The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

Background: Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized. Results: Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abol‑ ished hepatic colonization of FMC cells. Conclusions Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metas‑ tasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.

OBJECTIVE: The aim of this study was to determine changes in behaviour among patients with attention deficit/hyperactivity disorder (ADHD) by different informants during treatment in the clinical setting. METHODS: Seventy-nine patients with ADHD were recruited. They completed 12-months of treatment with oral short-acting methylphenidate, two-to-three times per day, at a dose of 0.3-1.0 mg/kg. Among the 79 patients (mean age, 9.1+/-1.9 years), 39 were classified as the ADHD-C/H type (hyperactive-impulsive type and combined type) and 40 as the ADHD-I type (inattentive type). At baseline, and after 12 months, their behaviour was assessed using the Child Behaviour Checklist (CBCL), Teacher's Report Form (TRF), ADHD Rating Scale (ADHD-RS), and Clinical Global Impression-Severity (CGI-S). RESULTS: Patients classified as the ADHD-C/H type had higher scores on three CBCL subscales, on the ADHD-RS and CGI-S compared to the ADHD-I type patients. After 12-months of treatment, for all patients, there were significant improvements in the four subscales of the TRF as well as the ADHD-RS and CGI-S scores, but not on the CBCL. In addition, the patients with the ADHD-C/H type had greater improvements on the four subscales of the TRF after treatment. However, there were no differences noted on the CBCL, ADHD-RS and CGI-S. CONCLUSION: The results of this study showed that during treatment, in the clinical setting, there are different assessments of behaviour symptoms, associated with ADHD, reported by different informants. Assessments of behaviour profiles from multiple informants are crucial for establishing a fuller picture of patients with ADHD.
Checklist ; Child ; Humans ; Methylphenidate ; Parents

Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene are associated with substantial clinical heterogeneity. Here, we report the first case of SYNE1 ataxia in Taiwan due to two novel truncating mutations. Our patient, a 53-year-old female, exhibited pure cerebellar ataxia with c.1922del in exon 18 and c. C3883T mutations in exon 31. Previous studies have indicated that the prevalence of SYNE1 ataxia among East Asian populations is low. In this study, we identified 27 cases of SYNE1 ataxia from 22 families in East Asia. Of the 28 patients recruited in this study (including our patient), 10 exhibited pure cerebellar ataxia, and 18 exhibited ataxia plus syndromes. We could not find an exact correlation between genotypes and phenotypes. Additionally, we established a precise molecular diagnosis in our patient’s family and extended the findings on the ethnic, phenotypic, and genotypic diversity of the SYNE1 mutational spectrum.

OBJECTIVE: We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings. METHODS: We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated. RESULTS: Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%–90% and 69%–75% for detection of EC, and 61% and 62%–69% for the detection of OC. CONCLUSION: The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.
Biomarkers ; DNA Methylation ; DNA ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Methylation ; Ovarian Neoplasms ; Ovary ; Polymerase Chain Reaction ; Sensitivity and Specificity

OBJECTIVE: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. METHODS: Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. RESULTS: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. CONCLUSION: Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.
Carcinoma, Squamous Cell* ; Cell Transformation, Neoplastic ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Epithelial Cells* ; Humans ; Incidence ; Ovarian Neoplasms ; Taiwan ; Teratoma*

Objective: The Schizophrenia Cognition Rating Scale (SCoRS) is an interview-based assessment tool for evaluating the cognitive deficit and daily functioning of patients with schizophrenia. Methods: Sixty-eight patients with schizophrenia and 68 age- and sex-matched healthy individuals were recruited to validate the Chinese version of SCoRS in this study. All participants underwent cognitive assessment using the SCoRS, which was verified by the Brief Assessment of Cognition in Schizophrenia (BACS), and the UCSD Performance-based Skills Assessment, Brief Version (UPSA-B). Patients with schizophrenia were additionally assessed using the Positive and Negative Syndrome Scale (PANSS). Results: SCoRS ratings reported by patients (SCoRS-S), those reported by the interviewer (SCoRS-I), and SCoRS global scores (SCoRS-G) showed significant correlation with all subscales of the BACS and the UPSA-B. On receiver operating characteristic curve analysis, SCoRS-S, SCoRS-I, and SCoRS-G significantly differentiated patients with schizophrenia from healthy controls. Moreover, SCoRS-S and SCoRS-I ratings showed positive correlation with the negative symptoms and general symptoms of PANSS. Conclusion The Chinese version of SCoRS showed good discriminant, concurrent, and external validity, suggesting that it is a useful and convenient tool for assessment of cognitive function among Mandarin-speaking patients with schizophrenia in clinical practice.

PURPOSE: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. MATERIALS AND METHODS: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and divided into two age groups: elderly (age > or =65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. RESULTS: Elderly patients with non-KPLA were associated with a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were related to the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. CONCLUSION: In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.
Adult ; Aged ; Aged, 80 and over ; Bacterial Infections/*complications/*radiography ; Female ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae ; Length of Stay ; Liver Abscess/complications/microbiology/*radiography ; Logistic Models ; Male ; Microscopy ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; Tomography, X-Ray Computed/*methods

PURPOSE: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. MATERIALS AND METHODS: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and divided into two age groups: elderly (age > or =65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. RESULTS: Elderly patients with non-KPLA were associated with a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were related to the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. CONCLUSION: In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.
Adult ; Aged ; Aged, 80 and over ; Bacterial Infections/*complications/*radiography ; Female ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae ; Length of Stay ; Liver Abscess/complications/microbiology/*radiography ; Logistic Models ; Male ; Microscopy ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; Tomography, X-Ray Computed/*methods