There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance-type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 19 Φεβρουαρίου 2016
Cyclic movement frequency is associated with muscle typology in athletes
Discriminant musculo-skeletal leg characteristics between sprint and endurance elite Caucasian runners
Excellence in either sprinting or endurance running requires specific musculo-skeletal characteristics of the legs. This study aims to investigate the morphology of the leg of sprinters and endurance runners of Caucasian ethnicity. Eight male sprinters and 11 male endurance runners volunteered to participate in this cross-sectional study. They underwent magnetic resonance imaging and after data collection, digital reconstruction was done to calculate muscle volumes and bone lengths. Sprinters have a higher total upper leg volume compared to endurance runners (7340 vs 6265 cm3 ). Specifically, the rectus femoris, vastus lateralis, and hamstrings showed significantly higher muscle volumes in the sprint group. For the lower leg, only a higher muscle volume was found in the gastrocnemius lateralis for the sprinters. No differences were found in muscle volume distribution, center of mass in the different muscles, or relative bone lengths. There was a significant positive correlation between ratio hamstrings/quadriceps volume and best running performance in the sprint group. Sprinters and endurance runners of Caucasian ethnicity showed the greatest distinctions in muscle volumes, rather than in muscle distributions or skeletal measures. Sprinters show higher volumes in mainly the proximal and lateral leg muscles than endurance runners.
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Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion
Purpose: The aim of this study was to identify the genetic cause of early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy in a consanguineous family. Methods: An affected 6-month-old child underwent neurological and ophthalmological examinations. Genetic analyses included homozygosity mapping, copy number analysis, conventional polymerase chain reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole-exome sequencing. Expression analysis of GRID2 was performed by quantitative polymerase chain reaction and immunohistochemistry. Results: A homozygous deletion of exon 2 of GRID2 (p.G1y30_Glu-81del) was identified in the proband. GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human adult retina and retinal pigment epithelium. In addition, Grid2 expression was demonstrated in different stages of murine retinal development. GRID2 immunostaining was shown in murine and human retina. Whole-exome sequencing in the proband did not provide arguments for other disease-causing mutations, supporting the idea that the phenotype observed represents a single clinical entity. Conclusion: We identified GRID2 as an underlying disease gene of early-onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina.
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Identity-by-descent-guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy
Purpose: Autosomal recessive retinal dystrophies are clinically and genetically heterogeneous, which hampers molecular diagnosis. We evaluated identity-by-descent-guided Sanger sequencing or whole-exome sequencing in 26 families with nonsyndromic (19) or syndromic (7) autosomal recessive retinal dystrophies to identify disease-causing mutations. Methods: Patients underwent genome-wide identity-by-descent mapping followed by Sanger sequencing (16) or whole-exome sequencing (10). Whole-exome sequencing data were filtered against identity-by-descent regions and known retinal dystrophy genes. The medical history was reviewed in mutation-positive families. Results: We identified mutations in 14 known retinal dystrophy genes in 20/26 (77%) families: ABCA4, CERKL, CLN3, CNNM4, C2orf71, IQCB1, LRAT, MERTK, NMNAT1, PCDH15, PDE6B, RDH12, RPGRIP1, and USH2A. Whole-exome sequencing in single individuals revealed mutations in either the largest or smaller identity-by-descent regions, and a compound heterozygous genotype in NMNAT1. Moreover, a novel deletion was found in PCDH15. In addition, we identified mutations in CLN3, CNNM4, and IQCB1 in patients initially diagnosed with nonsyndromic retinal dystrophies. Conclusion: Our study emphasized that identity-by-descent-guided mutation analysis and/or whole-exome sequencing are powerful tools for the molecular diagnosis of retinal dystrophy. Our approach uncovered unusual molecular findings and unmasked syndromic retinal dystrophies, guiding future medical management. Finally, elucidating ABCA4, LRAT, and MERTK mutations offers potential gene-specific therapeutic perspectives.
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"Exp Ther Med"[jour]; +60 new citations
60 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2016/02/19
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Initial Evaluation of the Pediatric PROMIS® Health Domains in Children and Adolescents With Sickle Cell Disease
Background
The Patient Reported Outcomes Measurement Information System (PROMIS®) has developed pediatric self-report scales measuring several unidimensional health attributes (domains) suitable for use in clinical research, but these measures have not yet been validated in sickle cell disease (SCD).
Procedure
A convenience sample of SCD children, aged 8–17 years, from two sickle cell programs was recruited at routine clinic visits, including some for hydroxyurea monitoring or monthly transfusions. Children completed PROMIS pediatric items using an online data collection platform, the PROMIS Assessment Center Web site.
Results
A total of 235 participants (mean age 12.5 ± 2.8 years, 49.8% female) participated in the study. Adolescents (ages 12–17 years) reported significantly higher pain interference and depressive symptoms, and worse lower extremity physical functioning domain scores compared to younger children (ages 8–11 years). Female participants reported significantly higher pain interference, fatigue, and depressive symptoms, and worse lower extremity physical functioning domain scores compared with their male counterparts. Participants with hip or joint problems that limited usual activities reported significantly higher pain, fatigue, and depressive symptoms scores, and worse upper/lower extremity physical functioning scores as did participants who had experienced sickle pain in the previous 7 days.
Conclusions
PROMIS pediatric measures are feasible in a research setting and identify expected differences in known group comparisons in a sample of SCD children. The large domain score differences between those with or without SCD-related complications suggest the potential usefulness of these measures in clinical research, but further validation studies are needed, particularly in clinical practice settings.
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Controlled production of the elusive metastable form II of acetaminophen (paracetamol): a fully scalable templating approach in a cooling environment
DOI: 10.1039/C6CC01032F, Communication
A scalable, transferable, cooling crystallisation route to the elusive, metastable, form II of the API acetaminophen (paracetamol) has been developed using a multicomponent "templating" approach, delivering 100% polymorphic phase pure...
The content of this RSS Feed (c) The Royal Society of Chemistry
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l-carnitine protects rat hepatocytes from oxidative stress induced by T-2 toxin.
l-carnitine protects rat hepatocytes from oxidative stress induced by T-2 toxin.
Drug Chem Toxicol. 2016 Feb 18;:1-6
Authors: Moosavi M, Rezaei M, Kalantari H, Behfar A, Varnaseri G
Abstract
CONTEXT: Oxidative stress and mitochondrial dysfunction are thought to be the main mechanism of T-2 toxin toxicity. T-2 toxin is the most potent trichothecene mycotoxin which is present in agricultural products. L-carnitine, besides its anti-oxidative properties, facilitates the transportation of long-chain fatty acids in to mitochondrial matrix.
OBJECTIVE: In this study we tested whether L-carnitine, an antioxidant and a facilitator for long-chain fatty acid transportation across mitochondrial membranes, could protect rat hepatocytes against toxicity induced by T-2 toxin.
MATERIALS AND METHODS: L-carnitine in low and high doses (50 and 500 mg/kg) was administered for five consecutive days to male Wistar rats. Hepatocytes were isolated and freshly exposed to appropriate concentration of T-2 toxin for 2 h followed by oxidative stress and cell death evaluations.
RESULTS: Glutathione depletion, ROS overproduction and mitochondrial membrane potential collapse were determined under T-2 toxin exposure. Pretreatment with L-carnitine particularly at high-dose reduced toxicity and prevented the hepatocytes from abnormal caspase-3 activity and apoptosis.
CONCLUSION: Low toxicity of L-carnitine and its mitochondrial protective effects promises an effective way to reduce or prevent the toxicity induced by certain environmental pollutants, including T-2 toxin.
PMID: 26888052 [PubMed - as supplied by publisher]
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Effects of artificial tears on rabbit ocular surface healing after exposure to benzalkonium chloride.
Effects of artificial tears on rabbit ocular surface healing after exposure to benzalkonium chloride.
Drug Chem Toxicol. 2016 Feb 18;:1-6
Authors: Zhang Y, Cao H, Lin T, Gong L
Abstract
The aim of the study was to observe the effect of different artificial tears on healing the drug-induced keratopathy. To this aim, 64 rabbits received topical administration of 0.01% benzalkonium chloride to establish models and were divided into four groups. The control group received ocular saline solution (Saline), while the others were treated with Refresh Plus® (RF), Hycosan® (H) and Systane® Ultra (SU). Surface abnormalities were examined daily using slit-lamp. Fluorescein staining, histopathological and transmission electron microscopic (TEM) examination were performed at day 0, 2 weeks, and 1 and 2 months. A significant difference was observed between RF and SU, but not between H and SU at 2 weeks. TEM examination revealed new microvilli close to the cavity surface, and the number of microvilli in SU was greater than in H at 2 weeks and 1 month. Based on the results, the effect in the SU group was the most significant. Eye drops with nontoxic preservative such as SU are an alternative to treat drug-induced keratopathy.
PMID: 26890221 [PubMed - as supplied by publisher]
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No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor.
No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor.
Drug Chem Toxicol. 2016 Feb 18;:1-4
Authors: Santa Maria PL, Kim S, Yang YP
Abstract
CONTEXT: Heparin-binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane (TM).
OBJECTIVE: Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation.
METHODS: A total of 12 mice had transtympanic injections of 5 μg/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10 μg/kg of HB-EGF. Intravenous blood samples were collected at 0-, 3-, 24-, 168-, 288- and 720-h post-injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum.
RESULTS: No mice in the transtympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls.
DISCUSSION: The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant.
CONCLUSIONS: HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.
PMID: 26887920 [PubMed - as supplied by publisher]
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Diagnosing oral squamous cell carcinoma: How much imaging do we really need? A review of the current literature
Publication date: Available online 18 February 2016
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Sebastian Blatt, Thomas Ziebart, Maximilian Krüger, Andreas Max Pabst
Complementary imaging techniques that round out the clinical examination are fundamentally important in the work-up of patients with oral squamous cell carcinoma (OSCC). Above all, exact determination of primary tumour extent, metastatic spread, and treatment response highly depend on accurate imaging methods. Despite a multitude of recently published reviews, there is still an ongoing debate regarding the best imaging method. In order to update the current literature with the latest evidence, a systematic literature search via Pubmed was performed. In total, 56 studies were enrolled, 4170 patients were analysed, and twenty different imaging methods were evaluated referring to their sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).In summary, CT (computed tomography) and MRI (magnetic resonance imaging) currently remain the gold standard for evaluating extension of the primary tumour site. No additional evidence could be obtained for functional imaging methods displaying metastatic spread in the cervical lymph nodes, but was found for distant metastases. Furthermore, functional imaging seems to be beneficial in evaluating treatment response. There is further evidence in the accuracy of the different imaging methods found in this update that could possibly be implemented into the revision of the current guidelines and obtain a clear and coherent approach in the clinical set-up.
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HyperLOPIT for the Mouse Stem Cell Proteome
When researchers want to know more about pluripotency and the push towards stem cell differentiation, they need to know more than just which genes are firing up. Christoforou et al. (2016) suggest that they also need to know what proteins are on the go, and furthermore, where they are spatially located within the cell.1 The researchers propose an upgrade of a technique Read the rest of this article
The post HyperLOPIT for the Mouse Stem Cell Proteome appeared first on Accelerating Science.
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Diffusion-weighted imaging outside the brain: Consensus statement from an ISMRM-sponsored workshop
The significant advances in magnetic resonance imaging (MRI) hardware and software, sequence design, and postprocessing methods have made diffusion-weighted imaging (DWI) an important part of body MRI protocols and have fueled extensive research on quantitative diffusion outside the brain, particularly in the oncologic setting. In this review, we summarize the most up-to-date information on DWI acquisition and clinical applications outside the brain, as discussed in an ISMRM-sponsored symposium held in April 2015. We first introduce recent advances in acquisition, processing, and quality control; then review scientific evidence in major organ systems; and finally describe future directions. J. Magn. Reson. Imaging 2016.
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Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge
Purpose
To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis.
Materials and Methods
Eleven volunteers (nine male and two female, mean age 33.5, range 27–41 years) and 10 patients (nine male and one female, mean age 68.9, range 56–87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free-breathing. Paired t-tests were performed to determine if the mean pre- and post-O2 differences were statistically significant.
Results
In patients with liver fibrosis (n = 8) the change in following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03–1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range –0.93–3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range –0.81–2.44 msec).
Conclusion
This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016.
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Diffusion-weighted quantitative MRI to diagnose benign conditions from malignancies of the anterior mediastinum: Improvement of diagnostic accuracy by comparing perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient
Purpose
To compare perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient (ADC) to diagnose benign conditions from malignancies of the anterior mediastinum.
Materials and Methods
Seventy-six subjects were divided into a "benign conditions" group (A, n = 44) and a "malignancies" group (B, n = 32), based on histological findings. diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at b of 0/150/800 sec/mm2. The ADCs were obtained on an ADC map by including (perfusion-sensitive = ADCb0-800) and excluding (perfusion-free = ADCb150-800) the b = 0 sec/mm2. The Mann–Whitney U-test was used to detect differences in ADCb0-800 compared with ADCb150-800 values between all cases, benign conditions, and malignancies. The same test was used to evaluate differences in ADCs between the two groups for each type of measurement (ADCb0-800 and ADCb150-800), and receiver-operating characteristic (ROC) curves were obtained to evaluate discrimination abilities with comparison of areas-under-ROC-curves (AUROC). Optimal cutpoints for discrimination between groups were determined by the Youden-Index with computation of accuracy.
Results
The median ADCb0-800 was significantly greater compared with ADCb150-800 for all cases (P = 0.0014), benign conditions (P = 0.0412), and malignancies (P = 0.0001). The median percentage of increase was 5.30% for group-A and 22.39% for group-B (P < 0.0001). AUROC of ADC in discriminating between groups was significantly greater for ADCb150-800 (0.932) compared with ADCb0-800 (0.831) (P = 0.001). The optimal cutpoint for distinction between groups was 1.52 × 10-3mm2/sec (sensitivity = 93.7%, specificity = 88.6%, accuracy = 90.8%) for ADCb150-800 and 1.75 × 10-3mm2/sec (sensitivity = 75.0%, specificity = 79.5%, accuracy = 77.6%) for ADCb0-800.
Conclusion
The use of perfusion-free ADC measurements significantly improves diagnostic accuracy of DW-MRI in differentiating benign conditions from malignancies of the anterior mediastinum. J. Magn. Reson. Imaging 2016.
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Mental fatigue impairs soccer-specific physical and technical performance
Purpose: To investigate the effects of mental fatigue on soccer-specific physical and technical performance. Methods: This investigation consisted of two separate studies. Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test, Level 1 (Yo-Yo IR1). Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests (LSPT, LSST). Each test was performed on two occasions and preceded, in a randomized, counterbalanced order, by 30 min of the Stroop task (mentally fatiguing treatment) or 30 min of reading magazines (control treatment). Subjective ratings of mental fatigue were measured before and after treatment, and mental effort and motivation were measured after treatment. Distance run, heart rate, and ratings of perceived exertion were recorded during the Yo-Yo IR1. LSPT performance time was calculated as original time plus penalty time. LSST performance was assessed using shot speed, shot accuracy, and shot sequence time. Results: Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies (P < 0.001), whereas motivation was similar between conditions. This mental fatigue significantly reduced running distance in the Yo-Yo IR1 (P < 0.001). No difference in heart rate existed between conditions, whereas ratings of perceived exertion were significantly higher at iso-time in the mental fatigue condition (P < 0.01). LSPT original time and performance time were not different between conditions; however, penalty time significantly increased in the mental fatigue condition (P = 0.015). Mental fatigue also impaired shot speed (P = 0.024) and accuracy (P < 0.01), whereas shot sequence time was similar between conditions. Conclusions: Mental fatigue impairs soccer-specific running, passing, and shooting performance.
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A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres
Purpose: To investigate and compare the quantitative accuracy of Y-90 imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of Y-90 solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter < 20 mm. For spheres > 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct Y-90 activity concentrations, but they underestimate activity concentrations in small structures (a parts per thousand currency sign37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer.
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Multilevel development models of explosive leg power in high-level soccer players
Purpose: The aim of the present study was to model developmental changes in explosive power based on the contribution of chronological age, anthropometrical characteristics, motor coordination parameters, and flexibility. Methods: Two different longitudinal, multilevel models were obtained to predict countermovement jump (CMJ) and standing broad jump (SBJ) performance in 356 high-level, youth soccer players, age 11-14 yr at baseline. Biological maturity status was estimated (age at peak height velocity [APHV]), and variation in the development of explosive power was examined based on three maturity groups (APHV; earliest < P33, P33 < average < P66, latest > P66). Results: The best-fitting model for the CMJ performance of the latest maturing players could be expressed as: 8.65 + 1.04 x age + 0.17 x age(2) + 0.15 x leg length + 0.12 x fat-free mass + 0.07 x sit-and-reach + 0.01 x moving sideways. The best models for average and earliest maturing players were the same as for the latest maturing players, minus 0.73 and 1.74 cm, respectively. The best-fitting model on the SBJ performance could be expressed as follows: 102.97 + 2.24 x age + 0.55 x leg length + 0.66 x fat-free mass + 0.16 x sit-and-reach + 0.13 jumping sideways. Maturity groups had a negligible effect on SBJ performance. Conclusions: These findings suggest that different jumping protocols (vertical vs long jump) highlight the need for special attention in the evaluation of jump performance. Both protocols emphasized growth, muscularity, flexibility, and motor coordination as longitudinal predictors. The use of the SBJ is recommended in youth soccer identification and selection programs because biological maturity status has no effect on its development through puberty.
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Cervical Cancer in Women Aged 35 Years and Younger
Publication date: Available online 18 February 2016
Source:Clinical Therapeutics
Author(s): Elizabeth Pelkofski, Jessica Stine, Nolan A. Wages, Paola A. Gehrig, Kenneth H. Kim, Leigh A. Cantrell
PurposeAge has been evaluated as a prognostic factor in cervical cancer in both hospital- and population-based studies. Results regarding the relation of age and cervical cancer prognosis are conflicting. This study pursued a contemporary assessment of the association of extreme young age at the time of a cervical cancer diagnosis on survival.MethodsInstitutional review board approval was obtained, and retrospective data collection at 2 academic institutions was performed. Inclusion criteria involved women ≤35 years diagnosed with cervical cancer between 1990 and 2012. Data included demographic and prognostic information pertinent to survival and progression. Characteristics of very young (≤25 years) and young (>25–35 years) women were compared. Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards modeling were used to assess the association of age, tumor histology, grade, stage, and parametrial involvement with progression-free survival (PFS) and overall survival (OS).FindingsIncident cases (n = 126) of cervical cancer in patients ≤35 years of age were identified of which complete clinical information was available for 114 women. Fifteen percent (17 of 114) were ≤25 years, with the remaining 85% (97 of 114) being 26 to 35 years of age. Race, smoking status, and marital status were comparable between the 2 groups. Squamous histology dominated overall (77 of 114; 68%) with adenocarcinoma contributing ~25% (30 of 114; 26%) of cases. The majority (96 of 114, 84%) had either stage 1A (31 of 114, 27%) or 1B (65 of 114, 57%) disease. A log-rank test revealed no evidence to infer a difference in either PFS or OS among the age groups (P = 0.511 and P = 0.340). In a univariate analysis, grade and stage significantly affected OS (P < 0.0001, P = 0.045), and stage significantly affected PFS (P < 0.0001). In multivariate modeling, presence of parametrial involvement and histologic cancer type significantly affected both PFS (P = 0.002, P = 0.001) and OS (P = 0.001, P = 0.001).ImplicationsTumor histology, parametrial involvement, and stage continue to be strong prognosticators for PFS and OS. Progression and survival outcomes are age independent in women with cervical cancer ≤35 years of age. Further study of a larger young cohort may potentially yield different outcomes.
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Examining Time to Initiation of Biologic Disease-Modifying Antirheumatic Drugs and Medication Adherence and Persistence Among Texas Medicaid Recipients With Rheumatoid Arthritis
Publication date: Available online 18 February 2016
Source:Clinical Therapeutics
Author(s): Gilwan Kim, Jamie C. Barner, Karen Rascati, Kristin Richards
PurposeLittle is known about the transition from nonbiologic disease-modifying antirheumatic drugs (DMARDs) to biologic DMARDs or about individual nonbiologic DMARD use patterns among patients with rheumatoid arthritis (RA). This study examined time to initiation of biologic DMARDs and nonbiologic DMARD medication adherence and persistence among Texas Medicaid recipients with RA taking nonbiologic DMARDs.MethodsIn this retrospective study (July 1, 2003–December 31, 2010) of the Texas Medicaid database, patients were aged 18 to 62 years at index, were diagnosed with RA (International Classification of Diseases, Ninth Revision, Clinical Modification, code 714.xx), had no claims for nonbiologic or biologic DMARDs in the preindex period, and had a minimum of 2 prescription claims for the same nonbiologic DMARD in the postindex period. Kaplan-Meier survival analysis and log-rank tests were used to compare time to initiation of biologic DMARDs according to nonbiologic DMARD type and therapy. Adherence and persistence were examined according to nonbiologic type and therapy by using ANOVA models and χ2, Duncan, and t tests.FindingsOn average, patients were 47.9 (±10.4) years of age, mostly female (89.1%) and Hispanic (55.2%). Methotrexate (MTX) and leflunomide (LEF) users took the shortest time to initiate biologic DMARDs (207 [190] days and 188 [205] days, respectively). LEF users had the highest mean adherence of 37.5% (27.5%), which was similar to MTX users (35.7% [26.9%]), whereas dual-therapy users had the lowest mean adherence at 17.1% (14.4%). Sulfasalazine users (108 [121] days) had the lowest persistence, whereas LEF (227 [231] days) and MTX (211 [222] days) users had the longest persistence. Nonbiologic DMARD monotherapy users were more adherent than dual-therapy users (32.6% [25.8%] vs 17.1% [14.4%]).ImplicationsThese results should be interpreted in light of some study limitations, such as using proportion of days covered as a proxy for adherence, not having clinical data to control for RA severity, and lack of generalizability to all US populations. Given the study findings, both clinicians and other decision makers may want to investigate the potential driving factors of initiation of biologic DMARDs to provide effective RA management and consider patient education programs to enhance medication adherence and persistence to RA medications.
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Translating Gastric Cancer Genomics into Targeted Therapies
Publication date: Available online 18 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Yvonne L.E. Ang, Wei Peng Yong, Patrick Tan
Gastric cancer is a common disease with limited treatment options and a poor prognosis. Many gastric cancers harbour potentially actionable targets, including over-expression and mutations in tyrosine kinase pathways. Agents have been developed against these targets with varying success- in particular, the use of trastuzumab in HER2-overexpressing gastric cancers has resulted in overall survival benefits. Gastric cancers also have high levels of somatic mutations, making them candidates for immunotherapy; early work in this field has been promising. Recent advances in whole genome and multi-platform sequencing have driven the development of molecular classification systems, which may in turn guide the selection of patients for targeted treatment. Moving forward, challenges will include the development of appropriate biomarkers to predict responses to targeted therapy, and the application of new molecular classifications into trial development and clinical practice.
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Chronic obstructive pulmonary disease and the risk of stroke: the Rotterdam study
Rationale: Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are leading causes of death. Increasing evidence suggests an association between both diseases, either caused by an increased atherosclerosis risk in patients with COPD, or as a consequence of shared risk factors between stroke and COPD. Objectives: To examine the associations between COPD and subtypes of stroke in the general population and to explore the role of cardiovascular risk factors and exacerbations on these associations. Methods: Within the prospective population-based Rotterdam Study, we followed 13115 participants without history of stroke for occurrence of stroke. Follow-up started in 1990-2008 and ended in 2012. COPD was related to stroke using a time-dependent Cox proportional hazard model. Measurements and Main Results: COPD was diagnosed in 1566 participants. During 126347 person-years, 1250 participants suffered a stroke, of which 701 were ischemic and 107 hemorrhagic. Adjusted for age, age2, and sex, COPD was significantly associated with all stroke (HR 1.20; 95%CI 1.00-1.43), ischemic stroke (HR 1.27; 1.02-1.59), and hemorrhagic stroke (HR 1.70; 1.01-2.84). Adjusting for cardiovascular risk factors gave similar effect sizes. In contrast, additional adjusting for smoking attenuated the effect sizes: HR 1.09 (0.91-1.31) for all stroke, HR 1.13 (0.91-1.42) for ischemic stroke, and HR 1.53 (0.91-2.59) for hemorrhagic stroke. Following an acute severe exacerbation subjects with COPD had a 6.66-fold (2.42-18.20) increased risk of stroke. Conclusion: Our cohort study demonstrated a higher risk of both ischemic and hemorrhagic stroke in subjects with COPD, and revealed the importance of smoking as a shared risk factor.
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Human rights in the age of economic globalization: the case of the Mogalakwena mine, South Africa
The mineral industry is one of the strongholds of South Africa's emerging economy. Nevertheless, the country is increasingly facing the adverse effects of unsustainable mining projects that insufficiently take into account the social and environmental impact of the quest for economic growth. One approach to analysing this problem takes the perspective of human rights law. Through the study of a particular case where local communities are opposing these adverse impacts of mining, this paper explores the responsibilities of the various actors involved, both state and non-state actors. Such an analysis demonstrates that holding South Africa to account for its human rights obligations is a necessary but insufficient step in establishing a comprehensive framework that ensures that powerful corporate actors respect human rights. The international human rights system can learn lessons from the South African experience, where the judiciary plays an important role in making rights real for the poor and vulnerable groups that are directly exposed to the adverse impacts of unsustainable development.
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Data-analytical stability in second-level fMRI inference
We investigate the impact of decisions in the second-level (i.e. over subjects) inferential process in functional Magnetic Resonance Imaging (fMRI) on 1) the balance between false positives and false negatives and on 2) the data-analytical stability (Qiu et al., 2006; Roels et al., 2015), both proxies for the reproducibility of results. Second-level analysis based on a mass univariate approach typically consists of 3 phases. First, one proceeds via a general linear model for a test image that consists of pooled information from different subjects (Beckmann et al., 2003). We evaluate models that take into account first-level (within-subjects) variability and models that do not take into account this variability. Second, one proceeds via permutation-based inference or via inference based on parametrical assumptions (Holmes et al., 1996). Third, we evaluate 3 commonly used procedures to address the multiple testing problem: family-wise error rate correction, false discovery rate correction and a two-step procedure with minimal cluster size (Lieberman and Cunningham, 2009; Bennett et al., 2009). Based on a simulation study and on real data we find that the two-step procedure with minimal cluster-size results in most stable results, followed by the family- wise error rate correction. The false discovery rate results in most variable results, both for permutation-based inference and parametrical inference. Modeling the subject-specific variability yields a better balance between false positives and false negatives when using parametric inference.
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Variants in the KCNE1 or KCNE3 gene and risk of Ménière's disease: A meta-analysis.
Variants in the KCNE1 or KCNE3 gene and risk of Ménière's disease: A meta-analysis.
J Vestib Res. 2016 Jan 28;25(5-6):211-218
Authors: Li YJ, Jin ZG, Xu XR
Abstract
BACKGROUND: Ménière's disease (MD) is defined as an idiopathic disorder of the inner ear characterized by the triad of tinnitus, vertigo, and sensorineural hearing loss. Although many studies have evaluated the association between variants in the KCNE1 or KCNE3 gene and MD risk, debates still exist.
OBJECTIVE: Our aim is to evaluate the association between KCNE gene variants, including KCNE1 rs1805127 and KCNE3 rs2270676, and the risk of MD by a systematic review.
METHODS: We searched the literature in PubMed, SCOPUS and EMBASE through May 2015. We calculated pooled odds ratios (OR) and 95% confidence intervals (CIs) using a fixed-effects model or a random-effects model for the risk to MD associated with different KCNE gene variants. The heterogeneity assumption decided the effect model.
RESULTS: A total of three relevant studies, with 302 MD cases and 515 controls, were included in this meta-analysis. The results indicated that neither the KCNE1 rs1805127 variant (for G vs. A: OR = 0.724, 95%CI 0.320, 1.638, P= 0.438), nor the KCNE3 rs2270676 variant (for T vs. C: OR = 0.714, 95%CI 0.327, 1.559, P = 0.398) was associated with MD risk.
CONCLUSIONS: Based on current evidence from published studies, neither of the two variants from KCNE was significantly associated with the risk of MD. Larger studies with mixed ethnicity subjects and stratified by clinical and sub-clinical characteristics are needed to validate our findings.
PMID: 26890422 [PubMed - as supplied by publisher]
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Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus.
Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus.
Restor Neurol Neurosci. 2016 Jan 30;
Authors: Schecklmann M, Giani A, Tupak S, Langguth B, Raab V, Polak T, Várallyay C, Harnisch W, Herrmann MJ, Fallgatter AJ
Abstract
PURPOSE: Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS).
METHODS: Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response.
RESULTS: Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group.
CONCLUSIONS: In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials.
PMID: 26890094 [PubMed - as supplied by publisher]
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[Middle ear adenoma: clinical and pathologic analysis].
[Middle ear adenoma: clinical and pathologic analysis].
Zhonghua Bing Li Xue Za Zhi. 2015 Dec;44(12):900-4
Authors: Bai Y, Yue C, Yang D, Han Y, Zhang Y, Liu H
Abstract
OBJECTIVE: To investigate the clinical and pathologic features of middle ear adenoma (MEA).
METHODS: Eight cases of MEA were collected from Beijing Tongren Hospital, Capital Medical University between 2004 and 2014, and immunohistochemical staining was performed.
RESULTS: The patients included five women and three men (mean age, 37.5 years; median 37 years; range, 21-51 years). All patients had unilateral lesions. Five MEA occurred on the left side, and three on the right. In seven patients the MEA was primary, and they presented with hearing loss (6 cases), tinnitus (5 cases), sense of ear blockage (3 cases), otalgia (1 case) and facial nerve paralysis (1 case). The remaining patient had recurrent MEA, and presented with otorrhea, aural fullness and tinnitus. Histologically, the tumor cells were arranged in a variety of patterns, including solid sheets, nests, glands, ribbons or trabeculae. Glandular structures were prominent in one case only. Immunohistochemically, the tumor cells were diffusely positive for keratin (8/8) and vimentin (8/8), and focally positive for CK 7(8/8) and CK5/6(8/8). CK7 and CK5/6 were predominantly positive in tumor cells with glandular growth pattern; CK7 was positive in the luminal cells while CK5/6 was positive in the abluminal cells. Both were also expressed focally in scattered tumor cells with non-glandular pattern. The tumor cells were also diffusely positive for synaptophysin(8/8), diffusely but weakly positive for NSE (5/8), and were diffusely or focally positive for chromogranin A (4/8). Both S-100 protein and calponin were negative in all cases. The proliferation rate was low, about 1%-2%. Six cases were followed up for one year and three months to ten years and six months, with an average follow-up period of four years and two months. Two patients developed recurrence, but there were no regional or distant metastases.
CONCLUSIONS: Diagnosis of MEA requires pathologic confirmation since the clinical symptoms are non-specific. MEA can show a variety of histologic patterns, and should be distinguished from other space-occupying lesions at this site. Immunohistochemical staining has greatly contributed to the diagnosis and differential diagnosis of MEA. The prognosis of this tumor is good. Patients with MEA require long-term follow-up for recurrences.
PMID: 26888509 [PubMed - in process]
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[Clinical features of sudden sensorineural hearing loss accompanied with inner ear hemorrhage].
[Clinical features of sudden sensorineural hearing loss accompanied with inner ear hemorrhage].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015 Dec;50(12):996-1000
Authors: Chen X, Lin C, Fang Z, Chen X, Ye S, Cheng J, Zhang R
Abstract
OBJECTIVE: To investigate the clinical features, diagnosis and prognosis of sudden sensorineural hearing loss accompanied with inner ear hemorrhage.
METHODS: Eleven cases of sudden sensorineural hearing loss accompanied with inner ear hemorrhage were retrospectively analyzed, including clinical manifestation, hematological and audiological examinations, as well as characteristics of inner ear three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI).
RESULTS: Eleven cases of sudden hearing loss with inner ear hemorrhage were accompanied by varying degrees of vertigo, lasting from several minutes to several hours, nine of whom had persistent tinnitus. The audiometry curves of the 11 cases included total deafness or flat descending type. The inner ear 3D-FLAIR MRI studies revealed abnormal high signals at different positions of the inner ear, one case with endolymphatic hydrops. After the treatment, seven cases were invalid, two cases had notable effect, and two cases were effective.
CONCLUSIONS: Abnormal high signals in the inner ear were sensitively detected by 3D-FLAIR MRI sequence, which was applied for the diagnosis of the sudden hearing loss accompanied with inner ear hemorrhage. The effect of conventional treatment was not good and the appropriate treatments for this type of sudden hearing loss need further investigation.
PMID: 26888129 [PubMed - in process]
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[Cinical and genetic characteristics of familial Meniere's disease: three families report].
[Cinical and genetic characteristics of familial Meniere's disease: three families report].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015 Nov;50(11):915-24
Authors: Gao Y, Wang D, Wang H, Guan J, Lan L, Wu Z, Xie L, Yu L, Zhang S, Shan X, Wang Q
Abstract
OBJECTIVE: To investigate the clinical and genetic characteristics of three Chinese Meniere's disease(MD) families and decipher the mechanism of MD further.
METHODS: Personal and family medical evidence of hearing loss, vestibular symptoms, and other clinical abnormalities of the participants were identified, clinical and genetic features were analyzed. Targeted 307 genes capture and high-throughput sequencing were performed on the two ascertained members of family 1007184.
RESULTS: Eight patients from these three families showed post-lingual sensorineural hearing loss, six women and two men were involved. Age of onset in these affected members concentrated in the middle age, with the average age of 39.3 years old. Among them, patients from 1407278 were accompanied by migraine. All of the three probands presented as recurrent vertigo firstly, and then fluctuated hearing loss showed up, accompanying by tinnitus and ear fullness feeling. The hearing loss manifested as late-onset, low frequency-involved pattern, with subsequent gradual progression from moderate to severe level. Some of the patients progressed to severe level involving all frequencies at higher ages. In addition, most of the cases showed revitalization. Four cases received vestibular function tests, three of which had varying dysfunction of vestibular function, while the other one had normal vestibular function. Patients who had abnormal vestibular function showed much more severe hearing impairment. The three-generation family 1007193 had an autosomal recessive genetic characteristics, family 1007184 showed autosomal dominant inheritance of characteristics, family 1407278 were either autosomal dominant or X-linked dominant pattern. Through target genes capture high-throughput sequencing technology, we identified two candidate variants in the two members of family 1007184, named c. 2057G>A in EGFLAM and c. 1961C>T in ITGA8.
CONCLUSION: Meniere's disease has some genetic and familial aggregation in Chinese population, but its complex genetic pathogenic mechanisms need further study.
PMID: 26887996 [PubMed - in process]
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