Objective　To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism,and whether there is any relationship between IL-1β and RA motif gene.Methods　IL-1 gene polymorphisms were analyzed in 65 RA patients who satisfied ACR criteria and 60 controls.The 2 polymorphisms in each gene for IL-1α－889 and IL-1β＋3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP.Fisher′s test and analysis of variance were used to analyze the data.Results　There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and controls.The β 2/2 genotype of IL-1β was more common in female RA patients compared with controls.A higher carriage rate of IL-1β 1 and low carriage rate of IL-1β 2 occurred in male RA patients.An increased IL-1β 2 carriage was associated with active rheumatoid disease as indicated by a higher CRP,ESR and pain score and a higher BMD,lower vit-D3 and Udpd/Crea level.A higher frequency of IL-1α 1 was associated with a lower CRP value and higher RF and SJC.A higher carriage rate of IL-1α 2 was associated with a higher ESR,HAQ score and vit-D3，but conversely a lower SJC,RF and BMD.The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time was not effective to clinical and laboratory parameters of RA.Conclusion　It is demonstrated that polymorphisms of the IL-1 gene may influence the occurrence of RA.Carriage of IL-1β 2 polymorphisms is associated with more active disease and higher BMD IN RA.The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time does not contribute to disease activity.

BACKGROUND: The Western Australian Family Study of Schizophrenia (WAFSS) has conducted genetic epidemiology studies of schizophrenia in Australia for two decades. Recently the WAFSS practices were adopted at the National Centre for for Mental Health in Mongolia, with a view tocollecting comparable data. Like the cited projects (supra), we are cognizant of the dangers of multi site data collection. We replicate common practices, such as training manuals and common site training and refreshment (CCRN WHO training centre). However in international (possibly multilingual) collection and pooling, identical assessment is difficult, it is impossible to replicate endophenotype instructions verbatim (Calkins 2007), and identical recording equipment may not be available indisparate sites. At the very least the data must be compared separately, with the option of weighting,before the pooling for genetic analysis. The use of endophenotypes (Gottesman& Gould) is well established in schizophrenia research for genetic analysis () as well as in more general neuroscience biomarker approaches. The use of electrophysiological markers, and particularly Event-Related Potentials (ERPs) is a well developedaspect of this approach (BraffDL, 2007, TuretskyBI, 2009). Electrophysiological endophenotypes include (inter alia) the Mismatch Negativity (MMN), P50 suppression ratio (P50), auditory oddball P300 (P300), and Antisaccade (AS) tasks. In this study, we seek to follow the multi centre quality assurance examples for pooled data on a smallerscale. This report details the validation of compatibility between the Western Australian Family Study of Schizophrenia (WAFSS) dataset (Perth, Australia), and a pilot dataset from the National Centre for Mental Health (NCMH) in Ulaanbaatar, Mongolia. The working hypothesis is that the psychiatric and endophenotype profiles in the two datasets are sufficiently similar to allow data ompatibility for genetic analysis.METHODS: The Mongolian version of the DIP was developed as part of a joint genetic investigation of schizophrenia between the Centre for Clinical Research in europsychiatry (CCRN) in Perth Western Australia, and the National Center of Mental Health (NCMH) in Ulaanbaatar, Mongolia.The DIP is a semi-structured interview for psychosis for use in epidemiological and clinical settings (CastleD, 2006). It is designed to provide a diagnosis, as well as to assess symptom profiles (present state, past year and lifetime), social functioning, disablement, and service utilisation. It was developed specifically for the National Mental Health Survey – Low Prevalence (Psychotic) Disorders Study(Jablensky et al, 1999, 2000), and has been translated to Italian (RossiA, 2010), Norwegion (SkorvenCS, 2010), and to Mongolian in 2012. The process started with the translation of the original English language version (Castle et al., 2006) by an experienced bilingual psychiatrist (GE) from the NCMH whose native language was Mongolian. Layout and formatting of the document were preserved. It was then back-translated by a non medical,tertiary educated professional, whose native language is Mongolian, but is now resident in Perth. The back-translation was reviewed by an original author (AJ) and experienced practitioners (GP). Grammatical and syntactical discrepancies were resolved directly with the original translator. Event Related Potentials To replicate the WAFSS ERP approach at NCMH, a new portable ERP recording system was deployed. This decision was based on several considerations: a) the WAFSS system could not be taken out of service; b) an identical system could not be replicated due to the age of the components; c) an equivalent system would be too substantial for easy, cost effective transport; d) the system was expected to be used in multiple sites in Mongolia; e) the same system was expected to be used in other Australian projects.The Portable ERP system uses NuAmps, with a hardware selected reference at the FPz location. While the ear references A1 and A2 were recorded, the mathematically re-referenced data is not the same as directly linking ears. (Citation ****). Instead the data was analysed as recorded, with cognizance traces (instead of 20) could not be used. This marks a variation from the original WAFSS processing. Instead of artifact rejection on any trace, only the relevant trace (Fz, Cz, Pz) was used for each ERP (MMN, P50, P300). Endophenotypes The ERP endophenotypes are clearly continous variables, and analysed with general linear modelling. Two tailed significance testing was used for between cohort comparisons, since there is no a priori indication which cohort would have the higher values. Single tailed testing was used in comparing Proband (Pb) and Control (Ctl) groups within the same cohort, as thedirection of any difference is well established.RESULTS: DIP The structure of the diagnostic module (DIP-DM) follows the Operational Criteria for Psychosis, OPCRIT, version 3.31 (McGuffin et al., 1991; Williams et al., 1996) 90-item checklist. It can be used to generate diagnoses according to the criteria of ICD-10 (World Health Organization, 1993); DSM-IV (American Psychiatric Association, 1994); the Research Diagnostic Criteria (Spitzer et al., 1978), and others. The summary of diagnoses (ICD-10 and DSM-IV) generated for each cohort are shown in Figure 1. Diagnostic distribution (%) of 30 interviewed cases from NCMH and 201 cases from the WAFSS cohorts, according to the DIP diagnostic algorithm, by diagnostic classification system. To facilitate omparisons between different criteria systems, Castle (2006) escribes aggregated diagnostic classification descriptors (with reservations) that are used in Figure 1. Greater detail of the DIP responses that support these descriptors is shown for similiarly aggregated questions in Figure 2. aMicrovolts for MMNAmp and P300Amp, numeric forothers.bFor MMN, P50, and AS, but not P300, the raw mean (notabsolute value) for the Pb and Fm groups are higher thanthat of the Ctl group. cEqual variances not assumed.Endophenotype values were each significantly “worse” inthe proband group of the NCMH cohort, for MMN (t=1.65;p=0.05), P300 (t=-2.02; p=0.02) and AS (t=2.12; p=0.02).The comparable values from the WAFSS cohort showed thesame behaviour for MMN (t=4.52; p<0.01), P300 (t=-3.35;p<0.01) and AS (t=3.93; p<0.01). The P50 endophenotypedid not show a significant difference between clinical groups in either NCMH (t=0.20) or WAFSS (t=1.12) cohort. DISCUSSION: This comparison has shown that there is not a significant difference (α= 0.05) between the NCMH and WAFSSpopulations (patient and control). This outcome is deemed sufficient to allow pooled analysis of genetic and electrophysiological data in future studies. It is acknowledged that the outcome does not show that the two populations are the same. Questions of international comparison (McGrathJJ, 2006) in incidence and prevalence, of mental illness and particularly of schizophrenia are eschewed. These were not the purpose of the study. Our experience from this study, as distinct from analysis, is that situational variation in equipment, protocol and recruitment likely outweigh any cultural differencesin epidemiology. The absolute value of the lectrophysiologicalendophenotypes was different between the two sites, butthe relative values were the same. The control group showed“better” responses than the patient group, with similareffect size. Moreover, the patient clinical profile was also slightly different. The incidence of neuroleptic medication was a substantial uncontrolled factor. The question becomes how to deal with these differences.In combining population groups, the data can be discarded,equalized, or transformed. Describe each. We seek to standardize comparisons between populations by transforming data by scaling prior to genetic analysis.Absolute value The raw amplitude data for both ERP eatures (MMN, P300) is significantly lower from the Mongolian cohort in both Patient and Control groups. Endophenotype characteristics.ScalingWhile the difference in absolute values precludes directlycombining data from different cohorts, the consistentendophenotype characteristics allows one possiblemethod to further genetic investigation of continuousendophenotype variables. The results are expected toderive from a combination of technical, situational, clinicaland endophenotype factors. Each of these factors could befurther investigated individually. However, if a combinedendophenotype analysis is even theoretically acceptable,then the endophenotypebehaviour in different cohorts hasto be defined as identical, and the standardized measuresfrom equivalent Control groups must be equal. If the WAFSScontrol group is considered as the standard in this study, then the scaling factors for the NCMH cohort are 13.5 (MMN), 1.0 (P50), 2.5 (P300) and 0.6 (AS).SUMMARY: The consistency in endophenotypebehaviour betweencohorts legitimizes the application of the genetic approachin Mongolia. DNA extraction and analysis for this cohort iscontinuing and, although for smaller numbers, preliminaryresults can be compared with the Australian cohort.

Background: Antiretroviral treatment (ART) can decreased the incidence of HIV dementia, but milder cognitive impairment may not resolve when patients receive ART. In Indonesia, cognitive screening of HIV patients is not routinely performed before starting ART. Here we assess cognitive impairment in ART- naïve HIV patients beginning treatment in Jakarta. Methods: This is a cross sectional study with inclusion criteria: HIV positive, ART naïve, CD4 T-cells below 200 cells/uL, Karnofsky Performance Score (KPS) above 70. HIV-associated neurocognitive disorder (HAND) was defined by performance at least 1 Standard Deviation (SD) below the mean of demographically adjusted normative scores in at least two cognitive areas. Results: We studied 82 subjects with median (range) age 31 (19-48) years. Fifty six subjects (68%) were males. HAND was found in 42 subjects (51%). Eight subjects (19%) had impairment in 4 domains, 15 subjects (36%) in 3 and 19 (45%) in 2. The most common domain affected was memory (63%). Conclusion: Our results show the prevalence of HAND is high among HIV naïve patients in Jakarta. This establishes the need for screening of cognitive function before initiating ART.
AIDS Dementia Complex ; HIV

Despite international and national guidelines, poor asthma control remains an issue. Asthma exacerbations are costly to both the individual, and the healthcare provider. Improvements in our understanding of the therapeutic benefit of asthma therapies suggest that, in general, while long-acting bronchodilator therapy improves asthma symptoms, the anti-inflammatory activity of inhaled corticosteroids reduces acute asthma exacerbations. Studies have explored factors which could be predictive of exacerbations. A history of previous exacerbations, poor asthma control, poor inhaler technique, a history of lower respiratory tract infections, poor adherence to medication, the presence of allergic rhinitis, gastro-oesophageal reflux disease, psychological dysfunction, smoking and obesity have all been implicated as having a predictive role in the future risk of asthma exacerbation. Here we review the current literature and discuss this in the context of primary care management of asthma.
Adrenal Cortex Hormones ; Asthma ; Disease Progression ; Gastroesophageal Reflux ; Health Personnel ; Humans ; Nebulizers and Vaporizers ; Obesity ; Primary Health Care ; Respiratory Tract Infections ; Rhinitis ; Rhinitis, Allergic, Perennial ; Smoke ; Smoking

Despite advances in surgical and clinical management, metastatic disease, notably to the lungs, liver, bone, and brain is the most common cause of death from breast cancer. Two basic principles govern the process of metastasis. First, that the tumors are heterogeneous populations of cells, and second, that the process of metastasis is a sequence of events that depends on tumor cell properties and interactions with the microenvironment at the sites of metastasis. In theory, inhibitors targeted at any of the steps of metastasis have the potential to inhibit metastatic progression. In vitro assays cannot simulate accurately the complex process of metastasis, and the use of appropriate animal model is necessary to model the process, and to test the impact of targeted inhibitors on the growth and development of breast cancer metastasis. Animal models for growth and metastasis of rodent and human breast cancer cells have been developed, including models that target the metastatic growth in key organs such as the bone and brain.
Brain ; Breast Neoplasms* ; Breast* ; Cause of Death ; Growth and Development ; Humans ; Liver ; Lung ; Models, Animal ; Neoplasm Metastasis ; Rodentia

PURPOSE: Smoking has detrimental effects on asthma symptom control and response to treatment and is prevalent among asthma patients in South Korea. The aim of this study is to determine the prevalence of smoking among asthma patients in South Korea and to compare the medication regimens of asthma patients who do and do not smoke. METHODS: A cross-sectional survey was conducted from August 2010 to January 2011. Participating physicians (N=25) recorded demographic and clinical data on all asthma patients presenting during the study period (N=2,032), and then recruited a subset of patients (N=500) for the survey such that half were self-reported current smokers. Recruited patients were between the ages of 18 and 60. RESULTS: Among presenting asthma patients, 17.3% were current smokers, 19.2% were former smokers, and 63.5% had never smoked. Within the analyzable study population (N=471), 212 patients reported smoking currently, 79 smoking formerly, and 180 never smoking. Among current and former smokers, 79.7% and 81.0%, respectively, were men, while women represented 80.5% of patients who had never smoked. Agreement was strong between physician-determined smoking status and patient-reported smoking status (kappa=0.82; P<0.001). However, asthma medication regimens examined according to GINA treatment steps did not differ by smoking status. In addition, mean quality of life scores and level of asthma control did not differ by smoking status. CONCLUSIONS: In South Korea, physicians are well aware of the smoking status of their patients. However, smoking status did not affect the prescribed medication regimens of this population of asthma patients.
Asthma* ; Cross-Sectional Studies ; Female ; Humans ; Korea ; Male ; Prevalence ; Quality of Life ; Seoul ; Smoke* ; Smoking*

The occupations involved in food animal production have long been recognized to carry significant health risks for workers, with special attention to injuries. However, risk of pathogen exposure in these occupations has been less extensively considered. Pathogens are a food safety issue and are known to be present throughout the food animal production chain. Workers employed at farms and slaughterhouses are at risk of pathogen exposure and bacterial infections. The industrialization of animal farming and the use of antimicrobials in animal feed to promote growth have increased the development of antimicrobial resistance. The changed nature of these pathogens exposes workers in this industry to new strains, thus modifying the risks and health consequences for these workers. These risks are not yet recognized by any work-related health and safety agency in the world.
Abattoirs ; Farmers ; Animal Feed ; Animals ; Bacterial Infections ; Campylobacter jejuni ; Drug Resistance, Microbial ; Food Safety ; Methicillin-Resistant Staphylococcus aureus ; Occupational Diseases ; Occupations

Cigarette smoking among asthma patients is associated with worsening symptoms and accelerated decline in lung function. Smoking asthma is also characterized by increased levels of neutrophils and macrophages, and greater small airway remodeling, resulting in increased airflow obstruction and impaired response to corticosteroid therapy. As a result, smokers are typically excluded from asthma randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used by asthma RCTs limits the extent to which their findings can be extrapolated to the routine care asthma population and to reflect the likely effectiveness of therapies in subgroups of particular clinical interest, such as smoking asthmatics. The inclusion of smokers in observational asthma studies and pragmatic trials in asthma provides a way of assessing the relative effectiveness of different treatment options for the management of this interesting clinical subgroup. Exploratory studies of possible treatment options for smoking asthma suggest potential utility in: prescribing higher-dose ICS; targeting the small airways of the lungs with extra-fine particle ICS formulations; targeting leukotreines, and possibly also combinations of these options. However, further studies are required. With the paucity of RCT data available, complementary streams of evidence (those from RCTs, pragmatic trials and observational studies) need to be combined to help guide judicious prescribing decisions in smokers with asthma.
Airway Remodeling ; Asthma* ; Humans ; Lung ; Macrophages ; Neutrophils ; Pragmatic Clinical Trials as Topic ; Rivers ; Smoke* ; Smoking

OBJECTIVEOur previous study shows that PURNE2 mRNA plays an important role in the differential diagnosis of leiomyosarcoma and gastrointestinal stromal tumor (GIST). Non-coding RNA PCA3 locates in the intron of PRUNE2 and may play a role in PRUNE2 expression. The aim of this study was to explore the expression of PCA3 mRNA and PRUNE2 in leiomyosarcoma and their correlation.

METHODSThe expression of PRUNE2 mRNA was analyzed by agilent gene expression microarray CHIP in 31 leiomyosarcomas and 37 GISTs, and the correlation of the PRUNE2 expression and prognosis of leiomyosarcoma was predicted. Real-Time PCR assay was used to detect the mRNA levels of PCA3 and PRUNE2 in 13 leiomyosarcomas and to investigate their correlation. Seven prostate cancer tissues were used as control of PCA3.

RESULTSThe level of PRUNE2 mRNA expression was significantly higher in the 31 leiomyosarcomas than that in the 37 GISTs, and the level of PRUNE2 mRNA expression was correlated with survival of the leiomyosarcoma patients. Compared with prostate cancer, the non-coding RNA PCA3 expression level was significantly lower in leiomyosarcoma, and it had no correlation with the prognosis of leiomyosarcoma. Most importantly, the PRUNE2 and PCA3 mRNA expressions were both upregulated in leiomyosarcoma and showed a significant positive correlation.

CONCLUSIONSOur findings demonstrate for the first time that PRUNE2 expression is correlated with the survival of leiomyosarcoma patients. Furthermore, non-coding RNA PCA3, which locates in the intron of PRUNE2, has a significant positive correlation with PRUNE2 and may play an important role in the pathogenesis of leiomyosarcoma.

Antigens, Neoplasm ; genetics ; metabolism ; Female ; Gastrointestinal Neoplasms ; genetics ; metabolism ; Gastrointestinal Stromal Tumors ; genetics ; metabolism ; Humans ; Leiomyosarcoma ; genetics ; metabolism ; Male ; Neoplasm Proteins ; genetics ; metabolism ; Prostatic Neoplasms ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Untranslated ; metabolism ; Retroperitoneal Neoplasms ; genetics ; metabolism ; Survival Rate ; Uterine Neoplasms ; genetics ; metabolism

OBJECTIVETo determine whether interleukin-1 alpha and 1 beta gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1 beta and rheumatoid arthritis (RA) motif gene.

METHODSIL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1 alpha-889 and IL-1 beta + 3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1 beta 2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.

RESULTSThere was no significant difference in the frequency and carriage rate of IL-1 alpha polymorphisms between RA patients and the controls. The beta 2/2 genotype of IL-1 beta was more common in female RA patients compared with controls (P = 0.001). A lower carriage rate of IL-1 beta 2 occurred in male RA patients (P = 0.001). A higher carriage rate of IL-1 alpha 2 is associated with a higher ESR (P = 0.008), HAQ score (P = 0.03), and vit-D3 (P < 0.001), but conversely a lower SJC (p = 0.002), a lower RF (P = 0.002) and a lower BMD at the lumbar spine (P = 0.001). A higher frequency of IL-1 alpha 1 is associated with a lower CRP value (P = 0.009). An increased IL-1 beta 2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P < 0.001), ESR (P < 0.001) and pain score (P = 0.001) and a higher BMD at the lumbar spine (P = 0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1 beta allele 2 at same time did not contribute to disease activity.

CONCLUSIONPolymorphisms of the IL-beta gene may affect the RA occurrence. Carriage of IL-1 beta 2 polymorphisms is associated with more active disease in RA and the presence of both the IL-1 alpha 2 and the IL-1 beta 1 allele in RA influences bone resorption.

Alleles ; Arthritis, Rheumatoid ; genetics ; metabolism ; Bone Density ; Female ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Interleukin-1 ; genetics ; Male ; Polymorphism, Genetic