Heart rate and lactate responses to taekwondo fight in elite women performers

The purpose of this study was to examine heart rate (HR) and blood lactate (LA) concentration before, during and after a competitive Tae kwon do (TKD) fight performed by elite women performers. Specifically, we were interested to see weather HR and LA responses to competitive fight were greater than to TKD or karate exercises published in scientific literature. Seven international-standard women TKD fighters participated in the study. HR was recorded continuously throughout the fight using Polar Vantage telemetric HR monitors. LA samples were taken before and 3 min after the fight and analysed using an Accusport portable lactate analyzer. At the beginning of the fight, HR significantly increased (p<0.01) from pre-fight values of 91.6±9.9 beats min-1 to 144.1±13.6 beats min-1. During the whole fight the HRmean was 186.6±2.5 beats min-1 and remained significantly elevated (p<0.01) at 3 min into recovery. HR values expressed as a percentage of HRmax averaged during the whole fight at 91.7±2.6% respectively. LA concentration significantly increased (p<0.01) 3 min after the fight and averaged 82% of LApeak values measured after the VO2max test. Results of the present study indicate that physiological demands of competitive TKD fight in women, measured by HR and LA responses, are considerably higher than the physiological demands of TKD or karate training exercises. The observed HR and LA responses suggest to us that conditioning for TKD should generally emphasise high-intensity anaerobic exercise

Growth and reproduction of <i>Xyrichthys novacula</i> (Pisces: Labridae) in the Mediterranean Sea

No disponibl

Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G&gt;C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n&nbsp;=&nbsp;2) or severe (n&nbsp;=&nbsp;1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p&nbsp;=&nbsp;0.016) and HbA1c (p&nbsp;=&nbsp;0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Determination of n-3 index and arachidonic acid/eicosapentaenoic acid ratio in dried blood spot by gas chromatography

Background: Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). Experimental: After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. Conclusion: This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability

Long QT syndrome and torsade de pointes after anthracycline chemotherapy

Anthracycline chemotherapy, which represents the treatment of choice for many hematologic and metastatic cancers, unfortunately carries with it the possibility of both early cardiotoxic phenomena, occuring during chemotherapy, and also late cardiotoxic manifestations, occuring even months or years from the completion of treatment

A computer simulation protocol to assess the accuracy of a Radio Stereometric Analysis (RSA) image processor according to the ISO-5725

Radio-Stereometric-Analysis and x-ray fluoroscopy are radiological techniques that require dedicated software to process data. The accurate calibration of these software is therefore critical. The aim of this work is to produce a protocol for evaluating the softwares' accuracy according to the ISO-5725. A series of computer simulations of the radiological setup and images were employed. The noise level of the images was also changed to evaluate the accuracy with different image qualities. The protocol was tested on a custom software developed by the authors. Radiological scene reconstruction accuracy was of (0.092 +- 0.14) mm for tube position, and (0.38 +- 0.31) mm / (2.09 +- 1.39) deg for detectors oriented in a direction other than the source-detector direction. In the source-detector direction the accuracy was of (2.68 +- 3.08) mm for tube position, and of (0.16 +- 0.27) mm / (0.075 +- 1.16) deg for the detectors. These disparate results are widely discussed in the literature. Model positioning and orientation was also highly accurate: (0.22 +- 0.46) mm / (0.26 +- 0.22) deg. Accuracy was not affected by the noise level. The protocol was able to assess the accuracy of the RSA system. It was also useful to detect and fix hidden bugs. It was also useful to detect and resolve hidden bugs in the software, and in optimizing the algorithms

QTc prolongation assessment in anticancer drug development: clinical and methodological issues

Cardiac safety assessments are commonly employed in the clinical development of investigational oncology medications. In anti-cancer drug development there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can potentially influence decision making at many levels during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Given the potential for serious and irreversible morbidity from cardiac adverse events, it is understandable that cardiac safety results can have broad impact on study conduct and patient management. The methodologies for risk management of QTc prolongation for non cardiac drugs have been developed out of experiences primarily from drugs used to treat non life-threatening illnesses in a chronic setting such as antibiotics or antihistamines. Extrapolating these approaches to drugs for treating cancer over an acute period may not be appropriate. Few specific guidelines are available for risk management of cardiac safety in the development and use of oncology drugs. In this manuscript, clinical and methodological issues related to QTc prolongation assessment will be reviewed. Discussions about limitations in phase-I design and oncology drug development will be highlighted. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. A thoughtful risk management plan generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development programme essential for oncology agents with cardiac safety concerns

The Magnetic Distortion Calibration System of the LHCb RICH1 Detector

The LHCb RICH1 detector uses hybrid photon detectors (HPDs) as its optical sensors. A calibration system has been constructed to provide corrections for distortions that are primarily due to external magnetic fields. We describe here the system design, construction, operation and performance.Comment: 9 pages, 14 figure

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients