XX Group Research Articles

Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children

To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

Isochromosome Xq and the risk of metabolic comorbidities in Turner syndrome

Background and aimSubjects with Turner syndrome (TS) are at increased risk of metabolic disorders. The objective of this study is to evaluate the prevalence of metabolic abnormalities in TS and compare the metabolic profiles of subjects with respect to their X chromosome dosage. MethodsSixty-four TS subjects with a mean age of 19 ± 4.9 years were included, and the prevalence of metabolic abnormalities was assessed. Out of these, 54 age and body mass index-matched TS subjects were divided into two groups based on karyotype: 45,X and 45,X/46,XX (group I; n = 33) and 46,X,i(X)(q10) and 45,X/46,X,i(X)(q10) (group II; n = 21). They were compared for blood pressure, fasting plasma glucose, homeostasis model assessment (HOMA) of insulin resistance (IR) and β cell function (HOMA-β), lipid profile, and percent total body fat mass (PTBFM) to assess if an extra copy of Xq contributes to a different metabolic profile. ResultsThe prevalence of impaired fasting glucose was 7.8%. 12% of subjects had higher systolic blood pressure (SBP), and 16% had higher diastolic blood pressure for age. 53% had a deranged lipid profile. Significant differences were noted in the two groups, with higher prevalence in group II vs. group I for SBP (p = 0.03), low-density lipoprotein cholesterol (LDL-c) (p = 0.03), and PTBFM (p = 0.02). When we applied a multiple regression analysis for these outcome variables while adjusting for potential confounders known to influence the cardiometabolic risk profile in TS, karyotype no longer remained a significant independent variable. ConclusionExtra copies of Xq do not contribute to an adverse metabolic risk profile.

Influence of Alpha-Actinin-3 R577X Polymorphism on Muscle Damage and the Inflammatory Response after an Acute Strength Training Session.

The objective of this study was to verify the influence of the ACTN3 R577X polymorphism on muscle damage and the inflammatory response after an acute strength training (ST) session. Twenty-seven healthy male individuals (age: 25 ± 4.3 years) participated in the study, including 18 RR/RX and 9 XX individuals. The participants were divided into two groups (RR/RX and XX groups) and subjected to an acute ST session, which consisted of a series of leg press, leg extension machine, and seated leg curl machine. The volunteers were instructed to perform the greatest volume of work until concentric muscle failure. Each volunteer's performance was analyzed as the load and total volume of training, and the blood concentrations of C-C motif chemokine ligand 2 (CCL2), interleukin-8 (IL-8), creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, testosterone, and cortisol were measured before the ST session and 30 min and 24 h postsession. The ACTN3 R577X polymorphism effect was observed, with increased concentrations of CCL2 (p < 0.01), IL-8 (p < 0.01), and LDH (p < 0.001) in XX individuals. There was an increase in the concentration of CK in the RR/RX group compared to XX at 24 h after training (p > 0.01). The testosterone/cortisol ratio increased more markedly in the XX group (p < 0.001). Regarding performance, the RR/RX group presented higher load and total volume values in the training exercises when compared to the XX group (p < 0.05). However, the XX group presented higher values of delayed onset muscle soreness (DOMS) than the RR/RX group (p < 0.05). The influence of ACTN3 R577X polymorphism on muscle damage and the inflammatory response was observed after an acute ST session, indicating that the RR/RX genotype shows more muscle damage and a catabolic profile due to a better performance in this activity, while the XX genotype shows more DOMS.

Comparisons of visual outcomes between bilateral implantation and mix-and-match implantation of three types intraocular lenses.

To compare binocular static visual acuity (SVA), stereopsis, contrast sensitivity (CS) and dynamic visual acuity (DVA) of 5 combinations of bifocal intraocular lenses (IOLs), trifocal IOLs and extended-depth-of-focus (EDOF) IOLs in age-related cataract patients. Two hundred and ninety-two eyes of 146 patients who underwent cataract surgery in the ophthalmology department of the First Affiliated Hospital of Chongqing Medical University were involved. Subgroups included group MM (33patients, bilaterally bifocal IOL, ZMB00), group TT (31patients, bilaterally trifocal IOL, AT LISA tri839MP), group XX (34patients, bilaterally EDOF IOL, ZXR00), group MX (25patients, bifocal IOL, ZMB00 + EDOF IOL, ZXR00) and group TX (23patients, trifocal IOL, AT LISA tri839MP + EDOF IOL, ZXR00). The uncorrected SVAs (UDVA, UIVA and UNVA), uncorrected DVAs (UDDVA, UIDVA and UNDVA), near and distance stereopsis, and CS were assessed 3months postoperatively. Subgroups of TT, XX, MX and TX showed better UIVA than MM (bP = 0.039, 0.021, 0.035 and 0.037, respectively). MX showed better UNVA than MM and TX (bP = 0.031 and 0.013, respectively). MX group had the optimal outcomes of both near and distance stereopsis. In the UDDVA, XX group and MX group showed better outcomes than TX group at 24 fps (frames per second) (bP = 0.019 and 0.023, respectively). XX group and MX group showed optimal outcomes at all speeds of UIDVA (P = 0.001, 0.005, 0.003 and 0.005, respectively). As the speed increased, the XX group and the MX group showed better UNDVA than the MM group and the TT group (P = 0.019, 0.002 and 0.003, respectively). Mix-and-match implantation of bifocal IOLs and EDOF IOLs provides excellent and stable binocular visual outcomes including SVA, stereopsis and DVA in distant and near distances.

Is ACTN3 R577X Genotype Associated with a Preference in Type of Exercise Such as Sprint or Endurance?

The purpose of this study was to determine whether genotypes in the α-actinin-3 gene are associated with preferences in the type of exercise (sprint vs. endurance) in male college students. The study enrolled 64 healthy male students aged 18-21 years old, excluding elite athletes. DNA was extracted from the subjects’ hair samples to determine the genotypes of the α-actinin-3 gene, whereas a simple questionnaire was used to investigate preference in the type of exercise. In summary, 35.5% of subjects with the RR and RX types (R-allele group) preferred sprint, whereas 47.3% of subjects with the XX type preferred endurance. Furthermore, 53.3% of the R-allele group and 31.6% of the XX group preferred endurance and sprint, respectively. This implies that the inconsistency (or mismatch) between muscle functional properties, which are characterized by genotypes and preference in type of exercise, tends to be greater in the R-allele group than in the XX type. In conclusion, the genotypes of α-actinin-3 did not play a significant role in deciding the preference in type of exercise. It can also be suspected that the mismatch between muscle functional properties and exercise preference is influenced by the daily life of students who are not exposed to high-intensity exercise stimuli.

Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study

BackgroundWe recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B.MethodsTwenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented.ResultsMedian follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3–10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7–77.4). The median follow-up time was 5.4 years (range 0.3–10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8–89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3).ConclusionsPreoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis.Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39

Quantitative comparative analysis uncovered the role of E2 in Nile tilapia GSD + TE

Nile tilapia is a GSD + TE (genotypic sex determination plus temperature effect) fish species. However, the role of 17β-estradiol (E2) during high-temperature-induced masculinization is unknown in fish species exhibiting GSD + TE. Because letrozole can specifically downregulate E2, the differences of the E2 level and sex ratio between the high-temperature-treated groups and various doses of letrozole treated groups could help quantitatively analyze the role of E2 in Nile tilapia GSD + TE. The results indicated that high-temperature could also significantly downregulate E2, and the level of E2 in the XX + HT (9 days postfertilization (dpf) larvae cultured in 36 °C water for 12 days) group at 21 dpf was only approximately half that in the XX group. Comparison of E2 and the sex reversal ratio between the high-temperature treated group and various letrozole treated groups showed that the level of E2 in the XX + HT group at 21 dpf was almost the same as that in the XX + L1.5 (9 dpf XX larvae cultured in 28 °C water with1.5 μg/L letrozole for 12 days) group, but the 70.00% male ratio in the XX + HT group was significantly higher than that in the XX + L1.5 (58.33%) group and was similar to that in the XX + L4.5 groups (66.25%) and the XX + L13.5 group (77.08%). Comparison of E2 and the female ratio between the high-temperature treated group and the HT + E2 compensation groups further indicated that the E2 level in the XX + HT + E:4 (9 dpf fry cultured in 36 °C water containing 4 μg/L E2 for 12 days) group was similar to that in the XX group at 21 dpf, and the female ratio was close between the two groups. qRT-PCR and western blot analysis showed that the high-temperature treatment significantly downregulated the expression of ovary-type P450 aromatase (cyp19a1a) and upregulated the expression of the male sex differentiation genes doublesex and mab-3 related transcription factor 1 (Dmrt1) at 21 dpf. Additionally, the high-temperature treatment also down-regulated Nile tilapia gonad aromatase activity. Collectively, the present study uncovered the role of E2 during high-temperature–induced Nile tilapia female sex reversal into pseudomales (phenotypic males) and the regulatory effect of high-temperature on the E2 pathway, providing an important foundation for understanding the mechanisms of high-temperature-induced Nile tilapia female sex reversal.

Effects of long term antiprogestine mifepristone (RU486) exposure on sexually dimorphic lncRNA expression and gonadal masculinization in Nile tilapia (Oreochromis niloticus)

Mifepristone (RU486), a clinical abortion agent and potential endocrine disruptor, binds to progestin and glucocorticoid receptors and has multiple functional importance in reproductive physiology. A long-term exposure of RU486 resulted in masculinization of female fish, however, the epigenetic landscape remains elusive. Recent studies demonstrated that long non-coding RNAs (lncRNAs) might play potential roles in epigenetic modulation of sex differentiation, ovarian cancer and germline stem cell survival. To further understand the influence of RU486 exposure on epigenetic regulation, we performed a comparative investigation on sex-biased gonadal lncRNAs profiles using control XX/XY and RU486-induced sex reversed XX Nile tilapia (Oreochromis niloticus) by RNA-seq. In total, 962 sexually differentially expressed lncRNAs and their target genes were screened from the gonads of control and sex reversed fish. In comparison with the control XX group, sex reversal induced by RU486 treatment led to significant up-regulation of 757 lncRNAs and down-regulation of 221 lncRNAs. Hierarchical clustering analysis revealed that global lncRNA expression profiles in RU486-treated XX group clustered into the same branch with the control XY, whereas XX control group formed a separate branch. The KEGG pathway enrichment analysis showed that the cis-target genes between RU486-XX and control-XX were concentrated in NOD − like receptor signaling pathway, Cell adhesion molecules (CAMs) and Biosynthesis of amino acids. Real-time PCR and in situ hybridization experiments demonstrate that lncRNAs showing intense fluctuation during RU486 treatment are also sexually dimorphic during early sex differentiation, which further proves the intimate relationship between lncRNAs and sex differentiation and sexual transdifferentiation. Taken together, our data strongly indicates that a long-term exposure of RU486 resulted in sex reversal of XX female fish and the altered expression of sexually dimorphic lncRNAs might partially account for the sex reversal via epigenetic modification.

ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners.

Background: Homozygosity for the X-allele in the ACTN3 R577X (rs1815739) polymorphism results in the complete absence of α-actinin-3 in sarcomeres of fast-type muscle fibers. In elite athletes, the ACTN3 XX genotype has been related to inferior performance in speed and power-oriented sports; however, its influence on exercise phenotypes in recreational athletes has received less attention. We sought to determine the influence of ACTN3 genotypes on common exercise phenotypes in recreational marathon runners. Methods: A total of 136 marathoners (116 men and 20 women) were subjected to laboratory testing that included measurements of body composition, isometric muscle force, muscle flexibility, ankle dorsiflexion, and the energy cost of running. ACTN3 genotyping was performed using TaqMan probes. Results: 37 runners (27.2%) had the RR genotype, 67 (49.3%) were RX and 32 (23.5%) were XX. There was a difference in body fat percentage between RR and XX genotype groups (15.7 ± 5.8 vs. 18.8 ± 5.5%; effect size, ES, = 0.5 ± 0.4, p = 0.024), whereas the distance obtained in the sit-and-reach-test was likely lower in the RX than in the XX group (15.3 ± 7.8 vs. 18.4 ± 9.9 cm; ES = 0.4 ± 0.4, p = 0.046). Maximal dorsiflexion during the weight-bearing lunge test was different in the RR and XX groups (54.8 ± 5.8 vs. 57.7 ± 5.1 degree; ES = 0.5 ± 0.5, p = 0.044). Maximal isometric force was higher in the RR than in the XX group (16.7 ± 4.7 vs. 14.7 ± 4.0 N/kg; ES = −0.5 ± 0.3, p = 0.038). There was no difference in the energy cost of running between genotypes (~4.8 J/kg/min for all three groups, ES ~0.2 ± 0.4). Conclusions: The ACTN3 genotype might influence several exercise phenotypes in recreational marathoners. Deficiency in α-actinin-3 might be accompanied by higher body fatness, lower muscle strength and higher muscle flexibility and range of motion. Although there is not yet a scientific rationale for the use of commercial genetic tests to predict sports performance, recreational marathon runners who have performed such types of testing and have the ACTN3 XX genotype might perhaps benefit from personalized strength training to improve their performance more than their counterparts with other ACTN3 genotypes.

ACE/ACTN3 GENETIC POLYMORPHISMS AND ATHLETIC PERFORMANCE OF FEMALE SOCCER PLAYERS`

ABSTRACT Objective: Previous studies have shown controversial relationships between ACE and ACTN3 gene polymorphisms and sports performance. Thus, the aim of our study was to assess anaerobic and aerobic performance indicators of young female soccer players with different ACE/ACTN3 gene profiles. Methods: Twenty-seven female soccer players aged 16-18 underwent acceleration, speed, strength, anaerobic power and aerobic endurance tests and had their ACE and ACTN3 polymorphisms determined. Results: Based on genetic analysis, they were divided into the following groups: ACE II (n=2), ACE ID (n=11), ACE DD (n=14), ACTN3 XX (n=5), ACTN3 RR (n=7) and ACTN3 RX (n=15). ACE DD and ACE ID groups differed significantly in terms of results achieved on the 5 m sprint test (1.15±0.05 s vs 1.10±0.05 s, P=0.42). ACTN3 RR and RX achieved better results than the ACTN3 XX group in seven continuous vertical jumps (26.57±1.59 cm vs 25.77±2.51 cm vs 22.86±1.16 cm, respectively; P=0.007 for RR vs XX and P=0.021 for RX vs XX). Conclusion: High prevalence of ACE DD and ACTN3 RX genotypes in our subjects may suggest that faster and more powerful young females tend to perform better in soccer. Nevertheless, the absence of differences in most of the physical test results indicates that different genotypes are compatible with high-level soccer performance, meaning that it is the phenotype-genotype interaction that makes a successful female soccer player. Level of Evidence I, Prognostic studies — Investigating the effect of a patient characteristic on disease outcome.

Comparative transcriptome profiling and characterization of gene expression for ovarian differentiation under RU486 treatment

17α, 20β-dihydroxypregn-4-en-3-one (17α, 20β-DP, DHP), a teleost specific biologically active progestin, has been proved to play a critical role in oocytes maturation, ovulation and spermiation. RU486 (Mifepristone, an antagonist of progestin receptor) has been applied in contraceptives, abortion and hormone therapy in clinical medicine. To get further insights into the molecular mechanisms of nuclear progestin receptor (Pgr) activated ovarian differentiation and maintenance, we conducted comparative gonadal transcriptome analysis, and investigated histological and transcriptional differences using 4 months after hatching (mah) RU486-treated XX and control XX/XY Nile tilapia (Oreochromis niloticus). DESeq analysis identified 7148 DEGs (differentially expressed genes) between RU486-treated and control XX gonads, while merely 442 DEGs were screened between the gonads of RU486-treated XX and control XY fish highlighting that RU486 treatment set forwards masculinity in XX fish. Comprehensive analysis of gene hierarchical clustering revealed that RU486 treatment in XX fish resulted in robust changes of gene expression profiles. In comparison with XX group, female-dominant genes were significantly repressed in RU486 treated XX fish gonads. Moreover, most parts of down-regulated genes in wild type female were evidently up-regulated genes in RU486-treated XX fish gonads. Comparing with control XY group, the majority of male-dominant genes represent a high level of expression. However, RU486-treatment led to an up-regulation of a cluster genes specifically which showed relative lower expression in both control XX and XY group. RU486-treatment mediated global changes of gene expression profiles in steroidogenesis, germ cell differentiation and follicular cell trans-differentiation were verified by quantitative PCR. Both morphological and immunohistochemistry results further proved that RU486 treatment initiates testicular-like gonads development in XX fish via simultaneously enhancing the male responsive genes and suppressing the female-dominant genes. Moreover, RU486 treatment caused significant decline of fshr, lhr and increase of ars. Taken together, our data confirms blocking of DHP physiology by RU486 treatment induces masculinization in XX gonad preferably via repressing of gonadotropin physiology, germ cell differentiation and promoting follicular trans-differentiation in teleosts.

The Effect Of ACTN3 Genotype On Self-reported One-mile Running Time In Young, Recreationally Active Women

Alpha-actinins form a crosslink between actin filaments and adjacent sarcomeres, and play a role in signaling and energy metabolism. Alpha-actinin-3, is encoded by the ACTN3 gene and only presents in Type II muscle fibers. Homozygosity for the 577X allele (XX) results in complete deficiency of α-actinin-3 and a compensatory upregulation of α-actinin-2, whereas heterozygosity (RX) and homozygosity for the 577R allele (RR) provide for the production of α-actinin-3. Research has reported a greater proportion of elite female distance runners are homozygous for the 577X allele compared to controls. However, no study to date has examined that apparent relationship in recreational women runners. PURPOSE: To examine the effect of ACTN3 genotype on self-reported one-mile running personal records (PR) in young, recreationally active women. METHODS: Thirty nine participants, grouped by the presence (RR+RX: n=27, age: 21.7 ± 3.8 years, BMI: 22.9 ± 3.3 kg/m2) or absence (XX: n=12, age: 21.2 ± 3.2 years, BMI: 21.5 ± 1.8 kg/m2) of the 577R allele, reported one-mile running PR. Genotype effects were examined using independent-sample t-tests and magnitude-based inference (MBI). RESULTS: A trend (p=0.065) toward faster one-mile times was observed in XX genotypes (415.7 ± 78.9 s) when compared to the RR+RX group (480.3 ± 104.8 s). MBI revealed a mechanistically beneficial effect of XX genotype (mean difference; ± 90% CI; -65 s, ± 57 s). Similar observations were made among a subset of thirteen faster runners, who reported a one-mile PR of less than seven minutes (RR+RX: n=7, age: 21.9 ± 5.0 years, BMI: 20.9 ± 3.4 kg/m2; XX: n=6, age: 19.5 ± 0.5 years; BMI: 21.8 ± 1.5 kg/m2). Though not statistically significant (p=0.378), those in the XX group (355.8 ± 46.5 s) reported 5.4% faster times than those in the RR+RX group (376.3 ± 33.6 s). MBI revealed a mechanistically beneficial effect of XX genotype (-20 s; ± 40 s). CONCLUSION: These findings suggest a potential benefit of XX genotype on middle-distance endurance performance. This is in agreement with prior investigations that have linked XX genotype to endurance capabilities in elite female athletes.

Birth Weight in Different Etiologies of Disorders of Sex Development.

It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.

History-dependent force, angular velocity and muscular endurance in ACTN3 genotypes.

This study aimed at determining the influence of the ACTN3 R577X polymorphism on muscle strength and muscle endurance in non-athletic young men. 266 healthy young men were included in this study. Each subject performed maximal isometric, concentric and eccentric contractions of the knee extensor muscles on an isokinetic dynamometer. Force depression, force enhancement and the fatigue index were derived from these data. In addition, handgrip strength, squat jump (SJ) and counter movement jump (CMJ) height were obtained. Our group included 83 RR (31 %), 131 RX (49 %) and 52 XX (20 %) individuals. The muscle bone cross-sectional area of the thigh was 5 % higher in RR compared to XX individuals (P = 0.033). RR genotypes showed 6 % higher handgrip strength compared to the XX group (P = 0.047). They also jumped 5 % higher in both the SJ and CMJ tests (P = 0.029; P = 0.031). No differences were found in force depression, force enhancement, isometric or eccentric strength. The relative concentric knee torque at 200°/s and at 300°/s was 7 and 8 % higher in RR compared to XX genotypes, respectively (P = 0.049; P = 0.048). Also, the fatigue index was found to be 4 % lower in XX genotypes (P = 0.037). Our findings are in agreement with the higher prevalence of the RR genotype in power-oriented activities. The better fatigue index of XX genotypes may be beneficial in endurance-type activities.

The ACTN3 R577X Polymorphism Is Associated With Muscle Power in Male Japanese Athletes

In this study, we investigated whether the ACTN3 R577X polymorphism is associated with muscular power in Japanese collegiate athletes by analyzing the mean and peak power results of a 30-second Wingate anaerobic test (WAnT) with respect to the ACTN3 R577X genotype in 253 Japanese athletes (144 men and 109 women). Each athlete performed a 30-second WAnT with a resistance equal to 7.5% of his or her body weight. Genotyping for the ACTN3 R577X (rs1815739) polymorphism was performed using the TaqMan approach. The ACTN3 R577X genotypes exhibited a Hardy-Weinberg equilibrium distribution in our population. The relative and absolute mean power results of the 30-second WAnT did not differ significantly among the genotypes. However, the relative peak power result of the WAnT was significantly higher in the R-allele-dominant model groups than in the XX group in male but not female athletes. These results suggest that the ACTN3 R allele is associated with the relative peak power during the WAnT in male Japanese collegiate athletes.

Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo

The emphasis on periodontal regeneration has been shifted towards the harmonization of bioactive molecules and physiological phases during regeneration. This study investigated whether the combination and sequential-release of platelet-derived growth factor (PDGF, mitogen) and simvastatin (differentiation factor) facilitated periodontal regeneration. PDGF and simvastatin were encapsulated in double-walled poly-( d,l-lactide) and poly-(d,l-lactide-co-glycolide) (PDLLA-PLGA) microspheres using the co-axial electrohydrodynamic atomization technique. Critical-sized periodontal defects on rat maxillae were filled with microspheres encapsulating BSA-in-core-shell (BB), PDGF-in-shell (XP), simvastatin-in-core and BSA-in-shell (SB), simvastatin-in-core and PDGF-in-shell, or unfilled with microspheres (XX), and examined at 14 and 28 days post-operatively. The resultant microspheres were around 15 μm diameter with distinct core–shell structure, and the fast-release of PDGF followed by slow-release of simvastatin was noted in the SP group. The SP group demonstrated significantly greater bone volume fraction and decreased trabecular separation compared to the XX group at day 14, and milder inflammatory cells infiltration and elevated tartrate-resistant acid phosphatase level were noted at day 28. Fibers were also well-aligned and obliquely inserted onto the root surface similar to native periodontal ligament with signs of cementogenesis in the SP group. In conclusion, the combination and sequential-release of PDGF-simvastatin accelerates the regeneration of the periodontal apparatus.

Explaining Seemingly Paradoxical Consumer Experiences: Conjoining Weekly Road Rage and Church Attendance

The purposes of the current study are threefold: Provide evidence that an extreme paradoxical group exists-people frequently attending church and exhibiting road rage, profile this group, and frame possible explanations for the seemingly paradoxical behaviors. This study employs data from a national (USA) lifestyle survey conducted by Market Facts with 3,350 American respondents. The major questions asked about church participation and road-rage behavior ("giving a finger" and "flashing headlights"). Nomologically, relevant activities include 3 items for church goers and 3 items for road-rage givers. Additionally, 14 items profiled the lifestyles of the unique paradoxical behavior segment. Utilizing cross-tabulation tables, property space analyses identify the double extreme (XX) group (18 people) and other 6 groups with a significant chi-square test, confirming the extreme group exists. Analyses of variance test results show that comparing nomologically relevant activities among the seven groups is all statistically significant, indicating the nomological validity is met. Overall, the XX group tends to have more males, be younger, and have a higher proportion of people working in sales. The profile of lifestyle analyses shows the XX group members have both high ambitions and expectations, might be very frustrated individuals, and equip with the adventurous and masculine traits related to aggression. The XX behavior group's demographic and psychographic characteristics portray similar lifestyles that differ from other groups. Case-based analyses provide further contextual information of nuances to XX segment individuals. The limited energy theory, the Eagleman's theory of unconscious mind, and justification theory help to explain why people conjointly go to church and commit road rage. Addressing chronic paradoxical behaviors provides implications for social de-marketing to reduce aggressive anti-social behavior such as road rage. Frequent church attendance may help make people more sensitive to their wrongdoings and gradually revise the anti-social behavior.

Does 45,X/46,XX mosaicism with 6–28% of aneuploidy affect the outcomes of IVF or ICSI?

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI. Forty-six women with a 45,X/46,XX karyotype with 6-28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype. No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p=0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p=0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p=0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p=0.51). 45,X/46,XX mosaicism with 6-28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies.

HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients

IntroductionThe revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines).MethodsGenomic DNA was analysed using high-resolution recombinant sequence-specific oligonucleotide PCR typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to 74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1) Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric procedure, and cytokines by multiplex bead array technology.ResultsOf the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12 (8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2, macrophage and fibroblast cytokines) were also generally higher in the SS group than in the SX and XX groups.ConclusionsRA susceptibility alleles investigated according to revised criteria for the classification of RA were significantly increased in South African RA patients and strongly associated with aCCP in particular as well as with circulating cytokines and disease severity.

Alpha-Actinin-3 (ACTN3) R577X Polymorphism Influences Knee Extensor Peak Power Response to Strength Training in Older Men and Women

The alpha-actinin-3 (ACTN3) R577X polymorphism has been associated with muscle power performance in cross-sectional studies. We examined baseline knee extensor concentric peak power (PP) and PP change with approximately 10 weeks of unilateral knee extensor strength training (ST) using air-powered resistance machines in 71 older men (65 [standard deviation = 8] years) and 86 older women (64 [standard deviation = 9] years). At baseline in women, the XX genotype group had an absolute (same resistance) PP that was higher than the RR (p =.005) and RX genotype groups (p =.02). The women XX group also had a relative (70% of one-repetition maximum [1-RM]) PP that was higher than that in the RR (p =.002) and RX groups (p =.008). No differences in baseline absolute or relative PP were observed between ACTN3 genotype groups in men. In men, absolute PP change with ST in the RR (n = 16) group approached a significantly higher value than in the XX group (n = 9; p =.07). In women, relative PP change with ST in the RR group (n = 16) was higher than in the XX group (n = 17; p =.02). The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults.