Effect of common sedation agents on feline splenic size determined via ultrasonography.

AIMS: To evaluate the effect of IM administration of three sedative drugs, acepromazine, alfaxalone and dexmedetomidine, in combination with morphine, on the size of the feline spleen using ultrasonography. METHODS: Twenty-four client-owned cats undergoing elective de-sexing or minor procedures were recruited for a focused ultrasonographic examination of the spleen prior to and at 10, 20 and 30 minutes following administration of one of three randomly assigned IM sedation protocols: 0.05 mg/kg acepromazine (ACE group), 3 mg/kg alfaxalone (ALF group), or 10 µg/kg dexmedetomidine (DEX group), in combination with 0.5 mg/kg morphine. B-mode images of the spleen were collected and measured following a standardised protocol. Cardiorespiratory parameters and sedation score were also recorded. Mean thickness of the head, body and tail of the spleen for each group at 10, 20 and 30 minutes after drug administration was compared to baseline. RESULTS: Mean splenic thickness increased over time in the ACE group (thickness of body at T0 = 8.9 (SE 2.1) mm and at T30 = 10.5 (SE 2.0) mm; p = 0.001) and the ALF group (thickness of body at T0 = 8.8 (SE 1.0) mm and at T30 = 10.3 (SE 1.7) mm; p = 0.022) but not in the DEX group (thickness of body at T0 = 8.6 mm (1.2) and at T30 = 8.9 mm (0.6); p = 0.67). Mean arterial blood pressure in the DEX group was significantly higher than in the other groups (p = 0.002). Sedation scores in the DEX group were consistently high for the entire period. However, the sedation score in the ACE group increased over 30 minutes (p = 0.007). Sedation score in the ALF group was highest at 10 minutes but gradually decreased over the following 20 minutes (p = 0.003). CONCLUSIONS: Sedation with IM dexmedetomidine and morphine did not change splenic size, whereas acepromazine or alfaxalone and morphine increased it regardless of the degree of sedation. CLINICAL RELEVANCE: Where splenomegaly is identified in a cat sedated with acepromazine or alfaxalone, the effects of the sedation protocol could be considered as a possible cause.

Bone density in youth with prediabetes: results from the National Health and Nutrition Examination Survey, 2005-2006.

Youth with type 2 diabetes might have suboptimal peak bone mass, but it is unknown whether similar effects are evident in youth with prediabetes. Results from this study suggest that diabetes-related effects on peak bone mass likely occur before disease onset, and involve the muscle-bone unit. INTRODUCTION: Type 2 diabetes might adversely influence bone health around the age of peak bone mass, but it is unknown whether diabetes-related effects on areal bone mineral density (aBMD) are evident in youth with prediabetes. We compared age-related trends in aBMD and associations between lean body mass (LBM) and aBMD between children and adolescents with prediabetes vs. normal glucose regulation. METHODS: Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (2005-2006) in youth ages 12-20 years (49% female, 34% black) with prediabetes (n = 267) and normal glucose regulation (n = 1664). Whole body aBMD and LBM were assessed via DXA. LBM index (LBMI) and Z-scores for aBMD and LBMI were computed. RESULTS: Unadjusted between-group comparisons revealed greater mean weight and LBMI Z-scores in youth with prediabetes vs. normal glucose regulation, but similar bone Z-scores between the two groups. While accounting for differences in BMI Z-score, there was a significant interaction between prediabetes status and age with respect to whole body aBMD Z-score (P < 0.05), such that children with prediabetes tended to have increased aBMD but adolescents and young adults with prediabetes tended have lower aBMD. Furthermore, the positive association between LBMI and whole body aBMD was moderated in youth with prediabetes (P < 0.001), who had slightly lower whole body aBMD for a given LBMI (P = 0.068). Lumbar spine bone measures did not differ between the two groups. CONCLUSIONS: Type 2 diabetes-related threats to peak bone mass might occur prior to disease onset, therefore potentially impacting a considerable proportion of US youth.

Precise Measurement of Differential Cross Sections of the Σ

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470

An essential receptor for adeno-associated virus infection.

Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Dynamic nuclear polarization and ESR hole burning in As doped silicon.

We present an experimental study of the Dynamic Nuclear Polarization (DNP) of 29Si nuclei in silicon crystals of natural abundance doped with As in the temperature range 0.1-1 K and in a strong magnetic field of 4.6 T. This ensures a very high degree of electron spin polarization, extremely slow nuclear relaxation and optimal conditions for realization of Overhauser and resolved solid effects. We found that the solid effect DNP leads to the appearance of a pattern of holes and peaks in the ESR line, separated by the super-hyperfine interaction between the donor electron and 29Si nuclei closest to the donor. On the contrary, the Overhauser effect DNP mainly affects the remote 29Si nuclei having the weakest interaction with the donor electron. This leads to the appearance of a very narrow (≈3 mG wide) hole in the ESR line. We studied relaxation of the holes after burning, which is caused by the nuclear spin diffusion. Analyzing the dynamics of the hole in the spectrum with a simple one-dimensional diffusion model leads to a value of the diffusion coefficient D = 8(3) × 10-9 G2 s-1. Our data indicate that the spin diffusion is not completely prevented even in the frozen core near the donors. The emergence of the narrow hole after the Overhauser DNP may be explained by a partial "softening" of the frozen core caused by decoupling of the donor electron and remote 29Si nuclei.

A candidate-SNP retrospective cohort study for fracture risk in Japanese Thoroughbred racehorses.

Fractures are medical conditions that compromise the athletic potential of horses and/or the safety of jockeys. Therefore, the reduction of fracture risk is an important horse and human welfare issue. The present study used molecular genetic approaches to determine the effect of genetic risk for fracture at four candidate SNPs spanning the myostatin (MSTN) gene on horse chromosome 18. Among the 3706 Japanese Thoroughbred racehorses, 1089 (29.4%) had experienced fractures in their athletic life, indicating the common occurrence of this injury in Thoroughbreds. In the case/control association study, fractures of the carpus (carpal bones and distal radius) were statistically associated with g.65809482T/C (P = 1.17 x 10-8 ), g.65868604G/T (P = 2.66 x 10-9 ), and g.66493737C/T (P = 6.41 x 10-8 ). In the retrospective cohort study using 1710 racehorses born in 2000, the relative risk (RR) was highest for male horses at g.65868604G/T, based on the dominant allele risk model (RR = 2.251, 95% confidence interval 1.407-3.604, P = 0.00041), and for female horses at g.65868604G/T, based on the recessive allele risk model (RR = 2.313, 95% confidence interval 1.380-3.877, P = 0.00163). Considering the association of these SNPs with racing performance traits such as speed, these genotypes may affect the occurrence of carpus fractures in Japanese Thoroughbred racehorses as a consequence of the non-genetic influence of the genotype on the distance and/or intensity of racing and training. The genetic information presented here may contribute to the development of strategic training programs and racing plans for racehorses that improve their health and welfare.

Comparison of spinal alignment, muscular strength, and quality of life between women with postmenopausal osteoporosis and healthy volunteers.

This study compared spinal alignment, muscular strength, and quality of life (QOL) between women with postmenopausal osteoporosis and healthy volunteers. The results indicated that lower QOL in osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean muscle mass, and generalized muscle weakness. INTRODUCTION: Increased spinal kyphosis is common in patients with osteoporosis and negatively impacts quality of life (QOL). Muscular strength is also important for QOL in patients with osteoporosis. However, spinal kyphosis and muscle weakness also occur in healthy individuals with advancing age. The purposes of this study were thus to compare spinal alignment, muscular strength, and QOL between women with postmenopausal osteoporosis and healthy volunteers. METHODS: Participants comprised 236 female patients with postmenopausal osteoporosis (mean age, 68.7 years) and 93 healthy volunteer women (mean age, 71.0 years). Body mass index (BMI), angles of spinal kyphosis, back extensor strength, grip strength, and QOL were compared between groups. RESULTS: BMI, back extensor strength, and grip strength were significantly higher in the volunteer group than in the osteoporosis group (p < 0.01). Both thoracic kyphosis and lumbar lordosis were significantly greater in the osteoporosis group than in the volunteer group (p < 0.01). With regard to QOL, the 36-Item Short-Form Health Survey (SF-36) subscale scores of role physical, bodily pain, general health, and role emotional were all significantly lower in the osteoporosis group than in the volunteer group (p < 0.05 each). SF-36 physical component summary (PCS) score was significantly lower in the osteoporosis group than in the volunteer group (p < 0.001). SF-36 PCS score correlated positively with thoracic kyphosis and negatively with BMI only in the osteoporosis group (p < 0.05 each). CONCLUSIONS: These results indicated that lower QOL in osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean muscle mass, and generalized muscle weakness.

Different views on treatment decisions by first-year interprofessional healthcare students.

This study explored ethical treatment decisions of healthcare professional students beginning their education. As part of a first-semester modern medicine and bioethics course, 311 students watched and discussed, in interprofessional groups, a video titled Dax's Case: Who Should Decide? regarding the treatment of a life-threatening infectious disease against Dax's wish. The students then discussed and made their decision regarding treating or not. Their decisions, recorded on a worksheet, were classified as "will treat" or "won't treat." Professional groups' decision patterns were compared using the chi-square test. Overall, 151 (71%) opinions from students were classified as "will treat," and 61 (29%) as "won't treat." Nursing students were more likely to decide "won't treat" (in line with Dax's preference); however, the majority of other professions' students favoured treatment (against Dax's wish). Given the students' limited exposure to profession-specific education, our preliminary study supports the notion that healthcare profession students hold different values that align with their chosen profession at the start of their studies.

A FISH-based chromosome map for the European corn borer yields insights into ancient chromosomal fusions in the silkworm.

A significant feature of the genomes of Lepidoptera, butterflies and moths, is the high conservation of chromosome organization. Recent remarkable progress in genome sequencing of Lepidoptera has revealed that syntenic gene order is extensively conserved across phylogenetically distant species. The ancestral karyotype of Lepidoptera is thought to be n=31; however, that of the most well-studied moth, Bombyx mori, is n=28, and diverse studies suggest that three chromosomal fusion events occurred in this lineage. To identify the boundaries between predicted ancient fusions involving B. mori chromosomes 11, 23 and 24, we constructed fluorescence in situ hybridization (FISH)-based chromosome maps of the European corn borer, Ostrinia nubilalis (n=31). We first determined a 511 Mb genomic sequence of the Asian corn borer, O. furnacalis, a congener of O. nubilalis, and isolated bacterial artificial chromosomes and fosmid clones that were expected to localize in candidate regions for the boundaries using these sequences. Combined with FISH and genetic analysis, we narrowed down the candidate regions to 40 kb-1.5 Mb, in strong agreement with a previous estimate based on the genome of a butterfly, Melitaea cinxia. The significant difference in the lengths of the candidate regions where no functional genes were observed may reflect the evolutionary time after fusion events.

The frequency of early colorectal cancer derived from sessile serrated adenoma/polyps among 1858 serrated polyps from a single institution.

BACKGROUND AND AIM: Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). METHODS: A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. RESULTS: Among 1160 HP lesions, 1 (0.1%) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7%) high-grade dysplasia (HGD/Tis) and 1 (0.2%) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1%) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16%) HGD/Tis and 1 (2%) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5%) HGD/Tis and 166 (1%) T1 cancers were identified. CONCLUSIONS: Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1%) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype.

Pharmacokinetics of procaterol in thoroughbred horses.

Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 µg/kg) and oral (2.0 µg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.

Stress tuning of the fundamental absorption edge of pure germanium waveguides.

One-dimensional stress dependence on the fundamental absorption edge of pure germanium (Ge) waveguide has theoretically and experimentally been studied, considering built-in two-dimensional stress-tensile Ge grown on Si. Based on the results, we have designed Ge Franz-Keldysh (FK) electroabsorption (EA) modulators to work at 1550 nm. Application of one-dimensional [110] compressive stress above -350 MPa on a pure Ge [-110] waveguide should allow 1550 nm light transmission, unless otherwise a pure Ge modulator can only operate at 1600 nm or longer due to the built-in two-dimensional tensile stress in Ge. The prediction has experimentally been verified using a SiNx stressor film. This concludes that the presented stress-tuning approach of the pure Ge waveguides should expand the operation wavelength of Ge FK-EA modulators to C band. Since stress tuning can be locally done in the back-end-of-line of complementary metal oxide semiconductor (CMOS) process, the presented stress-tuning method should enable "field-programable" control of the operation wavelengths of the monolithically integrated Ge modulators in Si photonics platform.

Local bandgap control of germanium by silicon nitride stressor.

We have proposed a new approach to tune the operation wavelength of Franz-Keldysh Ge electro-absorption modulation in Si photonics by controlling the local strain environment to cover the whole range of C + L bands (1.53 - 1.62 µm). The present paper shows a proof of strain-tuning modulator concept by the shift of the Ge absorption edge using SiN(x) stressor films and Franz-Keldysh effect in strain-controlled Ge.

Olanzapine increases hepatic glucose production through the activation of hypothalamic adenosine 5'-monophosphate-activated protein kinase.

AIMS: To investigate the mechanism of the metabolic disturbance induced by the atypical antipsychotic olanzapine, we examined whether adenosine 5'-monophosphate-activated protein kinase (AMPK) in the hypothalamus and hepatic glucose production are involved in the effect of olanzapine. METHODS: Male 6-week-old ICR mice were used. Blood glucose levels were determined by the glucose oxidase method. The mRNA levels of gluconeogenic or glycolytic enzymes were measured by reverse transcription polymerase chain reaction (RT-PCR). AMPK expression was measured by Western blotting. RESULTS: Systemic injection of olanzapine increased blood glucose levels in both unfasted and fasted mice. However, the increase in fasted mice was less than that in unfasted mice. Central administration of olanzapine also increased the blood glucose levels in unfasted mice, but not in fasted mice. In a pyruvate tolerance test, olanzapine significantly increased blood glucose levels. In addition, olanzapine increased the mRNA levels of glucose-6-phosphatase (G6Pase), a gluconeogenic enzyme, in the liver. Furthermore, olanzapine increased phosphorylated AMPK in the hypothalamus of unfasted mice, and olanzapine-induced hyperglycaemia was inhibited by the AMPK inhibitor compound C. Central administration of the AMPK activator AICAR significantly increased G6Pase mRNA levels in the liver and blood glucose levels. Moreover, both olanzapine- and AICAR-induced hyperglycaemia were attenuated by the ß-adrenergic receptor antagonist propranolol, suggesting that olanzapine and AICAR induce hepatic glucose production through the sympathetic nervous system. CONCLUSIONS: Our results indicate that olanzapine activates AMPK in the hypothalamus, which increases hepatic glucose production via the sympathetic nervous system.

Analysis of a questionnaire on adverse reactions to blood donation in Japan.

In 2007, the Japanese Red Cross Blood Center performed a large-scale questionnaire study of post-donation adverse reactions. The questionnaire was distributed to 98,389 donors, and the answers were returned by 55,231 (56.1%). In total, 2,877 (5.2%) complained of an adverse reaction. Assuming that there were no adverse reactions for the 46,150 donors who did not reply, the rate of adverse reaction can be speculated to be 2.8%. Our study strongly suggests that blood centers have long underestimated the risks of vaso-vagal reactions. Taking at least 6h of careful rest after donation would be a helpful counter measure.