copy number alteration in bladder cancer: Integrative analysis in patient-derived xenografts and cancer patients.

Bladder cancer (BlCa) is an extensively heterogeneous disease that leads to great variability in tumor evolution scenarios and lifelong patient surveillance, emphasizing the need for modern, minimally invasive precision medicine. Here, we explored the clinical significance of copy number alterations (CNAs) in BlCa. CNA profiling was performed in 15 patient-derived xenografts (PDXs) and validated in The Cancer Genome Atlas BlCa (TCGA-BLCA;  = 408) and Lindgren et al.

Hereditary angioedema with normal C1 inhibitor associated with carboxypeptidase N deficiency.

Background: Hereditary angioedema (HAE) is a potentially life-threatening disorder characterized by recurrent episodes of subcutaneous or submucosal swelling. HAE with normal C1 inhibitor (HAE-nC1-INH) is an underdiagnosed condition. Although the association with genetic variants has been identified for some families, the genetic causes in many patients with HAE-nC1-INH remain unknown.

Recovery during Successive 120-min Football Games: Results from the 120-min Placebo/Carbohydrate Randomized Controlled Trial.

Purpose: This study aimed to examine the recovery kinetics (i.e., time-dependent changes) of performance-related variables between two 120-min male football games performed 3 d apart with and without carbohydrate supplementation.

Extended Match Time Exacerbates Fatigue and Impacts Physiological Responses in Male Soccer Players.

Purpose: This study evaluated how extended match time (90 + 30 min) affected physiological responses and fatigue in male soccer players.

Methods: Twenty competitive players (mean ± SD: age, 20 ± 1 yr; maximal oxygen uptake, 59 ± 4 mL·min -1 ·kg -1 ) completed an experimental match with their activity pattern and heart rate assessed throughout the game, whereas countermovement jump performance and repeated sprint ability were tested and quadriceps muscle biopsies and venous blood samples were taken at baseline and after 90 and 120 min of match play.

Results: Less high-intensity running (12%) was performed in extra time in association with fewer intense accelerations and decelerations per minute compared with normal time.

Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE).

Existing evidence indicates that modifier genes could change the phenotypic outcome of the causal variant and thus explain the expression variability of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). To further examine this hypothesis, we investigated the presence or absence of 18 functional variants of genes encoding proteins involved in the metabolism and function of bradykinin, the main mediator of C1-INH-HAE attacks, in relation to three distinct phenotypic traits of patients with C1-INH-HAE, i.e.

Skeletal muscle phenotype and game performance in elite women football players.

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO ; 51 ± 6 ml/min/kg). Muscle monocarboxylate transporter 4 (MCT4) protein expression explained 46% of the variance in total game distance, while the ability to maintain high-intensity running (HIR) during the final 15 min of the game correlated to myosin heavy chain 1 (MHCI) and Na -K ATPase β1, FXYD1 (phospholemman) and superoxide dismutase 2 (SOD2) protein expression (range: r = 0.

Muscle metabolism and impaired sprint performance in an elite women's football game.

The present study examined skeletal muscle metabolism and changes in repeated sprint performance during match play for n = 20 competitive elite women outfield players. We obtained musculus vastus lateralis biopsies and blood samples before, after, and following intense periods in each half of a friendly match, along with 5 × 30-meter sprint tests and movement pattern analyses (10-Hz S5 Global Positioning System [GPS]). Muscle glycogen decreased by 39% and 42% after an intense period of the second half and after the match, respectively, compared to baseline (p < 0.

Recovery Kinetics Following Small-Sided Games in Competitive Soccer Players: Does Player Density Size Matter?

Purpose: To examine the recovery kinetics of exercise-induced muscle damage (EIMD), neuromuscular fatigue, and performance following small-sided games (SSGs) of different densities in soccer.

Methods: Ten male players randomly completed 3 trials: a control trial (no SSGs), 4v4 SSGs (62.5 m2/player), and 8v8 SSGs (284.

Deciphering the Genetics of Primary Angioedema with Normal Levels of C1 Inhibitor.

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with alterations as well as those with histaminergic acquired angioedema were excluded.

A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases.

ARSACS is an autosomal recessive disorder characterized by ataxia, spasticity, and polyneuropathy. A plethora of worldwide distributed mutations have been described so far. Here, we report two brothers, born to non-consanguineous parents, presenting with cerebellar ataxia and peripheral neuropathy.

High-intensity interval neuromuscular training promotes exercise behavioral regulation, adherence and weight loss in inactive obese women.

It is unclear how high-intensity, interval-type nontraditional exercise training programmes can be feasible and effective options for inactive obese individuals. This randomized controlled trial investigated the hypothesis that a 10-month high-intensity, interval-type neuromuscular training programme (DoIT) with adjunct portable modalities, performed in a small-group setting, induces improvements in psychological well-being, subjective vitality and exercise behavioural regulations in obese women. Associations between adherence, psychological and physiological indicators were also investigated.

Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency.

SERPING1 genotyping of subjects suspicious for hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is important for clinical practice as well as for research reasons. Conventional approaches towards the detection of C1-INH-HAE-associated SERPING1 variants are cumbersome and time-demanding with many pitfalls. To take advantage of the benefits of next-generation sequencing (NGS) technology, we developed and validated a custom NGS platform that, by targeting the entire SERPING1 gene, facilitates genetic testing of C1-INH-HAE patients in clinical practice.

Genetic Determinants of C1 Inhibitor Deficiency Angioedema Age of Onset.

Background: In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype.

Methods: We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism.

Fabry disease due to D313Y and novel GLA mutations.

Objectives: Our aim is to report four novel α-gal A gene () mutations resulting in Fabry disease (FD) and provide evidence of pathogenicity of the D313Y mutation regarding which contradictory data have been presented in the literature.

Setting And Participants: Twenty-five family members of nine unrelated patients with definite FD diagnosis, 10 clinically suspected cases and 18 members of their families were included in this polycentric cohort study.

Primary And Secondary Outcome Measures: Genotyping and measurement of lyso-Gb was performed in all individuals.

Increased Triacylglycerol Lipase Activity in Adipose Tissue of Lean and Obese Men During Endurance Exercise.

Context: Although there is increasing information on the mechanism of lipolysis in adipose tissue, the effect of exercise on individual factors of lipolysis is less well understood.

Objective: We compared changes in adipose-tissue triacylglycerol lipase activity and gene expression of adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase (HSL), monoacylglycerol lipase, perilipin 1, and comparative gene identification 58 (CGI-58) during exercise between lean and obese men.

Design And Participants: Seven lean and nine obese men cycled for 30 minutes at a heart rate of 130 to 140 beats per minute.

FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia.

Background: Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 x 109/L).

Foxp3 expression in human cancer cells.

Objective: Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types.

Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV.

Mutations in the SLC40A1 gene result in a dominant genetic disorder [ferroportin disease; hereditary hemochromatosis type (HH) IV], characterized by iron overload with two different clinical manifestations, normal transferrin saturation with macrophage iron accumulation (the most prevalent type) or high transferrin saturation with hepatocyte iron accumulation (classical hemochromatosis phenotype). In previous studies, the mutational analysis of SLC40A1 gene has been performed at the genomic DNA level by PCR amplification and direct sequencing of all coding regions and flanking intron-exon boundaries (usually in 9 PCR reactions). In this study, we analyzed the SLC40A1 gene at the mRNA level, in two RT-PCR reactions, followed by direct sequencing and/or NIRCA (non-isotopic RNase cleavage assay).