TNF-α -238, -308, -863 polymorphisms,and brucellosis infection

BackgroundBrucella abortus is an intracellular bacterium that affects humans and domestic animals. Tumor necrosis factor-alpha (TNF-α) has been shown as a key player in the induction of cell-mediated resistance against Brucella infection. We aimed to evaluate the possible influence of the TNF-α promoter polymorphisms (-308 G/A, -238 G/A, and -863 C/A) on the susceptibility of human brucellosis.MethodologyA total of 153 patients with active brucellosis and 128 healthy individuals were recruited. All subjects were genotyped for the polymorphisms in the TNF-α gene by Allele-Specific polymerase chain reaction analysis.ResultsOur results showed that the TNF-α -308 GG genotype was significantly more frequently present in controls than in brucellosis patients (91% vs. 75%), thus was a protective factor against developing brucellosis (OR = 0.313, p = 0.001). In contrast, the -308 GA genotype (OR = 3.026, p = 0.002) and minor allele (A) (OR = 3.058, p = 0.001) as well as AAG haplotype (OR = 4.014, p = 0.001) conferred an increased risk of brucellosis. However, the -238 G/A and -863 C/A polymorphisms were not associated with the risk of brucellosis at both allelic and genotypic levels (p > 0.05).ConclusionOur study revealed that the TNF-α -308 A allele or GA heterozygosity or AAG haplotype were associated with an increased risk of brucellosis in our population.     

Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis

BackgroundPeriodontitis is a chronic inflammatory disease triggered by the host immune response. Epigenetic modifications also affect the immune response. We assessed CpG methylation in 22 inflammatory candidate genes (ATF2, CCL25, CXCL14, CXCL3, CXCL5, CXCL6, FADD, GATA3, IL10RA, IL12A, IL12B, IL13, IL13RA1, IL15, IL17C, IL17RA, IL4R, IL6R, IL6ST, IL7, INHA, and TYK2) with respect to the occurrence of aggressive periodontitis (AgP).Patients and methodsIn this study 15 AgP patients (53.3% males, 41.4 ± 10.5 years) and 10 controls (40.0% males, 36.9 ± 17.5 years) were included. The methylation patterns of gingival biopsies were quantified using EpiTect® Methyl Signature PCR Array Human Inflammatory Response.ResultsIn gingival biopsies taken from patients with AgP, CpG methylation of CCL25 (1.73% vs. 2.59%, p = 0.015) and IL17C (6.89% vs. 19.27%, p = 0.002) was significantly reduced as compared with periodontally healthy tissues.DiscussionWe showed for the first time a differential methylation pattern for CCL25 and IL17C in periodontitis. CCL25 plays an important role in T-cell development, whereas IL17C regulates innate epithelial immune responses. The decrease in CpG methylation is presumably accompanied by an increase in gene expression. This could lead to a greater availability of CCL25 and interleukin 17C and support periodontal loss of attachment.     

Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13

AimExcessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.MethodsSixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5 ml), cecal ligation and puncture (CLP) plus PBS (5 ml), CLP plus UTI (5000 U/kg), CLP plus UTI (10,000 U/kg), CLP plus UTI (20,000 U/kg) and sham-operation plus UTI (10,000 U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.ResultsThe intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.ConclusionUlinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.     

Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients

Study backgroundInsulin resistance plays an important role in the pathogenesis of type 2 diabetes and the metabolic syndrome. Many of the genes and pathways involved have been identified but some remain to be defined. Metallothioneins (Mts) are a family of anti-oxidant proteins and metallothionein 2a (Mt2a) polymorphims have been recently associated with type 2 diabetes and related complications. Our objective was to determine the Mt2a gene expression levels in adipose tissues from diabetic patients and the effect of Mt treatment on adipocyte insulin sensitivity.MethodsSamples of subcutaneous and visceral adipose tissues from lean, type 2 diabetic and non-diabetic obese patients were analysed using RT-qPCR for Mt2a mRNA abundance. The regulation of Mt2a expression was further studied in 3T3-L1 adipocytes treated or not with TNFα (10 ng/ml, 72 h) to induce insulin resistance. The effects of Mt on glucose uptake were investigated in cultured adipocytes treated with recombinant Mt protein.ResultsWe found that the Mt2a gene expression was significantly higher in adipose tissue of type 2 diabetic patients in comparison to that of lean (p = 0.003) subjects. In 3T3-L1 adipocytes, insulin resistance induced by TNFα increased Mt2a mRNA levels (p = 3 × 10^? 4) and insulin-stimulated glucose uptake was significantly inhibited by 53% (p = 8 × 10^? 4) compared to vehicle, when 3T3-L1 adipocytes were treated with Mt protein.ConclusionsThese data suggest that Mt2a might be involved in insulin resistance through the up-regulation of Mt gene expression, which may lead to the modulation of insulin action in fat cells. These results suggest the concept of considering Mt proteins as markers and potential targets in type 2 diabetes.     

Guided self-determination improves life skills with Type 1 diabetes and A1C in randomized controlled trial

ObjectiveTo report 1-year results of newly developed method, guided self-determination (GSD), applied in group training (GSD-GT) for Type 1 diabetes patients with persistent poor glycaemic control.MethodsGSD was designed on the basis of qualitative research to help patients develop life skills with diabetes using worksheets filled in at home and coached by nurses in mutual reflection. We randomized 18–49-year-old adults at a Danish university hospital to either 16 h GSD-GT in 2001 or to similar training 1 year later. Inclusion criteria: mean A1C ≥ 8.0% for at least 2 years, disease onset ≤40 years and insulin treatment from onset.ResultsThirty GSD-GT patients and 20 controls completed the study. GSD-GT patients did better than control patients in terms of (a) increased autonomy support perceived from health professionals (p < 0.01); (b) higher frequency of self-monitored blood glucoses (p < 0.001); (c) increased perceived competence in managing diabetes (p < 0.01); (d) fewer diabetes-related problems (p < 0.05); and (e) improved glycaemic control (p < 0.01).ConclusionGSD was effective in improving life skills with diabetes, including A1C, over a period of 1 year.Practice implicationsGSD is a worthy candidate for further research. We consider it adjustable to people with type 2 diabetes and other chronic conditions.     

Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease

PurposeLeft main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3–5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD.Material/methodsWe enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups – with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes.ResultsWe observed more complications with wound healing (40.5% vs. 12.8%, p < 0.001) and sternal dehiscence (23.8% vs. 4.0%, p < 0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p = 0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p = 0.014).ConclusionsPatients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.     

Does patient activation predict the course of type 2 diabetes? A longitudinal study

ObjectiveTo examine whether patient activation is predictive of the course of diabetes over a three year period among patients with and without diabetes.MethodsLongitudinal analyses utilized electronic health record data from 2011 to 2014. We examined how the patient activation measure (PAM) was predictive of 2014 diabetes-related outcomes among patients with diabetes (n = 10,071); pre-diabetes (n = 1804); and neither diabetes nor pre-diabetes (n = 46,402). Outcomes were clinical indicators (blood pressure, cholesterol, and trigylcerides), costly utilization, and progression from no diabetes to pre-diabetes or diabetes.ResultsHigher PAM level predicted better clinical indicator control in patients with diabetes. In patients with pre-diabetes, PAM level predicted better clinical indicator control, and those in the highest level of PAM in 2011 had lower odds of having a hospitalization compared to those in the lowest level. In patients without diabetes or pre-diabetes in 2011, higher PAM level was associated with lower odds of developing pre-diabetes.ConclusionsMore activated patients with diabetes and pre-diabetes had better outcomes than less activated patients. More activated patients without diabetes or pre-diabetes were less likely to develop pre-diabetes over a three year period.Practice implicationsStrategies to improve patient activation may be useful to help curb the diabetes epidemic.     

Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children

Toll-like receptors (TLR) initiate innate and often affect adaptive immune response. This study aimed to determine if TLR response and T regulatory cell (Treg) function in peripheral blood mononuclear cells (PBMC) correlate with clinical severity in non-infectious asthma. TLR1–9 expression and representative response cytokine TNF-α, IL-6, and IFN-β secretions were analyzed after stimulation by TLR1–9 ligands from 17 non-infectious asthmatic children. TNF-α production was higher in TLR1/2 (median 385.4 vs. 250.3 pg/ml in 1 μg/ml Pam3CSK4, p = 0.0078), TLR4 (2392.4 vs. 1355.9 in 1 μg/ml LPS; p = 0.0005), and TLR7/8 (10,776.2 vs. 4237.0 pg/ml in 1 μg/ml R848, p = 0.0079) of patients in exacerbation than those in convalescence and healthy controls despite equal TLR expression. TNF-α production stimulated by TLR9 agonist was significantly lower in exacerbation (17.7 vs. 34.9 pg/ml in 1 μg/ml ODN2216, p = 0.0175), while IL-6 production had similar patterns but was significantly lower in TLR3 signaling (119.7 vs. 245.0 pg/ml in 0.1 μg/ml poly(I:C), p = 0.0033). IFN-β production by TLR3 agonist also decreased in exacerbation but not statistically significant. Six older children showed decreased FOXP3 percentage in CD4 + CD25^high and decreased suppression capability in exacerbation but restored in stabilization (82.8% vs. 90.0%, p = 0.0061 and 60.9% vs. 81.7%, p = 0.0071; respectively). In conclusion, normalizing imbalanced TLR signaling and enhancing Treg cell capability may guide possible therapeutic strategies for non-infectious asthma in exacerbation.     

High levels of plasma interferon gamma and +874T/A gene polymorphism is associated with HIV-TB co-infection

ObjectiveTuberculosis (TB) is one of the most frequent opportunistic infections in HIV patients leading to increased morbidity and death rate. This study was carried out to investigate the role of the cytokines IFN-γ and TNF-α level and their single nucleotide polymorphisms (SNPs) in HIV-TB co-infection.Methods247 HIV-TB (124 HIV-pulmonary TB, 123 HIV-extra pulmonary TB), 126 HIV positive individuals without tuberculosis and 129 healthy subjects (HS) were included to measure plasma levels of IFN-γ and TNF-α by sandwich ELISA and One way ANOVA statistical analysis was carried out among the groups. The SNPs of TNF-α-308 G/A, -238 G/A and IFN-γ + 874 T/A were also investigated using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The frequencies between the groups were compared by Pearson’s chi square statistical analysis.ResultsPlasma IFN-γ and TNF-α were significantly elevated in HIV-TB and TB (p < 0.05) as compared to those in HS group. There was significant association between IFN-γ + 874 ‘A’ allele and AA genotype in HIV-TB groups compared to HS and HIV (p < 0.05) and no such association was found for TNF-α-308 and -238. The plasma cytokine levels of TNF-α and IFN-γ reveals no significant association with levels of IFN-γ + 874 T/A, TNF-α -308 G/Aand-238 G/A genotypes in any of the study groups.ConclusionIn conclusion, the present study revealed elevated plasma IFN-γ and its +874 ‘A’ allele are associated with HIV-TB co-infection indicating 1.6 times increased risk for TB susceptibility. Elevated TNF-α levels in TB and HIV-TB suggest its involvement in TB pathogenesis.     

Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients

The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (?308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α ?308A (OR = 2.3, p = 0.0001, Pc = 0.0003) and LTα +252G (OR = 2.1, p < 0.0001, Pc < 0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR = 12.2, p = 0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α ?308G/A + A/A genotypes (p < 0.01) and LTα +252 A/G + G/G genotypes (p < 0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with ?308G/A + A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR = 3.9, p = 0.0014, Pc = 0.0098) and anti-Sm antibodies (OR = 4.1, p = 0.0002, Pc = 0.0014). The present study suggests TNF-α ?308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients.     

Mobilization of hematopoietic stem cells in patients undergoing HSCT as a treatment of early diabetes type 1

BackgroundThe immunoablation with autologous hematopoietic stem cell transplantation is a new experimental treatment of early diabetes type 1. The treatment is based on destruction of immune system with cytotoxic drugs which leads to halt of immune reaction directed against beta cells of pancreas. During that treatment young patients with diabetes type 1 who are otherwise healthy undergo mobilization with cyclophosphamide (CY) and G-CSF. They are naïve to cytotoxic drugs and mobilization is their first contact with chemotherapy. We analyzed the efficiency of mobilization with cyclophosphamide and G-CSF in this population.MethodsWe analyzed the medical records of 25 patients with diabetes who underwent mobilization with cyclophosphamide and G-CSF.ResultsThe median white blood cell count on the first day of apheresis was 14.6 × 10³/μL (range 1.5–33.3) in CY + G-CSF mobilized patients. Median absolute CD 34+ cell count in peripheral blood on the first apheresis day was 0.095 127 × 10³/μL (range 0.026–0.477). The median total number of collected CD34+ cells during one or two (if needed) aphereses was 466 × 10⁶ (range 204–816) or 7.24 × 10⁶ CD34+ cells per kg of patient body weight (range 3.03–13.1). There were no poor mobilizers who were unable to collect sufficient cell numbers.ConclusionThe mobilization of hematopoietic stem cells with CY + G-CSF in patients with early diabetes type 1 is efficient and the underlying diabetes does not impair the efficiency of hematopoietic stem cell collection.     

An EEG-based functional connectivity measure for automatic detection of alcohol use disorder

BackgroundThe abnormal alcohol consumption could cause toxicity and could alter the human brain’s structure and function, termed as alcohol used disorder (AUD). Unfortunately, the conventional screening methods for AUD patients are subjective and manual. Hence, to perform automatic screening of AUD patients, objective methods are needed. The electroencephalographic (EEG) data have been utilized to study the differences of brain signals between alcoholics and healthy controls that could further developed as an automatic screening tool for alcoholics.MethodIn this work, resting-state EEG-derived features were utilized as input data to the proposed feature selection and classification method. The aim was to perform automatic classification of AUD patients and healthy controls. The validation of the proposed method involved real-EEG data acquired from 30 AUD patients and 30 age-matched healthy controls. The resting-state EEG-derived features such as synchronization likelihood (SL) were computed involving 19 scalp locations resulted into 513 features. Furthermore, the features were rank-ordered to select the most discriminant features involving a rank-based feature selection method according to a criterion, i.e., receiver operating characteristics (ROC). Consequently, a reduced set of most discriminant features was identified and utilized further during classification of AUD patients and healthy controls. In this study, three different classification models such as Support Vector Machine (SVM), Naïve Bayesian (NB), and Logistic Regression (LR) were used.ResultsThe study resulted into SVM classification accuracy = 98%, sensitivity = 99.9%, specificity = 95%, and f-measure = 0.97; LR classification accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6%, and f-measure = 0.90; NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9%, and f-measure = 0.95.ConclusionThe SL features could be utilized as objective markers to screen the AUD patients and healthy controls.     

The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

BackgroundType 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. PTPN22 and IL2RA polymorphisms have been found to be associated with several autoimmune diseases including T1D.AimsWe aimed to elucidate the role of PTPN22 and IL2RA polymorphisms in predisposition of T1D in Egyptian children.MethodsWe studied 150 children and adolescents with T1D and 165 healthy controls. The PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms were genotyped using polymerase chain reaction.ResultsWe found that carriers of the T allele of PTPN22 were significantly more likely to develop T1D (OR = 2.2, 95% CI = 1.2–4, P = 0.01). Also, the carrier of TT genotype and T allele of IL2RA more likely to develop T1D (OR = 2.8, 1.4, respectively, P = 0.03). There was a statistically significant association between T allele of PTPN22 gene and females ⩽10 years old at the onset of diabetes (OR = 4, 95% CI = 1.2–13.4, P = 0.019).ConclusionThis study suggests a possible association between the T allele of PTPN22 gene and TT genotype of IL2RA with T1D in studied Egyptian children, especially, females with early onset diabetes who carried the 1858T allele.     

Association of CTLA4 exon-1 polymorphism with the tumor necrosis factor-α in the risk of systemic lupus erythematosus among South Indians

Cytotoxic T lymphocyte associated-antigen (CTLA4) is a potential negative regulatory molecule of T-cells and associated with several autoimmune diseases. Several reports from different ethnic groups showed that the polymorphisms of the CTLA4 gene have been associated with autoimmune diseases including SLE. Therefore, we aimed to investigate the +49 A/G polymorphism in South Indian SLE patients and its association with disease aetiology and serological markers. A total of 534 samples were genotyped for the +49 A/G polymorphism in exon 1 of the CTLA-4 gene through PCR-RFLP method. We found significant association of genotype and allele frequencies with +49 A/G polymorphism in SLE patients. The frequency of the +49 A/G polymorphism rs231775 ‘GG’ genotype was significantly higher in patients with SLE (12.32%) than those in healthy control subjects (4.6%) (OR: 1.797; 95% CI 1.264–2.554; p = 0.001). The frequency of mutant allele ‘G’ also found to be significantly higher in cases (36.01%) than controls (24.92%) (OR: 1.695, 95% CI: 1.298–2.214, p < 0.001). We observed significant increase in serum TNF-α, interferon-α, IL-10 and IL-12 in SLE cases compared to controls. We also found a significant association of serum TNF-α, interferon-α, IL-10 and IL-12 with SLE phenotypes. In addition there was a significant increase in serum TNF-α level in “GG” genotype SLE subjects suggesting that it might play a major role in the advancement of SLE disease.     

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women

ObjectiveThe aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.Study designWe genotyped the INHA polymorphisms c.-16C > T (rs35118453) and c.-124A > G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.ResultsThere were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T–G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR = 1.630, 95% CI = 1.081–2.457). Combination genotype analysis showed that the CT + TT/GG genotype frequency was higher in POI patients than in the controls (OR = 2.414, 95% CI = 1.190–4.895).ConclusionsWe provide evidence to suggest that when the two variant alleles are combined, the c.-16C > T and c.-124A > G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.     

Tumor necrosis factor-alpha single nucleotide polymorphisms in juvenile systemic lupus erythematosus

BackgroundJuvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study.MethodsFifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions −308 and −238 were evaluated, using polymerase chain reaction with sequence-specific primers method.ResultsThe G allele at position −238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value < 0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients’ group compared with control subjects (P value < 0.001). The GA haplotype of TNFA (positions −308, −238) was significantly less frequent in case group than in controls (P value < 0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value < 0.01).ConclusionsPro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.     

Patient adoption of an internet based diabetes medication tool to improve adherence: A pilot study

ObjectiveTo investigate the effect of a video intervention, Managing Your Diabetes Medicines, on patient self-efficacy, problems with using medication, and medication adherence in a rural, mostly African American population.MethodsPatients selected their problem areas in medication use and watched one of nine 2-min videos with a research assistant at a clinic or pharmacy and were given an access code to watch all the videos at their convenience. Outcomes were measured at baseline and 3-month follow-up.ResultsFifty-one patients were enrolled; 84% were African American and 80% were female (mean age: 54 years). Seventy-three percent watched at least one module after the initial visit. Improved self-efficacy was associated with a decrease in concerns about medications (r = −0.64). Low literate patients experienced greater improvement in self-efficacy than more literate patients (t = 2.54, p = 0.02). Patients’ mean number of problems declined from 6.14 to 5.03. The number of patients with high or medium adherence rose from 33% at baseline to 43% at 3-month follow-up.ConclusionsA practical, customized video intervention may help improve patient self-efficacy, reduce problems with medication use, and improve medication adherence in diabetes patients.Practice implicationsProviders should consider implementing technology-based interventions in the clinic to address common problems that patients have with self-management.     

High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4+CD25high cells in children with type 1 diabetes

PurposeDespite the rapidly rising incidence of diabetes in children, with the highest rise in children < 5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.Material/methodsThe study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children < 5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.ResultsThe frequency of CD4⁺CD25^highOX40⁺ was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p = 0.003). Moreover, T1D children had higher frequency of CD4⁺CD25^high4-1BB⁺ cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p = 0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r = 0.54, 95% CI [0.19–0.77], p = 0.004). In comparison with age-matched controls, children < 5 years had higher frequency of CD4⁺CD25^highOX40⁺ (p = 0.004) and CD4⁺CD25^high4-1BB⁺ cells (p = 0.079).ConclusionsOur study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children < 5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.