Effects of two wintering practices on behavioral and physiological indicators of welfare of non-lactating, pregnant dairy cattle in a pasture-based system.

In countries with pasture-based dairy systems and relatively cold winters, such as New Zealand, it is common to manage pregnant, nonlactating cows on forage crop paddocks rather than pasture due to slow pasture growth rates. Wintering dairy cattle on grazed crops can compromise welfare if wet and muddy underfoot conditions occur, which can reduce lying. This study investigated behavioral and physiological indicators of welfare of cows under 2 wintering practices: cows managed on and grazed kale crop (Brassica oleracea), and cows managed on pasture with baled hay. Following dry-off (d 0), 80 cows were randomly assigned to one of the 2 wintering practices (40 cows/practice) and monitored between d 4 and d 32 (phase 1). During this period, lying and stepping behavior was continuously recorded using leg-based accelerometers. Blood samples were obtained at d 0 and 32 for measurements of thyroxine (T4), nonesterified fatty acids (NEFA), white blood cells (WBC), and red blood cells (RBC). All data for phase 1 were presented descriptively due to the lack of treatment replication. Daily mean air temperature during this period was 5.2°C (range: 0.0 to 10.7°C), and rainfall was 1.1mm/d (range: 0 to 5.6mm/d). Between d 4 and 32, cows in both groups spent similar amounts of time lying (pasture with hay cows: 8.9h/24h ± 2.57, kale crop cows: 8.7h/24h ± 3.06, mean ± SEM). Both groups reduced their lying on wet and cold days and there was evidence of rebound lying once unfavorable weather conditions stopped. Cows on kale crop had numerically higher NEFA and lower WBC compared with cows managed on pasture, although most physiological values were within normal ranges. In a second phase of the study (d 34 and 35), cows were managed under controlled, replicated conditions in the 2 wintering practices using typical on-farm stocking rates (2 or 4 cows per group in the pasture with hay and kale crop treatments, respectively; n = 10 groups/treatment). During this period, cow behavior, skin and surface temperatures, hygiene scores, feed intakes and ground conditions were measured. Weather conditions during the 48-h exposure were mostly cold and dry (mean air temperature: 7.8°C, range: -2.2 to 20.5°C). Cows managed on pasture with hay spent more time lying down on the first day of exposure, however, this was likely due to less space being available to kale cows on this day. Cows managed on pasture with hay ruminated more than cows on kale crop on both days of observations (Day 1: 37.9% vs 30.9% of observations, Day 2: 36.8% vs 28.7% of observations for pasture with hay and kale crop groups, respectively) and were lying more often in postures indicative of greater thermal comfort. Cows managed on pasture with hay had higher skin and surface temperatures compared with cows on kale crop, whereas cows on kale crop had dirtier coats. Results suggest that opportunities for thermal comfort were greater for cows managed on pasture with hay bales, which may be due to increased rumination activities and more insulated lying areas.

Biopsychosocial factors associated with depression and anxiety in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Depression and anxiety are amongst the most prevalent mental health disorders in the older population with intellectual disability (ID). There is a paucity of research that pertains to associative biopsychosocial factors for depression and anxiety in this population. The aim of this study is to determine the biopsychosocial factors associated with depression and anxiety in a population of older adults with ID in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. Depressive symptoms were assessed using the Glasgow Depression Scale for people with a Learning Disability. Anxiety symptoms were measured using the Glasgow Anxiety Scale for people with a Learning Disability. The cross-sectional associations of depression and anxiety with biopsychosocial parameters were measured using a variety of self-report and proxy-completed questionnaires. RESULTS: For the study population, 9.97% met the criteria for depression, and 15.12% met the criteria for an anxiety disorder. Participants meeting criteria for depression were more likely to be taking regular mood stabiliser medications and to exhibit aggressive challenging behaviour. Participants meeting criteria for anxiety were more likely to have sleep difficulties and report loneliness. Participants meeting criteria for either/both depression and anxiety were more likely to report loneliness. CONCLUSIONS: This study identified both treatable and modifiable, as well as unmodifiable, biopsychosocial factors associated with depression and/or anxiety in older adults with ID. A longitudinal study follow-up will further develop our knowledge on the causality and direction of associated biopsychosocial factors with depression and anxiety in older adults with ID and better inform management strategies, prevention policies and funding of services.

The association of life events and mental ill health in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Exposures to life events are associated with emotional, psychological and behavioural problems in those with intellectual disability (ID). Older adults with ID may experience different life events given differences in living circumstances, cognitive decline, greater dependency on others and less autonomy. This study examines the relationship of life events and mental ill health in an older ID population in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. The frequency of life events was assessed using a 20-item checklist, and the level of stress experienced was assessed using a three-point Likert scale measuring the burden of the life event. The associations of life events with factors associated with mental ill health were measured using a variety of self-report and proxy completed questionnaires. RESULTS: For the study population, 88.1% had been exposed to at least one life event in the preceding 12 months and 64.5% to two or more life events. Frequency and burden of life events were significantly higher in individuals living in institutional settings and in individuals with any current psychiatric condition, increased depressive and anxiety symptoms, challenging behaviour and reported poorer self-rated mental and physical health. More life events were significantly associated with new psychiatric diagnoses as well as initiation and increased dosage of mood stabilising, hypnotic and sedative medications. CONCLUSIONS: Life events are significantly associated with mental ill health in the older ID population. Service providers must focus on limiting the exposure to these events and, in situations where they cannot be avoided, should support and manage individuals compassionately and effectively, prioritising their mental and physical well-being.

A visible-light photocatalytic thiolation of aryl, heteroaryl and vinyl iodides.

The general catalytic synthesis of aryl and vinyl thioethers from readily available halides remains a challenge. Herein we report a unified method for the thiolation of aryl and vinyl iodides with dialkyl disulfides using visible light photoredox catalysis. A range of thioether products bearing diverse functional groups can be accessed in high yield and with excellent chemoselectivity. We demonstrate the versatility of this method through the expedient synthesis of a family of thioether-rich natural products. A detailed investigation of the photocatalytic mechanism is presented from both steady-state and time-resolved luminescent quenching as well as transient absorption spectroscopy experiments.

Controlling wettability of PECVD-deposited dual organosilicon/carboxylic acid films to influence DNA hybridisation assay efficiency.

Herein, plasma polymerisation of a dual-layer tetraethyl orthosilicate (TEOS) and acrylic acid (AA) film under a specific recipe is performed. Newly deposited films are found to retain a weakly-bound soft layer of partially polymerised acrylic acid (wbAA), which can be ultimately removed by washing. However, when on the surface, this soft layer is shown to be influential in manipulating the properties of a robust covalently-bound AA (cbAA) underlayer when treated appropriately. Specifically, treatment of the as-deposited dual-layer TEOS/AA films via timed incubation in a humidity-controlled environment results in changes in the water contact angle (WCA) of the cbAA, and ultimately the surface of the TEOS/AA, enabling tuning of the wettability of the acrylic acid layer. Through the use of a controlled incubation environment of the TEOS/AA, followed by washing, we have demonstrated that carboxylic-acid containing surfaces with a WCA between 85° and 10° can be routinely generated, using basic apparatus and simple methodology. Moreover, these surfaces not only retain their AA functionality, demonstrated by covalent-linking of amine-terminated single-stranded DNA, but also strongly inhibit non-specific binding of the DNA strands. The efficiency of these surfaces to be used in DNA direct-binding hybridisation assays has been demonstrated, with limits of detection of 1.11 and 1.66 nM being measured.

A two reservoir model to predict Escherichia coli losses to water from pastures grazed by dairy cows.

Animal agriculture has been identified as an important source of diffuse faecal microbial pollution of water. Our current understanding of the losses of faecal microbes from grazed pasture systems is however poor. To help synthesise our current knowledge, a simple two reservoir model was constructed to represent the faecal and environmental sources of Escherichia coli found in a grazed pastoral system. The size of the faecal reservoir was modelled on a daily basis with inputs from grazing animals, and losses due to die-off of E. coli and decomposition of the faecal material. Estimates were made of transport coefficients of E. coli losses from the two reservoirs. The concentration of E. coli measured in overland flow and artificial drainage from grazed plots, used for calibration of the model, showed a significant (P<0.0001) decrease with days since last grazing - up to 120 days. Modelled E. coli runoff concentrations calibrated well with the regression line from the measured data up to 120 days. Variability of E. coli concentrations in the source faecal material could account for the variability in the measured runoff concentrations. Measured E. coli concentrations in artificial drainage water from 120 to 1300 days since last grazing appeared to be greater than the model predicted. The longer term data clearly illustrated the need for an environmental reservoir of E. coli in models of grazed pasture systems. Research is needed to understand the behaviour and impact of this environmental reservoir. Scenario analysis using the model indicated that rather than manipulating the faecal material itself post defecation, mitigation options should focus on manipulating grazing management.

Prioritisation of farm scale remediation efforts for reducing losses of nutrients and faecal indicator organisms to waterways: a case study of New Zealand dairy farming.

The international competitiveness of the New Zealand (NZ) dairy industry is built on low cost clover-based systems and a favourable temperate climate that enables cows to graze pastures mostly all year round. Whilst this grazed pasture farming system is very efficient at producing milk, it has also been identified as a significant source of nutrients (N and P) and faecal bacteria which have contributed to water quality degradation in some rivers and lakes. In response to these concerns, a tool-box of mitigation measures that farmers can apply on farm to reduce environmental emissions has been developed. Here we report the potential reduction in nutrient losses and costs to farm businesses arising from the implementation of individual best management practices (BMPs) within this tool-box. Modelling analysis was carried out for a range of BMPs targeting pollutant source reduction on case-study dairy farms, located in four contrasting catchments. Due to the contrasting physical resources and management systems present in the four dairy catchments evaluated, the effectiveness and costs of BMPs varied. Farm managements that optimised soil Olsen P levels or used nitrification inhibitors were observed to result in win-win outcomes whereby nutrient losses were consistently reduced and farm profitability was increased in three of the four case study farming systems. Other BMPs generally reduced nutrient and faecal bacteria losses but at a small cost to the farm business. Our analysis indicates that there are a range of technological measures that can deliver substantial reductions in nutrient losses to waterways from dairy farms, whilst not increasing or even reducing other environmental impacts (e.g. greenhouse gas emissions and energy use). Their implementation will first require clearly defined environmental goals for the catchment/water body that is to be protected. Secondly, given that the major sources of water pollutants often differed between catchments, it is important that BMPs are matched to the physical resources and management systems of the existing farm businesses.

Microbial transformation of N-heptyl physostigmine, a semisynthetic alkaloid inhibitor of cholinesterase.

The microbiological transformation of N-heptyl physostigmine (L-693,487) (1), a semisynthetic physostigmine cholinesterase inhibitor, was investigated using Verticillium lecanii MF 5713 (ATCC 74148), Acremonium sp MF 5723 (ATCC 74164) and Actinoplanes sp MA 6559 (ATCC 53771). Nine microbial metabolites (2-10) of 1 were isolated and purified using reversed-phase HPLC. The structures of the metabolites were established using spectroscopic techniques including MS and NMR. Some of the microbial metabolites were identical to metabolites present in urine of a dog treated with 1.

The preparation of zaragozic acid A analogues by directed biosynthesis.

Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro.

Aging exaggerates glucose intolerance following injury.

Hyperglycemia and glucose intolerance are characteristic of both the metabolic responses to injury and normal aging. To evaluate the interaction of such changes we conducted hyperglycemic glucose clamp studies (2-hour) in previously healthy young (20 +/- 4 years, Mean +/- SD) and older (73 +/- 9 years) trauma patients and volunteers (23 +/- 1 and 68 +/- 5 years), determining whole-body glucose disposal and insulin responses to hyperglycemia. Injury Severity Scores were similar in the young and older patient groups (range, 17-30). Plasma glucose levels were greater in patients than volunteers in both the basal and hyperglycemic periods. Basal serum insulin and C-peptide levels were similar among groups, but during hyperglycemia both were markedly higher in young patients than older (and both volunteer groups). Whole-body disposal of exogenous glucose was substantially lower in patients than volunteers and in the older groups. Aging has a major impact on postinjury metabolism, being associated with exaggerated glucose intolerance and diminished insulin responses to glucose infusion. These findings have important implications for the metabolic and nutritional care of older patients following trauma and during critical illness.

Microbial transformation of immunosuppressive compounds. III. Glucosylation of immunomycin (FR 900520) and FK 506 by Bacillus subtilis ATCC 55060.

The regiospecific glucosylation of FK 506 and immunomycin (FR 900520) at the 24-hydroxy position was performed using resting cells of Bacillus subtilis ATCC 55060. 24-Glucopyranosyl FK 506 and 24-glucopyranosyl immunomycin were isolated by methylene chloride extraction and purification using reverse phase HPLC. The metabolite structures were established using spectroscopic techniques including MS and NMR. The glucose conjugate was further confirmed by chemical degradation. Enzymatic glucosylation was demonstrated using cell-free extracts derived from Bacillus subtilis ATCC 55060. The 24-glucosyltransferase, which appears UDP-glucose dependent, was solubilized from cell membranes by treatment with 0.1% Nonidet P-40 detergent. The optimal conditions for assay of the enzyme have been determined.

Uptake of glucose during continuous arteriovenous hemofiltration.

OBJECTIVE: To quantify glucose balance related to continuous arteriovenous hemofiltration (CAVH) when a glucose-rich replacement fluid is used for the plasma ultrafiltrate removed. DESIGN: Prospective, nonintervention study. SETTING: Medical/surgical and cardiac surgical intensive care units of a university hospital. PATIENTS: Critically ill patients (n = 20) with acute oliguric renal failure undergoing CAVH. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timed collections of CAVH effluent were analyzed and other observations were made. Serum creatinine and blood urea nitrogen concentrations decreased substantially during CAVH in each patient. The mean measured glucose concentration of the replacement fluid (Dianeal 1.5%) was 1.40 +/- 0.11 (SD) g/dL (77 +/- 6 mmol/L) and rate of infusion was 1.39 +/- 0.43 L/hr. Effluent volume was 1.51 +/- 0.49 L/hr and glucose was 0.47 +/- 0.10 g/dL (26 +/- 5 mmol/L). The glucose content of the replacement fluid infused was consistently and substantially greater than that value of the effluent removed during the same period. Thus, the average net glucose uptake in relation to the CAVH circuit was 11.9 +/- 3.1 g/hr (range 4.3 to 17.6). Serum glucose concentrations increased in each patient with initiation of CAVH (from 135 +/- 44 to 278 +/- 80 mg/dL [7.4 +/- 2.4 to 15.3 +/- 4.4 mmol/L]; p < .001). Negative fluid balance achieved during CAVH was approximately 100 mL/hr. CONCLUSIONS: CAVH using predilution with replacement fluid is effective in managing uremia and fluid overload in critically ill patients. The use of a glucose-rich replacement fluid is accompanied by the net uptake of large amounts of glucose, approaching 300 g/day on average in our patients and representing a major exogenous calorie source. This finding has important implications for the metabolic management of critically ill patients during CAVH and should be taken into account in prescribing their nutritional support.

Microbial transformation of L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease.

The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments.

Improvement in the titer of echinocandin-type antibiotics: a magnesium-limited medium supporting the biphasic production of pneumocandins A0 and B0.

We have developed a liquid fermentation medium for the submerged culture of the fungus, Zalerion arboricola, which supports the rapid production of an echinocandin-type antibiotic, pneumocandin A0 (formerly L-671,329), in yields increased at least 4-fold over those reported previously. The improvements were achieved through medium simplification, substitution of high levels of mannitol for glycerol as the major source of carbon, and restriction of available magnesium. Antibiotic formation in batch cultures with this mannitol-based medium is not confined to the idiophase; rather production appears to be biphasic, with synthesis beginning during growth (i.e., at day 3) and increasing in rate at day 11, well after rapid growth has ended. Accumulation of antibiotic continues beyond 14 days, and by 21 days titers greater than 500 micrograms/ml are attained. For the synthesis of a related compound, pneumocandin B0, by a mutant strain of Z. arboricola, the medium gives similar production kinetics and a titer of 800 micrograms/ml. Although supplementation of the medium with magnesium ions stimulates growth, it decreases titer by preferentially affecting the second phase of antibiotic synthesis. This decline in synthesis in the magnesium-supplemented medium is explained by the depletion of mannitol before the second phase of synthesis can begin. In contrast, mannitol in the magnesium-limited medium is used more slowly with approximately half still available at day 11 to support continued antibiotic formation.

Microbial hydroxylation and glucuronidation of the angiotensin II (AII) receptor antagonist MK 954.

The microbial metabolism of MK 954 (Fig. 1), a novel nonpeptide angiotensin II receptor antagonist, was investigated using 40 microorganisms in an initial screen for cultures that will produce metabolites similar to those produced in the mammalian liver. The microbial transformation occurred under aerobic conditions in shake flasks incubated at 27 degrees C. Three metabolites of MK 954 were isolated and identified as the 1'-hydroxy M2, 3'-hydroxy M1, and glucuronic acid conjugated M3 derivatives. The structures of the metabolites were established by UV, 1H-NMR spectroscopy and FAB-MS spectrometry and are identical to metabolites produced by incubation of MK 954 with mammalian liver slices.

L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. I. The producing organism and its fermentation.

A novel cytochalasin, L-696,474, (18-dehydroxy cytochalasin H) that inhibits HIV-1 protease was discovered in fermentations of a bark-inhabiting Ascomycete, Hypoxylon fragiforme. The product was first identified from extracts of an agar medium. Fermentation studies on a number of media indicated that the product can be made on several solid and liquid media. Optimum production was obtained from growth in a complex medium composed of glycerol, glucose, citrate, Ardamine, soybean meal, tomato paste, and inorganic salts. Other Hypoxylon spp., related species of Xylariales, and other fungi known to produce cytochalasins, were also surveyed for their ability to make L-696,474. Only one other Hypoxylon fragiforme isolate was found to make this novel cytochalasin; none of the other cultures surveyed made L-696,474 or any other compounds which inhibit HIV-1 protease.

Microbial transformation of immunosuppressive compounds. I. Desmethylation of FK506 and immunomycin (FR 900520) by Actinoplanes sp. ATCC 53771.

The immunosuppressants FK506 and FR 900520 were desmethylated by Actinoplanes sp. ATCC 53771 to yield various O-desmethylated products. The products were isolated and purified by solvent extraction and HPLC chromatography, and identified by NMR and MS spectroscopy.

Expanded polytetrafluoroethylene patch in hernia repair: a review of clinical experience.

The use of an implantable prosthetic material is often needed to repair inguinal and incisional hernias, especially when the local tissue is of poor quality or there is a large defect that would cause excessive tension if closed without patching with prosthetic material. An expanded polytetrafluoroethylene (ePTFE) patch was used in 37 patients between May 1986 and May 1990 to repair 25 direct inguinal and 12 incisional hernias. There was one recurrence in the group of patients with incisional hernia but none in those with a direct inguinal hernia. The recurrence was due to poor collagen ingrowth into the patch and subsequent herniation between two sutures. There were no complications due to infection, adhesions, erosion or fistulization. On the basis of this clinical experience, the authors conclude that the ePTFE patch is almost an ideal abdominal wall substitute, but that because of poor anchorage with tissue reaction alone, the success of the repair depends on the technique of suture placement.