Stress Generation, Avoidance Coping, and Depressive Symptoms: A 10-Year Model.

This study examined (a) the role of avoidance coping in prospectively generating both chronic and acute life stressors and (b) the stress-generating role of avoidance coping as a prospective link to future depressive symptoms. Participants were 1,211 late-middle-aged individuals (500 women and 711 men) assessed 3 times over a 10-year period. As predicted, baseline avoidance coping was prospectively associated with both more chronic and more acute life stressors 4 years later. Furthermore, as predicted, these intervening life stressors linked baseline avoidance coping and depressive symptoms 10 years later, controlling for the influence of initial depressive symptoms. These findings broaden knowledge about the stress-generation process and elucidate a key mechanism through which avoidance coping is linked to depressive symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Small bowel perforation secondary to metastatic lung carcinoma

Since 1961, there have been a total of seven patients with small bowel perforation caused by metastatic lung carcinoma reported in the literature. Perforation of the small bowel to metastatic lung carcinoma must be considered when evaluating older patients who have histories of heavy cigarette smoking and signs and symptoms suggestive of pulmonary neoplasia. Primary resection and end-to-end anastomosis of the perforated bowel is the treatment of choice. No patient with small bowel perforation secondary to lung carcinoma has survived more than four months.     

Multivariate study of the patient-therapist system: A replication and extension.

Replicates and extends the work of R. H. Moos and S. R. Clemes (see record 1967-07395-001) and F. van der Veen (see record 1965-08090-001). Each of 6 patients saw each of 4 therapists twice. The variables total activity, feeling words, action words, reinforcements each was scored separately for patient and therapist for each interview. Patient problem expression and therapist accurate empathy were rated for each interview. Consistent differences between patients accounted for substantially more variance than consistent differences between therapists on all variables. Patient * Therapist * Session interactions generally accounted for large proportions of the total variance. Results indicate that the therapist behaviors studied were not the result of a trait, of a given tendency to be empathic, or of a consistently applied therapeutic technique, but rather were very substantially situationally or patient determined. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

SK119, a Novel Shikonin Derivative,Leads to Apoptosis in Melanoma Cell Lines and Exhibits Synergistic Effects with Vemurafenib and Cobimetinib

Melanoma is a complex and heterogenous disease, displays the deadliest form of skin cancer, and accounts for approx. 80% of all skin cancer deaths. In this study, we reported on the synthesis and pharmacological effects of a novel shikonin derivative (SK119), which is active in a nano-molar range and exhibits several promising in vitro effects in different human melanoma cells. SK119 was synthesized from shikonin as part of our search for novel, promising shikonin derivatives. It was screened against a panel of melanoma and non-tumorigenic cell lines using XTT viability assays. Moreover, we studied its pharmacological effects using apoptosis and Western blot experiments. Finally, it was combined with current clinically used melanoma therapeutics. SK119 exhibited IC₅₀ values in a nano-molar range, induced apoptosis and led to a dose-dependent increase in the expression and protein phosphorylation of HSP27 and HSP90 in WM9 and MUG-Mel 2 cells. Combinatorial treatment, which is highly recommended in melanoma, revealed the synergistic effects of SK119 with vemurafenib and cobimetinib. SK119 treatment changed the expression levels of apoptosis genes and death receptor expression and exhibited synergistic effects with vemurafenib and cobimetinib in human melanoma cells. Further research indicates a promising potential in melanoma therapy.     

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.     

Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells

Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence.     

Balanced Scheduling toward Loss-Free Packet Queuing and Delay Fairness

In current networks, packet losses can occur if routers do not provide sufficiently large buffers. This paper studies how many buffers should be provided in a router to eliminate packet losses. We assume a network router has m incoming queues, each corresponding to a single traffic stream, and must schedule at any time on-line from which queue to take the next packet to send out. To exclude packet losses with a small amount of buffers, the maximum queue length must be kept low over the entire scheduling period. We call this new on-line problem the balanced scheduling problem (BSP). By competitive analysis, we measure the power of on-line scheduling algorithms to prevent packet losses. We show that a simple greedy algorithm is Θ(log m)-competitive which is asymptotically optimal, while Round-Robin scheduling is not better than m-competitive, as actually is any deterministic on-line algorithm for BSP. We also give a polynomial time algorithm for solving off-line BSP optimally. We also study another on-line balancing problem that tries to balance the delay among the m traffic streams.