Prevalence Of Responders Research Articles

Long-term outcome of Graves' orbitopathy following treatment with sirolimus.

Sirolimus was found to be associated with a better outcome of Graves' orbitopathy (GO) at 24weeks compared to methylprednisolone. We conducted a retrospective study to investigate its efficacy and safety over a longer period. Data from 40 consecutive patients with moderate-to-severe, active GO, 20 treated with sirolimus and 20 with methylprednisolone, were collected. overall outcome (composite evaluation) of GO at 48weeks. (1) GO outcome at 24weeks, and, at 24 and 48weeks: (2) outcome of single eye features; (3) quality of life (GO-QoL); (4) TSH-receptor antibodies; (5) GO relapse at 48weeks; (6) adverse events. The overall GO outcome at 48weeks did not differ between the two groups (responders: 55% vs 55%). At 24weeks, prevalence of responders was greater in sirolimus group (65% vs 25%; P = 0.01). A reduction ≥ 1 point in clinical activity score (CAS) was more frequent in sirolimus patients at 24 (85% vs 40%; P = 0.005) and 48weeks (75% vs 60%; P = 0.03). The proportion of GO-QoL responders (appearance subscale) at 24weeks was greater in sirolimus group (62.5% vs 26.3%; P = 0.03). No difference was observed for the remaining outcome measures. Treatment with sirolimus is followed by a greater overall response of GO compared with methylprednisolone at 24weeks, but not at 48weeks, when only CAS is affected. A more prolonged period of treatment may be required for a better outcome to be observed over a longer period.

The Prevalence of Responders and Non-Responders for Body Composition, Resting Blood Pressure, Musculoskeletal, and Cardiorespiratory Fitness after Ten Weeks of School-Based High-Intensity Interval Training in Adolescents

Many observations have demonstrated great heterogeneity in the magnitude of the response to the physical exercise stimulus. Only a few studies have investigated the effects of high-intensity interval training (HIIT) on the prevalence of non-responders (NRs) in adolescents while considering health-related fitness measurements and other co-variables. Therefore, the aim of the current work was twofold: (1) to assess the effects of ten weeks of school-based HIIT on the prevalence of responders (Rs) and NRs for body composition, resting blood pressure (BP), cardiorespiratory and musculoskeletal fitness, and (2) to assess the relationship of this prevalence with sex, body mass category, and biological maturation status, while estimating the likelihood of a response. Adolescents aged 16 years (n = 73) were included in the study. Waist-to-hip ratio, body fat percentage (BFP), skeletal muscle mass (SMM), BP, cardiorespiratory fitness (CRF), and musculoskeletal fitness were the primary outcomes. Co-variables included sex, body mass index (BMI), and maturity offset. The percentages of the Rs and NRs were analyzed based on changes (Δ) between post-intervention and pre-intervention values. The typical error (TE) method was used to identify Rs and NRs. Results showed a variation in the relative size of changes (% of changes) depending on the variable and sex. The greatest changes were observed in females’ abdomen muscle strength (Δ% = 23.89%), and the difference from that of males (Δ% = 5.98%) was statistically significant (p < 0.001) with very large effect size of (Cohen’s d = 0.941). Similar significant differences in relative changes were observed in body composition, but in the reverse direction. Males gained more from HIIT in the decrease in the body fat percentage (Δ% = −8.24%) and increase in skeletal muscle mass (Δ% = 3.38%) comparing to females (Δ% = 0.46, p = 0.040 and Δ% = 1.06%, p = 0.007, respectively). Effect size for body fat was small (Cohen’s d = 0.469), and for skeletal muscle mass it was moderate (Cohen’s d = −0.659). The results also showed positive significant differences in the prevalence of Rs compared to NRs in BFP, SMM, systolic BP (SBP), diastolic BP (DBP), CRF, and abdominal muscular strength (ABS) (p = 0.047, p = 0.047, p < 0.001, p = 0.003, p = 0.014, and p = 0.014, respectively). The effect was greatest and largest for SBP (Cohen’s ω = 0.67). Sex was related to the prevalence of Rs for ABS and close to significance for SMM. More males than females benefited from HIIT in SMM (p = 0.058), but more females than males had ABS benefits (p = 0.050). Males were more likely (2.5-fold) to be Rs than females in SMM. BMI was not related to the prevalence of Rs and NRs. Biological maturation was related to the prevalence of Rs and NRs in SMM (p = 0.036) and SBP (p = 0.016). In SBP, 100% of the early matured derived benefit from HIIT, but the effect size was small (Cramer’s V = 0.27). Those who maturated later were more likely (almost 70%) to be Rs. Thus, the HIIT program introduced to a typical physical education (PE) lesson can be considered partially effective. Therefore, there is a need to continue the search for an optimal and effective program for all health-related parameters. The close relationship between analyzed values and sex and biological maturation, but not BMI, indicates that the intervention programs should be tailored specifically for males and females.

Effects and individual response of continuous and interval training on adiponectin concentration, cardiometabolic risk factors, and physical fitness in overweight adolescents.

This study aimed to evaluate the effect and individual responsiveness after 12weeks of high-intensity interval training (HIIT) and moderate-intensity of continuous training (MICT) on adiponectin, cardiometabolic risk factors and physical fitness in overweight adolescents. This study was participated by 52 adolescents, both sexes, 11 and 16years old, separated into HIIT (n = 13), MICT (n = 15), and control group (CG, n = 24). Body mass, height, waist circumference (WC), fat mass (FM), fat-free mass (FFM), blood pressure, high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), triglycerides, glucose, insulin, adiponectin, and C-reactive protein (CRP) were evaluated. Body mass index z-score (BMI-z), waist-to-height ratio (WHtR), insulin resistance, and insulin sensitivity were calculated. Resting heart rate (HRrest), peak oxygen consumption (VO2peak), right handgrip strength (HGS-right), left handgrip strength (HGS-left), and abdominal resistance (ABD) was evaluated. HIIT session lasted around 35min and MICT of 60min of exercises on stationary bicycle, three times a weekday for 12weeks. ANOVA, effect size, and prevalence of responders were used for statistical analysis. HIIT reduced BMI-z, WHtR, LDL-c, and CRP, while increased of physical fitness. MICT reduced HDL-c, while increased of physical fitness. CG reduced FM, HDL-c, and CRP, while increased FFM and HRrest. Frequencies of respondents in HIIT were observed for CRP, VO2peak, HGS-right, and HGS-left. Frequencies of respondents in MICT were observed for CRP and HGS-right. Frequencies of no-respondents in CG were observed for WC, WHtR, CRP, HRrest, and ABD. Conclusion: Interventions with exercises were effective to adiposity, metabolic health, and physical fitness improvements. Individual responses were observed in inflammatory process and physical fitness, important changes in overweight adolescent's therapy. Trial registration number and date of registration: This study was registered with the Brazilian Registry of Clinical Trials (REBEC), the number RBR-6343y7, date of registration May 3, 2017. What is Known: • Effect of regular physical exercise positively affects overweight, comorbidities, and metabolic diseases, recommended mainly for children and adolescents. What is New: • Due to the great inter-individual variability, the same stimulus can provide different responses; adolescents who benefit from the stimulus are considered responsive. • Intervention of HIIT and MICT did not alter the concentrations of adiponectin; however, the adolescents presented responsiveness to the inflammatory process and physical fitness.

Interindividual variability of adaptations following either traditional strength or power training combined to endurance training in older men: A secondary analysis of a randomized clinical trial

This study aimed to investigate the interindividual responses following two different concurrent training (CT) regimens in neuromuscular, cardiorespiratory and functional outcomes of older men. Thirty-five older men (65.8 ± 3.9 years) were randomly allocated into one of two CT groups: power training (PT) + high-intensity interval training (HIIT) (n = 17); or traditional strength training (TST) + HIIT (n = 18). Maximal dynamic strength (one-repetition maximum, 1RM), rate of force development at 100 milliseconds (RDF100), countermovement jump power (CMJ), quadriceps femoris muscle thickness (QF MT), functional tests (sit-to-stand, timed-up-and-go, and stair climbing), and peak oxygen consumption (VO2peak) were assessed pre-, post-8 and post-16 weeks of training. The Chi-squared test was used for assessing differences in the prevalence of responders (Rs), non-responders (NRs), and adverse responders (ARs). Similar prevalence of individual responses (Rs, NRs and ARs) between groups were observed after intervention in almost all outcomes: 1RM; power at CMJ; QF MT, and functional tests (P > 0.05). However, a significant difference in the distribution of Rs, NRs and ARs between groups was observed in the RFD100 after 16 weeks (p = 0.003), with PT + HIIT group presenting high prevalence of Rs than TST + HIIT (100 % vs. 50 %). The inclusion of explosive-type of contractions in a concurrent training regime induces greater responsiveness in the RFD100 in older men, while no differences compared to traditional strength training are observed in maximal strength, muscle size, VO2peak, and functional performance.

Prevalence of responders of a school intervention at physical fitness and mental health of children: a quasi-experimental study

Aim: to verify the effect of a physical education program at school on physical fitness and mental health in children and to determine the individual prevalence of responders. Methods: This is a quasi-experimental study, developed with 67 children aged between 6 and 11 years old. (8.09 ± 1.81). A 21-week intervention was performed, that intervention condition (IC) consisted of sports and circuit training, and nutritional education. For the control condition (CC) classes followed to the Common Curricular National Base. The following variables were evaluated at baseline and post-intervention: physical fitness and mental health through the strength and difficulties questionnaire. Mixed analysis of variance and the prevalence of responders were used for statistical analysis. Results: The main results indicate that there were improvements in the IC in the components of physical fitness (cardiorespiratory fitness, speed, and agility) and mental health indicators (total difficulties, emotional symptoms, problems with peers, and prosocial behavior) after a school physical education program in comparison with the CC. Concerning the prevalence of responders between groups, it was found differences in cardiorespiratory fitness (CC: 33.33%; IC: 65.38%), agility (CC: 36.66%; IC: 73.07%), speed (CC: 43.33%; IC: 79.16%), emotional symptoms (CC: 28.57%; IC: 50.00%), and prosocial behavior (CC: 17.14%; IC: 46.87%). Conclusion: It is reinforced that well-planned physical education classes and simple intervention programs can be adopted at the school level and are capable of promoting children's physical and mental health.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. The study comprised 94 overweight adolescents, aged between 10 and 16years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45min of indoor cycling, 45min of walking, and 20min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. Level I, evidence obtained from well-designed controlled trials randomization. Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

Symptom response to mobilization and outcomes in patients with subacromial pain syndrome: A cohort study.

The objectives of this study were the following: (1) to determine if there was a difference in outcomes between immediate responders to glenohumeral mobilizations at the initial evaluation, 2-week, 4-week, and 6-month follow-up as compared to those that do not respond in participants with subacromial pain syndrome; (2) to see if there were statistically significant differences in outcomes within these groups between these time frames of interest, and (3) to see if symptom response at the initial evaluation was predictive of a favorable recovery. This was a prospective, single-group observational design. Clinicians pragmatically identified positive responders as improving at least two points on the Numeric Pain Rating Scale and/or a 20° improvement in shoulder active range of motion (AROM) following shoulder mobilization at the initial evaluation. Data were collected for the subjective and objective variables of interest at the initial evaluation, 2-week, 4-week, and 6-month follow-up. The prevalence of responders at the initial evaluation was 99 (81.8%). There were no statistically significant between-group differences for the variables of interest except for the Global Rating of Change (GRoC; f=2.79, p=0.006). The shoulder abduction AROM between-group difference exceeded the minimal detectable change at 4weeks. The pair-wise comparison showed statistically significant differences for the outcomes of interest at each time point except for the GRoC between 4weeks and 6months. There was a statistically significant correlation between responders at the initial evaluation and shoulder abduction AROM at the 4-week follow-up (rpb (112)=0.27, p=0.004). Individuals with SAPS may benefit from shoulder mobilization independent of their within-session response to shoulder mobilization at the initial evaluation. Future research should seek to differentiate if these improvements are related to the within-session positive treatment response at the initial evaluation in individuals who are randomized to receive shoulder mobilization or not.

Abstract C002: Racial and geographic variation in knowledge of palliative care among American adults

Abstract Introduction Palliative care provides clinical and economic benefits for patients diagnosed with life limiting illness and their family caregivers. The extent to which variation in knowledge of palliative care exits in racial groups and geographic regions within the United States is not known. The aim of the study was to present the up-to-date data on the knowledge penetration of palliative care by racial and geographic regions. Methodology We assessed variations in knowledge of palliative care using the 2018 National Cancer Institute’s Health Information National Trends Survey. We used the Pearson chi-square test and multivariable logistic regression models to assess the association of race and having knowledge of palliative care for each census geographic region. The state-level prevalence of no knowledge of palliative care were plotted in a map. Results The study population included 3194 respondents (weighted sample size: 229,591,005; median age: 58). About 15 % of the study population was Hispanic, 10% non-Hispanic-Black, and 61% non-Hispanic White. About 84% Hispanic respondents, 75% non-Hispanic Blacks and 65% non-Hispanic Whites had no knowledge of palliative care (P &amp;lt;0.001). For Hispanic, the prevalence of no knowledge of palliative care ranged from 48% in East South Central region to 96% in East North Central and West North Central region. For non-Hispanic Blacks, the prevalence of no knowledge of palliative care ranged from 32% in New England region to 97% in West North Central region. For non-Hispanic Whites, the prevalence of no knowledge of palliative care ranged from 44% in New England region to 78% in Mountain region. Both racial group and census geographic regions were statistically significant variables in the multivariable model predicting no knowledge of palliative care. Conclusions In the United States, substantial geographic variations in the knowledge of palliative care exist. The prevalence of responders who had no knowledge of palliative care were greater in Hispanic and non-Hispanic Black than non-Hispanic White groups. This finding represents an opportunity for targeted future education to increase the knowledge gap overall and in patients of non-White decent. Citation Format: Kayanna Jacobs, Young Rock Hong, Jiang Bian, Sheri Kittelson, Diana J. Wilkie, Jinhai Huo. Racial and geographic variation in knowledge of palliative care among American adults [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C002.

Guanidinoacetic acid loading for improved location-specific brain creatine.

We conducted here a secondary analysis of previously completed guanidinoacetic acid (GAA) loading trials categorizing participants into responders and non-responders using cut-off points for an increase in the location-specific levels of brain creatine (e.g. thalamus, cerebellum, white and grey matter). A total of 19 healthy men (mean age=24.8 years) who were supplemented with 3g/d of GAA for 4 weeks, with total brain creatine evaluated using 1.5T magnetic resonance spectroscopy (MRS) were included in this report. An average elevation in total creatine content after 28-day GAA loading was 17.3% in the cerebellum (95% confidence interval [CI] from 9.7 to 24.9), 12.1% in the white matter (95% CI from 5.1 to 19.1), and 8.9% in the grey matter (95% CI from 5.2 to 12.6), while total creatine actually dropped in the thalamus at a follow-up for 9.1% (95% CI from 6.8 to 11.4). The prevalence of responders was the highest for the cerebellum (73.6%), followed by the white matter (47.3%) and the grey matter (42.1%), while only two individuals (10.5%) experienced a relevant rise in the thalamus creatine content at 28-day follow-up (P<0.001). This aftermath evaluation of previously published data suggests a relatively favorable (and location-specific) response rate to short-term GAA loading in healthy young men. A somewhat contrasting location-dependent pattern for GAA and creatine to positively affect brain creatine may be of great interest to the scientific community by dispensing different interventions to tackle poor bioenergetics in distinct brain regions.

Effects and prevalence of responders after a multicomponent intervention on cardiometabolic risk factors in children and adolescents with overweight/obesity: Action for health study

ABSTRACT This study aimed to verify the effect of a multicomponent intervention on cardiometabolic risk factors (CMRF), and to determine the prevalence of responders on CMRF among children and adolescents with overweight/obesity. This is a quasi-experimental study, developed with 35 children and adolescents with overweight/obesity (control group (CG) = 18; intervention group (IG) = 17), aged between 7 and 13 years. Participants in IG underwent a multicomponent intervention for 12 weeks. The following variables were evaluated: anthropometric measures, maturational stages and CMRF (body fatness, HOMA-IR, triglycerides, high-density and low-density lipoprotein) (HDL-C, LDL-C), total cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio. Mixed analysis of variance and the prevalence of responders were used for statistical analysis. There was a significant time x group interaction on body fatness (p < 0.001), HOMA-IR (p = 0.01), HDL-C (p < 0.001), LDL-C (p = 0.009) and TC (p < 0.001). The prevalence of responders for CMRF in IG and CG was respectively: body fatness (47%; 0%; p = 0.04), HOMA-IR (58.8%; 16.6%; p = 0.04); triglycerides (17.6%; 5.5%; p = 0.31); HDL-C (76.4%; 5.5%; p = 0.01), LDL-C (35.3%; 5%; p = 0.08), TC (64.7%; 5%; p = 0.01), AST (5.8%; 0%; p = 0.87), ALT (29.4%; 11.1%; p = 0.24) and AST/ALT ratio (24.4%; 22.2%; p = 0.67). Multicomponent intervention induced positive changes on CMRF along with a higher prevalence of positive adaptations in IG than the CG in some of the cardiometabolic outcomes assessed.

Unexpected high circulation of Plasmodium vivax in asymptomatic children from K\xe9dougou, southeastern Senegal

BackgroundMalaria in Senegal is due essentially to infections by Plasmodium falciparum and, to a lesser extent to Plasmodium malariae and Plasmodium ovale. By the use of molecular methods, detection of Plasmodium vivax has been recently reported in the region of Kedougou, raising the question of appraisal of its potential prevalence in this setting.MethodsA retrospective serological study was carried out using 188 samples taken from 2010 to 2011 in a longitudinal school survey during which 48 asymptomatic children (9–11 years) were recruited. Four collections of samples collected during two successive dry and rainy seasons were analysed for antibody responses to P. vivax and P. falciparum. Recombinant P. falciparum and P. vivax MSP1 antigens and total P. falciparum schizont lysate from African 07/03 strain (adapted to culture) were used for ELISA. Nested PCR amplification was used for molecular detection of P. vivax.ResultsA surprising high prevalence of IgG responses against P. vivax MSP1 was evidenced with 53% of positive samples and 58% of the individuals that were found positive to this antigen. There was 77% of responders to P. falciparum outlined by 63% of positive samples. Prevalence of responders did not differ as function of seasons. Levels of antibodies to P. falciparum fluctuated with significant increasing between dry and rainy season (P < 0.05), contrary to responses to P. vivax. There was a significant reciprocal relationship (P < 10−3) between antibody responses to the different antigens, but with weak coefficient of correlation (Rho around 0.3) underlining a variable profile at the individual level. Clear molecular signature was found in positive IgG to P. vivax msp1 samples by PCR.ConclusionThis cross-sectional longitudinal study highlights the unexpected high circulation of P. vivax in this endemic area. Sero-immunology and molecular methods are powerful additive tools to identify endemic sites where relevant control measures have to be settled and monitored.

Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance

Little evidence exists on which variables of body composition or muscular strength mediates more glucose control improvements taking into account inter-individual metabolic variability to different modes of exercise training. We examined 'mediators' to the effects of 6-weeks of resistance training (RT) or high-intensity interval training (HIT) on glucose control parameters in physically inactive schoolchildren with insulin resistance (IR). Second, we also determined both training-induce changes and the prevalence of responders (R) and non-responders (NR) to decrease the IR level. Fifty-six physically inactive children diagnosed with IR followed a RT or supervised HIT program for 6 weeks. Participants were classified based on ΔHOMA-IR into glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) <3.0 after intervention) and NRs (no changes or values HOMA-IR⩾3.0 after intervention). The primary outcome was HOMA-IR associated with their mediators; second, the training-induced changes to glucose control parameters; and third the report of R and NR to improve body composition, cardiovascular, metabolic and performance variables. Mediation analysis revealed that improvements (decreases) in abdominal fat by the waist circumference can explain more the effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or HIT regimes. The same analysis showed that increased one-maximum repetition leg-extension was correlated with the change in HOMA-IR (β=-0.058; P=0.049). Furthermore, a change in the waist circumference fully mediated the dose-response relationship between changes in the leg-extension strength and HOMA-IR (β'=-0.004; P=0.178). RT or HIT were associated with significant improvements in body composition, muscular strength, blood pressure and cardiometabolic parameters irrespective of improvement in glycemic control response. Both glucose control RT-R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean muscular strength leg-extension and mean measures of adiposity. The improvements in the lower body strength and the decreases in waist circumference can explain more the effects of the improvements in glucose control of IR schoolchildren in R group after 6 weeks of RT or HIT, showing both regimes similar effects on body composition or muscular strength independent of interindividual metabolic response variability.

Naturally acquired immune responses to thrombospondin-related adhesion protein (TRAP) of Plasmodium vivax in patients from areas of unstable malaria transmission

A key tool for the control, elimination, and eradication of Plasmodium vivax is the development of an effective vaccine. The thrombospondin-related adhesion protein (TRAP) is one of the major sporozoite antigens that plays an important role in the invasion of mosquito salivary glands and hepatocytes by sporozoites. The main goal of this study was to evaluate the naturally acquired antibodies to the P. vivax TRAP (PvTRAP) in patients from malaria-endemic areas of Iran (n=116), Afghanistan (n=50), and Pakistan (n=50). The PvTRAP gene was expressed in Escherichia coli Rosetta (DE3)-pET23a and used as antigen in enzyme-linked immunosorbent assay (ELISA). The profile of immunoglobulin G (IgG) isotype and the avidity of IgG, IgG1, and IgG3 to PvTRAP, as well as the association between anti-PvTRAP isotype responses and host age were evaluated. Only 42.24% of Iranian, 38% of Afghani, and 44% of Pakistani patients infected with P. vivax had positive anti-PvTRAP IgG, and the prevalence of responders in the three countries did not differ significantly (P>0.05). Moreover, the prevalence of IgG1 and IgG3 antibody responses to PvTRAP showed no significant correlation with age (P>0.05). Individuals exposed to vivax malaria in the unstable malaria transmission areas are able to produce antibodies to the TRAP antigen at all ages in response to P. vivax infections. Finally, the presence of mature IgG1 and IgG3 antibodies with high to intermediate avidity against PvTRAP antigen (>60%) provide more information to understand the interactions between the host and P. vivax parasite. In summary, the present study provides data that support the rational development of an effective pre-erythrocytic stage vaccine based on PvTRAP antigen.

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis.

To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.

Comparative analysis of the profiles of IgG subclass-specific responses to Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-1 in naturally exposed individuals living in malaria hypoendemic settings, Iran.

BackgroundPlasmodium falciparum apical membrane antigen-1 (PfAMA-1) and the 19-kDa C-terminal region of merozoite surface protein-1 (PfMSP-119) are candidate malaria vaccine antigens expressed on merozoites and sporozoites. This investigation was performed to evaluate simultaneously the naturally-acquired antibodies to PfAMA-1 and PfMSP-119 and to compare IgG subclass profiles to both antigens in naturally exposed individuals living in malaria hypoendemic areas in Iran to determine which antigen has better ability to detect sero-positive individuals infected with P. falciparum.MethodsIn this investigation, 101 individuals from the malaria-endemic areas in Iran were examined. PfAMA-1 and PfMSP-119 were expressed in Escherichia coli, and IgG isotype composition of naturally acquired antibodies to the antigens (as single or in combination) was measured by ELISA assay.ResultsThe result showed that 87.1% and 84.2% of the studied individuals had positive anti-PfAMA-1 and -PfMSP-119 IgG antibody responses, respectively, and the prevalence of responders did not differ significantly (P > 0.05). Moreover, IgG1 and IgG3 were predominant over IgG2 and IgG4 antibodies and the prevalence of IgG and its subclasses to two tested antigens had no significant correlation with age and exposure (P > 0.05). The present data confirmed that when recombinant PfAMA-1 and recombinant PfMSP-119 antigens were combined in ELISA at equal ratios of 200 ng (100 ng each antigen/well) and 400 ng (200 ng each antigen/well), 86.1% and 87.1% of positives sera were detected among the examined samples, respectively.ConclusionsThe two tested recombinant antigens are immunogenic molecules, and individuals in low transmission areas in Iran could develop and maintain equal immune responses to PfAMA-1 and PfMSP-119. Therefore, these results could support the design of a universal PfAMA-1- and PfMSP-119-based vaccine. Also, both recombinant antigens could be used in combination as reliable serology markers to perform immuno-epidemiological studies in malaria-endemic areas of Iran during elimination strategy. The present information could be of use in control and elimination programmes in Iran and other similar malaria settings.

Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.

Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable outcomes in up to 80% of patients. However, little is known on the factors that may affect GO outcome in the long term, an issue that we investigated here. We studied retrospectively 96 untreated patients with GO, identified out of 787 consecutive patients who came to our GO Clinic for a follow-up visit between September 2010 and June 2013. After the first observation, patients were treated with ivGC and ORT and were then re-examined after a median period of 55.5 months. The primary end-point was the possible relation between GO outcome and several individual variables. Exophthalmometry, eyelid aperture, CAS, diplopia and visual acuity (the latter only in patients with an initial reduction) improved significantly after treatment. Overall, 67.7% of patients had improved and were considered as responders, whereas the remaining (29.1% stable and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual GO features at first observation did not affect the outcome of GO, which, in contrast, was affected by gender and by the time elapsed between first and last observation. Thus, the prevalence of responders was higher in females (76.4 vs 48% in males, P = 0.02) and the time elapsed between first and last observation was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas the prevalence of responders and non-responders was similar up to 36 months, there was an increase in responders beginning between 37 and 48 months and reaching a peak of ~80% between 61 and 72 months, to plateau thereafter. Given the limitations of retrospective investigations, our study confirms that the combination of GC and ORT is effective in GO and shows that females have greater chances to respond to treatment. The notorious tendency of GO to improve spontaneously with time most likely contributes the long-term outcome of the eye syndrome.

Development of new IL28B genotyping method using Invader Plus assay

IL28B polymorphism is associated with the response to pegylated interferon-α with ribavirin (PEG-IFN-α/RBV) treatment in chronic hepatitis C patients. As a genotyping assay for IL28B single nucleotide polymorphisms (SNPs) in clinical practice, the Invader Plus assay was developed. The accuracy, intra-assay, inter-assay precision, and the limit of detection of the Invader Plus assay were evaluated. Two SNPs (rs8099917 and rs12979860) associated with IL28B were genotyped by the Invader Plus and TaqMan assay in 512 Japanese patients. In comparison with direct sequencing, the Invader Plus assay showed 99% accuracy in rs8099917 and 100% accuracy in rs12979860. Intra-assay and inter-assay precision were sufficient to use in clinical practice and the detection limit was 1ngDNA/assay. Genotyping by rs8099917 showed that 361 (71%), 144 (28%) and seven (1%) of the patients were major homozygous, heterozygous and minor homozygous types, respectively. Five of the 512 cases (1%) had haplotype differences, but none showed differences between the two genotyping methods. For patients with HCV genotype 1, the prevalence of responders in the major homozygous type was 83.3%, and that of non-responders in the minor heterozygous/homozygous type was 72.5%. A convenient IL28B genotyping method using the Invader Plus assay could be useful to predict the treatment outcome in clinical practice.

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

Plasmodium vivax remains an important cause of morbidity outside Africa, and no effective vaccine is available against this parasite. The P. vivax Duffy binding protein (PvDBP) is essential during merozoite invasion into erythrocytes, and it is a target for protective immunity against malaria. This investigation was designed to evaluate naturally acquired antibodies to two variant forms of PvDBP-II antigen (DBP-I and -VI) in malaria individuals (N = 85; median = 22 years) who were living in hypoendemic areas in Iran. The two PvDBP-II variants were expressed in Escherichia coli, and immunoglobulin G (IgG) isotype composition and avidity of naturally acquired antibodies to these antigens were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that almost 32% of the studied individuals had positive antibody responses to the two PvDBP-II variants, and the prevalence of responders did not differ significantly (P > 0.05; χ(2) test). The IgG-positive samples exhibited 37.03% and 40.8% high-avidity antibodies for PvDBP-I and PvDBP-VI variants, respectively. Furthermore, high-avidity IgG1 antibody was found in 39.1% of positive sera for each examined variant antigen. The avidity of antibodies for both PvDBP variant antigens and the prevalence of responders with high- and intermediate-avidity IgG, IgG1, and IgG3 antibodies were similar in patients (P > 0.05; χ(2) test). Moreover, the prevalence of IgG antibody responses to the two variants significantly increased with exposure and host age. To sum up, the results provided additional data in our understanding of blood-stage immunity to PvDBP, supporting the rational development of an effective blood-stage vaccine based on this antigen.

IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-119) in an area with unstable malaria transmission in Iran

Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface protein 1 (PfMSP-119) is a target for protective immunity against malaria and the major concern in development of vaccine based on this antigen is the presence of polymorphisms. This investigation was designed to evaluate naturally acquired antibodies and antigen-binding avidity of IgG antibodies to three variant forms of PfMSP-119 antigen (E/TSG/L, E/KNG/F and Q/KNG/L) in malaria individuals who are living in hypoendemic areas in Iran (n=92, 4–75years old). The three variant forms of PfMSP-119 were expressed in Escherichia coli and IgG isotype composition and avidity of naturally acquired antibodies to the 19-kDa antigen were measured by ELISA assay. Results showed that almost 72% of the studied individuals had positive antibody responses to three PfMSP-119 variants and the prevalence of responders did not differ significantly (P>0.05). High-avidity IgG (62.7%, 65.7% and 47.76%) and IgG1 (64.2%, 50.75%, and 50.75%) were found in positive sera for E/TSG/L, E/KNG/F and Q/KNG/L variants, respectively. Moreover, the prevalence and titers of IgG1 antibody responses to the three variants increased with age (P<0.05). In summary, individuals in low transmission areas in Iran can develop and maintain equal immune responses with high avidity to the PfMSP-119 variants (E/TSG/L, E/KNG/F and Q/KNG/L); however, the precise role of the total IgG and its isotypes in protection requires further investigation. These results could support the design of a universal PfMSP-119-based vaccine.

Life satisfaction in patients with long-term non-malignant pain–relation to demographic factors and pain intensity

Purpose. Life satisfaction can be defined as a measure of a patient's perception of the difference between his reality and his needs or wants. Here we compare life satisfaction in patients with long-term pain to a reference group sampled from the normal population, and relate the results to pain intensity and to demographic factors.Method. Questionnaires containing the Life satisfaction (LiSat-11) checklist, a visual analogue scale (VAS) for pain, and questions on demographic background.Results. The prevalence of responders with low level of life satisfaction was larger among the patients than in the reference group. In particular, patients born outside Northern Europe scored significantly lower than patients born in Northern Europe in many of the LiSat-11 domains. Pain intensity did not correlate well to the level of life satisfaction, except for weak negative correlations to satisfaction with physical health and with financial situation.Conclusion. Long-term pain is strongly associated with low life satisfaction. In order to increase life satisfaction, interventions related to social factors seem to be important.