Survival outcomes of radium-223 therapy for metastatic castration-resistant prostate cancer following national health insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at four-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1‒5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≦ five bone metastases (p = 0.0018), baseline prostate-specific antigen (PSA) ≦ 36 ng/mL (p = 0.0004), baseline alkaline phosphate (ALP) < 115 U/L (p = 0.0007), and baseline hemoglobin (Hb) > 12 g/dL (p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not (p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.

Functional near-infrared spectroscopy evidence of cognitive-motor interference in different dual tasks.

Dual tasks (DTs) combining walking with a cognitive task can cause various levels of cognitive-motor interference, depending on which brain resources are recruited in each case. However, the brain activation and functional connectivity underlying cognitive-motor interferences remain to be elucidated. Therefore, this study investigated the neural correlation during different DT conditions in 40 healthy young adults (mean age: 27.53 years, 28 women). The DTs included walking during subtraction or N-Back tasks. Cognitive-motor interference was calculated, and brain activation and functional connectivity were analysed. Portable functional near-infrared spectroscopy was utilized to monitor haemodynamics in the prefrontal cortex (PFC), motor cortex and parietal cortex during each task. Walking interference (decrease in walking speed during DT) was greater than cognitive interference (decrease in cognitive performance during DT), regardless of the type of task. Brain activation in the bilateral PFC and parietal cortex was greater for walking during subtraction than for standing subtraction. Furthermore, brain activation was higher in the bilateral motor and parietal and PFCs for walking during subtraction than for walking alone, but only increased in the PFC for walking during N-Back. Coherence between the bilateral lateral PFC and between the left lateral PFC and left motor cortex was significantly greater for walking during 2-Back than for walking. The PFC, a critical brain region for organizing cognitive and motor functions, played a crucial role in integrating information coming from multiple brain networks required for completing DTs. Therefore, the PFC could be a potential target for the modulation and improvement of cognitive-motor functions during neurorehabilitation.

Standardized approach for accurate and reliable model development of ion-exchange chromatography based on parameter-by-parameter method and consideration of extra-column effects.

Developing an accurate and reliable model for chromatographic separation that meets regulatory requirements and ensures consistency in model development remains challenging. In order to address this challenge, a standardized approach was proposed in this study with ion-exchange chromatography (IEC). The approach includes the following steps: liquid flow identification, system and column-specific parameters determination and validation, multi-component system identification, protein amount validation, steric mass action parameters determination and evaluation, and validation of the calibrated model's generalization ability. The parameter-by-parameter (PbP) calibration method and the consideration of extra-column effects were integrated to enhance the accuracy of the developed models. The experiments designed for implementing the PbP method (five gradient experiments for model calibration and one stepwise experiment for model validation) not only streamline the experimental workload but also ensure the extrapolation abilities of the model. The effectiveness of the standardized approach is successfully validated through an application about the IEC separation of industrial antibody variants, and satisfactory results were observed with R2 ≈ 0.9 for the majority of calibration and validation experiments. The standardized approach proposed in this work contributes significantly to improve the accuracy and reliability of the developed IEC models. Models developed using this standardized approach are ready to be applied to a broader range of industrial separation systems, and are likely find further applications in model-assisted decision-making of process development.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Efficacy of non-invasive brain stimulation for post-stroke dysphagia: a meta-analysis.

BACKGROUND: Given the potential harms of dysphagia after stroke, we noticed the possibility of non-invasive brain stimulation treatments in the management process. METHODS: The meta-analysis search for articles published before May 2023 in databases. We used STATA 12.0 software to compute the standard mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The study showed a greater improvement in swallowing function in post-stroke dysphagia given transcranial direct current stimulation (tDCS) immediately after treatment, compared to those given sham tDCS (SMD = 2.99, 95% CI = 1.86-4.11). The study showed a greater improvement in swallowing function in post-stroke dysphagia given tDCS some days after treatment, compared to those given sham tDCS (SMD = 2.01, 95% CI = 0.87-3.16). The study showed a greater improvement in swallowing function in post-stroke dysphagia given repetitive transcranial magnetic stimulation (rTMS) immediately after treatment, compared to those given sham rTMS (SMD = 4.17, 95% CI = 3.11-5.23). The study showed a greater improvement in swallowing function in post-stroke dysphagia given rTMS some days after treatment, compared to those given sham rTMS (SMD = 1.77, 95% CI = 0.94-2.60). CONCLUSIONS: In conclusion, our study showed the beneficial effects of non-invasive brain stimulation on difficulty swallowing for stroke patients and speculated about the potential application of non-invasive brain stimulation on post-stroke dysphagia improvement.

Parameter-by-parameter estimation method for adsorption isotherm in hydrophobic interaction chromatography.

Hydrophobic interaction chromatography (HIC) is used as a critical polishing step in the downstream processing of biopharmaceuticals. Normally the process development of HIC is a cumbersome and time-consuming task, and the mechanical models can provide a powerful tool to characterize the process, assist process design and accelerate process development. However, the current estimation of model parameters relies on the inverse method, which lacks an efficient and logical parameter estimation strategy. In this study, a parameter-by-parameter (PbP) method based on the theoretical derivation and simplifying assumptions was proposed to estimate the Mollerup isotherm parameters for HIC. The method involves three key steps: (1) linear regression (LR) to estimate the salt-protein interaction parameter and the equilibrium constant; (2) linear approximation (LA) to estimate the stoichiometric parameter and the maximum binding capacity; and (3) inverse method to estimate the protein-protein interaction parameter and the kinetic coefficient. The results indicated that the LR step should be used for dilution condition (loading factor below 5%), while the LA step should be conducted when the isotherm is in the transition or nonlinear regions. Six numerical experiments were conducted to implement the PbP method. The results demonstrated that the PbP method developed allows for the systematic estimation of HIC parameters one-by-one, effectively reducing the number of parameters required for inverse method estimation from six to two. This helps prevent non-identifiability of structural parameters. The feasibility of the PbP-HIC method was further validated by real-world experiments. Moreover, the PbP method enhances the mechanistic understanding of adsorption behavior of HIC and shows a promising application to other stoichiometric displacement model-derived isotherms.

Cu-modified InVO4 photocatalysts for enhanced N2 fixation using chemical reagents and electroplating sludge as the Cu source.

Inspired by simulation analysis, we found that Cu decoration could enhance the NH3 production rate of InVO4 through promoting N2 adsorption and reducing the activation energy of the key hydrogenation step. 5% Cu/InVO4 exhibited an optimal NH3 yield of 195.11 µmol gcat-1 h-1, approximately six times higher than that of InVO4. Cu/InVO4 was also fabricated by upcycling Cu from electroplating sludge, achieving a gratifying nitrogen fixation performance of 154.13 µmol gcat-1 h-1.

Abdominal Diffusion-Weighted MRI With Simultaneous Multi-Slice Acquisition: Agreement and Reproducibility of Apparent Diffusion Coefficients Measurements.

BACKGROUND: Simultaneous multi-slice diffusion-weighted imaging (SMS-DWI) can shorten acquisition time in abdominal imaging. PURPOSE: To investigate the agreement and reproducibility of apparent diffusion coefficient (ADC) from abdominal SMS-DWI acquired with different vendors and different breathing schemes. STUDY TYPE: Prospective. SUBJECTS: Twenty volunteers and 10 patients. FIELD STRENGTH/SEQUENCE: 3.0 T, SMS-DWI with a diffusion-weighted echo-planar imaging sequence. ASSESSMENT: SMS-DWI was acquired using breath-hold and free-breathing techniques in scanners from two vendors, yielding four scans in each participant. Average ADC values were measured in the liver, pancreas, spleen, and both kidneys. Non-normalized ADC and ADCs normalized to the spleen were compared between vendors and breathing schemes. STATISTICAL TESTS: Paired t-test or Wilcoxon signed rank test; intraclass correlation coefficient (ICC); Bland-Altman method; coefficient of variation (CV) analysis; significance level: P < 0.05. RESULTS: Non-normalized ADCs from the four SMS-DWI scans did not differ significantly in the spleen (P = 0.262, 0.330, 0.166, 0.122), right kidney (P = 0.167, 0.538, 0.957, 0.086), and left kidney (P = 0.182, 0.281, 0.504, 0.405), but there were significant differences in the liver and pancreas. For normalized ADCs, there were no significant differences in the liver (P = 0.315, 0.915, 0.198, 0.799), spleen (P = 0.815, 0.689, 0.347, 0.423), pancreas (P = 0.165, 0.336, 0.304, 0.584), right kidney (P = 0.165, 0.336, 0.304, 0.584), and left kidney (P = 0.496, 0.304, 0.443, 0.371). Inter-reader agreements of non-normalized ADCs were good to excellent (ICCs ranged from 0.861 to 0.983), and agreement and reproducibility were good to excellent depending on anatomic location (CVs ranged from 3.55% to 13.98%). Overall CVs for abdominal ADCs from the four scans were 6.25%, 7.62%, 7.08, and 7.60%. DATA CONCLUSION: The normalized ADCs from abdominal SMS-DWI may be comparable between different vendors and breathing schemes, showing good agreement and reproducibility. ADC changes above approximately 8% may potentially be considered as a reliable quantitative biomarker to assess disease or treatment-related changes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of dynamic control of continuous capture with periodic counter-current chromatography under feedstock variations.

Multi-column periodic counter-current chromatography is a promising technology for continuous antibody capture. However, dynamic changes due to disturbances and drifts pose some potential risks for continuous processes during long-term operation. In this study, a model-based approach was used to describe the changes in breakthrough curves with feedstock variations in target proteins and impurities. The performances of continuous capture of three-column periodic counter-current chromatography under ΔUV dynamic control were systematically evaluated with modeling to assess the risks under different feedstock variations. As the concentration of target protein decreased rapidly, the protein might not breakthrough from the first column, resulting in the failure of ΔUV control. Small reductions in the concentrations of target proteins or impurities would cause protein losses, which could be predicted by the modeling. The combination of target protein and impurity variations showed complicated effects on the process performance of continuous capture. A contour map was proposed to describe the comprehensive impacts under different situations, and nonoperation areas could be identified due to control failure or protein loss. With the model-based approach, after the model parameters are estimated from the breakthrough curves, it can rapidly predict the process stability under dynamic control and assess the risks under feedstock variations or UV signal drifts. In conclusion, the model-based approach is a powerful tool for continuous process evaluation under dynamic changes and would be useful for establishing a new real-time dynamic control strategy.

Quantitative diffusion weighted imaging in patients with hepatocellular carcinoma: effects of simultaneous multi-slice acceleration and gadoxetic acid administration.

PURPOSE: To investigate whether simultaneous multi-slice (SMS) acceleration and gadoxetic acid administration affect the quantitative apparent diffusion coefficient (ADC) and signal-to-noise ratio (SNR) measurement of DWI in patients with HCC. METHODS: This prospective study initially enrolled 208 patients with clinically suspected HCC. Free breathing SMS-DWI and conventional DWI (CON-DWI) were performed before and after gadoxetic acid administration. Lesion conspicuity, ADCs and SNRs of the HCC lesion and normal liver parenchyma were independently measured by two radiologists. The paired t test or Wilcoxon signed rank test was used to evaluate the differences of lesion conspicuity, ADCs and SNRs between SMS-DWI and CON-DWI, as well as those before and after gadoxetic acid administration. RESULTS: A total of 102 HCC patients (90 men and 12 women; mean age, 54.6 ± 11.7 years) were finally included for analysis. SMS-DWI and CON-DWI demonstrated comparable lesion conspicuity (P = 0.081-0.566). For the influence of SMS acceleration, the SNRs of liver parenchyma on enhanced SMS-DWI were significantly higher than enhanced CON-DWI (P = 0.015). For the influence of gadoxetic acid administration, the mean ADCs were significantly higher on enhanced SMS-DWI than unenhanced SMS-DWI (HCC, P = 0.013; liver parenchyma, P = 0.032). CONCLUSION: Quantitative ADC measurements of HCC and liver parenchyma were not affected by SMS acceleration, and SMS-DWI can provide higher SNR than CON-DWI. However, the ADC measurements can be affected by gadoxetic acid administration on SMS-DWI, so it is recommended to perform SMS-DWI before gadoxetic acid administration.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease.

OBJECTIVES: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. METHODS: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5- DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. RESULTS: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5-. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5- DM-ILD- (all P < 0.001) as well as CD3-CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/µL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/µL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/µL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics. CONCLUSION: Significant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

TRiC/CCT chaperonin is required for the folding and inhibitory effect of WDTC1 on adipogenesis.

Obesity has become a global pandemic. WDTC1 is a WD40-containing protein that functions as an anti-obesity factor. WDTC1 inhibits adipogenesis by working as an adaptor of the CUL4-DDB1 E3 ligase complex. It remains unclear about how WDTC1 is regulated. Here, we show that the TRiC/CCT functions as a chaperone to facilitate the protein folding of WDTC1 and proper function in adipogenesis. Through tandem purification, we identified the molecular chaperone TRiC/CCT as WDTC1-interacting proteins. WDTC1 bound the TRiC/CCT through its ADP domain, and the TRiC/CCT recognized WDTC1 through the CCT5 subunit. Disruption of the TRiC/CCT by knocking down CCT1 or CCT5 led to misfolding and lysosomal degradation of WDTC1. Furthermore, the knockdown of CCT1 or CCT5 eliminated the inhibitory effect of WDTC1 on adipogenesis. Our studies uncovered a critical role of the TRiC/CCT in the folding of WDTC1 and expanded our knowledge on the regulation of adipogenesis.

Physics-informed neural networks to solve lumped kinetic model for chromatography process.

Numerical method is widely used for solving the mechanistic models of chromatography process, but it is time-consuming and hard to response in real-time. Physics-informed neural network (PINN) as an emerging technology combines the structure of neural network with physics laws, and is getting noticed for solving physics problems with a balanced accuracy and calculation speed. In this research, a proof-of-concept study was carried out to apply PINN to chromatography process simulation. The PINN model structure was designed for the lumped kinetic model (LKM) with all LKM parameters. The PINN structure, training data and model complexity were optimized, and an optimal mode was obtained by adopting an in-series structure with a nonuniform training data set focusing on the breakthrough transition region. A PINN for LKM (LKM-PINN) consisting of four neural networks, 12 layers and 606 neurons was then used for the simulation of breakthrough curves of chromatography processes. The LKM parameters were estimated with two breakthrough curves and used to infer the breakthrough curves at different residence times, loading concentrations and column sizes. The results were comparable to that obtained with numerical methods. With the same raw data and constraints, the average fitting error for LKM-PINN model was 0.075, which was 0.081 for numerical method. With the same initial guess, the LKM-PINN model took 160 s to complete the fitting, while the numerical method took 7 to 72 min, depending on the fitting settings. The fitting speed of LKM-PINN model was further improved to 30 s with random initial guess. Thus, the LKM-PINN model developed in this study is capable to be applied to real-time simulation for digital twin.

Calibration of local chemical pressure by optical probe.

Chemical stabilization of a high-pressure metastable state is a major challenge for the development of advanced materials. Although chemical pressure (Pchem) can effectively simulate the effect of physical pressure (Pphy), experimental calibration of the pressure passed to local structural motifs, denoted as local chemical pressure (Pchem-Δ) which significantly governs the function of solid materials, remains absent due to the challenge of probing techniques. Here we establish an innovative methodology to experimentally calibrate the Pchem-Δ and build a bridge between Pchem and Pphy via an optical probe strategy. Site-selective Bi3+-traced REVO4 (RE = Y, Gd) is adopted as a prototype to introduce Bi3+ optical probes and on-site sense of the Pchem-Δ experienced by the REO8 motif. The cell compression of RE0.98Bi0.02VO4 under Pphy is chemically simulated by smaller-ion substitution (Sc3+ → RE3+) in RE0.98-xScxBi0.02VO4. The consistent red shift (Δλ) of the emission spectra of Bi3+, which is dominated by locally pressure-induced REO8 dodecahedral variation in RE0.98Bi0.02VO4 (Pphy) and RE0.98-xScxBi0.02VO4 (Pchem-Δ), respectively, is evidence of their similar pressure-dependent local structure evolution. This innovative Δλ-based experimental calibration of Pchem-Δ in the crystal-field dimension portrays the anisotropic transmission of Pchem to the local structure and builds a bridge between Pchem-Δ and Pphy to guide a new perspective for affordable and practical interception of metastable states.

Improved process design for monoclonal antibody charge variants separation with multicolumn counter-current solvent gradient purification.

The multicolumn counter-current solvent gradient purification (MCSGP) method has proven effective in addressing the issue of elution profile overlap for difficult-to-separate proteins, leading to improved purity and recovery. However, during the MCSGP process, the flow rate and proportion of loaded proteins undergo changes, causing a significant discrepancy between the elution profiles of batch process design and the actual MCSGP process. This mismatch negatively impacts the purity and recovery of the target protein. To address this challenge, an improved process design (reDesign) was proposed with the first-run MCSGP to mimic the actual continuous process and obtain elution profiles that closely resemble the real ones. The reDesign was demonstrated with both a model protein mixture and a sample of monoclonal antibody (mAb) with charge variants. For model protein mixture, the reDesign-based MCSGP process (reMCSGP) showed a remarkable improvement in recovery, increasing from 83.6% to 97.8% while maintaining a purity of more than 95%. For mAb sample, the recovery of reMCSGP improved significantly to 93.9%, surpassing the performance of normal MCSGP processes at a given purity level of more than 84%. In general, the new process design strategy developed in this work could generate a more representative elution profile that closely mirrors actual conditions in continuous processes, which enhances the separation performance of MCSGP.

Model-assisted process development, characterization and design of continuous chromatography for antibody separation.

Continuous manufacturing in monoclonal antibody production has generated increased interest due to its consistent quality, high productivity, high equipment utilization, and low cost. One of the major challenges in realizing continuous biological manufacturing lies in implementing continuous chromatography. Given the complex operation mode and various operation parameters, it is challenging to develop a continuous process. Due to the process parameters being mainly determined by the breakthrough curves and elution behaviors, chromatographic modeling has gradually been used to assist in process development and characterization. Model-assisted approaches could realize multi-parameter interaction investigation and multi-objective optimization by integrating continuous process models. These approaches could reduce time and resource consumption while achieving a comprehensive and systematic understanding of the process. This paper reviews the application of modeling tools in continuous chromatography process development, characterization and design. Model-assisted process development approaches for continuous capture and polishing steps are introduced and summarized. The challenges and potential of model-assisted process characterization are discussed, emphasizing the need for further research on the design space determination strategy and parameter robustness analysis method. Additionally, some model applications for process design were highlighted to promote the establishment of the process optimization and process simulation platform.

Transcriptional profiling of mucus production and modification in rhesus macaque endocervical cells under hormonal regulation.

Objective: Endocervical mucus production is a key regulator of fertility throughout the menstrual cycle. With cycle-dependent variability in mucus quality and quantity, cervical mucus can either facilitate or block sperm ascension into the upper female reproductive tract. This study seeks to identify genes involved in the hormonal regulation of mucus production, modification, and regulation through profiling the transcriptome of endocervical cells from the non-human primate, the Rhesus Macaque (Macaca mulatta). Design: Experimental. Setting: Translational science laboratory. Intervention: We treated differentiated primary endocervical cultures with estradiol (E2) and progesterone (P4) to mimic peri-ovulatory and luteal-phase hormonal changes. Using RNA-sequencing, we identified differential expression of gene pathways and mucus producing and modifying genes in cells treated with E2 compared to hormone-free conditions and E2 compared to E2-primed cells treated with P4. Main Outcome Measures: We pursued differential gene expression analysis on RNA-sequenced cells. Sequence validation was done using qPCR. Results: Our study identified 158 genes that show significant differential expression in E2-only conditions compared to hormone-free control, and 250 genes that show significant differential expression in P4-treated conditions compared to E2-only conditions. From this list, we found hormone-induced changes in transcriptional profiles for genes across several classes of mucus production, including ion channels and enzymes involved in post-translational mucin modification that have not previously been described as hormonally regulated. Conclusion: Our study is the first to use an in vitro culture system to create an epithelial-cell specific transcriptome of the endocervix. As a result, our study identifies new genes and pathways that are altered by sex-steroids in cervical mucus production.

Multiple mycotoxins in commonly used edible oils: Occurrence and evaluation of potential health risks.

In this study, the contamination of 51 mycotoxins in 416 edible oils were determined by UPLC-MS/MS. Totally, twenty-four mycotoxins were detected and nearly half of the samples (46.9%, n = 195) were contaminated simultaneously with six to nine kinds of mycotoxins. The predominant mycotoxins and contamination characteristics varied depending on the type of oils. More specifically, four enniatins, alternariol monomethyl ether (AME) and zearalenone were the most frequent combination. Overall, peanut and sesame oils (10.7-11.7 mycotoxins on average) were found to be the most contaminated matrices whereas camellia and sunflower seed oils (1.8-2.7 species) were the opposite. Dietary exposure risks of mycotoxins were acceptable in most cases, however, the ingestion of aflatoxins (especially aflatoxin B1) through peanut and sesame oil (margin of exposure: 239.4-386.3 < 10000) exceeded the acceptable carcinogenic risk level. Meanwhile, the risks of cumulative ingestion through the food chain should be of great concern, especially sterigmatocystin, ochratoxin A, AME and zearalenone.

Measurements of elemental iodine in soy sauces in Taiwan using a modified microplate method.

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Soybean and most soybean products, including soy sauces, are listed as prohibited foods in a low iodine diet. However, the iodine content in soy sauces is largely unknown. The aim of this study was to determine the iodine content in domestic soy sauces in Taiwan. Methods: Twenty-five different kinds of soy sauces were diluted with distilled water and with a dilution factor of fifty or above. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated twelve times on three different days for determination of mean and standard deviation (SD), and coefficients of variance (CV). Serial dilution and recovery tests were also performed for validation. The results were confirmed by an inductively coupled plasma mass spectrometry (ICP-MS) method. Results: Among the twenty-five surveyed soy sauces, most of them (n=22) were iodine-free (<16 ug/L, and thus un-detectable). The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.7 ± 0.1, 5.1 ± 0.2, and 10.8 ± 0.6 mg/L, respectively. The inter-assay, intra-assay and total CVs were all <5.3% for the modified microplate method. The results obtained by ICP-MS were consistent with those of the modified microplate method. The recovery rates in the serial dilution test and recovery test ranged from 94.7% to 118.6%. Two of the three iodine-containing soy sauces were supplemented with kelp extract, while the other one without kelp extract had the highest amount of salt among the three iodine-containing soy sauces. Therefore, we postulate that iodized salt instead of kelp extract is the source of higher iodine content in that sauce. Conclusion: The results suggest that most soy sauces are iodine-free and may be allowed during low iodine diets.

Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.

OBJECTIVE: To characterize ion channel expression and localization in the endocervix under different hormonal conditions using a nonhuman primate primary endocervical epithelial cell model. DESIGN: Experimental. SETTING: University-based, translational science laboratory. INTERVENTIONS: We cultured and treated conditionally reprogrammed primary rhesus macaque endocervix cells with estradiol and progesterone and measured gene expression changes for several known ion channel and ion channel regulators of mucus secreting epithelia. Using both rhesus macaque endocervical samples and human samples, we localized channels in the endocervix using immunohistochemistry. MAIN OUTCOME MEASURES: The relative abundance of transcripts was evaluated using real-time polymerase chain reaction. Immunostaining results were evaluated qualitatively. RESULTS: Compared with controls, we found that estradiol increased gene expression for ANO6, NKCC1, CLCA1, and PDE4D. Progesterone down-regulated gene expression for ANO6, SCNN1A, SCNN1B, NKCC1, and PDE4D (P≤.05). Immunohistochemistry confirmed endocervical cell membrane localization of ANO1, ANO6, KCNN4, LRR8CA, and NKCC1. CONCLUSIONS: We found several ion channels and ion channel regulators that are hormonally sensitive in the endocervix. These channels, therefore, may play a role in the cyclic fertility changes in the endocervix and could be further investigated as targets for future fertility and contraceptive studies.