Personality and risk of hospital diagnosed mental disorder: a 35 years' prospective study.

PURPOSE: The present study examined the prospective association of neuroticism, extraversion and psychoticism with risk of hospital diagnosed mental disorder, examining intelligence as a potential confounder of this association. METHODS: A total of 1118 Danish men and women completed the Eysenck personality questionnaire at the mean age of 27 years. Information on psychiatric diagnoses was obtained by linking the study population to the national Danish psychiatric registers, and risk of diagnoses associated with each personality trait was examined using multiple Cox regression in models including the three personality traits unadjusted and adjusted for intelligence. Participants with diagnosis from a psychiatric department prior to the personality assessment were excluded. RESULTS: In total, 122 participants were diagnosed with a mental disorder during follow-up. Neuroticism significantly predicted risk of anxiety-, adjustment-, personality- and alcohol and substance abuse diagnoses. Extraversion did not significantly predict any diagnosis type, while psychoticism predicted a combined category of mood and anxiety diagnoses. Despite intelligence being a significant predictor of the majority of the included diagnoses, adjusting for intelligence did not substantially influence any trait-disorder associations. CONCLUSION: The results confirm high neuroticism as a prospective vulnerability factor for mental disorder and indicate high psychoticism to be a potential risk factor for mood and anxiety disorders. These associations are not confounded by intelligence.

High suicide rates during psychiatric inpatient stay and shortly after discharge.

OBJECTIVE: Over recent decades, intense efforts to address suicides in psychiatric admitted people have been initiated. The aim was to calculate suicide rates, rate ratios, population attributable risks (PAR) and trends among people admitted to or recently discharged from psychiatric wards. METHODS: Using a cohort design, we obtained nationwide register data on 6 292 932 individuals aged 15+ living in Denmark during 1995-2016. Of these, 178 703 (5.73%) males and 201 033 females (6.33%) had been admitted to psychiatric hospital. Incidence rate ratios (IRR) were obtained using Poisson regression analyses while adjusting for age and calendar period. Trends were assessed using joinpoint analyses. RESULTS: In total, 15 075 persons died by suicide, of which 6174 had been psychiatrically admitted. Among males, the suicide rate during the first week of admission and after discharge was 3409 and 3148 per 100 000 person-years, respectively. The corresponding values for females were 1267 and 1631. Generally, estimated suicide rates were highest in those with affective or anxiety stress disorders. During first week of hospitalization, the IRR was 237 for males and of 322 for females when compared with those never hospitalized. In first week after discharge, the IRR was 225 and 425 for males and females, respectively. PAR estimates indicated 6% of male suicides and 13% of female suicides attributes to first week of admission and discharge. The inpatient suicide rate decreased annually 2.5% until 2009 followed by a 7.5% annual percentage increase. The suicide rate after discharge decreased steadily annually over the study period. CONCLUSION: Despite finding declining post-discharge suicide rates, the period surrounding a psychiatric admission was still associated with extremely high suicide rates.

Population, general practitioner and practice characteristics are associated with screening procedures for microvascular complications in Type 2 diabetes care in Norway.

AIMS: To assess population, general practitioner (GP) and practice characteristics associated with the performance of microvascular screening procedures and to propose strategies to improve Type 2 diabetes care. METHODS: A cross-sectional survey in Norway (281 GPs from 77 practices) identified 8246 people with a Type 2 diabetes duration of 1 year or more. We used multilevel regression models with either the recording of at least two of three recommended screening procedures (albuminuria, monofilament, eye examination) or each procedure separately as dependent variable (yes/no), and characteristics related to the person with diabetes, GP or practice as independent variables. RESULTS: The performance of recommended screening procedures was recorded in the following percentages: albuminuria 31.5%, monofilament 27.5% and eye examination 60.0%. There was substantial heterogeneity between practices, and between GPs within practices for all procedures. Compared with people aged 60-69 years, those aged < 50 years were less likely to have an albuminuria test performed [odds ratio (OR) 0.75, 95% CI 0.61 to 0.93] and eye examination (OR 0.79, 95% CI 0.66 to 0.95). People with macrovascular disease had fewer screening procedures recorded (OR 0.68, 95% CI 0.59 to 0.78). Use of an electronic diabetes form was associated with improved screening  (OR 2.65, 95% CI 1.86 to 3.78). GPs with high workload recorded fewer procedures (OR 0.59, 95% CI 0.39 to 0.90). CONCLUSIONS: Performance of screening procedures was suboptimal overall, and in people who should be prioritized. Performance varied substantially between GPs and practices. The use of a structured diabetes form should be mandatory.

Comparing post-deployment mental health services utilization in soldiers deployed to Balkan, Iraq and Afghanistan.

OBJECTIVE: Insight on how different missions have impacted rates of mental health service (MHS) utilization is unexplored. We compared postdeployment MHS utilization in a national cohort of first-time deployed to missions in Balkan, Iraq, and Afghanistan respectively. METHODS: A prospective national cohort study of 13 246 first-time deployed in the period 1996 through 2012 to missions in Balkan area, Iraq, or Afghanistan respectively. Soldiers 'MHS utilization was also compared with a 5:1 sex-, age-, and calendar year-matched never-deployed background population. Postdeployment utilization of MHS was retrieved from national coverage registers. Using Cox survival analyses, participants were followed and compared with regard to receiving three different types of psychiatric services: (i) admission to psychiatric hospital, (ii) psychiatric outpatient contact, and (iii) prescriptions of psychotropics. RESULTS: Utilizing of psychiatric outpatient services and psychotropics was significantly higher in first-time deployed to Iraq and Afghanistan compared with deployed to Balkan. However, the rate of postdeployment admission to psychiatric hospital did not differ between missions. Postdeployment rates of psychiatric admission and psychiatric outpatient treatment were significantly higher in Afghanistan-deployed personnel compared with the background population. CONCLUSIONS: Utilization of MHS differed significantly between mission areas and was highest after the latest mission to Afghanistan.

Exploring social cognition in schizophrenia.

The aim of the study was to compare social cognition between groups of patients diagnosed with schizophrenia and healthy controls and to replicate two previous studies using tests of social cognition that may be particularly sensitive to social cognitive deficits in schizophrenia. Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 11 "imaginary conversation (i.e., theory of mind)" items, 10 "psychological understanding" items, and 10 "practical understanding" items. Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance. Healthy controls performed better than patients on all types of social cognitive tests, particularly on "psychological understanding." However, after adjusting for intelligence and neuropsychological test performance, all group differences became nonsignificant. When intelligence and global cognitive functioning is taken into account, schizophrenia patients and healthy controls perform similarly on social cognitive tests.

Predicting extraction and uptake of arterial energy metabolites by the mammary glands of lactating cows when blood flow is perturbed.

Previous work shows that mammary uptake of milk precursors from blood can be affected by the rate of blood flow (F) to the glands. The purpose of the current work was to test the ability of compartmental and cylindrical capillary models to account for the variation in mammary extraction and net uptake of plasma metabolites produced by perturbation of mammary F. The data for model fitting were obtained from a previous experiment in which mammary arteriovenous differences of acetate + ß-hydroxybutyrate (2C), glucose, triacylglycerol (TAG), and long-chain fatty acids (LCFA) were measured in 4 cows before, during, and after intraarterial infusion of inhibitors of endothelial nitric oxide synthase and cyclooxygenase, which are 2 major systems of F control in the mammary glands. The 4 models tested were (1) constant extraction within each cow, (2) clearance from an extracellular compartment is a linear function of F with an intercept, (3) total capillary volume in a cylindrical representation is a linear function of F with an intercept, and (4) uptake from an extracellular compartment obeys Henri-Michaelis-Menten kinetics, where maximum velocity (Vmax) is a linear function of F with an intercept. According to prediction errors, model 4 fitted 2C extraction data best, accounting for 82% of the observed variation. The estimated Km (Henri-Michaelis-Menten constant) for venous 2C was 0.4 mM. For glucose clearance, a variant of model 2 with a positive effect of 2C uptake on clearance was identified as best, producing a coefficient of determination (R(2)) of 0.31. For TAG, model 2 with a positive effect of arterial TAG concentration on TAG clearance was best, with an R(2) of 0.22. For LCFA, model 2 with a positive effect of arterial LCFA on LCFA clearance was best, with an R(2) of 0.29. Models 2 and 3 fitted the extraction data with the same R(2)-values and prediction errors, so both compartmental and cylindrical approaches to describing the vascular bed were equally capable of describing the effect of F on mammary uptakes. A combined fit of all best-fit models to extraction data for all 4 metabolites at once explained 52, 42, 73, and 77% of variation in net uptakes of 2C, glucose, TAG, and LCFA, respectively. According to the fitted model, each 1 L/min increase in F increased the mammary volumes of distribution of 2C, glucose, TAG, and LCFA by 13, 14, 18, and 7%, respectively.

Inhibition of local blood flow control systems in the mammary glands of lactating cows affects uptakes of energy metabolites from blood.

To test the effect of mammary blood flow on net uptakes of milk precursors by the mammary glands, inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX) were infused into the mammary circulation of 4 lactating cows. Inhibitors were infused in a 4×4 Latin square design, where treatments were infusion for 1 h of saline, NOS inhibitor (Nω-nitro-l-arginine methyl ester hydrochloride), COX inhibitor (indomethacin), or both NOS + COX inhibitors into one external iliac artery. Para-aminohippuric acid was also infused to allow for estimation of iliac plasma flow (IPF), of which approximately 80% flows to the mammary glands. Blood samples were collected before, during, and after inhibitor infusion from the contralateral external iliac artery and ipsilateral mammary vein. Inhibition of COX and NOS each produced a decrease in IPF, although the NOS effect was smaller and IPF continued to be depressed throughout the recovery period. The combination of COX and NOS inhibition produced a 50% depression in IPF and there was no carryover into the recovery period. Treatments that depressed IPF also increased arterial concentrations of acetate, ß-hydroxybutyrate (BHBA), and glucose. Similarly, arteriovenous differences of acetate, BHBA, and glucose were all increased during IPF depression. To correct for a potential effect of arterial concentration, arteriovenous differences were normalized to arterial concentration, producing an extraction percentage. Inhibition of COX increased glucose extraction and tended to increase acetate and BHBA extraction. Dual inhibition only increased BHBA extraction and had no effect on mammary extraction of other metabolites. These extractions did not increase because clearances of glucose and TAG decreased as IPF decreased, and clearances of acetate and BHBA tended to decrease. Net uptake of TAG was depressed by dual NOS/COX inhibition, whereas uptakes of acetate, BHBA, and glucose were not affected by any of the treatments. To separate effects of flow from effects of arterial concentration, uptakes were regressed against IPF and arterial concentration simultaneously. According to the slopes of the regressions, a 10% decrease in IPF from the mean observed during saline infusion resulted in 3.8, 7.3, and 10.4% decreases in uptakes of acetate, glucose, and triacylglycerol, respectively. These findings indicate that mammary blood flow affects milk precursor uptake, and that clearance should not be assumed constant to predict mammary uptakes of milk precursors in situations where blood flow is changing.

Comparing tailored and untailored text messages for smoking cessation: a randomized controlled trial among adolescent and young adult smokers.

The aim was to compare the effectiveness of untailored text messages for smoking cessation to tailored text messages delivered at a higher frequency. From February 2007 to August 2009, 2030 users of an internet-based smoking cessation program with optional text message support aged 15-25 years were consecutively randomized to versions of the program that offered either tailored or untailored text messages. Thirty-day point abstinence from smoking was measured self-reportedly at 12-months follow-up. Response rates were 36.3% and 38.1% in the tailored and untailored group, respectively. We analyzed the entire study population, as well as those opting for text messages (n = 1619). In intention-to-treat analysis with multiple imputation of missing data, the odds ratio for 30-day point abstinence was 1.28 (95% CI 0.91-2.08) for the tailored compared with untailored messages. When restricting the analysis to those who had chosen to receive text messages, the corresponding odds ratio was 1.45 (95% CI 1.01-2.08). The higher long-term quit rates in the group receiving the tailored text messages compared with untailored text messages in the restricted analysis indicated that tailoring and higher frequency of text messages increases quit rates among young smokers.

Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial function, so the glucose-induced increase in IPF was interpreted as feedback on mammary adenosine release from an anabolic response to glucose. Because NO synthase was not inhibited during indomethacin infusion, the feedback system is postulated to act through endothelial NO synthase. In the presence of L-NAME, glucose infusion had no effect on IPF, indicating that endothelial cyclooxygenase is not involved in glucose-induced changes in MBF.

Early motor developmental milestones and level of neuroticism in young adulthood: a 23-year follow-up study of the Copenhagen Perinatal Cohort.

BACKGROUND: Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors and personality traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. A subsample of the cohort comprising 1182 individuals participated in a follow-up when they were aged 20-34 years and were administered the Eysenck Personality Questionnaire (EPQ). Associations between motor developmental milestones and level of neuroticism, extraversion and psychoticism were analysed by multiple linear regression adjusting for for sex, single-mother status, parity, mother's age, father's age, parental social status and birth weight. RESULTS: Among the 1182 participants with information on the EPQ, information on milestones was available for 968 participants. Infants who developed high levels of neuroticism as adults tended to sit without support, crawl, and walk with and without support significantly later than individuals with low levels of neuroticism (p values <0.05). These results remained significant after adjustment for the included covariates and for adult intelligence. CONCLUSIONS: The findings are the first of their kind and suggest that delays in early motor development may not only characterize psychopathological disorders such as schizophrenia, but may also be associated with the personality dimension of neuroticism in adulthood.

Powerful inhibition of kainic acid seizures by neuropeptide Y via Y5-like receptors.

Neuropeptide Y (NPY) is widely distributed in interneurons of the central nervous system (CNS), including the hippocampus and cerebral cortex, in concentrations exceeding those of any other known neuropeptides. Sequence data comparing different species show that NPY is highly conserved. This suggests a critical role in regulation of regional neuronal excitability. Kainic acid, a glutamate agonist at kainic acid receptors, causes severe limbic motor seizures culminating in status epilepticus. We here report that NPY administered into the lateral ventricle is a powerful inhibitor of motor as well as electroencephalographic (EEG) seizures induced by kainic acid. This effect was mediated via receptors with a pharmacological profile similar to the recently cloned rat Y5 receptor. The present study is the first to demonstrate that NPY possesses anticonvulsant activity. This is consistent with the concept that NPY is an endogenous anticonvulsant and suggests that agonists acting at Y5-like receptors may constitute a novel group of drugs in antiepileptic therapy.

Changes in muscle strength and morphology after muscle unloading in Special Forces missions.

The purpose of the present study was to determine the changes in maximal muscle strength, rapid force capacity, jumping performance and muscle morphology following a Special Forces military operation involving 8 days of muscle unloading. Nine male Special Forces soldiers were tested before (pre) and immediately after (post1) an 8-day simulated special support and reconnaissance (SSR) mission and after 3 h of active recovery (post2). Maximal muscle strength (MVC) and rate of force development (RFD) were measured along with maximal counter movement jump height (JH). Muscle biopsies were obtained from the vastus lateralis at pre and post1. Acute reductions were found in MVC (11%), JH (10%) and RFD (17-22%) after 8 days of muscle unloading (post1) (P≤0.05). Type IIX fiber type area% increased (P≤0.05) at post1 together with a tendency toward increased type IIX fiber type % (P=0.09) and decreased type I fiber type % (P=0.06), suggesting a transition toward a less fatigue-resistant fiber-type profile. In conclusion, short-term unloading during SSR missions led to marked reductions in mechanical muscle function and functional performance, which may be partly explained by the changes in muscle morphology. Future studies should identify intervention strategies to counter-act the observed impairments.

Cardiac arrhythmias in poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters undergoing high-speed treadmill testing.

The significance of cardiac arrhythmias and their possible association with upper airway obstruction are frequently considered in the clinical investigation of poor performance. The specific aims of this retrospective study of a group of poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters were to: (1) describe the overall frequency and frequency distributions of arrhythmias; (2) describe arrhythmia characteristics including percent prematurity, relative recovery cycle lengths and QRS morphology; (3) describe variability of normal RR intervals; and (4) explore possible associations between upper airway abnormalities and arrhythmia categories during peak exercise and recovery. The records of 103 trotters presented to the Norwegian University of Life Sciences for high-speed treadmill testing were reviewed. The occurrence of at least one arrhythmic event was high (77-78%) when considering all exercise periods and 6-10% prematurity criteria. Triplets, salvos, and/or paroxysmal tachyarrhythmias occurred in 8% of horses during peak exercise. Complex ventricular arrhythmias occurred in 15% of horses in the first 2 min of recovery. Evaluation of QRS morphology and return cycle lengths demonstrated areas of overlap in characteristics typically attributed to either supraventricular or ventricular arrhythmias. There was no association between airway diagnosis and arrhythmias during any exercise period. The maximum average HR during peak exercise was an excellent predicter for complex ventricular arrhythmias during recovery. Because perfect categorization of arrhythmias is not possible, future studies should report descriptive arrhythmia information. Prospective studies that evaluate various degrees of upper airway obstruction and the effect on known initiators of arrhythmogenesis are needed.

N-3 fatty acids and cardiac autonomic function in humans.

Studies suggest that marine n-3 polyunsaturated fatty acids (PUFA) offer some protection against sudden cardiac death (SCD). The autonomic nervous system is involved in the pathogenesis of SCD and due to the fact that n-3 PUFA is abundant in the brain and other nervous tissue it is likely that n-3 PUFA might modulate autonomic control of the heart. Heart rate variability (HRV) is a non-invasive marker of cardiac autonomic function and an attenuated HRV is a predictor for SCD and arrhythmic events. Studies on HRV and n-3 PUFA have been performed in several populations such as patients with ischaemic heart disease, patients with diabetes mellitus, patients with chronic renal failure, and in healthy subjects. Many studies have demonstrated a positive association between cellular content of n-3 PUFA and HRV as well as supplementation with n-3 PUFA seems to increase HRV and thereby decreasing the risk of arrhythmic events and SCD.

Observation unit admission as an alternative to inpatient admission for trauma activation patients.

BACKGROUND: At this 35 000 visits/year emergency department (ED) at a level one trauma centre, a trauma protocol was implemented for the ED observation unit. Data on all trauma observation unit admissions were then collected to evaluate for safety, efficiency and admission rates. METHODS: A retrospective chart review was performed of all trauma patients in the observation unit during a 14-month period. Exclusion criteria for observation unit admission included: abnormal vital signs, positive focussed abdominal sonography for trauma examination, abnormal ECG, abnormal chest radiograph, abnormal head computed tomography, Glasgow coma score less than 14, or multisystem trauma. RESULTS: 364 trauma patients were admitted to the observation unit. 84.6% were trauma II activations and 3.8% were trauma I activations. There were no deaths, intubations, loss of vital signs or other adverse events. The average length of stay was 12 h 46 minutes and 11.5% of patients were admitted to an inpatient unit. At 30-day follow-up, there were no significant missed injuries. CONCLUSION: The observation unit is a safe alternative to inpatient admission for the evaluation of the minimally injured trauma activation patient.

A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity.

BACKGROUND: NYX-2925 is a novel N-methyl-D-aspartate receptor (NMDAR) modulator that has been shown to facilitate both NMDAR-dependent long-term potentiation (LTP) in vitro and learning and memory in vivo. OBJECTIVE: The present studies examine the effects of NYX-2925 on NMDAR-dependent auditory LTP (aLTP) in vivo. METHODS: NMDAR-dependent aLTP and NMDAR-dependent auditory mismatch negativity (MMN) was measured, as well as changes in resting-state qEEG power. RESULTS: NYX-2925 (1, 10 mg/kg PO) increased aLTP 1 h after auditory tetanus measured by the post- minus pre-tetanus difference waveform 140-180 ms post tone onset. NYX-2925 (0.1, 1 mg/kg PO) facilitated MMN measured by the difference waveform (i.e., deviant minus standard tones). NYX-2925 (0.1, 1, 10 mg/kg PO) also enhanced resting-state alpha qEEG power. Conversely, the NMDAR glutamate site antagonist CPP (10 mg/kg IP) reduces alpha power and MMN and produces an opposite effect as NYX-2925 on aLTP. CONCLUSIONS: Together, these data suggest that the activation of the NMDAR by NYX-2925 enhances synaptic plasticity in vivo, which may both reduce symptoms of neurological disorders and serve as a biomarker for drug effects. This is the first demonstration of a long-lasting (1-h post-tetanus) effect of NMDAR modulation on synaptic plasticity processes in vivo using a noninvasive technique in freely behaving animals.

Male-biased dispersal in a tropical Australian snake (Stegonotus cucullatus, Colubridae).

Sex-based differences in dispersal distances can affect critical population parameters such as inbreeding rates and the spatial scale of local adaptation. Males tend to disperse further than females in mammals, whereas the reverse is true for birds; too few reptiles have been studied to reveal generalities for that group. Although reptiles are most diverse and abundant in the tropics, few tropical reptiles have been studied in this respect. We combine data from a long-term (10-year) mark-recapture study with genetic information (based on nine microsatellite markers) on slatey-grey snakes (Stegonotus cucullatus, Colubridae) in the Australian wet-dry tropics. Males attain larger body sizes than females, and both genetic and mark-recapture data show that males also disperse further than females. Recapture records show that hatchling males dispersed away from their release points whereas hatchling females did not, and adult males moved further than adult females. In the genetic analysis, males contributed less to overall FST and relatedness than did females (F(STm) = 0.0025, F(STf) = 0.0275, P < 0.001; r(m) = 0.0053; r(f) = 0.0550; P < 0.001). Spatial autocorrelation analyses within the largest population revealed a similar pattern, with spatial structuring stronger for females than males. Overall, our genetic analyses not only supported the mark-recapture data, but also extended our insights by revealing occasional long-distance dispersal not detected by the mark-recapture study.

Continuous lactation in dairy cows: effect on milk production and mammary nutrient supply and extraction.

Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic function may be achievable in continuously milked high-yielding dairy cows as a result of the genetic selection for lactation performance and hence longevity of mammary epithelial cells. The milk production and mammary nutrient uptake in response to omission of the dry period for cows with an expected peak milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy cows experienced a 7-wk prepartum dry period. Continuous milking during the prepartum period reduced milk production in the following early lactation period by >20%. The reduced milk production could not be readily ascribed to inefficiency of the mechanisms responsible for nutrient uptake by the lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum triggered by as yet unknown local mechanisms. Milk protein content was elevated by 0.4 percentage units in the continuously milked cows. The underlying reason is unknown, but given the current pricing system for milk, it deserves to be further investigated.

The histamine H1 receptor is not involved in local control of mammary blood flow in dairy cows.

Low concentrations of the essential amino acid histidine in circulation have been shown to increase mammary blood flow and it has been suggested that this effect is mediated by histamine. The hypotheses tested in this experiment were that interstitial histamine concentrations in the mammary gland are related to arterial His concentrations and that mammary blood flow is reduced by extracellular histamine via H(1) receptors. The hypotheses were tested by infusing saline or chlorpheniramine, a blocker of the H(1) histamine receptor, into the arterial supply of the mammary glands of lactating cows infused with 44 g/h of amino acid mixtures with or without His for 10 h. Infusates were administered in a 2 x 2 factorial arrangement within a 4 x 4 Latin square to 4 multiparous Holstein cows in mid lactation. Exclusion of His from the infusate decreased protein content in milk from the infused udder half from 3.98 to 3.77%, and increased arterial alpha-aminonitrogen concentration from 3.2 to 3.4 mM. Neither the decreased arterial His concentration nor the H(1) blocker affected plasma flow to the infused udder half. We conclude that histamine is not involved in the regulation of mammary blood flow. The H(1) blocker decreased milk production in the infused udder half from 4.6 to 3.5 kg without affecting protein, fat, and lactose percentages, suggesting an inhibition of milk ejection. Cows on chlorpheniramine ate less feed during the infusion than saline-infused cows, which resulted in lower arterial concentrations and mammary uptakes of acetate. The efficiency of plasma triacylglycerol uptake across the mammary glands was decreased by chlorpheniramine but net uptake of long-chain fatty acids was not affected. The mechanism by which an amino acid deficiency influences mammary blood flow does not involve histamine signaling through the H(1) receptor and remains unidentified.

Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.

BACKGROUND: Plasma homocysteine (tHCY) has been associated with coronary artery disease (CAD). We tested whether tHCY also increases secondary risk, after initial CAD diagnosis, and whether it is independent of traditional risk factors, C-reactive protein (CRP), and methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS AND RESULTS: Blood samples were collected from 1412 patients with severe angiographically defined CAD (stenosis >/=70%). Plasma tHCY was measured by fluorescence polarization immunoassay. The study cohort was evaluated for survival after a mean of 3.0+/-1.0 years of follow-up (minimum 1.5 years, maximum 5.0 years). The average age of the patients was 65+/-11 years, 77% were males, and 166 died during follow-up. Mortality was greater in patients with tHCY in tertile 3 than in tertiles 1 and 2 (mortality 15.7% versus 9.6%, P:=0.001 [log-rank test], hazard ratio [HR] 1.63). The relative hazard increased 16% for each 5-micromol/L increase in tHCY (P:<0.001). In multivariate Cox regression analysis, controlling for univariate clinical and laboratory predictors, elevated tHCY remained predictive of mortality (HR 1.64, P:=0.009), together with age (HR 1. 72 per 10-year increment, P:<0.0001), ejection fraction (HR 0.84 per 10% increment, P:=0.0001), diabetes (HR 1.98, P:=0.001), CRP (HR 1. 42 per tertile, P:=0.004), and hyperlipidemia. Homozygosity for the MTHFR variant was weakly predictive of tHCY levels but not mortality. CONCLUSIONS: In patients with angiographically defined CAD, tHCY is a significant predictor of mortality, independent of traditional risk factors, CRP, and MTHFR genotype. These findings increase interest in tHCY as a secondary risk marker and in secondary prevention trials (ie, with folate/B vitamins) to determine whether reduction in tHCY will reduce risk.