Reduction of brain stem pathology and transient amelioration of early cognitive symptoms in transgenic mice treated with a monoclonal antibody against α-synuclein oligomers/protofibrils.

Immunotherapy against alpha-synuclein (α-syn) is a promising novel treatment strategy for Parkinson's disease (PD) and related α-synucleinopathies. We have previously shown that systemic treatment with the monoclonal oligomer/protofibril-selective antibody mAb47 targeting cytotoxic α-syn leads to reduced central nervous system levels of such species as well as an indication of reduced late-stage symptoms in aged (Thy-1)-h[A30P] α-syn transgenic mice. Here, we performed an early-onset long-term treatment study with this antibody to evaluate effects on brain pathology and behavioral outcomes in the same mouse model. Compared to the placebo group, the treatment strongly reduced phosphorylated α-syn (pS129 α-syn) pathology in the upper brain stem. Moreover, a preserved recognition memory and risk assessment behavior could be seen in antibody-treated mice at six months of age, even although these effects were no longer significant at eleven months of age. Importantly, no evidence of inflammatory responses or other potential toxic effects was seen with the treatment. Taken together, this study supports the strategy to target α-syn oligomers/protofibrils with monoclonal antibodies to counteract early symptoms and slow down the progression of PD and other α-synucleinopathies.

Effects of increased levels of supplemental vitamins during the summer in a commercial artificial insemination boar stud.

Heat stress due to increasing extremes in ambient temperature and humidity results in reduced semen quality in boars. This has caused reduced efficiency of the swine industry, requiring more boars to breed the same number of sows. Vitamins such as vitamin C (VC) and E (VE) have been shown to improve semen quality in boars. Recently, vitamin D has been shown to improve semen quality in boars. The purpose of this experiment was to evaluate the effects of increased supplemental vitamins on boar reproduction during the summer season in a commercial boar stud. One hundred and sixty Pig Improvement Company (PIC) terminal line boars (n = 32 per treatment) and 39 maternal, heat-sensitive boars (n = 7 or 8 per treatment) were randomly allocated to treatment and fed a corn and soybean meal-based diet adjusted based on individual boar body condition score. A control (CNT) diet was used that met PIC recommendations for boars. Increased supplementation of specific vitamins was given in the form of a top-dress and consisted of CNT wheat middlings, CNT plus VC (560 mg/day), CNT plus 25-hydroxy vitamin D3 (VD) (125 µg/day), CNT plus VE (275 mg/day) and CNT plus VC, VD and VE (CDE). The experiment was split into three periods based on maximum daily high temperatures in the barn, where period 1 was weeks 1 to 4, period 2 was weeks 5 to 11 and period 3 was weeks 12 to 14. Semen was collected from boars as needed using the stud's normal production schedule and was analyzed for sperm quantity and quality characteristics. There were no dietary effects on semen volume, sperm concentration or total sperm production (P ≥ 0.553). Total motility of sperm was not impacted by diet (P = 0.115); although, VC tended (P = 0.064) to have a greater progressive motility than CDE. Percentages of morphologically normal sperm and normal acrosomes were not affected by dietary supplementation (P ≥ 0.157). Period effects were observed for most semen quality parameters, with quality generally becoming reduced over time. The present study demonstrates that increased supplementation of vitamins beyond PIC recommendations was not beneficial for boar reproduction during the summer.

Standardized total tract digestible phosphorus requirement of 6 to 13 kg pigs fed diets without or with phytase.

Dietary phosphorus concentration greatly affects pig's growth performance, environmental impact and diet cost. A total of 1080 pigs (initially 5.9 ± 1.08 kg) from three commercial research rooms were used to determine the effects of increasing standardized total tract digestible (STTD) P concentrations in diets without and with phytase on growth performance and percentage bone ash. Pens (10 pigs/pen, 9 pens/treatment) were balanced for equal weights and randomly allotted to 12 treatments. Treatments were arranged in two dose titrations (without or with 2000 units of phytase) with six levels of STTD P each. The STTD P levels were expressed as a percentage of NRC (2012) requirement estimates (% of NRC; 0.45 and 0.40% for phases 1 and 2, respectively) and were: 80%, 90%, 100%, 110%, 125% and 140% of NRC in diets without phytase and 100%, 110%, 125%, 140%, 155% and 170% of NRC in diets with phytase. Diets were provided in three phases, with experimental diets fed during phases 1 (days 0 to 11) and 2 (days 11 to 25), followed by a common diet from days 25 to 46. On day 25, radius samples from one median-weight gilt per pen were collected for analysis of bone ash. During the treatment period, increasing STTD P from 80% to 140% of NRC in diets without phytase improved average daily gain (ADG; quadratic, P < 0.01), average daily feed intake (ADFI; quadratic, P < 0.05) and gain-feed ratio (G : F; linear, P < 0.01). Estimated STTD P requirement in diets without phytase was 117% and 91% of NRC for maximum ADG according to quadratic polynomial (QP) and broken-line linear (BLL) models, respectively, and was 102%, 119% and >140% of NRC for maximum G : F using BLL, broken-line quadratic and linear models, respectively. When diets contained phytase, increasing STTD P from 100% to 170% of NRC improved ADG (quadratic, P < 0.05) and G : F (linear, P < 0.01). Estimated STTD P requirement in diets containing phytase was 138% for maximum ADG (QP), and 147% (QP) and 116% (BLL) of NRC for maximum G : F. Increasing STTD P increased (linear, P < 0.01) the percentage bone ash regardless of phytase addition. When comparing diets containing the same STTD P levels, phytase increased (P < 0.01) ADG, ADFI and G : F. In summary, estimated STTD P requirements varied depending on the response criteria and statistical models and ranged from 91% to >140% of NRC (0.41% to >0.63% of phase 1 diet and 0.36% to >0.56% of phase 2 diet) in diets without phytase, and from 116% to >170% of NRC (0.52% to >0.77% of phase 1 diet and 0.46% to >0.68% of phase 2 diet) for diets containing phytase. Phytase exerted an extra-phosphoric effect on promoting pig's growth and improved the P dose-responses for ADG and G : F.

Trunk lean mass and its association with 4 different measures of thoracic kyphosis in older community dwelling persons.

BACKGROUND: The causes of age-related hyperkyphosis (HK) include osteoporosis, but only 1/3 of those most severely affected have vertebral fractures, suggesting that there are other important, and potentially modifiable causes. We hypothesized that muscle mass and quality may be important determinants of kyphosis in older persons. METHODS: We recruited 72 persons >65 years to participate in a prospective study designed to evaluate kyphosis and fall risk. At the baseline visit, participants had their body composition measures completed using Dual Energy X-ray Absorptiometry (DXA). They had kyphosis measured in either the standing [S] or lying [L] position: 1) Cobb angle from DXA [L]; 2) Debrunner kyphometer [S]; 3) architect's flexicurve ruler [S]; and 4) blocks method [L]. Multivariable linear/logistic regression analyses were done to assess the association between each body composition and 4 kyphosis measures. RESULTS: Women (n = 52) were an average age of 76.8 (SD 6.7) and men 80.5 (SD 7.8) years. They reported overall good/excellent health (93%), the average body mass index was 25.3 (SD 4.6) and 35% reported a fall in the past year. Using published cut-offs, about 20-30% were determined to have HK. For the standing assessments of kyphosis only, after adjusting for age, sex, weight and hip BMD, persons with lower TLM were more likely to be hyperkyphotic. CONCLUSIONS: Lower TLM is associated with HK in older persons. The results were stronger when standing measures of kyphosis were used, suggesting that the effects of muscle on thoracic kyphosis are best appreciated under spinal loading conditions.

Evaluating the impact of maternal vitamin D supplementation: I. Sow performance, serum vitamin metabolites, and neonatal muscle characteristics.

In Exp. 1, 56 gestating sows (PIC 1050; 35 d postinsemination) were used in a 30-d trial to determine serum 25(OH)D response to increasing concentrations of dietary vitamin D. Sows were randomly allotted to 1 of 7 dietary D treatments (200, 800, 1,600, 3,200, 6,400, 12,800, or 25,600 IU of added D per kilogram of complete diet) with 8 sows per treatment. Increasing D increased (quadratic; < 0.001) serum 25(OH)D with the response depicted by the prediction equation: serum 25(OH)D, ng/mL = 35.1746 + (0.002353 × dietary D, IU/d) - (0.0000000156 × dietary D, IU/d). In Exp. 2, 112 sows and their litters were used to determine the effects of dietary vitamin D regimen on sow performance, subsequent preweaning pig performance, neonatal bone and muscle characteristics, and serum vitamin metabolites. Sows were allotted to 1 of 4 dietary treatments 3 to 5 d following breeding: 800, 2,000, or 9,600 IU of D per kilogram of the diet or 50 µg of 25(OH)D (2,000 IU of D equivalent from Hy-D, DSM Nutritional Products, Parsippany, NJ) per kilogram of diet. There were 25 to 27 sows per treatment. Increasing dietary D increased (linear, = 0.001) serum 25(OH)D of sows on d 100 of gestation, at farrowing, and at weaning. Increasing D in sow diets increased piglet serum 25(OH)D at birth (linear, = 0.001) and weaning (quadratic, = 0.033). Sows fed 50 µg of 25(OH)D/kg had intermediate ( < 0.004) serum 25(OH)D concentrations on d 100 of gestation, at farrowing, and at weaning compared with sows fed 2,000 IU of D/kg and sows fed 9,600 IU of D/kg. Pigs from sows fed 50 µg of 25(OH)D/kg had greater serum 25(OH)D compared with pigs from sows fed 2,000 IU of D/kg, but at weaning, serum 25(OH)D concentrations were similar. Also, pigs from sows fed 9,600 IU of D/kg had greater ( = 0.011) serum 25(OH)D at birth and weaning compared with pigs from sows fed 50 µg of 25(OH)D/kg. Maternal performance, litter characteristics, neonatal bone ash content, and neonatal muscle fiber characteristics were largely unaffected by the dietary vitamin D treatments. Overall, D and 25(OH)D are both useful at increasing serum 25(OH)D concentrations, but more D (on an equivalent IU basis) is needed to achieve similar serum 25(OH)D responses compared with feeding 25(OH)D. Concentration of maternal vitamin D supplementation in lactation impacted milk transfer of the vitamin more so than the form of the vitamin, as evidence by the weaned pig serum 25(OH)D concentrations.

Evaluating the impact of maternal vitamin D supplementation on sow performance: II. Subsequent growth performance and carcass characteristics of growing pigs.

A of subsample of 448 growing pigs (PIC 327 × 1050) weaned from 52 sows fed varying dietary vitamin D regimens were used in a split-plot design to determine the effects of maternal and nursery dietary vitamin D on growth performance. Sows were previously administered diets containing vitamin D as vitamin D (800, 2,000, or 9,600 IU/kg) or as 25(OH)D (50 µg [or 2,000 IU vitamin D equivalent]/kg from HyD; DSM Nutritional Products, Parsippany, NJ). Once weaned, pigs were allotted to pens on the basis of previous maternal vitamin D treatment, and then pens were randomly assigned to 1 of 2 nursery vitamin D dietary regimens (2,000 IU of vitamin D/kg or 50 µg 25(OH)D/kg). Pigs remained on nursery vitamin D treatments for 35 d, and then they were provided common finishing diets until market (135 kg). Growing pig serum 25(OH)D suggested that maternal dietary vitamin D influenced ( < 0.001 at weaning) serum concentrations early after weaning, but nursery vitamin D regimen had a larger impact ( < 0.001) on d 17 and 35 postweaning. Overall growth performance was not influenced by nursery vitamin D dietary treatments. From d 0 to 35 in the nursery, pigs from sows fed increasing vitamin D had increased (quadratic, < 0.003) ADG and ADFI, but G:F was similar regardless of maternal vitamin D regimen. Also, pigs from sows fed 50 µg/kg of 25(OH)D had increased ( = 0.002) ADG compared with pigs weaned from sows fed 800 IU of vitamin D. Throughout finishing (d 35 postweaning until 135 kg), ADG was increased (quadratic, = 0.005) and G:F was improved (quadratic, = 0.049) with increasing maternal dietary vitamin D. Also, pigs from sows fed 50 µg/kg of 25(OH)D had increased ( = 0.002) ADG compared with pigs weaned from sows fed 800 IU of vitamin D. Carcass data were collected from a subsample population separate from that used for the growth performance portion of the study, and a total of 642 carcasses from progeny of sows fed the varying dietary vitamin D treatments were used. Live BW of pigs at marketing and HCW were heavier ( < 0.030) for pigs from sows previously fed 25(OH)D compared with pigs from sows fed 9,600 IU of vitamin D. Overall, pigs from sows fed 2,000 IU of vitamin D grew faster after weaning compared with pigs from sows fed 800 or 9,600 IU of vitamin D. Pigs from sows fed 25(OH)D hag greater ADG compared with pigs from sows fed 800 IU of vitamin D, and they had increased final BW and HCW compared with pigs from sows fed 9,600 IU of vitamin D.

Correlations among four measures of thoracic kyphosis in older adults.

SUMMARY: There are many ways to measure thoracic kyphosis ranging from simple clinical to more complex assessments. We evaluated the correlation among four commonly used kyphosis measures: Cobb angle, Debrunner kyphometer, kyphotic index, and the blocks method. Each measure was correlated with the others, confirming high clinical and research applicability. INTRODUCTION: The purpose of this study was to assess the associations among four commonly used measures of thoracic kyphosis in older adults. METHODS: Seventy two men and women aged 65-96 were recruited from the San Diego community. Four kyphosis measures were assessed in the same person during a baseline clinic visit. Two measures were done in the lying (L) and two in the standing (ST) position: (1) Cobb angle calculated from dual X-Ray absorptiometry (DXA) images (L), (2) Debrunner kyphometer (DK) angle measured by a protractor (ST), (3) kyphotic index (KI) calculated using an architect's flexicurve ruler (ST), and (4) the blocks method involving counting the number of 1.7 cm-thick blocks required to achieve a neutral head position while lying flat on the DXA table (L). Spearman rank correlation coefficients were used to determine the strength of the association between each kyphosis measure. RESULTS: Using the Cobb angle as the gold standard, the blocks method demonstrated the lowest correlation (r(s) = 0.63, p < 0.0001), the Debrunner method had a moderate correlation (r(s) = 0.65, p < 0.0001), and the kyphotic index had the highest correlation (r(s) = 0.68, p < 0.0001). The correlation was strongest between the kyphotic index and the Debrunner kyphometer (r(s) = 0.76, p < 0.0001). CONCLUSION: In older men and women, all four measures of thoracic kyphosis were significantly correlated with each other, whether assessed in the lying or standing position. Thus, any of these measures demonstrate both potential clinical and research utility.

Observation of Wakefields and Resonances in Coherent Synchrotron Radiation.

We report on high resolution measurements of resonances in the spectrum of coherent synchrotron radiation (CSR) at the Canadian Light Source (CLS). The resonances permeate the spectrum at wave number intervals of 0.074 cm(-1), and are highly stable under changes in the machine setup (energy, bucket filling pattern, CSR in bursting or continuous mode). Analogous resonances were predicted long ago in an idealized theory as eigenmodes of a smooth toroidal vacuum chamber driven by a bunched beam moving on a circular orbit. A corollary of peaks in the spectrum is the presence of pulses in the wakefield of the bunch at well-defined spatial intervals. Through experiments and further calculations we elucidate the resonance and wakefield mechanisms in the CLS vacuum chamber, which has a fluted form much different from a smooth torus. The wakefield is observed directly in the 30-110 GHz range by rf diodes, and indirectly by an interferometer in the THz range. The wake pulse sequence found by diodes is less regular than in the toroidal model, and depends on the point of observation, but is accounted for in a simulation of fields in the fluted chamber. Attention is paid to polarization of the observed fields, and possible coherence of fields produced in adjacent bending magnets. Low frequency wakefield production appears to be mainly local in a single bend, but multibend effects cannot be excluded entirely, and could play a role in high frequency resonances. New simulation techniques have been developed, which should be invaluable in further work.

Equations generated to predict iodine value of pork carcass back, belly, and jowl fat.

Data from existing literature were used to generate equations to predict finishing pig back, belly, and jowl fat iodine values (IV) and an experiment was conducted to evaluate these equations. The final database included 24, 21, and 29 papers for back, belly, and jowl fat IV, respectively. For experiments that changed dietary fatty acid composition, initial (INT) diets were defined as those fed before the change in diet composition and final (FIN) diets were those fed after. The predictor variables tested were divided into 5 groups: 1) diet fat composition (dietary percent C16:1, C18:1, C18:2, C18:3, EFA, unsaturated fatty acids, and IV product) for both INT and FIN diets, 2) day feeding the INT and FIN diets, 3) ME or NE of the INT and FIN diet, 4) live performance criteria (initial BW, final BW, ADG, ADFI, and G:F), and 5) carcass criteria (HCW and backfat thickness). The PROC MIXED procedure of SAS (SAS Inst., Inc., Cary, NC) was used to develop regression equations. Evaluation of models with significant terms was then conducted based on the Bayesian information criterion. The optimum equations to predict back, belly, and jowl fat IV were backfat IV = 84.83 + (6.87 × INT EFA) - (3.90 × FIN EFA) - (0.12 × INT days) - (1.30 × FIN days) - (0.11 × INT EFA × FIN days) + (0.048 × FIN EFA × INT days) + (0.12 × FIN EFA × FIN days) - (0.0060 × FIN NE) + (0.0005 × FIN NE × FIN days) - (0.26 × backfat depth); belly fat IV = 106.16 + (6.21 × INT EFA) - (1.50 × FIN days) - (0.11 × INT EFA × FIN days) - (0.012 × INT NE) + (0.00069 × INT NE × FIN days) - (0.18 × HCW) - (0.25 × backfat depth); and jowl fat IV = 85.50 + (1.08 × INT EFA) + (0.87 × FIN EFA) - (0.014 × INT days) - (0.050 × FIN days) + (0.038 × INT EFA × INT days) + (0.054 × FIN EFA × FIN days) - (0.0066 × INT NE) + (0.071 × INT BW) - (2.19 × ADFI) - (0.29 × backfat depth). Dietary treatments from the evaluation experiment consisted of a corn-soybean meal control diet with no added fat or a 3 × 3 factorial arrangement with main effects of fat source (4% tallow, 4% soybean oil, or a blend of 2% tallow and 2% soybean oil) and feeding duration (d 0 to 42, 42 to 84, or 0 to 84). The back, belly, and jowl fat IV equations tended to overestimate IV when observed IV were less than approximately 65 g/100 g and underestimate belly fat IV when actual IV are greater than approximately 74 g/100 g or when the fat blend was fed from d 0 to 84 or 42 to 84. Overall, with the exceptions noted, the regression equations were an accurate tool for predicting carcass fat quality based on dietary and pig performance factors.

Effects of drought-affected corn and nonstarch polysaccharide enzyme inclusion on nursery pig growth performance.

The effectiveness of carbohydrase enzymes has been inconsistent in corn-based swine diets; however, the increased substrate of nonstarch polysaccharides in drought-affected corn may provide an economic model for enzyme inclusion, but this has not been evaluated. A total of 360 barrows (PIC 1050 × 337, initially 5.85 kg BW) were used to determine the effects of drought-affected corn inclusion with or without supplementation of commercial carbohydrases on growth performance and nutrient digestibility of nursery pigs. Initially, 34 corn samples were collected to find representatives of normal and drought-affected corn. The lot selected to represent the normal corn had a test weight of 719.4 kg/m3, 15.0% moisture, and 4.2% xylan. The lot selected to represent drought-affected corn had a test weight of 698.8 kg/m3, 14.3% moisture, and 4.7% xylan. After a 10-d acclimation period postweaning, nursery pigs were randomly allotted to 1 of 8 dietary treatments in a completely randomized design. Treatments were arranged in a 2 × 4 factorial with main effects of corn (normal vs. drought affected) and enzyme inclusion (none vs. 100 mg/kg Enzyme A vs. 250 mg/kg Enzyme B vs. 100 mg/kg Enzyme A + 250 mg/kg Enzyme B). Both enzymes were included blends of ß-glucanase, cellulose, and xylanase (Enzyme A) or hemicellulase and pectinases (Enzyme B). Pigs were fed treatment diets from d 10 to 35 postweaning in 2 phases. Feed and fecal samples were collected on d 30 postweaning to determine apparent total tract digestibility of nutrients. The nutrient concentrations of normal and drought-affected corn were similar, which resulted in few treatment or main effects differences of corn type or enzyme inclusion. No interactions were observed (P > 0.10) between corn source and enzyme inclusion. Overall (d 10 to 35), treatments had no effect on ADG or ADFI, but enzyme A inclusion tended to improve (P < 0.10; 0.74 vs. 0.69) G:F, which was primarily driven by the improved feed efficiency (0.76 vs. 0.72; P < 0.05) of pigs fed Enzyme A in Phase 2 (d 10 to 25 postweaning) and was likely a result of improved xylan utilization. In conclusion, drought stress did not alter the nonstarch polysaccharide concentration of corn beyond xylan concentration, so it was not surprising that enzyme inclusion showed little benefit to nursery pig growth performance. However, improved feed efficiency of pigs fed diets containing Enzyme A from d 10 to 25 postweaning warrants further investigation

New developments in goblet cell mucus secretion and function.

Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell that can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example, after endocytosis or in response to acetyl choline. However, despite much progress in recent years, our understanding of goblet cell function and regulation is still in its infancy.

Surveillance of infant pertussis in Sweden 1998-2012; severity of disease in relation to the national vaccination programme.

In Sweden, pertussis was excluded from the national vaccination programme in 1979 until acellular vaccination was introduced in a highly endemic setting in 1996. The general incidence dropped 10-fold within a decade, less in infants. Infant pertussis reached 40-45 cases per 100,000 in 2008 to 2012; few of these cases were older than five months. We present an observational 15-year study on the severity of infant pertussis based on 1,443 laboratory-confirmed cases prospectively identified from 1998 to 2012 in the national mandatory reporting system and followed up by telephone contact. Analyses were made in relation to age at onset of symptoms and vaccination history. Pertussis decreased in non-vaccinated infants (2003 to 2012, p<0.001), indicating herd immunity, both in those too young to be vaccinated and those older than three months. The hospitalisation rates also decreased (last five-year period vs the previous five-year periods, p <0.001), but 70% of all cases in under three month-old infants and 99% of cases with apnoea due to pertussis were admitted to hospital in 1998 to 2012. Median duration of hospitalisation was seven days for unvaccinated vs four days for vaccinated infants aged 3-5 months. Nine unvaccinated infants died during the study period.

Evaluation of conditioning time and temperature on gelatinized starch and vitamin retention in a pelleted swine diet.

Two key feed processing parameters, conditioning temperature and time, were altered to determine their effects on concentration of gelatinized starch and vitamin retention in a pelleted finishing swine diet. Diet formulation (corn­soybean meal based with 30% distillers dried grains with solubles) was held constant. Treatments were arranged in a 2 × 3 factorial design plus a control with 2 conditioning temperatures (77 vs. 88°C) and 3 conditioner retention times (15, 30, and 60 s). In addition, a mash diet not subjected to conditioning served as a control for a total of 7 treatments. Samples were collected after conditioning but before pelleting (hot mash), after pelleting but before cooling (hot pellet), and after pelleting and cooling (cold pellet) and analyzed for percentage total starch, percentage gelatinized starch, and riboflavin, niacin, and vitamin D3 concentrations. Total percentage starch was increased by greater conditioning temperature (P = 0.041) but not time (P > 0.10), whereas higher temperature and longer time both increased (P < 0.05) percentage gelatinized starch, with increasing time resulting in a linear increase in percentage starch gelatinization (P = 0.013). The interaction between conditioning temperature and time increased percentage gelatinized starch (P = 0.003) but not percentage total starch (P > 0.10). Sample location also affected both percentage total starch and gelatinized starch (P < 0.05), with the greatest increase in percentage gelatinized starch occurring between hot mash and hot pellet samples. As expected, the pelleting process increased percentage gelatinized starch (P = 0.035; 7.3 vs. 11.7% gelatinized starch for hot mash vs. hot pellet samples, respectively), but there was no difference in total starch concentrations (P > 0.10). Finally, neither conditioning temperature nor time affected riboflavin, niacin, or vitamin D3 concentrations (P > 0.10). In summary, both increasing conditioningtemperature and time effect percentage gelatinized starch, but not to the extent of forcing the diet through a pelleting die.

Point-of-care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy.

We previously demonstrated in adult patients with haemophilia (PWH) that hemarthrosis is present in only ~1/3rd of acutely painful joints by using point-of-care-musculoskeletal ultrasound (MSKUS). Therefore, other unrecognized tissue abnormalities must contribute to pain. Using high resolution MSKUS, employing grey scale and power Doppler, we sought to retrospectively (i) investigate soft tissue abnormalities in painful haemophilic joints and (ii) to determine to what extent MSKUS findings, functional or radiographic joint scores correlate with biomarkers of inflammation in PWH. Findings were correlated with Hemophilia Joint Health Scores (HJHS), Pettersson scores, high sensitivity C-reactive protein and von Willebrand factor activity and antigen levels. A total of 65 MSKUS examinations for acute and chronic joint pains were performed for 34 adult haemophilia patients, mostly for chronic joint pains (72.3%). The most prominent findings (66.5%) pertained to inflammatory soft tissue changes including synovitis, tendinitis, enthesitis, bursitis and fat pad inflammation. Effusions were present in 55.5% and 46.8% of MSKUS performed for acute and chronic pain, respectively. Of those, 90.0% were bloody during acute and 47.6% during persistent pains. While inflammatory biomarkers correlated well with overall HJHS and total Pettersson scores (P < 0.05), they did not differ between those patients with synovitis and those without. MSKUS is emerging as an important modality to diagnose treatable musculoskeletal abnormalities contributing to pain in haemophilic arthropathy, and therefore seems critical for a personalized approach to haemophilia care. The role of biomarkers in this setting remains less clear and requires further investigation.

The effects of feeder design and dietary dried distillers' grains with solubles on the performance and carcass characteristics of finishing pigs.

Three experiments were conducted to compare the effects of a conventional dry (five 30.5-cm spaces 152.4 cm wide; Staco Inc., Schaefferstown, PA) vs. a wet-dry (double sided; each side = 38.1-cm space; Crystal Spring; GroMaster Inc., Omaha, NE) finishing feeder (Exp. 1 and 2) and to evaluate the effects of feeder design and dietary level of dried distillers' grains with solubles (DDGS; >10% oil; Exp. 3) on performance and carcass characteristics of finishing pigs. In Exp. 1, 1,186 pigs (32.1 kg BW) were used in a 69-d experiment. There were 26 to 28 pigs per pen and 22 pens per feeder design, and all pigs received the same diets in 4 phases. In Exp. 2, 1,236 pigs (28.7 kg BW) were used in a 104-d experiment, with 25 to 28 pigs per pen and 23 pens per feeder design, and all pigs received the same diets in 5 phases. Carcass measurements were obtained from 11 pens of each feeder design after harvest. In Exp. 3, 1,080 pigs (35.1 kg BW) were used in a 99-d 2 × 2 factorial with main effects of feeder design (dry vs. wet-dry feeders) and DDGS (20 vs. 60%) with 10 pens of 27 pigs per treatment and all diets fed in 4 phases. Jowl fat samples were collected from 2 pigs per pen for fatty acid analysis and iodine value (IV) determination. In all experiments, pigs fed with the wet-dry feeder had greater (P < 0.05) ADG, ADFI, and final BW. In Exp. 2 and 3, HCW and backfat depth were increased (P < 0.05) for pigs fed with a wet-dry feeder, but G:F and fat-free lean index (FFLI) were reduced. Jowl IV was also reduced (P < 0.05) with a wet-dry feeder in Exp. 3. Pigs fed 60% DDGS in Exp. 3 had decreased (P < 0.05) ADG, G:F, final BW, HCW, and backfat but increased jowl IV and a tendency (P < 0.07) toward greater FFLI regardless of feeder type. In conclusion, pigs fed with this specific type of wet-dry feeder had improved ADG and ADFI, poorer G:F, and increased backfat depth compared to pigs fed with a conventional dry feeder. The poorer growth performance and increased jowl IV of pigs fed diets with 60% DDGS was similarly exhibited for pigs fed on both feeders.

Risk assessment for coronary heart disease in patients with haemophilia: a single centre study in the United States.

In haemophilia, coronary heart disease (CHD) occurs at a similar frequency as in the general population, but the contributing risk factors in haemophilia are incompletely understood. To investigate risk factors and 10-year CHD risk in a single centre cohort of patients with haemophilia (PWH) ≥20 years old (n = 89). We retrospectively applied the modified Framingham National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP) III risk prediction equation. Three risk levels were defined: <10% (low), 10-20% (intermediate) and >20% (high). Results were compared to the National Health and Nutrition Examination Survey (NHANES). Mean age in both cohorts was similar. Compared to NHANES, systolic blood pressures were significantly higher in PWH, but current smoking and cholesterol were lower. CHD risk differed significantly between PWH and NHANES (P = 0.005) with a higher proportion of PWH classified at low risk (77.5% vs. 61.0%). The proportion of low risk patients was also significantly higher for severe haemophilia patients compared to non-severe haemophilia patients (88.6% vs. 66.7%, P = 0.02). Among PWH, and compared to PWH who were hepatitis C (HepC) negative, HepC positive patients had significantly lower cholesterol, LDL and triglycerides. The CHD risk of HepC positive patients differed significantly from NHANES (P = 0.03) with a lower proportion of HepC positives being classified as high risk (5.7% vs. 17.3%). Favourable CHD risk classification in PWH may be influenced by low cholesterol associated with HepC infection. Estimates of CHD risk in PWH by composite scoring may not be accurate and will require studies correlating risk factors with incident CHD.

A radiometabolite study of the serotonin transporter PET radioligand [(11)C]MADAM.

INTRODUCTION: (11)C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [(11)C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO2MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. METHODS: Comparative PET imaging studies in non-human primate brain with [(11)C]MADAM and [(11)C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [(11)C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET. RESULTS: PET imaging studies in non-human primate brain using [(11)C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [(11)C]SOMADAM in non-human primate plasma was approximately 5% at 4min and 1% at 15min after [(11)C]MADAM injection. HPLC analysis of brain sample after [(11)C]MADAM injection to rats demonstrated that [(11)C]SOMADAM was not detected in the brain. CONCLUSIONS: (11)C]SOMADAM is not superior over [(11)C]MADAM as a SERT PET radioligand. Nevertheless, [(11)C]SOMADAM has been identified as a minor labeled metabolite of [(11)C]MADAM measured in monkey plasma. [(11)C]SOMADAM was not detected in rat brain.

An evaluation of the effects of added vitamin D3 in maternal diets on sow and pig performance.

A total of 84 sows (PIC 1050) and their litters were used to determine the effects of supplementing maternal diet with vitamin D3 on sow and pig performance, serum 25-hydroxyvitamin D3 (25(OH)D3), milk vitamin D3, neonatal bone mineralization, and neonatal tissue vitamin D3. After breeding, sows were randomly assigned to 1 of 3 dietary vitamin D3 treatments (1,500, 3,000, or 6,000 IU/kg of complete diets). Sows were bled on d 0 and 100 of gestation and at farrowing and weaning (d 21). Pig BW was recorded at birth and weaning, and serum was collected from 2 pigs/litter at birth, on d 10 and at weaning. A total of 54 pigs (18/treatment) were euthanized at birth and necropsied to sample bones and tissues. Sow and suckling pig performance and neonatal bone ash and bone density did not differ among maternal vitamin D3 treatments; however, sow 25(OH)D3 and milk vitamin D3 increased (linear, P < 0.01) with increasing maternal vitamin D3 supplementation. Piglet serum 25(OH)D3 increased (quadratic, P < 0.03) with increased maternal vitamin D3. Neonatal kidney vitamin D3 tended (quadratic, P = 0.08) to decrease with increasing maternal vitamin D3, but liver vitamin D3 tended (linear, P = 0.09) to increase with increasing maternal vitamin D3. At weaning, a subsample of 180 pigs (PIC 327 × 1050) were used in a 3 × 2 split plot design for 35 d to determine the effects of maternal vitamin D3 and 2 levels of dietary vitamin D3 (1,800 or 18,000 IU/kg) from d 0 to 10 postweaning on nursery growth and serum 25(OH)D3. Overall (d 0 to 35), nursery ADG and G:F were not affected by either concentration of vitamin D3, but ADFI tended (quadratic, P < 0.06) to decrease with increasing maternal vitamin D3 as pigs from sows fed 3,000 IU had lower ADFI compared with pigs from sows fed 1,500 or 6,000 IU/kg. Nursery pig serum 25(OH)D3 increased with increasing maternal vitamin D3 (weaning) on d 0 (linear, P < 0.01), and maternal × diet interactions (P < 0.01) were observed on d 10 and 21 because pigs from sows fed 1,500 IU had greater increases in serum 25(OH)D3 when fed 18,000 IU compared with pigs from sows fed 3,000 IU. In conclusion, sow and pig serum 25(OH)D3, milk vitamin D3, and neonatal tissue vitamin D3 can be increased by increasing maternal vitamin D3, and nursery pig 25(OH)D3 can be increased by increasing dietary vitamin D3; however, sow and pig performance and neonatal bone mineralization was not influenced by increasing vitamin D3 dietary levels.

Effectiveness of internet-based cognitive behaviour therapy for panic disorder in routine psychiatric care.

OBJECTIVE: Guided Internet-based cognitive behaviour therapy (ICBT) for panic disorder has been shown to be efficacious in several randomized controlled trials. However, the effectiveness of the treatment when delivered within routine psychiatric care has not been studied. The aim of this study was to investigate the effectiveness of ICBT for panic disorder within the context of routine psychiatric care. METHOD: We conducted a cohort study investigating all patients (n = 570) who had received guided ICBT for panic disorder between 2007 and 2012 in a routine care setting at an out-patient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Panic Disorder Severity Scale-Self-report (PDSS-SR). RESULTS: Participants made large improvements from screening and pretreatment assessments to posttreatment (Cohen's d range on the PDSS-SR = 1.07-1.55). Improvements were sustained at 6-month follow-up. CONCLUSION: This study suggests that ICBT for panic disorder is as effective when delivered in a routine care context as in the previously published randomized controlled trials.