Publications by authors named "Hsiu-Ling Chen"

121 Publications

The effects of phthalate ester exposure on human health: A review.

Sci Total Environ 2021 Sep 28;786:147371. Epub 2021 Apr 28.

Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Research Center of Environmental Trace Toxic Substances, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Electronic address:

Phthalate esters (PAEs) are one of the most widely used plasticizers in polymer products and humans are increasingly exposed to them. The constant exposure to PAEs-contained products has raised some concerns against human health. Thus, the impacts of PAEs and their metabolites on human health require a comprehensive study for a better understanding of the associated risks. Here, we attempt to review eight main health effects of PAE exposure according to the most up-to-date studies. We found that epidemiological studies demonstrated a consistent association between PAE exposure (especially DEHP and its metabolites) and a decrease in sperm quality in males and symptom development of ADHD in children. Overall, we found insufficient evidence and lack of consistency of the association between PAE exposure and cardiovascular diseases (hypertension, atherosclerosis, and CHD), thyroid diseases, respiratory diseases, diabetes, obesity, kidney diseases, intelligence performance in children, and other reproductive system-related diseases (anogenital distance, girl precocious puberty, and endometriosis). Future studies (longitudinal and follow-up investigations) need to thoroughly perform in large-scale populations to yield more consistent and powerful results and increase the precision of the association as well as enhance the overall understanding of potential human health risks of PAEs in long-term exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147371DOI Listing
September 2021

Associations among Cognitive Functions, Plasma DNA, and Diffusion Tensor Image along the Perivascular Space (DTI-ALPS) in Patients with Parkinson's Disease.

Oxid Med Cell Longev 2021 16;2021:4034509. Epub 2021 Feb 16.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Parkinson's disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation, which may further impair the glymphatic system. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship with systemic oxidative stress status in PD patients.

Methods: Magnetic resonance imaging and neuropsychological tests were conducted on 25 PD patients with normal cognition (PDN), 25 PD patients with mild cognitive impairment (PD-MCI), 38 PD patients with dementia (PDD), and 47 normal controls (NC). Oxidative stress status was assessed by plasma DNA level. Differences in ALPS-index among the subgroups were assessed and further correlated with cognitive functions and plasma DNA levels.

Results: The PD-MCI and PDD groups showed significantly lower ALPS-index compared to normal controls. The ALPS-index was inversely correlated with plasma nuclear DNA, mitochondrial DNA levels, and cognitive scores.

Conclusions: Lower diffusivity along the perivascular space, represented by lower ALPS-index, indicates impairment of the glymphatic system in PD patients. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations.
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http://dx.doi.org/10.1155/2021/4034509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904342PMC
May 2021

Vertically integrated diffractive gratings on photonic crystal surface emitting lasers.

Sci Rep 2021 Jan 28;11(1):2427. Epub 2021 Jan 28.

Department of Photonics, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu City, 30010, Taiwan.

We designed and fabricated a photonic crystal surface emitting laser (PCSEL) with vertically integrated diffractive optical elements on their top to study the mechanism of static beam steering on a single chip. The deflected output beam by the self-formed periodic ITO cladding layer of the PCSEL can be further steered by changing the grating period and azimuthal angle of the diffractive gratings relative to the photonic crystal. Through the analysis of photonic band structure and lasing characteristics, the periodic ITO structure is coupled to the photonic crystal band, whereas the integrated grating serves the diffractive function only. The findings pave the way for the design of PCSELs enabling single or multiple output beam with varying direction capability. This type of laser is regarded as an ideal light source for various applications, such as light detection and ranging and three-dimensional sensing systems.
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http://dx.doi.org/10.1038/s41598-021-82194-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844237PMC
January 2021

Nonthermal plasma-activated water: A comprehensive review of this new tool for enhanced food safety and quality.

Compr Rev Food Sci Food Saf 2021 Jan 23;20(1):583-626. Epub 2020 Nov 23.

Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.

Nonthermal plasma (NTP) is an advanced technology that has gained extensive attention because of its capacity for decontaminating food from both biological and chemical sources. Plasma-activated water (PAW), a product of NTP's reaction with water containing a rich diversity of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS), is now being considered as the primary reactive chemical component in food decontamination. Despite exciting developments in this field recently, at present there is no comprehensive review specifically focusing on the comprehensive effects of PAW on food safety and quality. Although PAW applications in biological decontamination have been extensively evaluated, a complete analysis of the most recent developments in PAW technology (e.g., PAW combined with other treatments, and PAW applications in chemical degradation and as curing agents) is nevertheless lacking. Therefore, this review focuses on PAW applications for enhanced food safety (both biological and chemical safeties) according to the latest studies. Further, the subsequent effects on food quality (chemical, physical, and sensory properties) are discussed in detail. In addition, several recent trends of PAW developments, such as curing agents, thawing media, preservation of aquatic products, and the synergistic effects of PAW in combination with other traditional treatments, are also presented. Finally, this review outlines several limitations presented by PAW treatment, suggesting several future research directions and challenges that may hinder the translation of these technologies into real-life applications.
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http://dx.doi.org/10.1111/1541-4337.12667DOI Listing
January 2021

The corticolimbic structural covariance network as an early predictive biosignature for cognitive impairment in Parkinson's disease.

Sci Rep 2021 Jan 13;11(1):862. Epub 2021 Jan 13.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.

Structural covariance assesses similarities in gray matter between brain regions and can be applied to study networks of the brain. In this study, we explored correlations between structural covariance networks (SCNs) and cognitive impairment in Parkinson's disease patients. 101 PD patients and 58 age- and sex-matched healthy controls were enrolled in the study. For each participant, comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted. Structural brain MR images were acquired using a 3.0T whole body GE Signa MRI system. T1 structural images were preprocessed and analyzed using Statistical Parametric Mapping software (SPM12) running on Matlab R2016a for voxel-based morphometric analysis and SCN analysis. PD patients with normal cognition received follow-up neuropsychological testing at 1-year interval. Cognitive impairment in PD is associated with degeneration of the amygdala/hippocampus SCN. PD patients with dementia exhibited increased covariance over the prefrontal cortex compared to PD patients with normal cognition (PDN). PDN patients who had developed cognitive impairment at follow-up exhibited decreased gray matter volume of the amygdala/hippocampus SCN in the initial MRI. Our results support a neural network-based mechanism for cognitive impairment in PD patients. SCN analysis may reveal vulnerable networks that can be used to early predict cognitive decline in PD patients.
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http://dx.doi.org/10.1038/s41598-020-79403-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806769PMC
January 2021

Fish consumption is an indicator of exposure to non-dioxin like polychlorinated biphenyls in cumulative risk assessments based on a probabilistic and sensitive approach.

Environ Pollut 2021 Jan 5;268(Pt B):115732. Epub 2020 Oct 5.

Department of Food Safety/Hygiene and Risk Management, National Cheng Kung University, Taiwan; Department of Environmental Trace Toxic Substances Research Center, Medical College, National Cheng Kung University, Tainan, Taiwan. Electronic address:

The health effects of non-dioxin like polychlorinated biphenyls (NDL-PCBs) include liver, immune, neurodevelopmental, and neurobehavioral effects in addition to hormone alteration. Among 209 PCB congeners, six indicator PCBs (ICES-6) account for about half of NDL-PCBs present in feed and food. The objectives of the current study were first to examine the levels of total PCBs, NDL-PCBs, and ICES-6 PCBs in 200 foods commonly consumed in Taiwan and, second, to estimate the cumulative health risks of NDL-PCB consumption. We suggest a risk management strategy that identifies foodstuffs with particularly high NDL-PCB content. In 200 food samples, which were grouped into 12 categories and 64 food types, 51 PCB congeners were detected. The concentrations of ICES-6 PCBs in all samples were lower than the maximum levels for NDL-PCBs in foodstuffs set by the European Union. PCB-153, PCB-138, and PCB-180 were the major congeners in all food, indicating that the food was contaminated in the past. ICES-6 PCBs contributed 42.2%-52.9% of total NDL-PCBs in all tested foodstuffs. The average estimated daily intake (EDI) of PCBs ranged from 1.22 ng/kg bw/day to 2.89 ng/kg bw/day in different age groups (95th quantile [P95]: 4.12-10.28 ng/kg bw/day). The P95 EDI in 3-6-year-olds was higher than 10 ng/kg/day. A qualitative sensitivity analysis in ICES-6 PCBs exposure showed that for the 3- to 6-year-old group, the highest sensitivity was how much fish they ate (37.6%) and its concentration (32.5%). The consumption of pork, eggs, fish, and other seafood accounts for over 90% of ICES-6 PCBs intake, and these foods should be highlighted in guidelines regarding NDL-PCB intake.
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http://dx.doi.org/10.1016/j.envpol.2020.115732DOI Listing
January 2021

Efficacy and safety of single-session radiofrequency ablation for benign thyroid nodules of different sizes: a retrospective study.

Int J Hyperthermia 2020 ;37(1):1082-1089

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Purpose: To compare the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules (BTNs) among groups presenting with different nodule volumes.

Materials And Methods: This retrospective study evaluated 186 patients with BTNs who underwent ultrasound guided RFA treatment. The BTNs were categorized into small (≤10 ml); medium (10-30 ml); and large (>30 ml) according to the initial volume of BTNs before ablation. The RFA procedures were performed using the moving shot technique. The volume reduction ratio (VRR) of each nodule, cosmetic score, symptomatic score, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared.

Results: At 1-month follow-up, the large nodules group showed significantly greater VRR compared to the other two groups (small, 31.88% ± 37.91; medium, 38.9% ± 19.18; large, 48.7% ± 20.43,  = .03). At 6-month follow-up, there was no significant difference of VRR among the three groups (small, 74.6% ± 20.92; medium, 68.1% ± 17.07; large, 75.0% ± 11.88). The most common presented complication was temporary vocal palsy (6 patients; small,  = 1; medium,  = 1; large,  = 3). Additionally, one skin burn, one hematoma, and one nodular rupture of BTNs occurred after the procedures. The complication rate of the large nodules group was highest among the three groups and showed a considerable difference (8 patients; small,  = 1, 2.1%; medium,  = 2, 4.5%; large,  = 5, 11.4%,  = .061).

Conclusions: RFA was confirmed as effective in patients with large thyroid nodule (>30ml), with therapeutic efficacy similar to patients with smaller thyroid nodules.
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http://dx.doi.org/10.1080/02656736.2020.1782485DOI Listing
January 2020

Dietary exposure assessment to perchlorate in the Taiwanese population: A risk assessment based on the probabilistic approach.

Environ Pollut 2020 Dec 23;267:115486. Epub 2020 Aug 23.

Research Center of Environmental Trace Toxic Substances, National Cheng Kung University, Tainan, 701, Taiwan; Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, 704, Taiwan. Electronic address:

Perchlorate is an endocrine-disrupting chemical (EDC) that contaminate various foodstuffs. Exposure to perchlorate may cause severe health problems, mainly thyroid dysfunction. However, information on perchlorate contamination of consumer foods in Taiwan is limited. This study investigated perchlorate levels in 310 food samples belonging to 12 food groups collected from Taiwanese markets. A probabilistic risk assessment was conducted to assess the related exposure to Taiwanese people. Perchlorate was detected in 65% of the samples and high levels were identified in certain plant-origin, fruit, and processed food samples. A probabilistic approach was used to estimate daily dietary dose (Monte Carlo-estimated 95th percentile dietary exposure [MCS 95]) by using the Taiwan National Food Consumption database for 14 sex/age groups. The highest and lowest average daily doses (ADDs) were in the age groups of >65 years (MCS 95 = 3.60/3.90 [male/female] μg/kg bw/day) and 16-18 years (MCS 95 = 1.70/1.47 [M/F] μg/kg bw/day), respectively. The 95th percentile of the hazard index of exposure to perchlorate of all sex/age groups far exceeded the tolerable daily intake (0.3 μg/kg bw/day) and reference dose (0.7 μg/kg bw/day) set by the European Food Safety Authority and US EPA, respectively, but it was lower than the provisional maximum tolerable daily intake (10 μg/kg bw/day) suggested by the Joint FAO/WHO Expert Committee on Food Additives. The intake quantity and concentrations of perchlorate from vegetables, fruits, and whole grains are the critical contributors for the ADDs and integrated risk of dietary exposure to perchlorate. Long-term exposure through diets should be considered, instead of focusing on individual EDC during dietary risk assessment in specific populations. Furthermore, cumulative risks for exposure to multiple contaminants, particularly those causing thyroid adverse effects, may be higher than that from perchlorate exposure alone.
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http://dx.doi.org/10.1016/j.envpol.2020.115486DOI Listing
December 2020

Alterations in sympathetic and parasympathetic brain networks in obstructive sleep apnea.

Sleep Med 2020 09 4;73:135-142. Epub 2020 Jun 4.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

Objective/background: Obstructive sleep apnea (OSA) patients experience hypoxia and, potentially, autonomic impairments stemming from neural damage. In this study, the executive control networks (ECNs), salience networks (SNs), and default mode networks (DMNs) of adult OSA patients, as well as their relationships with autonomic impairment, were investigated through independent component analysis (ICA).

Patients/methods: A total of 41 OSA patients and 19 healthy controls volunteers were recruited and subjected to polysomnography to ascertain their degree, if any, of sleep apnea. Each participant also underwent a cardiovascular autonomic survey, with the participant's baroreflex sensitivity (BRS) being determined based on heart rate and blood pressure alterations. The resting fMRI data of the participants was separated using probabilistic ICA, and six autonomic resting-state networks were established for group comparisons. The differences in autonomic parameters, autonomic functional connectivity (FC), and clinical severity were then correlated.

Results: The OSA group had significantly worse BRS values than the controls, as well as lower FC in the posterior and anterior SNs, bilateral ECNs, and the ventral DMN, and higher FC in the left ECN. These intrinsic connectivity networks showed dissociable correlations with greater baroreflex impairment and clinical disease severity. The higher FC in the left ECN was associated with the lower FC in the ventral DMN.

Conclusions: Our findings suggest that autonomic dysfunction in OSA might be accompanied by central autonomic network alterations. The stronger sympathetic-associated regions in ECNs and the weaker parasympathetic-associated regions in DMNs may represent intrinsic neural architecture fluctuations underlining their consequent processes in OSA.
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http://dx.doi.org/10.1016/j.sleep.2020.05.038DOI Listing
September 2020

Vascular Inflammation Is a Risk Factor Associated with Brain Atrophy and Disease Severity in Parkinson's Disease: A Case-Control Study.

Oxid Med Cell Longev 2020 14;2020:2591248. Epub 2020 Jul 14.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Introduction: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson's disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD.

Objective: Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis.

Methods: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis.

Results: The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation.

Conclusion: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.
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http://dx.doi.org/10.1155/2020/2591248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376437PMC
May 2021

Reduced Gray Matter Volume and Risk of Falls in Parkinson's Disease with Dementia Patients: A Voxel-Based Morphometry Study.

Int J Environ Res Public Health 2020 07 26;17(15). Epub 2020 Jul 26.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.

: Risk of falls is a common sequela affecting patients with Parkinson's disease (PD). Although motor impairment and dementia are correlated with falls, associations of brain structure and cognition deficits with falls remain unclear. : Thirty-five PD patients with dementia (PDD), and 37 age- and sex-matched healthy subjects were recruited for this study. All participants received structural magnetic resonance imaging (MRI) scans, and disease severity and cognitive evaluations. Additionally, patient fall history was recorded. Regional structural differences between PDD with and without fall groups were performed using voxel-based morphometry processing. Stepwise logistic regression analysis was used to predict the fall risk in PDD patients. The results revealed that 48% of PDD patients experienced falls. Significantly lower gray matter volume (GMV) in the left calcarine and right inferior frontal gyrus in PDD patients with fall compared to PDD patients without fall were noted. The PDD patients with fall exhibited worse UPDRS-II scores compared to PDD patients without fall and were negatively correlated with lower GMV in the left calcarine (/ = 0.004/-0.492). Furthermore, lower GMV in the left calcarine and right inferior frontal gyrus correlated with poor attention and executive functional test scores. Multiple logistic regression analysis showed that the left calcarine was the only variable ( = 0.004, 95% CI = 0.00-0.00) negatively associated with the fall event. PDD patients exhibiting impaired motor function, lower GMV in the left calcarine and right inferior frontal gyrus, and notable cognitive deficits may have increased risk of falls.
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http://dx.doi.org/10.3390/ijerph17155374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432132PMC
July 2020

Plasma Levels of α-Synuclein, Aβ-40 and T-tau as Biomarkers to Predict Cognitive Impairment in Parkinson's Disease.

Front Aging Neurosci 2020 28;12:112. Epub 2020 Apr 28.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Objective: In this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson's disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR).

Methods: The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of ≦26 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aβ-40, Aβ-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed.

Results: Compared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aβ-40 ( < 0.05). Plasma levels of α-synuclein ( = -0.323, = 0.002), Aβ-40 ( = 0.276, = 0.01), and T-tau ( = -0.322, = 0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aβ-40 and PD. Multiple regression analysis showed that the plasma levels of Aβ-40 (OR = 0.921, 95% CI = 0.879-0.962), α-synuclein (OR = 3.016, 95% CI = 1.703-5.339), and T-tau (OR = 1.069, 95% CI = 1.026-1.115) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aβ-40, (Area under curve (AUC) = 0.791), 0.389 pg/ml of α-synuclein, (AUC = 0.790), and 30.555 pg/ml of T-tau (AUC = 0.726).

Conclusion: Plasma levels of α-synuclein, Aβ-40, and T-tau are potential biomarkers to detect cognitive impairment in PD patients.
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http://dx.doi.org/10.3389/fnagi.2020.00112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198695PMC
April 2020

Hyperexpression of type III secretion system of Salmonella Typhi linked to a higher cytotoxic effect to monocyte-derived macrophages by activating inflammasome.

Microb Pathog 2020 Sep 6;146:104222. Epub 2020 May 6.

Graduate Institute of Biomedical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address:

Inflammasome activation is an important host response to infectious diseases, but the difference in inflammasome activation between typhoid fever and non-typhoidal Salmonella infection has been rarely studied. To determine whether inflammasome activation in macrophages after S. Typhi and S. Typhimurium infection is different, we measured pyroptosis, caspase-1 activation, and IL-1β secretion in monocyte-derived macrophages infected with S. Typhi or S. Typhimurium both in vitro and ex vivo. The role of Vi capsule and virulence genes in Salmonella pathogenicity island-1 (SPI-1), belonging to type III secretion system, was also examined. S. Typhi caused more pyroptosis, caspase-1 activation, and IL-1β production than S. Typhimurium did, predominantly within 2 h of infection, in the context of high number of infecting bacteria. Mutagenesis and complementation experiments confirmed that SPI-1 effectors but not Vi were associated with greater inflammasome activation. The expression levels of invA and hilA were significantly higher in S. Typhi than in S. Typhimurium at early log phase in SPI-1 environment. Thus, S. Typhi, relative to its non-typhoidal counterpart, S. Typhimurium, induces greater SPI-1-dependent inflammasome activation in monocyte-derived macrophages. This finding may explain why S. Typhi causes a hyperinflammatory state at bacteremic stage in typhoid fever.
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http://dx.doi.org/10.1016/j.micpath.2020.104222DOI Listing
September 2020

Activation of apoptosis by Salmonella pathogenicity island-1 effectors through both intrinsic and extrinsic pathways in Salmonella-infected macrophages.

J Microbiol Immunol Infect 2020 Feb 26. Epub 2020 Feb 26.

Graduate Institute of Biomedical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background: Salmonella enterica serovar Typhimurium, a non-typhoidal food-borne pathogen, causes acute enterocolitis, bacteremia, extraintestinal focal infections in humans. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) contribute to invading into host cellular cytosol, residing in Salmonella-containing vacuoles for intracellular survival, and inducing cellular apoptosis. This study aimed to better understand the mechanism underlying apoptosis in Salmonella-infected macrophages.

Methods: S. Typhimurium SL1344 was used to evaluate extrinsic and intrinsic apoptosis pathways in THP-1 monocyte-derived macrophages in response to Salmonella infection.

Results: Activated caspase-3-induced apoptosis pathways, including extrinsic (caspase-8-mediated) and intrinsic (caspase-9-mediated) pathways, in Salmonella-infected macrophages were verified. THP-1 cells with dysfunction of TLR-4 and TLR-5 and Salmonella SPI-1 and SPI-2 mutants were constructed to identify the roles of the genes associated with programmed cell death in the macrophages. Caspase-3 activation in THP-1 macrophages was induced by Salmonella through TLR-4 and TLR-5 signaling pathways. We also identified that SPI-1 structure protein PrgH and effectors SipB and SipD, but not SPI-2 structure protein SsaV, could induce apoptosis via caspase-3 activation and reduce the secretion of inflammation marker TNF-α in the Salmonella-infected cells. The two effectors also reduced the translocation of the p65 subunit of NF-κB into the nucleus and the expression of TNF-α, and then inflammation was diminished.

Conclusion: Non-typhoid Salmonella induced apoptosis of macrophages and thereby reduced inflammatory cytokine production through the expression of SPI-1. This mechanism in host-pathogen interaction may explain why Salmonella usually manifests as occult bacteremia with less systemic inflammatory response syndrome in the bloodstream infection of children.
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http://dx.doi.org/10.1016/j.jmii.2020.02.008DOI Listing
February 2020

White matter alteration and autonomic impairment in obstructive sleep apnea.

J Clin Sleep Med 2020 02 13;16(2):293-302. Epub 2020 Jan 13.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Study Objectives: Autonomic impairment and white matter (WM) alterations have been noted as effects of obstructive sleep apnea (OSA). This study sought to evaluate the change of WM integrity in patients with OSA using diffusion tensor imaging (DTI) and to determine its relationship with autonomic impairment.

Methods: A total of 30 patients with moderate and severe OSA and 19 healthy volunteers were recruited. A cardiovascular autonomic survey was performed and the baroreflex sensitivity (BRS) for each participant was derived from changes in heart rate and blood pressure during the early part of phase II of the Valsalva maneuver. DTI-related indices were derived from DTI. The fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were compared using voxel-based statistics to determine differences between the patients with OSA and the healthy controls. The correlations among DTI indices, clinical severity, and autonomic parameters were investigated.

Results: The BRS values were significantly worse in the OSA group than in the control patients. An exploratory group-wise comparison between the two groups revealed that the patients with OSA exhibited low FA, increased MD, AD, and RD in several brain locations. The declined DTI indices in autonomic-related areas were significantly correlated with increased clinical disease severity and baroreflex impairment.

Conclusions: OSA alters WM integrity in the cingulum and temporal lobe, and this impairment might play some role in autonomic dysfunction. The possible interaction between autonomic dysfunction and central nervous system microstructural alterations may represent variant hypoxic patterns, sympathetic activation, and their consequent processes in OSA.
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http://dx.doi.org/10.5664/jcsm.8186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053037PMC
February 2020

Associations between Brain Structural Damage and Core Muscle Loss in Patients with Parkinson's Disease.

J Clin Med 2020 Jan 16;9(1). Epub 2020 Jan 16.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan.

Background: Parkinson's disease (PD) is a common neurodegenerative disease associated with progressive gray matter atrophy. In addition to motor function disorder, frailty and decreased muscle mass potentially contribute to increased morbidity risk.

Objective: This study aimed to investigate the associations between lean muscle loss and gray matter volume (GMV) in PD patients.

Methods: Thirty patients with PD and fifteen healthy controls underwent brain and bilateral thigh MRIs. The IDEAL sequence was employed, measuring the regions of interest (ROI) of fat percentage at the 50% point of femur length. Voxel-base morphometry (VBM) was used to assess regional gray matter volume differences between groups. Further correlation analysis was performed to evaluate the changes between gray matter volume and fatty percentage of the bilateral thigh after adjusting for age and gender. Multiple linear regression analysis was applied to evaluate the risk factor of core muscle loss in PD patients.

Results: Compared with controls, patients with PD had significantly higher thigh fat percentage and smaller gray matter volume of several brain locations of the default mode network (DMN), specifically the left superior temporal gyrus, right uncus, and left inferior temporal gyrus, revealing association with higher thigh fat percentage. Further multiple linear regression analysis indicated that higher thigh fat percentage is associated with gender (female), increased disease duration, and smaller gray matter volume of the left superior temporal gyrus and right uncus in PD patients.

Conclusions: Patients with PD experience core muscle loss in the thigh, associated with default mode network (DMN) degeneration, longer disease duration, and female gender. Identification of risk factors associated with lean muscle mass loss may assist in early prevention of comorbidities such as sarcopenia.
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http://dx.doi.org/10.3390/jcm9010239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019762PMC
January 2020

Alteration of brain temperature and systemic inflammation in Parkinson's disease.

Neurol Sci 2020 May 10;41(5):1267-1276. Epub 2020 Jan 10.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd. Niaosong Dist, Kaohsiung City, 83301, Taiwan, Republic of China.

Objectives: Parkinson's disease (PD) is known to be related to various factors, including neuroinflammation, increased oxidative stress, and brain temperature alteration. We aimed to evaluate the correlation between these factors using diffusion-weighted imaging (DWI) thermometry and blood tests of systemic inflammation.

Methods: From July 2012 to Jun 2017, 103 patients with PD (44 men and 59 women; mean age, 60.43 ± 9.12 years) and 106 sex- and age-matched healthy volunteers (48 men and 58 women; mean age, 58.16 ± 8.45 years) retrospectively underwent magnetic resonance DWI thermometry to estimate brain intraventricular temperature (T). Subjects were divided into three subgroups in light of their ages. The tested inflammatory markers included plasma nuclear DNA, mitochondrial DNA, apoptotic leukocytes, and serum adhesion molecules. The correlations among the T values, clinical severity, and systemic inflammatory markers were then calculated.

Results: The PD patients did not show a natural trend of decline in T with age. Comparisons among the different age groups revealed that the younger PD subjects had significantly lower T values than the younger controls, but the older subjects had no significant group differences. Overall, the PD patients exhibited lower T values than the controls, as well as increased oxidative stress. The brain temperature showed positive correlations with inflammatory markers, including plasma nuclear DNA and L-selectin levels, in all the subjects.

Conclusions: Possible pathophysiological correlations between systemic inflammation and brain temperature were indicated by the results of this study, a finding which may aid us in investigating the underlying pathogenesis of PD.
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http://dx.doi.org/10.1007/s10072-019-04217-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196953PMC
May 2020

Correlation between Executive Network Integrity and Sarcopenia in Patients with Parkinson's Disease.

Int J Environ Res Public Health 2019 12 4;16(24). Epub 2019 Dec 4.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan.

: Sarcopenia is critically associated with morbidity and mortality in the progression of Parkinson's disease (PD). However, analyses of clinical severity and brain changes, such as white matter (WM) alterations in PD patients with sarcopenia are limited. Further understanding of the factors associated with sarcopenia may provide a focused screen and potential for early intervention in PD patients. : 52 PD patients and 19 healthy participants accepted dual-energy X-ray absorptiometry to measure the body composition. Using diffusion tensor imaging, the difference of WM integrity was measured between PD patients with sarcopenia (PDSa) and without sarcopenia (PDNSa). Multivariate analysis was performed to explore the relationships between clinical factors, WM integrity, and sarcopenia in PD patients. : 21 PD patients (40.4%) had sarcopenia. PDSa had a higher Unified Parkinson's Disease Rating Scale (UPDRS III) score, lower body mass index (BMI) and lower fat weight compared with the PDNSa. Additionally, PDSa patients exhibited lower fractional anisotropy accompanied by higher radial diffusivity and/or higher mean diffusivity in the fronto-striato-thalamic circuits, including bilateral cingulum, left superior longitudinal fasciculus, left genu of corpus callosum, and right anterior thalamic radiation, which participate in the executive function. In addition, decreased muscle mass was associated with worse WM integrity in these regions. Multiple linear regression analysis revealed that WM integrity in the left cingulum, right anterior thalamic radiation, together with gender (male) significantly predicted muscle mass in PD patients. : WM alterations in the executive network, such as the fronto-striato-thalamic circuits, may indicate a risk factor for ongoing sarcopenia in PD patients. The effectiveness of using executive function to serve as a prodromal marker of sarcopenia in PD patients should be evaluated in future studies.
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http://dx.doi.org/10.3390/ijerph16244884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950743PMC
December 2019

Associations Between Cognitive Functions and Physical Frailty in Patients With Parkinson's Disease.

Front Aging Neurosci 2019 30;11:283. Epub 2019 Oct 30.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

: Parkinson's disease (PD) is a neurodegenerative disease manifested by both motor and non-motor dysfunctions and co-existence of cognitive impairment and physical frailty is common. Given that research in this area is limited, a better understanding of associated factors with physical frailty could provide a focused screening method and facilitate early intervention in PD. : Seventy-six patients with idiopathic PD were recruited and Fried's criteria of physical frailty were used to group all participants. Comprehensive cognitive tests and clinical characteristics were measured, and univariate and multivariate analysis was performed to explore the relationship between clinical factors or neuropsychological functions. : Twenty-nine patients with PD (38%) exhibited physical frailty. Compared to PD patients without frailty, PD patients with frailty were older in age and demonstrated worse disease severity and poorer cognitive functions, including attention, executive function, memory, speech and language, and visuospatial function ( < 0.05). Further, stepwise logistic regression analysis revealed that disease severity by the Unified Parkinson's Disease Rating Scale (UPDRS) total score (OR: 1.065; 95% CI: 1.033-1.099) and executive function (OR: 0.724; 95% CI: 0.581-0.877) were independent risk factors for predicting physical frailty ( = 0.003 and 0.002). The best cut-off points are 46 in UPDRS (sensitivity: 62.1%; specificity: 91.5%). : Executive function impairment is an independent risk factor for the development of physical frailty with disease progression. Awareness of such comorbidity might provide a screening tool to facilitate investigation in their underlying etiology and early intervention for frailty prevention.
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http://dx.doi.org/10.3389/fnagi.2019.00283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831640PMC
October 2019

Evaluation of Outcomes following Radiofrequency Ablation for Treatment of Parotid Tail Warthin Tumors.

J Vasc Interv Radiol 2019 Oct 27;30(10):1574-1580. Epub 2019 Aug 27.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. Electronic address:

Purpose: To evaluate efficacy and safety of radiofrequency (RF) ablation for parotid Warthin tumor.

Materials And Methods: From September 2016 to August 2017, 7 consecutive patients with biopsy-proven parotid Warthin tumors who did not undergo surgery presented with symptoms or cosmetic concerns and underwent US-guided percutaneous RF ablation treatment. RF ablation procedures were performed using the moving shot technique. US, contrast-enhanced CT, or MR imaging was performed 6-12 months after each procedure. Complications and cosmetic scale improvement after RF ablation were also evaluated.

Results: There was a significant reduction in mean tumor volume from 14.6 cm ± 13.1 (range, 1.9-35.5 cm) to 0.8 cm ± 0.5 (range, 0.2-1.54 cm) and a mean cosmetic scale improvement (from 4 to 1) on imaging studies 6-12 months after RF ablation compared with before RF ablation (P < .05). Volume reduction ratios at 1-2 months, 5-6 months, and 10-12 months after RF ablation were 51.2% ± 18.1%, 87.8% ± 10.6%, and 94.3% ± 2.0%. There was no facial nerve injury. One patient with parotitis and hematoma recovered in 1 week.

Conclusions: RF ablation using the moving shot technique could be an effective and safe alternative treatment for parotid tail Warthin tumors in patients unsuitable for or unwilling to undergo surgical resection.
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http://dx.doi.org/10.1016/j.jvir.2019.04.031DOI Listing
October 2019

Dietary exposure and risk assessment of exposure to hexabromocyclododecanes in a Taiwan population.

Environ Pollut 2019 Jun 14;249:728-734. Epub 2019 Mar 14.

Department of Food Safety/Hygiene and Risk Management, National Cheng Kung University, Tainan, 701, Taiwan; Research Center of Environmental Trace Toxic Substances, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address:

Hexabromocyclododecane (HBCD) is commonly used in commercial products and factories. HBCDs can be detected in the air, bioaccumulated deposits, water, soil, sediments, and in biota and foodstuffs in the food-chain because they are not chemically bound to the polymer. We determined the levels of α-, β-, and γ-HBCDs in 270 foodstuffs and the doses of HBCDs Taiwanese are normally exposed to. We also wanted to create a strategy of risk management for HBCDs based on margins of exposure (MOE). HBCDs were frequently detectible in fish, seafood, and poultry. Their highest concentrations were in fish, oil, poultry, and livestock. The highest estimated daily intake was in 0- to 3-year-olds (1.576 ng/kg/day), and lower in 3- to 6- (1.064 ng/kg/day), 6- to 12- (0.899 ng/kg/day), and lowest in 12- to 16- (0.632 ng/kg/day) year-olds. The exposure doses to HBCDs indicated no health concern for Taiwanese. Except for fish, significant concentrations of α- and γ-HBCDs were detected in many other foodstuffs, which might indicate that exposure to HBCD is a relatively recent problem. Therefore, one goal of a management policy should be to follow-up the flow direction of HBCDs in Taiwan.
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http://dx.doi.org/10.1016/j.envpol.2019.03.040DOI Listing
June 2019

Oxidative damage in patients with benign prostatic hyperplasia and prostate cancer co-exposed to phthalates and to trace elements.

Environ Int 2018 12 26;121(Pt 2):1179-1184. Epub 2018 Oct 26.

Department of Food Safety/Hygiene and Risk Management, National Cheng Kung University, Taiwan; Department of Environmental Trace Toxic Substances Research Center, Medical College, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Evidence indicates that prostates exposed to environmental endocrine disruptors and trace metals will cause adverse health outcomes. We assessed the association between urinary phthalate metabolites and serum trace metal levels, and oxidative damage in benign prostatic hyperplasia (BPH) patients, prostate cancer (PCa) patients, and healthy controls. Levels of cadmium (Cd), nickel (Ni), and copper (Cu) were significantly higher in BPH patients than in controls, and mercury (Hg) was highest in PCa patients. An Hg level >1 μg/L posed a significant risk (OR: 42.86, 95% CI: 1.092-1684) for PCa, but a zinc (Zn) level >1 μg/L was marginally negative (OR: 0.979, 95% CI: 0.957-1.002). We also found strong associations between PCa and mono-isononyl phthalate (MiNP), and between BPH and mono-isodecyl phthalate (MiDP), malonyldialdehyde (MDA) were significantly higher in PCa and BPH patients than in controls; 8‑hydroxydeoxyguanosine (8‑OH‑dG) and DNA strand breakage were highest in BPH patients and lowest in controls. When the prostate was simultaneously co-exposed to phthalates and trace metals, phthalates had a less significant effect on PCa and BPH. Thus, we hypothesize that, for patients with prostate disease, exposure to trace metals is more significant than is exposure to phthalates.
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http://dx.doi.org/10.1016/j.envint.2018.10.034DOI Listing
December 2018

Sex hormones and oxidative stress mediated phthalate-induced effects in prostatic enlargement.

Environ Int 2019 05 22;126:184-192. Epub 2019 Feb 22.

Research Center of Environmental Trace Toxic Substance, National Cheng Kung University, Tainan, Taiwan; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.
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http://dx.doi.org/10.1016/j.envint.2019.02.006DOI Listing
May 2019

Reduced lateral occipital gray matter volume is associated with physical frailty and cognitive impairment in Parkinson's disease.

Eur Radiol 2019 May 6;29(5):2659-2668. Epub 2018 Dec 6.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.

Introduction: To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients.

Methods: Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model.

Results: The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV.

Conclusion: Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients.

Key Points: • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.
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http://dx.doi.org/10.1007/s00330-018-5855-7DOI Listing
May 2019

Dietary intake of 4-nonylphenol and bisphenol A in Taiwanese population: Integrated risk assessment based on probabilistic and sensitive approach.

Environ Pollut 2019 Jan 10;244:143-152. Epub 2018 Oct 10.

Research Center of Environmental Trace Toxic Substances, National Cheng Kung University, Tainan, 701, Taiwan; Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, 704, Taiwan. Electronic address:

4-Nonylphenol (NP) and bisphenol A (BPA) are high-production and high-volume chemicals used to manufacture various commercial products. They are also ubiquitous contaminants that disrupt endocrine systems in wildlife and humans. We collected, from Taiwan cities with the highest food production, and analyzed, using high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS), 278 food samples for NP and BPA from 11 categories. We found background levels of 100% for NP and 72% for BPA in total samples. High levels of contamination (up to 918 and 49.4 μg/kg) were found in some foods of seafood and animal origin. We used a probabilistic approach to calculate daily dietary dose (Monte Carlo-estimated 95th percentile dietary exposure [MCS 95]) from the Taiwan National Food Consumption database for each sex- and age-specified population. For NP and BPA, the highest average daily dose (ADDs) were in the 4- to 6-year-old group (MCS 95 = 1.57/1.28 and 0.157/0.147 [Male/Female] μg/kg bw/day, respectively), and the lowest ADDs were in the ≥65-year-old group (MCS 95 = 0.674/0.581 and 0.054/0.045 [M/F] μg/kg bw/day, respectively). Based on the European Food Safety Authority (4 μg/kg bw/day for BPA) and Danish Institute of Safety and Toxicology guidelines (5 μg/kg bw/day for NP), the 95th percentile HQ of NP and BPA intake in different sex- and age-specified groups in Taiwan posed no risks through dietary exposure. The intake quantity and concentrations of grains, livestock, and seafood are important variables for the integrated risk of NP and BPA. In conclusion, a combination of multiple and long-term exposure via food consumption should be considered rather than individual endocrine-disrupting chemicals during dietary risk assessment in specific populations. SUMMARY: The 95th percentile HQ of NP and BPA intake in different age and sex groups in Taiwan posed no risks through dietary exposure based on probabilistic and sensitive approach.
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http://dx.doi.org/10.1016/j.envpol.2018.10.040DOI Listing
January 2019

Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson's disease with and without cognitive impairment.

J Neuroinflammation 2018 Sep 26;15(1):281. Epub 2018 Sep 26.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.

Background: To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson's disease (PD) patients with and without cognitive impairment.

Methods: This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas.

Results: The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment.

Conclusion: The MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson's disease.
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http://dx.doi.org/10.1186/s12974-018-1317-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158841PMC
September 2018

Reduced gray matter volume and respiratory dysfunction in Parkinson's disease: a voxel-based morphometry study.

BMC Neurol 2018 May 26;18(1):73. Epub 2018 May 26.

Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.

Background: The respiratory dysfunction of patients with Parkinson's disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morphometry (VBM), and respiratory dysfunction in patients with PD and correlated it with systemic inflammatory markers.

Methods: Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 25 PD patients with abnormal pulmonary function (13 men, 12 women; mean age: 62.9 ± 10.8 years) and, for comparison, on 25 sex- and age-matched PD patients with normal pulmonary function (14 men, 11 women; mean age: 62.3 ± 6.9 years). Inflammatory markers were determined by flow cytometry. The differences and correlations in regional GMV, clinical severity and inflammatory markers were determined after adjusting for age, gender and total intracranial volume (TIV).

Results: Compared with the normal pulmonary function group, the abnormal pulmonary function group had smaller GMV in several brain regions, including the left parahippocampal formation, right fusiform gyrus, right cerebellum crus, and left postcentral gyri. Forced expiratory volume in 1 s (FEV1) and maximal expiratory flow after expiration of 50% of forced vital capacity (MEF50) were positively correlated with regional GMV. There were no significant differences in the level of serum inflammatory markers between two groups.

Conclusion: Our findings suggested that involvement of the central autonomic network and GM loss may underlie the respiratory dysfunction in PD patients.
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http://dx.doi.org/10.1186/s12883-018-1074-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970473PMC
May 2018

Extraction of large-scale structural covariance networks from grey matter volume for Parkinson's disease classification.

Eur Radiol 2018 Aug 12;28(8):3296-3305. Epub 2018 Mar 12.

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.

Objectives: To identify disease-related spatial covariance patterns of grey matter volume as an aid in the classification of Parkinson's disease (PD).

Methods: Seventy structural covariance networks (SCNs) based on grey matter volume covariance patterns were defined using independent component analysis with T1-weighted structural MRI scans (discovery sample, 70 PD patients and 70 healthy controls). An image-based classifier was constructed from SCNs using a multiple logistic regression analysis with a leave-one-out cross-validation-based feature selection scheme. A validation sample (26 PD patients and 26 healthy controls) was further collected to evaluate the generalization ability of the constructed classifier.

Results: In the discovery sample, 13 SCNs, including the cerebellum, anterior temporal poles, parahippocampal gyrus, parietal operculum, occipital lobes, supramarginal gyri, superior parietal lobes, paracingulate gyri and precentral gyri, had higher classification performance for PD. In the validation sample, the classifier had moderate generalization ability, with a mean sensitivity of 81%, specificity of 69% and overall accuracy of 75%. Furthermore, certain individual SCNs were also associated with disease severity.

Conclusions: Although not applicable for routine care at present, our results provide empirical evidence that disease-specific, large-scale structural networks can provide a foundation for the further improvement of diagnostic MRI in movement disorders.

Key Points: • Disease-specific, large-scale SCNs can be identified from structural MRI. • A new network-based framework for PD classification is proposed. • An SCN-based classifier had moderate generalization ability in PD classification. • The selected SCNs provide valuable functional information regarding PD patients.
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http://dx.doi.org/10.1007/s00330-018-5342-1DOI Listing
August 2018

Site-Selective Functionalization of Flagellin by Steric Self-Protection: A Strategy To Facilitate Flagellin as a Self-Adjuvanting Carrier in Conjugate Vaccine.

Chembiochem 2018 04 14;19(8):805-814. Epub 2018 Mar 14.

Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.

Flagellin (FliC) can act as a carrier protein in the preparation of conjugate vaccines to elicit a T-cell-dependent immune response and as an intrinsic adjuvant to activate the toll-like receptor 5 (TLR5) to enhance vaccine potency. To enable the use of FliC as a self-adjuvanting carrier, an effective method for site-selective modification (SSM) of pertinent amino-acid residues in the D2 and D3 domains of FliC is explored without excessive modification of the D0 and D1 domains, which are responsible for activating and binding with TLR5. In highly concentrated Na SO solution, FliC monomers form flagellar filaments, in which the D0 and D1 domains are situated inside the tubular structure. Thus, the lysine residues (K219, K224, K324, and K331) in the D2 and D3 domains of flagellin are selectively modified by a diazo-transfer reaction with imidazole-1-sulfonyl azide. The sites with azido modification are confirmed by MALDI-TOF-MS, ESI-TOF-MS, and LC-MS/MS analyses along with label-free quantitation. The azido-modified filament dissolves to give FliC monomers, which can conjugate with alkyne-hinged saccharides by the click reaction. Transmission electron microscopy imaging, dynamic light scattering measurements, and the secreted embryonic alkaline phosphatase reporter assay indicate that the modified FliC monomers retain the ability either to bind with TLR5 or to reassemble into filaments. Overall, this study establishes a feasible method for the SSM of FliC by steric self-protection of the D0 and D1 domains.
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http://dx.doi.org/10.1002/cbic.201700634DOI Listing
April 2018

Correlation between Dopamine Transporter Degradation and Striatocortical Network Alteration in Parkinson's Disease.

Front Neurol 2017 17;8:323. Epub 2017 Jul 17.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson's disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed Tc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration ( = -0.533,  = 0.004), higher HY stage ( = -0.431,  = 0.020), and lower activities of daily living score ( = 0.369,  = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.
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http://dx.doi.org/10.3389/fneur.2017.00323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511968PMC
July 2017