Background:Reports on the aquaporin-4 immunoglobulin G (AQP4-IgG) status for cognitive performance and neuroimaging correlations are limited in neuromyelitis optica (NMO) and multiple sclerosis (MS) literature. Methods: Cognitive results of 19 MS and 15 NMO patients were compared with 47 agematched controls. Apparent diffusion coeffi cient (ADC) values were used to delineate gray matter and white matter damages and correlate with neuropsychological results. Results: Verbal memory test showed signifi cant differences between MS and NMO in the late registration, early and delay recall (p<0.05), while their retention rates were even. In MS, ADC values were signifi cantly elevated in the dorsolateral prefrontal and occipital gray matter which was in contrast with NMO group that showed elevation in the dorsolateral prefrontal gray matter and parieto-occcipital white matter. AQP4-IgG status exerted a limited effect on ADC values and neuropsychological results. Conclusions: Verbal memory test might be helpful in differentiating NMO and MS. ADC values can be used as a surrogate marker for tissue injury in NMO and MS since they were in line with the cognition scores. Anatomical regions with elevated ADC values were different in NMO and MS.

Background: Compared with the Western population, central demyelinating disorders are relatively rare while the data on the prognostic value of autoantibodies together with clinical characteristics and cognitive dysfunction has rarely been explored in neuromyelitis optica (NMO) and multiple sclerosis (MS). Methods: Nineteen patients with MS and 14 with NMO underwent clinical profiling and cognitive assessment. According to serology tests, they are divided into four subgroups for further analysis. Results: There was higher frequency of aquaporin-4 immunoglobulin G. sero-positivity (64.3% vs. 10.5%; p=0.003) and antinuclear antibodies (ANA) and/or antibodies to extractable nuclear antigens (anti-ENA) in NMO compared to MS (42.9% vs. 5.2%; p=0.026). The presence of anti-ENA represented a unique clinical phenotype, with longer segment of myelitis (p=0.049), female preponderance, and an inverse correlation between age-of-onset and annual relapse rate (ρ= -0.88, p=0.021). Among patients with anti-ENA positivity, comprehensive serology panels revealed Sjögren’s syndrome A antibodies as the most common (83%), in contrast to limited clinical documentation of Sjögren’s syndrome (16%). There was no significant difference in cognitive assessment by anti-ENA status. MS and NMO represent two different serologic entities. Conclusions: Anti-ENA may have prognostic value for its linkage to a unique clinical phenotype, which has longer initial segment of myelitis, female preponderance, and higher annual relapse rate on earlier age-of-onset, but has limited clinical impact on cognition. Further studies are warranted to investigate whether anti-ENA represents an epiphenomenon of myelitis or simply a systemic inflammatory state.

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.
Blotting, Western ; Breast Neoplasms ; Breast ; Cell Movement ; Doxorubicin ; Myosin Light Chains ; Paclitaxel ; Phenotype ; Phosphorylation ; Up-Regulation

The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS.
Anemia, Aplastic/*complications/microbiology ; Humans ; Male ; Middle Aged ; Psoas Abscess/*etiology/*microbiology ; Salmonella Infections/*complications

This study evaluated the value of procalcitonin (PCT) levels in pleural effusion to differentiate the etiology of parapneumonic effusion (PPE). Forty-one consecutive PPE patients were enrolled and were divided into bacterial and non-bacterial PPE. Blood and pleural effusion samples were collected for PCT measurement on admission and analyzed for diagnostic evaluation. PCT of pleural fluid was significantly increased in the bacterial PPE group (0.24 ng/mL) compared to the non-bacterial PPE group (0.09 ng/mL), but there was no significant difference for serum PCT. A PCT concentration of pleural fluid >0.174 ng/mL (best cut-off value) was considered positive for a diagnosis of bacterial PPE (sensitivity, 80%; specificity, 76%; AUC, 0.84). Pleural effusion PCT in the bacterial PPE is significantly different from those of the non-bacterial PPE and control groups, so the diagnostic use of PCT still warrants further investigation.
Aged ; Bacterial Infections/*diagnosis ; Calcitonin/*analysis/blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pleural Effusion/*diagnosis ; Pneumonia/*diagnosis ; Predictive Value of Tests ; Protein Precursors/*analysis/blood ; ROC Curve

AIMTo complete comprehensive haplotype analysis of USP26 for both fertile and infertile men.

METHODSTwo hundred infertile men with severe oligospermia or non-obstructive azoospermia were subjected to sequence analysis for the entire coding sequences of the USP26 gene. Two hundred men with proven fertility were genotyped by primer extension methods. Allele/genotype frequencies, linkage disequilibrium (LD) characteristics and haplotypes of fertile men were compared with infertile men.

RESULTSThe allele frequencies of five single nucleotide polymorphisms (370-371insACA, 494T>C, 576G>A, ss6202791C>T, 1737G>A) were significantly higher in infertile patients than control subjects. The major haplotypes in infertile men were TACCGA (28% of the population), TGCCGA (15%), TACCAA (8%), TGCCAA (6%), TATCAA (5%) and CATCAA (5%). The major haplotypes for the control subjects were TACCGA (58% of the population), CACCGA (7%), CATCGA (6%) and TGCCGA (5%). Haplotypes TGCCGA, TATCAA, CATCAA, CATCGC, TACCAA and TGCCAA were over-transmitted in patients with spermatogenic defect, whereas haplotypes TACCGA, CACCGA, and CATCGA were under-transmitted in these patients.

CONCLUSIONSome USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan, China.

Adult ; Alleles ; Azoospermia ; epidemiology ; genetics ; Cysteine Endopeptidases ; genetics ; DNA Primers ; Gene Frequency ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Infertility, Male ; epidemiology ; genetics ; Linkage Disequilibrium ; Male ; Multigene Family ; Oligospermia ; epidemiology ; genetics ; Polymorphism, Genetic ; Spermatogenesis ; genetics ; physiology ; Taiwan ; epidemiology

Objective: To assess whether carbon monoxide (CO) poisoning increases the incidence of dementia. Methods: We searched the Cochrane Library, PubMed, and EMBASE from inception to 14 August 2022. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included for systematic reviews and meta-analysis. Results: Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence (adjusted hazard ratio 2.61, 95% confidence interval 1.56 to 4.36, p=0.0003). Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one. Conclusion Overall the evidence from prospective cohort studies supported a link between CO exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.