 14 of the 15 in the inhaled salbutamol group (P = 0.02)In Browne 1997 there was a higher proportion of tremor in the IV plus inhaled salbutamol group than in the inhaled salbutamol group (P < 0.02). Nowak 2010 did not report any statistically significant adverse effects associated with adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids). Troponin levels were elevated in three children in the IV terbutaline + nebulised albuterol group at 12 and 24 hours in Bogie 2007 AUTHORS' CONCLUSIONS: There is very limited evidence from one study (Browne 1997) to support the use of IV beta(2)-agonists in children with severe acute asthma with respect to shorter recovery time, and similarly there is limited evidence (again from one study Browne 1997) suggesting benefit with regard to pulmonary index scores; however this advantage needs to be considered carefully in relation to the increased side effects associated with IV beta(2)-agonists. We identified no significant benefits for adults with severe acute asthma. Until more, adequately powered, high quality clinical trials in this area are conducted it is not possible to form a robust evaluation of the addition of IV beta(2)-agonists in children or adults with severe acute asthma.

Intravenous beta(2)-agonists versus intravenous aminophylline for acute asthma.

BACKGROUND: Inhaled beta(2)-agonist therapy is central to the management of acute asthma. For rapid bronchodilation in severe cases, penetration of inhaled drug to the affected small conducting airway may be impeded, and the intravenous (IV) rather than inhaled administration of bronchodilators may provide an earlier response. IV beta(2)-agonist agents and IV aminophylline may also be considered as additional interventions in this setting and this review compares IV beta-agonist agents and IV aminophylline in the treatment of people with acute asthma. OBJECTIVES: To compare the benefit of IV beta(2)-agonists versus IV aminophylline for acute asthma treated in the emergency department and in patients admitted to hospital with acute severe asthma. SEARCH METHODS: Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register, which is compiled from systematic searches of bibliographic databases as well as handsearching of respiratory journals and conference abstracts. The latest search was run in September 2012. We searched bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. SELECTION CRITERIA: We included RCTs of patients who presented to the emergency department with acute asthma, and patients admitted to hospital with acute severe asthma, and were treated with IV beta(2)-agonists versus IV aminophylline. Two review authors independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two review authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random-effects model for odds ratios (OR) or mean differences (MD) and reported with 95% confidence intervals (95% CI). MAIN RESULTS: Eleven studies met our inclusion criteria and in total they included 350 patients. However, opportunities to combine these studies in meta-analyses were limited by the variations in the range of outcomes reported in the trials.Length of stayTwo studies reported length of stay. They were both paediatric trials (with one in paediatric intensive care unit), and there was no significant difference between the two groups (MD 23.19 hours; 95% CI -2.40 to 48.77 hours; 2 studies; N = 73). Individual separate MD analyses for the two studies also indicated no significant difference between the aminophylline and beta(2)-agonist on this outcome. However, this finding should be interpreted with caution owing to the small number of trials and participants the analysis.Pulmonary functionThere were no significant differences in the sequential or summative pulmonary function demonstrated across the studies.Heart rateData for serial heart rates were reported in three studies at various points from 15 to 60 minutes and in each case there were no significant differences between people in the IV aminophylline or beta(2)-agonist groups. The difference between the two groups with respect to final heart rate was statistically significant (MD 10.00; 95% CI 0.99 to 19.01), although these data are from a single, small study and should be interpreted with caution.Adverse effectsThe analyses for giddiness (OR 59.22; 95% CI 2.80 to 1253.05; 1 study; N = 30), nausea/vomiting (where reported as a combined outcome) (OR 14.18; 95% CI 1.62 to 124.52; 2 studies; N = 96) and nausea (OR 6.53; 95% CI 1.60 to 26.72; 2 studies; N = 49) all significantly favoured beta(2)-agonists. In view of the very small number of studies and number of patients contributing to these analyses these results should be interpreted with caution. A closely related review considering the possible benefits of adding IV aminophylline to beta-agonists in adults with acute asthma also indicates a higher incidence of adverse effects associated with IV aminophylline. AUTHORS' CONCLUSIONS: In the included RCTs there was no consistent evidence favouring either IV beta(2)-agonists or IV aminophylline for patients with acute asthma. The opportunity to draw clear conclusions is limited by the heterogeneity of outcomes evaluated and the small sample sizes in the included studies. It is recommended that these data should be viewed carefully alongside the conclusions from separate Cochrane reviews comparing IV beta(2)-agonists plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone and IV aminophylline plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone.

Identification of BAHD acyltransferases associated with acylinositol biosynthesis in Solanum quitoense (naranjilla).

Plants make a variety of specialized metabolites that can mediate interactions with animals, microbes, and competitor plants. Understanding how plants synthesize these compounds enables studies of their biological roles by manipulating their synthesis in vivo as well as producing them in vitro. Acylsugars are a group of protective metabolites that accumulate in the trichomes of many Solanaceae family plants. Acylinositol biosynthesis is of interest because it appears to be restricted to a subgroup of species within the Solanum genus. Previous work characterized a triacylinositol acetyltransferase involved in acylinositol biosynthesis in the Andean fruit plant Solanum quitoense (lulo or naranjilla). We characterized three additional S. quitoense trichome expressed enzymes and found that virus-induced gene silencing of each caused changes in acylinositol accumulation. pH was shown to influence the stability and rearrangement of the product of ASAT1H and could potentially play a role in acylinositol biosynthesis. Surprisingly, the in vitro triacylinositol products of these enzymes are distinct from those that accumulate in planta. This suggests that additional enzymes are required in acylinositol biosynthesis. These characterized S. quitoense enzymes, nonetheless, provide opportunities to test the biological impact and properties of these triacylinositols in vitro.

WITHDRAWN: Bronchopulmonary hygiene physical therapy for chronic obstructive pulmonary disease and bronchiectasis.

BACKGROUND: Bronchopulmonary hygiene physical therapy is a form of chest physical therapy including chest percussion and postural drainage to remove lung secretions. These are applied commonly to patients with both acute and chronic airway diseases. Despite controversies in the literature regarding its efficacy, it remains in use in a variety of clinical settings. The various forms of this therapy are labour intensive and need to be evaluated. OBJECTIVES: The objective of this review was to assess the effects of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles up to January 2007. We also wrote to study authors. SELECTION CRITERIA: Randomised trials in which postural drainage, chest percussion, vibration, chest shaking, directed coughing or forced exhalation technique was compared to other drainage or breathing techniques, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers applied the inclusion and exclusion criteria on masked publications independently. They assessed the trial quality independently. Only data from the first arm of crossover trials were included. MAIN RESULTS: The seven included trials involved six comparisons and a total of 126 people. The trials were small and not generally of high quality. The results could not be combined as trials addressed different patient groups and outcomes. In most comparisons, bronchial hygiene physical therapy produced no significant effects on pulmonary function, apart from clearing sputum in chronic obstructive pulmonary disease and in bronchiectasis. An update search carried out in January 2007 did not identify any new studies for inclusion. AUTHORS' CONCLUSIONS: There is not enough evidence to support or refute the use of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis.

Finite element modelling of cell wall properties for onion epidermis using a fibre-reinforced hyperelastic model.

A combined finite element method and inverse modelling approach is used to model the mechanical deformation of onion epidermis. A fibre-reinforced hyperelastic composite material model considering the fibre distribution has been used to simulate the mechanical behaviour of samples under tension. The mechanical parameters of onion epidermis are determined using an inverse modelling approach. The simulated results show a good correlation with experimental observations.

Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism.

BACKGROUND: Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. RESULTS: Volatile compounds were examined using solid phase microextraction--gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. CONCLUSIONS: 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary metabolites with catabolism of branched chain amino acids, alcohol biosynthesis, and ß-oxidation of fatty acids. 3) Intracellular chemical development in A. parasiticus is linked to morphological development. 4) Understanding carbon flow through secondary metabolic pathways and catabolism of branched chain amino acids is essential for controlling and customizing production of natural products.

A novel, robust method for quantification of multiple kynurenine pathway metabolites in the cerebrospinal fluid.

Aim: Kynurenine metabolites are potential modulators of psychiatric disease. We aimed to develop a highly sensitive biochemical analysis of cerebrospinal fluid (CSF) tryptophan (TRP) metabolites, to investigate the stability of metabolites and to confirm our previous findings of aberrant CSF quinolinic acid (QUIN) and picolinic acid (PIC) in suicide attempters using this method. Methodology & results: Ten CSF TRP metabolites were analyzed with ultraperformance LC-MS/MS. The method showed small intra- and interassay variation. Metabolites were stable following freeze-thaw cycles. A decreased CSF PIC/QUIN ratio was found in suicide attempters. Conclusion: The feasibility of reliably determining CSF TRP metabolites were demonstrated, including separation of the two isomers PIC and nicotinic acid (NA) and the finding of a reduced PIC/QUIN ratio replicated in suicide attempters.

Lipophilic modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor.

Platelet P2Y12 receptors play a central role in the regulation of platelet function and inhibition of this receptor by treatment with drugs such as clopidogrel results in a reduction of atherothrombotic events. We discovered that modification of natural and synthetic dinucleoside polyphosphates and nucleotides with lipophilic substituents on the ribose and base conferred P2Y12 receptor antagonist properties to these molecules producing potent inhibitors of ADP-mediated platelet aggregation. We describe methods for the preparation of these functionalized dinucleoside polyphosphates and nucleotides and report their associated activities. By analysis of these results and by deconstruction of the necessary structural elements through selected syntheses, we prepared a series of highly functionalized nucleotides, resulting in the selection of an adenosine monophosphate derivative (62) for further clinical development.

Cattle Assessment On-Site During Emergencies.

Veterinary assessment of the condition and needs of livestock and their owners in an emergency is an essential element of the disaster response. The emergency response for livestock has 4 critical components: assessing the need for and attending to the immediate medical needs of injured or affected livestock, determining the resources available to meet the needs, including feed and facilities, identifying any ongoing threats or potential hazards to livestock health and welfare, and appropriate documentation of damages and actions by responders. Information gathered from cattle assessments by veterinarians is used to prioritize resources and plan for anticipated needs.

Using performance data and reproductive measurements to predict fertility in replacement beef heifers.

This study investigated the predictive value of reproductive tract evaluation and growth characteristics measured 30-70 d prior to the breeding season on 1) pregnancy outcome and 2) time to conception in replacement beef heifers. A total of 1,992 heifers (BW 329 ± 42 kg; age 347 ± 27 d) were delivered for enrollment in the Georgia Heifer Evaluation and Reproductive Development (HERD) program between 2006 and 2011 at two locations. Physical traits were selected to assess management of heifers prior to entering the program in addition to developmental traits traditionally measured in the HERD program and included: reproductive tract maturity score (RTS), weight 70 d prior to breeding as a percentage of target weight, hip height (HH) 40-50 d prior to breeding, and average daily gain 40-50 d prior to breeding. Cattle entered in the program were of similar age and subjected to comparable nutritional and management programs. Chi-square test of homogeneity (pregnancy status) and the Kaplan-Meier product limit method (number of days from initial breeding to conception) were used to analyze univariate associations with predictor variables. Multivariate analyses of pregnancy status and time to conception were performed using logistic regression and Cox regression, respectively. The odds of pregnancy increased by 15% for every 2.5 cm increase in HH (P = 0.001), and by 20% for every 30-d increase in heifer age at the start of the breeding period (P = 0.019). Although RTS was associated (P = 0.015) with pregnancy status in the univariate analysis, after adjusting for the other variables included in the final multivariable model there was no significant association (P > 0.05). RTS and heifer age were not associated (P > 0.05) with time to conception in the multivariable analysis and were not included in the final model. However, HH was significantly (P = 0.005) associated with the time to conception after adjusting for location and year of enrollment. After 35 d, the hazard rate for conception increased 15% for every 2.5 cm increase in HH [hazard ratio (95% confidence interval) = 1.15 (1.04, 1.26); P = 0.005]. Variables intended to indicate prior management (average daily gain and weight 70 d prior to breeding as a percentage of target weight) were not found to be associated with pregnancy or time to conception. The results suggest that factors relating to maturity can be used to select heifers that are more likely to achieve pregnancy and have reduced times to conception.

Estimating regression standard errors with data from the Current Population Survey's public use file.

This study examines whether reasonable standard errors for multivariate models can be calculated using the public use file of the Current Population Survey's Annual Social and Economic Supplement (CPS ASEC). We restrict our analysis to the 2003 CPS ASEC and model three dependent variables at the individual level. income, poverty, and health insurance coverage. We compare standard error estimates performed on the CPS ASEC public use file with those obtained from the Census Bureau's restricted internal data that include all the relevant sampling information needed to compute standard errors adjusted for the complex survey sample design. Our analysis shows that the multivariate standard error estimates derived from the public use CPS ASEC following our specification perform relatively well compared to the estimates derived from the internal Census Bureau file. However, it is essential that users of CPS ASEC data do not simply choose any available method since three of the methods commonly used for adjusting for the complex sample design produce substantially different estimates.