Interaction between the APOE epsilon4 allele and the APH-1b c + 651T > G SNP in Alzheimer's disease

The γ-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid β-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the γ-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651T > G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) 4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P = 0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR = 28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.     

Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients

Warfarin is the most commonly used oral anticoagulant for treatment of thromboembolism, but adjustment of the dose appropriate to each patient is not so easy because of the large inter-individual variation in dose requirement. We analyzed single nucleotide polymorphism (SNP) genotypes of the VKORC1 and CYP2C9 genes using DNA from 828 Japanese patients treated with warfarin, and investigated association between SNP genotype and warfarin-maintenance dose. Five SNPs in VKORC1, 5 flanking–1413A>G, intron 1–136T>C, intron 2+124C>G, intron 2+837T>C and exon 3 343G>A, were in absolute linkage disequilibrium, and showed a significant association with daily warfarin dose of these patients. The median warfarin dose of patients with homozygosity for the minor allele was 4.0 mg/day, which is significantly higher than those heterozygous for the minor allele (3.5 mg/day) or those homozygous for the major allele (2.5 mg/day; P=5.1×10^–11 in the case of intron 1–136T>C SNP). We then genotyped the CYP2C9 gene for the Japanese common genetic variant, CYP2C9*3 and, based on the genotype of these two genes, classified patients into three categories, which we call warfarin-responsive index. The median warfarin daily dose varied significantly in this classification according to the warfarin-responsive index (2.0 mg/day for index 0 group, 2.5 mg/day for index 1 group, and 3.5 mg/day for index 2 group; P=4.4×10^–13). Thus, analysis of the combination of VKORC1 and CYP2C9 genotypes should identify warfarin-sensitive patients who require a lower dose of drug, allowing personalized warfarin treatment.     

Alpha-2-macroglobulin gene, oxidized low-density lipoprotein receptor-1 locus, and sporadic Alzheimer's disease

A total sample of 169 AD patients, and 264 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotypized for alpha-2-macroglobulin (A2M) Val1000/Ile single-nucleotide polymorphism (SNP) (rs669), apolipoprotein E (APOE), and SNPs (+1073 and +1071) in the oxidized low-density lipoprotein receptor-1 (OLR1) gene on chromosome 12. A2M allele and genotype frequencies were similar between AD patients and controls, also after stratification for late onset (≥70 years) and early onset (<70 years) or APOE 4 status. However, there was evidence in support of LD between the OLR1 + 1071, the OLR1 + 1073, and the rs669 SNPs, with T-C-A haplotype being associated with significant increased risk of AD in both the whole sample and when we stratified according to early and late onset AD subjects, with the allelic association with AD predominantly from the OLR1 + 1073 SNP, further supporting the role of OLR1 as a candidate risk gene for sporadic AD.     

TPH2 polymorphisms may modify clinical picture in treatment-resistant depression

The association of two tryptophan hydroxylase 2 (TPH2) polymorphisms and treatment response in electroconvulsive therapy (ECT) and the risk of depression was studied. The patient sample consisted of 119 subjects with treatment-resistant major depressive disorder who were treated with ECT. Treatment response was assessed by the Montgomery and Åsberg Depression Rating Scale (MADRS) scores. Patients who had <8 scores in post-treatment MADRS were considered remitters; scores >15 indicated non-response. The polymorphisms studied (rs1386494 and rs1843809) were not associated with treatment response to ECT. However, TPH2 rs1386494 A/A genotype carrying patients had significantly higher MADRS scores before ECT than A/G + G/G genotype carriers (p < 0.001). A/A genotype carriers also had a greater decline in MADRS scores than A/G + G/G genotype carriers during the course of ECT treatment (p = 0.03). This polymorphism may be associated with the severity of treatment-resistant depression. ECT may able to counteract a putative genetically driven worse depressive phenotype.     

Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case–control study

Hyperactivation of N-methyl-d-aspartate receptors (NMDARs) leads to neuronal excitotoxicity and is suggested to play a role in many brain disorders, including Alzheimer's disease and schizophrenia. However, the association between polymorphisms in the genes that code for NMDAR subunits, N-methyl-d-aspartate 1 and 2B (GRIN1 and GRIN2B) and Parkinson's disease (PD) remains unclear. In a hospital-based case–control study of PD, DNA samples were collected from 101 PD patients and 205 healthy controls. Genotyping assays were used to screen for polymorphisms in the GRIN1 (rs2301364 T > C, rs28489906 T > C, and rs4880213 T > C) and GRIN2B (C366G, C2664T, and rs1805476 T > G) genes, and logistic regression analysis was then used to assess the association between these single nucleotide polymorphisms (SNPs) and PD susceptibility. None of the 6 SNPs were significantly associated with PD risk on their own. However, in conjunction with putative low-risk genotypes for the GRIN1 gene, the GRIN2BC366G variant was significantly associated with reduced PD risk compared with the homozygous genotype 366CC (OR = 0.38, 95%CI = 0.17–0.93, P = 0.033). A synergistic effect on risk reduction was observed in subjects who carried multiple polymorphisms of GRIN1 and the GRIN2BC366G polymorphism (OR = 0.78, 95%CI = 0.59–1.02, P_trend = 0.073). Our results suggest that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.     

Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.     

Apolipoprotein E and α-1-antichymotrypsin allele polymorphism in sporadic and familial Alzheimer's disease

Alzheimer disease (AD) patients with both sporadic and familial forms of AD and non-demented controls were genotyped for common polymorphisms in the signal peptide for α-1-antichymotrypsin (ACT) gene and in two different regions of apolipoprotein E (APOE) gene. The ACT TT genotype was over-represented (P=0.025) in patients with early onset of sporadic AD. In this patient's group ACT TT genotype conferred a significant crude odds ratio for the disease (OR=2.09; 95% CI=1.09–4.00, P=0.025). After adjustment for the APOE ε4 and APOE −491 genotypes, logistic regression analysis confirmed that the ACT TT genotype resulted independently associated with early onset AD (adjusted OR=2.56; 85% C.I.=1.3–5.2, P=0.009). The frequency of APOE ε4 allele was increased in AD, as expected (OR=5.92, 95% CI=3.60–9.70, P=0.0001). On the contrary, the APOE −491 A/T genotypes were not associated with AD. No preferential association of the APOE ε4 allele or APOE −491 A/T genotypes with ACT A/T alleles was observed in AD. Present findings indicated that subjects with ACT TT genotype had an increased risk of developing AD and suggested that this genotype influenced the risk of an early onset of the disease by affecting the production of ACT molecules.     

IL28B gene variants and glucose metabolism in Type 2 Diabetes

Type 2 Diabetes (T2D) develops, when β-cell insulin response fails to compensate for insulin resistance. Recent studies reported associations between the IL28B polymorphisms (rs12979860 and rs8099917) and T2D development in Hepatitis C virus (HCV) patients. To identify possible association with T2D independent from virus infection, we investigated both IL28B polymorphisms in T2D patients and healthy controls (HC). No association was found comparing the genotype and allele frequencies of both IL28B polymorphisms between T2D patients and HC. However, higher glucose levels were found in T2D patients carrying the IL28B CT/TT rs12979860 and GT/GG rs8099917 HCV risk genotypes compared to those with the protective CC and TT genotype (p = 0.06 and p = 0.02, respectively). Moreover, T2D patients with CT/TT rs12979860 HCV risk genotypes possessed significantly higher HbA1c levels than CC carriers (p = 0.04). In conclusion, the IL28B HCV risk genotypes may influence glucose homeostasis in T2D patients without HCV.     

Cultured peripheral blood mast cells from chronic idiopathic urticaria patients spontaneously degranulate upon IgE sensitization: Relationship to expression of Syk and SHIP-2

Recently, signaling changes in the FcRI pathway involving inositol lipid phosphatases have been identified in the basophils of chronic idiopathic urticaria (CIU) subjects. Based on the profile of basophil FcRI-mediated histamine degranulation, we have segregated CIU subjects into two groups, CIU Responder (CIU R) or CIU Nonresponder (CIU NR). In the present study, we compared expression of SHIP-1, SHIP-2, and Syk protein to histamine release (HR) from mast cells (MC) cultured from the peripheral blood of CIU R, CIU NR, and normal subjects. The MC of CIU R donors contained significantly increased Syk and decreased SHIP-2 as compared to CIU NR (Syk: p = 0.038, SHIP-2: p = 0.038) and normals (Syk: p = 0.042, SHIP-2: p = 0.027). Spontaneous HR from CIU donors was increased two-fold compared to normals (p = 0.04). In summary, our results suggest a possible predilection for urticarial MC to spontaneously degranulate upon IgE sensitization contributing to the increased pruritis associated with CIU.     

Genetic variant of IL28B rs12979860, as predictive marker of interferon‐based therapy in Pakistani population

Hepatitis C virus (HCV) genotypes and genetic variants of interleukin 28B (IL28B) are significantly associated with interferon plus ribavirin treatment of HCV infection. We investigated the distribution of HCV genotypes and single‐nucleotide polymorphisms (SNPs) of IL28B (rs12979860 and rs8099917) in Pakistani population. IL28B genotyping was performed by allele‐specific PCR and restriction fragment length polymorphism PCR in 140 chronic hepatitis C patients (CHC) and 120 healthy controls. HCV genotype 3 (HCVG3) was the most prevalent genotype, 71.4% (n = 100/140) and with the highest treatment response of 90% (n = 90/100). The overall treatment response of all the HCV genotypes was 82% (n = 115/140). The distribution of IL28B rs12979860CC genotype in treatment responder and non‐responder groups was 40.8% (n = 47/115) and 16% (n = 4/25) respectively. IL28B rs12979860CC genotype demonstrated a significant correlation (p = 0.019) with interferon‐based therapy of HCV infection. However, there was no observed association of IL28B rs8099917 polymorphism with treatment response in CHC patients (p = 0.264). In conclusion, HCV genotypes and IL28B rs12979860 are predictive markers for the efficiency of interferon plus ribavirin combinational therapy of HCV infection. We recommend the inclusion of testing for these markers in the clinical criteria for decision making for HCV therapy in Pakistani population.     

PSEN1 polymorphisms alter the rate of cognitive decline in sporadic Alzheimer's disease patients

Mutations in amyloid precursor protein (APP) and presenilin (PSEN) genes are known to cause familial early-onset Alzheimer's disease (AD), which account for around 5% of AD cases. Genetic associations for the remaining “sporadic” cases, other than the risks associated with the apolipoprotein (APOE) 4 allele are currently not fully established. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in PSEN1 are associated with a modified risk for sporadic AD or a modified disease phenotype. Eight tag SNPs were identified using linkage disequilibrium (LD) data from the International HapMap project providing coverage of the entire PSEN1 gene. These SNPs were investigated for AD susceptibility in a case-control haplotype association study (N = 714) and for genotype-specific effects on cognitive performance in AD patients (N = 169) using non-linear mixed effects modelling. Replication of a mild associated-risk of an intronic PSEN1 polymorphism with AD was achieved (P = 0.03). No other single SNPs or haplotypes were associated with AD risk. However, 3 SNPs were associated with an altered rate of cognitive decline underlining their role as genetic modifiers of disease.     

Combination of CTLA-4 and TGFβ1 gene polymorphisms associated with dengue hemorrhagic fever and virus load in a dengue-2 outbreak

The pathogenesis of dengue hemorrhagic fever (DHF) has been considered to be massive immune activation of T cells. Abnormal expression of the immune regulatory molecules, CTLA-4 and TGFβ1, leads to disturbances of regulatory T cell immune response. We investigate the contribution of CTLA-4 and TGFβ1 in DHF by analyzing them for association with virus load in blood and polymorphisms of CTLA-4 +49A/G, and TGFβ1 −509C/T in a DEN-2 outbreak. The increased frequency of the TGFβ1 −509 CC genotype in patients with DHF was compared to those with dengue fever (OR = 1.9, p = 0.034). Moreover, the presence of the CTLA-4 +49 G allele and TGFβ1 −509 CC genotype increased the susceptibility to risk of DHF (OR = 2.1, p = 0.028) and significantly higher virus load (p = 0.013). This finding suggests that a combination of CTLA-4 and TGFβ1 polymorphisms is associated with the susceptibility of DHF and higher virus load.     

Genetic polymorphisms in the cytochromes P-450 (1A1, 2E1), microsomal epoxide hydrolase and glutathione S-transferase M1, T1, and P1 genes, and their relationship with chronic bronchitis and relapsing pneumonia in children

The purpose of this study was to investigate the possible roles of the genes functioning in xenobiotic metabolism and antioxidant pathways in the development of severe chronic lung disease in children. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1 were investigated in cases of Tatar children with chronic bronchitis (n=129) and relapsing pneumonia (n=50) and in cases of ethnically matched healthy individuals (n=227) living in the city of Ufa, the Republic of Bashkortostan (South Ural region of Russia), by polymerase chain reaction–restriction fragment length polymorphism (PCR-RLFP) method. The frequency of the *2C allele of the CYP1A1 gene was significantly higher in patients than in the healthy control group (²=15.02, P=0.0007, P_cor=0.0021). This allele was associated with a higher risk of chronic bronchitis in children (OR 4.14, 95% CI 1.83–9.53; P_cor=0.0024). Similar results were obtained in cases of patients with relapsing pneumonia (OR 3.86, 95% CI 1.34–10.95; P_cor=0.027 for the *2C allele of the CYP1A1 gene). The frequency of the *5B allele of the CYP2E1 gene was higher in the relapsing pneumonia patients (7.0 vs 1.98% in the control group; ²=5.68, P=0.018, P_cor=0.054; OR 3.72, 95% CI 1.21–11.24). The increase in the GSTT1 gene deletion was significant only in cases of chronic bronchitis (39.53 compared to 21.15% in the control group; ²=12.96, P=0.001, P_cor=0.003; OR 2.44, 95% CI 1.48–4.04). Our results show that the presence of the GSTM1 gene deletion is unfavorable for the development of chronic lung disease in females (²=9.57; P=0.0029, P_cor=0.0116) and was associated with increased risk (OR 2.44, 95% CI 1.36–4.38). The distribution of EPHX1 and GSTP1 gene genotypes was similar in the control and patient groups. Our findings indicate that the polymorphisms of the CYP1A1, CYP2E1, and GSTT1 genes probably play a substantial part in susceptibility to severe airway and lung injury in cases of children with chronic bronchitis and relapsing pneumonia.     

Putative risk alleles for LATE‐NC with hippocampal sclerosis in population‐representative autopsy cohorts

Limbic‐predominant age‐related TAR‐DNA‐binding protein‐43 (TDP‐43) encephalopathy with hippocampal sclerosis pathology (LATE‐NC + HS) is a neurodegenerative disorder characterized by severe hippocampal CA1 neuron loss and TDP‐43‐pathology, leading to cognitive dysfunction and dementia. Polymorphisms in GRN, TMEM106B and ABCC9 are proposed as LATE‐NC + HS risk factors in brain bank collections. To replicate these results in independent population‐representative cohorts, hippocampal sections from brains donated to three such studies (Cambridge City over 75‐Cohort [CC75C], Cognitive Function and Ageing Study [CFAS], and Vantaa 85+ Study) were stained with hematoxylin–eosin (n = 744) and anti‐pTDP‐43 (n = 713), and evaluated for LATE‐NC + HS and TDP‐43 pathology. Single nucleotide polymorphism genotypes in GRN rs5848, TMEM106B rs1990622 and ABCC9 rs704178 were determined. LATE‐NC + HS (n = 58) was significantly associated with the GRN rs5848 genotype (χ²(2) = 20.61, P < 0.001) and T‐allele (χ²(1) = 21.04, P < 0.001), and TMEM106B rs1990622 genotype (Fisher's exact test, P < 0.001) and A‐allele (χ²(1) = 25.75, P < 0.001). No differences in ABCC9 rs704178 genotype or allele frequency were found between LATE‐NC + HS and non‐LATE‐NC + HS neuropathology cases. Dentate gyrus TDP‐43 pathology associated with GRN and TMEM106B variations, but the association with TMEM106B nullified when LATE‐NC + HS cases were excluded. Our results indicate that GRN and TMEM106B are associated with severe loss of CA1 neurons in the aging brain, while ABCC9 was not confirmed as a genetic risk factor for LATE‐NC + HS. The association between TMEM106B and LATE‐NC + HS may be independent of dentate TDP‐43 pathology.     

DNMBP is genetically associated with Alzheimer dementia in the Belgian population

Genetic association of the dynamin binding protein gene (DNMBP) on chromosome 10 with late-onset Alzheimer's disease (AD) was reported among Japanese. Here, we assessed the genetic role of DNMBP in an extended Belgian AD group using a gene-wide association approach. A total of 18 SNPs across the DNMBP locus were genotyped in 555 late-onset AD patients and 638 healthy control individuals. Significant associations were observed for two SNPs (rs3740057 and rs10883421). Haplotype analysis identified association with haplotype blocks in the 3’ region of DNMBP comprising rs2862919, rs11190302, rs10509739, rs2256700 and comprising rs3740057 and rs6584331. Stratification for APOE 4 status showed that association was only present in the APOE 4 negative subgroup. Sliding-window analyses provided further evidence for association with the 3’–end of DNMBP both for the total and for the APOE 4 negative group. Taken together our findings underscore a role for DNMBP in the genetic risk for late-onset AD in the Belgian population.     

Genetic Variants in IL‐12B and IL‐27 in the Polish Patients with Systemic Lupus Erythematosus

To investigate the potential association between IL‐12B and IL‐27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case–control study based on the Polish population. Patients with SLE and healthy individuals were examined for ?6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL‐12B and ?924A/G (rs153109) and 4730T/C (rs181206) in IL‐27 gene polymorphisms using the high‐resolution melting method, PCR–RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL‐12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL‐12B rs3212227 and IL‐27 rs153109 and rs181206 variants between patients with SLE and controls. IL‐27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL‐12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL‐12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL‐12B rs17860508 and IL‐27 haplotype CG are genetic risk factors for SLE and that both IL‐12B rs17860508 and rs3212227 predict disease phenotype.     

Bio-energetic profile in 144 boys aged from 6 to 15 years with special reference to sexual maturation

Summary The effects of growth and pubertal development on bio-energetic characteristics were studied in boys aged 6–15 years (n = 144; transverse study). Maximal oxygen consumption (VO_2max, direct method), mechanical power at (VO_2max ( ), maximal anaerobic power (P_max; force-velocity test), mean power in 30-s sprint (P _30s; Wingate test) were evaluated and the ratios between P_max,P _30s and were calculated. Sexual maturation was determined using salivary testosterone as an objective indicator. Normalized for body massVO_2max remained constant from 6 to 15 years (49 ml· min^–1 · kg^–1, SD 6), whilst P_max andP _30s increased from 6–8 to 14–15 years, from 6.2 W · kg^–1, SD 1.1 to 10.8 W · kg^–1, SD 1.4 and from 4.7 W · kg^–1, SD 1.0 to 7.6 W · kg^–1, SD 1.0, respectively, (P < 0.001). The ratio P_max: was 1.7 SD 3.0 at 6–8 years and reached 2.8 SD 0.5 at 14–15 years and the ratioP _30s: changed similarly from 1.3 SD 0.3 to 1.9 SD 0.3. In contrast, the ratio P_max:P _30s remained unchanged (1.4 SD 0.2). Significant relationships (P < 0.001) were observed between P_max (W · kg^–1),P _30s (W · kg^–1), blood lactate concentrations after the Wingate test, and age, height, mass and salivary testosterone concentration. This indicates that growth and maturation have together an important role in the development of anaerobic metabolism.     

Hyperpnoea and CO2 sensitivity of the respiratory centres during exercise

Summary The aim of this study was to specify whether exercise hyperpnoea was related to the CO₂ sensitivity of the respiratory centres measured during steady-state exercise of mild intensity. Thus, ventilation , breathing pattern [tidal volume (V _T), respiratory frequency (f), inspiratory time (T _I), total time of the respiratory cycle (T _TOT),V _T/T _I,T _I/T _TOT] and CO₂ sensitivity of the respiratory centres determined by the rebreathing method were measured at rest (SCO_{2 re}) and during steady-state exercise (SCO_{2 ex}) of mild intensity [CO₂ output =20 ml·kg⁻¹·min⁻¹] in 11 sedentary male subjects (aged 20–34 years). The results showed that SCO_{2 re} and SCO_{2 ex} were not significantly different. During exercise, there was no correlation between and SCO_{2 ex} and, for the same , all subjects had very close values normalized for body mass (bm), regardless of their SCO_{2 ex} ( =1.44 l·min⁻¹·kg⁻¹ SD 0.10). A highly significant positive correlation between SCO_{2 ex} andV _T (normalised for bm) (r=0.80,P<0.01),T _I (r=0.77,P<0.01) andT _TOT (r=0.77,P<0.01) existed, as well as a highly significant negative correlation between SCO_{2 ex} and (normalised for bm^−0.25) (r=−0.73,P<0.01). We conclude that the hyperpnoea during steady-state exercise of mild intensity is not related to the SCO_{2 ex}. The relationship between breathing pattern and SCO_{2 ex} suggests that the breathing pattern could influence the determination of the SCO_{2 ex}. This finding needs further investigation.     

The effect of different treadmill speeds on the variability of \dot VO_2 max 2 in children

Summary Eight boys aged 10–12 years performed three tests on each of three treadmill protocols. Each test was a continuous, progressively graded performance to exhaustion, but protocols differed in speed — (walk: 90 m·min^–1, jog: 110 m·min^–1, run: 130 m·min^–1). The walk protocol was found inappropriate for jackeO₂ max determination in children. Compared to the faster speeds, the walk test elicited a lower at exhaustion, and had lower reliability (0.56) and a high coefficient of variation (8%). For the at exhaustion on the jog and run protocols the coefficient of variation was 3–5% and the reliability coefficient averaged 0.90, comparable to values seen for repeated trials in adults. The usually accepted criterion of a plateau of with increasing work levels was inappropriate for use with children. Attempts to derive plateau criteria suitable for use with children proved unsuccessful. Plateau criteria may be difficult to achieve with children in light of their apparently weaker glycolytic energy capacity. Nevertheless, the highest measured at jog or run speeds has a consistency similar to that found for measurement in adults.Supported in part by a grant from the Ministry of Health and Welfare Canada, and in part from the Ministry of Culture and Recreation, Ontario, Canada