Scalable manufacturing of high-index atomic layer-polymer hybrid metasurfaces for metaphotonics in the visible.

Metalenses are attractive alternatives to conventional bulky refractive lenses owing to their superior light-modulating performance and sub-micrometre-scale thicknesses; however, limitations in existing fabrication techniques, including high cost, low throughput and small patterning area, have hindered their mass production. Here we demonstrate low-cost and high-throughput mass production of large-aperture visible metalenses using deep-ultraviolet argon fluoride immersion lithography and wafer-scale nanoimprint lithography. Once a 12″ master stamp is imprinted, hundreds of centimetre-scale metalenses can be fabricated using a thinly coated high-index film to enhance light confinement, resulting in a substantial increase in conversion efficiency. As a proof of concept, an ultrathin virtual reality device created with the printed metalens demonstrates its potential towards the scalable manufacturing of metaphotonic devices.

Non-brachycephalic dogs with stertor have higher nasopharyngeal collapsibility compared with dogs without stertor and foramen lacerum level is ideal for evaluating nasopharyngeal collapse on dynamic CT.

Stertor, a clinical sign associated with obstructive airway syndrome, is often observed in non-brachycephalic dogs. This prospective, case-control study aimed to compare soft palate dimensions, nasopharyngeal cross-sectional area (CSA), and nasopharyngeal collapsibility at various locations in non-brachycephalic dogs with and without stertor. A total of 50 dogs were recruited and stratified into control (n = 34) and stertor (n = 13) groups. Static and dynamic computed tomography was conducted without tracheal intubation, and the following variables were calculated: normalized soft palate length and thickness, normalized maximum and minimum nasopharyngeal CSAs (rCSAmax and rCSAmin), and nasopharyngeal collapsibility at the level of the cranial end of the soft palate, pterygoid hamulus, foramen lacerum, bony labyrinth, and caudal end of the soft palate. The stertor group demonstrated significantly lower rCSAmax and rCSAmin, as well as higher nasopharyngeal collapsibility compared with the control group, while no significant differences were noted in the soft palate dimension. Evaluating nasopharyngeal collapse at the foramen lacerum level was recommended due to the clear presence of identifiable bony landmarks and lower overlap in the nasopharyngeal collapsibility between dogs with and without stertor. Physical dimensions of the soft palate may not be the primary contributing factor to nasopharyngeal collapse and clinical signs in non-brachycephalic dogs.

NXC736 Attenuates Radiation-Induced Lung Fibrosis via Regulating NLRP3/IL-1ß Signaling Pathway.

Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1ß and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.

Deep learning-based reconstruction for canine brain magnetic resonance imaging could improve image quality while reducing scan time.

Optimal magnetic resonance imaging (MRI) quality and shorter scan time are challenging to achieve in veterinary practices. Recently, deep learning-based reconstruction (DLR) has been proposed for ideal image quality. We hypothesized that DLR-based MRI will improve brain imaging quality and reduce scan time. This prospective, methods comparison study compared the MR image denoising performances of DLR and conventional methods, with the aim of reducing scan time and improving canine brain image quality. Transverse T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences of the brain were performed in 12 clinically healthy beagle dogs. Different numbers of excitations (NEX) were used to obtain the image groups NEX4, NEX2, and NEX1. DLR was applied to NEX2 and NEX1 to obtain NEX2DL and NEX1DL . The scan times were recorded, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for quantitative analysis. Five blinded veterinarians assessed the overall quality, contrast, and perceived SNR on four-point Likert scales. Quantitative and qualitative values were compared among the five groups. Compared with NEX4, NEX2 and NEX1 reduced scan time by 50% and 75%, respectively. The mean SNR and CNR of NEX2DL and NEX1DL were significantly superior to those of NEX4, NEX2, and NEX1 (P < 0.05). In all image quality indices, DLR-applied images for both T2-weighted and FLAIR images were significantly higher than NEX4 and NEX2DL had significantly better quality than NEX1DL for FLAIR (P < 0.05). Findings indicated that DLR reduced scan time and improved image quality compared with conventional MRI images in a sample of clinically healthy beagles.

Increased radiographic opacity in the region of the gallbladder can be identified in dogs with large amounts of gallbladder sediment, sludge balls, and gallbladder mucocele.

Increased soft-tissue opacity in the region of the canine gallbladder is incidentally detected on radiographs. We hypothesized that there is a difference in the detection of gallbladder sediment on radiographs depending on the amount or mobility of the sediment. In this retrospective and analytical study, we aimed to assess the ultrasonographic features of gallbladder sediment that were detected radiographically. We also aimed to assess the differences in the detection of increased opacity of the gallbladder between radiographic views. We included 223 dogs that underwent thoracic radiography, abdominal radiography, and gallbladder ultrasonography. Ultrasonographic images of the gallbladder were divided into five groups: group 1, gravity-dependent sediment occupying < 50% of the gallbladder; group 2, gravity-dependent sediment occupying ≥50%; group 3, sediment attached to the gallbladder wall; group 4, sludge ball; and group 5, gallbladder mucocele. Dogs showing increased opacity on subjective assessment of any radiographic view were recorded, and the sensitivity of radiographic views for detecting gallbladder sediment was analyzed. Of 168 dogs with gallbladder sediment, 37 had increased opacity on at least one radiographic projection. The frequency was compared as a percentage within each category, and Group 4 was the highest percentage with increased radiographic gallbladder opacity, followed by Groups 2 and 5. The sensitivity for detecting increased opacity was highest in the thoracic ventrodorsal view. Thus, in dogs with increased gallbladder opacity on radiographs, large amounts of gallbladder sediment, sludge balls, and gallbladder mucocele should be considered differential diagnoses. In addition, the thoracic ventrodorsal view is recommended to evaluate gallbladder opacity.

Thyroid carcinosarcoma masquerading as a paraesophageal abscess in a Cane Corso dog.

A 12-year-old castrated male Cane Corso dog was presented with cervical swelling, lethargy, anorexia, and cough. An extensive neck mass with necrotic cysts was observed, severely adherent to surrounding tissues. Based on diagnostic imaging including ultrasound, computed tomography, and fine-needle aspiration cytology, paraesophageal abscess was tentatively diagnosed. However, after the mass was surgically removed, a diagnosis of thyroid carcinosarcoma composed of neoplastic cell populations with epithelial and mesenchymal origins was made via histopathology and immunohistochemistry. The dog died of a recurrent mass with pulmonary metastasis 105 d after surgery. This report describes a rare type of canine thyroid cancer, thyroid carcinosarcoma, preoperatively masquerading as an abscess and postoperatively confirmed by histopathology. Key clinical message: Thyroid carcinosarcoma, despite its rarity in dogs, should be included in the differential diagnoses of cervical mass especially with an aggressive progression.

Carcinosarcome thyroïdien déguisé en abcès paraoesophagien chez un chien Cane Corso. Un chien Cane Corso mâle castré de 12 ans a été présenté avec de l'enflure cervicale, de la léthargie, de l'anorexie et une toux. Une masse étendue du cou avec des kystes nécrotiques a été observée, adhérente fortement aux tissus environnants. Sur la base de l'imagerie diagnostique comprenant l'échographie, la tomodensitométrie et la cytologie par aspiration à l'aiguille fine, un abcès paraoesophagien a été provisoirement diagnostiqué. Cependant, après l'ablation chirurgicale de la masse, un diagnostic de carcinosarcome thyroïdien composé de populations de cellules néoplasiques d'origine épithéliale et mésenchymateuse a été posé par histopathologie et immunohistochimie. Le chien est décédé d'une masse récurrente avec métastase pulmonaire 105 jours après la chirurgie. Ce rapport décrit un type rare de cancer de la thyroïde canine, le carcinosarcome thyroïdien, se faisant passer pour un abcès en préopératoire et confirmé en postopératoire par histopathologie.Message clinique clé:Le carcinosarcome thyroïdien, malgré sa rareté chez le chien, doit être inclus dans les diagnostics différentiels de masse cervicale surtout à évolution agressive.(Traduit par Dr Serge Messier).

Nasopharyngeal collapse can be identified on radiography in healthy male Beagle dogs without cardiopulmonary diseases.

Pharyngeal collapse has been described as a decrease of more than 50% in the diameter of the lumen. However, there has been no study on changes in the pharyngeal lumen in clinically normal dogs. The hypothesis of this prospective, observational, and pilot study was that change in nasopharyngeal lumen would be over 50% in Beagle dogs without cardiopulmonary diseases. Thus, we assessed the nasopharyngeal luminal change using cervical radiography in Beagle dogs without respiratory signs or cardiac abnormalities. The study sample included 42 Beagle dogs without cardiopulmonary diseases. Cervical radiographies were acquired during inspiration and expiration, and nasopharyngeal luminal change (%) was calculated. The median nasopharyngeal luminal change was 16.6%, and nasopharyngeal luminal change over 50% was identified in two dogs. The nasopharyngeal luminal change was significantly associated with body condition score and body weight. There was no correlation between nasopharyngeal luminal change and age. This study revealed that change in nasopharyngeal lumen over 50% can be identified in Beagle dogs without cardiopulmonary diseases and may be over-diagnosed as partial pharyngeal collapse. Further studies for comparing change in nasopharyngeal lumen between clinically normal dogs and dogs with respiratory signs are warranted.

Pancreatic adenocarcinoma with atypical imaging features mimicking chronic pancreatitis in a dog.

An 11-year-old intact female Pomeranian dog was referred for jaundice, anorexia, and vomiting. The blood analysis revealed increased alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase. The serum canine pancreatic lipase immunoreactivity was within the normal reference range. The radiography revealed no significant findings. On ultrasound, the gallbladder was enlarged with a markedly distended common bile duct (CBD) measuring up to 6 mm in diameter. The pancreas had an irregular contour, a hypoechoic peripheral rim, multiple hyperechoic foci with acoustic shadowing, and showed increased echogenicity of the adjacent mesentery. Based on these results, an extrahepatic biliary obstruction secondary to the presumed chronic pancreatitis was diagnosed. The computed tomography (CT) images showed a hypoattenuating pancreatic parenchyma compared to the liver in the early phase, as well as multiple calcifications. A laparotomy was performed to reserve the patency of the CBD. The histopathological examination of the pancreas revealed exocrine pancreatic adenocarcinoma. While various appearances of exocrine pancreatic adenocarcinoma on CT have been reported in humans, CT features of pancreatic adenocarcinoma have not been well-established in dogs. The purpose of this report is to describe the atypical imaging features of pancreatic adenocarcinoma that are similar to those of chronic pancreatitis in a dog.

Downregulation of NKG2DLs by TGF-ß in human lung cancer cells.

BACKGROUND: Transforming growth factor beta (TGF-ß) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-ß and a TGF-ß inhibitor, Galunisertib (LY2157299). RESULTS: TGF-ß reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-ß on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-ß, it was thought that TGF-ß induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-ß or Galunisertib. CONCLUSIONS: Therefore, inhibition of TGF-ß might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Using force data to self-pace an instrumented treadmill and measure self-selected walking speed.

BACKGROUND: Self-selected speed is an important functional index of walking. A self-pacing controller that reliably matches walking speed without additional hardware can be useful for measuring self-selected speed in a treadmill-based laboratory. METHODS: We adapted a previously proposed self-pacing controller for force-instrumented treadmills and validated its use for measuring self-selected speeds. We first evaluated the controller's estimation of subject speed and position from the force-plates by comparing it to those from motion capture data. We then compared five tests of self-selected speed. Ten healthy adults completed a standard 10-meter walk test, a 150-meter walk test, a commonly used manual treadmill speed selection test, a two-minute self-paced treadmill test, and a 150-meter self-paced treadmill test. In each case, subjects were instructed to walk at or select their comfortable speed. We also assessed the time taken for a trial and a survey on comfort and ease of choosing a speed in all the tests. RESULTS: The self-pacing algorithm estimated subject speed and position accurately, with root mean square differences compared to motion capture of 0.023 m s -1 and 0.014 m, respectively. Self-selected speeds from both self-paced treadmill tests correlated well with those from the 10-meter walk test (R>0.93,p<1×10-13). Subjects walked slower on average in the self-paced treadmill tests (1.23±0.27 ms-1) than in the 10-meter walk test (1.32±0.18 ms-1) but the speed differences within subjects were consistent. These correlations and walking speeds are comparable to those from the manual treadmill speed selection test (R=0.89,p=3×10-11;1.18±0.24 ms-1). Comfort and ease of speed selection were similar in the self-paced tests and the manual speed selection test, but the self-paced tests required only about a third of the time to complete. Our results demonstrate that these self-paced treadmill tests can be a strong alternative to the commonly used manual treadmill speed selection test. CONCLUSIONS: The self-paced force-instrumented treadmill well adapts to subject walking speed and reliably measures self-selected walking speeds. We provide the self-pacing software to facilitate use by gait researchers and clinicians.

Changes of ultrasonographic pattern of the spleen examined with a high-frequency linear transducer during growth in puppies.

A normal spleen is a homogeneous, finely textured, and hyperechoic organ. The development of high-frequency transducers has enabled the examination of the structural features of the spleen. Thus, the spleen can appear mildly mottled, even in normal dogs, and this could be misinterpreted as an abnormality. The purpose of this prospective, longitudinal, descriptive study was to describe the ultrasonographic pattern of the splenic parenchyma using a high-frequency transducer in puppies. The study included nine, normal, client-owned puppies that were born healthy. Transabdominal ultrasonographic examination was performed from 4 to 60 weeks serially every 4 weeks. Ultrasonographic patterns of the spleen were graded as follows: granular, mild reticulonodular, moderate reticulonodular, and marked reticulonodular pattern. The examinations were performed by one veterinary clinician, and the grades of the ultrasonographic patterns were determined by two veterinary clinicians experienced in ultrasonography, based on consensus. Differences and associations between time and the grade of the splenic parenchyma were determined using the paired t-test and scatter plots. There was a strong quadratic relationship between time and the grade of the splenic parenchyma. It was found that the splenic parenchymal patterns changed with increasing age, with a granular appearance initially at 4 weeks, followed by a reticulonodular pattern with well-defined hypoechoic nodules-most marked between 28 and 36 weeks, after which this pattern decreased until there was a homogeneous granular pattern again at 60 weeks. These findings should not be misinterpreted as being indicative of a disease in normal puppies, particularly those aged between 28 and 36 weeks.

Copper Ions Removal from Water using A2B3 Type Hyperbranched Poly(amidoamine) Hydrogel Particles.

Micrometer-sized hyperbranched poly(amidoamine) (hPAMAM) particles are prepared with a simple A2B3 type Aza-Michael addition reaction between aminoethylpiperazine (AEP) and methylenebisacrylamide (MBA) in an inverse suspension polymerization condition. The synthesized particles exhibited surprisingly high Cu2+ sorption capacity (0.223g/g) for a solid-type absorbent. In addition to the high sorption ability of the particle, its simple synthetic process and convenience, due to its micrometer-sized spherical shape and recyclability, make it a practical and attractive absorbent for heavy metal ion removal from aqueous solutions.

CT variants of the caudal vena cava in 121 small breed dogs.

Computed tomography is increasingly used as a treatment planning method in canine patients with diseases of the retroperitoneum, however, published information on normal variations in the caudal vena cava (CVC) are currently lacking. The objectives of this retrospective descriptive study were to characterize CVC variants using CT angiography in a sample of small breed dogs and localize the CVC bifurcations for each variant. Inclusion criteria were small breed dogs (weight ≤ 15) that underwent contrast-enhanced CT scans of the CVC, abdominal aorta, and CVC tributaries. A total of 121 small breed dogs were sampled. Four right-sided and one left-sided CVC variations were identified: normal (88/121, 72.7%), caudal-partial split (17/121, 14.0%), partial duplication (8/121, 6.6%), complete duplication (7/121, 5.8%), and left-sidedness (1/121, 0.8%). The mean lumbar vertebral levels of the CVC bifurcation were L6.39 ± 0.41, L5.70 ± 0.35, L4.39 ± 0.42, L2.74 ± 0.38, and L6.4 in the normal, caudal-partial split, partial duplication, complete duplication, and left-sidedness types, respectively. The location of the CVC bifurcation, the relationship between the aortic trifurcation and the CVC bifurcation, and the location of the bilateral deep circumflex iliac veins with respect to the CVC bifurcation were significantly different among the right-sided types (P ≤ .001). Bilateral deep circumflex iliac veins joined to the ipsilateral common iliac veins and the CVC in the caudal-partial split and duplication types, respectively. The results of this study indicated that canine CVC variants may be frequent and should be considered during surgery or diagnostic imaging of the retroperitoneum.

Design, synthesis, and effects of novel phenylpyrimidines as glucagon receptor antagonists.

The hormone glucagon increases blood glucose levels through increasing hepatic glucose output. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, the inhibition of glucagon receptor is one target for the treatment of hyperglycemia in type 2 diabetes. Here we designed and synthesized a series of small molecules based on phenylpyrimidine. Of these, the compound (R)-7a most significantly decreased the glucagon-induced cAMP production and glucagon-induced glucose production during in vitro and in vivo assays. In addition, (R)-7a showed good efficacy in glucagon challenge tests and lowered blood glucose levels in diabetic db/db mice. Our results suggest that the compound (R)-7a could be a potential glucose-lowering agent for treating type 2 diabetes.

The Effect of Phloroglucinol, A Component of Ecklonia cava Extract, on Hepatic Glucose Production.

Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels.

Evaluation of interthalamic adhesion size as an indicator of brain atrophy in dogs with and without cognitive dysfunction.

Interthalamic adhesion thickness has been previously described as a parameter for quantifying canine brain atrophy and hypothesized to correlate with brain height or ventricular size. However, studies testing this hypothesis are lacking. This retrospective cross-sectional study aimed to compare interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio values in dogs with and without cognitive dysfunction. Medical records for dogs meeting the following inclusion criteria were retrieved from two hospitals: available brain magnetic resonance imaging (MRI) or computed tomography (CT) studies, no cerebral parenchymal lesions, and no prior neurological treatment. For each included dog, values of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio were measured by one observer from transverse CT or MRI images and a consensus was reached. A total of 113 dogs met inclusion criteria. Dogs were divided into three groups based on the following criteria: Young group (no cognitive dysfunction, <9-year-old, n = 43), Aging group (no cognitive dysfunction, ≥9-year-old, n = 61), and Dementia group (n = 9). All three parameters were significantly lower in the dementia group than in the Young and Aging groups. In the Young and Aging groups, there was significant negative correlation of all three parameters with age and positive correlation of interthalamic adhesion thickness and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio with body weight, while there was no correlation of interthalamic adhesion thickness/brain height ratio with body weight (P < 0.05). There were no differences in all three parameters according to skull type or gender. Findings from the current study supported the use of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio for quantifying brain atrophy in dogs with cognitive dysfunction.

Polyphenol-Rich Fraction of Ecklonia cava Improves Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Mice.

Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1), the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.

Design and Evaluation of a 3-DoF Haptic Device for Directional Shear Cues on the Forearm.

Wearable haptic devices on the forearm can relay information from virtual agents, robots, and other humans while leaving the hands free. We introduce and test a new wearable haptic device that uses soft actuators to provide normal and shear force to the skin of the forearm. A rigid housing and gear motor are used to control the direction of the shear force. A 6-axis force/torque sensor, distance sensor, and pressure sensors are integrated to quantify how the soft tactor interacts with the skin. When worn by participants, the device delivered consistent shear forces of up to 0.64 N and normal forces of up to 0.56 N over distances as large as 14.3 mm. To understand cue saliency, we conducted a user study asking participants to identify linear shear directional cues in a 4-direction task and an 8-direction task with different cue speeds, travel distances, and contact patterns. Participants identified cues with longer travel distances best, with an 85.1% accuracy in the 4-direction task, and a 43.5% accuracy in the 8-direction task. Participants had a directional bias, with a preferential response in the axis towards and away from the wrist bone.

Computed tomographic evaluation of portal vein indices in cats with the extrahepatic portosystemic shunts.

IMPORTANCE: The portal vein to aorta (PV/Ao) ratio is used to assess the clinical significance of extrahepatic portosystemic shunt (EHPSS). Previous studies using computed tomography (CT) were conducted in dogs but not in cats. OBJECTIVE: This study aimed to establish normal reference values for PV indices (PV/Ao ratio and PV diameter) in cats and determine the usefulness of these for predicting symptomatic EHPSS. METHODS: This study included 95 dogs and 114 cats that underwent abdominal CT. The canine normal (CN) group included dogs without EHPSS. The cats were classified into feline normal (FN, 88/114), feline asymptomatic (FA, 16/114), and feline symptomatic (FS, 10/114) groups. The PV and Ao diameters were measured in axial cross-sections. RESULTS: The group FN had a higher PV/Ao ratio than the group CN (p < 0.001). Within the feline groups, the PV indices were in the order FN > FA > FS (both p < 0.001). The mean PV diameter and PV/Ao ratio for group FN were 5.23 ± 0.77 mm and 1.46 ± 0.19, respectively. The cutoff values between groups FN and FS were 4.115 mm for PV diameter (sensitivity, 100%; specificity, 97.7%) and 1.170 for PV/Ao ratio (90%, 92.1%). The cutoff values between group FA and FS were 3.835 mm (90%, 93.8%) and 1.010 (70%, 100%), respectively. CONCLUSIONS AND RELEVANCE: The results demonstrated significant differences in PV indices between dogs and cats. In cats, the PV/Ao ratio demonstrated high diagnostic performance for symptomatic EHPSS. The PV diameter also performed well, in contrast to dogs.

Val43 residue of NsrR is crucial for the nitric oxide response of Salmonella Typhimurium.

ABSTRACT: In pathogenic bacteria, the flavohemoglobin Hmp is crucial in metabolizing the cytotoxic levels of nitric oxide (NO) produced in phagocytic cells, contributing to bacterial virulence. Hmp expression is predominantly regulated by the Rrf2 family transcription repressor NsrR in an NO-dependent manner; however, the underlying molecular mechanism in enterobacteria remains poorly understood. In this study, we identified Val43 of Salmonella Typhimurium NsrR (StNsrR) as a critical amino acid residue for regulating Hmp expression. The Val43-to-Ala-substituted mutant NsrR isolated through random and site-directed mutagenesis showed high binding affinity to the target DNA irrespective of NO exposure, resulting in a severe reduction in hmp transcription and slow NO metabolism in Salmonella under NO-producing conditions. Conversely, the Val43-to-Glu-substituted NsrR caused effects similar to nsrR null mutation, which directed hmp transcription and NO metabolism in a constitutive way. Comparative analysis of the primary sequences of NsrR and another NO-sensing Rrf2 family regulator, IscR, from diverse bacteria, revealed that Val43 of enterobacterial NsrR corresponds to Ala in Pseudomonas aeruginosa or Streptomyces coelicolor NsrR and Glu in enterobacterial IscR, all of which are located in the DNA recognition helix α3. The predicted structure of StNsrR in complex with the hmp DNA suggests dissimilar spatial stoichiometry in the interactions of Val43 and its substituted residues with the target DNA, consistent with the observed phenotypic changes in StNsrR Val43 mutants. Our findings highlight the discriminative roles of the NsrR recognition helix in regulating species-specific target gene expression, facilitating effective NO detoxification strategies in bacteria across diverse environments. IMPORTANCE: The precise regulation of flavohemoglobin Hmp expression by NsrR is critical for bacterial fitness, as excessive Hmp expression in the absence of NO can disturb bacterial redox homeostasis. While the molecular structure of Streptomyces coelicolor NsrR has been recently identified, the specific molecular structures of NsrR proteins in enterobacteria remain unknown. Our discovery of the crucial role of Val43 in the DNA recognition helix α3 of Salmonella NsrR offers valuable insights into the Hmp modulation under NO stress. Furthermore, the observed amino acid polymorphisms in the α3 helices of NsrR proteins across different bacterial species suggest the diverse evolution of NsrR structure and gene regulation in response to varying levels of NO pressure within their ecological niches.