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Over the last decade, studies have shown an increased incidence of colorectal cancer (CRC), particularly early onset colorectal cancer (EOCRC). Researchers have demonstrated that dietary behavior, especially among young adults, influences alterations in the gut microbial community, leading to an increased accumulation of pathogenic gut microbiota and a decrease in beneficial ones. Unfortunately, CRC is likely to be diagnosed at a late stage, increasing CRC-related mortality. However, this alteration in the gut microbiota (gut dysbiosis) can be harnessed as a biomarker for non-invasive diagnosis, prognosis, prevention, and treatment of CRC in an effort to prevent late diagnosis and poor prognosis associated with CRC.This review discusses identification of potential biomarkers by targeting diet-mediated gut dysbiosis for the stage-specific diagnosis, prognosis, treatment, and prevention of CRC. Our findings provide a comprehensive insight into the potential of protumorigenic bacteria (e.g.pathogenic Escherichia coli,enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum) and their metabolites (e.g., colibactin and B. fragilis toxin) from gut dysbiosis as biomarkers for the diagnosis of CRC.Collectively, a detailed understanding of the available data from current studies suggests that, further research on quantification of metabolites and stage-specific pathogenic microbial abundance is required for the diagnosis and treatment of CRC based on microbial dysbiosis. Specifically, future studies on faecal samples, from patient with CRC, should be conducted for F. nucleatum among different opportunistic bacteria, given its repeated occurrence in faecal samples and CRC biopsies in numerous studies. Finally, we discuss the potential of faecal microbial transplantation (FMT) as an intervention to restore damaged gut microbiota during CRC treatment and management.

Heavy metal release from harsh ultramafic settings influences microbial diversity and function in soil ecology. This study aimed to determine how serpentine mineralosphere bacterial assemblies and their functions differed in two different plate-tectonic plains and mining exposure sites under heavy metal release conditions. The results showed that the Proteobacteria, Actinobacteria, Cyanobacteria, Planctomycetes, and Chloroflexi were the most abundant bacterial groups among all the sites. The log10-based LDA scores highlighted that some specific groups of bacterial assemblies were enriched in plate-tectonic plains and mining activity areas of the serpentine mineralosphere. Functional prediction revealed that the abundance of heavy metal (Cr and Ni) resistance and biogeochemical cycles involving functional KEGG orthology varied in samples from plate-tectonic plains and mining activity sites. The bipartite plot showed that the enrichment of the biogeochemical cycle and heavy metal resistance functional genes correlated with the abundance of serpentine mineralosphere bacterial groups at a 0.005% confidence level. The co-occurrence network plot revealed that the interconnection pattern of the indigenous bacterial assemblies changed in different plate-tectonic plains and mining exposure areas. Finally, this study concluded that due to heavy metal release, the variation in bacterial assemblies, their functioning, and intercommunity co-occurrence patterns were clarified the synergetic effect of mineral-microbial geochemical weathering process in serpentine mining areas.

Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer’s Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076–0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145–0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.

Acanthamoeba spp. are opportunistic human pathogens that cause granulomatous amoebic encephalitis and keratitis, and their accurate detection and enumeration in environmental samples is a challenge. In addition, information regarding the genotyping of Acanthamoeba spp. using various PCR methods is equally critical. Therefore, considering the diverse niches of habitats, it is necessary to develop an even more efficient genotyping method for Acanthamoeba spp. detection. This study improved the sensitivity of detection to avoid underestimation of Acanthamoeba spp. occurrence in aquatic environmental samples, and to accurately define the pathogenic risk by developing an efficient PCR method. In this study, a new nested genotyping method was established and compared with various PCR-based methods using in silico, lab, and empirical tests. The in silico test showed that many PCR-based methods could not successfully align specific genotypes of Acanthamoeba, except for the newly designed nested PCR and real-time PCR method. Furthermore, 52 water samples from rivers, reservoirs, and a river basin in Taiwan were analysed by six different PCR methods and compared for genotyping and detection efficiency of Acanthamoeba. The newly developed nested-PCR-based method of genotyping was found to be significantly sensitive as it could effectively detect the occurrence of Acanthamoeba spp., which was underestimated by the JDP-PCR method. Additionally, the present results are consistent with previous studies indicating that the high prevalence of Acanthamoeba in the aquatic environment of Taiwan is attributed to the commonly found T4 genotype. Ultimately, we report the development of a small volume procedure, which is a combination of recent genotyping PCR and conventional real-time PCR for enumeration of aquatic Acanthamoeba and acquirement of biologically meaningful genotyping information. We anticipate that the newly developed detection method will contribute to the precise estimation, evaluation, and reduction of the contamination risk of pathogenic Acanthamoeba spp., which is regularly found in the water resources utilised for domestic purposes.

Microorganisms developed a mechanism that copes with heat, acidity, and high dissolved metal concentrations that likely first evolved. The geothermal fluids emerging in the geothermal springs of Taiwan, located at a subduction zone, are still under signs of progress in the characterization of the various microbial taxonomic changes over time. However, no systematic studies have been performed to compare water, biofilms, and sediment bacterial communities and the primary driving force of dissolved and mineral substrates capable of supporting microbial metabolism. In this study, 16S rRNA gene sequencing was employed for bacterial community exploration, and their potential metabolic pathways involved from water, biofilms, and sediment samples, collected from the geothermal valley (Ti-re-ku). Metagenomic data revealed that the water samples had higher bacterial diversity and richness than biofilms and sediment samples. At the genus level, Alicyclobacillus, Thiomonas, Acidocella, Metallibacterium, Picrophilus, and Legionella were significantly abundant in the water samples. The biofilms were rich in Aciditerrimonas, Bacillus, Acidithiobacillus, and Lysinibacillus, whereas the sediment samples were abundant in Sulfobacillus. The PICRUSt2-predicted functional results revealed that heavy metal-related functions such as heavy-metal exporter system, cobalt‑zinc‑cadmium resistance, arsenical pump, high-affinity nickel-transport, and copper resistance metabolisms were significant in the water samples. Moreover, sulfur-related pathways such as thiosulfate oxidation, dissimilatory sulfate reduction, and assimilatory sulfate reduction were important in water samples, followed by biofilms and sediment. Therefore, our findings highlighted the comparative taxonomic diversity and functional composition contributions to geothermal fluid, with implications for understanding the evolution and ecological niche dimension of microbes which are the key to geothermal ecosystem function.

Mud volcanoes are the most dynamic and unstable sedimentary structures in the areas of tectonic compression like the subduction zones. In this study, we comprehensively analyzed the distribution of minerals as well as diversity, abundance and metabolic potential of the microbial communities of major mud volcanic groups across Taiwan namely Chu-kou Fault (CKF), Gu-ting-keng Anticline (GTKA), Chi-shan Fault (CSF), and Longitudinal Valley Fault (LVF). The mud volcano fluids recorded relatively higher Na and Cl contents than the other elements, particularly in the CKF and GTKA groups. The highest microbial diversity and richness were observed in the CSF group, followed by the GTKA group, whereas the lowest microbial diversity was observed in the CKF and LVF groups. Proteobacteria were common in all the sampling sites, except WST-7 and WST-H (Wu-Shan-Ting) of the CSF group, which were abundant in Chloroflexi. The halophilic genus Alterococcus was abundant in the Na-and Cl-rich CL-A sites of the CKF group. Sulfurovum was dominant in the CLHS (Chung-Lun hot spring) site of the CKF group and was positively correlated with sulfur/thiosulfate respiration, which might have resulted in a higher expression of these pathways in the respective group. Aerobic methane-oxidizing microbial communities, such as Methylobacter, Methylomicrobium, Methylomonas, and Methylosoma, constituted a dominant part of the LVF and CSF groups, except for the YNH-A and YNH-B (Yang-Nyu-Hu) sites. The WST-7 and JS sites were abundant in both methane-producing and methane-oxidizing microbial communities. The LGH-F1 (Lei-Gong-Huo) site was dominated by both methanotrophic and methylotrophic genera, such as Methylomicrobium and Methylophaga, respectively. Methylotrophy, methanotrophs, and hydrocarbon-degrading pathways were more abundant in the LVF and CSF groups but not in the remaining groups. The results of this study extend our knowledge of the diversity, abundance, and metabolic functions of prokaryotes in major terrestrial mud volcanoes in Taiwan.

The microbial characteristics of water bodies located in the outflow of hot springs may affect the water quality parameters of the associated river ecosystem. Using 16S rRNA amplicon sequencing, we investigated the bacterial diversity and functional profiles of the Huang Gang (HG) Creek, located in the trace metal-rich, acid-sulfate thermal springs zone of the Tatun Volcano Group (TVG). Biofilms and water samples were collected from the upstream, midstream, and geothermal valleys and downstream of the creek. The results showed that the biofilm and water samples had distinct bacterial diversity and abundance profiles. Acidophilic sulfur-oxidizing bacteria were found to be more abundant in water samples, whereas aquatic photosynthetic bacterial communities were dominant in biofilms. The water samples were contaminated with Legionella and Chlamydiae, which could contaminate the nearby river and cause clinical infections in humans. The upstream samples were highly unique and displayed higher diversity than the other sites. Moderate thermo-acidophiles were dominant in the upstream and midstream regions, whereas the geothermal valley and downstream samples were abundant in thermo-acidophiles. In addition, functional profiling revealed higher expression of sulfur, arsenic, and iron-related functions in water and lead-related functions in the biofilms of the creek. As described in previous studies, the hydrochemical properties of the HG Creek were influenced by the TVG hot springs. Our findings indicated that the hydrochemical properties of the HG Creek were highly correlated with the bacterial diversity and functional potential of running water as compared to biofilms.

This study investigated the effect of environmental physical factors on the relative abundance of bacteria and the consequential landscape evolution in karst topography, focusing mainly on the effects of ureolytic microbial CaCO3 precipitation. The narrow-sky located in the upper part of Tangshan is a small gulch of Pleistocene coralline limestone formation in southern Taiwan. A 16S-metagenomic approach was used to determine the relationship of microbial community structures on the landscapes in various habitats. Our results showed that the biomass of habitats in the opening of the gulch was two times higher than the inside where light penetration was lower. We also found that speleothems only occurred at the inner wall inside the gulch, where the environment exhibited water drips running through the surface of speleothems and less light penetration. The sequence reads of operational taxonomic units relative to urease-producing bacteria and weathering-associated bacteria from each habitat were determined by NCBI database. Our data revealed that the 16S-metagenomics of the inner wall and water samples exhibited more sequences that were similar to those of urease-producing bacteria, whereas the outer wall showed more sequences that were similar to those of weathering-associated bacteria, suggesting that bacteria facilitated the formation of limestone weathering and calcite precipitation for various habitats. The semi-quantitative PCR for determining bacterial urease gene (ureC) levels confirmed that the inner limestone habitat had higher ureC gene levels than the outer limestone habitat. This study revealed the pivotal role of microorganisms in governing the geological evolution in the lightless limestone landscape.

Adenoviruses (AdVs) are a major cause of clinical infections and have been proposed as indicators of water quality. However, quantitative data on the environmental prevalence of AdVs is lacking. We investigated the prevalence, distribution, seasonal occurrence, quantity, and genotype of AdVs in 13 fishing harbours in Taiwan. AdVs in the water samples were isolated by membrane filtration and the AdV DNA was extracted. Next, AdVs were detected using nested polymerase chain reaction. Genotyping and phylogenetic analysis were performed to identify various AdV genotypes present in the water samples. The F species human AdV (HAdV) serotype 41 (63.6%) and C species porcine AdV (PAdV) serotype 5 (33.3%) were more prevalent than the other serotypes. The prevalence of AdVs was highest in the fall, followed by in the spring and summer. Among the fishing harbours, the highest detection rate of AdVs was observed in Yenpudongang in all seasons. However, Puoziliao was the only site at which AdVs were not detected during the study period. AdV detection at sampling sites may be correlated with sewage and livestock wastewater discharge via outflow of nearby rivers to fishing ports. Statistical analysis (Mann-Whitney U test) based on data from water quality indicators revealed that the presence of AdVs was significantly associated with the heterotrophic plate count, pH, and salinity. Human and swine population data from nearby local townships and river/drainage basins were collected from the Taiwan Central Government's website. The data were analyzed using Spearman's rank correlation coefficient to determine the relationship between the prevalence of AdVs, HAdVs, and PAdVs in fishing harbours, and microbial water quality indicators. Statistical evidence indicated that the detection levels of HAdVs and PAdVs in fishing harbours were mainly associated with human and swine populations in the corresponding river/drainage basin, respectively. Additionally, the swine population in the river/drainage basin was positively correlated with microbial water quality indicators.

To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA isolates were characterized from 246 samples collected from LTCFs, medical tubes of LTCF residents, and hospital environments of two cities, Chiayi and Changhua. Species identification, molecular characterization, and drug resistance analysis were performed. Hospital environments had a higher MRSA detection rate than that of LTCF environments, where moist samples are a hotspot of MRSA habitats, including tube samples from LTCF residents. All MRSA isolates in this study carried the exfoliative toxin eta gene (100%). The majority of MRSA isolates were resistant to erythromycin (76.7%), gentamicin (60%), and ciprofloxacin (55%). The percentage of multidrug-resistant MRSA isolates was approximately 50%. The enterobacterial repetitive intergenic consensus polymerase chain reaction results showed that 18 MRSA isolates belonged to a specific cluster. This implied that genetically similar isolates were spread between hospitals and LTCFs in Changhua city. This study highlights the threat to the health of LTCFs’ residents posed by hospital contact with MRSA.

This study aims to determine and compare the bacterial community and functional profiles associated with serpentine sites, innate hyper-accumulating weed, downgradient agricultural farmlands and non-serpentine sites using 16S rRNA gene sequencing. Elemental analysis revealed that the serpentine rock and weathered soil have higher magnesium, nickel, chromium, magnesium/calcium and lower calcium/magnesium ratios and agricultural farmlands have recorded elevated chromium. Proteobacteria were found predominant, except the non-serpentine site which was rich in Cyanobacteria. PCA analysis at the genus level indicates the uniqueness of different experimental groups, except the hyperaccumulators which exhibited relatively less dissimilarity. The shift analysis showed the serpentine sites were characterized by the abundance of bacteria having heavy metal effluxion. The hyper-accumulating weeds were higher in plant growth-promoting bacteria expressing tolerance against heavy metals toxicity such as nickel, chromium, cobalt and arsenic. Besides, the agricultural lands were abundant in wetland-associated methanogens and metal (manganese, iron and zinc) transporting function related bacteria. The results suggest that the inherent edaphic factors including heavy metal content, the interacting behavior of hyperaccumulator's rhizosphere microbiota with soil and anthropogenic activities such as agricultural practices could be a major determinant of the variation in the bacterial community selection and abundance in the respective study sites.

Objective: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD. Methods: We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I2 statistic. Moderators of effects were explored using metaregression. Results: Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, p < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = −0.1203, p = 0.0004). Conclusions: Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association.

Bacterial strains of the Bacillus cereus group produce various toxins that cause diarrheal and emetic food poisoning. In this study, five main oyster farming areas and 15 fishing ports in Taiwan were examined for the status of B. cereus group bacteria inhabiting seawater and shellfish. On average, bacteria of the B. cereus group were detected in 32.6% of the seawater samples (n = 89) and 2.5% of the oysters (n = 81) in the oyster farming areas and in 7.9% of the seawater samples (n = 202) and 0.68% of the shellfish products (n = 292) in fishing ports. To trace the potential source of B. cereus group bacteria in intertidal oyster farming areas, we simultaneously explored their terrestrial river basins. In total, 44 B. cereus group strains were purified and cultured from water and shellfish for the analysis of virulence genes, panC gene typing, antibiotic susceptibility testing, and enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) fingerprinting. The enterotoxin-coding genes nheABC, hblCDA, entFM, cytK-1, and cytK-2 were detected in 70.4%, 84.1%, 97.7%, 72.7%, and 75% of the total isolates, among which 40.9% carried all these genes. According to panC gene analysis, the dominant isolates belonged to the panC group IV. In antibiotic susceptibility tests, most B. cereus group isolates were resistant to ampicillin (97.7%) and sulfamethoxazole/trimethoprim (100%). The percentage of multidrug resistant B. cereus group isolates was 34.6%. Finally, the 44 B. cereus group isolates were classified into 43 types and categorized into five clusters using ERIC-PCR fingerprinting. The B. cereus group isolates from different oyster farming areas were concentrated within the two main clusters; however, those from river basins displayed a wide genetic diversity, indicating the presence of multiple sources of B. cereus group bacteria in river basins.

Chun-Hung Chang,1,2 Chieh-Yu Liu,3 Shaw-Ji Chen,4,5 Hsin-Chi Tsai6,7 1Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 2Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 3Biostatistical Consulting Laboratory, Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 4Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung, Taiwan; 5Department of Medicine, Mackay Medical College, New Taipei, Taiwan; 6Department of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan; 7Department of Psychiatry, School of Medicine, Tzu-Chi University, Hualien City, Taiwan Objective: The aim of this study was to examine the effectiveness of light therapy in the treatment of geriatric depression. Methods: A systematic review and meta-analysis were carried out. Data sources for the literature search were PubMed, Cochrane Collaboration’s Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov. Controlled trials of light therapy on older patients with nonseasonal depression and depression rating scales were eligible. Studies were pooled using a random-effect model for comparisons with light therapy. We used effect size (ES), which expresses changes in depression severity, in each selected meta-analysis to calculate the standardized mean difference on the basis of Hedges’ adjusted g; positive values indicated that the depression severity improved after light therapy. All results were presented with 95% CIs. Statistical heterogeneity was explored through visual inspection of funnel plots and the I2 statistic. Moderators of effects were explored using meta-regression. Results: We identified eight trials involving 395 participants that met the inclusion criteria. Light therapy was significantly more effective than comparative treatments, including placebo or dim light, with an ES of 0.422 (95% CI: 0.174–0.709, P=0.001). In addition, six of the eight trials used bright (white) light, resulting in significantly reduced severity of geriatric depression (N=273, ES: 0.460, 95% CI: 0.085–0.836, P=0.016). Furthermore, pale blue light therapy reduced the severity of geriatric depression (N=89, ES: 0.464, 95% CI: 0.046–0.882, P=0.030). Conclusion: Our results highlighted the significant efficacy of light therapy in the treatment of geriatric depression. Additional well-designed, controlled studies are necessary to adopt standard parameters, adequate group sizes, and randomized assignment to evaluate more thoroughly the efficacy of light therapy for treating geriatric depression. Keywords: depression, elderly adults, light therapy

Salmonella is one of the most common pathogens of waterborne and foodborne disease-causing pathogens. In this study, we collected 172 surface water samples from Puzih River and Kaoping River between the years 2010 and 2011. Salmonella was detected in 31.7% (32/101) and 42.2% (30/71) of the samples from the two rivers, respectively. From these positive samples, 44 Salmonella isolates were obtained from these positive samples and were characterized using serotyping and pulsed-field gel electrophoresis (PFGE) genotyping. The isolates were found with 17 serovars and 32 PFGE patterns. Salmonella enterica Newport, Bareilly, Kedougou, Albany and subspecies IIIb 50:k:z were the five most common serovars in aquatic environmental Salmonella isolates. In addition, of the total clinical samples from Chiayi and Kaohsiung, 33.7% (60/178) Newport serovars were isolated. After conducting categorical analysis, we found that the serovar Newport was not uniformly distributed cross the cities. The serovar Newport was over-represented (p

Chun-Hung Chang,1,2 Shaw-Ji Chen,3,4 Chieh-Yu Liu,5 Hsin-Chi Tsai6,7 1Brain Disease Research Center, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan; 2Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 3Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung, Taiwan; 4Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; 5Biostatistical Consulting Lab, Institute of Nursing-Midwifery, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 6Department of Psychiatry, Tzu-Chi General Hospital, Hualien, Taiwan; 7Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan Purpose: The purpose of this study was to investigate the incidence and risk of suicidal drug overdose (SDO) after stroke in older patients. Methods: We enrolled patients aged 60–99years who were diagnosed with new-onset stroke between 2002 and 2013 and age-, sex-, and index-year-matched controls who did not have stroke. Patients with a history of SDO before enrollment were excluded. Both groups were observed until December 31, 2013. The primary end point was the occurrence of newly diagnosed SDO. The cumulative incidence rates of the study and control groups were estimated using the Kaplan–Meier method. Furthermore, we used the Cox proportional hazards model to identify risk factors for SDO. Results: We selected 22,770 individuals. Among them, 11,385 were older patients (aged 60–99years) who had newly diagnosed stroke and 11,385 were controls. Of the 22,770 individuals, 275 (1.21%) had SDO during a mean follow-up period of 5.33±3.30years, comprising 191 (1.68%) from the stroke group and 84 (0.74%) from the control group. Older patients with stroke had a significantly higher risk of SDO than the controls (adjusted hazard ratio: 2.288, 95% confidence interval [CI]: 1.746–2.999, p

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to public health that causes infections in hospitals, communities, and animal husbandry. Livestock-associated MRSA (LA-MRSA) is defined as MRSA possessing staphylococcal cassette chromosome mec (SCCmec) IV or V, both of which lacks the Panton–Valentine leukocidin (PVL) gene but has variable combinations of antimicrobial susceptibility. This study focused on Taiwan's subtropical river basin and the Puzih River, which converges from tributaries flowing through downtown and animal husbandry areas. MRSA was detected at a rate of 7.8% in the tributaries, which was higher than downstream (2.1%). The ratio of multidrug-resistant (MDR) MRSA (n = 30) to total MRSA isolates (n = 39) was 0.769, and most of the MDR MRSA isolates (66.7%, 20/30) exhibited resistance to chloramphenicol, ciprofloxacin, clindamycin, erythromycin, sulfamethoxazole-trimethoprim, and tetracycline. The number of MDR MRSA isolates in the tributaries was also higher than the downstream regions of the Puzih River. The majority of MRSA isolates (64.1%) observed in this study possessed SCCmec type IV without PVL, which is typical for LA-MRSA. Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) typing aided the discrimination of resistance patterns among SCCmec types. This study highlights the threat to human health posed by the waterborne transmission of MDR LA-MRSA.

This study investigated the long-term effect of environmental physical factors on the relative abundance of bacteria and the consequential landscape evolution in karst topography, focusing mainly on the effects of limestone weathering and calcite precipitation. The Narrow-Sky located in the upper part of Takangshan is a small gulch of Pleistocene coralline limestone formation in southern Taiwan. The landscapes were different in the karst walls between the opening and the inner of gulch due to the variation of physical parameters such as sunlight penetration, humidity, and temperature. A metagenomic approach was used out to determine the relationship of microbial community structures on the landscapes in various habitats around the gulch, namely on the inner and outer limestone wall, the water collected from speleothems surface, and the ground soil at the outer wall. The total organic carbon content was measured in solid samples to evaluate the biomass of the habitats. Our results showed that the biomass of habitats in the opening of the gulch was two times higher than the that inside where light penetration was lower. We also found that speleothems only occurred at the inner wall inside the gulch, where the environment exhibited water drips running through the surface of speleothems and less light penetration. The metagenomics in each habitat was surveyed to measure the sequence similarity of operational taxonomic units relative to urease-producing bacteria and weathering-associated bacteria available in the National Center for Biotechnology Information database. Our data revealed that the metagenomics of the inner wall and water samples exhibited more sequences that were similar to those of urease-producing bacteria, whereas the outer wall showed more sequences that were similar to those of weathering-associated bacteria, suggesting that bacteria facilitated the formation of limestone weathering and calcite precipitation for various habitats. This study revealed the pivotal roles of microorganisms in governing the geological evolution of the limestone landscape.

This study evaluated the severe hepatic outcome (SHO) in patients with schizophrenia and viral hepatitis who received antipsychotics. Using the nationwide Taiwan National Health Insurance Research Database, patients first diagnosed with schizophrenia between 2002 and 2013 were identified. Patients diagnosed with schizophrenia who had viral hepatitis, including hepatitis B virus (HBV) or hepatitis C virus (HCV), were designated as the viral hepatitis group. A control group without viral hepatitis was matched for age, sex, and index year in a 2:1 ratio. Patients with severe hepatic outcomes before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of a SHO, including liver cancer, liver failure, liver decompensation, or transplantation. Among the 16,365 patients newly diagnosed with schizophrenia between January 2002 and December 2013, we identified 614 patients with viral hepatitis and 1228 matched patients without viral hepatitis. Of these 1842 patients, 41 (2.22%) developed SHOs, including 26 (4.23%) in the viral hepatitis group and 15 (1.22%) in the control group, during the mean follow-up period of 3.71 ± 2.49 years. Cox proportional hazard analysis indicated that the SHO risk increased by 3.58 (95% confidence interval [CI]: 1.859–6.754; P

Acinetobacter baumannii is an important health care-associated bacterium and a common multidrug-resistant pathogen. The use of antibiotics in the husbandry industry has raised concerns about drug-resistant A. baumannii strains, which may affect humans. This study aimed to investigate the seasonal distribution of A. baumannii in aquatic environments near areas of livestock farming. The geographic distribution, antibiotic resistance characteristic, and DNA fingerprinting genotype of A. baumannii were also studied. The results showed that environmental A. baumannii was prevalent during the summer and autumn. The hotspots for A. baumannii were found at the sampling sites of livestock wastewater channels (21.4%, 3/14) and the tributaries adjacent to livestock farms (15.4%, 2/13). The prevalence of A. baumannii at these locations was significantly higher than those adjacent to the Puzi River. Multidrug-resistant strain of A. baumannii was not found in this study, with only one strain (5%, 1/20) being resistant to tetracycline. Of the isolates that were obtained, 10% (2/20) and 20% (4/20) were found to be intermediately resistant to tetracycline and sulphamethoxazole/trimethoprim, respectively. The genotyping patterns and clustering analysis indicated that enterobacterial repetitive intergenic consensus sequence polymerase chain reaction (ERIC-PCR) differentiated A. baumannii strains effectively. There were two major clusters that could then be subtyped into 20 A. baumannii strains with 15 profiles. The A. baumannii strains that were isolated from upstream of the Puzi River and livestock wastewater channels were composed of Cluster I. Cluster II only contained isolates from downstream of the Puzi River area. Furthermore, isolates from adjacent sites were shown to have identical profiles (100%). These results suggest that A. baumannii may have spread through free-flowing water in this study. Therefore, we propose that livestock wastewater is one of the sources that contribute to A. baumannii pollution in water bodies. In summary, continuous monitoring of antibiotic pollution in livestock wastewater is required.

Vittaforma corneae belongs to microsporidia, which include over 1500 species of opportunistic obligate intracellular fungi infecting almost all known animal taxa. Although outbreaks of ocular infections caused by waterborne V. corneae have been reported in recent years, little is known about the occurrence of this pathogen in aquatic environments. In this study, 50 water samples from rivers and reservoirs around Taiwan in two seasons were analyzed to explore the presence of this pathogen in natural aquatic environments. A high detection rate of Vittaforma-like amplicons (94%; 47/50) was observed in the water samples when examined by nested PCR with primer pairs specific to the small ribosomal subunit (SSU) rRNA gene. After electrophoresis, many lanes showed multiband patterns with expected molecular weights. After confirmation by DNA sequencing and by sequence alignment in the NCBI database, we identified a variety of Vittaforma-like microsporidia with weak sequence similarity, with approximately 85% identity to V. corneae, thus indicating high diversity of microsporidia in aquatic environments. Phylogenetic analysis showed clear-cut microsporidian clade classification and indicated that the most Vittaforma-like microsporidia in this study belong to clade IV and cluster into four major groups. The first group is similar to the microsporidia associated with ocular microsporidiosis. The second group is associated with the diarrheal pathogens, whereas the third and fourth groups are a novel group and a zoonotic group, respectively. This study provides abundant sequencing information, which will be useful for future molecular biological studies on microsporidia. Because microsporidia are important pathogens of animals and humans, it is urgently necessary to determine via a survey whether there are species with potential threats that have not yet been revealed.

Aim Obsessive–compulsive disorder (OCD) is a chronic disabling neuropsychiatric disorder. Current treatment modalities, such as pharmacological and behavioral methods, are sometimes unsatisfactory. The mesolimbic dopaminergic pathway is supposed to have a role in the pathogenesis of OCD. In this study, L-3,4-Dihydroxy-6-[F-18]fluorophenylalanine (F-18 FDOPA) positron emission tomography (PET) is exploited to investigate the possible abnormality of dopaminergic neuronal circuits in the brains of OCD patients in vivo. Methods The study subjects were recruited after psychological assessment and gave written informed consent to participate. The F-18 FDOPA PET scans were performed on five OCD patients and six healthy volunteers at 120 min after 185 MBq of F-18 FDOPA intravenous injection. The PET results were analyzed with the Statistical Parametric Mapping tool. Results Compared to the healthy subjects, the OCD brains showed increased dopaminergic metabolism in the left frontal premotor cortex (P

Hsin-Chi Tsai,1,2 Chun-Hung Chang,3,4 Jiann-I Pan,5 Hung-Jen Hsieh,6 Sheng-Tzung Tsai,7 Hsiang-Yi Hung,7 Shin-Yuan Chen1,71Institute of Medical Science, Tzu-Chi University, Hualien City, Taiwan; 2Department of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan; 3Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan; 4China Medical University, Taichung, Taiwan; 5Department of Medical Informatics, Tzu-Chi University, Hualien, Taiwan; 6Nuclear Medicine, Tzu Chi General Hospital, Hualien City, Taiwan; 7Department of Neurosurgery, Tzu-Chi General Hospital, Hualien City, TaiwanObjective: Deep-brain stimulation (DBS) for treating refractory obsessive–compulsive disorder (OCD) has shown positive results in small clinical trials. Ventral capsule/ventral striatum (VC/VS) is one of the promising targets; however, whether or not acute stimulation test can provide substantial information for chronic stimulation is not yet known. We evaluated postoperative test stimulation and examined the relationship of acute simulation-induced smile/laughter and 15-month clinical outcome.Methods: Four adult patients with refractory OCD were implanted with Model 3387 leads bilaterally in an area of VC/VS. Postoperative test stimulation was performed at least 2 weeks after surgery. We performed double-blinded postoperative test stimulation with different contact and voltage. The relationship of stimulation-induced smile/laughter and chronic response was examined.Results: Patients presented smile, laughter, euphoria, increased heart rate, increased blood pressure, smell, chest vibration, dizziness, nausea, heat, or increased sexual drive during acute stimulation. We found that the higher the percentage of smile/laughter (34.3%, 31.3%, 56.3%, and 12.5% for four cases), the greater the reduction in the Yale-Brown Obsessive Compulsive Scale (30.6%, 38.9%, 58.8%, and 7.7% respectively at 15-month DBS).Conclusion: This study showed that acute DBS of the VC/VS might cause mood change, cardiovascular, sensory, or motor effects. These effects were transient or habituated over six months. We suggest stimulation-induced smile/laughter may be a possible predictor for long-term DBS outcome. Larger studies, genetic studies, and imaging studies are needed to evaluate the effects of different parameters and possible predictors in the treatment of OCD.Keywords: deep-brain stimulation, DBS, OCD, VC/VS, nucleus accumbens, NAcc

Human adenoviruses (HAdVs) are DNA viruses found in recreational water, such as water parks and swimming pools. Human adenovirus 41 (HAdV-41) is the most common serotype detected and is a leading cause of acute diarrheal disease. The focus of this study is to determine the prevalence of HAdVs in hot springs. Of 57 samples collected from four different geological sites, 16 samples have shown evidence of HAdVs (28.1%). HAdV-41 and porcine adenovirus 5 (PAdV-5) were the two types isolated, with a greater frequency of HAdV-41, which in other settings has been associated with acute diarrhea. The highest occurrence was found in private hot tubs/Yuya (37.5%), followed by an outlet of hot springs (30.8%); public pools and foot pools shared the same detection rate of 21.4% (3/14). However, there was no evidence supporting a link between water quality indicators and HAdV detection rate. From a phylogenic analysis and BLAST against the NCBI database, it was concluded that HAdV-41 obtained from hot spring areas are closely related to global environmental genotypes.

Multilocus sequence typing (MLST) is an approach for prediction of Salmonella servoar and eBRUST groups (eBGs) based on seven typing scheme of housekeeping genes. Up to date, >220.000 allelic profiles and 65,973 Salmonella strains have been established in the MLST database. Several studies have modified MLST method with fewer targeted housekeeping genes for the purpose of economy and efficiency. Nevertheless, no study has conducted systematically to evaluate the correlation between the numbers of housekeeping genes targeted and the accuracy of prediction rate. In this study, we aimed to tackle this problem by extracting data from the MLST database as a whole using the software RStudio. Our results indicated that as the numbers of genes in MLST scheme increased, the accuracy of the eBGs prediction rate increased and reached 100% when the gene numbers are greater than or equal to 5. To examine the applicability of the approach, 395 environmental water samples were subjected to this study. A set of 52 Salmonella enterica isolates was initially used to develop MLST targeting seven housekeeping genes. A total of 29 sequence types, including 11 new sequence types were found among the 52 sequenced isolates that differentiated into 19 serotypes. Moreover, two novel sequence types did not belong to current classification. Our results show that the outcome in the three-gene sequence typing (aroC, hisD, and purE) was as accurate as in the seven-gene sequence typing for prediction of environmental Salmonella isolates. Our data suggested that this five-gene and reduced gene-number sequence-typing scheme can serve as an alternative modified MLST when effectiveness and financial management were the concerns.

N -of-1 trials are an effective evidence-based approach in individual patient management. It has been suggested that deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective in the treatment of refractory obsessive–compulsive disorder (OCD). However, it has not been documented in the literature whether a perioperative acute stimulation test can provide substantial information for chronic stimulation. A 21-year-old man with a 6-year history of medication-refractory OCD underwent bilateral DBS on the VC/VS. Two weeks after surgery, an acute stimulation test was performed in an N -of-1 trial. Olfactory hallucinations, laughter, and euphoria were observed during the acute stimulation test. At follow-up after 17 months, the patient's scores improved from 34 at baseline to 14 on the Yale–Brown Obsessive Compulsive Scale, from 34 to 20 (41.2% improvement) on the Hamilton Anxiety Rating scale, and from 41 to 71 (75% improvement) on the Global Assessment of Functioning scale. According to our N -of-1 trial, olfactory hallucinations, in addition to laughter, induced by a perioperative acute stimulation test may be an indicator of good outcome in OCDDBS during chronic stimulation.

Aims: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a promising alternative to ablative surgery in treatment of refractory obsessive–compulsive disorder (OCD). A pilot study was conducted to assess 15-month outcomes of DBS in patients with refractory OCD in Taiwan. Methods: Four adult patients with a 3-year or more history of refractory OCD (Yale–Brown Obsessive– Compulsive Scale [Y-BOCS] score of at least 28) met the criteria for DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric evaluation was conducted preoperatively, postoperatively, and at follow up at every 3 months for 15 months. Primary outcome measure was Y-BOCS. Secondary outcomes included the Hamilton Depression Rating Scale (HAM-D), and the Global Assessment of Function Scale. Results: Mean severity of OCD was a Y-BOCS score of 36.3 2.1. At the end of 15 months’ follow up, there was a 33.06% decrease in OCD severity (P = 0.001). Similar findings were seen for HAM-D (32.51% reduction, P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026). In terms of adverse effects, two patients suffered from hypomania episodes after several weeks of DBS stimulation, and one had transient hypomania-like syndrome during DBS initial programming. One patient (Case 1) had an allergic reaction to implantation of the pulse generator in the chest, and another patient (Case 3) exhibited vertigo. Conclusions: We confirm that DBS of the VC/VS appears to be beneficial for improvements in function and mood among patients with treatmentresistant OCD. Compared to previous studies examining the therapeutic effects of DBS, no serious adverse effects were observed.

Objective: The prevention of infections is crucial in long-term care programs. Investigations of the occurrence and sources of pathogens in long-term care facilities (LTCFs) are still lacking, especially in eastern Taiwan. In this study, we conducted a surveillance of two common pathogens, Acinetobacter baumannii (AB) and methicillin-resistant Staphylococcus aureus (MRSA), in LTCFs in Hualien. Materials and Methods: Pathogenic assays including isolation, identification, and antimicrobial susceptibility tests were conducted for AB and MRSA at LTCFs in Eastern Taiwan. Staphylococcal cassette chromosome mec typing assays were done to understand the relatedness of clonal strains of MRSA. Results: All AB-positive samples in the LTCFs were mainly from water-rich samples and were drug susceptible. Our data indicated that the AB strains from LTCFs were similar to those from Puzi River watersheds in Taiwan, which were not drug resistant to commonly used antibiotics. On the other hand, the drug resistance analysis of MRSA indicated that the genotypes from the LTCFs were similar to those from nearby hospitals. Eight strains of MRSA were isolated from four LTCFs, of which five were identified as hospital-acquired strains according to SSCmed typing assays. Conclusion: These findings suggest that MRSA in LTCFs might propagate from hospitals and could be transmitted between hospitals and LTCFs. Health authorities should be aware of this risk. The long-term follow-up of MRSA is recommended in local medical institutions as well as in LTCFs for correlative analysis.

Listeria innocua retains many conserved homologous domains with Listeria monocytogenes, which is a food-borne and water-borne diarrhea-causing bacterium. Studies of antimicrobial resistance in L. innocua showed that this microbe is more prone to acquire resistance than other bacteria in the genus Listeria. However, little is known about the seasonal population distribution and antimicrobial resistance patterns of L. innocua in natural water environments. The aims of the study were: (1) to investigate the occurrence of L. innocua isolates in a subtropical watershed and reconstruct the population structure and (2) to analyze the antibacterial resistance patterns of the identified L. innocua isolates according to ERIC type. A total of 288 water samples was collected from the Puzi River basin (23&deg, 28&rsquo, N, 120&deg, 13&rsquo, E) between March 2014 and March 2015, and 36 L. innocua isolates were recovered from 15 positive water samples. With regard to seasonal variation, L. innocua was only detected in the spring and summer. Eighteen enterobacterial repetitive intergenic consensus (ERIC)-PCR types were identified, and two genogroups with four subgroups were reconstructed in a minimum spanning tree. Isolates from different sampling areas that were located near each other were genetically different. All L. innocua isolates (including 41.7% of the multidrug-resistant (MDR) isolates) were resistant to oxacillin and showed high minimum inhibitory concentrations of tetracycline. These findings demonstrate the seasonal variations and differing geographical distributions of L. innocua in this subtropical water environment, as well as the existence of strong population structures and MDR and antimicrobial resistance patterns. Phylogenetic analysis based on ERIC-type showed that the Cluster A isolates were resistant to more antibiotics, and two types, ERIC8 and ERIC15 were multidrug resistant. The more commonly detected types, such as ERIC1 and ERIC12, were also more likely to be resistant to two or more antibiotics. Close monitoring of drug resistance in environmental L. innocua is warranted due to its potential for transferring antimicrobial resistance determinants to pathogenic Listeria.

Three types of supported cobalt catalysts (CoO x /SiO2, CoO x /TiO2 and CoO x /Al2O3) were prepared by incipient wetness impregnation with aqueous Co(NO3)2·6H2O solution. The phase composition and the interactions of cobalt with supports under different calcined temperatures were investigated using thermogravimetry (TG), N2-adsorption at −196 °C, X-ray diffraction (XRD), temperature-programmed reduction (TPR) and diffuse reflectance spectroscopy (DRS). Their catalytic activities towards the CO oxidation were further studied in a continuous flow micro-reactor. The results showed that the interaction of cobalt oxide with supports was much stronger in the kinds of Al2O3 and TiO2, while no conclusive evidence of any interaction was found for SiO2. Besides the crystalline Co3O4 which was formed in three supported catalysts, both high-temperature phases CoAl2O4 and CoTiO3 spinel were also detected under XRD, DRS and TPR analysis. The degree of interaction between cobalt oxide and the support not only affected the surface area and reduction behavior of the catalysts, the catalytic activity toward the CO oxidation also affected simultaneously. As the CoAl2O4 and CoTiO3 spinel formed, both the surface area and catalytic activity decreased significantly.

Three types of supported cobalt catalysts (5% as metal Co loading on SiO2, Al2O3 and TiO2) were prepared by incipient wetness impregnation with aqueous Co(NO3)2·6H2O solution. Then, all catalysts were calcined in air at 400 °C (assigned as 5Co/Si C400, 5Co/Al C400 and 5Co/Ti C400). Their catalytic activities towards the CO oxidation were studied in a continuous flow micro-reactor. Adsorption of carbon monoxide (CO) and the co-adsorption of CO/O2 over cobalt oxide were further tested under in situ FT-IR. The results showed that both 5Co/Si C400 and 5Co/Al C400 had higher activity than 5Co/Ti C400. The T50 (50% conversion) for both 5Co/Si C400 and 5Co/Al C400 was reached at temperatures as low as ambient temperature. According to the in situ FT-IR analysis, the variation in oxidation of CO was interpreted with different mechanisms, i.e., the reaction between adsorbed CO and lattice oxygen of cobalt oxide, and part of CO2 formation via carbonates on 5Co/Si C400; both types of carbonates are formed on 5Co/Al C400 to promote the CO oxidation; while both strong adsorption of CO on TiO2 and CO2 on cobalt oxide for 5Co/Ti C400 leads to affect the activity.