Fonsecaea pedrosoi‐induced Th17‐cell differentiation in mice is fostered by Dectin‐2 and suppressed by Mincle recognition

Chromoblastomycosis is a chronic skin infection caused by the pigmented saprophytic mould Fonsecaea pedrosoi. Chronicity of infection can be broken by a coordinated innate recognition of the spores by pattern recognition receptors. While Mincle signaling via the Syk/Card9 pathway is required for fungal recognition by host cells, it is not sufficient for host control. Exogenously applied TLR agonists are necessary to promote the induction of proinflammatory cytokines and clearance of infection in vivo. Here, we investigated whether costimulation by TLR agonists fosters the development of adaptive immune responses, by examining the development of fungus‐specific T cells. Subcutaneous infection of mice with F. pedrosoi spores induced the activation, expansion, and differentiation of Ag‐specific CD4⁺ T cells but TLR costimulation did not further augment these T‐cell responses. The Dectin‐2/FcRγ/Card9 signaling pathway promoted the differentiation of fungus‐specific CD4⁺ T cells into Th17 cells, whereas Mincle inhibited the development of this T‐helper subset in infected mice. These results indicate differential roles for Dectin‐2 and Mincle in the generation of adaptive immune responses to F. pedrosoi infection.     

Participatory capacity building in occupational disease surveillance among primary care unit (pcu) health personnel

This study aimed to demonstrate participatory capacity building regarding occupational disease surveillance (ODS) could enable the Primary Care Unit (PCU) health personnel provide satisfactory occupational health services for workers in the community. A needs assessment was carried out to identify gaps in PCU health personnel skills and knowledge so these areas could be strengthened. An ODS training program was developed. Fifty-nine health personnel participated in a 5 day workshop and received instructions regarding a wide range of occupational diseases, surveillance methods, prevention measures, and Ministry of Public Health (MOPH) surveillance systems. Participants self reported positive changes in knowledge and skills, as well as a high level of satisfaction with the workshop. However, many participants noted barriers to consistently implementing reporting procedures.     

The incidence,risk factor,and time to develop rheumatologic diseases after isolated inflammatory eye diseases: a 12-year cohort study

Clinical Rheumatology - The incidence, risk factors, and time to diagnosis of rheumatologic disease (RD) in patients with isolated inflammatory eye diseases (IED) were investigated. A 12-year...     

Development of an Anti-Elicitin Antibody-Based Immunohistochemical Assay for Diagnosis of Pythiosis

Pythiosis is an emerging and life-threatening infectious disease of humans and animals living in tropical and subtropical countries and is caused by the fungus-like organism Pythium insidiosum. Antifungals are ineffective against this pathogen. Most patients undergo surgical removal of the infected organ, and many die from advanced infections. Early and accurate diagnosis leads to prompt management and promotes better prognosis for affected patients. Immunohistochemical assays (IHCs) have been developed using rabbit antibodies raised against P. insidiosum crude extract, i.e., culture filtrate antigen (CFA), for the histodiagnosis of pythiosis, but cross-reactivity with pathogenic fungi compromises the diagnostic performance of the IHC. Therefore, there is a need to improve detection specificity. Recently, the elicitin protein, ELI025, was identified in P. insidiosum, but it was not identified in other human pathogens, including true fungi. The ELI025-encoding gene was successfully cloned and expressed as a recombinant protein in Escherichia coli. This study aims to develop a new IHC using the rabbit anti-ELI025 antibody (anti-ELI) and to compare its performance with the previously reported anti-CFA-based IHC. Thirty-eight P. insidiosum histological sections stained positive by anti-ELI-based and anti-CFA-based IHCs indicating 100% detection sensitivity for the two assays. The anti-ELI antibody stained negative for all 49 negative-control sections indicating 100% detection specificity. In contrast, the anti-CFA antibody stained positive for one of the 49 negative controls (a slide prepared from Fusarium-infected tissue) indicating 98% detection specificity. In conclusion, the anti-ELI based IHC is sensitive and specific for the histodiagnosis of pythiosis and is an improvement over the anti-CFA-based assay.     

Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area

AIM To determine the role of screening and surveillance of hepatocellular carcinoma(HCC) in treatment-na?ve chronic hepatitis B(CHB) patients. METHODS We recruited 2293 CHB patients(both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography(AUS) and serum alpha-fetoprotein(AFP) assay every 6 mo. The diagnosis,staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.RESULTS Among 2293 treatment-na?ve CHB patients,seven cases had HCC at initial screening,giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis,all of which were Child-Pugh class A. With a median follow-up time of 42(range,3-48) mo,10 additional cases were diagnosed with HCC,resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage(Stage 0,A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation,with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis,increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 mg/L at diagnosis were observed in only 7/17 patients,most with a tumor size 5 cm. For HCC screening and surveillance,AUS had a sensitivity and specificity of 94% and 82%,respectively,whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 mg/L were 41% and 98%,respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION Implementation of active screening and surveillance using AUS to detect early-stage HCC in na?ve CHB patients aged ≥ 40 years in an endemic area is of benefit.     

Reliability and validity of the Exercise Self-Regulatory Efficacy Scale for individuals with chronic obstructive pulmonary disease

BACKGROUND: Exercise has important benefits for individuals with chronic obstructive pulmonary disease (COPD). However, to sustain long-term benefits of exercise, adherence is needed. Adherence requires self-regulation. No scale is available to measure exercise self-regulation in individuals with COPD. OBJECTIVES: We developed and tested the reliability and validity of an "Exercise Self-Regulatory Efficacy Scale (Ex-SRES)" for individuals with COPD. METHODS: A convenience sample of 109 subjects with COPD was recruited. Cronbach's alpha was used to assess the internal consistency reliability of the Ex-SRES. Subjects' exercise behaviors and health status were used to assess the validity of the Ex-SRES. RESULTS: The Ex-SRES demonstrated evidence of reliability (Cronbach's alpha .917) and validity (correlation with minutes of exercise per week [r = .41; P < .0001] and health status [r = .37; P < .0001]). CONCLUSION: The Ex-SRES is a short (16-items) and easy to use questionnaire that may be valuable for assessing patients in clinical settings, as well as for future research studies in behaviors related to exercise.     

Temporal patterns and forecast of dengue infection in Northeastern Thailand

This study aimed to determine temporal patterns and develop a forecasting model for dengue incidence in northeastern Thailand. Reported cases were obtained from the Thailand national surveillance system. The temporal patterns were displayed by plotting monthly rates, the seasonal-trend decomposition procedure based on loess (STL) was performed using R 2.2.1 software, and the trend was assessed using Poisson regression. The forecasting model for dengue incidence was performed in R 2.2.1 and Intercooled Stata 9.2 using the seasonal Autoregressive Integrated Moving Average (ARIMA) model. The model was evaluated by comparing predicted versus actual rates of dengue for 1996 to 2005 and used to forecast monthly rates during January to December 2006. The results reveal that epidemics occurred every two years, with approximately three years per epidemic, and that the next epidemic will take place in 2006 to 2008. It was found that if a month increased, the rate ratio for dengue infection decreased by a factor 0.9919 for overall region and 0.9776 to 0.9984 for individual provinces. The amplitude of the peak, which was evident in June or July, was 11.32 to 88.08 times greater than the rest of the year. The seasonal ARIMA (2, 1, 0) (0, 1, 1)12 model was model with the best fit for regionwide data of total dengue incidence whereas the models with the best fit varied by province. The forecasted regional monthly rates during January to December 2006 should range from 0.27 to 17.89 per 100,000 population. The peak for 2006 should be much higher than the peak for 2005. The highest peaks in 2006 should be in Loei, Buri Ram, Surin, Nakhon Phanom, and Ubon Ratchathani Provinces.     

Risk factors for hypertension among rural Thais

A community based case-control study was conducted to determine the risk factors for hypertension among a rural population in Nakhon Ratchasima Province, Thailand. Seventy-two subjects diagnosed with hypertension (BP > or = 140/ 90 mmHg) were randomly selected. Seventy-two controls with normal blood pressure (BP < 120-80 mmHg) were also randomly selected from the same or nearest house to the subjects. Data collection was carried out in February 2010 using a structured questionnaire. Statistics used were percentages, arithmetic means, standard deviations, odds ratios (OR), adjusted odds ratios (aOR), confidence interval (95% CI) for the OR and logistic regression. After adjusting for the effect of other variables in the study, significant risk factors for hypertension were age > or = 50 years old (aOR 5.67, 95% CI 1.98-16.24), education level of primary school or lower (aOR 8.09, 95% CI 2.17-30.20), occupation of farmer or unemployed (aOR 2.88, 95% CI 1.14-7.30), body mass index 230.0 kg/m2 (aOR 7.43, 95% CI 1.68-32.87), presence of high cholesterol (aOR 11.26, 95% CI 2.55-49.75), and having mild stress to high stress (aOR 5.33, 95% CI 1.45-19.61). Forty percent of the variation in the presence of hypertension is explained by the developed model for the above risk factors. These findings are useful for health education and health promotion program development in order to prevent hypertension among rural Thai populations.     

HNF1A mutation in a Thai patient with maturity-onset diabetes of the young: A case report

BACKGROUND Maturity-onset diabetes of the young(MODY) is the most common form of monogenic diabetes. The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year. MODY 3 is caused by mutation of hepatocyte nuclear factor(HNF) 1 A genes and is the most common MODY subtype. Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea. In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued.CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old. The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance. Sanger sequencing of proband's DNA identified mutation of HNF1 A at codon 203 which changed amino acid from arginine to cysteine(R203 C). This mutation was carried only by family members who have diabetes. The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide(20 mg/d). Insulin therapy was successfully discontinued.CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient. Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.     

The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis

C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRγ as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen Blastomyces dermatitidis. MCL^−/− mice showed impaired vaccine resistance against B. dermatitidis infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes in vitro. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with B. dermatitidis.