Effects of replacing magnesium oxide with calcium-magnesium carbonate with or without sodium bicarbonate on ruminal fermentation and nutrient flow in vitro.

The objective of this study was to evaluate the effects of replacing magnesium oxide (MgO) with calcium-magnesium carbonate [CaMg(CO3)2] on ruminal fermentation with or without the addition of sodium bicarbonate (NaHCO3). Eight fermentors of a dual-flow continuous-culture system were distributed in a replicated (2) 4 × 4 Latin square design in a 2 × 2 factorial arrangement of treatments (magnesium sources × NaHCO3). The treatments tested were 0.21% MgO [MgO; dry matter (DM) basis; 144.8 mEq of dietary cation-anion difference (DCAD)]; 0.21% MgO + 0.50% NaHCO3 (MgO+NaHCO3; DM basis; 205.6 mEq of DCAD); 1.00% CaMg(CO3)2 [CaMg(CO3)2; DM basis; 144.8 mEq of DCAD]; and 1.00% CaMg(CO3)2 + 0.50% NaHCO3 [CaMg(CO3)2+NaHCO3; DM basis; 205.6 mEq of DCAD]. Diets were formulated to have a total of 0.28% of Mg (DM basis). The experiment consisted of 40 d, which was divided into 4 periods of 10 d each, where 7 d were used for adaptation and 3 d for sampling to determine pH, volatile fatty acids (VFA), ammonia (NH3-N), lactate, mineral solubility, N metabolism, and nutrient digestibility. The effects of Mg source [MgO vs. CaMg(CO3)2], NaHCO3 (with vs. without), and the interaction were tested with the MIXED procedure of SAS version 9.4 (SAS Institute). There was no Mg source × NaHCO3 interaction in the pH variables and mineral solubility, and Mg sources evaluated did not affect the variables related to ruminal pH and solubility of Mg. On the other hand, the inclusion of NaHCO3 increased the pH daily average, independent of Mg source, which led to a reduced time that pH was below 5.8 and decreased area under the curve. Total VFA and lactate concentration were similar among treatments regardless of NaHCO3 and Mg source; however, the molar proportion of isobutyrate and NH3-N concentration were lower in diets with CaMg(CO3)2 compared with MgO. Moreover, NaHCO3 inclusion increased NH3-N, total daily NH3-N flow, isobutyrate concentration, and acid detergent fiber digestibility. Our results showed that CaMg(CO3)2 leads to a lower NH3-N concentration and isobutyrate proportion. Therefore, because most of the tested variables were not significantly different between MgO and CaMg(CO3)2 when combined or not with NaHCO3, CaMg(CO3)2 can be a viable alternative source to replace MgO in dairy cow diets without affecting mineral solubility, ruminal pH, nutrient digestibility, total VFA, and the main ruminal VFA. Although Mg sources are known to have an alkalizing effect, NaHCO3 inclusion in diets with Mg supplementation allowed an increase in ruminal pH, as well as an increase in isobutyrate and NH3-N flow.

Correction to: Antipsychotic Prescribing to Patients Diagnosed with Dementia Without a Diagnosis of Psychosis in the Context of National Guidance and Drug Safety Warnings: Longitudinal Study in UK General Practice.

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Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.

Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.

Antipsychotic Prescribing to Patients Diagnosed with Dementia Without a Diagnosis of Psychosis in the Context of National Guidance and Drug Safety Warnings: Longitudinal Study in UK General Practice.

INTRODUCTION: Policy interventions to address inappropriate prescribing of antipsychotic drugs to older people diagnosed with dementia are commonplace. In the UK, warnings were issued by the Medicines Healthcare products Regulatory Agency in 2004, 2009 and 2012 and the National Institute for Health and Care Excellence guidance was published in 2006. It is important to evaluate the impact of such interventions. METHODS: We analysed routinely collected primary-care data from 111,346 patients attending one of 689 general practices contributing to the Clinical Practice Research Datalink to describe the temporal changes in the prescribing of antipsychotic drugs to patients aged 65 years or over diagnosed with dementia without a concomitant psychosis diagnosis from 2001 to 2014 using an interrupted time series and a before-and-after design. Logistic regression methods were used to quantify the impact of patient and practice level variables on prescribing prevalence. RESULTS: Prescribing of first-generation antipsychotic drugs reduced from 8.9% in 2001 to 1.4% in 2014 (prevalence ratio 2014/2001 adjusted for age, sex and clustering within practices (0.14, 95% confidence interval 0.12-0.16), whereas there was little change for second-generation antipsychotic drugs (1.01, confidence interval 0.94-1.17). Between 2004 and 2012, several policy interventions coincided with a pattern of ups and downs, whereas the 2006 National Institute for Health and Care Excellence guidance was followed by a gradual longer term reduction. Since 2013, the decreasing trend in second-generation antipsychotic drug prescribing has plateaued largely driven by the increasing prescribing of risperidone. CONCLUSIONS: Increased surveillance and evaluation of drug safety warnings and guidance are needed to improve the impact of future interventions.

Temporal trends in antidepressant prescribing to children in UK primary care, 2000-2015.

BACKGROUND: The prevalence of antidepressant prescribing in children and adolescents increased steadily in the United States and parts of Europe between 2005 and 2012 despite regulatory safety warnings. Little is known about the characteristics of those being prescribed antidepressants for the first time. METHODS: A longitudinal study of antidepressant prescribing in 3-17 year olds was carried out using data from the UK Clinical Practice Research Datalink (CPRD) between 2000 and 2015. Changes in the incidence of first ever antidepressant prescriptions and the characteristics of those being prescribed them was examined. RESULTS: Incidence of first ever prescriptions nearly doubled between 2006 and 2015 rising from 1.60 (95%CI: 1.51, 1.69) to 3.12 (3.00, 3.25) per 1000 person years. Only 21% of the 1721 patients with incident prescriptions in 2015 could be linked to a depression diagnosis, with an additional 22% of prescriptions linked to alternative indications. The incidence of prescriptions linked to a depression diagnosis increased between 2012 and 2015, with an adjusted incidence rate ratio of 1.46 (1.26, 1.70). Antidepressant prescribing for depression and other indications has been increasing most rapidly in 15 to 17 year old females. LIMITATIONS: Diagnoses are not directly linked to prescriptions in CPRD, so linkage must be inferred by temporal proximity. CONCLUSIONS: Antidepressant prescribing in children increased between 2006 and 2015. This is, at least in part, due to a rise in alternative uses of antidepressants, including the treatment of anxiety, chronic pain and migraines.

Incidence rates of occupational diseases in the Dutch construction sector, 2010-2014.

OBJECTIVE: To estimate incidence and trends in incidence of occupational diseases (ODs) in the Dutch construction sector. METHODS: In a dynamic prospective cohort over a 5-year period (2010-2014), ODs assessed by occupational physicians (OPs) participating in a voluntary construction workers health surveillance (WHS) were reported to the Netherlands Centre for Occupational Diseases (NCOD). ODs were defined as a disease with a specific clinical diagnosis (International Classification of Diseases) that was predominantly caused by work-related factors as assessed by an OP. Annual incidences were determined for the total number of ODs and six frequently occurring OD groups. Trends in incidence were estimated using a multilevel negative binominal regression model. RESULTS: In 2014 the incidence of all OD was 12 964 per 100 000 workers and there was no significant change in incidence between 2010 and 2014 (3%; 95% CI -2% to +9%). Hearing loss (8125 per 100 000 workers) and musculoskeletal disorders (2081 per 100 000 workers) were the most frequently occurring ODs. Noise-induced hearing loss (+7%; 95% CI 1% to 13%) and contact dermatitis (+19%; 95% CI 6% to 33%) showed increasing trends. There was no statistically significant change in the incidence of low back pain, arthrosis, repetitive strain injuries, distress/burnout and chronic obstructive pulmonary disease/asthma. CONCLUSIONS: In total, 13% of workers participating in WHS in the Dutch construction industry during 2014 had an OD diagnosed and reported by an OP. Over a 5-year period the annual incidence of reported ODs showed a statistically non-significant increase. Incidences in noise-induced hearing loss and contact dermatitis showed statistically significant increasing trends, 7% and 19%, respectively.

Effects of abomasal infusion of nicotinic acid on responses to glucose and ß-agonist challenges in underfed lactating cows.

The objectives were to assess the use of nicotinic acid (NA) to chronically (i.e., 74 h) manipulate plasma nonesterified fatty acid (NEFA) concentrations in partially feed-restricted lactating cows, determine whether the reduction of plasma NEFA altered responses to i.v. glucose tolerance test (ivGTT) and whether NA would attenuate an acute lipolytic stimuli of a ß-agonist challenge (ivBAC). Eight lactating dairy cows [244 ± 31 d in milk; 696 ± 63 kg of body weight (BW)] were blocked by breed and body condition score (3.2 ± 0.4) and randomly assigned to a sequence of 2 treatments in a crossover design. Treatments were 74-h continuous abomasal infusion of NA solution (3mg/h per kg of BW) as an antilipolytic agent to decrease plasma NEFA concentrations or the same volume of water (200 mL/h), concomitant with partial feed restriction. From 0 to 74 h of each experimental period, cows were feed-restricted to 33% of the ad libitum intake recorded during the prior 5 d. An ivGTT (0.25 g/kg of BW of glucose i.v.) and an ivBAC (4 nmol/kg of BW of isoproterenol hydrochloride, i.v.) were performed at 48 and 72 h, respectively. Intake was 24.1, 8.2, 8.0, and 8.0 kg of dry matter/d before restriction, on d 1, 2 and 3, respectively. Nicotinic acid decreased plasma NEFA and increased insulin and glucose concentrations during feed restriction. Nicotinic acid also led to greater glucose and insulin response areas under the curve during ivGTT [glucose: 6,562 vs. 5,056 (mg/dL) × 180 min; insulin: 6,042 vs. 2,502 (µIU/mL) × 180 min] and ivBAC [glucose: 535 vs. 240 (mg/dL) × 120 min; insulin: 1,283 vs. 222 (µIU/mL) × 120 min], and enhanced NEFA area under the curve during ivBAC [45,521 vs. 22,862 (µEq/L) × 120 min]. Milk, fat, and protein yields (29.1, 1.2, and 0.93 kg on d -2, respectively) decreased to 17.9, 0.81, and 0.56 kg for control, and 11.5, 0.54, and 0.39 kg for NA on d 3, respectively. Nicotinic acid may have decreased production by inhibiting the supply of NEFA for energy and milk fat synthesis. Milk urea nitrogen was increased by NA on d 2 (12.8 vs. 19.1mg/dL) and d 3 (11.6 vs. 17.8 mg/dL), probably due to a greater reliance on mobilized amino acids. Somatic cell count was increased by NA on d 3 (187 vs. 848 × 1,000 cells/mL). Patterns of glucose and insulin concentration observed during 74 h of NA infusion reflect a state of insulin resistance, which contrasts with shorter-term responses in nonlactating cows. Data suggest that long-term supraphysiological infusion of NA affected intermediary metabolism beyond antilipolysis and did not inhibit acute lipolytic stimuli of ivBAC.

Examining variations in prescribing safety in UK general practice: cross sectional study using the Clinical Practice Research Datalink.

STUDY QUESTION: What is the prevalence of different types of potentially hazardous prescribing in general practice in the United Kingdom, and what is the variation between practices? METHODS: A cross sectional study included all adult patients potentially at risk of a prescribing or monitoring error defined by a combination of diagnoses and prescriptions in 526 general practices contributing to the Clinical Practice Research Datalink (CPRD) up to 1 April 2013. Primary outcomes were the prevalence of potentially hazardous prescriptions of anticoagulants, anti-platelets, NSAIDs, ß blockers, glitazones, metformin, digoxin, antipsychotics, combined hormonal contraceptives, and oestrogens and monitoring by blood test less frequently than recommended for patients with repeated prescriptions of angiotensin converting enzyme inhibitors and loop diuretics, amiodarone, methotrexate, lithium, or warfarin. STUDY ANSWER AND LIMITATIONS: 49 927 of 949 552 patients at risk triggered at least one prescribing indicator (5.26%, 95% confidence interval 5.21% to 5.30%) and 21 501 of 182 721 (11.8%, 11.6% to 11.9%) triggered at least one monitoring indicator. The prevalence of different types of potentially hazardous prescribing ranged from almost zero to 10.2%, and for inadequate monitoring ranged from 10.4% to 41.9%. Older patients and those prescribed multiple repeat medications had significantly higher risks of triggering a prescribing indicator whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator. There was high variation between practices for some indicators. Though prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified. Furthermore there is the possibility that some information is not captured by CPRD for some practices-for example, INR results in patients receiving warfarin. WHAT THIS STUDY ADDS: The high prevalence for certain indicators emphasises existing prescribing risks and the need for their appropriate consideration within primary care, particularly for older patients and those taking multiple medications. The high variation between practices indicates potential for improvement through targeted practice level intervention. FUNDING, COMPETING INTERESTS, DATA SHARING: National Institute for Health Research through the Greater Manchester Primary Care Patient Safety Translational Research Centre (grant No GMPSTRC-2012-1). Data from CPRD cannot be shared because of licensing restrictions.

A refined QSAR model for prediction of chemical asthma hazard.

BACKGROUND: A previously developed quantitative structure-activity relationship (QSAR) model has been extern ally validated as a good predictor of chemical asthma hazard (sensitivity: 79-86%, specificity: 93-99%). AIMS: To develop and validate a second version of this model. METHODS: Learning dataset asthmagenic chemicals with molecular weight (MW) <1 kDa were identified from reports published in the peer-reviewed literature before the end of 2012. Control chemicals for which no reported case(s) of occupational asthma had been identified were selected at random from UK and US occupational exposure limit tables. MW banding was used in an attempt to categorically match the control group for MW distribution of the asthmagens. About 10% of chemicals in each MW category were excluded for use as an external validation set. An independent researcher utilized a logistic regression approach to compare the molecular descriptors present in asthmagens and controls. The resulting equation generated a hazard index (HI), with a value between zero and one, as an estimate of the probability that the chemical had asthmagenic potential. The HI was determined for each compound in the external validation set. RESULTS: The model development sets comprised 99 chemical asthmagens and 204 controls. The external validation showed that using a cut-point HI of 0.39, 9/10 asthmagenic (sensitivity: 90%) and 23/24 non-asthmagenic (specificity: 96%) compounds were correctly predicted. The new QSAR model showed a better receiver operating characteristic plot than the original. CONCLUSIONS: QSAR refinement by iteration has resulted in an improved model for the prediction of chemical asthma hazard.

Isocyanate exposure and asthma in the UK vehicle repair industry.

BACKGROUND: Organic diisocyanates are a common cause of occupational asthma, particularly in motor vehicle repair (MVR) workers. The UK Health & Safety Laboratory provides screening for urinary hexamethylenediamine (UHDA), a biomarker of exposure to 1,6-hexamethylene diisocyanate (HDI). The UK Surveillance of Work-related and Occupational Respiratory Disease scheme (SWORD) has collected reports of occupational asthma since 1996. AIMS: To compare trends in HDI exposure with trends in the incidence of work-related asthma attributed to isocyanates or paint spraying in MVR workers reported to SWORD. METHODS: Two-level regression models were used to estimate trends in UHDA levels and work-related asthma in MVR workers reported to SWORD. The direction and magnitude of the trends were compared descriptively. RESULTS: From 2006 to 2014, there was a significant decline in the number of urine samples with detectable levels of UHDA (odds ratio = 0.96; 95% confidence intervals 0.94-0.98) and minimal change in those over the guidance value (1.03; 1.00-1.06). Over the same period, there was a significant decline in all asthma cases attributed to isocyanates or paint spraying reported to SWORD (0.90; 0.86-0.94) and a non-significant decline among MVR workers (0.94; 0.86-1.02). CONCLUSIONS: The simultaneous decrease in HDI exposure and incident cases of asthma reported to SWORD is temporally consistent with a reduction in exposure to airborne isocyanate leading to a reduction in asthma. Although this is not direct evidence of a causal relationship between the two trends, it is suggestive.

The impact of national-level interventions to improve hygiene on the incidence of irritant contact dermatitis in healthcare workers: changes in incidence from 1996 to 2012 and interrupted times series analysis.

BACKGROUND: Reducing healthcare-associated infections (HCAI) has been a priority in the U.K. over recent decades and this has been reflected in interventions focusing on improving hygiene procedures. OBJECTIVES: To evaluate whether these interventions coincided with an increased incidence of work-related irritant contact dermatitis (ICD) attributed to hand hygiene or/and other hygiene measures in healthcare workers (HCWs). METHODS: A quasi-experimental (interrupted time series) design was used to compare trends in incidence of ICD in HCWs attributed to hygiene before and after interventions to reduce HCAI with trends in the same periods in control groups (ICD in other workers). Cases of ICD reported to a U.K. surveillance scheme from 1996 to 2012 were analysed. The time periods compared were defined objectively based on the dates of the publication of national evidence-based guidelines, the U.K. Health Act 2006 and the Cleanyourhands campaign. RESULTS: The reported incidence of ICD in HCWs attributed to hygiene has increased steadily from 1996 to 2012 [annual incidence rate ratio (95% confidence interval): hand hygiene only 1.10 (1.07-1.12); all hygiene 1.05 (1.03-1.07)], whereas the incidence in other workers is declining. An increase in incidence of ICD in HCWs attributed to hand hygiene was observed at the beginning of the Cleanyourhands campaign. CONCLUSIONS: The increasing incidence of ICD in HCWs combined with the popularity of interventions to reduce HCAI warrants increased efforts towards identifying products and implementing practices posing the least risk of ICD.

Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012.

OBJECTIVES: The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. METHODS: OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of 'centres', requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. RESULTS: Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. CONCLUSIONS: This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods.

Pesticide exposure and screen-positive neuropsychiatric disease in British sheep farmers.

BACKGROUND: Epidemiological evidence linking low dose pesticide exposure and chronic ill-health in UK sheep farmers is limited. Our aim was to examine whether neuropsychiatric disorders were associated with low dose chronic and/or more acute pesticide exposure in sheep farmers. METHODS: A cohort of British farmers working in the 1970s was sent a screening questionnaire which asked about their health and work history. The prevalence of screen-positive depression, dementia, Parkinsonism and neuropathy was determined using a priori algorithms. Self-reported pesticide exposure was assessed by whether the participant had ever handled the pesticide concentrate (for low dose chronic exposure) or sought advice for pesticide poisoning (acute exposure) and participants categorised into those with only acute or chronic exposure, those with both acute and chronic exposure and those with neither acute nor chronic exposure. Associations between acute and chronic pesticide exposure, and screen-positive ill-health were determined after adjustment for demographic, lifestyle, occupation and somatic severity scores and other variables. RESULTS: In those participants, who had never sought advice for pesticide poisoning, handling the pesticide concentrate for treating sheep was associated with elevated ORs for screen-positive neuropathy (ORadi 1.57 95%CI 0.97-2.54) and Parkinsonism (ORadj 1.56 95%CI 0.95-2.56) but not depression or dementia. In those participants who had handled the pesticide concentrate, seeking advice for pesticide poisoning was associated with screen-positive depression (Odds ratio, ORadj=9.97 95%CI 4.76-20.8 ), dementia (OR=6.94 95%CI 3.44-14.0), Parkinsonism (ORadj=4.77 95% 2.39-9.52), and neuropathy (ORadj=4.77 95%CI 2.39-9.52). Adjustment for somatic severity score modified little the associations with pesticide handling in those not acutely exposed but reduced the ORs for seeking advice for pesticide poisoning in those exposed chronically. Furthermore, stratification of results based upon somatic severity score indicated that the highest ORs for handling the pesticide concentrate associated with neuropathy and Parkinsonism were found in those participants whose somatic score was minimal. CONCLUSIONS: Results are consistent with low-dose exposure to pesticides being associated with screen-positive neuropathy and Parkinsonism but the stronger associations between seeking advice for pesticide poisoning and screen-positive ill-health suggest that acute pesticide exposure remains an important determinant of ill-health. Further work is required to better delineate to what extent low dose exposures may contribute to ill-health in populations without acute exposures. Somatising tendency does not appear to play an important role in this population.

Occupational allergic contact dermatitis and major allergens in France: temporal trends for the period 2001-2010.

BACKGROUND: Occupational allergic contact dermatitis (OACD) is one of the most common occupational skin diseases in developed countries, but data about its temporal trends in incidence remain sparse. OBJECTIVES: The aim of this study is to describe OACD trends in terms of industrial activities and main causal agents in France over the period 2001-2010. MATERIALS AND METHODS: Data were collected from the French National Network of Occupational Disease Vigilance and Prevention (RNV3P, Réseau National de Vigilance et de Prévention des Pathologies Professionnelles). All OACD considered probably or certainly associated with an occupational exposure were included in the study. Trends were examined (i) on annual crude numbers of OACD and (ii) on reported odds ratios of OACD calculated using logistic regression models. RESULTS: Overall, 3738 cases of OACD were reported and the mean age of OACD cases was 35 years, 52% being women. The most frequent occupations were hairdressers, health care workers, cleaning staff and masons. The total number of OACD cases remained stable over the study period, but increases in OACD related to isothiazolinones (P = 0·002), epoxy resins (P = 0·012) and fragrances (P = 0·005) were observed. Conversely, decreases were noted for cement compounds (P = 0·002) and plant products (P = 0·031). These trends highlight specific sectors and exposures at risk of OACD. CONCLUSIONS: Trends in OACD depend on the nature of exposure. Observed decreases were consistent with prevention measures taken during the study period, and the increases observed serve to highlight those areas where preventative efforts need to be made to reduce skin allergies in the workplace.

Effects of lipid and propionic acid infusions on feed intake of lactating dairy cows.

Propionic acid is more hypophagic for cows with elevated hepatic acetyl coenzyme A (CoA) concentration in the postpartum period. The objective of this experiment was to evaluate the interaction of hepatic acetyl CoA concentration, which is elevated by intravenous lipid infusion, and intraruminal propionic acid infusion on feed intake and feeding behavior responses of lactating cows. Eight multiparous, ruminally cannulated, Holstein dairy cows past peak lactation were used in a replicated 4×4 Latin square experiment with a 2×2 factorial arrangement of treatments. Treatments were propionic acid (PI) infused intraruminally at 0.5mol/h for 18h starting 6h before feeding and behavior monitoring or sham control (CO), and intravenous jugular infusion of lipid (LI, Intralipid 20%; Baxter US, Deerfield, IL) or saline (SI, 0.9% NaCl; Baxter US) infused at 250mL/h for 12h before feeding and behavior monitoring, and then 500mL/h for 12h after feeding. Changes in plasma concentrations of metabolites and hormones and hepatic acetyl CoA from before infusion until the end of infusion were evaluated. We observed a tendency for an interaction between PI and LI for the change in plasma nonesterified fatty acid (NEFA) concentration from the preliminary day to the end of the infusion period. Infusion of propionic acid decreased dry matter intake (DMI) 15% compared with CO, but lipid infusion did not affect DMI over the 12h following feeding. Infusion of propionic acid tended to decrease hepatic acetyl CoA concentration from the preliminary day to the end of the infusion compared with CO, consistent with PI decreasing DMI by stimulating oxidation of acetyl CoA. Contrary to our expectations, LI did not increase concentration of NEFA or ß-hydroxybutyrate in plasma, concentration of acetyl CoA in the liver, or milk fat yield, suggesting that the infused lipid was stored or oxidized by extra-hepatic tissues. As a result, we detected no interaction between PI and LI for DMI. Although the effect of PI on DMI was consistent with our previous results, this lipid infusion model using cows past peak lactation was not useful to simulate the lipolytic state of cows in the postpartum period in this experiment.

Hypophagic effects of propionic acid are not attenuated during a 3-day infusion in the early postpartum period in Holstein cows.

We previously showed that propionic acid was more hypophagic than acetic acid when infused intraruminally in cows in the postpartum period and that the degree of hypophagia from short-term propionic acid infusion (18 h) was related to the acetyl coenzyme A (CoA) concentration in the liver. The objective of this experiment was to evaluate adaptation over time with longer-term infusions over 3 d. Twelve multiparous cows (2-13 d postpartum) were blocked by calving date and assigned randomly to treatment sequence in a crossover design experiment. The experiment was 12 d long with covariate periods preceding each 3-d infusion period. Treatments were 1.0 M propionic acid or 1.0 M acetic acid, infused intraruminally at 0.5 mol of volatile fatty acids/h beginning 6 h before feeding and continuing for 78 h with 3 d between infusions. Propionic acid decreased dry matter intake (DMI) relative to acetic acid (15.9 vs. 17.0 kg/d). However, a period-by- treatment interaction was detected for DMI. During period 1, propionic acid decreased DMI relative to acetic acid (14.3 vs. 17.5 kg/d) because of a reduction in meal size (1.30 vs. 1.65 kg), with no effect on intermeal interval. Propionic acid decreased DMI over the first 4 h following feeding (5.86 vs. 8.23 kg) but did not affect DMI 4 to 24 h after feeding. The depression in DMI in period 1 was positively related to hepatic acetyl-CoA concentration during the covariate period. Propionic acid was increasingly more hypophagic than acetic acid as hepatic acetyl-CoA concentration was elevated. No treatment-by-day interaction for DMI was observed, suggesting little or no measurable adaptation to treatment over the 3-d infusion period. These results suggest that hypophagia from propionic acid is enhanced when hepatic acetyl-CoA concentrations are elevated, such as when cows are in a lipolytic state.

Assessing the impact of national level interventions on workplace respiratory disease in the UK: part 2--regulatory activity by the Health and Safety Executive.

OBJECTIVE: To investigate whether interventions implemented by the UK Health and Safety Executive addressing exposure to isocyanate-based spray paints in motor vehicle repair (MVR), flour dust in craft bakeries, rosin-based solder flux fume (RBSFF) in the electronics industry, metalworking fluids and wood dust coincided with a decline in incidence of work-related short latency respiratory disease (SLRD) or asthma in the target groups. METHOD: Changes in the incidence of SLRD reported to a UK-based surveillance scheme were compared using a longitudinal, negative binomial regression model with ß distributed random effects. An interrupted time series design was used and comparisons according to inclusion or exclusion in the target group were made by including a statistical interactions expressed as a ratio of incidence rate ratios (RIRRs) in the model. RESULTS: The incidence of SLRD attributed to flour dust significantly increased relative to all other agents (RIRR: 1.10; 95% CI 1.06 to 1.16) whereas SLRD attributed to RBSFF significantly declined relative to all other agents (0.94; 0.90 to 0.99). No significant changes in the incidence of SLRD attributed to wood dust (1.03; 0.91 to 1.16) or spray paints (1.03; 0.95 to 1.11) relative to all other agents were observed. A higher proportion of reports originated from the industries targeted by the intervention for RBSFF (65/107; 61%) than spray painting (27/93; 27%) or wood dust (16/42; 38%). CONCLUSIONS: These data support a beneficial effect of interventions to reduce exposure to RBSFF but an increase in SLRD attributed to flour dust may indicate increased exposure or increased awareness of the problem.

Assessing the impact of national level interventions on workplace respiratory disease in the UK: part 1--changes in workplace exposure legislation and market forces.

OBJECTIVE: The 2004 amendment to the Control of Substances Hazardous to Health 2002 regulations (COSHH 2004) introducing workplace exposure limits (WELs) was enacted in the UK in 2005. This study aimed to determine whether introducing this legislation coincided with a reduction in the incidence of work-related short latency respiratory disease (SLRD) attributed to the agents with a WEL. The second objective was to determine whether changes in legislation, WELs and market forces coincided with a reduction in the incidence of SLRD attributed to glutaraldehyde and latex. METHOD: Reports of SLRD made to the Surveillance of Work-related and Occupational Respiratory Disease scheme were used to estimate the change in incidence within reporters between two time periods (interrupted time series design) using a longitudinal, negative binomial regression model with ß distributed random effects. A statistical interaction term was included in the model to make comparisons between the groups defined by suspected causal agent and/or occupation, essentially comparing two interrupted time series. Time periods were defined prospectively representing the changes in legislation or market forces. RESULTS: The introduction of the COSHH 2004 legislation in the UK coincided with a significant reduction in reports of SLRD attributed to agents with a WEL relative to those without a WEL (ratio of incidence rate ratios: 0.70; 95% CI 0.52 to 0.93) and a significant reduction in SLRD attributed to glutaraldehyde in healthcare workers (0.20; 0.07 to 0.57) and latex in all workers (0.37; 0.16 to 0.85). CONCLUSIONS: These data are consistent with a beneficial effect of legislation aiming to reduce workplace exposures.

Development of mechanism-based structural alerts for respiratory sensitization hazard identification.

This study outlines how mechanistic organic chemistry related to covalent bond formation can be used to rationalize the ability of low molecular weight chemicals to cause respiratory sensitization. The results of an analysis of 104 chemicals which have been reported to cause respiratory sensitization in humans showed that most of the sensitizing chemicals could be distinguished from 82 control chemicals for which no clinical reports of respiratory sensitization exist. This study resulted in the development of a set of mechanism-based structural alerts for chemicals with the potential to cause respiratory sensitization. Their potential for use in a predictive algorithm for this purpose alongside an externally validated quantitative structure-activity relationship model is discussed.