Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway.

PURPOSE: Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence. We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway EXPERIMENTAL DESIGN: Western blots and/or immunohistochemistry were performed to determine whether phosphorylation of mTOR and activation of its downstream molecules eIF4E-binding protein-1 (4E-BP1) and p70 S6 kinase and the upstream modulator of mTOR, Akt, were expressed in margins overexpressing eIF4E. RESULTS: There was a significant association between phospho-4E-BP1 and eIF4E expression of a margin or a significant difference in phospho-4E-BP1 expression between the eIF4E-positive and -negative margins (P < 0.01). A significant association between eIF4E and phospho-p70 S6 kinase as well as eIF4E and phospho-mTOR was also noted (P < 0.05). Western blot analysis indicated a highly significant difference in the phosphorylation status of 4E-BP1 between tumors and resection margins. A total of 89% of the 4E-BP1-expressing margins expressed more of the phosphorylated (beta, gamma, and delta) isoforms, whereas 81% of the 4E-BP1-expressing tumors expressed more of the unphosphorylated alpha isoform. A similar difference in Akt activation was noted between eIF4E-positive margins and tumors (P < 0.05). CONCLUSIONS: Overexpression of eIF4E is functionally active in tumor margins through activation of the Akt/mTOR signaling pathway. The greater degree of expression of downstream targets and upstream regulators of mTOR in margins compared with the tumors indicates preferential activation of the Akt/mTOR signaling pathway in margins overexpressing eIF4E. Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins.     

Development of eight microsatellite loci from the Green and Golden Bell Frog (Litoria aurea) through GS-FLX pyrosequencing and cross-amplification with other species of the Litoria aurea species group

A next generation sequencing approach was used to develop eight new microsatellite loci for the endangered Green and Golden Bell Frog (GGBF) Litoria aurea. Microsatellite loci were developed from six individuals and tested on another 20. Genetic variation and heterozygosity was high in most loci (mean number of alleles per locus?=?7.785; mean heterozygosity?=?0.785375). Samples from six other closely related species L. cyclorhyncha, L. dahlii (Queensland), L. dahlii (Northern Territory), L. moorei, L. raniformis, Cyclorana australis and C. maini were also genotyped. While these markers will be useful for studies involving L. aurea their use in other closely related species will be limited.     

Poverty status of worker compensation claimants with permanent impairments

Poverty levels have proven to be pernicious in Canada, with particular groups at heightened risk of poverty. Given that people with disabilities are consistently identified as among those ‘at risk’, we seek to determine the extent to which injured workers/worker compensation claimants who had sustained bodily impairments live in poverty. Employing two poverty indicators, we describe the poverty levels of Ontario injured workers with permanent impairments at an average of 52 months post-injury. For one indicator, we describe proximity to/depth of poverty; and in bivariate and multivariate analyses, we examine the factors associated with poverty in the post-injury period. Estimated poverty rates for the injured worker sample – ranging from 17 to 26% – compare unfavourably to published estimates of poverty in the general population of working-aged Canadians/Ontarians and equate to those of Canadians/Ontarians with disabilities. Pre-injury employment characteristics and income status only partly account for post-injury poverty, pre-injury health does not. Sample members in post-injury poverty were more likely to report having sustained multiple injuries at the workplace, were less likely to have returned to employment or to have recovered pre-injury earnings, and yet contributed significantly more to post-injury household incomes than those not in post-injury poverty. We discuss the implications of the findings for worker compensation boards that adjudicate and have final authority on worker claims for compensation for harms sustained in the workplace.     

The Impact of Economic Pressure on Parent Positivity,Parenting, and Adolescent Positivity into Emerging Adulthood

This study describes how positivity can be incorporated into the family stress model to explain resilience to disrupted family processes in the face of economic distress. Prospective, longitudinal data came from 451 mothers, fathers, and youth participating from their adolescence through early adulthood. Assessments included observational and self‐report measures. Information regarding economic pressure, parental positivity, and parenting were collected during early adolescence, positivity was collected in late adolescence and emerging adulthood. Results indicated that economic pressure was indirectly associated with adolescent positivity through parental positivity. Economic pressure was negatively associated with parent positivity, whereas parental positivity was positively associated with parenting. Moreover, parental positivity and parenting were related to positivity in adolescence. Results suggest that personal resources linked to a positive outlook can foster nurturant parenting, even in times of economic strain. Such parenting seems to positively influence adolescent development into emerging adulthood.     

Argatroban for therapeutic anticoagulation for heparin resistance associated with Covid-19 infection

Journal of Thrombosis and Thrombolysis -     

Biomarkers of Cardiac Stress and Injury in Athletes: What Do They Mean?

Purpose of the Review

Markers of myocardial stress, including troponin, creatine kinase, and brain natriuretic peptide are frequently elevated after endurance athletic pursuits. Here, we summarize the current literature pertaining to the potential mechanism of cardiac enzyme release in athletes and seek to determine the clinical implications of these findings.

Recent Findings

Recent studies have highlighted the potential adverse cardiac effects of long-term extreme endurance exercise. While troponin release occurs in a pattern distinct from ischemic damage, BNP release has been correlated with right ventricular dysfunction and is likely related to wall stress from prolonged increases in cardiac output. Higher intensity pre-race training regimes are associated with lower race-day enzyme release.

Summary

While the holistic benefits of regular moderate exercise are indisputable, recent studies have raised concerns about the potential risks of extreme endurance exercise. Release of serum biomarkers suggesting myocardial damage was first described in the 1970s, yet our understanding of the implications of these findings remains incomplete. The mechanisms of release are complex but appear to be primarily physiological phenomena rather than pathologic.

     

Autonomic function in elderly patients with chronic heart failure

AIMS: Autonomic function (AF) is attenuated by heart failure (HF). Reports have been based on studies of young patients with systolic heart failure (SHF). However, HF is a disease of older patients who are more likely to have diastolic heart failure (DHF). We investigated whether age alters AF in elderly HF patients and whether the haemodynamic type of HF influences AF. METHOD AND RESULTS: Thirty-six elderly HF (Framingham criteria) patients (11 with SHF, 25 with DHF) and 21 matched healthy subjects underwent simple bedside AF tests. Compared with the reference values for healthy adults, the mean E:I ratios and the median 30:15 ratios standing were all essentially normal. The median 30:15 ratios tilt and the mean Valsalva ratios were all significantly below the reference value (P for all cases <0.050). Comparing three groups, there were no significant differences for mean E:I ratio (P=0.111), 30:15 tilt (P=0.619) and 30:15 standing (P=0.167), whereas there were significant differences for the mean Valsalva ratios (P=0.001). The mean Valsalva ratio of the SHF patients was significantly lower than that for the DHF patients (P<0.001) which in turn was significantly lower than the result of the healthy subjects (P<0.001). CONCLUSION: There is an age-related impairment in AF with further impairment occurring in patients with HF. However, the severity of autonomic dysfunction is less in patients with DHF compared with patients with SHF.