Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging.

PURPOSE: To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model. MATERIALS AND METHODS: Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured. RESULTS: Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters. CONCLUSION: IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.

Evaluation of the clinical usefulness of pancreatic alpha amylase as a novel biomarker in dogs with acute pancreatitis: a pilot study.

Pancreatic alpha amylase (P-AMY) is used as a biomarker of acute pancreatitis (AP) in human medicine. To our knowledge, there are no studies evaluating the usefulness of P-AMY in dogs with AP. In this study, we evaluated the diagnostic value of P-AMY, currently not verified in veterinary medicine. The AP group (n = 40) consisted of dogs with AP diagnosed using clinical signs and laboratory examinations, including abnormal canine pancreatic lipase (cPL) concentration, and compatible abdominal ultrasound examination at first presentation. Evaluation of the canine AP severity (CAPS) score was performed. The control group (n = 38) was composed of normal dogs without any abnormalities in clinical findings, blood exams or diagnostic imaging. The correlation of P-AMY with cPL was confirmed by Pearson's correlation analysis (r = 0.564, p < .001). The sensitivity and specificity for the most appropriate cut-off values of P-AMY were recorded similar to the values of DGGR. The dogs with AP and CAPS ≥11 had significantly higher serum P-AMY (p = .016) contrary to DGGR lipase and cPL. Furthermore, there was a significant difference in the median P-AMY dependent on the presence of systemic inflammatory response syndrome (p = .001). P-AMY showed similar level of diagnostic accuracy along with sensitivity and specificity compared to DGGR lipase. In addition, P-AMY showed a significant association with CAPS score, contrary to cPL and DGGR lipase. Along with other biomarkers associated with AP, P-AMY has the potential of usefulness as a supportive diagnostic and prognostic biomarker of AP in dogs.

Simplified image-based dosimetry using planar images and patient-specific S-values.

BACKGROUND: Single time point measurement approach and hybrid dosimetry were proposed to simplify the dosimetry process. It is anticipated that utilizing patient-specific S-value would enable more accurate dosimetry assessment based on imaging compared to using the conventional MIRD S-values. PURPOSE: We performed planar image-based dosimetry scaled with a single SPECT image for the entire treatment cycle using patient-specific S-values (PSS dosimetry) of organs. PSS dosimetry could further simplify the dosimetry procedure compared with a conventional 2D planar/3D SPECT hybrid dosimetry, as PSS dosimetry requires only one SPECT/CT image for the treatment of the entire cycle, whereas the conventional hybrid dosimetry requires a SPECT/CT image for each treatment cycle. METHODS: 177Lu-DOTATATE SPECT/CT and planar image datasets acquired from Seoul National University Hospital (SNUH, Seoul, Republic of Korea) were utilized for the evaluation. Images were acquired 4, 24, 48, and 120 h after patients' intravenous injection of 177Lu-DOTATATE. Dose estimations based on a Monte Carlo (MC) simulation using the Geant4 Application for Emission Tomography (GATE) (v.8.2) were considered as the reference. Planar image-based dosimetry scaled with a single SPECT image was performed using the patient-specific S-value (PSS). Briefly, the CT image was considered as the patient's anatomical reference and PSSs were quantified using the multiple voxel S-value (VSV) method. Then, PSS dosimetry was performed by obtaining activity information from sequential planar images and a scaling factor derived from a single SPECT/planar image pair. Hybrid dosimetry using sequential planar images and a single SPECT image was performed for comparison. The absorbed doses of the kidneys, bone marrow (BM) in the lumbar spine, liver, and spleen calculated using the PSS and hybrid dosimetries were compared with the reference MC results. RESULTS: The mean differences (MDs) of the self-absorption S-values between S-value of OLINDA/EXM and PSS for the kidneys, liver, and spleen were -0.04%, -2.39%, and -2.62%, respectively. However, the differences in the self-absorption S-values were significantly higher for the BM (84.99%) and the remainder of the body (ROB) (280.84%). The absorbed doses estimated by the PSS and hybrid dosimetries showed relatively high errors compared with MC simulation result, regardless of the organ. In contrast, the PSS and hybrid dosimetries produced similar dose estimates. For the entire cycles of the treatment, the MDs of absorbed doses between PSS and hybrid dosimetries were -3.31%, -6.04%, 3.37%, and -2.17% for the kidneys, BM, liver, and spleen, respectively. Through a correlation analysis and the Wilcoxon signed-rank test, we concluded that there was no significant difference between the results obtained by the two dosimetry methods. CONCLUSIONS: As the PSS was derived using CT images with actual anatomical information and organ-specific volume of interest (VOI), PSS dosimetry provided reliable results. PSS dosimetry was robust in estimating the absorbed dose for the later treatment cycles. Therefore, PSS dosimetry outperformed hybrid dosimetry in terms of dose estimation for a greater number of treatment cycles.

Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice.

Klotho, an anti-aging protein, has gained attention for its protective effects against various diseases, including metabolic disorders, through recombinant Klotho administration. However, the potential of Klotho as a target for gene therapy requires further exploration, as it remains relatively understudied in the context of metabolic disorders. In this study, we demonstrate that AAV-full length(FL)-Klotho administration induces weight loss in mice and provides protection against high-fat diet (HFD)-induced obesity and hepatic steatosis, concurrently reducing the weights of white adipose tissue and liver. AAV-FL-Klotho administration also enhanced thermogenic gene expression in brown adipose tissue (BAT) and improved the morphology of interscapular BAT. The weight loss effect of AAV-FL-Klotho was found to be, at least in part, mediated by UCP1-dependent thermogenesis in brown adipocytes, potentially influenced by hepatokines secreted from AAV-FL-Klotho-transduced hepatocytes. These findings suggest that AAV-FL-Klotho is an attractive candidate for gene therapy to combat obesity. Nevertheless, unbiased experiments have also revealed disturbances in lipid metabolism due to AAV-FL-Klotho, as evidenced by the emergence of lipomas and increased expression of hepatic lipogenic proteins.

2,4,6-Triphenyl-1-hexene, an Anti-Melanogenic Compound from Marine-Derived Bacillus sp. APmarine135.

Although melanin protects against ultraviolet radiation, its overproduction causes freckles and senile lentigines. Recently, various biological effects of metabolites derived from marine microorganisms have been highlighted due to their potential for biological and pharmacological applications. In this study, we discovered the anti-melanogenic effect of Bacillus sp. APmarine135 and verified the skin-whitening effect. Fractions of APmarine135 showed the melanin synthesis inhibition effect in B16 melanoma cells, and 2,4,6-triphenyl-1-hexene was identified as an active compound. The melanogenic capacity of 2,4,6-triphenyl-1-hexene (1) was investigated by assessing the intracellular melanin content in B16 cells. Treatment with 5 ppm of 2,4,6-triphenyl-1-hexene (1) for 72 h suppressed the α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin increase to the same level as in the untreated control group. Additionally, 2,4,6-triphenyl-1-hexene (1) treatment suppressed the activity of tyrosinase, the rate-limiting enzyme for melanogenesis. Moreover, 2,4,6-triphenyl-1-hexene (1) treatment downregulated tyrosinase, Tyrp-1, and Tyrp-2 expression by inhibiting the microphthalmia-associated transcription factor (MITF). Furthermore, 2,4,6-triphenyl-1-hexene (1) treatment decreased the melanin content in the three-dimensional (3D) human-pigmented epidermis model MelanoDerm and exerted skin-whitening effects. Mechanistically, 2,4,6-triphenyl-1-hexene (1) exerted anti-melanogenic effects by suppressing tyrosinase, Tyrp-1, and Tyrp-2 expression and activities via inhibition of the MITF. Collectively, these findings suggest that 2,4,6-triphenyl-1-hexene (1) is a promising anti-melanogenic agent in the cosmetic industry.

Evaluation of the Significance of Persistent Remnant Filling and Enlargement After Flow Diversion for Intracranial Aneurysms.

BACKGROUND: This study aimed to evaluate the clinical course after flow diversion (FD) treatment with a focus on aneurysms with remnant sac filling, by analyzing angiographic outcomes, aneurysm volume, and clinical events. METHODS: We retrospectively reviewed the medical records of 61 patients who underwent FD for intracranial aneurysms between July 2014 and June 2021. RESULTS: The majority of aneurysms (52.5%) were located in the internal carotid artery, with a median diameter of 16.6 mm and neck size of 9.3 mm. Remnant filling was observed in 17 aneurysms (27.9%) more than 18 months after FD, 10 (16.4%) of these aneurysms underwent enlargement, which occurred only in cases with subtotal filling or entry remnant states. Eleven patients experienced major adverse events, and three exhibited unfavorable functional outcomes. The incidence of major adverse events and unfavorable functional outcomes was significantly higher in the aneurysm enlargement group than that in the no-filling or stable remnant filling groups (P < 0.001). Aneurysmal diameter and the presence of incorporated branches were independent predictors of aneurysm enlargement, while the presence of incorporated branches was the only independent predictor of persistent remnant filling. CONCLUSIONS: Aneurysm enlargement after FD is not uncommon, particularly when the aneurysm is large, has incorporated vessels, or does not undergo occlusion within 12 months, often culminating in major adverse events and unfavorable functional outcomes. In addition to investigating angiographic results, it is necessary to evaluate the changes in aneurysm size and clinical events when assessing the efficacy of FD.

Low-Temperature, Universal Synthetic Route for Mesoporous Metal Oxides by Exploiting Synergistic Effect of Thermal Activation and Plasma.

Mesoporous metal oxides exhibit excellent physicochemical properties and are widely used in various fields, including energy storage/conversion, catalysis, and sensors. Although several soft-template approaches are reported, high-temperature calcination for both metal oxide formation and template removal is necessary, which limits direct synthesis on a plastic substrate for flexible devices. Here, a universal synthetic approach that combines thermal activation and oxygen plasma to synthesize diverse mesoporous metal oxides (V2O5, V6O13, TiO2, Nb2O5, WO3, and MoO3) at low temperatures (150-200 °C), which can be applicable to a flexible polymeric substrate is introduced. As a demonstration, a flexible micro-supercapacitor is fabricated by directly synthesizing mesoporous V2O5 on an indium-tin oxide-coated colorless polyimide film. The energy storage performance is well maintained under severe bending conditions.

NG ,NG -Dimethylarginine Dimethylaminohydrolase 1 Expression Is Dispensable for Cold- or Diet-Induced Thermogenesis.

The strategy to activate thermogenic adipocytes has therapeutic potential to overcome obesity as they dissipate surplus energy as heat through various mechanisms. NG,NG-dimethylarginine dimethylaminohydrolases (DDAHs) are enzymes involved in the nitric oxide-protein kinase G signaling axis which increases thermogenic gene expression. However, the role of DDAHs in thermogenic adipocytes has not been elucidated. The adipocyte-specific Ddah1 knockout mice are generated by crossing Ddah1fl/fl mice with adiponectin Cre recombinase mice. Adipocyte-specific DDAH1 overexpressing mice are generated using adeno-associated virus-double-floxed inverse open reading frame (AAV-DIO) system. These mice are analyzed under basal, cold exposure, or high-fat diet (HFD) conditions. Primary inguinal white adipose tissue cells from adipocyte-specific Ddah1 knockout mice expressed comparable amounts of Ucp1 mRNA. Adipocyte-specific DDAH1 overexpressing mice do not exhibit enhanced activation of thermogenic adipocytes. In addition, when these mice are exposed to cold environment or fed an HFD, their body temperature/weight and thermogenesis-related gene and protein expressions are unchanged. These findings indicate that DDAH1 does not play a role in either cold- or diet-induced thermogenesis. Therefore, adipocyte targeting DDAH1 gene therapy for the treatment of obesity is unlikely to be effective.

Clinical relevance of serum ionized magnesium concentration in dogs with myxomatous mitral valve disease.

BACKGROUND: Hypomagnesemia is associated with a poor prognosis in humans with congestive heart failure (CHF), but studies in veterinary medicine are limited. HYPOTHESIS: Serum ionized magnesium concentration [iMg2+ ] would decrease as CHF progresses compared with the initial diagnostic levels and that lower [iMg2+ ] would be negatively associated with prognosis in dogs with CHF. ANIMALS: A total of 181 client-owned dogs with myxomatous mitral valve disease (MMVD) were included. They were classified into the preclinical stage (NO-CHF, n = 108), stage C (n = 42), and stage D (n = 31) based on the American College of Veterinary Internal Medicine MMVD classification. METHODS: This is a retrospective study from 2 referral centers. The [iMg2+ ] was compared among the NO-CHF, stage C, and stage D groups. Kaplan-Meier curves and the log-rank test were used to compare the incidence of death between groups. Multivariable Cox regression analysis was used to estimate the association of hypomagnesemia with the death. RESULTS: In the stage D group, the [iMg2+ ] was lower than that in the NO-CHF (P < .0001) and stage C groups (P < .003). In the Kaplan-Meier survival analysis, the 1-year cumulative survival rate in hypomagnesemic dogs was 53% compared with 91.5% in normomagnesemic dogs (log-rank test, P < .0001). In the multivariable Cox analysis, lower concentration of [K+ ] and [iMg2+ ], along with higher Evel , were associated with negative prognoses. Specifically, hypomagnesemia was associated with an approximately 4-fold increased risk of death (hazard ratio = 4.015; 95% confidence interval, 1.537-10.488; P = .005). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessing the [iMg2+ ] might serve as a potential marker for estimating the severity and prognosis indirectly in dogs with MMVD. Combining [iMg2+ ] measurement with other diagnostic methods, such as echocardiography, could improve the prognostic evaluation of MMVD in dogs.

3D nitrogen-doped carbon frameworks with hierarchical pores and graphitic carbon channels for high-performance hybrid energy storages.

In principle, hybrid energy storages can utilize the advantages of capacitor-type cathodes and battery-type anodes, but their cathode and anode materials still cannot realize a high energy density, fast rechargeable capability, and long-cycle stability. Herein, we report a strategy to synthesize cathode and anode materials as a solution to overcome this challenge. Firstly, 3D nitrogen-doped hierarchical porous graphitic carbon (NHPGC) frameworks were synthesized as cathode materials using Co-Zn mixed metal-organic frameworks (MOFs). A high capacity is achieved due to the abundant nitrogen and micropores produced by the MOF nanocages and evaporation of Zn. Also, fast ion/electron transport channels were derived through the Co-catalyzed hierarchical porosity control and graphitization. Moreover, tin oxide precursors were introduced in NHPGC to form the SnO2@NHPGC anode. Operando X-ray diffraction revealed that the rescaled subnanoparticles as anodic units facilitated the high capacity during ion insertion-induced rescaling. Besides, the Sn-N bonds endowed the anode with a cycling stability. Furthermore, the NHPGC cathode and SnO2@NHPGC achieved an ultrahigh energy density (up to 244.5 W h kg-1 for Li and 146.1 W h kg-1 for Na), fast rechargeable capability (up to 93C-rate for Li and 147C-rate for Na) as exhibited by photovoltaic recharge within a minute and a long-cycle stability with ∼100% coulombic efficiency over 10 000 cycles.

Intrabasal Plane Defect Formation in NiFe Layered Double Hydroxides Enabling Efficient Electrochemical Water Oxidation.

Defect engineering has proven to be one of the most effective approaches for the design of high-performance electrocatalysts. Current methods to create defects typically follow a top-down strategy, cutting down the pristine materials into fragmented pieces with surface defects yet also heavily destroying the framework of materials that imposes restrictions on the further improvements in catalytic activity. Herein, we describe a bottom-up strategy to prepare free-standing NiFe layered double hydroxide (LDH) nanoplatelets with abundant internal defects by controlling their growth behavior in acidic conditions. Our best-performing nanoplatelets exhibited the lowest overpotential of 241 mV and the lowest Tafel slope of 43 mV/dec for the oxygen evolution reaction (OER) process, superior to the pristine LDHs and other reference cation-defective LDHs obtained by traditional etching methods. Using both material characterization and density functional theory (DFT) simulation has enabled us to develop relationships between the structure and electrochemical properties of these catalysts, suggesting that the enhanced electrocatalytic activity of nanoplatelets mainly results from their defect-abundant structure and stable layered framework with enhanced exposure of the (001) surface.

Norepinephrine prevents hypotension in older patients under spinal anesthesia with intravenous propofol sedation: a randomized controlled trial.

Reducing hypotension is crucial as hypotension is the most common side effect of spinal anesthesia, and in older patients with various comorbidities, it can lead to fatality. We hypothesized that continuous infusion of norepinephrine could effectively prevent hypotension in older patients undergoing hip surgery under spinal anesthesia with propofol sedation. The study randomly assigned patients aged ≥ 70 years to either a control (Group C, n = 35) or a norepinephrine group (Group N, n = 35). After spinal anesthesia, continuous infusion of propofol and normal saline or norepinephrine was initiated. The number of hypotensive episodes, the primary outcome, as well as other intraoperative hemodynamic events and postoperative complications were compared. In total, 67 patients were included in the final analysis. The number of hypotensive episodes was significantly higher in Group C than in Group N (p < 0.001). Furthermore, Group C required a greater amount of fluid to maintain normovolemia (p = 0.008) and showed less urine output (p = 0.019). However, there was no difference in postoperative complications between the two groups. Continuous intravenous infusion of prophylactic norepinephrine prevented hypotensive episodes, reduced the requirement of fluid, and increased the urine output in older patients undergoing unilateral hip surgery under spinal anesthesia with propofol sedation.Clinical trial registration number: KCT0005046 ( https://cris.nih.go.kr ). IRB number: 2020-0533 (Institutional Review Board of Asan Medical Center, approval date: 13/APR/2020).

AAV-mediated skeletal muscle specific irisin expression does not contribute to weight loss in mice.

Obesity, a chronic disease, significantly increases the risk of various diseases, including diabetes, cardiovascular diseases, and cancers. Exercise is crucial for weight management not only through energy expenditure by muscle activity but also through stimulating the secretion of myokines, which affect various tissues. Irisin, derived from the proteolytic processing of fibronectin type III domain-containing protein 5 (Fndc5), is a well-studied myokine with beneficial effects on metabolism. This study explored the feasibility of adeno-associated virus (AAV)-mediated Fndc5 gene therapy to treat obesity in a mouse model using the AAV-DIO system to express Fndc5 specifically in skeletal muscle, and investigated its anti-obesity effect. Although Fndc5 was specifically expressed in the muscle, no significant impact on body weight under normal chow or high-fat diets was observed, and no change in thermogenic gene expression in inguinal white adipose tissue was detected. Notably, Fndc5 transduction did affect bone metabolism, consistent with previous reports. These findings suggest that AAV-mediated Fndc5 gene therapy may not be an efficient strategy for obesity, contrary to our expectations. Further research is needed to elucidate the complex mechanisms involved in irisin's role in obesity and related disorders.

Genome-wide association study of mammary gland tumors in Maltese dogs.

Background: A genome-wide association study (GWAS) is a valuable tool for investigating genetic and phenotypic variation in many diseases. Objective: The objective of this study was to identify variations in the genomes of Maltese dogs that are associated with the mammary gland tumor (MGT) phenotype and to assess the association between each biological condition and MGT phenotype in Maltese dogs. Methods: DNA was extracted from 22 tumor samples and 11 whole blood samples from dogs with MGTs. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed, and the top 20 SNPs associated with various conditions and genetic variations were mapped to their corresponding gene locations. Results: The genotyping process successfully identified 173,662 loci, with an overall genotype completion rate of 99.92%. Through the quality control analysis, 46,912 of these SNPs were excluded. Allelic tests were conducted to generate Manhattan plots, which showed several significant SNPs associated with MGT phenotype in intergenic region. The most prominent SNP, located within a region associated with transcription and linked to the malignancy grade of MGT, was identified on chromosome 5 (p = 0.00001) though there may be lack of statistical significance. Other SNPs were also found in several genes associated with oncogenesis, including TNFSF18, WDR3, ASIC5, STAR, and IL1RAP. Conclusion: To our knowledge, this is the first GWAS to analyze the genetic predisposition to MGT in Maltese dogs. Despite the limited number of cases, these analyzed data could provide the basis for further research on the genetic predisposition to MGTs in Maltese dogs.

Appendicular Skeletal Muscle Mass Associated with Sarcopenia as a Predictor of Poor Functional Outcomes in Ischemic Stroke.

Purpose: Several studies have examined the clinical impact of poststroke and stroke-related sarcopenia on stroke recovery. However, few studies have investigated the effect of sarcopenia detected shortly after stroke on functional prognosis. We predicted functional outcomes using early screening for sarcopenia in patients with acute ischemic stroke. We also examined the effect of sarcopenia detected shortly after stroke on functional prognosis. Patients and Methods: Patients diagnosed with acute ischemic stroke within 2 days of symptom onset were consecutively enrolled at a tertiary university hospital. Appendicular skeletal muscle mass (ASM) was measured using dual-energy X-ray absorptiometry during early hospitalization. Sarcopenia was diagnosed based on low ASM and strength criteria of the Asian Working Group for Sarcopenia (AWGS) and European Working Group on Sarcopenia in Older People (EWGSOP2). The primary outcome was poor functional outcome, defined as a modified Rankin score of 4-6 and all-cause mortality at 3 months. Results: Of the 653 patients, 214 (32.8%) and 174 (26.6%) had sarcopenia according to the AWGS and EWGSOP2 criteria, respectively. Irrespective of the definition, the sarcopenia group had a significantly higher proportion of patients with poor functional outcomes and all-cause mortality. Multivariate logistic regression analysis revealed that height-adjusted ASM was independently associated with poor functional outcomes (odds ratio: 0.61; 95% confidence interval: 0.40-0.91; P <0.005), and they were negatively correlated. However, the association between 3-month mortality, skeletal muscle mass, and sarcopenia was not sustained in multivariate analyses. Conclusion: Height-adjusted ASM associated with sarcopenia is a potential predictor of poor functional outcomes at 3 months in patients with acute stroke. However, owing to the limitations of this study, further research is required to confirm these findings.

Case report: Successful medical management of adrenocortical carcinoma with metastasis in a Maltese dog.

Introduction: Adrenocortical carcinoma (ACC) with metastasis has a grave prognosis, and adrenalectomy is associated with a high perioperative mortality rate in dogs. A favorable outcome following trilostane treatment in patients with metastatic ACC confirmed by a decreased size of the adrenal tumor and metastatic lesions has not been reported in dogs. Case description: A 12-year-old neutered male Maltese dog was diagnosed with a right adrenal tumor and a hepatic mass. Adrenal-dependent hyperadrenocorticism (ADH) was diagnosed based on clinical signs and an adrenocorticotropic hormone stimulation test (ACTHST). In addition, tests for plasma metanephrine and normetanephrine ruled out a pheochromocytoma. Based on cytology and computed tomography, unresectable metastatic ACC was confirmed. The dog was managed with trilostane due to the presence of distant metastasis. Medical management improved the clinical signs and post-ACTHST cortisol concentrations. One year after the first presentation, the clinical signs and ACTHST test showed a favorable outcome. In addition, computed tomography revealed a decreased size of the right adrenal tumor and resolution of the hepatic mass. Conclusions: Trilostane could be considered as a treatment option for unresectable metastatic ACC. A decrease in tumor size following treatment with trilostane has not been reported in dogs. This case report is the first to demonstrate a favorable outcome of metastatic ACC following trilostane mono therapy for >1 year.

Cold-induced adaptive thermogenesis is impaired by exposure of Asian sand dust in mice.

Desertification and desert sandstorms caused by the worsening global warming pose increasing risks to human health. In particular, Asian sand dust (ASD) exposure has been related to an increase in mortality and hospital admissions for respiratory diseases. In this study, we investigated the effects of ASD on metabolic tissues in comparison to diesel particulate matter (DPM) that is known to cause adverse health effects. We found that larger lipid droplets were accumulated in the brown adipose tissues (BAT) of ASD-administered but not DPM-administered mice. Thermogenic gene expression was decreased in these mice as well. When ASD-administered mice were exposed to the cold, they failed to maintain their body temperature, suggesting that the ASD administration had led to impairments in cold-induced adaptive thermogenesis. However, impaired thermogenesis was not observed in DPM-administered mice. Furthermore, mice fed a high-fat diet that were chronically administered ASD demonstrated unexplained weight loss, indicating that chronic administration of ASD could be lethal in obese mice. We further identified that ASD-induced lung inflammation was not exacerbated in uncoupling protein 1 knockout mice, whose thermogenic capacity is impaired. Collectively, ASD exposure can impair cold-induced adaptive thermogenic responses in mice and increase the risk of mortality in obese mice.

Evaluation of plasma prealbumin as a novel inflammatory biomarker in dogs: a pilot study.

Introduction: Prealbumin (PAB) is a plasma protein synthesized in the hepatic parenchymal cells. PAB has a short half-life (~2 days), and its concentration is affected by changes in transcapillary escape. Measurement of PAB is widely used in hospitalized patients in human medicine due to its decreasing concentration in states of inflammation and malnutrition. However, only a few studies are available in dogs. The aim of this study is to determine whether the plasma PAB concentration decreases in dogs with inflammation and to evaluate the relationship between the plasma PAB concentration and inflammation-related parameters in dogs. Methods: A total of 94 dogs were divided into healthy (n = 33) and diseased (n = 61) groups. These were further divided into group A (n = 24) and group B (n = 37) according to plasma C-reactive protein (CRP) levels. Group A included dogs with a plasma CRP < 10 mg/L, and group B consisted of dogs with a plasma CRP ≥ 10 mg/L. Patient signalment, history, physical examination findings, hematologic and biochemical parameters, various inflammatory markers, and plasma PAB levels were investigated and compared between groups. Results: The plasma PAB concentration was found to be lower in group B than in the other groups (p < 0.001), but no statistical difference was found when comparing the control group and group A (p > 0.05). A plasma PAB < 6.3 mg/dL predicted an increased CRP level (10 mg/L or greater) with a sensitivity of 89.5% and a specificity of 86.5%. Receiver operating characteristic curve analysis revealed that the area under the curve for PAB was higher than that for the white blood cell count, neutrophil count, albumin level, lactate level, neutrophil-to-lymphocyte ratio, and neutrophil percentage-to-albumin ratio. In addition, the PAB concentration was significantly negatively correlated with the CRP concentration (r = -0.670, p < 0.001). Conclusion: In conclusion, this is the first study to demonstrate the clinical usefulness of the plasma PAB concentration as an inflammatory marker in dogs. These findings suggest that measuring the plasma PAB concentration along with the CRP concentration may be more useful for evaluating inflammation than measuring CRP alone in canine patients.

Fiber support prevents colloid-facilitated contamination induced by dissolution-precipitation of a calcium phosphate adsorbent.

During the adsorptive removal of hazardous metal contaminants, dissolution-precipitation of sparingly soluble adsorbents may result in the formation of toxic colloidal suspensions, triggering secondary pollution. Therefore, we studied the prevention of colloid-facilitated contamination in a model adsorption system of dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) and Cd2+ as an adsorbent and adsorbate. Upon adding pure DCPD powder into a 500 mg L-1 Cd2+ solution of pH â‰Œ 7.0, aggregates of spheroidal Cd-bearing primary particles, within 0.040-0.95 µm size range, were generated via dissolution-precipitation. The accumulated volume of these submicron particles (10.8%) was greater than that of the submicron particles from the exposure of DCPD to deionized water (4.48%). While the Cd-carrying submicron particles, which are responsible for colloidal recontamination, appeared to form via homogeneous nucleation, their formation was suppressed using polyacrylonitrile fibers (PANFs) as supporting substrates. Thus, heterogeneous nucleation on PANFs formed hexagonal columnar microparticles of a new phase, pentacadmium dihydrogen tetrakis (phosphate) tetrahydrate (Cd5H2(PO4)4·4H2O). Together with dissolution-precipitation on the native DCPD, nucleation and growth on the PANFs accelerated the depletion of the dissolved species, reducing the degree of supersaturation along the DCPD-water interface. Although the PANFs decreased the Cd adsorption capacity to 56.7% of that of DCPD, they prevented the formation of small aggregates of Cd-bearing particles. Other sparingly soluble adsorbents can be compounded with PANF to prevent the generation of toxic colloids.

Facile synthesis of porous transition metal hydroxides from a poly(4-vinyl pyridine) film by controlling pH.

Non-noble transition metal hydroxides have been widely used in electrochemical devices because of low cost and multiple redox states. In particular, self-supported porous transition metal hydroxides are used to improve the electrical conductivity, as well as achieving fast electron and mass transfer and a large effective surface area. Herein, we introduce facile synthesis of self-supported porous transition metal hydroxides using a poly(4-vinyl pyridine) (P4VP) film. We used metal cyanide as a transition metal precursor capable of forming metal hydroxide anions in aqueous solution, which is the seed for transition metal hydroxides. To increase the coordination between P4VP and the transition metal cyanide precursors, we dissolved the precursors in buffer solutions with various pH. When the P4VP film was immersed in the precursor solution with lower pH, the metal cyanide precursors were sufficiently coordinated with the protonated nitrogen in P4VP. When reactive ion etching was performed on the precursor-containing P4VP film, the P4VP region without coordination was etched out and became pores. Then, the coordinated precursors were aggregated as metal hydroxide seeds and became the metal hydroxide backbone, resulting in the formation of porous transition metal hydroxide structures. We successfully fabricated various self-supported porous transition metal hydroxides (Ni(OH)2, Co(OH)2, and FeOOH). Finally, we prepared a pseudo-capacitor based on self-supported porous Ni(OH)2, which showed a good specific capacitance (780 F g-1 at 5 A g-1).