MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin Lymphoma patients

Background: In recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways. Design and Methods: We analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS). Results: The KRT81 (rs3660) GG genotype was associated with an increased risk of neurological toxicity (P=0.016), while patients with XPO5 (rs11077) AA or CC genotypes had a higher rate of bleomycin-associated pulmonary toxicity (P=0.048). Both miR-SNPs emerged as independent factors in the multivariate analysis. The XPO5 AA and CC genotypes were also associated with a lower response rate (P=0.036). XPO5 (P=0.039) and TRBP (rs784567) (P=0.022) genotypes emerged as prognostic markers for DFS, and XPO5 was also associated with OS (P=0.033). In the multivariate analysis, only XPO5 emerged as an independent prognostic factor for DFS (HR: 2.622; 95%CI 1.039-6.620; P=0.041). Given the influence of XPO5 and TRBP as individual markers, we then investigated the combined effect of these miR-SNPs. Patients with both the XPO5 AA/CC and TRBP TT/TC genotypes had the shortest DFS (P=0.008) and OS (P=0.008). Conclusion: miR-SNPs can add useful prognostic information on treatment-related toxicity and clinical outcome in Hodgkin lymphoma and can be used to identify patients likely to be chemoresistant or to relapse.

Weber's law in decision making: integrating behavioral data in humans with a neurophysiological model

Recent single-cell studies in monkeys (Romo et al., 2004) show that the activity of neurons in the ventral premotor cortex covaries with the animal's decisions in a perceptual comparison task regarding the frequency of vibrotactile events. The firing rate response of these neurons was dependent only on the frequency differences between the two applied vibrations, the sign of that difference being the determining factor for correct task performance. We present a biophysically realistic neurodynamical model that can account for the most relevant characteristics of this decision-making-related neural activity. One of the nontrivial predictions of this model is that Weber's law will underlie the perceptual discrimination behavior. We confirmed this prediction in behavioral tests of vibrotactile discrimination in humans and propose a computational explanation of perceptual discrimination that accounts naturally for the emergence of Weber's law. We conclude that the neurodynamical mechanisms and computational principles underlying the decision-making processes in this perceptual discrimination task are consistent with a fluctuation-driven scenario in a multistable regime.

Association of calcemia and serum vitamin D with 24H-urinary calcium excretion in a swiss population-based study

Background: Elevated urinary calcium excretion is associated with reduced bone mineral density. Population-based data on urinary calcium excretion are scarce. We explored the association of serum calcium and circulating levels of vitamin D (including 25(OH)D2 and 25(OH)D3) with urinary calcium excretion in men and women in a population-based study. Methods: We used data from the "Swiss Survey on Salt" conducted between 2010 and 2012 and including people aged 15 years and over. Twenty-four hour urine collection, blood analysis, clinical examination and anthropometric measures were collected in 11 centres from the 3 linguistic regions of Switzerland. Vitamin D was measured centrally using liquid chromatography - tandem mass spectrometry. Hypercalciuria was defined as urinary calcium excretion >0.1 mmol/kg/24h. Multivariable linear regression was used to explore factors associated with 24-hour urinary calcium excretion (mmol/24h) squared root transformed, taken as the dependant variable. Vitamin D was divided into monthspecific tertiles with the first tertile having the lowest value and the third tertile having the highest value. Results: The 669 men and 624 women had mean (SD) age of 49.2 (18.1) and 47 (17.9) years and a prevalence of hypercalciuria of 8.9% and 8.0%, respectively. In adjusted models, the association of urinary calcium excretion with protein-corrected serum calcium was (β coefficient } standard error, according to urinary calcium squared root transformed) 1.125 } 0.184 mmol/L per square-root (mmol/24h) (P<0.001) in women and 0.374 } 0.224 (P=0.096) in men. Men in the third month-specific vitamin D tertile had higher urinary calcium excretion than men in the first tertile (0.170 } 0.05 nmol/L per mmol/24h, P=0.001) and the corresponding association was 0.048 } 0.043, P= 0.272 in women. Conclusion: About one in eleven person has hypercalciuria in the Swiss population. The positive association of serum calcium with urinary calcium excretion was steeper in women than in men, independently of menopausal status. Circulating vitamin D was associated positively with urinary calcium excretion only in men. The reasons underlying the observed sex differences in the hormonal control of urinary calcium excretion need to be explored in further studies.

Searching for sex-reversals to explain population demography and the evolution of sex chromosomes.

Sex determination can be purely genetic (as in mammals and birds), purely environmental (as in many reptiles), or genetic but reversible by environmental factors during a sensitive period in life, as in many fish and amphibians (Wallace et al. 1999; Baroiller et al. 2009a; Stelkens & Wedekind 2010). Such environmental sex reversal (ESR) can be induced, for example, by temperature changes or by exposure to hormone-active substances. ESR has long been recognized as a means to produce more profitable single-sex cultures in fish farms (Cnaani & Levavi-Sivan 2009), but we know very little about its prevalence in the wild. Obviously, induced feminization or masculinization may immediately distort population sex ratios, and distorted sex ratios are indeed reported from some amphibian and fish populations (Olsen et al. 2006; Alho et al. 2008; Brykov et al. 2008). However, sex ratios can also be skewed by, for example, segregation distorters or sex-specific mortality. Demonstrating ESR in the wild therefore requires the identification of sex-linked genetic markers (in the absence of heteromorphic sex chromosomes) followed by comparison of genotypes and phenotypes, or experimental crosses with individuals who seem sex reversed, followed by sexing of offspring after rearing under non-ESR conditions and at low mortality. In this issue, Alho et al. (2010) investigate the role of ESR in the common frog (Rana temporaria) and a population that has a distorted adult sex ratio. They developed new sex-linked microsatellite markers and tested wild-caught male and female adults for potential mismatches between phenotype and genotype. They found a significant proportion of phenotypic males with a female genotype. This suggests environmental masculinization, here with a prevalence of 9%. The authors then tested whether XX males naturally reproduce with XX females. They collected egg clutches and found that some had indeed a primary sex ratio of 100% daughters. Other clutches seemed to result from multi-male fertilizations of which at least one male had the female genotype. These results suggest that sex-reversed individuals affect the sex ratio in the following generation. But how relevant is ESR if its prevalence is rather low, and what are the implications of successful reproduction of sex-reversed individuals in the wild?

Ventilation, Oxidative Stress, and Nitric Oxide in Hypobaric versus Normobaric Hypoxia.

PURPOSE: Slight differences in physiological responses and nitric oxide (NO) have been reported at rest between hypobaric hypoxia (HH) and normobaric hypoxia (NH) during short exposure.Our study reports NO and oxidative stress at rest and physiological responses during moderate exercise in HH versus NH. METHODS: Ten subjects were randomly exposed for 24 h to HH (3000 m; FIO2, 20.9%; BP, 530 ± 6 mm Hg) or to NH (FIO2, 14.7%; BP, 720 ± 1 mm Hg). Before and every 8 h during the hypoxic exposures, pulse oxygen saturation (SpO2), HR, and gas exchanges were measured during a 6-min submaximal cycling exercise. At rest, the partial pressure of exhaled NO, blood nitrate and nitrite (NOx), plasma levels of oxidative stress, and pH levels were additionally measured. RESULTS: During exercise, minute ventilation was lower in HH compared with NH (-13% after 8 h, P < 0.05). End-tidal CO2 pressure was lower (P < 0.01) than PRE both in HH and NH but decreased less in HH than that in NH (-25% vs -37%, P < 0.05).At rest, exhaled NO and NOx decreased in HH (-46% and -36% after 24 h, respectively, P < 0.05) whereas stable in NH. By contrast, oxidative stress was higher in HH than that in NH after 24 h (P < 0.05). The plasma pH level was stable in HH but increased in NH (P < 0.01). When compared with prenormoxic values, SpO2, HR, oxygen consumption, breathing frequency, and end-tidal O2 pressure showed similar changes in HH and NH. CONCLUSION: Lower ventilatory responses to a similar hypoxic stimulus during rest and exercise in HH versus NH were sustained for 24 h and associated with lower plasma pH level, exaggerated oxidative stress, and impaired NO bioavailability.

Measuring service quality in sport management: an application of the SERVQUAL scale

The aim of this study is to provide an instrument for measuring service quality in sports enterprises from the point of view of the customers. For this purpose we intend to elaborate an enquiry starting out from a more general scale called SERVIQUAL. We have limited our research project to sports enterprises where the customer participates actively, i.e., we have excluded sports clubs and other organizations which offer sport as entertainment. Our choice is mainly due to the fact that few studies have been carried out in this area and that sports has been earning an increasing amount of adepts during the last decades in Spain. The DELPHI method has been applied with the collaboration of a panel of experts in order to evaluate the viability and adequacy of the modified SERVQUAL scale.

Consensus recommendations on training and competing in the heat.

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimize performance is to heat acclimatize. Heat acclimatization should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimizing the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events for hydration and body cooling opportunities when competitions are held in the heat.

Plantar flexor neuromuscular adjustments following match-play football in hot and cool conditions.

We assessed neuromuscular fatigue and recovery of the plantar flexors after playing football with or without severe heat stress. Neuromuscular characteristics of the plantar flexors were assessed in 17 male players at baseline and ∼30 min, 24, and 48 h after two 90-min football matches in temperate (∼20 °C and 55% rH) and hot (∼43 °C and 20% rH) environments. Measurements included maximal voluntary strength, muscle activation, twitch contractile properties, and rate of torque development and soleus EMG (i.e., root mean square activity) rise from 0 to 30, -50, -100, and -200 ms during maximal isometric contractions for plantar flexors. Voluntary activation and peak twitch torque were equally reduced (-1.5% and -16.5%, respectively; P < 0.05) post-matches relative to baseline in both conditions, the latter persisting for at least 48 h, whereas strength losses (∼5%) were not significant. Absolute explosive force production declined (P < 0.05) 30 ms after contraction onset independently of condition, with no change at any other epochs. Globally, normalized rate of force development and soleus EMG activity rise values remained unchanged. In football, match-induced alterations in maximal and rapid torque production capacities of the plantar flexors are moderate and do not differ after competing in temperate and hot environments.

Tendinopathies du sportif: étiologie, diagnostic et traitement [Tendinitis in athletes: etiology, diagnosis and treatment].

Tendinopathy is one of the most common diagnosis in sports. Knowledges about their etiology, the repair process to their diagnosis and their treatment have improved thanks to the development of imaging, especially ultra- sound. The disorder whose etiology could be mechanical or degenerative can cause long- term disability and sometimes the end of the sport carreer. The risk of reccurence is com- mon; this may lead to tendon rupture whose functional effects can be significative. The management should be early: it must respect the deadlines for tendon healing and pro- pose a gradual recovery efforts after elimina tion of the contributing factors involved.

Postnatal ontogenesis of the tibia. Implications for age and sex estimation

The growth of five variables of the tibia (diaphyseal length, diaphyseal length plus distal epiphysis, condylo-malleolar length, sagittal diameter of the proximal epiphysis, maximum breadth of the distal epiphysis) were analysed using polynomial regression in order to evaluate their significance and capacity for age and sex determination during and after growth. Data were collected from 181 (90♂ and 91♀) individuals ranging from birth to 25 years of age and belonging to three documented collections from Western Europe. Results indicate that all five variables exhibit linear behaviour during growth, which can be expressed by a first-degree polynomial function. Sexual significant differences were observed from age 15 onward in the two epiphysis measurements and condylo-malleolar length, suggesting that these three variables could be useful for sex determination in individuals older than 15 years. Strong correlation coefficients were identified between the five tibial variables and age. These results indicate that any of the studied tibial measurements is likely to serve as a useful source for estimating sub-adult age in both archaeological and forensic samples.

Plant Mating Systems: Female Sterility in the Driver's Seat.

Violation of Mendel's Law of Segregation by selfish X chromosomes that favour their own transmission is known for a number of organisms. Now, a new study reveals sex-ratio distortion favouring males and explains previously puzzling sex ratios in a Mediterranean shrub.

Bystander responses to a violent incident in an immersive virtual environment

Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the ingroup condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation.

Manipulation of arthropod sex determination by endosymbionts: diversity and molecular mechanisms.

Arthropods exhibit a large variety of sex determination systems both at the chromosomal and molecular level. Male heterogamety, female heterogamety, and haplodiploidy occur frequently, but partially different genes are involved. Endosymbionts, such as Wolbachia, Cardinium,Rickettsia, and Spiroplasma, can manipulate host reproduction and sex determination. Four major reproductive manipulation types are distinguished: cytoplasmic incompatibility, thelytokous parthenogenesis, male killing, and feminization. In this review, the effects of these manipulation types and how they interfere with arthropod sex determination in terms of host developmental timing, alteration of sex determination, and modification of sexual differentiation pathways are summarized. Transitions between different manipulation types occur frequently which suggests that they are based on similar molecular processes. It is also discussed how mechanisms of reproductive manipulation and host sex determination can be informative on each other, with a special focus on haplodiploidy. Future directions on how the study of endosymbiotic manipulation of host reproduction can be key to further studies of arthropod sex determination are shown.

Steroid hormones interrelationships in the metabolic syndrome: an introduction to the ponderostat hypothesis

Sexual dimorphism in the metabolic syndrome. The clairvoyant early implication of sex hormones in the characterization of the metabolic syndrome (MS) was detected early, and in accordance with the well-known sex-related main patterns of fat deposition in obesity: gynoid and android. The differences point to a direct implication of androgens and estrogens in the development, properties and maintenance of obesity and, by extension, to the cumulus of diseases grouped in the MS. For a long time, the key issue of the MS, i.e. the metabolic event explaining (and justifying) most of the derangements of the MS, has been considered to be insulin resistance (...)

Personality effects and sex differences on the international affective picture system (IAPS) : a Spanish and Swiss study

The present study analyses the relationship between Anxiety and Impulsivity personality factors and emotions, by controlling for country and sex effects in a sample of Spanish and Swiss university students. Emotions were assessed through the International Affective Picture System (IAPS) of pictures (valence/arousal) using the Self-Assessment Manikin (SAM) procedure. The mixed valence/arousal groups' pictures were formed according to Tok, Koyuncu, Dural and Catikkas procedure (2010). Results showed that females scored significantly higher in Anxiety factor and men in Impulsivity factor in both countries. The effect of sex was highly significant for Anxiety (ŋ2: 0.12), but there was no significant effect of the country. Also, females obtained higher scores in the four valence/arousal pictures groups. The sex effect was particularly robust for negative valence-high arousal (ŋ2: 0.13). Impulsivity correlated with high ratings of positive valence-high arousal while Anxiety correlated with high ratings of negative valence-high arousal and with high ratings of negative valence-low arousal in both sexes, although scores were higher for females. Structural Equation Modelling confirmed these relationships. Nevertheless, Anxiety and Impulsivity explained only a small amount of the accounted variance of the self-reported valence and arousal of the pictures.