Changes in body composition and bone of female collegiate soccer players through the competitive season and off-season.

OBJECTIVES: To assess body composition and bone changes pre- to post-season (pre-post) and post- to off-season (post-off) in female soccer athletes (SC). METHODS: Outcomes were assessed using DXA and pQCT in 23 SC and 17 controls at three times throughout season. RESULTS: SC, non-starters in particular, lost lean mass pre-post (-0.9±0.2 kg, p<0.01; not different from controls, p=0.2) and gained fat mass post-off (1.4±0.3 kg, p<0.01; differed from controls, p=0.01). Baseline femoral neck and hip aBMD were higher in SC than controls (both,p<0.04), but increased in controls more than SC in pre-post and decreased post-off. SC cortical bone mineral content (BMC), cortical area and periosteal circumference increased pre-post (all, p<0.01; differed from controls, p<0.05) and trabecular vBMD decreased post-off (-3.0±1.3 mg/cm3; p=0.02; not different from controls, p=0.4). Both SC and controls increased cortical BMC, cortical area, and thickness post-off (all, p<0.01). CONCLUSION: Soccer players lost lean mass over the competitive season that was not recovered during off-season. Bone size increased pre- to post-season. Female soccer athletes experience body composition and bone geometry changes that differ depending on the time of season and on athlete's playing status. Evaluations of athletes at key times across the training season are necessary to understand changes that occur.

The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain.

Fabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphingolipids, and accompanied by clinical manifestations, such as cardiac disorders, renal failure, pain and peripheral neuropathy. Globotriaosylsphingosine (lyso-Gb3), a deacylated form of globotriaosylceramide (Gb3), has emerged as a marker of Fabry disease. We investigated the link between Gb3, lyso-Gb3 and pain. Plantar administration of lyso-Gb3 or Gb3 caused mechanical allodynia in healthy mice. In vitro application of 100nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1µM, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca(2+) channels were substantially enhanced by application of 1µM lyso-Gb3. These studies suggest a direct role for lyso-Gb3 in the sensitisation of peripheral nociceptive neurons that may provide an opportunity for therapeutic intervention in the treatment of Fabry disease-associated pain.

A role for Piezo2 in EPAC1-dependent mechanical allodynia.

Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1-/- mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1-Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain.

The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers.

AIM: Although radiation-induced cardiotoxicity has been described in patients with breast cancer and Hodgkin's disease, the effect of oesophageal radiotherapy on the heart has not been evaluated. This study was designed to evaluate the dose received by the heart during chemoradiotherapy (CT-RT) for oesophageal cancer, to assess its impact on cardiac function, and explore methods of reducing this dose. METHODS: Cardiac doses were calculated from dose-volume histograms in 15 patients with carcinoma of mid and lower oesophagus undergoing combined technique treatment, in whom pre- and post-treatment multigated acquisition scans were available. Chemotherapy consisted of cisplatin and 5-fluorouracil with or without paclitaxel. The radiotherapy was delivered in two phases to a total dose of 45-50 Gy in 25 fractions. RESULTS: There was a significant reduction in median ejection fraction after CT-RT (63% to 58%, P = 0.003). The median dose received by the heart using three-dimensional conformal technique was 27.4 Gy (interquartile range 25.8-34.2 Gy). If shielding blocks were not used, as would be the case with conventional planning, the median dose would have been 35 Gy (interquartile range 28.2-37.7 Gy), which is significantly higher (P = 0.002). The use of a three-field technique throughout treatment also reduced the median cardiac dose from 27.4 Gy to 22.7 Gy (P = 0.001) and the volume of heart receiving 70% of total dose from 63.8% to 25% (P = 0.001). CONCLUSION: This study highlights the significant dose of radiation received by the heart during oesophageal CT-RT, with consequent reduction in cardiac ejection fraction. Conformal radiotherapy reduces cardiac doses received. The cardiac, as well as the pulmonary, side effects of CT-RT needs to be borne in mind, especially when using this treatment before radical surgery.