Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China

<p>Abstract</p> <p>Background</p> <p>Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitocondrial autoantibodies (AMA) which has an essential role also for diagnosis. In addition, also some anti-nuclear antibodies (ANA) have been shown to be highly specific PBC. The purpose of this study was to assess the prevalence of PBC among the adults referring hospital for annual health check-up in Southern China by screening sera for PBC-specific autoantibodies.</p> <p>Methods</p> <p>AMA and ANA were screened in 8,126 adults (mean age 44 ± 15 years, 48% females) by indirect immunofluorenscence (IIF). Positive sera were tested by ELISA/immunoblotting for AMA-M2, anti-sp100 and anti-gp210. A diagnosis of PBC was re-assessed six months after the initial testing.</p> <p>Results</p> <p>Out of 8,126 individuals 35 were positive for AMA and 79 positive for ANA. Nineteen, 4, and 3 of the subjects positive for AMA and/or ANA showed reactivity for AMA-M2, anti-sp100 or gp210, respectively, further tested with ELISA/immunoblotting. Fourteen in the 39 individuals positive for AMA at IIF, AMA-M2, anti-gp210, or anti-sp100 had abnormal cholestatic liver functional indices. One definite and 3 probable PBC diagnosis could be made in 4 cases including 3 females and 1 male after half a year.</p> <p>Conclusions</p> <p>We found a point prevalence rate of PBC among Southern Chinese adults attending for yearly health check-up of 492 cases per million (95% CI, 128 to 1,093) and 1,558 cases per million (95% CI, 294 to 3,815) for women over 40, a finding similar to prevalence reported in other geographical areas.</p

Readmission Rates of Patients Discharged against Medical Advice: A Matched Cohort Study

OBJECTIVE: We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period. METHODS: A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group. PRINCIPAL FINDINGS: AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7-38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3-2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01). CONCLUSIONS: Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested

Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies

Nutritional strategies of British professional and amateur natural bodybuilders during competition preparation

Background: To prepare for competition, bodybuilders employ strategies based around: energy restriction, resistance training, cardiovascular exercise, isometric "posing", and supplementation. Cohorts of professional (PRO) natural bodybuilders offer insights into how these strategies are implemented by elite competitors, and are undocumented in the scientific literature. Methods: Forty-seven competitors (33 male (8 PRO, 25 amateur (AMA), 14 female (5 PRO, 9 AMA) participated in the study. All PROs were eligible to compete with the Drug Free Athletes Coalition (DFAC), and all AMAs were recruited from the British Natural Bodybuilding Federation (BNBF). Competitors in these organisations are subject to a polygraph and are drug tested in accordance with the World Anti-Doping Agency. We report the results of a cross-sectional study of drug free bodybuilders competing at BNBF qualifying events, and the DFAC and World Natural Bodybuilding Federation finals. Participants completed a 34-item questionnaire assessing dietary intake at three time points (start, middle and end) of competition preparation. Participants recorded their food intake over a 24-h period in grams and/or portions. Dietary intakes of PRO and AMA competitors were then compared. Repeated measures ANOVA was used to test if nutrient intake changed over time, and for associations with division. Results: Male PROs reported significantly (p < 0.05) more bodybuilding experience than AMAs (PRO: 12.3 +/- 9.2, AMA: 2.4 +/- 1.4 yrs). Male PROs lost less body mass per week (PRO: 0.5 +/- 0.1, AMA: 0.7 +/- 0.2%, p < 0.05), and reported more weeks dieting (PRO: 28.1 +/- 8.1, AMA: 21.0 +/- 9.4 wks, P = 0.06). Significant differences (p < 0.05) of carbohydrate and energy were also recorded, as well as a difference (p = 0.03) in the estimated energy deficit (EED), between male PRO (2.0 +/- 5.5 kcal) and AMA (- 3.4 +/- 5.5 kcal) competitors. Conclusions: Longer diets and slower weight loss utilized by PROs likely contributed towards a lower EED compared to the AMAs. Slower weight loss may constitute an effective strategy for maintaining energy availability and muscle mass during an energy deficit. These findings require corroboration, but will interest bodybuilders and coaches

Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis

To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease.A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA.High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Research and Development Department of Fleury Medicine and HealthConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, UNIFESP, Div Rheumatol, BR-04023900 São Paulo, BrazilFleury Med & Hlth Labs, Div Res & Dev, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Gastroenterol, São Paulo, BrazilUniv São Paulo, Inst Trop, Lab Med Invest LIM 06, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Hosp Servidor Publ Estadual Francisco Morato Oliv, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Stat, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Div Rheumatol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Hosp Servidor Publ Estadual Francisco Morato Oliv, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Stat, São Paulo, BrazilFAPESP: 2009/51887-0CNPq: 476356/2008-3Web of Scienc

The relationship of Plasmodium falciparum humeral immunity with HIV-1 immunosuppression and treatment efficacy in Zambia

<p>Abstract</p> <p>Background</p> <p>HIV-1 infection affects malaria humeral immunity during pregnancy, but data for non-pregnant adults are lacking. This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure.</p> <p>Methods</p> <p>Sera of 224 HIV-1 infected and 115 uninfected adults were compared for IgG to merozoite antigens AMA-1 and MSP2 (3D7 and FC27 types) determined by ELISA, and for IgG to the Variant Surface Antigens (VSA) of three different parasite line E8B, A4 and HCD6 determined by flow cytometry.</p> <p>Results</p> <p>Compared to HIV-1 uninfected adults, AMA-1 IgG was lower in HIV-1 infected (<it>P </it>= 0.02) and associated with low CD4 count AMA-1 IgG (<it>P </it>= 0.003). Low IgG to all three merozoite antigens was associated with less anemia (<it>P </it>= 0.03). High parasite load was associated with low MSP2 IgG 3D7 and FC27 types (<it>P </it>= 0.02 and <it>P </it>= 0.08). Antibody levels to VSA did not differ between HIV-1 infected and uninfected adults. However, low VSA IgGs were associated with high parasite load (<it>P </it>≤ 0.002 for each parasite line) and with treatment failure (<it>P </it>≤ 0.04 for each parasite line).</p> <p>Conclusion</p> <p>HIV-1 affects humeral responses to AMA-1, but seems to marginally or not affect humeral responses to other merozoite antigens and VSAs. The latter were important for controlling parasite density and predict treatment outcome.</p

CD8+ T-cell Activation in Mice Injected with a Plasmid DNA Vaccine Encoding AMA-1 of the Reemerging Korean Plasmodium vivax

Relatively little has been studied on the AMA-1 vaccine against Plasmodium vivax and on the plasmid DNA vaccine encoding P. vivax AMA-1 (PvAMA-1). In the present study, a plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax has been constructed and a preliminary study was done on its cellular immunogenicity to recipient BALB/c mice. The PvAMA-1 gene was cloned and expressed in the plasmid vector UBpcAMA-1, and a protein band of approximately 56.8 kDa was obtained from the transfected COS7 cells. BALB/c mice were immunized intramuscularly or using a gene gun 4 times with the vaccine, and the proportions of splenic T-cell subsets were examined by fluorocytometry at week 2 after the last injection. The spleen cells from intramuscularly injected mice revealed no significant changes in the proportions of CD8+ T-cells and CD4+ T-cells. However, in mice immunized using a gene gun, significantly higher (P<0.05) proportions of CD8+ cells were observed compared to UB vector-injected control mice. The results indicated that cellular immunogenicity of the plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax was weak when it was injected intramuscularly; however, a promising effect was observed using the gene gun injection technique

Polymorphism at the apical membrane antigen 1 locus reflects the world population history of Plasmodium vivax

<p>Abstract</p> <p>Background</p> <p>In malaria parasites (genus <it>Plasmodium</it>), <it>ama-1 </it>is a highly polymorphic locus encoding the Apical Membrane Protein-1, and there is evidence that the polymorphism at this locus is selectively maintained. We tested the hypothesis that polymorphism at the <it>ama-1 </it>locus reflects population history in <it>Plasmodium vivax</it>, which is believed to have originated in Southeast Asia and is widely geographically distributed. In particular, we tested for a signature of the introduction of <it>P. vivax </it>into the New World at the time of the European conquest and African slave trade and subsequent population expansion.</p> <p>Results</p> <p>One hundred and five ama<it>-1 </it>sequences were generated and analyzed from samples from six different Brazilian states and compared with database sequences from the Old World. Old World populations of <it>P. vivax </it>showed substantial evidence of population substructure, with high sequence divergence among localities at both synonymous and nonsynonymous sites, while Brazilian isolates showed reduced diversity and little population substructure.</p> <p>Conclusion</p> <p>These results show that genetic diversity in <it>P. vivax </it>AMA-1 reflects population history, with population substructure characterizing long-established Old World populations, whereas Brazilian populations show evidence of loss of diversity and recent population expansion.</p> <p>Note</p> <p>Nucleotide sequence data reported is this paper are available in the GenBank™ database under the accession numbers <ext-link ext-link-type="gen" ext-link-id="EF031154">EF031154</ext-link> – <ext-link ext-link-type="gen" ext-link-id="EF031216">EF031216</ext-link> and <ext-link ext-link-type="gen" ext-link-id="EF057446">EF057446</ext-link> – <ext-link ext-link-type="gen" ext-link-id="EF05487">EF057487</ext-link></p

Patients in a private hospital in India leave the emergency department against medical advice for financial reasons

BACKGROUND: Some reports indicate financial concerns as a factor affecting ED patients leaving the acute care setting against medical advice (AMA). In India, no person is supposed to be denied urgent care because of inability to pay. Since a large proportion of the Indian health care system is financed by out-of-pocket expenses, we investigate the role of financial constraints for ED patients at a private hospital in India in leaving AMA. METHODS: A prospective ED-based cross-sectional survey of patients leaving AMA was conducted at a private hospital in India from 1 October 2010 to 31 December 2010. Descriptive statistics and the chi-square test were used to identify associations between financial factors and the decision to leave the hospital AMA. RESULTS: Overall, 55 (3.84%) ED patients left AMA, of which 46 (84%) reported leaving because of financial restrictions. Thirty-nine (71%) respondents indicated the medical bill would represent more that 25% of their annual income. Females (19/19) were more likely to leave AMA for financial reasons compared to males (27/36, p = 0.017). Among females who signed out AMA, the decision was never made by the female herself. CONCLUSION: The number of people leaving the ED AMA in a private Indian hospital is relatively high, with most leaving for financial reasons. In most cases, women did not decide to leave the ED AMA for themselves, whereas males did. This survey suggests that steps are needed to ensure that the inability to pay does not prevent emergent care from being provided

Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine

The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p &lt; 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p &lt; 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients