Who are the most vulnerable populations for primary care? Avoidable hospitalizations across individuals with different types of disabilities in South Korea.

BACKGROUND: Individuals with disabilities have limited access to primary care, the quality of care must be examined. OBJECTIVE: To examine avoidable hospitalizations among individuals with disabilities and determine the most vulnerable populations across types of disabilities. METHODS: Using the Korean National Health Insurance Claims Database, we compared hypertension- and diabetes-related avoidable hospitalizations (HRAH and DRAH, respectively) across disability status and disability type based on age-sex standardized rates from 2011 to 2020 and logistic regression. RESULTS: The gap between those with and without disabilities in age-sex standardized HRAH and DRAH increased over 10 years. Odds ratios for HRAH were higher for those with disabilities, with individuals with mental disabilities having the highest odds ratio, followed by those with intellectual/developmental disabilities, then those with physical disabilities; for DRAH, the three highest odds ratios belonged to individuals with mental, intellectual/developmental, and visual disabilities. Among those with disabilities, HRAH was higher for those with mental, intellectual/developmental, and severe physical disabilities, whereas DRAH was higher for those with mental, severe visual, and intellectual/developmental disabilities compared to those with mild physical disabilities. CONCLUSION: This study reveals high avoidable hospitalization rates among individuals with disabilities and calls for policies supporting quality primary care and comprehensively addressing disparities.

Antifungal activity of streptavidin C1 and C2 against pathogens causing Fusarium wilt.

Fusarium wilt is caused by the soil-inhabiting fungus Fusarium oxysporum ff. spp. and is one of the most devastating plant diseases, resulting in losses and decreasing the quality and safety of agricultural crops. We recently reported the structures and biochemical properties of two biotin-binding proteins, streptavidin C1 and C2 (isolated from Streptomyces cinnamonensis strain KPP02129). In the present study, the potential of the biotin-binding proteins as antifungal agent for Fusarium wilt pathogens was investigated using recombinant streptavidin C1 and C2. The minimum inhibitory concentration of streptavidin C2 was found to be 16 µg ml-1 for inhibiting the mycelial growth of F. oxysporum f.sp. cucumerinum and F. oxysporum f.sp. lycopersici, while that of streptavidin C1 was found to be 64 µg ml-1 . Compared with the nontreated control soil, the population density of F. oxysporum f.sp. lycopersici in the soil was reduced to 49·5% and 39·6% on treatment with streptavidin C1 (500 µg ml-1 ) and C2 (500 µg ml-1 ), respectively. A greenhouse experiment revealed that Fusarium wilt of tomato plants was completely inhibited on soil drenching using a 50-ml culture filtrate of the streptavidin-producing strain KPP02129.

Cognitive decline in association with hyposmia in idiopathic rapid eye movement sleep behavior disorder: a prospective 2-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to analyze the characteristics and progression of cognitive dysfunction in non-demented idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with baseline olfactory function. METHODS: From a prospective polysomnography-confirmed iRBD cohort, 25 patients (16 patients in 2-year follow-up) and 13 normal controls were included. Initial and 2-year follow-up cognitive functions were analyzed with olfactory function and 18 F-fluorinated-N-3-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)-nortropane (18 F-FP-CIT) uptake in deep nuclei initially. RESULTS: Idiopathic RBD patients had impaired attention, memory and executive function compared to controls. Baseline cognitive tests were comparable between the iRBD subgroups with and without hyposmia. 18 F-FP-CIT uptake tended to be lower in the hyposmic group than in the normosmic group. The olfactory test score was positively correlated with amygdala uptake in iRBD patients (P = 0.027). After 2 years, visuospatial and verbal memory dysfunction worsened more in hyposmics than in normosmics. Lower initial olfactory test score was associated with more severe declines in verbal memory function. CONCLUSIONS: Hyposmia may be a predictive sign of cognitive decline in iRBD patients.

The clinical efficacy of stem cell therapy for complex perianal fistulas: a meta-analysis.

BACKGROUND: Treatment of complex anal fistulas remains difficult. However, treatment with stem cells has had an encouraging success rate when applied to complex perianal fistulas. We systematically reviewed the current evidence through meta-analysis. METHODS: We performed an electronic literature search on PubMed, Embase, and the Cochrane Library and identified studies (published between January 1946 and August 2017) that used stem cells to treat patients with complex perianal fistula. Each paper was evaluated for treatment success rate, target patients, types of stem cells used, number of cells used, and criteria for complete healing. Potential publication bias was assessed via visual inspection of a funnel plot and Orwin's fail-safe N. Out of 171 papers, 16 were included in the meta-analysis. RESULTS: The overall healing rate of stem cell injection therapy for patients with complex perianal fistulas was 62.8% (95% CI 53.5-71.2, I2 = 54.05%), whereas those for patients with Crohn's perianal fistulas alone and complex anal fistulas not associated with Crohn's disease were 64.1% and 61.5% (p = 0.840), respectively. Healing rates for autologous and allogenic stem cell treatment were 69.4% and 50.7% (p = 0.020), respectively. Four comparative studies out of 16 studies were analyzed separately. Stem cell therapy increased the healing rate compared to the control groups (OR 0.379, 95% CI 0.152-0.947). CONCLUSIONS: Stem cell therapy is a good treatment option for complex perianal fistulas, which cannot be healed by conventional operative procedures. However, further research for additional supportive evidence, such as a large-scale randomized controlled trial, is required.

Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK.

BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

Antifungal activity of rimocidin and a new rimocidin derivative BU16 produced by Streptomyces mauvecolor BU16 and their effects on pepper anthracnose.

AIMS: The objective of this study was to explore antifungal metabolites targeting fungal cell envelope and to evaluate the control efficacy against anthracnose development in pepper plants. METHODS AND RESULTS: A natural product library comprising 3000 microbial culture extracts was screened via an adenylate kinase (AK)-based cell lysis assay to detect antifungal metabolites targeting the cell envelope of plant-pathogenic fungi. The culture extract of Streptomyces mauvecolor strain BU16 displayed potent AK-releasing activity. Rimocidin and a new rimocidin derivative, BU16, were identified from the extract as active constituents. BU16 is a tetraene macrolide containing a six-membered hemiketal ring with an ethyl group side chain instead of the propyl group in rimocidin. Rimocidin and BU16 showed broad-spectrum antifungal activity against various plant-pathogenic fungi and demonstrated potent control efficacy against anthracnose development in pepper plants. CONCLUSIONS: Antifungal metabolites produced by S. mauvecolor strain BU16 were identified to be rimocidin and BU16. The compounds displayed potent control efficacy against pepper anthracnose. SIGNIFICANCE AND IMPACT OF THE STUDY: Rimocidin and BU16 would be active ingredients of disease control agents disrupting cell envelope of plant-pathogenic fungi. The structure and antifungal activity of rimocidin derivative BU16 is first described in this study.

Microscopic mechanism underlying double-state lasing in an InAs/GaAs quantum dot laser diode elucidated using coupled rate equations and the spontaneous emission recorded from a window structure.

We investigated the microscopic mechanism underlying the double-state lasing behavior (simultaneous lasing at the ground state [GS] and excited state [ES]) in InAs/GaAs quantum dot (QD) laser diodes. The ES and GS lasing processes that contributed to double-state lasing were examined experimentally and theoretically. Experiments were conducted in which spontaneous emission from a window of a QD laser diode was examined under lasing conditions, and numerical simulations were performed using a coupled rate equation model of the QD microstates. The findings showed that, when carrier relaxation from the ES to the GS was sufficiently slow, double-state lasing occurred. Additionally, ES lasing was found to arise not from the QD group undergoing GS lasing, but rather from another QD group in which the states were lower in energy and outside of the homogeneous bandwidth.

Chlorpyrifos-induced changes in the antioxidants and fatty acid compositions of Chroococcus turgidus NTMS12.

UNLABELLED: This study investigated the effect of pesticide chlorpyrifos (CP) on a freshwater cyanobacterium Chroococcus turgidus NTMS12. The changes in chlorophyll-a, proline, superoxide dismutase (SOD), catalase (CAT) activities and fatty acid composition of the test organism were analysed. Organism was grown at 6, 9 and 12 mg l(-1) of CP, and based on the chlorophyll-a content, 6 mg l(-1) of CP was found to be the tolerable concentration. Hence, 6 mg l(-1) of CP was taken to evaluate the concentration of proline and activities of SOD and CAT at 48-h exposure. The changes in the fatty acid profile were analysed after 7 days of exposure. Upon pesticide exposure, increased concentration of proline and activities of SOD and CAT were found. Significant changes in fatty acid profile have also been observed. However, polyunsaturated fatty acid content was decreased in treated cultures when compared with the untreated control. Changes in biochemical activities indicate that cyanobacteria C. turgidus NTMS12 undergo adaptive changes against CP-induced oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: : Chlorpyrifos induces oxidative stress in Chroococcus turgidus NTMS12. A strong inference was made on increased activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and proline content and lowering the level of unsaturated fatty acids under the pesticide-exposed condition. These significant changes are the defence mechanisms against the oxidative stress. Thus, this organism holds great promise in resisting toxic pesticide.

Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post-exposure mouse models.

Identification of antigens that provide protective immunity via prophylactic and therapeutic vaccination against Mycobacterium tuberculosis is critical for the development of subunit vaccines for tuberculosis (TB). In this study, we performed a head-to-head comparison of seven well-known TB antigens delivered by DNA vaccine, and evaluated their respective immunogenicities and protective efficacies in pre- and post-exposure mouse models. All TB antigens were designed as a chimeric fusion with Flt3-L to enhance antigen-specific T-cell immunity upon vaccination. Prophylactic vaccination with the Flt3L (F)-Mtb32 DNA vaccine elicited significant protection in both the spleen and lungs against M. tuberculosis challenge, comparable to the Bacillus Calmette-Guerin vaccine. F-Ag85A and F-Mtb32 DNA vaccines, in combination with chemotherapy, reduced the bacterial burden to undetectable levels in the lungs of all mice infected with M. tuberculosis. These data collectively indicate that the F-Mtb32 DNA vaccine confers the most efficient protective immunity that suppresses bacterial growth in the active or latent status of M. tuberculosis.

Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early-onset Parkinson disease.

Exon rearrangements and point mutations are common in PARK2, the most important causative gene of autosomal recessive early-onset Parkinson disease (EOPD). However, gene dosage analysis alone cannot conclusively determine the phase of exon rearrangements and the incidence of molecularly confirmed parkin-type EOPD may be underestimated. To fully characterize the mutation spectrum, we performed sequencing and gene dosage analyses of SNCA, PARK2, PINK1, and PARK7 in 114 unrelated EOPD patients with onset age ≤40 years. Mutational phase of exon rearrangements was determined by reverse-transcriptase PCR (RT-PCR) and sequence analysis using a patient's own RNA. Fourteen different PARK2 mutations (3 point mutations plus 11 exon rearrangements) were identified in 18 patients, comprising 1 homozygote (0.9%), 13 compound heterozygotes (11.4%), 3 single heterozygotes (2.6%), and 1 with unknown phase (0.9%). By phase determination, more than 80% (5 of 6) of patients with apparently contiguous multi-exon deletions and 30% (5 of 18) of all PARK2 mutation carriers were additionally diagnosed as compound heterozygotes, respectively. This study shows that compound heterozygous mutations constituted a significant portion of patients with apparently contiguous multi-exon deletions. Phase determination is a prerequisite to molecular diagnosis for autosomal recessive EOPD, especially in subjects with PARK2 exon rearrangements.

Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the mutation status of PANK2 among Korean patients with pantothenate kinase-associated neurodegeneration (PKAN) and to document the outcome of pallidal deep brain stimulation (DBS). METHODS: Direct sequencing and deletion/duplication analysis of PANK2 were conducted in 12 patients (11 unrelated) with PKAN, diagnosed on the basis of extrapyramidal dysfunction and the 'eye-of-the-tiger sign' on brain magnetic resonance imaging (MRI). Pallidal DBS was conducted in four patients, and the outcomes were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: A PANK2 mutation was identified in both alleles in all patients. The most prevalent mutation was c.1319G>C (p.R440P) in 8/22 mutated alleles (36%). An intragenic deletion ranging from exons 2 to 4 was found in one allele (1/22, 4.5%) using deletion/duplication analysis. The outcome of pallidal DBS was favorable in two patients with atypical PKAN and moderate severity of dystonia. However, two patients with typical PKAN and relatively severe symptoms showed variable responses. CONCLUSIONS: The c.1319G>C (p.R440P) mutation appears to be a founder genotype among Korean patients with PKAN. Furthermore, this study provides additional data for the recent international effort to evaluate the efficacy of pallidal DBS in the treatment of patients with PKAN.

Bacille Calmette Guérin (BCG) can induce Kawasaki disease-like features in programmed death-1 (PD-1) gene knockout mice.

OBJECTIVES: Various genetic variants of inhibitory immune signals have been suspected as feasible causes of Kawasaki disease (KD). We investigated the associative role of programmed death-1 (PD-1) gene in the pathogenesis of KD by injecting bacilli Calmette Guérin (BCG) to PD-1 gene knockout (PD-1KO) mice. METHODS: In order to induce KD-like clinical manifestations in young PD-1KO mice, intradermal injection of the bacilli Calmette Guérin (BCG) was performed twice on the abdominal skin with a 4-week interval. For defining the role of BCG, heat shock protein (HSP) 65 was challenged. In addition, Staphylococcus aureus was adopted as a microorganism that does not contain HSP65 structure. One month after the second injection, heart, liver, and kidneys were removed and examined. RESULTS: PD-1KO mice showed KD-like features including prolonged fever for more than 5 days, erythematous swelling on soles, tail skin desquamation, and gallbladder (GB) hydrops. Inflammatory cell aggregation and intimal proliferation in at least more than one coronary artery was found in all PD-1KO mice whereas scanty coronary lesion was found in wild type (WT) mice. When the PD-1KO mice were injected twice with HSP65, coronary arterial lesions similar to those seen after BCG injection were observed. Inflammatory reactions in other organs including hepatic arteries, renal arteries, and biliary arteries were also observed in PD-1KO mice. CONCLUSIONS: Our data suggest that PD-1 gene may be one of the genetic predispositions of KD and antigens containing HSP65 structure could be a triggering factor of KD by our animal model of KD.

Satisfaction with mammography in the National Cancer Screening Programme participants of age 40s in Korea.

The aim of this study was to evaluate satisfaction with the National Cancer Screening Programme of mammography in Korea and to examine the association between subscales of satisfaction and general satisfaction. We conducted a cross-sectional telephone survey for women who had obtained a National Cancer Screening Programme mammographic screening at general hospitals between May and October 2008. The present study included 2005 women in their forties. We performed multivariate linear regression using dependent variable as general satisfaction and independent variables as subscales of satisfaction, such as pre-screening information transfer, staff interpersonal skills, physical surroundings and results reporting. Participants were stratified according to the result of their mammogram as negative or positive. Mean score of satisfaction was above 2.5 of 4 for all subscales. Women who received positive results were less satisfied with all of subscale factors. Staff interpersonal skills were the most important factor that contributed to general satisfaction. Future efforts such as staff training programme of communication/attitude skills, ensuring privacy and explanation of possible discomfort of the screening would be needed.

Protection of spermatogenesis against gamma ray-induced damage by granulocyte colony-stimulating factor in mice.

The radioprotective effects of granulocyte colony-stimulating factor (GCSF) were further investigated with respect to the testicular system. Recombinant human GCSF (100 µg kg(-1) body weight/day) was administrated to male C3H/HeN mice by subcutaneous injection for three consecutive days before pelvic irradiation (5 Gy) and histopathological parameters were assessed at 12 h and 21 days post-irradiation (pi). The GCSF protected the germ cells from radiation induced- apoptosis (P < 0.01 vs. irradiated group at 12 h pi). GCSF remarkably attenuated radiation-induced reduction in testis weight, seminiferous tubular diameter, seminiferous epithelial depth and sperm head count in the testes (P < 0.05 versus irradiated group at 21 days pi). Repopulation index and stem cell survival index of the seminiferous tubules were increased in the GCSF-treated group when compared with the radiation group (P < 0.01). The frequency of abnormal sperm in the GCSF group was lower than that in the irradiated group at 21 days pi (P < 0.01). The decrease in the sperm count and in sperm liability in the epididymis caused by irradiation was counteracted by GCSF. The present study suggests that GCSF protects from radiation-induced testicular dysfunction via an anti-apoptotic effect and recovery of spermatogenesis.

In vitro developmental potential of nuclear transfer embryos cloned with enucleation methods using pre-denuded bovine oocytes.

Enucleation of a recipient oocyte is an important essential process in the procedure of somatic cell nuclear transfer (SCNT). The present study investigated a method for the improvement of enucleation efficiency. Oocytes were denuded of cumulus cells before the completion of nuclear maturation (pre-denuded) after 12 h of culture at MI stage and subsequently cultured for additional 6 h until the completion of nuclear maturation and extrusion of the first polar body (PB1). The extrusion rate of PB1 was not significantly different in the pre-denuded oocyte group, compared with control oocyte group matured for 18 h. However, the number of oocytes showing the metaphase II (MII) located just underneath the PB1 was significantly higher (p<0.05) in the pre-denuded oocyte group than those in control oocyte group. To test the effect of pre-denuding on the enucleation rate and developmental potential of embryos to blastocyst stage, subsequent somatic cell nuclear transfer comparisons were made with three different methods of enucleation at MII stage using vital dyes (demicoline and Hoescht) or the PB1 (blind enucleation) to localize the chromosome plate. Enucleation rate of the oocytes with demicoline, Hoechst and pre-denuding enucleation groups were significantly higher (p<0.05) than those of blind enucleation groups. However, cleavage rate to two-cell stage and, developmental rate to blastocyst and hatched blastocyst stage, the mean numbers of total and ICM cells in the SCNT embryos with Hoechst enucleation groups were significantly decreased (p<0.05), compared to those of blind, demicoline and pre-denuding enucleation groups. Moreover, the level of telomerase activity was also significantly (p<0.05) decreased in SCNT blastocysts of Hoechst enucleation group, compared to those of blind, demicoline and pre-denuding enucleation groups. Taken together, pre-denuding enucleation group using pre-denuded oocytes was a useful and simple enucleation method for bovine SCNT embryos.

AMP-activated protein kinase contributes to ROS-mediated p53 activation in cisplatin-induced nephrotoxicity.

OBJECTIVE: Cisplatin is a widely used anticancer drug that provokes various side effects. Nephrotoxicity is one of the well-known major side effects in the chemotherapeutic use of cisplatin. Reactive oxygen species (ROS) and p53 play important roles in cisplatin-induced nephrotoxicity. AMP-activated protein kinase (AMPK) is known to be sensitively activated by ROS and can directly activate p53. The present study investigated the role of AMPK on cisplatin-induced apoptosis in rat renal epithelial NRK-52E cells. MATERIALS AND METHODS: NRK-52E cells were treated with cisplatin in the absence or presence of specific ROS scavenger and AMPK inhibitor for indicated times under the serum-free condition. The expression and phosphorylation levels of proteins were evaluated by Western blot and densitometry analysis. RESULTS: Cisplatin induced apoptotic cell death through ROS-mediated p53 activation, which is associated with AMPK activation. AMPK inhibitor suppressed cisplatin-induced p53 activation, as well as AMPK activation. Interestingly, ROS scavenger also diminished cisplatin-induced p53 activation and AMPK activation. Furthermore, cisplatin induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which attenuated p53 activation, but did not affect the expression levels of total p53, cleaved caspase-3 and PARP. Meanwhile, inhibition of AMPK induced premature phosphorylation of eIF2α in cisplatin-treated cells. CONCLUSIONS: Taken together, these suggest that AMPK may be required for activation of p53 by oxidative stress in cisplatin-induced nephrotoxicity. Moreover, eIF2α phosphorylation may interrupt the AMPK-activated p53 in NRK-52E cells exposed to cisplatin, but does not critically affect cisplatin-induced nephrotoxicity because AMPK activation can be disrupted eIF2α phosphorylation.

Cigarette smoke extraxt influences intracellular calcium concentration in A549 cells.

Cigarette smoking is a major risk factor for pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and cancer. Cigarette smoke is reported to contain over 4,000 chemical compounds. Therefore, it needs to study the effects of cigarette smoke extract (CSE) administration on intracellular calcium concentration. In this study, we investigated how CSE influences intracellular calcium concentration in human lung adenocarcinoma A549 cells. The CSE concentrations used (0.4, 2, 3%) did not influence cell viability. However, at these CSE concentrations, calcium influx transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential vanilloid 6 (TRPV6) proteins significantly increased, whereas calcium efflux sodium-calcium exchanger (NCX1) and plasma membrane Ca2+ ATPase (PMCA1) proteins significantly decreased from those of the control cells. The 3% CSE treatment produced an intracellular calcium concentration higher than that of the control treatment through methods of co-transfection of pGP-CMV-GCaMP6f/CMV-R-GECO1.2 and Rhod-4 Assay. CSE induced concentration-dependent increments in hypoxia-inducible factor (HIF)-1α and HIF-2α protein levels. Moreover, phosphorylation of ERK and Akt was induced by CSE treatment. Also, mitochondrial marker B-cell lymphoma 2 (Bcl-2) protein level decreased and Bcl-2-associated X (Bax) protein level increased following CSE treatment. Also, endoplasmic reticulum (ER) stress markers BiP, CHOP, p-SAPK, and p-eIF2α levels were increased by CSE treatment. These results suggest that CSE may increase the concentration of intracellular calcium, thus increasing mitochondrial and ER stress.

Survivors from beta-fluoroethyl acetate poisoning show a selective cerebellar syndrome.

UNLABELLED: AIM/ BACKGROUND: beta-Fluoroethyl acetate (FEA), a derivative of sodium fluoroacetate (Compound 1080, FA), is one of the high-potency toxic chemicals, and it has been used against rats and wild animals. Human casualties from FA or FEA poisoning, accidental or suicidal, have been reported. Survivors of the poisoning are extremely rare. The objective of this study is to present survivors of FEA poisoning. METHOD: Data on the survivors were collected at the Department of Neurology over the past 20 years. Reviews of the medical record and brain imaging were performed. RESULTS: A total of 10 survivors of FEA poisoning were found. All of the cases were suicide attempts. The amount of FEA ingested varied from 600 to 1800 mg with a mean of 1200 mg, which is close to the lethal dose of FEA. Immediately after ingestion, all of the patients had an altered mental status. On awakening, all of the patients had severe cerebellar dysfunction, such as ataxic gait, dysarthria and intention tremor. The cerebellar dysfunction usually improved gradually over the years after the event, but this improvement eventually plateaued, resulting in residual and persistent cerebellar dysfunction. Serial imaging showed swelling in the posterior fossa during the acute phase and progressive cerebellar atrophy on follow-up. CONCLUSION: In summary, FEA poisoning causes a selective cerebellar syndrome in its survivors. The pathomechanism underlying the selective cerebellar toxicity of FEA remains to be elucidated. The selective involvement of the cerebellum might provide a useful model for cerebellar degeneration.

Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis.

A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and pharmacokinetic characteristics of tuberculosis therapeutics. While membrane transporters play important roles in drug disposition and physiological homeostasis, their expressional changes and contribution have never been analysed in a tuberculosis animal model. The mRNA expression level of 20 Abc family transporters and 32 Slc family transporters in tuberculosis-infected mice were compared with those in naïve uninfected mice using real-time polymerase chain reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic expression changes of families of both Abc transporters and Slc transporters at 4 and 8 weeks, as observed in the livers, kidneys, and intestines of test mice--and in a different mode, in the lungs and spleens as well. These changes were dependent on the tuberculosis progression with the tissue-specific manner, that is, in the lungs, the number of transporters of which the expression level changed due to M. tuberculosis infection had increased, and the magnitude of change also greater at 8 weeks, while in the spleen, the transcription of most transporters except Mrps had not changed or had recovered back to the same level of naïve transcription at 8 weeks. Understanding the expression changes of transporters will assist in setting up rational preclinical dosing plans through the ability to predict the pharmacokinetics of new anti-tuberculosis chemotherapeutics and, furthermore, will assist in the design of safer and more efficient drug regimens.