Metabolic sensitivity of pancreatic tumour cell apoptosis to glycogen phosphorylase inhibitor treatment

Inhibitors of glycogen breakdown regulate glucose homeostasis by limiting glucose production in diabetes. Here we demonstrate that restrained glycogen breakdown also inhibits cancer cell proliferation and induces apoptosis through limiting glucose oxidation, as well as nucleic acid and de novo fatty acid synthesis. Increasing doses (50-100 microM) of the glycogen phosphorylase inhibitor CP-320626 inhibited [1,2-(13)C(2)]glucose stable isotope substrate re-distribution among glycolysis, pentose and de novo fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Limited oxidative pentose-phosphate synthesis, glucose contribution to acetyl CoA and de novo fatty acid synthesis closely correlated with decreased cell proliferation. The stable isotope-based dynamic metabolic profile of MIA cells indicated a significant dose-dependent decrease in macromolecule synthesis, which was detected at lower drug doses and before the appearance of apoptosis markers. Normal fibroblasts (CRL-1501) did not show morphological or metabolic signs of apoptosis likely due to their slow rate of growth and metabolic activity. This indicates that limiting carbon re-cycling and rapid substrate mobilisation from glycogen may be an effective and selective target site for new drug development in rapidly dividing cancer cells. In conclusion, pancreatic cancer cell growth arrest and death are closely associated with a characteristic decrease in glycogen breakdown and glucose carbon re-distribution towards RNA/DNA and fatty acids during CP-320626 treatment

Testing for hybridisation of the Critically Endangered Iguana delicatissima on Anguilla to inform conservation efforts

The Caribbean Island of Anguilla in the north-eastern Lesser Antilles is home to one of the last populations of the Critically Endangered Lesser Antillean iguana Iguana delicatissima. This population is highly threatened primarily because of hybridisation with non-native Iguana iguana. This study assesses the degree of hybridisation between Anguilla’s Iguana species firstly using morphological characteristics and then genetic analysis to validate the genetic integrity of morphologically identified I. delicatissima. We also examined the genetic diversity of Anguilla’s I. delicatissima population, and that of a population on the nearby island of Îlet Fourchue, St Barthélemy. Forty-five iguanas were captured in Anguilla and 10 in St Barthélemy, and sequences from 3 nuclear and 1 mtDNA genes were obtained for each. Of the 45 iguanas captured in Anguilla, 22 were morphologically identified as I. delicatissima, 12 as I. iguana and the remainder were identified as hybrids. Morphological assignments were all confirmed by genetic analyses except for one I. iguana and one hybrid individual. These two individuals appeared likely to have originated following ancestral hybridisation events several generations ago. A significant paucity of genetic diversity was found within Anguillan and St Barthélemy I. delicatissima populations, with a single haplotype being identified for each of the three nuclear genes and the mtDNA sequence. This study highlights the urgency for immediate action to conserve Anguilla’s remnant I. delicatissima population. Protection from hybridisation will require translocation to I. iguana-free offshore cays, with supplementary individuals being sourced from neighbouring islands to enhance the genetic diversity of the population

Genetic testing in professional football: perspectives of key stakeholders

Purpose: Genetic research in football is currently in it’s infancy but is growing rapidly. However, the practical application of genetic testing in football and the views concerning its use are unknown. Thus, the purpose of this study was to assess the current practical application of genetic testing in professional football and provide an insight into the perspectives of key stakeholders (i.e., coaches, practitioners, players). Methods: In total, 122 participants completed an online anonymous survey. This consisted of 21 multiple choice and Likert scale questions, with the option of providing an explanation for each response. Results: Findings revealed genetic testing is rarely utilised by key stakeholders (10%) or their respective organisations (14%). However, three quarters (75%) had the opinion that genetic testing will have great utility in the future. The majority (72%) believed genetic testing should be used for athlete development and injury risk, whilst 35% believed that genetic testing should be utilised for talent identification purposes. However, most key stakeholders viewed their own (89%) and their colleagues’ (79%) knowledge related to genetic testing as insufficient; mainly due to ineffective current communication methods (91%). Most believed educational workshops are required (71%), whilst nearly all (91%) were interested in developing their expertise on the utility of genetic testing. Conclusion: Genetic testing is rarely used within professional football, although key stakeholders anticipate that it will be utilised more in the future. As such, educational support may prove valuable in improving key stakeholder knowledge and the practical application of genetic testing in professional football

Genetic variations between youth and professional development phase english academy football players

The purpose of this study was to examine differences in the genotype frequency distribution of thirty-three single nucleotide variants (SNVs) between youth development phase (YDP) and professional development phase (PDP) academy football players. One hundred and sixty-six male football players from two Category 1 and Category 3 English academies were examined within their specific age phase: YDP (n = 92; aged 13.84 ± 1.63 years) and PDP (n = 74; aged 18.09 ± 1.51 years). Fisher’s exact tests were used to compare individual genotype frequencies, whereas unweighted and weighted total genotype scores (TGS; TWGS) were computed to assess differences in polygenic profiles. In isolation, the IL6 (rs1800795) G allele was overrepresented in PDP players (90.5%) compared to YDP players (77.2%; p = 0.023), whereby PDP players had nearly three times the odds of possessing a G allele (OR = 2.83, 95% CI: 1.13–7.09). The TGS (p = 0.001) and TWGS (p < 0.001) were significant, but poor, in distinguishing YDP and PDP players (AUC = 0.643–0.694), with PDP players exhibiting an overall more power-orientated polygenic profile. If validated in larger independent youth football cohorts, these findings may have important implications for future studies examining genetic associations in youth football

Consumer use of “Dr Google”: a survey on health information-seeking behaviors and navigational needs

BACKGROUND: The Internet provides a platform to access health information and support self-management by consumers with chronic health conditions. Despite recognized barriers to accessing Web-based health information, there is a lack of research quantitatively exploring whether consumers report difficulty finding desired health information on the Internet and whether these consumers would like assistance (ie, navigational needs). Understanding navigational needs can provide a basis for interventions guiding consumers to quality Web-based health resources. OBJECTIVE: We aimed to (1) estimate the proportion of consumers with navigational needs among seekers of Web-based health information with chronic health conditions, (2) describe Web-based health information-seeking behaviors, level of patient activation, and level of eHealth literacy among consumers with navigational needs, and (3) explore variables predicting navigational needs. METHODS: A questionnaire was developed based on findings from a qualitative study on Web-based health information-seeking behaviors and navigational needs. This questionnaire also incorporated the eHealth Literacy Scale (eHEALS; a measure of self-perceived eHealth literacy) and PAM-13 (a measure of patient activation). The target population was consumers of Web-based health information with chronic health conditions. We surveyed a sample of 400 Australian adults, with recruitment coordinated by Qualtrics. This sample size was required to estimate the proportion of consumers identified with navigational needs with a precision of 4.9% either side of the true population value, with 95% confidence. A subsample was invited to retake the survey after 2 weeks to assess the test-retest reliability of the eHEALS and PAM-13.RESULTS: Of 514 individuals who met our eligibility criteria, 400 (77.8%) completed the questionnaire and 43 participants completed the retest. Approximately half (51.3%; 95% CI 46.4-56.2) of the population was identified with navigational needs. Participants with navigational needs appeared to look for more types of health information on the Internet and from a greater variety of information sources compared to participants without navigational needs. However, participants with navigational needs were significantly less likely to have high levels of eHealth literacy (adjusted odds ratio=0.83, 95% CI 0.78-0.89, P<.001). Age was also a significant predictor (P=.02). CONCLUSIONS: Approximately half of the population of consumers of Web-based health information with chronic health conditions would benefit from support in finding health information on the Internet. Despite the popularity of the Internet as a source of health information, further work is recommended to maximize its potential as a tool to assist self-management in consumers with chronic health conditions

Plasmonically Enhanced Reflectance of Heat Radiation from Low-Bandgap Semiconductor Microinclusions

Increased reflectance from the inclusion of highly scattering particles at low volume fractions in an insulating dielectric offers a promising way to reduce radiative thermal losses at high temperatures. Here, we investigate plasmonic resonance driven enhanced scattering from microinclusions of low-bandgap semiconductors (InP, Si, Ge, PbS, InAs and Te) in an insulating composite to tailor its infrared reflectance for minimizing thermal losses from radiative transfer. To this end, we compute the spectral properties of the microcomposites using Monte Carlo modeling and compare them with results from Fresnel equations. The role of particle size-dependent Mie scattering and absorption efficiencies, and, scattering anisotropy are studied to identify the optimal microinclusion size and material parameters for maximizing the reflectance of the thermal radiation. For composites with Si and Ge microinclusions we obtain reflectance efficiencies of 57 - 65% for the incident blackbody radiation from sources at temperatures in the range 400 - 1600 {\deg}C. Furthermore, we observe a broadbanding of the reflectance spectra from the plasmonic resonances due to charge carriers generated from defect states within the semiconductor bandgap. Our results thus open up the possibility of developing efficient high-temperature thermal insulators through use of the low-bandgap semiconductor microinclusions in insulating dielectrics.Comment: Main article (8 Figures and 2 Tables) + Supporting Information (8 Figures

Mesenteric gastrointestinal stromal tumour presenting as intracranial space occupying lesion

BACKGROUND: Gastrointestinal stromal tumours (GIST) usually present with non-specific gastrointestinal symptoms such as abdominal mass, pain, anorexia and bowel obstruction. METHODS: We report a case of a 42 year old male who presented with a solitary intracranial space occupying lesion which was established as a metastasis from a mesenteric tumour. RESULTS: The patient was initially treated as a metastatic sarcoma, but a lack of response to chemotherapy prompted testing for CD117 which returned positive. A diagnosis of mesenteric GIST presenting as solitary brain metastasis was made, and the patient was treated with imatinib. CONCLUSION: We recommend that all sarcomas with either an intraabdominal or unknown origin be routinely tested for CD117 to rule out GIST

Reliability of videotaped observational gait analysis in patients with orthopedic impairments

BACKGROUND: In clinical practice, visual gait observation is often used to determine gait disorders and to evaluate treatment. Several reliability studies on observational gait analysis have been described in the literature and generally showed moderate reliability. However, patients with orthopedic disorders have received little attention. The objective of this study is to determine the reliability levels of visual observation of gait in patients with orthopedic disorders. METHODS: The gait of thirty patients referred to a physical therapist for gait treatment was videotaped. Ten raters, 4 experienced, 4 inexperienced and 2 experts, individually evaluated these videotaped gait patterns of the patients twice, by using a structured gait analysis form. Reliability levels were established by calculating the Intraclass Correlation Coefficient (ICC), using a two-way random design and based on absolute agreement. RESULTS: The inter-rater reliability among experienced raters (ICC = 0.42; 95%CI: 0.38–0.46) was comparable to that of the inexperienced raters (ICC = 0.40; 95%CI: 0.36–0.44). The expert raters reached a higher inter-rater reliability level (ICC = 0.54; 95%CI: 0.48–0.60). The average intra-rater reliability of the experienced raters was 0.63 (ICCs ranging from 0.57 to 0.70). The inexperienced raters reached an average intra-rater reliability of 0.57 (ICCs ranging from 0.52 to 0.62). The two expert raters attained ICC values of 0.70 and 0.74 respectively. CONCLUSION: Structured visual gait observation by use of a gait analysis form as described in this study was found to be moderately reliable. Clinical experience appears to increase the reliability of visual gait analysis