Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: The PRO-BONE study

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Purpose: Soft tissues, such as fat mass (FM) and lean mass (LM), play an important role in bone development but this is poorly understood in highly active youths. The objective of this study was to determine whether FM or LM is a stronger predictor of areal bone mineral density (aBMD) and hip geometry estimates in a group of physically active boys after adjusting for height, chronological age, moderate-to-vigorous physical activity (MVPA), FM, and LM. Methods: Participants included 121 boys (13.1±1.0 years) from the PRO-BONE study. Bone mineral content (BMC) and aBMD measured at total body, femoral neck and lumbar spine using dual-energy X-ray absorptiometry (DXA), and hip structural analysis was used to estimate bone geometry at the femoral neck. Body composition was assessed using DXA. The relationships of FM and LM with bone outcomes were analysed using simple and multiple linear regression analyses. Results: Pearson correlation coefficients showed that total body (less head) aBMD was significantly correlated with LM but not FM. Multiple linear regression analyses showed that FM, after accounting for height, age, MVPA and LM had no significant relationship with aBMD or hip geometry estimates, except for arms aBMD. By contrast, there were positive associations between LM and most aBMD and hip geometry estimates, after accounting height, age, MVPA and FM. Conclusions: The results of this study suggest that LM, and not FM, is the stronger predictor of aBMD and hip geometry estimates in physically active boys.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007–2013] under grant agreement no. PCIG13-GA-2013-618496

Lean mass explains the association between muscular fitness and bone outcomes in 13-year-old boys

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record AIM: This study investigated the associations between fitness indices and bone outcomes in young males. METHODS: Data were collected between autumn and winter 2014-2015 on 121 males with a mean age of 13.1 ± 0.1 years: 41 swimmers, 37 footballers, 29 cyclists and 14 nonathletes. Participants were recruited from athletic clubs and schools across South West England. Lean mass, areal bone mineral density and hip structural estimates were measured using dual-energy X-ray absorptiometry. The relationships between bone outcomes and the vertical jump, standing long jump and the 20-m shuttle run test were analysed using three regression models: model 1 was adjusted by age and stature, model 2 added vigorous physical activity and model 3 then added lean mass. RESULTS: The boys' performance in the vertical jump and standing long jump was positively associated with the majority of bone outcomes in models 1 and 2, but most of these disappeared in model 3. The 20-m shuttle run test was positively associated with most bone outcomes in all three models. Lean mass played a key role in the association between muscular fitness and bone outcomes. CONCLUSION: Vigorous physical activity did not explain the associations between fitness and bone outcomes, but lean mass did.European Union Seventh Framework Programme (FP7/2007–2013

Hemodynamic effects of local anesthetics intoxication. Experimental study in swine with levobupivacaine and bupivacaine

Purpose: To compare the hemodynamic repercussions following a toxic dose of levobupivacaine and bupivacaine intravascularly injected in swines. Methods: Large White pigs were anesthetized with thiopental, tracheal intubation was performed and mechanical ventilation was instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization (Swan-Ganz catheter). After a 30-minute resting period, the animals were randomly divided into two groups in a double-blinded fashion and received a bolus injection of 4 mg/kg of either agent for intoxication. Hemodynamic results were then evaluated at 1, 5, 10, 15, 20 and 30 minutes. Results: Levobupivacaine had greater hemodynamic repercussions than racemic bupivacaine. These results disagree with those found when the levorotatory isomer of bupivacaine was used in humans, but are in agreement with recently reported findings in animals. Conclusion: Levobupivacaine was shown to be more toxic in pigs than racemic bupivacaine when large doses are injected intravenously.231556

The Relationship Between Rating of Perceived Exertion and Muscle Activity During Exhaustive Constant-Load Cycling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The aims of this study were to verify the relationship between rating of perceived exertion (RPE) and electromyography (EMG) increases during exhaustive constant-load cycling bouts and, to compare and to correlate the power outputs corresponding to perceived exertion threshold (PET) and neuromuscular fatigue threshold (NFT). 11 men completed 3-4 different exhaustive constant-load cycling bouts on a cycle ergometer, being RPE and EMG measured throughout the bouts. The linear regression of the RPE(slope) and EMG(slope) against the power output identified the PET and NFT intensity, respectively. There was a significant relationship between RPE slope and EMG(slope) (R(2) = 0.69; P < 0.01). However, the linearity of RPE(slope) (R(2) = 0.93 +/- 0.07) was significantly higher (P < 0.001) than EMG(slope) (R(2) = 0.63 +/- 0.25). In addition, the RPE(slope) and EMG(slope) were related to time to exhaustion (r = -0.59 and r = -0.60; P < 0.001). There was no significant difference (P = 0.42) between PET (201.5 +/- 27.9W) and NFT (210.3 +/- 22.6W) and they were significantly correlated (r = 0.78; P = 0.005). Therefore, the RPE and EMG increases during exhaustive constant-load cycling bouts are related and, PET and NFT intensities are similar and closely associated.3110683688Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [04/12589-0

2-Methoxyestradiol-3,17-O,O-bis-sulfamate (STX140) inhibits proliferation and invasion via senescence pathway induction in human BRAFi-resistant melanoma cells

The endogenous estradiol derivative 2-Methoxyestradiol (2-ME) has shown good and wide anticancer activity but suffers from poor oral bioavailability and extensive metabolic conjugation. However, its sulfamoylated derivative, 2-methoxyestradiol-3,17-O,O-bis-sulfamate (STX140), has superior potential as a therapeutic agent, acts by disrupting microtubule polymerization, leading to cell cycle arrest and apoptosis in cancer cells and possesses much better pharmaceutical properties. This study investigated the antiproliferative and anti-invasive activities of STX140 in both SKMEL-28 naïve melanoma (SKMEL28-P) cells and resistant melanoma cells (SKMEL-28R). STX140 inhibited cell proliferation in the nanomolar range while having a less pronounced effect on human melanocytes. Additionally, STX140 induced cell cycle arrest in the G2/M phase and sub-G1, reduced migration, and clonogenic potential in monolayer models, and inhibited invasion in a 3D human skin model with melanoma cells. Furthermore, STX140 induced senescence features in melanoma and activated the senescence machinery by upregulating the expression of senescence genes and proteins related to senescence signaling. These findings suggest that STX140 may hold potential as a therapeutic agent for melanoma treatment

Fatal CTLA-4 Heterozygosity With Autoimmunity and Recurrent Infections: a De Novo Mutation

Primary immunodeficiency disorders are rarely diagnosed in adults but must be considered in the differential diagnosis of combined recurrent infections and autoimmune disease. We describe a patient with CTLA-4 haploinsufficiency and an abnormal regulatory T-cell phenotype. Unusually, infections were more severe than autoimmunity, illustrating therapeutic challenges in disease course.info:eu-repo/semantics/publishedVersio

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets