Outcome of neurological early rehabilitation patients carrying multi-drug resistant bacteria: results from a German multi-center study.

BACKGROUND: Colonization or infection with multi-drug resistant (MDR) bacteria is considered detrimental to the outcome of neurological and neurosurgical early rehabilitation patients. METHODS: In a German multi-center study, 754 neurological early rehabilitation patients were enrolled and and reviewed in respect to MDR status, length of stay (LOS) and the following outcome variables: Barthel Index (BI), Early Rehabilitation Index (ERI), Glasgow Outcome Score Extended (GOSE), Coma Remission Scale (CRS), Functional Ambulation Categories (FAC). RESULTS: The mean age of the study population was 68.0 ± 14.8 years. Upon admission, the following prevalence for MDRs was observed: MRSA (methicillin resistant staphylococcus aureus) 7.0% (53/754), ESBL- (extended spectrum beta-lactamase) producing bacteria strains 12.6% (95/754), VRE (vancomycin resistant enterococci) 2.8% (21/754). Patients colonized or infected with MDR bacteria (MDR+) were significantly more frequently diagnosed with a critical illness polyneuropathy - CIP - than non-colonized (MDR-) patients: 29.0% vs. 14.8%. In addition, they were more frequently mechanically ventilated (MDR+: 55/138, 39.9%; MDR- 137/616, 22.2%). MDR+ patients were referred to rehabilitation earlier, had a longer LOS in early rehabilitation, lower BI on admission and at discharge, lower ERI on admission and lower CRS at discharge than MDR- patients. There was a highly significant correlation of the BI upon admission with the BI at discharge (rs = 0.492, p < 0.001). GOSE at discharge differed significantly between both groups (χ 2-test, p < 0.01). Perhaps of greatest importance, mortality among MDR+ was higher in comparison to MDR- (18.1% vs. 7.6%). CONCLUSIONS: The outcome of neurological early rehabilitation patients colonized or infected with MDR bacteria including MRSA or ESBL producing strains is significantly poorer than by non-colonized patients. There is some evidence that the poor outcome could be related to the higher morbidity and lower functional status upon admission.

[Prolonged weaning during early neurological and neurosurgical rehabilitation : S2k guideline published by the Weaning Committee of the German Neurorehabilitation Society (DGNR)]. / Prolongiertes Weaning in der neurologisch-neurochirurgischen Frührehabilitation : S2k-Leitlinie herausgegeben von der Weaning-Kommission der Deutschen Gesellschaft für Neurorehabilitation e. V. (DGNR).

Prolonged weaning of patients with neurological or neurosurgery disorders is associated with specific characteristics, which are taken into account by the German Society for Neurorehabilitation (DGNR) in its own guideline. The current S2k guideline of the German Society for Pneumology and Respiratory Medicine is referred to explicitly with regard to definitions (e.g., weaning and weaning failure), weaning categories, pathophysiology of weaning failure, and general weaning strategies. In early neurological and neurosurgery rehabilitation, patients with central of respiratory regulation disturbances (e.g., cerebral stem lesions), swallowing disturbances (neurogenic dysphagia), neuromuscular problems (e.g., critical illness polyneuropathy, Guillain-Barre syndrome, paraplegia, Myasthenia gravis) and/or cognitive disturbances (e.g., disturbed consciousness and vigilance disorders, severe communication disorders), whose care during the weaning of ventilation requires, in addition to intensive medical competence, neurological or neurosurgical and neurorehabilitation expertise. In Germany, this competence is present in centers of early neurological and neurosurgery rehabilitation, as a hospital treatment. The guideline is based on a systematic search of guideline databases and MEDLINE. Consensus was established by means of a nominal group process and Delphi procedure moderated by the Association of the Scientific Medical Societies in Germany (AWMF). In the present guideline of the DGNR, the special structural and substantive characteristics of early neurological and neurosurgery rehabilitation and existing studies on weaning in early rehabilitation facilities are examined.Addressees of the guideline are neurologists, neurosurgeons, anesthesiologists, palliative physicians, speech therapists, intensive care staff, ergotherapists, physiotherapists, and neuropsychologists. In addition, this guideline is intended to provide information to specialists for physical medicine and rehabilitation (PMR), pneumologists, internists, respiratory therapists, the German Medical Service of Health Insurance Funds (MDK) and the German Association of Health Insurance Funds (MDS). The main goal of this guideline is to convey the current knowledge on the subject of "Prolonged weaning in early neurological and neurosurgery rehabilitation".

[Efficacy of early neurological and neurosurgical rehabilitation : Evidence-based treatment, outcome and prognostic factors]. / Wirksamkeit der neurologisch-neurochirurgischen Frührehabilitation : Evidenzbasierte Therapieformen, Outcome und Prognosefaktoren.

BACKGROUND: Early neurological and neurosurgical rehabilitation (ENNR) as a complex post-acute form of treatment for patients with severe neurological diseases and continued need for intensive care is well established in Germany. OBJECTIVE: To assess the efficacy of ENNR from the perspective of evidence-based medicine as well as to present data on the outcome of ENNR patients including the analysis of prognostic factors. MATERIAL AND METHODS: A search was carried out in PubMed databases to identify early rehabilitation treatment forms evaluated by randomized controlled trials and with respect to large multicenter surveys of outcome and prognostic factors. RESULTS: For ENNR as a complex treatment concept, effectiveness not has been shown with regard to evidence-based medicine but it includes individually effective treatment forms. In two large multicenter evaluations the average duration of treatment was between 51 and 57 days and mortality was between 6 % and 10 %, increasing with the proportion of mechanically ventilated patients. Lower need for nursing support on admission indicated better outcome, whereas mechanical ventilation was more likely to be associated with poor outcome. Long-term outcome was negatively influenced by mechanical ventilation as well as severe neurogenic dysphagia with and without the need for a tracheal cannula and/or percutaneous endoscopic gastrostomy (PEG) and also by severely impaired communication at the end of ENNR. DISCUSSION: These prognostic factors indicate the primary aims of ENNR, which are to reduce the need for nursing support and to establish the capability for rehabilitation. If these aims are achieved, favorable functional and long-term outcome can be expected for ENNR patients. The presented studies verify the sustained efficacy of ENNR as an essential part of the overall treatment concept for severely neurologically impaired patients.

[Course of rehabilitation in early neurological/neurosurgical rehabilitation. Results of a 2014 multi-center evaluation in Germany]. / Rehabilitationsverlauf von Patienten in der neurologisch-neurochirurgischen Frührehabilitation.

BACKGROUND: In Germany, neurological-neurosurgical early rehabilitation is well established in the treatment of severe neurological diseases. To develop quality standards, knowledge of the current rehabilitation course is required. PATIENTS AND METHODS: A retrospective analysis was performed on the course of rehabilitation from patients in an early neurological/neurosurgical rehabilitation program in 16 centers from 10 German states. The odds for a good or poor outcome were investigated using a multivariate logistic regression model. RESULTS: Seven hundred and fifty-four patients were included in the study. The average age of the patients was 68 ± 15 years. Of the patients studied, 26 % were on mechanical ventilation commencing their neurological rehabilitation. The average duration of stay was 56 ± 51 days. Weaning rate from mechanical ventilation was 65 % and the rate of weaning from tracheal cannula was 54 %. Mean improvement in the Barthel Index of 17 points, significant reduction of dysphagia (from 62 to 30 %) and depended walking (from 99 to 82 %), and the achievement of phase C (the next stage of rehabilitation) in 38 % can still be counted as signs of successful rehabilitation. During their course of stay, near 10 % of the patients died. Of these, 67 % received solely palliative care. In the multivariate logistic models, the absence of the factor "necessity for mechanical ventilation on admission" (odds ratio 0.61; 95 % confidence interval (CI): 0.42 … 0.89) increased the chance for good outcome and the presence of this factor the risk of dying with an odds ratio of 8.07 (95 % CI: 4.54-14.34). DISCUSSION: In spite of the severity of neurological deficits, significant functional progress has been made. These results could be interpret as positive proof of the efficacy of neurological/neurosurgical early rehabilitation programs.

Fine-Tuning of Photoautotrophic Protein Production by Combining Promoters and Neutral Sites in the Cyanobacterium Synechocystis sp. Strain PCC 6803.

Cyanobacteria are photosynthetic cell factories that use solar energy to convert CO2 into useful products. Despite this attractive feature, the development of tools for engineering cyanobacterial chassis has lagged behind that for heterotrophs such as Escherichia coli or Saccharomyces cerevisiae. Heterologous genes in cyanobacteria are often integrated at presumptively "neutral" chromosomal sites, with unknown effects. We used transcriptome sequencing (RNA-seq) data for the model cyanobacterium Synechocystis sp. strain PCC 6803 to identify neutral sites from which no transcripts are expressed. We characterized the two largest such sites on the chromosome, a site on an endogenous plasmid, and a shuttle vector by integrating an enhanced yellow fluorescent protein (EYFP) expression cassette expressed from either the Pcpc560 or the Ptrc1O promoter into each locus. Expression from the endogenous plasmid was as much as 14-fold higher than that from the chromosome, with intermediate expression from the shuttle vector. The expression characteristics of each locus correlated predictably with the promoters used. These findings provide novel, characterized tools for synthetic biology and metabolic engineering in cyanobacteria.

Fall-grown oat to extend the fall grazing season for replacement dairy heifers.

Our objective was to assess the pasture productivity and forage characteristics of 2 fall-grown oat (Avena sativa L.) cultivars, specifically for extending the grazing season and reducing reliance on harvested forages by replacement dairy heifers. A total of 160 gravid Holstein heifers (80 heifers/yr) were stratified by weight, and assigned to 1 of 10 identical research pens (8 heifers/pen). Initial body weights were 480 ± 43.5 kg in 2011 and 509 ± 39.4 kg in 2012. During both years of the trial, four 1.0-ha pasture replicates were seeded in August with Ogle oat (Schumitsch Seed Inc., Antigo, WI), and 4 separate, but similarly configured, pasture replicates were seeded with Forage Plus oat (Kratz Farms, Slinger, WI). Heifer groups were maintained as units, assigned to specific pastures, and then allowed to graze fall-oat pastures for 6h daily before returning to the barn, where they were offered a forage-based basal total mixed ration. Two heifer groups were retained in confinement (without grazing) as controls and offered the identical total mixed ration as pasture groups. During 2011, available forage mass increased with strong linear and quadratic effects for both cultivars, peaking at almost 9 Mg/ha on October 31. In contrast, forage mass was not affected by evaluation date in 2012, remaining ≤ 2,639 kg/ha across all dates because of droughty climatic conditions. During 2012, Ogle exhibited greater forage mass than Forage Plus across all sampling dates (2,678 vs. 1,856 kg/ha), largely because of its more rapid maturation rate and greater canopy height. Estimates of energy density for oat forage ranged from 59.6 to 69.1% during 2011, and ranged narrowly from 68.4 to 70.4% during 2012. For 2011, responses for both cultivars had strong quadratic character, in which the most energy-dense forages occurred in mid November, largely due to accumulation of water-soluble carbohydrates that reached maximum concentrations of 18.2 and 15.1% for Forage Plus and Ogle, respectively. Across the 2-yr trial, average daily gain for grazing heifer groups tended to be greater than heifers remaining in confinement (0.85 vs. 0.74 kg/d), but both management strategies produced weight gains within reasonable proximity to normal targets for heifers in this weight range. Fall-grown oat should be managed as stockpiled forage for deferred grazing, and good utilization of fall-oat forage can be accomplished by a one-time removal of standing forage, facilitated by a single lead wire advanced daily to prevent waste.

Effects of dairy slurry on silage fermentation characteristics and nutritive value of alfalfa.

Dairy producers frequently ask questions about the risks associated with applying dairy slurry to growing alfalfa (Medicago sativa L.). Our objectives were to determine the effects of applying dairy slurry on the subsequent nutritive value and fermentation characteristics of alfalfa balage. Dairy slurry was applied to 0.17-ha plots of alfalfa; applications were made to the second (HARV1) and third (HARV2) cuttings during June and July of 2012, respectively, at mean rates of 42,400 ± 5271 and 41,700 ± 2397 L/ha, respectively. Application strategies included (1) no slurry, (2) slurry applied directly to stubble immediately after the preceding harvest, (3) slurry applied after 1 wk of post-ensiled regrowth, or (4) slurry applied after 2 wk of regrowth. All harvested forage was packaged in large, rectangular bales that were ensiled as wrapped balage. Yields of DM harvested from HARV1 (2,477 kg/ha) and HARV2 (781 kg/ha) were not affected by slurry application treatment. By May 2013, all silages appeared to be well preserved, with no indication of undesirable odors characteristic of clostridial fermentations. Clostridium tyrobutyricum, which is known to negatively affect cheese production, was not detected in any forage on either a pre- or post-ensiled basis. On a pre-ensiled basis, counts for Clostridium cluster 1 were greater for slurry-applied plots than for those receiving no slurry, and this response was consistent for HARV1 (4.44 vs. 3.29 log10 genomic copies/g) and HARV2 (4.99 vs. 3.88 log10 genomic copies/g). Similar responses were observed on a post-ensiled basis; however, post-ensiled counts also were greater for HARV1 (5.51 vs. 5.17 log10 genomic copies/g) and HARV2 (5.84 vs. 5.28 log10 genomic copies/g) when slurry was applied to regrowth compared with stubble. For HARV2, counts also were greater following a 2-wk application delay compared with a 1-wk delay (6.23 vs. 5.45 log10 genomic copies/g). These results suggest that the risk of clostridial fermentations in alfalfa silages is greater following applications of slurry. Based on pre- and post-ensiled clostridial counts, applications of dairy slurry on stubble are preferred (and less risky) compared with delayed applications on growing alfalfa.

Coronary artery bypass grafting using the radial artery: clinical outcomes, patency, and need for reintervention.

BACKGROUND: Radial artery (RA) grafts are an attractive second arterial conduit after the left internal thoracic artery (LITA) for coronary artery bypass graft (CABG) surgery. However, long-term outcomes and the need for subsequent reintervention have not been defined. METHODS AND RESULTS: We performed a retrospective cohort study of our single institution's 16-year experience with 1851 consecutive patients (average age, 58 years; 82% men, 36% diabetic) undergoing primary, isolated CABG with the LITA, RA, and saphenous vein as needed. Average grafts per patient were 3.8, with 2.4 arterial grafts per patient. Survival was determined using the Social Security Death Index. Grafts were nonpatent if they had a >50% stenosis, a string sign, or were occluded. Five patients (0.3%) died in hospital and 0.8% had a myocardial infarction, 1.1% a stroke, and 0.6% renal failure. Kaplan-Meier-estimated 1-, 5-, 10-, and 15-year survival was 99%, 96%, 89%, and 75%, respectively. Of the cohort, 278 symptomatic patients underwent cardiac catheterization at our institution an average of 5.0±3.8 years (range, 0.1-12 years) after CABG. Overall RA (n=420 grafts) patency was 82% and SV (n=364 grafts) patency, 47% (P<0.0001). LITA (n=287 grafts including 9 sequential grafts) patency was 85% and right internal thoracic artery (n=15 grafts) patency was 80% (P=0.6). RA patency was not different from LITA patency (P=0.3). Overall freedom from catheterization, percutaneous coronary intervention, and CABG was 85%, 97%, and 99%, respectively. CONCLUSIONS: RA grafting is a highly effective revascularization strategy providing excellent short and long-term outcomes with very low rates of reintervention. RA patency is similar to LITA patency and is much better than SV patency. RA grafting should be more widely utilized in patients undergoing CABG.

Storage characteristics, nutritive value, energy content, and in vivo digestibility of moist, large rectangular bales of alfalfa-orchardgrass hay treated with a propionic acid-based preservative.

Unstable weather, poor drying conditions, and unpredictable rainfall events often place valuable hay crops at risk. Recent research with large round bales composed of alfalfa (Medicago sativa L.) and orchardgrass (Dactylis glomerata L.) has shown that these large-bale packages are particularly sensitive to spontaneous heating and dry matter (DM) losses, as well as other undesirable changes with respect to forage fiber, protein, and energy density. Various formulations of organic acids have been marketed as preservatives, normally for use on hays that are not desiccated adequately in the field to facilitate safe bale storage. Our objectives for this study were to (1) evaluate the efficacy of applying a commercial (buffered) propionic acid-based preservative at 3 rates (0, 0.6, and 1.0% of wet-bale weight) to hays baled at 3 moisture concentrations (19.6, 23.8, and 27.4%) on the subsequent storage characteristics and poststorage nutritive value of alfalfa-orchardgrass forages packaged in large rectangular (285-kg) bales, and then (2) evaluate the in vivo digestibility of these hays in growing lambs. Over a 73-d storage period, the preservative was effective at limiting spontaneous heating in these hays, and a clear effect of application rate was observed for the wettest (27.4%) bales. For drier hays, both acid-application rates (1.0 and 0.6%) yielded comparable reductions in heating degree days >30°C relative to untreated controls. Reductions in spontaneous heating could not be associated with improved recovery of forage DM after storage. In this study, most changes in nutritive value during storage were related to measures of spontaneous heating in simple linear regression relationships; this suggests that the modest advantages in nutritive value resulting from acid treatment were largely associated with perturbations of normal heating patterns during bale storage. Although somewhat erratic, apparent digestibilities of both DM (Y=-0.0080x + 55.6; R(2)=0.45) and organic matter (Y=-0.0085x + 55.5; R(2)=0.53) evaluated in growing lambs were also directly related to heating degree days in simple linear relationships. Based on these data, applying propionic acid-based preservatives to large rectangular bales is likely to provide good insurance against spontaneous heating during storage, as well as modest benefits with respect to nutritive value and digestibility.

Unique interrelationships between fiber composition, water-soluble carbohydrates, and in vitro gas production for fall-grown oat forages.

Sixty samples of 'ForagePlus' oat were selected from a previous plot study for analysis of in vitro gas production (IVGP) on the basis of 2 factors: (1) high (n=29) or low (n=31) neutral detergent fiber (NDF; 62.7±2.61 and 45.1±3.91%, respectively); and (2) the range of water-soluble carbohydrates (WSC) within the high- and low-NDF groups. For the WSC selection factor, concentrations ranged from 4.7 to 13.4% (mean=7.9±2.06%) and from 3.5 to 19.4% (mean=9.7±4.57%) within high- and low-NDF forages, respectively. Our objectives were to assess the relationships between IVGP and various agronomic or nutritional characteristics for high- and low-NDF fall-oat forages. Cumulative IVGP was fitted to a single-pool nonlinear regression model: Y=MAX × (1 - e ([-)(K)(× (t - lag)])), where Y=cumulative gas produced (mL), MAX=maximum cumulative gas produced with infinite incubation time (mL), K=rate constant, t=incubation time (h), and lag=discrete lag time (h). Generally, cumulative IVGP after 12, 24, 36, or 48h within high-NDF fall-oat forages was negatively correlated with NDF, hemicellulose, lignin, and ash, but positively correlated with WSC, nonfiber carbohydrate (NFC), and total digestible nutrients (TDN). For low-NDF fall-grown oat forages, IVGP was positively correlated with growth stage, canopy height, WSC, NFC, and TDN; negative correlations were observed with ash and crude protein (CP) but not generally with fiber components. These responses were also reflected in multiple regression analysis for high- and low-NDF forages. After 12, 24, or 36h of incubation, cumulative IVGP within high-NDF fall-oat forages was explained by complex regression equations utilizing (lignin:NDF)(2), lignin:NDF, hemicellulose, lignin, and TDN(2) as independent variables (R(2)≥0.43). Within low-NDF fall-grown oat forages, cumulative IVGP at these incubation intervals was explained by positive linear relationships with NFC that also exhibited high coefficients of determination (R(2)≥0.75). Gas production was accelerated at early incubation times within low-NDF forages, specifically in response to large pools of WSC that were most likely to be present as forages approached boot stage by late-fall.

Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome.

The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are DYT1, encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa-responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the recessive form of the disease. Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles. Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease. In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior. In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs. 11-13). Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region of about 3.2 Mb. SGCE is expressed in all brain regions examined. Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele. This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse epsilon-sarcoglycan gene.

Upregulation of plasmid genes during stationary phase in Synechocystis sp. strain PCC 6803, a cyanobacterium.

We analyzed DNA microarrays to identify highly expressed genes during stationary-phase growth of Synechocystis sp. PCC 6803. Many identified genes are on endogenous plasmids, with copy numbers between 0.4 and 7 per chromosome. The promoters of such genes will be useful for synthetic biology applications with this phototrophic host.

Effects of a propionic acid-based preservative on storage characteristics, nutritive value, and energy content for alfalfa hays packaged in large round bales.

During 2009 and 2010, alfalfa (Medicago sativa L.) hays from 2 cuttings harvested from the same field site were used to evaluate the effects of a propionic acid-based preservative on the storage characteristics and nutritive value of hays stored as large round bales. A total of 87 large round bales (diameter = 1.5m) were included in the study; of these, 45 bales served as controls, whereas 42 were treated with a commercial propionic acid-based preservative at mean application rates of 0.5±0.14 and 0.7±0.19% of bale weight, expressed on a wet (as is) or dry matter basis, respectively. Initial bale moisture concentrations ranged from 10.2 to 40.4%. Internal bale temperatures were monitored daily during an outdoor storage period, and heating characteristics were summarized for each bale as heating degree days (HDD) >30°C. For acid-treated bales, the regression relationship between HDD and initial bale moisture was best fitted to a quadratic model in which the linear term was dropped to improve fit (Y=2.02x(2) - 401; R(2)=0.77); control hays were best fitted to a nonlinear model in which the independent variable was squared [Y=4,112 - (4,549×e(-0.000559x*x)); R(2)=0.77]. Based on these regressions, acid-treated bales accumulated more HDD than control hays when the initial bale moisture was >27.7%; this occurred largely because acid treatment tended to prolong active heating relative to control hays. Linear regressions of recoveries of dry matter on HDD did not differ on the basis of treatment, yielding a common linear relationship of Y=-0.0066x+96.3 (R(2)=0.75). Regressions relating changes (post-storage - pre-storage) in concentrations of several nutritional components (neutral detergent fiber, lignin, ash, crude protein, and total digestible nutrients) with HDD for acid-treated hays typically exhibited more inflection points or were higher-ordered polynomial regressions than those of control hays. These more complex responses probably reflected the perturbation of normal heating patterns following acid treatment; however, overall effects on post-storage nutritive value were relatively limited in scope. The potential to improve nutritive value relative to cost for these large round bales was not especially favorable, and hay producers may find that diligence to achieve adequate field desiccation before baling, or use of oxygen-exclusion methods, such as wrapping in plastic, may be better alternatives for preserving moist hays.

Using eastern gamagrass to construct diets that limit intake and caloric density for dairy replacement heifers.

Previous research has shown that eastern gamagrass (EGG; Tripsacum dactyloides L.) will survive winter climatic conditions common throughout central Wisconsin, and will produce yields of dry matter (DM) ranging approximately from 7,000 to 10,000 kg/ha annually when managed with a 1-cut harvest system. The objective of this research was to determine whether the fibrous nature of this perennial warm-season grass could be effective in reducing the caloric density and DMI of corn silage/alfalfa haylage diets for replacement dairy heifers. A total of 120 Holstein dairy heifers were blocked by body weight (heavy, 424 ± 15.9 kg; medium, 369 ± 11.8 kg; light, 324 ± 22.4 kg), and then assigned to 15 individual pens containing 8heifers each. Eastern gamagrass forage was harvested, ensiled, and subsequently incorporated into blended corn silage/alfalfa haylage diets at rates of 0, 9.1, 18.3, or 27.4% of the total dietary DM (EGG0, EGG9, EGG18, and EGG27, respectively). These diets were offered during a 105-d evaluation period for ad libitum intake; however, the EGG0 diet also was offered on a limit-fed basis (LF), which was set at 85% of the voluntary intake of EGG0. Serial additions of EGG increased concentrations of neutral detergent fiber in blended diets from 39.6 (EGG0) to 48.7% (EGG27), and simultaneously reduced corresponding estimates of total digestible nutrients (TDN) from 68.2 to 61.3%, and net energy for gain from 1.07 to 0.83 Mcal/kg. Dry matter intakes for all diets offered ad libitum were greater than observed for LF (9.06 vs. 8.07 kg/d); however, DM intakes for diets containing EGG were reduced relative to EGG0 (9.40 vs. 8.94 kg/d). Similarly, intakes of TDN were greater for diets offered for ad libitum intake than for LF (5.84 vs. 5.50 kg/d); however, inclusion of EGG reduced TDN intakes relative to EGG0 (6.41 vs. 5.65 kg/d). This reduction was explained by both linear and quadratic effects of the inclusion rate of EGG in the diet. Over the 105-d trial, total weight gains ranged from 89 kg (0.85 kg/d) for heifers offered EGG27 up to 114 kg (1.09 kg/d) for those offered EGG0. Performance was similar between heifers offered EGG27 and LF diets (0.85 vs. 0.88 kg/d). Eastern gamagrass haylage proved to be a completely nonsortable additive within corn silage/alfalfa haylage diets. It also was effective in limiting the caloric density and DM intake of these diets, as well as undesirable weight gains by dairy heifers.

Water temperature affects the biotransformation and accumulation of a psychoactive pharmaceutical and its metabolite in aquatic organisms.

Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental factor in nature, affects uptake, biotransformation, and the subsequent accumulation of PhACs in aquatic organisms is limited. In this study, we tested to what extent bioconcentration of an anxiolytic drugs (temazepam and oxazepam) is affected by two temperature regimes (10 and 20 °C) and how the temperature affects the temazepam biotransformation and subsequent accumulation of its metabolite (oxazepam) in aquatic organisms. We used European perch (Perca fluviatilis) and dragonfly larvae (Sympetrum sp.), which represent predator and prey species of high ecological relevance in food chains of boreal and temperate aquatic ecosystems. Experimental organisms were exposed to target pharmaceuticals at a range of concentrations (0.2-6 µg L-1) to study concentration dependent differences in bioconcentration and biotransformation. We found that the bioconcentration of temazepam in perch was significantly reduced at higher temperatures. Also, temperature had a strong effect on temazepam biotransformation in the fish, with the production and subsequent accumulation of its metabolite (oxazepam) being two-fold higher at 20 °C compared to 10 °C. In contrast, we found no temperature dependency for temazepam bioconcentration in dragonfly larvae and no detectable biotransformation of the parent compound that would result in measurable concentrations of oxazepam in this organism. Our results highlight that while organisms may share the same aquatic ecosystem, their exposure to PhACs may change differently across temperature gradients in the environment.

The cost-effectiveness of banning highly hazardous pesticides to prevent suicides due to pesticide self-ingestion across 14 countries: an economic modelling study.

BACKGROUND: Reducing suicides is a key Sustainable Development Goal target for improving global health. Highly hazardous pesticides are among the leading causes of death by suicide in low-income and middle-income countries. National bans of acutely toxic highly hazardous pesticides have led to substantial reductions in pesticide-attributable suicides across several countries. This study evaluated the cost-effectiveness of implementing national bans of highly hazardous pesticides to reduce the burden of pesticide suicides. METHODS: A Markov model was developed to examine the costs and health effects of implementing a national ban of highly hazardous pesticides to prevent suicides due to pesticide self-poisoning, compared with a null comparator. We used WHO cost-effectiveness and strategic planning (WHO-CHOICE) methods to estimate pesticide-attributable suicide rates for 100 years from 2017. Country-specific costs were obtained from the WHO-CHOICE database and denominated in 2017 international dollars (I$), discounted at a 3% annual rate, and health effects were measured in healthy life-years gained (HLYGs). We used a demographic projection model beginning with the country population in the baseline year (2017), split by 1-year age group and sex. Country-specific data on overall suicide rates were obtained for 2017 by age and sex from the Global Burden of Disease Study 2017 Data Resources. The analysis involved 14 countries spanning low-income to high-income settings, and cost-effectiveness ratios were analysed at the country-specific level and aggregated according to country income group and the proportion of suicides due to pesticides. FINDINGS: Banning highly hazardous pesticides across the 14 countries studied could result in about 28 000 (95% uncertainty interval [UI] 24 000-32 000) fewer suicide deaths each year at an annual cost of I$0·007 per capita (95% UI 0·006-0·008). In the population-standardised results for the base case analysis, national bans produced cost-effectiveness ratios of $94 per HLYG (95% UI 73-123) across low-income and lower-middle-income countries and $237 per HLYG (95% UI 191-303) across upper-middle-income and high-income countries. Bans were more cost-effective in countries where a high proportion of suicides are attributable to pesticide self-poisoning, reaching a cost-effectiveness ratio of $75 per HLYG (95% UI 58-99) in two countries with proportions of more than 30%. INTERPRETATION: National bans of highly hazardous pesticides are a potentially cost-effective and affordable intervention for reducing suicide deaths in countries with a high burden of suicides attributable to pesticides. However, our study findings are limited by imperfect data and assumptions that could be improved upon by future studies. FUNDING: WHO.

Assessing the cost-effectiveness of drug and lifestyle intervention following opportunistic screening for pre-diabetes in primary care.

AIMS/HYPOTHESIS: This study aims to evaluate the cost-effectiveness of a screening programme for pre-diabetes, which was followed up by treatment with pharmaceutical interventions (acarbose, metformin, orlistat) or lifestyle interventions (diet, exercise, diet and exercise) in order to prevent or slow the onset of diabetes in those at high risk. METHODS: To approximate the experience of individuals with pre-diabetes in the Australian population, we used a microsimulation approach, following patient progression through diabetes, cardiovascular disease and renal failure. The model compares costs and disability-adjusted life years lived in people identified through an opportunistic screening programme for each intervention compared with a 'do nothing' scenario, which is representative of current practice. It is assumed that the effect of a lifestyle change will decay by 10% per year, while the effect of a pharmaceutical intervention remains constant throughout use. RESULTS: The most cost-effective intervention options are diet and exercise combined, with a cost-effectiveness ratio of AUD 22,500 per disability-adjusted life year (DALY) averted, and metformin with a cost-effectiveness ratio of AUD 21,500 per DALY averted. The incremental addition of one intervention to the other is not cost-effective. CONCLUSIONS/INTERPRETATION: Screening for pre-diabetes followed by diet and exercise, or metformin treatment is cost-effective and should be considered for incorporation into current practice. The number of dietitians and exercise physiologists needed to deliver such lifestyle change interventions will need to be increased to appropriately support the intervention.

Comprehensive analysis of the Brassica juncea root proteome in response to cadmium exposure by complementary proteomic approaches.

Indian mustard (Brassica juncea L.) is known to both accumulate and tolerate high levels of heavy metals from polluted soils. To gain a comprehensive understanding of the effect of cadmium (Cd) treatment on B. juncea roots, two quantitative proteomics approaches--fluorescence two-dimensional difference gel electrophoresis (2-D DIGE) and multiplexed isobaric tagging technology (iTRAQ)--were implemented. Several proteins involved in sulfur assimilation, redox homeostasis, and xenobiotic detoxification were found to be up-regulated. Multiple proteins involved in protein synthesis and processing were down-regulated. While the two proteomics approaches identified different sets of proteins, the proteins identified in both datasets are involved in similar biological processes. We show that 2-D DIGE and iTRAQ results are complementary, that the data obtained independently using the two techniques validate one another, and that the quality of iTRAQ results depends on both the number of biological replicates and the number of sample injections. This study determined the involvement of enzymes such as peptide methionine sulfoxide reductase and 2-nitropropane dioxygenase in alternatives redox-regulation mechanisms, as well as O-acetylserine sulfhydrylase, glutathione-S-transferase and glutathione-conjugate membrane transporter, as essential players in the Cd hyperaccumation and tolerance of B. juncea.