Is arthritis an associated risk factor for trigger finger occurrence after carpal tunnel release? A nationwide, population-based study in Korea.

PURPOSE: We hypothesized that increased friction between the flexor tendon and surrounding structures due to hand arthritis is an important risk factor for trigger finger (TF) after carpal tunnel release (CTR). Therefore, we compared TF development according to the presence or absence of arthritis in carpal tunnel syndrome (CTS) patients treated with CTR. METHODS: This retrospective study was based on data collected from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in the Republic of Korea between January 1, 2002, and December 31, 2015. Patients diagnosed with TF between one month and one year after the CTR date or with a history of surgery were included in the study. During subsequent follow-up, the patients were divided into subgroups of those (1) with TF and (2) without TF. Sex, age, arthritis, and TF-related comorbidities were compared between the subgroups. RESULTS: The subgroup with TF had a higher proportion of women (9.43% vs 90.57%), the highest age range between 50 and 59 years, more cases of arthritis (32.55% vs 16.79%), and a higher proportion of patients with hypothyroidism (10.85% vs 4.60%) than the group without TF. The association between arthritis and TF after CTR was examined using a multivariate logistic regression model, showing arthritis to be a significant risk factor for TF after CTR (odds ratio, 1.35; P = 0.049). CONCLUSIONS: We identified arthritis as an important risk factor for the development of TF after CTR.

Do multiple fractures affect risk of fixation failure after surgical treatment of midshaft clavicle fracture? A retrospective cohort study.

BACKGROUND: Surgical treatment of midshaft clavicle fractures is associated with quick recovery and low risk of non-union. However, fixation failure may occur in case of severe comminution fractures. Moreover, clinical outcomes may be affected when clavicle fractures occur in combination with other injuries, particularly those involving the lower extremities, as the use of crutches or walkers may hinder the process of rehabilitation by adding strain on the acromioclavicular (AC) joint, resulting in possible fixation failure. This study aims to identify risk factors for fixation failure of midshaft clavicle fractures and elucidate the role of combined fractures in treatment outcomes. METHODS: This study included patients diagnosed with midshaft clavicle fractures who underwent initial surgery between January 2012 and November 2021 at a designated regional trauma center hospital. Retrospective evaluation of fixation failure was carried out in 352 patients with midshaft clavicle fractures using standard clinical evaluation protocols and conventional radiographs. The prevalence of fixation failure and the effects of several demographic variables on the risk of fixation failure and non-union were examined. Multivariate logistic regression analysis was carried out to identify independent risk factors for fixation failure. RESULTS: Fixation failure occurred in 40 patients (11.4%). Multivariate analysis identified comminution [odds ratio (OR) 3.532, p value = 0.003, 95% confidence interval (CI) 1.55-8.05)] and fewer number of screws (OR 0.223, p value = 0.022, 95% CI 0.06-0.80) as risk factors for fixation failure. Surgical techniques using wire cerclage reduced the chances of fixation failure in comminuted fractures (OR 0.63, p value = 0.033, 95% CI 0.05-0.80). Combined fractures that required rehabilitation using walkers or crutches increased the risk of non-union (OR 19.043, p value = 0.032, 95% CI 1.28-282.46). CONCLUSIONS: Additional fixation of comminuted fractures using cerclage can reduce the risk of treatment failure, while multiple fractures or rehabilitation for ambulation increases the risk of the same. LEVEL OF EVIDENCE: III.

The stability and in vitro antibacterial efficacy of enrofloxacin and gentamicin solutions against Staphylococcus pseudintermedius over 28 days.

BACKGROUND: Many clinicians prepare compounded otic solutions to treat otitis externa (OE). Research evaluating the stability and antimicrobial efficacy of these solutions is limited. HYPOTHESIS/OBJECTIVES: This study determined the chemical stability and in vitro bactericidal efficacy of compounded solutions of enrofloxacin and gentamicin during storage for 28 days. MATERIALS AND METHODS: Solutions of enrofloxacin (10 mg/mL, 1%) and gentamicin (3 mg/mL, 0.3%) were prepared with normal saline and 1 mg/mL dexamethasone. Solutions were stored at room temperature (25°C) for 0, 14 and 28 days. The chemical stability of the antibiotics and dexamethasone were determined using liquid chromatography tandem mass spectrometry in triplicate. Efficacy assessment was made with 10 isolates of Staphylococcus pseudintermedius obtained from dogs with OE. Serial 10-fold dilutions of the bacteria with the compounded solutions were prepared and the colony count results were converted into colony-forming units (cfus). The mean cfu/mL and cfu/mL reduction rates were compared between Day (D)0, D14 and D28. All of the antimicrobial testing solutions were performed in triplicate. RESULTS: Chromatography showed that both antibiotics and dexamethasone were stable for 28 days. No significant differences were observed in the antibiotic bactericidal efficacy of stored solutions at D0, D14 or D28. CONCLUSIONS AND CLINICAL RELEVANCE: Solutions of 1% enrofloxacin and 0.3% gentamicin in normal saline with 0.1% dexamethasone maintained chemical stability and bactericidal efficacy over 28 days. These solutions can be considered as alternatives to commercial preparations for treatment of canine OE when indicated.

Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis.

Canine atopic dermatitis (AD) is a common chronic inflammatory skin disorder resulting from imbalance between T lymphocytes. Current canine AD treatments use immunomodulatory drugs, but some of the dogs have limitations that do not respond to standard treatment, or relapse after a period of time. Thus, the purpose of this study was to evaluate the immunomodulatory effect of mesenchymal stem cells derived from canine adipose tissue (cASCs) and cASCs-derived extracellular vesicles (cASC-EVs) on AD. First, we isolated and characterized cASCs and cASCs-EVs to use for the improvement of canine atopic dermatitis. Here, we investigated the effect of cASCs or cASC-EVs on DNCB-induced AD in mice, before using for canine AD. Interestingly, we found that cASCs and cASC-EVs improved AD-like dermatitis, and markedly decreased levels of serum IgE, (49.6%, p = 0.002 and 32.1%, p = 0.016 respectively) epidermal inflammatory cytokines and chemokines, such as IL-4 (32%, p = 0.197 and 44%, p = 0.094 respectively), IL-13 (47.4%, p = 0.163, and 50.0%, p = 0.039 respectively), IL-31 (64.3%, p = 0.030 and 76.2%, p = 0.016 respectively), RANTES (66.7%, p = 0.002 and 55.6%, p = 0.007) and TARC (64%, p = 0.016 and 86%, p = 0.010 respectively). In addition, cASCs or cASC-EVs promoted skin barrier repair by restoring transepidermal water loss, enhancing stratum corneum hydration and upregulating the expression levels of epidermal differentiation proteins. Moreover, cASCs or cASC-EVs reduced IL-31/TRPA1-mediated pruritus and activation of JAK/STAT signaling pathway. Taken together, these results suggest the potential of cASCs or cASC-EVs for the treatment of chronic inflammation and damaged skin barrier in AD or canine AD.

Combination of immunosuppressive drugs and allogeneic stem cell treatment in a dog with suspected nephrotic syndrome.

The case study aims to describe the nephrotic syndrome (NS) in a castrated 3-year-old male Cocker Spaniel dog. The patient arrived at the hospital with a loss of appetite and weakness. Skin oedema with ascites was observed along with hypoalbuminaemia, hypoproteinaemia, hyperlipidaemia, hypercholesterolaemia, and proteinuria (urine protein to creatinine ratio = 22.4). Based on these findings, the patient was diagnosed with NS, although a renal biopsy was not conducted. Prednisolone (1 mg/kg, p.o. q12 h) and mycophenolate mofetil (10 mg/kg, p.o. q12 h) were prescribed as the immunosuppressive drugs, and previously cryopreserved allogeneic adipose tissue-derived mesenchymal stem cells (2 × 107 cells/kg) were injected intravenously. After several weeks of treatment, the patient recovered from NS. This is the first case report on immunosuppressive drugs and allogeneic mesenchymal stem cells being used to treat a dog with NS.

Tox4 modulates cell fate reprogramming.

Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate through an assay that determined the efficiency of iPSC reprogramming. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of the reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression, and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that the TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.This article has an associated First Person interview with the first author of the paper.

Blood Transfusion for Elderly Patients with Hip Fracture: a Nationwide Cohort Study.

BACKGROUND: This nationwide study aimed to investigate the blood transfusion status of elderly hip fracture patients and to examine the effect of packed red blood cell transfusion on all-cause mortality. METHODS: From the Korean National Health Insurance Service-Senior cohort consisting of 588,147 participants aged over 60 years in 2002, a total of 14,744 new-onset hip fracture patients aged 65-99 years were followed up for 11 years. The adjusted hazard ratios (aHRs), risk ratios, and their 95% confidence intervals were estimated by the Cox proportional hazard model and Poisson regression model. RESULTS: There were 10,973 patients (74.42%) in the transfusion group and 3,771 (25.58%) patients in the non-transfusion group. The mean volume of blood transfusion was 1,164.51 mL (± 865.25; median, 800 mL; interquartile range, 640-1,440). In the multivariable-adjusted Cox proportional hazard model, the transfusion group had 1.34-fold more risk of all-cause mortality than the non-transfusion group (aHR, 1.34; 95% confidence interval [CI], 1.26-1.42). In the multivariate-adjusted Poisson regression model, hip fracture patients in the transfusion group were 1.43 (adjusted risk ratio [aRR], 1.43; 95% CI, 1.09-1.87; P = 0.009) folds more likely to die within 30 days than those in the non-transfusion group. The mortality risk was highest at 90 days (aRR, 1.64; 95% CI, 1.40-1.93; P < 0.001) and slightly decreased at 180 days (aRR, 1.58; 95% CI, 1.40-1.79; P < 0.001) and 1 year (aRR, 1.43; 95% CI, 1.31-1.58; P < 0.001). CONCLUSION: In this nationwide representative cohort study, blood transfusion was performed in 75% of hip fracture patients. Even after adjusting for comorbidity and anticoagulant use, the postoperative results (hospitalization, mortality) of the transfusion group did not show significantly worse results than the non-transfusion group. Therefore, adequate patient blood management can only improve the patient's outcome after hip fracture surgery.

Anti-Photoaging Effects of Low Molecular-Weight Fucoidan on Ultraviolet B-Irradiated Mice.

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm² (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1ß release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging.

In vitro bactericidal activity of 465-470 nm blue light phototherapy and aminolevulinic acid on Staphylococcus pseudintermedius.

BACKGROUND: Staphylococcus pseudintermedius is the principal pathogen causing bacterial skin infections in dogs. Photodynamic therapy (PDT) involving the combination of light and a topical photosensitizer is used to treat human skin infections. Although the antimicrobial effects of PDT have been demonstrated using in vivo and in vitro studies in humans, its effects on dogs and their pathogens are unclear. OBJECTIVES: The aim of this study was to demonstrate the in vitro efficacy of PDT over a 465-470 nm spectrum to kill S. pseudintermedius using δ-aminolevulinic acid (ALA) as the photosensitizer. METHODS: Six S. pseudintermedius isolates from canine skin were exposed to blue light-emitting diodes (LEDs) at 465-470 nm, with or without ALA. The light doses were 18.4, 36.8 and 55.2 J/cm2 . The number of colony-forming units and optical densities of broth cultures were measured and then compared with Dunnett's test. Bacterial viability was monitored using fluorescence microscopy and the fluorescence intensity values were compared with a paired Student's t-test. RESULTS: Blue light inhibited the growth of S. pseudintermedius; the effect significantly increased with the addition of ALA as a photosensitizer and with increasing light doses. Live/dead staining confirmed that PDT reduced bacterial viability and exerted an antibacterial effect. CONCLUSION AND CLINICAL IMPORTANCE: Blue light has a strong antibacterial effect on S. pseudintermedius in a light dose-dependent manner. ALA alone did not exhibit bactericidal action, but its combination with blue light increased the effect of PDT compared to blue light alone.

The effect of an ex vivo boosted immune cell therapy on canine atopic dermatitis: an open, uncontrolled pilot study.

BACKGROUND: Canine atopic dermatitis (cAD) is associated with an imbalance between multiple T lymphocytes and cytokines. Ex vivo boosted immune cell (EBIC) therapy is the sequential administration of ex vivo cultured and activated lymphocytes to patients to improve immune function. OBJECTIVE: This pilot study aimed to assess the safety of EBIC therapy and demonstrate its efficacy as a novel treatment for cAD. ANIMALS: Ten dogs with AD. METHODS AND MATERIALS: The phenotypes of the immune cells before and after ex vivo culture were analysed by flow cytometry. EBICs (1.0-5.0 × 108 cells/animal) were administered to dogs every two weeks, with a total of six injections. The cAD extent and severity index (CADESI)-03 and pruritus scores were calculated to evaluate the efficacy of EBIC therapy for cAD. For safety assessment, regular blood examination was conducted, and any adverse events recorded. The serum levels of interleukin (IL)-4, IL-10, IL-31 and interferon-gamma (IFN-γ) were evaluated. RESULTS: The cells expanded by an average of 57.52-fold and the proportions of CD8+ cells and IFN-γ-producing cells significantly increased after ex vivo culture. Sequential EBIC therapy improved CADESI-03, and pruritus scores significantly. After stopping treatment the improvement rates increased for the CADESI score and were maintained for the pruritus score. There were no significant changes in cytokine levels. No significant adverse events were observed. CONCLUSIONS AND CLINICAL SIGNIFICANCE: EBIC therapy is a safe and efficient treatment for cAD. This therapy could correct the immunological imbalance in dogs with AD by infusing activated T lymphocytes.

Commentary on Current Trends in Rising Drug Costs and Reimbursement Below Cost.

PURPOSE: To quantify prescription drug price increases over a span of 3 years (2012-2015), as well as extrapolate current reimbursement rates expected by independent retail pharmacies. In addition, we investigate potential reasons for these increasing drug costs. DESIGN: Descriptive analysis. METHODOLOGY: National average drug acquisition costs (NADAC) data published by the Centers for Medicare & Medicaid Services were examined. Specifically, December 2012, 2013, and 2014, and July 2015 NADAC files were analyzed to identify generic and branded products with the highest percentage price increases. Percentage price differences were also calculated for 17 first-in-class drugs and their "me-too" competitors. The margin and margin percentage were calculated for claims adjudicated through four major payers. RESULTS: The top 50 generic drug price increases ranged from 474% to over 18,000% from December 2012 to July 2015. The top 50 branded drug price increases ranged from 63% to 391% during the same time period. The percentage price difference for the first-in-class drugs versus their me-too analogues ranged from -2.3% to 61,259%. The margin for generic drug claims adjudicated ranged from -$237.11 to-$1,105.96. The margin for branded drug claims adjudicated ranged from $272.42 to $360.17. CONCLUSION: Several potential reasons for the surge in prescription drug prices include manufacturer competition, industry consolidation, and capitalization on me-too drugs. This increase has compelled PBMs, health plan sponsors, and retail pharmacies to find novel ways to turn a profit, often at the expense of the consumer. Although there are no immediate solutions, legislation regulating PBM functions and the use of therapeutic interchange programs may offer health plans some assistance in managing drug costs.

Effects of driver's braking behavior by the real-time pedestrian scale warning system.

A driver warning system can improve pedestrian safety by providing drivers with alerts about potential hazards. Most driver warning systems have primarily focused on detecting the presence of pedestrians, without considering other factors, such as the pedestrian's gender and speed, and whether pedestrians are carrying luggage, that can affect driver braking behavior. Therefore, this study aims to investigate how driver braking behavior changes based on the information about the number of pedestrians in a crowd and examine if a developed warning system based on this information can induce safe braking behavior. For this purpose, an experiment scenario was conducted using a virtual reality-based driving simulator and an eye tracker. The collected driver data were analyzed using mixed ANOVA to derive meaningful conclusions. The research findings indicate that providing information about the number of pedestrians in a crowd has a positive impact on driver braking behavior, including deceleration, yielding intention, and attention. Particularly, It was found that in scenarios with a larger number of pedestrians, the Time to Collision (TTC) and distance to the crosswalk were increased by 12%, and the pupil diameter was increased by 9%. This research also verified the applicability of the proposed warning system in complex road environments, especially under conditions with poor visibility such as nighttime. The system was able to induce safe braking behavior even at night and exhibited consistent performance regardless of gender. In conclusion, considering various factors that influence driver behavior, this research provides a comprehensive understanding of the potential and effectiveness of a driver warning system based on information about the number of pedestrians in a crowd in complex road environments.

Enhancing mutual understanding of e-scooter user's perspective in overtaking maneuver through replaying own driving trajectory.

The global adoption of e-scooters as a convenient mode of micro-mobility transportation is on the rise, offering a flexible solution for covering first- and last-mile journeys. However, this surge in usage brings challenges, particularly concerning road safety, as e-scooter riders often share road space with other vehicles, heightening the risk of serious accidents. While numerous studies have explored safe overtaking behaviors and safety perceptions from drivers' viewpoints, limited attention has been given to understanding the varying safety perceptions of both drivers and e-scooter riders, particularly after riding an e-scooter and being overtaken by their own vehicles. This research aims to bridge this gap by examining variations in safety perceptions and assessing behavioral changes before and after experiencing overtaking scenarios. Specifically, the study focuses on scenarios where an e-scooter rider experiences being overtaken by a vehicle they had previously driven. A Unity-based sequential simulation process is employed to replay scenarios obtained from a vehicle simulator during an e-scooter experiment involving the same participant without their awareness. This innovative approach allows e-scooter rider participants to relive their own prior vehicle overtaking maneuvers while riding an e-scooter. The findings reveal that most participants (64%) felt less safe as e-scooter riders, influenced by factors like relative speed and acceleration of overtaking vehicles. After experiencing being overtaken by their own pre-driven vehicles, a noteworthy positive correlation emerged between safety perception and lateral distance, indicating that greater distance is derived from a better understanding of e-scooter safety. The study demonstrates the effectiveness of the sequential simulation strategy in fostering safe driving behavior and raising road safety awareness. Experiencing overtaking behaviors firsthand as an e-scooter rider, previously behind the wheel of the overtaking vehicle, encourages a heightened awareness of road safety. These findings have significant implications for road safety authorities, suggesting the potential application of this approach in driver education programs. By incorporating such interventions tailored to improve the safety of vulnerable road users, authorities can take proactive steps towards mitigating risks associated with micro-mobility transportation.

Assessment of Stress Caused by Environmental Changes for Improving the Welfare of Laboratory Beagle Dogs.

Animal stress is influenced by environmental factors, yet only a few studies have evaluated the effects of environmental stress on captive dogs. This study aimed to evaluate the effects of environmental and social enrichment on the stress levels of captive dogs housed in a lab. We assessed stress levels in eight Beagle dogs by measuring their body weight, cortisol levels, a stress hormone, the alkaline phosphatase activity in serum, the number of steps per hour, as well as clinical sign observations in a changed environment for 6 weeks. Four dogs assigned to a control group were raised alone in a relatively narrow place without toys; four dogs assigned to an experimental group were raised together in a relatively large place with toys. The body weight of the control group remained unchanged, while that of the experimental group decreased. Cortisol levels in the control group increased throughout, whereas those in the experimental group increased for up to 2 weeks and decreased thereafter. Consequently, cortisol levels in the experimental group significantly decreased compared to the control group at 6 weeks (p = 0.048). Fighting was observed among the dogs in the experimental group at 3 weeks; thus, one dog was separated from the group. The number of steps per hour was more than twice as high in the experimental than in the control group. Thereby, we determined that social housing, with appropriate companions and environmental enrichment materials, can reduce stress levels in captive dogs more efficiently than in single housing without such materials. Our study provides useful insights for captive animal organizations, such as kenneled dogs' management, to improve animal welfare.

Multiple time-dependent pathophysiological changes in a rabbit model of high-fat diet-induced hyperlipidemia.

High-fat diets (HFD) adversely affect organ systems. Several studies have examined HFD-related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time-dependent HFD-induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low-density lipoprotein, high-density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time-dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.

Regular medical checkup program (in K-MEDI hub) to enhance the welfare of laboratory dogs and pigs.

BACKGROUND: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. RESULTS: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. CONCLUSIONS: Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

Simultaneous determination of zolazepam and tiletamine in dog plasma by liquid chromatography coupled to a tandem mass spectrometry.

A mixture of tiletamine, a dissociative anesthetic, and zolazepam, a minor tranquilizer, has been widely used as an anesthetic or an immobilizing agent in a variety of animal species. However, interestingly, their pharmacokinetic behaviors have been published only in polar bears and pigs. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining the two drugs in dog plasma. After simple protein precipitation with acetonitrile including midazolam (internal standard), the analytes were chromatographed on a reversed-phase column with a mobile phase of 10 m m ammonium acetate aqueous solution and acetonitrile (1:4, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of zolazepam and tiletamine in plasma after a single intramuscular 10 mg dose of each in beagle dogs.

Are shared streets acceptable to pedestrians and drivers? Evidence from Virtual Reality experiments.

While the development of cities tends to focus on improving traffic mobility, it has gradually neglected people's demand for safety and comfort walking on the streets. To address this problem, shared streets that can integrate traditional street life and traffic mobility are getting more attention as pedestrian-friendly development. In order to measure the performance of shared streets, it is essential to identify how people feel when driving and walking around. However, investigating the various factors that influence the real world is not straightforward because of cost, time-consuming, and safety problems. Virtual reality and the Human-in-the-loop (HITL) have become valuable tools for conducting experiments without compromising them. The experiments are performed on both pedestrians' and drivers' sides. The three shared street layouts in a virtual environment are designed according to Europe's real shared street cases. To evaluate shared street effects, questions in five aspects: amenity, walking or driving experience, safety, economy or priority, and environmental perception are asked to participants, respectively. MPR, EWM, and Fuzzy Comprehension Evaluation methods are used to assess the performance. The result revealed that different groups of people have different sensitivity and preferences for each evaluation criteria. However, the results of the comprehensive evalutation showed that scenario C with the largest isolation measurement is preferable in both pedestrian and driver's groups based on shared street design elements. The city planners can get help from this shared street analysis, where the new design and layout could be tested in advance.

Canine Stem Cell Conditioned Media Accelerates Epithelial Migration in the Canine Tympanic Membrane.

Similar to skin, epithelia in the tympanic membrane (TM) regenerate and move toward the opening of the external ear canal, a process called epithelial migration (EM). EM is important for maintaining healthy ears because this process removes cerumen and debris. Therefore, increasing the rate of EM or TM regeneration could be very important for healthy ear maintenance and function. Stem cells or their conditioned media have been used in medical therapy in humans to increase the rate and efficacy of EM. The purpose of this study was to evaluate the ability of canine stem cell conditioned media to accelerate EM in canine TMs. Canine adipose tissue derived-mesenchymal stem cell conditioned media (cAD-MSCCM), and several cytokines related to keratinocyte growth or migration within the media were quantified using ELISA. Ink drops were placed on the TMs of four normal beagles. Then, cAD-MSCCM was applied weekly, a total of three times to the TMs of one ear, and nothing was applied to the other eye. The results showed a higher TM EM rate in the treatment group than in the control group (p < 0.05). No adverse events were recorded. These results suggest that the weekly application of cAD-MSCCM accelerates the TM EM rate.

A suspected case of a multiple autoimmune syndrome in a poodle dog.

A 9-year-old castrated male poodle dog was presented with icterus, anorexia, and lethargy. The dog was diagnosed with hypothyroidism 1 month before and was treated with levothyroxine. Severe anaemia with spherocytes, positive saline agglutination test, and hyperbilirubinemia indicated immune-mediated haemolytic anaemia (IMHA). Therefore, immunosuppressive therapy with prednisolone, mycophenolate mofetil, and danazol was started. Although the IMHA was well controlled, during tapering of prednisolone, acute multiple joint swelling and oedema suspected immune-mediated polyarthritis occurred twice. First, clinical symptoms improved as the dosage of prednisolone increased. However, the dog showed severe adverse effects to the steroid. Second time, we added leflunomide as another immunosuppressant, and clinical signs of arthritis disappeared. About 3 weeks later, despite the immunosuppressive therapy, skin lesions resembling an autoimmune dermatologic disorder spread throughout the body. Addition of cyclosporine resolved the skin lesions. This is a case report of a dog showing several sporadic clinical signs related to multiple autoimmune syndromes and their management using different immunosuppressant drugs.