Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

Clinical and Immunological Characterization of Perilla Seed Allergy in Children.

BACKGROUND AND OBJECTIVES: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergy are limited to a few case reports worldwide, and there is currently no diagnostic test for this allergy. Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. METHODS: Twenty-one children with clinical perilla seed allergy were enrolled from 2 tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) and an IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of perilla seed allergy. IgE immunoblotting was performed to identify putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. SPT was performed with perilla seed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31-35, and 14-16 kDa bound to the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these 3 protein fractions showed 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. CONCLUSIONS: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds.

Clinical and Immunological Characterization of Perilla Seed Allergy in Children

Background: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergy are limited to a few case reports worldwide, and there is currently no diagnostic test for this allergy. Objective: Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. Methods: Twenty-one children with clinical perilla seed allergy were enrolled from 2 tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) and an IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of perilla seed allergy. IgE immunoblotting was performed to identify putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. SPT was performed with perilla seed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31-35, and 14-16 kDa bound to the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these 3 protein fractions showed 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. Conclusion: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds (AU)

Antecedentes: Las semillas de perilla pueden causar reacciones alérgicas inmediatas. Sin embargo, existen escasos estudios, limitados a escasos casos clínicos, sin que existan pruebas diagnósticas para esta alergia alimentaria.Objetivo: El objetivo de este trabajo es analizar las características clínicas e inmunológicas de los pacientes con alergia a semillas de perilla e identificar los alérgenos responsables con el fin de desarrollar nuevos métodos diagnósticos. Métodos: Se reclutaron 21 niños con alergia a semillas de perilla procedentes de dos hospitales entre septiembre de 2016 y 2019. Se realizaron prick test y determinación de IgE específica in vitro mediante ELISA utilizando un extracto de perilla. Igualmente se realizó immunoblotting para identificar los componentes alergénicos y determinar su composición mediante cromatografía líquida y espectometría de masas (LC-MS/MS). Resultados: Los niños con alergia a perilla tienen una mediana de edad de 3 años. El 28,6% de estos niños presentaron anafilaxia. Se realizó prick test con el extracto de perilla en 15/21 niños con resultado positivo en todos ellos. La IgE específica in vitro mediante ELISA fue positiva en el 85,7% de los casos. Más del 50% de los niños reconocían proteínas de 50, 31–35 y 14–16 kDa. El análisis mediante LC-MS/MS de estas tres fracciones identificó 8 proteínas diferentes, incluyendo una oleosina (Accession No. 9963891), como posibles alérgenos. Conclusiones: Este trabajo describe las características clínicas e inmunológicas de 21 niños con alergia a semillas de perilla. Nuestros resultados sugieren que una oleosina es uno de los alérgenos mayores en los pacientes con alergia a semillas de perilla (AU)

Lactobacillus intestinalis YT2 restores the gut microbiota and improves menopausal symptoms in ovariectomized rats.

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes/Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Successful infusion of obinutuzumab by desensitization: a case of anaphylactic shock during desensitization

No disponible

Detection of viable but nonculturable Vibrio parahaemolyticus induced by prolonged cold-starvation using propidium monoazide real-time polymerase chain reaction.

Viable but nonculturable (VBNC) Vibrio parahaemolyticus cannot be detected by the standard cultivation-based methods. In this study, commonly used viability assessment methods were evaluated for the detection of V. parahaemolyticus in a VBNC state. Vibrio parahaemolyticus cells exposed to nutrient deficiency at cold temperature were used for epifluorescence microscopy with SYTO9 and propidium iodide (PI) staining and real-time polymerase chain reaction (qPCR) with propidium monoazide (PMA), and its resuscitative ability was determined by a temperature upshift in freshly prepared artificial sea water (ASW; pH 7) fluids. Viable cells with intact membranes always exceeded 5·0 log CFU per ml in ASW microcosms at 4°C. After 80 days, cycle thresholds for V. parahaemolyticus ATCC 27969 were 16·15-16·69. During cold-starvation, PMA qPCR selectively excluded DNAs from heat-killed cells. However, there may be some penetration of PMA into undamaged cells that persisted in ASW for 150 days, as evidenced by their ability to resuscitate from a VBNC state after a temperature upshift (25°C); V. parahaemolyticus ATCC 33844 and V. parahaemolyticus ATCC 27969 were successfully reactivated from a VBNC state in ASW microcosms containing <5% NaCl, following enrichment in ASW medium (pH 7). SIGNIFICANCE AND IMPACT OF THE STUDY: Few studies have evaluated the characteristics of and detection methods for viable but nonculturable (VBNC) Vibrio parahaemolyticus induced by cold-starvation. Currently, VBNC cells are routinely detected by SYTO9 and propidium iodide double staining. However, viable cell counts might be overestimated by this approach, suggesting that the fluorescence dyes may be ineffective for accurately determining the viability of bacterial cells. We demonstrated that quantitative real-time polymerase chain reaction with propidium monoazide, which selectively permeates damaged cell membranes, can be used to obtain viable cell counts of V. parahaemolyticus after its evolution to a VBNC state under cold-starvation conditions.

Multicentre study evaluating matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of clinically isolated Elizabethkingia species and analysis of antimicrobial susceptibility.

OBJECTIVES: Rapid identification of Elizabethkingia species is essential because these species show variations in antibiotic susceptibility and clinical outcomes. Many recent inaccuracies in Elizabethkingia identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) have been noted. Accordingly, in this study, we evaluated the use of MALDI-TOF MS with an amended database to identify isolates of Elizabethkingia anophelis, E. miricola and E. meningoseptica. We then investigated the antimicrobial susceptibility of Elizabethkingia. METHODS: MALDI-TOF MS spectra were acquired from formic acid extracts overlaid with α-cyano-4-hydroxycinnamic acid matrix on target slides in linear positive ion mode for m/z 2000 to 20 000 Da. Spectra were analysed and SuperSpectra were created with SARAMIS premium software. 16S rRNA gene sequencing was used as the reference standard for species identification. Antibiotic susceptibility was assessed by broth microdilution. RESULTS: A total of 103 E. anophelis, 21 E. miricola and 11 E. meningoseptica isolates were used to calculate the average spectra and exclude common peaks. SuperSpectra were added to the SARAMIS taxonomy database; all validation results were correct, even for isolates not included in SuperSpectra. Confirmation by direct colony formation was also performed. Overall, the positive predictive value of SuperSpectra was 100% for all isolates. E. miricola (77%, 17/22) was more susceptible to levofloxacin than E. anophelis (16%, 17/105). Doxycycline and minocycline were effective against all Elizabethkingia species. CONCLUSIONS: Spectral analysis software identified significant species-specific peaks to create reference masses for efficient and accurate identification of Elizabethkingia species, providing accurate information for clinical treatment of Elizabethkingia infections.

Incidence and risk factors of immediate hypersensitivity reactions associated with low-osmolar iodinated contrast media: a longitudinal study based on a real-time monitoring system

OBJECTIVES: We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM. METHODS: This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS). RESULTS: The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not. CONCLUSION: The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM

OBJETIVOS: Estudio de la incidencia de reacciones de hipersensibilidad inmediata frente a diferentes medios de contraste de baja osmolaridad, así como la incidencia global de dichas reacciones con estos contrastes yodados. MÉTODOS: Estudio de cohortes en el que se incluyó de forma consecutiva a todos los pacientes a los que se realizó TAC con contraste yodados de baja osmolaridad durante los años 2012 a 2014. Se emplearon 5 contrastes yodados: iobitridol, iohexol, iomeprol, iopamidol, y iopromide. En todos los pacientes se valoró la presencia de efectos adversos. La aparición de cualquier síntoma fue registrada en el mismo momento de su aparición en el Contrast Safety Monitoring and Management System (CoSM2oS) en tiempo real. RESULTADOS: La incidencia global de reacciones de hipersensibilidad inmediata a medios de contraste yodados de baja osmolaridad fue de 0,97% (2.004 reacciones en 205.726 exploraciones con contraste). La incidencia fue significativamente mayor en los pacientes con historia previa de reacción adversa (16,99%) frente a tan solo 0,80% en los pacientes sin historia previa de reacción (p=.001). La incidencia de estas reacciones osciló desde el 0,72% con iohexol al 1,34% con iomeprol, sin alcanzar diferencias significativas entre los cinco contrastes. Un análisis longitudinal mostró que la incidencia de reacciones inmediatas de hipersensiblidad se incrementa de forma gradual en los pacientes con historia de reacciones previas con medios de contraste yodados (CR=2,006 (1.517-2.653), p<.001). este incremento solo se observaba en los pacientes con historia de reacciones previas, pero no en los sujetos sin historia previa de estas reacciones. CONCLUSIÓN: La incidencia de las reacciones de hipersensibilidad inmediata no fue significativamente diferente entre ninguno de los 5 contrastes utilizados en el estudio. Exposiciones repetidas a estos medios de contraste no aumentan el riesgo de este tipo de reacciones de hipersensibilidad inmediata en los pacientes que no habían presentado previamente este tipo de reacciones

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-glucoside potentiates self-renewal of human dental pulp stem cells via the AMPK/ERK/SIRT1 axis.

AIM: To evaluate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) on cell proliferation and examine the mechanisms of THSG-enhanced proliferative potential in human dental pulp stem cells (hDPSC). METHODOLOGY: After treatment with THSG, hDPSC were collected. Cell viability was determined by MTS assay, while messenger RNA (mRNA) expressions of proliferation and stem cell markers were analyzed using real-time PCR. Flow cytometry was also conducted to analysis protein expression of stem cell markers. A colony-forming unit assay of hDPSC was carried out. Cellular telomerase activity was also identified using real-time PCR. In addition, proliferation-related proteins involved in the effects of THSG on hDPSC were analyzed by Western blotting. Data were analyzed using one-way analysis of variance and two-tailed Student's t-test. RESULTS: Cell viability, colony-forming rates and telomerase activities of hDPSCs were enhanced after THSG treatment. mRNA expressions of proliferation markers (including expressions of NAD+-dependent histone deacetylase sirtuin 1 (SIRT1), proliferating cell nuclear antigen (PCNA), cyclin D1 and ribonucleotide reductase subunit M2 (RRM2)) increased significantly after THSG treatment (P < 0.05). Treatment with THSG for 3 h significantly augmented SIRT1 protein expression (P < 0.05). Furthermore, activities of proliferation-related proteins (including AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) had also significantly increased at 3 h (P < 0.05). After THSG treatment, increased gene and protein expressions of pluripotent-like stem cell markers (including NANOG, OCT4, and SOX2) were observed. CONCLUSIONS: 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-glucoside treatment enhanced the renewal ability and proliferative potential of hDPSCs via the AMPK/ERK/SIRT1 axis, which may provide a novel autogenic cell-based therapeutic strategy in regenerative dentistry.

Differentiating bipolar disorders from unipolar depression by applying the Brief Assessment of Cognition in Affective Disorders.

BACKGROUND: Scholars continue to argue about whether bipolar disorders (BD) and unipolar depression (UD) are distinguishable with regard to neurocognitive function. This study aims to explore the cognitive profiles of UD and BD by applying the Brief Assessment of Cognition in Affective Disorders (BAC-A) for neuropsychological assessment. METHOD: This cross-sectional study included 68 patients with UD, 67 patients with BD, and 135 healthy control subjects. We evaluated the participants' cognitive functions at euthymic status using the BAC-A, which is made up of six traditional cognitive subtests and the Affective Processing Test. We then used a discriminant function analysis (DFA) to determine whether cognitive performance can be used to distinguish these participant groups. RESULTS: Healthy controls demonstrated better performance in all subtests of the BAC-A than both the UD and BD patients, with the exception of delayed recognition of affective interference. Compared with the BD group, the UD group exhibited better performance in working memory and emotion inhibition. Furthermore, using all BAC-A indexes, a total of 70% of participants could be correctly classified using a DFA model, and the discriminating validity between UD and BD was superior to using either the traditional cognitive domains or the Affective Processing Test alone. CONCLUSIONS: We have found that UD patients may exhibit an intermediate performance between healthy subjects and BD patients in working memory and emotional inhibition tests. The BAC-A can potentially assist in differentiating BD patients from UD patients at euthymic status in clinical settings.

Identifying the mechanism of Escherichia coli O157:H7 survival by the addition of salt in the treatment with organic acids.

AIM: In this study, the effects of the addition of salt to treatment with acids (one of several organic acids and salt in various solutions including rich or minimal broth, buffer, or distilled water) on the reduction of Escherichia coli O157:H7 were investigated. The protein expression profiles corresponding to acid stress (acetic acid) with or without salt addition were studied using a comparative proteomic analysis of E. coli O157:H7. METHODS AND RESULTS: When acetic, lactic, or propionic acid was combined with 3% NaCl, mutually antagonistic effects of acid and salt on viability of E. coli O157:H7 were observed only in tryptone and yeast extract broth. After exposure to acetic acid alone or in combination with salt, approximately 851 and 916 protein spots were detected, respectively. Analysis of 10 statistically significant differentially expressed proteins revealed that these proteins are mainly related to energy metabolism. CONCLUSIONS: When we compared protein expression of E. coli O157:H7 treated with acetic acid and the combination of the acid and salt, the differentially expressed proteins were not related to acid stress- and salt stress-inducible proteins such as stress shock proteins. SIGNIFICANCE AND IMPACT OF THE STUDY: According to these results, the increased resistance of E. coli O157:H7 to acetic acid after the addition of salt may not be the result of synthesis of proteins related to these phenomena; therefore, further research needs to be conducted to identify the mechanism of the mutually antagonistic effect of some organic acids and salt.

Once-daily dosing of amikacin for treatment of Mycobacterium abscessus lung disease.

SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 µg/ml was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047). CONCLUSION: Our results suggest that once-daily AMK for 4 weeks with a target Cmax of 55-65 µg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.

SHP2 is induced by the HBx-NF-κB pathway and contributes to fibrosis during human early hepatocellular carcinoma development.

The non-receptor tyrosine phosphatase SHP2 has scaffolding functions in signal transduction cascades downstream of growth receptors. A recent study suggested that SHP2 acts as a tumor suppressor during hepatocellular carcinoma (HCC) development. Herein we examined whether SHP2 links the HBx-NF-κB pathway to EGFR signaling during HCC development. The overexpression of HBx or NF-κB led to increased SHP2 expression via NF-κB binding to the Shp2 promoter. EGF treatment induced ERK activation as well as the rapid assembly of SHP2, EGFR, and Gab1. Upon LPS stimulation, NF-κB-SHP2-ERK activation and phosphorylated STAT3 levels exhibited a negative correlation in vitro. By contrast, in patients with HBV-associated HCC, NF-κB-SHP2-ERK and IL-6-JAK-STAT3 pathway activity levels were concomitantly higher in adjacent non-neoplastic tissues than in HCC tissues. The immunohistochemical analysis of 162 tissues of patients with HCC revealed that SHP2 levels were significantly higher in non-neoplastic background tissues than in corresponding HCC tissues and considerably increased in background liver tissues with advanced fibrosis (P < 0.001). SHP2 expression increased gradually from normal liver to chronic hepatitis, cirrhosis, and background liver with a dysplastic nodule, but was decreased or lost in dysplastic nodules and HCC. This is the first report to describe the existence of the HBx-NF-κB-SHP2 pathway, linking HBV infection to the EGFR-RAS-RAF-MAPK pathway in the liver. SHP2 depletion from the negative crosstalk between NF-κB and STAT3 accelerates HCC development.

Effects of Gender and Age on Immune Responses of Human Peripheral Blood Mononuclear Cells to Probiotics: A Large Scale Pilot Study.

BACKGROUND: Despite the widely accepted concept that probiotics confer miscellaneous benefits to hosts, the controversies surrounding these health-promoting claims cannot be ignored. These controversies hinder development and innovation in this field. RESULTS: To clarify the effects of age and gender on probiotic-induced immune responses, we recruited 1613 Taiwanese individuals and calculated the ratio of IFN-γ to IL-10 production after each individual's PBMCs were stimulated by six probiotic strains (L. paracasei BRAP01, L. acidophilus AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500 and L. reuteri BR101). Our results indicated that gender and age have only minor effects on the immune modulation of probiotics. Additionally, we showed that L. paracasei BRAP01 and L. acidophilus AD300 are the two dominant strains inducing IFN-γ/IL-10 production in Taiwanese individuals and that L. reuteri BR101 was the most effective stimulator of IL-10/IFN-γ. Additionally, a significant inverse relationship between the ability of L. paracasei BRAP01 and L. rhamnosus AD500 to stimulate IFN-γ/IL-10 or IL-10/IFN-γ production was also observed. CONCLUSIONS: Our results indicated that age and gender have only minor effects on the immune modulation abilities of probiotics.

[Zinc induces normoxic accumulation of transcriptionally active hypoxia-inducible factor 1-alpha in mammary epithelial cells].

Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A mammary epithelial cell lines, the toxicity levels of zinc differ. Interestingly, both cell lines overexpress HIF-1α following zinc treatment. As it was evident from an up-regulation of its specific target gene CA9 that encodes carbonic anhydrase IX, the stabilized HIF-1α translocated to the nucleus and was transcriptionally active. Hence, we conclude that zinc causes normoxic accumulation of transcriptionally active HIF-1α by interfering with its post-translational regulation.

A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate.

This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit ß-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P-values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course.

Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011.

AIMS: Public controversy regarding the potential overdiagnosis and overmedication of children with attention-deficit/hyperactivity disorder (ADHD) has continued for decades. This study used the National Health Insurance Research Database of Taiwan (NHIRD-TW) to explore trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan. METHOD: Youths (age ≤18 years) who had at least two NHIRD-TW claims records with ADHD diagnosis between January 2000 and December 2011 were selected as the subject cohort. In total, the study sample comprised 145 018 patients with ADHD (mean age at a diagnosis of ADHD: 7.7 ± 3.1 years; 21.4% females). The number of cases of ADHD were calculated annually for each year (from 2000 to 2011), and the number of cases per year who received medication was determined as those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine) in each year. RESULTS: The prevalence rates of a diagnosis of ADHD in the youths ranged from 0.11% in 2000 to 1.24% in 2011. Compared with children under 6 years of age, the ADHD diagnosis rates in children aged between 7 and 12 years (ratio of prevalence rates = 4.36) and in those aged between 13 and 18 years (ratio of prevalence rates = 1.42) were significantly higher during the study period. The prevalence in males was higher than that in females (ratio of prevalence rates = 4.09). Among the youths with ADHD, 50.2% received medications in 2000 compared with 61.0% in 2011. The probability of receiving ADHD medication increased with age. More male ADHD patients received medications that females patients (ratio of prevalence rates = 1.16). CONCLUSIONS: The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews. Approximately 40-50% of the youths with ADHD did not receive any medications. These findings are not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan.