Impact of IL-27p28 (rs153109) and TNF-α (rs1800629) Genetic Polymorphisms on the Progression of HCV Infection in Egyptian Patients

Background: Hepatitis C virus (HCV) is a universal health problem. HCV infection may proceed to liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). The latest is the third leading global cause of cancer-related mortality. Cytokines including IL-27 and TNF-α play a major role as a link between innate and adaptive immunity which in turn deduct the outcome of HCV infection.

Aim: The present study examined the role of both (-964 A/G) single-nucleotide polymorphism (SNP) of IL-27p28 rs153109 and (-308 G/A) SNP of TNF-α rs1800629 on the progression of HCV infection in genotype 4a infected patients.

Patients and Methods: The patients enrolled in the study were divided into three main groups group I: 38 fibrotic patients, group II: 51 cirrhotic patients, and finally group III: 29 HCC patients. Sixteen healthy volunteers were used as controls. IL-27p28 rs153109 and TNF-α rs1800629 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism assay.

Results: There was no statistically significant difference between the studied groups regarding the IL-27p28 genotypes. However, TNF-α (-308) studied polymorphism showed a significant difference between the HCC and fibrosis group (p = 0.00), and also between the cirrhosis and fibrosis group (p = 0.031) revealing that AA genotype is the genotype of risk. Furthermore, the association found between allele frequencies of two studied SNPs and the four studied groups were non-significant.

Conclusion: TNF-α rs1800629 polymorphism is a potential genetic-susceptibility factor for HCV related cirrhosis and HCC progression.     

Analysis of the Association of Polymorphisms rs5743708 in TLR2 and rs4986790 in TLR4 with Atopic Dermatitis Risk

Background: We carried out a meta-analysis to assess whether Toll-like receptor 2 (TLR2) rs5743708 and Toll-like receptor 4 (TLR4) rs4986790 polymorphisms are associated with the risk of atopic dermatitis.

Methods: A systematic search of PubMed, Embase, and Web of Science was performed to identify eligible case–control studies on the association of rs5743708 and rs4986790 with the risk of atopic dermatitis. Statistical analyses of the odds ratio (OR), 95% confidence interval (CI), and p value were performed using STATA software.

Results: Our meta-analysis included a total of nine case–control studies, all involving Caucasian populations. With respect to the TLR2 rs5743708 G/A polymorphism, there was a statistically significant difference in the overall risk of atopic dermatitis between the case and control groups [OR = 2.07, p value of association test, p_{(association)} = 0.001 in allele (A vs. G) model; OR = 1.93, p_{(association)} = 0.004 in carrier (A vs. G) model; OR = 2.07, p_{(association)} = 0.001 in heterozygote (GA vs. GG) model; OR = 1.99, p_{(association)} = 0.001 in dominant (GA+ AA vs. GG) model]. Similar positive results were observed in the subgroup analysis of “population-based control.” For the TLR4 rs4986790 A/G polymorphism, an increased atopic dermatitis risk was detected in the case group under the allele [OR = 1.78, p_{(association)} = 0.013], carrier [OR = 1.69, p_{(association)} = 0.027] and heterozygote [OR = 1.74, p_{(association)} = 0.020] models, but not the dominant [OR = 1.44, p_{(association)} = 0.070] model, in comparison to the population-based control group.

Conclusion: Our meta-analysis revealed a novel finding that the heterogeneous “GA” genotype of the TLR2 rs5743708 and “AG” genotype of the TLR4 rs4986790 may be associated with increased susceptibility to atopic dermatitis in Caucasians.     

The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age,and related clinical characteristics in Chinese Han population

Objective: To investigate the association between polymorphisms in PTPN2 (rs1893217 and rs478582) and type 1 diabetes (T1D) risk with different diagnosed age, as well as related clinical characteristics in Chinese Han population.

Methods: A total of 2270 Chinese Han individuals (1023 T1D patients and 1247 healthy controls) were genotyped for rs1893217 and rs478582. And 306 newly diagnosed T1D patients were measured for C-peptide levels based on a standard mixed-meal tolerance test. In addition, 40 healthy controls were analyzed for different T cell subsets by multi-color flow cytometry.

Results: Neither rs1893217 nor rs478582 showed any association with T1D risk under an additive model. Stratified analysis for T1D diagnosed age revealed that rs1893217, but not rs478582, was significantly associated with T1D patients diagnosed age ≤18 (OR =0.80, 95% CI: 0.67–0.97, p?=?0.02). For those diagnosed age >18, neither of them showed any association. We also found that rs1893217 had a higher positive rate of ZnT8A (CC vs. TT carrier, OR = 2.07, 95% CI: 1.07–4.03, p?=?0.026) and IA-2A (CT vs. TT carrier, OR = 1.36, 95% CI: 1.02–1.80, p?=?0.038). Furthermore, for rs478582, compared with TT, healthy individuals carrying CC/CT carriers had significantly lower frequency and Helios expression of naive Treg subsets (p?=?0.049 and 0.048 respectively), but not secreting or activating Treg subsets. In addition, we did not find any association between these two polymorphisms and residual β-cell function in newly diagnosed T1D patients.

Conclusions: Our results suggest that rs1893217 may increase the risk of early-onset T1D and affect humoral immunity, while rs478582 may affect Treg subsets.     

Direct Engagement of TLR9 Ligand with T Helper Cells Leads to Cell Proliferation & Up-regulation of Cytokines

Purpose: Toll like receptor (TLR) engagement is primarily a function of the innate immune cells. The purpose of the study was to assess direct uptake of ODN 2216 in T helper cells and effects on cell proliferation and cytokine expression.

Methods: We isolated CD4+ CD25- T helper cells by magnetic sorting and studied the uptake of ODN 2216 using flow cytometry and confocal microscopy. We then studied the effect of ODN 2216 engagement on cell proliferation and cytokine expression using flow cytometry and gene expression of TLR9 signaling genes using real time RT-PCR.

Results: We made a chance observation that purified T helper cells from healthy individuals consistently bind to the TLR9 ligand ODN 2216. In PBMCs, on the other hand, 98% of monocytes preferentially bound to ODN 2216 FITC, indicating that they competed with the lymphocytes. We confirmed intracellular localization of ODN 2216 FITC as well as intracellular expression of TLR9 in Thelper cells. Furthermore, ODN 2216 FITC was also co-localized with the lysosomal membrane associated protein 1. The uptake of TLR9 ligand culminated in cellular proliferation, up-regulation of cytokines and increased mRNA expression of TLR9 and IRF7 in T helper cells, in the absence of antigen presenting cells. ODN 2216 uptake was inhibited by promethazine as well as by TLR9 antagonist.

Conclusions: Our results show a direct engagement of TLR9 ligand in T helper cells and suggest involvement of TLR9 signalling in CD4+T cells, which may envisage novel targets for TLR inhibitors.     

Sinomenine regulates CD14/TLR4, JAK2/STAT3 pathway and calcium signal via α7nAChR to inhibit inflammation in LPS-stimulated macrophages

Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR).

Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AM

Results: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR.

Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.     

Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection

Background: Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC).

Patients and Methods: Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC.

Results: The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042–4.581, P = 0.037, P value by Bonferroni correction [P_c] = 0.074) and allele A (OR 1.435, 95% CI 1.023–2.013, P_c = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011–3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025–3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067–3.482, P = 0.032).

Conclusion: These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC.

Abbreviations: HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet’s disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers’ pneumoconiosis; TNF-α: tumor necrosis factor-α     

Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory,anti-hyperuricemic,and NLRP3 inhibition

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.

Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.

Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.

Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.

Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.     

Forensic characteristics and phylogenetic analysis of 23 Y-STR loci in the Miao population from Guizhou province,southwest China

Background: Investigation of haplotype/allele frequency data of Y-STR loci in ethnically diverse populations is essential for forensic reference database construction and genetic application. However, the population genetic characteristics of the Chinese Miao minority from Guizhou Province remain uncharacterised.

Aim: To assess forensic characteristics for 23 Y-Chromosomal STR loci in Guizhou Miao and explore population genetic relationships with geographically neighbouring populations.

Subjects and methods: Twenty-three Y-Chromosomal STRs were genotyped using the Powerplex^® Y23 system in 103 unrelated Chinese Miao males from Guizhou Province, southwest China. Haplotypes and forensic parameters were obtained. Population relationships of Guizhou Miao with others were revealed using AMOVA and an MDS plot.

Results: A total of 96 haplotypes were identified with overall haplotype diversity (HD) and discrimination capacity (DC) of 0.9985 and 0.9320, respectively. Genetic differentiation was observed with most of the comparison populations, prominently for Guizhou Shui.

Conclusion: The 23 Y-STR loci were highly polymorphic and discriminating in the Guizhou Miao population and could be used for forensic practice and population genetic studies. Population relationship analysis revealed Guizhou Miao had a close genetic relationship with geographically close Guizhou Gelao, as well as Han majorities derived from different regions.     

Genetic Relationship Between IL-6 rs1800796 Polymorphism and Susceptibility to Periodontitis

Background: There are accumulating reports for the potential role of Interleukin-6 (IL-6) rs1800796 polymorphism in the risk of periodontitis. However, distinct conclusions are observed. In this study, we have an interest in comprehensively analyzing the genetic relationship between IL-6 rs1800796 and the susceptibility to periodontitis.

Methods: We retrieved the eligible case-control studies from on-line database and conducted a meta-analysis. P-value of association test, OR (odd ratios) and 95% CI (confidence interval) were calculated for the assessment of potential genetic association.

Results: We enrolled a total of 20 case-control studies for pooling analysis. A positive association between periodontitis cases and controls was observed in the overall meta-analysis under all genetic models (all P < 0.05, OR > 1). Similar results were detected in the “population-based, PB” and “China” subgroups (all P < 0.05, OR > 1). In the “Asian” subgroup, there is an increased periodontitis risk under the allele, homozygote, heterozygote, dominant and carrier models (all P < 0.05, OR > 1). Nevertheless, negative results were found in the “Caucasian” subgroup under all models [all P > 0.05]. In addition, a positive association between IL-6 rs1800796 and the risk of chronic periodontitis was detected under the models of allele [G vs. C], GG vs. CC, GG vs. CC+ CG and carrier [G vs. C] (all P < 0.05, OR > 1).

Conclusion: IL-6 rs1800796 may serve as one genetic risk factor for periodontitis patients in the Asian population, especially the Chinese population. G/G genotype of IL-6 rs1800796 appears to be associated with an increased risk of chronic periodontitis.     

Tachykinin upregulation in atopic dermatitis

Context: Atopic dermatitis (AD) is a chronic, inflammatory, itching skin disorder, which may worsen due to stress, depression and anxiety. Tachykinins may be involved in inflammation signaling as well as they may have a role in stress, depression and anxiety.

Objective: This study aimed to measure the expression of tachykinin markers, in the skin of patients with AD, and the correlation of these tachykinins with clinical and psychodemographic parameters.

Materials and methods: Twenty-eight adult patients with AD were investigated regarding tachykinin expression in skin biopsies, using an immunohistochemical technique. The patients were characterized with clinical and psychodemographic parameters.

Results: The number of substance P and neurokinin (NK)A positive nerve fibers, as well as NKA positive mononuclear dermal cells, was increased in lesional compared to non-lesional skin. Interestingly, the depression score and the number of dermal NK-1 receptor (R) positive cells in lesional as well as in non-lesional skin showed a correlation.

Conclusion: These findings indicate an upregulation of the tachykinergic system in the inflamed skin of AD.     

Sex-dependent effect of post-migration adaptation on height and relative lower leg length in Polish youth

Background: Growth in tibia length is considered to be particularly sensitive to environmental stress.

Aim: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children.

Subjects and methods: Data included a nationwide random sample of 17,155 schoolchildren, 7–18?years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio.

Results: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio.

Conclusion: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children.     

The Association between Genetic Variation in Wnt Transcription Factor TCF7L2 (TCF4) and Alopecia Areata

Background: Alopecia areata (AA) is a non-scarring hair loss with a polymorphous presentation ranging from patchy lesions to involvement of the entire scalp. The disease is the consequence of an autoimmune attack on hair bulbs that results in a premature transition of hair follicles to catagen and telogen. Thus the Wnt/β-catenin signaling pathway that regulates the hair cycling might be involved in the pathogenesis of AA. Genetic variations in the components of Wnt/β-catenin could greatly alter their adaptive mechanisms against an immunologic attack.

Objectives: Our aim was to investigate the association between AA and genetic polymorphisms in the TCF7L2 gene, one of the most important components of the Wnt/β-catenin pathway.

Methods: This is a case-control study of 145 patients with AA and 152 healthy controls. Genotyping of the TCF7L2 gene (rs7903146) was performed via the ARMS—PCR method (amplification refractory mutation system- polymerase chain reaction). The allele and genotype distribution was compared between the two groups.

Results: The frequency of the T allele (0.38 vs. 0.28, odds ratio = 1.56, 95% CI = 1.09–2.17, p = 0.013) and TT + CT genotypes (0.68 vs. 0.53, odds ratio = 1.88, 95% CI = 1.17–3.02, p = 0.008) were significantly higher in AA patients.

Conclusions: This study indicates that the TCF7L2 gene variant is associated with AA. Its contribution to disease pathogenesis could either be through a hair cycling defect or dendritic cell dysregulation.     

Maternal Serum sEndoglin and Cell-Free Fetal DNA as Probable Markers of Preeclampsia: A Study in Single Center,Egypt

Background: This study was conducted to compare the levels of maternal serum soluble endoglin (sEng) and cell-free fetal DNA (cffDNA) in pregnant females with PE to normotensive pregnant ones, together with relating these levels to preeclampsia (PE) severity and onset.

Method of the study: It was a comparative study in Mansoura University Hospital, Egypt, to detect the levels of serum sEng by ELISA besides the levels of cffDNA by quantitative real-time polymerase chain reaction in 80 pregnant females suffering from PE in addition to 80 normotensive pregnant ones that were included as control.

Results: Levels of serum sEng and cffDNA were higher in PE cases than control (p < 0.0001? both) and were significantly related to the severity of the disease. Levels were also higher in early than late onset PE (p < 0.003? and <0.002?, respectively). Sensitivities, specificities, positive, and negative predictive values in addition to accuracy of serum sEng and cffDNA were 97.5%, 98.8%, 98.7%, 97.5%, and 98.1% and 97.5%, 93.8%, 94.0%, 97.4%, and 95.6%, respectively.

Conclusion: Maternal serum sEng and cffDNA can be good markers for diagnosis of PE in Egyptian patients. They are positively related to the disease severity.

Abbreviations: cffDNA; Cell-Free Fetal DNA, sEng; soluble Endoglin, PE; preeclampsia, qRT PCR; Quantitative real-time polymerase chain reaction.     

Disengagement and reengagement of HIV continuum of care in a single center cohort in northern Italy

Background: Despite the progress in HIV care, adherence to follow up remains critical. Disengagement impairs the benefit of HIV care and the increasing number of data that associates failed retention with worse outcomes has led public health institutions to consider retention in care as a new tool to fight against HIV pandemic.

Objective: The aim of this retrospective, observational study was to estimate the burden of disengagement and reengagement in care in our HIV cohort and to identify the characteristics of our LTFU and reengaged patients. Moreover, we build our cascade of care to explore how closely our center aligned with the “90–90–90” targets.

Methods: From the local electronic database we extracted all HIV-infected patients with at least one contact with HIV Clinic between 2012 and 2018 excluding deceased and transferred patients.

Our definition of LTFU was based on the lack of any visit during at least 1 year after the last visit. Patients re-engaged were defined as those firstly considered as LTFU patients who subsequently were newly linked to HIV care.

Results: About 8% of patients were lost to follow up during the period of study, with a rate of less than 2% per year and 14.1% of them were re-engaged in care. The cascade of care shows, among HIV cases diagnosed between 2011 and 2018, 86.7% patients retained in care, 94.1% of whom were on cART and 95.6% of whom were virologically suppressed.

A higher attrition was found among infections diagnosed since 2011 than before 2011, such as women, patients coming from foreign countries and those with poor virological control.

Conclusions: The retention rate found in our cohort is high and is in accordance with the 90–90–90 strategy. Nevertheless, understanding disengagement and re-engagement determinants is important to strengthen retention in care in the most fragile population.     

Preclinical evidences of safety of a new synthetic adjuvant to formulate with the influenza human vaccine: absence of subchronic toxicity and mutagenicity

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5?years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations.

GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice.

Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted.

Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines.

Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally.

Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.     

UBASH3A gene polymorphisms and expression profile in rheumatoid arthritis

Objectives: Recent evidence has demonstrated that UBASH3A play a pivotal role in multiple autoimmune diseases. In this study, we explored the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also comparatively evaluated the UBASH3A expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls.

Methods: Four UBASH3A polymorphisms (rs1893592, rs11203203, rs2277798, and rs3788013) were studied in 553 patients with RA and 587 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array Integrated Fluidic Circuit (IFC). For gene expression study, UBASH3A mRNA levels of 30 RA patients and 31 healthy individuals were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Data were analyzed by SPSS 19.0 software.

Results: A significant association between rs1893592 polymorphism and RA was found under all genetic models (all p<.05). We also discovered a significant association between rs3788013 polymorphism and RA in the allele and genotype distributions, as well as the recessive model (all p<.05). Moreover, we found the genotype distribution and allele frequency of rs1893592 were significantly associated with RF phenotype in the RA patients (χ²?=?6.786, p=.034; χ²?=?4.534, p=.033; respectively). We also found the genotype distribution and allele frequency of rs2277798 were significantly associated with anti-CCP phenotype in the RA patients (χ²?=?7.873, p=.020; χ²?=?4.473, p=.034; respectively). However, we did not detect any significant associations between rs11203203 and RA susceptibility and autoantibody profiles (all p>.05). The mRNA expression of UBASH3A was increased in PBMCs of patients with RA when compared to healthy controls (p=.001).

Conclusions: Our observations suggested that the dysregulation of UBASH3A might be associated with the pathogenesis of RA, and UBASH3A gene polymorphisms (rs1893592 and rs3788013) might contribute to RA susceptibility in Chinese Han population.     

Further Evidence for Embedded Performance Validity Tests in Children within the Conners’ Continuous Performance Test – Second Edition

Objective: To replicate previous research on Conners’ Continuous Performance Test – Second Edition subscales as performance validity tests (PVTs) in children.

Method: Classification accuracy for the Omissions (OMI), Hit Reaction Time (HRT), and Perseverations (PER) subscales was computed for 414 children and adolescents.

Results: Overall, OMI, HRT, and PER demonstrated good specificity but low and variable sensitivity across cutoffs.

Conclusions: Results suggest that OMI, HRT, and PER can function as embedded PVTs in mixed clinical samples of children, although their clinical utility is limited by their low sensitivity. Implications for the use of these PVTs in the context of attention-deficit/hyperactivity disorder evaluations, medication-seeking patients, and sports concussion clinics are discussed.     

Anti-inflammatory potential of pyocyanin in LPS-stimulated murine macrophages

Context: Pyocyanin is a typical Pseudomonas aeruginosa virulence factor, a common Gram-negative rod responsible for a wide range of severe nosocomial infections. There is evidence indicating that pyocyanin has multiple biological activities, but little is known about anti-inflammatory properties.

Objective: This study investigated pyocyanin effect on nitric oxide and cytokine production in lipopolysaccharide (LPS)-activated murine peritoneal macrophages.

Materials and methods: Macrophages were incubated in the presence and absence of pyocyanin (1, 5, 10, 50, and 100 µM) with and without LPS (1 µg/mL). Nitric oxide production was determined by Griess reagent and tumor necrosis factor (TNF)-α and interleukin (IL)-1β production was assessed by enzyme-linked immunosorbent assay. In addition, pyocyanin effects on zymosan A-induced peritonitis in mice were evaluated.

Results: Pyocyanin (5 and 10 µM) decreased nitric oxide, TNF-α, and IL-1β production independent of macrophage death. On the other hand, in vivo, pyocyanin (5 mg/kg) was not able to affect leukocyte migration into the site of inflammation.

Discussion and conclusion: Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless more detailed studies should be performed to confirm this hypothesis.     

Timing of puberty and reserve capacity in adolescence as pathways to educational level in adulthood—a longitudinal study

Background: Family socioeconomic status (SES) is related to a child’s educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence.

Aim: To study whether family SES affects a child’s adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence.

Subjects and methods: Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n?=?37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29–43?years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used.

Results: Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model.

Conclusions: The results show that family SES affects the child’s adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.     

RNA protein kinase SNP at −226 C<T is a biomarker for the clearance of HCV among Egyptian patients

Background: RNA-dependant protein kinase R (PKR) is a primary mediator in the defence mechanism of interferon against viral replication and pathogenesis during Hepatitis C virus (HCV) infection. In the present study, we have examined the role of Single Nucleotide Polymorphisms (SNPs) in the promoter region of PKR and the serum level of the same protein on the outcome of HCV-infected Egyptian patients.

Patients and Methods: Genomic DNA was extracted from a total of 135 subjects, including 15 healthy controls, 40 HCV spontaneous resolvers (SRs), and 80 patients with chronic HCV infection. PKR genotyping was assessed using DNA sequencing. Finally, serum levels of PKR, TNF-α, INF-γ, and IL-10 were measured using ELISA technique.

Results: Serum levels of PKR, TNF-α, and INF-γ showed a significant increase in SRs as compared to chronic HCV patients. On the other hand, serum levels of IL-10 were significantly higher in chronic HCV patients compared to SRs. The present study demonstrated two novel SNPs in the PKR promoter region: at ?226 C/T and ?141 C/G. The PKR SNP at ?226 C < T correlated with HCV-infected patients (genotype 4a) outcome among Egyptians. Our data showed the unique presence of the TT genotype in SRs group (three patients: 7.5%) in PKR ?226 C/T. Interestingly, subjects with the TT genotype were more likely to clear their HCV infection than those with the CC genotype.

Conclusion: Our work provides more detail about PKR gene polymorphism in HCV genotype 4a as a new clinical tool for anticipating HCV-4a infection outcome.