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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Inhibition of microbial biofuel production in drought-stressed switchgrass hydrolysate.

BACKGROUND: Interannual variability in precipitation, particularly drought, can affect lignocellulosic crop biomass yields and composition, and is expected to increase biofuel yield variability. However, the effect of precipitation on downstream fermentation processes has never been directly characterized. In order to investigate the impact of interannual climate variability on biofuel production, corn stover and switchgrass were collected during 3 years with significantly different precipitation profiles, representing a major drought year (2012) and 2 years with average precipitation for the entire season (2010 and 2013). All feedstocks were AFEX (ammonia fiber expansion)-pretreated, enzymatically hydrolyzed, and the hydrolysates separately fermented using xylose-utilizing strains of Saccharomyces cerevisiae and Zymomonas mobilis. A chemical genomics approach was also used to evaluate the growth of yeast mutants in the hydrolysates. RESULTS: While most corn stover and switchgrass hydrolysates were readily fermented, growth of S. cerevisiae was completely inhibited in hydrolysate generated from drought-stressed switchgrass. Based on chemical genomics analysis, yeast strains deficient in genes related to protein trafficking within the cell were significantly more resistant to the drought-year switchgrass hydrolysate. Detailed biomass and hydrolysate characterization revealed that switchgrass accumulated greater concentrations of soluble sugars in response to the drought and these sugars were subsequently degraded to pyrazines and imidazoles during ammonia-based pretreatment. When added ex situ to normal switchgrass hydrolysate, imidazoles and pyrazines caused anaerobic growth inhibition of S. cerevisiae. CONCLUSIONS: In response to the osmotic pressures experienced during drought stress, plants accumulate soluble sugars that are susceptible to degradation during chemical pretreatments. For ammonia-based pretreatment, these sugars degrade to imidazoles and pyrazines. These compounds contribute to S. cerevisiae growth inhibition in drought-year switchgrass hydrolysate. This work discovered that variation in environmental conditions during the growth of bioenergy crops could have significant detrimental effects on fermentation organisms during biofuel production. These findings are relevant to regions where climate change is predicted to cause an increased incidence of drought and to marginal lands with poor water-holding capacity, where fluctuations in soil moisture may trigger frequent drought stress response in lignocellulosic feedstocks.

For Third Enrollment Period, Marketplaces Expand Decision Support Tools To Assist Consumers.

The design of the Affordable Care Act's online health insurance Marketplaces can improve how consumers make complex health plan choices. We examined the choice environment on the state-based Marketplaces and HealthCare.gov in the third open enrollment period. Compared to previous enrollment periods, we found greater adoption of some decision support tools, such as total cost estimators and integrated provider lookups. Total cost estimators differed in how they generated estimates: In some Marketplaces, consumers categorized their own utilization, while in others, consumers answered detailed questions and were assigned a utilization profile. The tools available before creating an account (in the window-shopping period) and afterward (in the real-shopping period) differed in several Marketplaces. For example, five Marketplaces provided total cost estimators to window shoppers, but only two provided them to real shoppers. Further research is needed on the impact of different choice environments and on which tools are most effective in helping consumers pick optimal plans.

Comparison of 4- versus 5-day Co-Synch + controlled internal drug release (CIDR) + timed artificial insemination protocols in dairy heifers.

The objective of this study was to compare the pregnancy rate after timed artificial insemination (P/TAI) in dairy heifers treated with 4- versus 5-day Co-Synch + controlled internal drug release (CIDR) protocols. A total of 120 Holstein heifers were randomly assigned to one of two groups. The heifers received an intravaginal CIDR insert containing 1.38 g of progesterone for 4 days (Monday-Friday 4-day Co-Synch + CIDR; n = 60) or 5 days (5-day Co-Synch + CIDR; n = 60). At the time of CIDR removal, 25 mg of PGF2α was injected intramuscularly, and 72 hours after CIDR removal, the heifers received 100 µg of GnRH intramuscularly and were artificially inseminated. Artificial insemination was performed by an experienced technician, using commercial frozen-thawed semen from a single sire. Pregnancy diagnosis was performed by ultrasonography per rectum 32 days after TAI. Categorical data were analyzed using proc logistic and the chi-square test, whereas continuous variables were analyzed using the t-test of Statistical Analysis Systems. Heifers in the 4-day Co-Synch + CIDR group had an acceptable P/TAI32 (55.0%, 33 of 60), which was not different (P = 0.35) from that observed in the 5-day Co-Synch + CIDR group (63.3%, 38 of 60). Progesterone concentration at CIDR insertion or estradiol concentration at TAI did not influence the pregnancy outcomes. Interestingly, estradiol concentration at TAI was greater in the 4-day Co-Synch + CIDR group compared to the 5-day Co-Synch + CIDR group (P < 0.01). In conclusion, the Monday to Friday 4-day Co-Synch + CIDR protocol resulted in adequate P/TAI in dairy heifers, which was similar to that of the 5-day Co-Synch + CIDR protocol. This novel protocol might represent a promising hormonal treatment for TAI in dairy heifers, facilitating their reproductive management routine, while maintaining an adequate fertility.

Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease.

Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn's disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne's Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne's disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis), or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 × 10(9) CFU divided in two consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate). All kids were necropsied at 13 months post-challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318) do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329) reduced fecal shedding and tissue colonization.

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.

Dietary fat is a lipid source in 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD)-elicited hepatic steatosis in C57BL/6 mice.

2,3,7,8-Tetrachlorodibenzo-ρ-dioxin (TCDD) increases fatty acid (FA) transport and FA levels resulting in hepatic steatosis in mice. Diet as a source of lipids was investigated using customized diets, stearoyl-CoA desaturase 1 (Scd1) null mice, and (14)C-oleate (18:1n9) uptake studies. C57BL/6 mice fed with 5, 10, or 15% fat or 50, 60 or 70% carbohydrate diets exhibited increased relative liver weight following gavage with 30 µg/kg TCDD for 168 h. Hepatic lipid extract analysis from mice fed with 5, 10, and 15% fat diets identified a dose-dependent increase in total FAs induced by TCDD. Mice fed with fat diet also exhibited a dose-dependent increase in the dietary essential linoleic (18:2n6) and α-linolenic (18:3n3) acids. No dose-dependent FA increase was detected on carbohydrate diets, suggesting dietary fat as a source of lipids in TCDD-induced steatosis as opposed to de novo lipogenesis. TCDD also induced oleate levels threefold in Scd1 null mice that are incapable of desaturating stearate (18:0). This is consistent with oleate representing > 90% of all monounsaturated FAs in rodent chow. Moreover, TCDD increased hepatic (14)C-oleate levels twofold in wild type and 2.4-fold in Scd1 null mice concurrent with the induction of intestinal and hepatic lipid transport genes (Slc27a, Fabp, Ldlr, Cd36, and Apob). In addition, computational scanning identified putative dioxin response elements and in vivo ChIP-chip analysis revealed regions of aryl hydrocarbon receptor (AhR) enrichment in lipid transport genes differentially regulated by TCDD. Collectively, these results suggest the AhR mediates increased uptake of dietary fats that contribute to TCDD-elicited hepatic steatosis.

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.