A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia

We applied a family-based association approach to investigate the role of the DYX1C1 gene on chromosome 15q as a candidate gene for developmental dyslexia (DD) to 158 families containing at least one dyslexic child. We directly sequenced exons 2 and 10 of the DYX1C1 gene and found eight single nucleotide polymorphism (SNPs), three of which (-3G>A, 1249 G>T, 1259 C>G) were suitable for the genetic analyses. We performed single- and multimarker association analyses with DD as a categorical trait by FBAT version 1.4 and TRANSMIT version 2.5.4 programs. Our sample had a power of at least 80% to detect an association between the selected phenotypes and the informative polymorphisms at a significance level of 5%. The results of the categorical analyses did not support the involvement of the DYX1C1 gene variants in this sample of dyslexics and their relatives. Quantitative and multimarker analyses, which provide greater power to detect loci with a minor effect, consistently yielded nonsignificant results. While D1X1C1 is a good candidate gene for DD, we were unable to replicate the original findings between DYX1C1 gene and DD, perhaps due to genetic heterogeneity.     

Investigation of Dyslexia and SLI Risk Variants in Reading- and Language-Impaired Subjects

Dyslexia (or reading disability) and specific language impairment (or SLI) are common childhood disorders that show considerable co-morbidity and diagnostic overlaps and have been suggested to share some genetic aetiology. Recently, genetic risk variants have been identified for SLI and dyslexia enabling the direct evaluation of possible shared genetic influences between these disorders. In this study we investigate the role of variants in these genes (namely MRPL19/C20RF3, ROBO1, DCDC2, KIAA0319, DYX1C1, CNTNAP2, ATP2C2 and CMIP) in the aetiology of SLI and dyslexia. We perform case–control and quantitative association analyses using measures of oral and written language skills in samples of SLI and dyslexic families and cases. We replicate association between KIAA0319 and DCDC2 and dyslexia and provide evidence to support a role for KIAA0319 in oral language ability. In addition, we find association between reading-related measures and variants in CNTNAP2 and CMIP in the SLI families.     

Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia.

Dyslexia is a common heterogeneous disorder with a significant genetic component. Multiple studies have replicated the evidence for linkage between variously defined phenotypes of dyslexia and chromosomal regions on 15q21 (DYX1) and 6p22.2 (DYX2). Based on association studies and the possibility for functional significance of several polymorphisms, candidate genes responsible for the observed linkage signal have been proposed-DYX1C1 for 15q21, and KIAA0319 and DCDC2 for 6p22.2. We investigated the evidence for contribution of these candidate genes to dyslexia in our sample of multigenerational families. Our previous quantitative linkage analyses in this dataset provided supportive evidence for linkage of dyslexia to the locus on chromosome 15, but not to the locus on chromosome 6. In the current study, we used probands from 191 families for a case control analysis, and proband-parent trios for family-based TDT analyses. The observation of weak evidence for transmission disequilibrium for one of the two studied polymorphisms in DYX1C1 suggests involvement of this gene in dyslexia in our dataset. We did not find evidence for the association of KIAA0319 or DCDC2 alleles to dyslexia in our sample. We observed a slight tendency for an intronic deletion in DCDC2 to be associated with worse performance on some quantitative measures of dyslexia in the probands in our sample, but not in their parents.     

A Dyslexia-Associated Variant in <Emphasis Type="Italic">DCDC2</Emphasis> Changes Gene Expression

Reading disability (RD) or dyslexia is a common neurogenetic disorder. Two genes, KIAA0319 and DCDC2, have been identified by association studies of the DYX2 locus on 6p21.3. We previously identified a 2445 bp deletion, and a compound STR within the deleted region (BV677278), in intron 2 of DCDC2. The deletion and several alleles of the STR are strongly associated with RD (P = 0.00002). In this study we investigated whether BV677278 is a regulatory region for DCDC2 by electrophoretic mobility shift and luciferase reporter assays. We show that oligonucleotide probes from the STR bind nuclear protein from human brain, and that alleles of the STR have a range of DCDC2-specific enhancer activities. Five alleles displayed strong enhancer activity and increased gene expression, while allele 1 showed no enhancer activity. These studies suggest that the association of BV677278 with RD reflects a role as a modifier of DCDC2 expression.     

Genetic Association of IL-10 Gene Promoter Polymorphism and HIV-1 Infection in North Indians

Introduction  Cytokines play a significant role in host immune defense. IL-10 is an anti-inflammatory, immunomodulatory cytokine that can both stimulate and suppress the immune response and inhibits HIV-1 replication in vivo. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. Aims  The aim of this study was to investigate the association of IL-10 gene promoter −1082 G/A, −819 C/T, and 592 C/A polymorphism on HIV-1 transmission /progression in North Indian individuals. Patients and Methods  A total of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, and III), 50 HIV-1 exposed seronegative (HES) and 305 HIV-1 seronegative (HSN) individuals were genotyped for IL-10 gene promoter by polymerase chain reaction-restriction fragment length polymorphism. A suggestive evidence of association was obtained for IL-10 592 C/A promoter polymorphism at the level of allele and genotype distribution. The frequency of IL-10 592 A allele and genotype was significantly increased in HSP compared to HSN (p = 0.013; OR = 1.412 and p = 0.034; OR = 1.685 respectively). Further comparison in between different clinical stages of HIV-1 infected patients of IL-10 592 A allele and genotype revealed a significant increase in its frequency in the stage III compared with those together in stage I (p = 0.004, OR = 2.181 and p = 0.002, OR = 4.156, respectively). This study reports for the first time that IL-10 gene promoter 592 C/A polymorphism may be a risk factor for HIV-1 transmission/progression in HIV-1 infected North Indian individuals.     

In vivo anthelmintic activity of chelidonine from Chelidonium majus L. against Dactylogyrus intermedius in Carassius auratus

Dactylogyrus intermedius is one of the most common and serious cause of parasitic diseases of freshwater fish in aquaculture, and can cause morbidity and high mortality in most species of freshwater fish worldwide. To attempt controlling this parasite and explore novel potential antiparasitic agents, the present study was designed to ascertain the anthelmintic activity of Chelidonium majus L. whole plant and to isolate and characterize the active constituents against D. intermedius. The ethanol extract from C. majus whole plant showed significant anthelmintic activity against D. intermedius [EC₅₀ (median effective concentration) value = 71.5 mg L⁻¹] and therefore subjected to further isolation and purification using various chromatographic techniques. A quaternary benzo[c]phenanthridine alkaloid exhibited significant activity against D. intermedius was obtained and identified as chelidonine. In vivo anthelmintic efficacy tests exhibited that chelidonine was 100% effective against D. intermedius at a concentration of 0.9 mg L⁻¹, with EC₅₀ value of 0.48 mg L⁻¹ after 48 h of exposure, which is more effective than the positive control, mebendazole (EC₅₀ value = 1.3 mg L⁻¹). In addition, the 48-h median lethal concentration (LC₅₀) for chelidonine against the host (Carassius auratus) was 4.54 mg L⁻¹. The resulting therapeutic index for chelidonine was 9.46. These results provided evidence that chelidonine might be potential sources of new antiparasitic drugs for the control of Dactylogyrus.     

An Examination of Candidate Gene SNPs for Dyslexia in an Indian Sample

Developmental dyslexia (DD) is a complex neuro-genetic disorder associated with difficulty in learning to read despite adequate intelligence and educational opportunities. Studies in different populations have established associations between DD and single nucleotide polymorphisms (SNPs) in a number of candidate genes, including DYX1C1, KIAA0319 and DCDC2. In an ongoing DD study in India, we screened twenty SNPs located within the coding region of these three candidate genes by massARRAY technique. At this point, there is no statistical evidence of association between the allelic variation in the three candidate genes and DD in our sample, although there might be some promising leads for future research that should involve a large and a better characterized sample.     

Higher prevalence of exercise-associated hyponatremia in female than in male open-water ultra-endurance swimmers: the 'Marathon-Swim' in Lake Zurich

We investigated the prevalence of exercise-associated hyponatremia (EAH) in 25 male and 11 female open-water ultra-endurance swimmers participating in the ‘Marathon-Swim’ in Lake Zurich, Switzerland, covering a distance of 26.4 km. Changes in body mass, fat mass, skeletal muscle mass, total body water, urine specific gravity, plasma sodium concentration [Na⁺] and haematocrit were determined. Two males (8%) and four females (36%) developed EAH where one female was symptomatic with plasma sodium [Na⁺] of 127 mmol/L. Body mass and plasma [Na⁺] decreased (p < 0.05). The changes in body mass correlated in both male and female swimmers to post-race plasma [Na⁺] (r = −0.67, p = 0.0002 and r = −0.80, p = 0.0034, respectively) and changes in plasma [Na⁺] (r = −0.68, p = 0.0002 and r = −0.79, p = 0.0039, respectively). Fluid intake was neither associated with changes in body mass, post-race plasma [Na⁺] or the change in plasma [Na⁺]. Sodium intake showed no association with either the changes in plasma [Na⁺] or post-race plasma [Na⁺]. We concluded that the prevalence of EAH was greater in female than in male open-water ultra-endurance swimmers.     

Vascular and baroreceptor abnormalities in young males with a family history of hypertension

Vascular and baroreceptor abnormalities in 44 young males, mean age 21 years, comprising of offspring with (FH⁺; n = 22) and without (FH⁻; n = 22) hypertensive parents, were investigated. Peak forearm blood flow (FBF), which was defined as the highest blood flow obtained following reactive hyperaemia, was assessed using strain gauge plethysmography following 5 min of ischemia. Cardiopulmonary baroreceptor sensitivity was assessed using lower body negative pressure for 5 min at −20 mmHg and was determined by calculating change of stroke volume and forearm vascular resistance (FVR) to lower body negative pressure. Carotid baroreceptor sensitivity was assessed using neck suction at −20, −40, −60, and −80 mmHg and was calculated by dividing RR interval by systolic blood pressure. Augmentation index, a measure of wave reflection, was assessed using applanation tonometry and was calculated as the ratio of augmented pressure and pulse pressure. Peak FBF of FH⁺ was 19% lower than the FH⁻ (p = 0.02). Also FH⁺ had 17% higher peak FVR compared to FH⁻ (p = 0.04). However, there were no significant differences between groups for cardiopulmonary, carotid baroreceptor sensitivity, and augmentation index. These results suggest that peripheral vascular dysfunction appears earlier than abnormal baroreceptor sensitivity in young males with a family history of hypertension.     

Effect of cold water immersion on 100-m sprint performance in well-trained swimmers

The aim of the present study was to examine the effect of cold water immersion (CWI) on sprint swimming performance in simulated competition conditions. Ten well-trained swimmers (5 males, 5 females; 19.0 ± 3.9 years) performed two 100-m swimming sprints (S1 and S2) interspersed with a 30-min passive recovery period, during which athletes were randomly assigned to 5 min of CWI (14°C) or an out-of-water control condition (CON 28°C). During tests, sprint times, heart rate (HR), pre- and post-race parasympathetic activity via HR variability (natural logarithm of the square root of the mean of the sum of the squares of differences between adjacent normal R–R intervals; Ln rMSSD) and blood lactate accumulation ([La]_ac) and clearance ([La]_cle) were recorded. Rates of perceived recovery (RPR) and exertion (RPE) were evaluated before and after each sprint. CWI was associated with a ‘likely’ decrease in swimming performance [1.8% (90% CI 0.2, 3.5)], as well as ‘likely’ lower peak HR [−1.9% (−3.6, −0.2)]. CWI was also associated with a ‘likely’ smaller decrease in Ln rMSSD after the first sprint [−16.7% (−30.9, −4.1)]. RPR was ‘likely’ better [+27.2% (−3.7, 68.0)] following CWI. ‘unclear’ effects were observed for [La]_ac [+24.7% (−13.4, 79.5)], [La]_cle [−7.6% (−24.2, 12.7)] or RPE [+2.0% (−12.3, 18.5)]. Following CWI, changes in sprint times were ‘largely’ correlated with changes in peak HR (r = 0.80). Despite a subjective perception of improved recovery following CWI, this recovery intervention resulted in slower swimming times in well-trained athletes swimming in simulated competition conditions.     

Relationship between CYP2E1 polymorphism and increase of ALT activity during therapy of patients with pulmonary tuberculosis

Association of CYP2E1 polymorphism with ALT activity increase was studied in patients with pulmonary tuberculosis receiving therapy by intermittent and daily protocols. The greatest increment of ALT activity in the group receiving therapy by intermittent protocol was seen in the patients with CYP2E1*7632TA genotype. In patients with wild homozygotic 1 C/1 C (6/6) genotype, ALT activity signifi cantly increased, but remained within the normal range (p = 0.048). In the group on daily regimen, activity of ALT increased signifi cantly in patients with all genotypes identifi ed. A more pronounced elevation surpassing the median of the upper threshold of ALT norm was observed in patients with 7632TA genotype (p = 0.0051) and in patients with 7632TA or -71GT or 1 C/1D genotypes in combinations with wild type alleles by other detected polymorphisms (p = 0.0277). Detection of the CYP2E1 gene 7632 T > A polymorphism was found to be the most informative test for prediction of the hepatotoxic reactions during therapy for tuberculosis.     

Fluid balance, thermal stress, and post exercise response in women's Islamic athletic clothing

This study examined heat stress, heart rate (HR), fluid balance, micro-environment temperature and humidity with Islamic athletic clothing (IC) compared to traditional soccer uniform (SC). Ratings of perceived exertion (RPE), session RPE (S-RPE), comfort, and cooling response were also examined. Female volunteers (N = 8) completed a treadmill [(V)\dot]\textO_2\textpeak \dot{V}{\text{O}}_{{2{\text{peak}}}} test and then, in a randomized, counter-balanced order, two intermittent running bouts (45 min total) in a hot environment (30.0°C WBGT) in IC and SC. Thereafter, participants sat for 40 min in the hot ambient environment. Repeated measures ANOVA revealed significantly greater micro-environment temperature (p = 0.02) (IC 33.3 ± 3.2°C, SC 32.0 ± 2.8°C) and humidity (p = 0.04) (IC 48.4 ± 8.1%, SC 42.9 ± 7.9%) in IC during the exercise trial but no difference in the 40-min recovery period for micro-environment temperature (p = 0.25) or humidity (p = 0.18). No significant difference (p > 0.05) was shown for core temperature (T _rec) (IC 38.3 ± 0.4°C, SC 38.2 ± 0.4°C), HR (IC l54 ± 28 beats min⁻¹, SC 151 ± 26 beats min⁻¹) or RPE (IC 4.7 ± 2.1, SC 3.8 ± 1.7) during the exercise trial or recovery period. Results from a paired t test revealed a significantly greater (p < 0.05) S-RPE (IC 5.8 ± 1.2, SC 4.3 ± 1.9), sweat loss (IC 1.4 ± 0.4 L h⁻¹, SC 1.2 ± 0.4 L h⁻¹) and greater discomfort during the exercise and recovery period for the IC. IC clothing appears to have no detrimental effects on heat storage or heat strain during exercise or recovery.     

Induction and decay of short-term heat acclimation

The purpose of this work was to investigate adaptation and decay from short-term (5-day) heat acclimation (STHA). Ten moderately trained males (mean ± SD age 28 ± 7 years; body mass 74.6 ± 4.4 kg; [(V)\dot]_{\textO 2\textpeak} \dot{V}_{{{\text{O}}_{ 2{\text{peak}}} }} 4.26 ± 0.37 l min⁻¹) underwent heat acclimation (Acc) for 90-min on 5-days consecutively (T _a = 39.5°C, 60% RH), under controlled hyperthermia (rectal temperature 38.5°C). Participants completed a heat stress test (HST) 1 week before acclimation (Acc), then on the 2nd and 8th day (1 week) following Acc (T _a = 35°C, 60% RH). Seven participants completed HSTs 2 and 3 weeks after Acc. HST consisted of 90-min cycling at 40% peak power output before an incremental performance test. Rectal temperature at rest (37.1 ± 0.4°C) was not lowered by Acc (95% CI −0.3 to 0.2°C), after 90-min exercise (38.6 ± 0.5°C) it reduced 0.3°C (−0.5 to −0.1°C) and remained at this level 1 week later (−0.5 to −0.1°C), but not two (0.1°C −0.4 to 0.5°C; n = 7) or 3 weeks. Similarly, heart rate after 90-min exercise (146 ± 21 b min⁻¹) was reduced (−13: −6 to −20 b min⁻¹) and remained at this level after 1 week (−13: −6 to −20 b min⁻¹) but not two (−9: 6 to −23 b min⁻¹; n = 7) or 3 weeks. Performance (746 s) increased 106 s: 59 to 152 s after Acc and remained higher after one (76 s: 31 to 122) but not two (15 s: −88 to 142 s; n = 7) or 3 weeks. Therefore, STHA (5-day) induced adaptations permitting increased heat loss and this persisted 1 week but not 2 weeks following Acc.     

Family-based association study of DYX1C1 variants in autism

DYX1C1: was recently identified as a candidate gene for developmental dyslexia, which is characterized by an unexpected difficulty in learning to read and write despite adequate intelligence, motivation, and education. It will be important to clarify, whether the phenotype caused by DYX1C1 extends to other language-related or comorbid disorders. Impaired language development is one of the essential features in autism. Therefore, we analyzed the allelic distribution of the DYX1C1 gene by family-based association method in 100 Finnish autism families. No evidence for association was observed with any intragenic marker or with haplotypes constructed from alleles of several adjacent markers. No evidence for deviated allelic diversity was either observed: the frequency of expected dyslexia risk haplotype was comparable to its frequency in Finnish controls. Thus it seems unlikely that DYX1C1 gene would be involved in the genetic etiology of autism in Finnish patients.     

Oxidative stress, inflammation and recovery of muscle function after damaging exercise: effect of 6-week mixed antioxidant supplementation

There is no consensus regarding the effects of mixed antioxidant vitamin C and/or vitamin E supplementation on oxidative stress responses to exercise and restoration of muscle function. Thirty-eight men were randomly assigned to receive either placebo group (n = 18) or mixed antioxidant (primarily vitamin C & E) supplements (n = 20) in a double-blind manner. After 6 weeks, participants performed 90 min of intermittent shuttle-running. Peak isometric torque of the knee flexors/extensors and range of motion at this joint were determined before and after exercise, with recovery of these variables tracked for up to 168 h post-exercise. Antioxidant supplementation elevated pre-exercise plasma vitamin C (93 ± 8 μmol l⁻¹) and vitamin E (11 ± 3 μmol l⁻¹) concentrations relative to baseline (P < 0.001) and the placebo group (P ≤ 0.02). Exercise reduced peak isometric torque (i.e. 9–19% relative to baseline; P ≤ 0.001), which persisted for the first 48 h of recovery with no difference between treatment groups. In contrast, changes in the urine concentration of F₂-isoprostanes responded differently to each treatment (P = 0.04), with a tendency for higher concentrations after 48 h of recovery in the supplemented group (6.2 ± 6.1 vs. 3.7 ± 3.4 ng ml⁻¹). Vitamin C & E supplementation also affected serum cortisol concentrations, with an attenuated increase from baseline to the peak values reached after 1 h of recovery compared with the placebo group (P = 0.02) and serum interleukin-6 concentrations were higher after 1 h of recovery in the antioxidant group (11.3 ± 3.4 pg ml⁻¹) than the placebo group (6.2 ± 3.8 pg ml⁻¹; P = 0.05). Combined vitamin C & E supplementation neither reduced markers of oxidative stress or inflammation nor did it facilitate recovery of muscle function after exercise-induced muscle damage.     

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

Among genetic factors that may contribute to the development and progression of Graves’ disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (−1098T/G, −590T/C, −33C/T), IL-10 (−1082A/G, −819C/T, −592C/A) and TGF-β (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 −1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 −33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 −1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 −819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 −592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-β +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-β +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 −590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.     

Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO₂ difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO_2peak), and cardiac variables (thoracic bioimpedance)—cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)—at rest and during cycling exercise at 65% of VO_2peak. Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO_2peak and VO_2peak relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min⁻¹, p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM⁻¹ min⁻¹, p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min⁻¹, p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min⁻¹, p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min⁻¹ m⁻², p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min⁻¹, p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min⁻¹, p < 0.001, respectively) and a lower a-vO₂ difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml⁻¹, p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.     

Pressure and coverage effects of sporting compression garments on cardiovascular function,thermoregulatory function,and exercise performance

Sporting compression garments (CG) are used widely during exercise despite little evidence of benefits. The purpose of this study was to investigate coverage and pressure effects of full-body CG on cardiovascular and thermoregulatory function at rest and during prolonged exercise, and on exercise performance. Twelve recreationally trained male cyclists [mean (SD) age, 26 (7) years; [(V)\dot]\textO_2max \dot{V}{\text{O}}_{2\max } , 53 (8) mL kg⁻¹ min⁻¹] completed three sessions (counterbalanced order), wearing either correctly-sized CG (CSG; 11–15 mmHg), over-sized CG (OSG; 8–13 mmHg), or gym shorts (CONT). Test sessions were conducted in temperate conditions [24 (1)°C, 60 (4)% relative humidity; ~2 m s⁻¹ air velocity during exercise], consisting of resting on a chair then on a cycle ergometer, before 60-min fixed-load cycling at ~65% [(V)\dot]\textO_2max \dot{V}{\text{O}}_{2\max } and a 6-km time trial. Wearing CG (CSG or OSG) did not mitigate cardiovascular strain during mild orthostatic stress at rest (p = 0.20–0.93 for garment effects). During exercise, cardiac output was ~5% higher in the CG conditions (p < 0.05), which appears to be accounted for via non-significant higher end-exercise heart rate (~4–7%, p = 0.30; p = 0.06 for greater heart rate drift in CSG); other cardiovascular variables, including stroke volume, were similar among conditions (p = 0.23–0.91). Covered-skin temperature was higher in CG conditions (p < 0.001) but core (oesophageal) temperature was not (p = 0.79). Time-trial performance (mean power, time taken) was similar with or without CG (p = 0.24–0.44). In conclusion, any demonstrable physiological or psychophysical effects of full-body CG were mild and seemingly reflective more of surface coverage than pressure. No benefit was evident for exercise performance.     

Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR‐RFLP technique was used to detect IL10 promoter genotypes at the positions of ?1082 (G/A), ?819 (C/T) and ?592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of ?1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21–5.82), p‐value = 0.046]. The CC genotype in ?819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26–9.07), p‐value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15–3.01), p‐value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of ?592 SNP and decreased in AA genotype carriers of ?1082. IL10 was also increased in SLE patients with CGT (?592/?1082/?819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of ?592 and TT genotype carriers at the region of ?819. SLEDAI was also elevated among patients with CGC (?592/?1082/?819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 –819(C/T), ?1082(G/A) and ?592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings.     

Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes: alveolar-capillary membrane conductance in type 1 diabetes

Lung diffusing capacity (DLCO) is influenced by alveolar-capillary membrane conductance (D _M) and pulmonary capillary blood volume (V _C), both of which can be impaired in sedentary type 1 diabetes mellitus (T1DM) subjects due to hyperglycemia. We sought to determine if T1DM, and glycemic control, affected DLNO, DLCO, D _M, V _C and SaO₂ during maximal exercise in aerobically fit T1DM subjects. We recruited 12 T1DM subjects and 18 non-diabetic subjects measuring DLNO, DLCO, D _M, and V _C along with SaO₂ and cardiac output (Q) at peak exercise. The T1DM subjects had significantly lower DLCO/Q and D _M/Q with no difference in Q, DLNO, DLCO, D _M, or V _C (DLCO/Q = 2.1 ± 0.4 vs. 1.7 ± 0.3, D _M/Q = 2.8 ± 0.6 vs. 2.4 ± 0.5, non-diabetic and T1DM, p < 0.05). In addition, when considering all subjects there was a relationship between DLCO/Q and SaO₂ at peak exercise (r = 0.46, p = 0.01). Within the T1DM group, the optimal glycemic control group (HbA1c <7%, n = 6) had higher DLNO, DLCO, and D _M/Q than the poor glycemic control subjects (HbA1c ≥7%, n = 6) at peak exercise (DLCO = 38.3 ± 8.0 vs. 28.5 ± 6.9 ml/min/mmHg, DLNO = 120.3 ± 24.3 vs. 89.1 ± 21.0 ml/min/mmHg, D _M/Q = 3.8 ± 0.8 vs. 2.7 ± 0.2, optimal vs. poor control, p < 0.05). There was a negative correlation between HbA1c with DLCO, D _M and D _M/Q at peak exercise (DLCO: r = −0.70, p = 0.01; D _M: r = −0.70, p = 0.01; D _M/Q: r = −0.68, p = 0.02). These results demonstrate that there is a reduction in lung diffusing capacity in aerobically fit athletes with T1DM at peak exercise, but suggests that maintaining near-normoglycemia potentially averts lung diffusion impairments.