Heavily T2-weighted imaging findings of spinal cord swelling in dogs with intervertebral disc extrusion.

ABSTRACT: This study investigated causes of attenuation of cerebrospinal fluid (CSF) signal on heavily T2-weighted (T2W) images in dogs with thoracolumbar disc extrusion. Medical records and magnetic resonance images were retrospectively reviewed. Dogs were classified into the following grades; grade 1, non-ambulatory paraparesis; grade 2, paraplegia with deep pain perception and grade 3, paraplegia without deep pain perception. The length of intramedullary T2W hyperintensity of the spinal cord, cranial/ caudal expansion of extradural compressive materials (ECM), and the CSF signal attenuation were measured. Ratios to the second lumbar vertebra (L2) were calculated for the length of intramedullary T2W hyperintensity (T2W:L2), cranial/caudal expansion of ECM (ECML:L2), and CSF signal attenuation (CSF:L2). The dogs were classified into focal or extended T2W hyperintensity groups according to the length [focal, shorter than length of L2; extended, longer than L2]. The area of EMC and the spinal canal were measured on transverse images at the lesion deriving occupancy ratio. The correlation between CSF:L2 and other data were analysed, and CSF:L2 was compared between the grades. In dogs with intramedullary T2W hyperintensity, the locations of CSF attenuation and the hyperintensity were compared if those locations were matched. Fifty-five dogs were included, 36 of which showed intramedullary T2W hyperintensity. Twenty-two of 36 dogs were considered as match of the location of the CSF attenuation and hyperintensity. CSF:L2 was significantly correlated with T2W:L2 in dogs with extended T2W hyperintensity (p = 0.0002), while CSF:L2 was significantly correlated with ECML:L2 in dogs with focal or no T2W hyperintensity (p = 0.0103 and p = 0.0364, respectively). CSF:L2 in grade 3 was significantly greater than those in patients who were grade 1 or 2 (both p < 0.001). In conclusion, higher CSF:L2, which was frequently seen in grade 3, would be most consistent with a higher T2W:L2 which might indicate spinal cord swelling.

An experimental setup for creating and imaging 4He2 * excimer cluster tracers in superfluid helium-4 via neutron-3He absorption reaction.

For the purpose of future visualization of the flow field in superfluid helium-4, clusters of the triplet state excimer 4He2 * are generated along the micro-scale recoil tracks of the neutron-absorption reaction n + 3He → 3T + p. This reaction is induced by neutron irradiation of the 3He fraction contained in natural isotopic abundance liquid helium with neutron beams either from the Japan Proton Accelerator Research Complex, Materials and Life Science Experimental Facility (JPARC)/Materials and Life Science Experimental Facility or from the Kyoto University Institute for Integrated Radiation and Nuclear Science. These 4He2 * clusters are expected to be ideal tracers of the normal-fluid component in superfluid helium with several advantageous properties. Evidence of the excimer generation is inferred by detection of laser induced fluorescence emitted from the 4He2 * clusters excited by a purpose-built short pulse gain-switched titanium:sapphire (Ti:sa) laser operating at a wavelength of 905 nm. The setup and performance characteristics of the laser system including the Ti:sa and two continuous wave re-pumping lasers are described. Detection at the fluorescence wavelength of 640 nm is performed by using optical bandpass filtered photomultiplier tubes (PMT). Electrical noise in the PMT acquisition traces could successfully be suppressed by post-processing with a simple algorithm. Despite other laser-related backgrounds, the excimer was clearly identified by its fluorescence decay characteristics. Production of the excimer was found to be proportional to the neutron flux, adjusted via insertion of different collimators into the neutron beam. These observations suggest that the apparatus we constructed does function in the expected manner and, therefore, has the potential for groundbreaking turbulence research with superfluid helium.

Peripheral administration of κ-opioid receptor antagonist stimulates gonadotropin-releasing hormone pulse generator activity in ovariectomized, estrogen-treated female goats.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is indispensable for reproduction in mammals. Kisspeptin neurons in the hypothalamic arcuate nucleus (ARC), referred to as KNDy neurons because of the coexpression of neurokinin B and dynorphin A, are considered as components of the GnRH pulse generator that produces rhythmic GnRH secretion. The present study aimed to investigate if peripheral administration of PF-4455242, a κ-opioid receptor (KOR, a dynorphin A receptor) antagonist, facilitates pulsatile luteinizing hormone (LH) secretion and GnRH pulse generator activity in estrogen-treated ovariectomized Shiba goats to determine the possibility of using KOR antagonists to artificially control ovarian activities. PF-4455242 was intravenously infused for 4 h (1 or 10 µmol/kg body weight/4 h) or as a single subcutaneous injection (1 or 10 µmol/kg body weight). In a separate experiment, the same KOR antagonist (10 µmol/kg body weight/4 h) was intravenously infused during the recording of multiple unit activity (MUA) in the ARC that reflects the activity of the GnRH pulse generator to test the effects of KOR antagonist administration on GnRH pulse generator activity. Intravenous infusion and single subcutaneous injection of the KOR antagonist significantly increased the frequency of LH pulses compared with controls. Intravenous infusion of KOR antagonist also significantly increased the frequency of episodic bursts in the MUA. The present study demonstrates that peripherally administered KOR antagonist stimulates pulsatile LH secretion by acting on the GnRH pulse generator, and peripheral administration of PF-4455242 can be used to facilitate pulsatile LH secretion, which in turn facilitates ovarian activities in farm animals.

Phase Angle Is a Useful indicator for Muscle Function in Older Adults.

AIM: Phase angle (PhA) can be determined through bioelectrical impedance analysis and is a unique variable for skeletal muscle. The objective of this study was to evaluate the relationship between PhA and muscle mass/quality in older adults. In addition, we attempted to determine the cutoff value of PhA for poor muscle function. METHODS: Community-dwelling Japanese older men (n=285, 81.1±7.1 years) and women (n=724, 80.4±6.8 years) participated in this study and were classified into four groups based on the Asian Working Group for Sarcopenia (normal, presarcopenia, dynapenia, and sarcopenia). We measured PhA using bioelectrical impedance analysis, muscle quantity and quality indicators using ultrasonography, muscle strength, and physical performance and compared them in four groups. We also tried to determine the cutoff value of PhA for poor muscle function. RESULTS: We found a significant difference in PhA among the four groups in men (P<0.05), and the dynapenia (3.61±0.75°) and sarcopenia groups (3.40±0.74°) showed significantly lower values than the normal group (4.50±0.86°) (P<0.05), but not the presarcopenia group (4.12±0.85°). In women, a significant difference was also observed among the four groups (P<0.05), and the dynapenia (3.41±0.65°) and sarcopenia groups (3.31±0.66°) showed significantly lower measures than the normal group (4.14±0.71°) (P<0.05), but not the presarcopenia group (4.07±0.51°). The receiver-operating characteristic curve analysis indicated the best cutoff value of PhA (men: 4.05°, women: 3.55°) to discriminate sarcopenia and dynapenia from normal and presarcopenia. CONCLUSION: These findings suggest that PhA is a useful indicator for muscle function.

A computational fluid dynamics analysis of the effects of size and shape of anterior nasal septal perforations.

BACKGROUND: Nasal septal perforations (NSPs) often cause bleeding, crusting, obstruction, and/or whistling. The objective was to analyze the impact of anterior NSP size and shape on nasal physiology using computational fluid dynamics (CFD). METHODS: A 3-dimensional model of the nasal cavity was constructed from a radiologically normal CT scan using imaging software. Anterior NSPs (ovoid (ONSP): 0.5, 1, 2, and 3 cm long anterior-to-posteriorly and round (RNSP, 0.5 and 1 cm)) were virtually created in the model and divided into ventral, dorsal, anterior, and posterior regions. Steady-state inspiratory airflow, heat, and water vapor transport were simulated using Fluent CFD software. Air crossover through the perforation, wall shear, heat flux, water vapor flux, resistance, and humidification were analyzed. RESULTS: Air crossover and wall shear increased with perforation size. Regionally, wall shear and heat and water vapor flux were highest posteriorly and lowest anteriorly, generally increasing with size in those regions. RNSPs had greater heat and water vapor flux compared to corresponding size ONSPs. Resistance decreased by 10% or more from normal only in the 3 cm ONSP. Maximum water content was achieved more posteriorly in larger NSP nasal cavities. CONCLUSIONS: High wall shear and heat and water vapor flux in posterior perforation regions may explain the crusting most commonly noted on posterior NSP edges. This preliminary study suggests that larger NSPs have a greater effect on nasal resistance and water content. Decrease in resistance with larger NSP size may be implicated in reported symptomatic improvement following enlargement of NSPs for treatment.

Plasma Amino Acid Concentrations Are Associated with Muscle Function in Older Japanese Women.

BACKGROUND: Although several previous studies have found benefits for amino acid supplementation in terms of muscle function, the role of plasma amino acid concentrations on sarcopenia are not well addressed yet. OBJECTIVE: The aim of this study was to compare the amino acid concentrations at each stage of sarcopenia (normal, pre-sarcopenia, dynapenia, and sarcopenia) in community-dwelling older Japanese adults. SETTING AND SUBJECTS: Community-dwelling older Japanese women (n=232, 79.4±7.0 years) participated in this study. MEASUREMENTS: We measured plasma amino acid concentrations, 5-m walking speed, grip strength, and skeletal muscle mass using a bioelectrical impedance data acquisition system and compared them among participants at each stage of sarcopenia. RESULTS: The proportions of normal, pre-sarcopenia, dynapenia, and sarcopenia patients were 40.5% (n=94), 12.1% (n=28), 26.3% (n=61), and 21.1% (n=49), respectively. Significant differences were observed for concentrations of leucine, branched-chain amino acid (BCAAs), and essential amino acid (EAAs) among the four groups (p<0.05), and the dynapenia and sarcopenia groups showed significantly lower concentrations of leucine than the normal group (p<0.05). CONCLUSIONS: This study indicated a positive relationship between plasma leucine, BCAA and EAA concentrations and muscle function. A longitudinal study is needed to determine the causal relationship between leucine/BCAA concentrations and muscle function.

Evaluation of the safety of ramucirumab in Japanese patients with advanced gastric cancer.

As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.

Two-Year Follow-Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease.

A 13-month-old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient ß-N-acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N-acetylaspartate, and glycine-myo-inositol and lactate-alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.

Safety of an oral anticancer agent (trifluridine/tipiracil combination tablet) in patients with advanced and recurrent colorectal cancer.

We retrospectively studied the safety of trifluridine/tipiracil combination tablet (TAS-102) monotherapy in patients with advanced and recurrent colorectal cancer. Adverse events to TAS-102 monotherapy were observed in 22 out of 23 cases (95.7%). The most frequent adverse events were neutropenia (69.6%), nausea (53.2%), and malaise (30.4%). Treatment was postponed in 54 (59.3%) out of 91 courses, and in 34 (66.7%) of these 54 courses, the delay in treatment was due to bone marrow suppression. Seven patients with peritoneal metastases suffered from nausea, whilst none of the patients without peritoneal metastases had nausea (p = 0.0139). Nausea and vomiting during a previous chemotherapy cycle was significantly associated with nausea after TAS-102 treatment (p = 0.0007), and the treatment cycles were significantly longer in patients with grade 3 or 4 neutropenia (p = 0.0061). Our results suggest that the incidence of nausea was higher in patients treated with TAS-102. Therefore, it is important to inform patients of the risk of these toxicities and to provide enhanced supportive care. Moreover, we recommend that, for patients with repeated treatment postponement due to neutropenia, the dosage should be fixed based on therapeutic efficacy and prognosis.

Synergistic Functions of Enzymes Bound to Semiconducting Layers.

Synthesis and cooperative functions of hybrid materials composed of enzyme and semiconducting layers are described in this chapter. The hybrids were produced via a simple physical interaction between the components, that is, electrostatic interaction in an aqueous solution. To form interstratifying enzymes in the galleries, solution pH, which is a key parameter to decide surface potential, should be adjusted appropriately. In other words, enzymes should have an opposite charge when compared to that of the layers at an identical pH. Even though the intercalation slightly reduced enzymatic activity as compared to those of the free enzymes, stability under cruel conditions was drastically improved due to screening effect of semiconducting layers from extrinsic stimuli. In addition, photochemical control of redox enzymes sandwiched between semiconducting layers was accomplished. Light irradiation of the hybrids induced band gap excitation of the layers, and holes produced in the valence band activated the enzymes. It was revealed that the semiconducting layers with magnetic elements might be useful to magnetic application (separation) of enzymes as similar to conventional magnetic beads.

Health-related quality of life assessment in haemophilia patients on prophylaxis therapy: a systematic review of results from prospective clinical trials.

INTRODUCTION: Prophylaxis is effective in reducing the number of bleeding episodes in patients with severe or moderately severe haemophilia A and B, including those with inhibitors. However, data, predominantly from observational studies, suggest more equivocal effects on health-related quality of life (HRQoL). AIM: To examine the impact of prophylaxis on HRQoL from prospective clinical trials. METHODS: We performed a systematic literature review of clinical trials evaluating the efficacy of prophylaxis with factor VIII, FIX or bypassing agents. Trials assessing HRQoL via validated instruments were selected and summarized. RESULTS: Thirteen trials (haemophilia A [n = 8]; haemophilia B [n = 2]; inhibitors [n = 3]) met all inclusion criteria. HRQoL instruments included the EQ-5D, SF-36, Haem-QoL-A, Haem-A-QoL, Haemo-QoL and CHO-KLAT. Improvements in HRQoL following prophylaxis were observed with the EQ-VAS, SF-36 and haemophilia-specific instruments in adult patients and were associated with reduced pain, fewer restrictions in physical activities and better general health. Prophylaxis led to statistically significant or clinically meaningful HRQoL improvement in six trials and non-significant improvement in four trials; two trials found no improvement and one reported no data. Despite study differences, consistent trends suggested that patients previously treated solely on-demand and those who experienced marked reductions in the frequency of bleeding with prophylaxis had a greater improvement in HRQoL. CONCLUSION: Contrary to findings of observational studies, the results from the majority of prospective trials using validated instruments showed positive trends for improved HRQoL with prophylaxis in adults.

A computational study of functional endoscopic sinus surgery and maxillary sinus drug delivery.

BACKGROUND: Topical medication is increasingly used following functional endoscopic sinus surgery (FESS). Information on particle sizes that maximise maxillary sinus (MS) delivery is conflicting, and the effect of antrostomy size on delivery is unclear. The purpose of this study was to estimate antrostomy and particle size effects on topical MS drug delivery. METHODOLOGY: Sinonasal reconstructions were created from a pre- and a post-FESS CT scan in each of four chronic rhinosinusitis patients. Additional models were created from each post-FESS reconstruction representing four alternative antrostomy sizes. Airflow and particle deposition were simulated in each reconstruction using computational fluid dynamics for nebulised and sprayed delivery. RESULTS: MS ventilation and drug delivery increased following FESS, the largest virtual antrostomy led to greatest delivery, and MS delivery was sensitive to particle size. Particles within a 5-18 µm and 5-20 µm size range led to peak MS deposition for nebulised and sprayed particles, respectively. Post-FESS increases in drug delivery varied across individuals and within individuals by the type of antrostomy created. CONCLUSION: Our findings suggest that FESS, particularly with larger antrostomies, improves topical drug delivery, and that certain particle sizes improve this delivery. Further research is needed to contextualise these findings with other post-surgical effects.

The luteinising hormone surge-generating system is functional in male goats as in females: involvement of kisspeptin neurones in the medial preoptic area.

A luteinising hormone (LH) surge is fundamental to the induction of ovulation in mammalian females. The administration of a preovulatory level of oestrogen evokes an LH surge in ovariectomised females, whereas the response to oestrogen in castrated males differs among species; namely, the LH surge-generating system is sexually differentiated in some species (e.g. rodents and sheep) but not in others (e.g. primates). In the present study, we aimed to determine whether there is a functional LH surge-generating system in male goats, and whether hypothalamic kisspeptin neurones in male goats are involved in the regulation of surge-like LH secretion. By i.v. infusion of oestradiol (E2; 6 µg/h) for 16 h, a surge-like LH increase occurred in both castrated male and ovariectomised female goats, although the mean peak LH concentration was lower and the mean peak of the LH surge was later in males compared to females. Dual staining with KISS1 in situ hybridisation and c-Fos immunohistochemistry revealed that E2 treatment significantly increased c-Fos expression in the medial preoptic area (mPOA) KISS1 cells in castrated males, as well as ovariectomised females. By contrast, dual-labelled cells were scarcely detected in the arcuate nucleus (ARC) after E2 treatment in both sexes. These data suggest that kisspeptin neurones in the mPOA, but not those in the ARC, are involved in the induction of surge-like LH secretion in both male and female goats. In summary, our data show that the mechanism that initiates the LH surge in response to oestrogen, the mPOA kisspeptin neurones, is functional in male goats. Thus, sexual differentiation of the LH surge-generating system would not be applicable to goats.

Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted.