Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords

<正>Conventional vs.polyethylene glycol(PEG)-fusion technologies to repair severed spinal axons:Most spinal cord injuries(SCIs)involve cut-or crush-severance of spinal tract axons in the central nervous system(CNS).Clinical outcomes after CNS axonal severance is very poor because proximal segments of CNS axons lack a suitable environment for     

Women's angiographic vitamin and estrogen trial: design and methods

The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.     

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co‐morbidity in prostate cancer patients may positively impact overall survival.

OBJECTIVE

• ? To evaluate the relationship between pre‐treatment erectile function and all‐cause mortality in patients with prostate cancer treated with brachytherapy.

PATIENTS AND METHODS

• ? In all, 1279 consecutive patients with clinically localized prostate cancer and pre‐implant erectile function assessed by the International Index of Erectile Function‐6 (IIEF‐6) underwent brachytherapy.
• ? Potency was defined as an IIEF‐6 score of ≥13 without pharmacological or mechanical support.
• ? Patients were stratified into IIEF‐6‐score cohorts (≤12, 13–23 and 24–30).
• ? The median follow‐up was 5.0 years.

RESULTS

• ? The 8‐year overall survival (OS) of the study population was 85.1%.
• ? The 8‐year OS for IIEF‐6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001).
• ? Cardiovascular events accounted for a significant portion of deaths in each IIEF‐6 group.
• ? When combined with other risk factors for cardiovascular disease, an IIEF‐6 score of ≤12 had an additive effect on all‐cause mortality (IIEF‐6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).

CONCLUSIONS

• ? A pre‐implant IIEF‐6score of ≤12 was associated with a higher incidence of all‐cause mortality.
• ? Pre‐treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients.
• ? Aggressive treatment of medical co‐morbidity is warranted to impactOS.

     

The two‐pore domain K2P channel TASK2 drives human NK‐cell proliferation and cytolytic function

Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor‐ and virus‐infected cells without prior stimulation. Killing of target cells is a multistep process including adhesion to target cells, formation of an immunological synapse, and polarization and release of cytolytic granules. The role of distinct potassium channels in this orchestrated process is still poorly understood. The current study reveals that in addition to the voltage‐gated K_V1.3 and the calcium‐activated K_Ca3.1 channels, human NK cells also express the two‐pore domain K₂P channel TASK2 (TWIK‐related acid‐sensitive potassium channel). Expression of Task2 varies among NK‐cell subsets and depends on their differentiation and activation state. Despite its different expression in TASK2^highCD56^brightCD16^? and TASK2^lowCD56^dimCD16⁺ NK cells, TASK2 is involved in cytokine‐induced proliferation and cytolytic function of both subsets. TASK2 is crucial for leukocyte functional antigen (LFA‐1) mediated adhesion of both resting and cytokine‐activated NK cells to target cells, an early step in killing of target cells. With regard to the following mechanism, TASK2 plays a role in release of cytotoxic granules by resting, but not IL‐15‐induced NK cells. Taken together, our data exhibit two‐pore potassium channels as important players in NK‐cell activation and effector function.     

Dual connection of the left anterior descending coronary artery to the left and right coronary arteries

Origin of the left anterior descending coronary artery from the right coronary artery is a well-described but rare congenital coronary anomaly. In this report, we describe two cases in which the mid left anterior descending coronary artery is connected to the right coronary artery through an intraseptal connecting vessel, while the proximal left anterior descending coronary artery originates normally from the left main coronary artery. This previously unreported pattern suggests partial persistence of the peritruncal ring, which occurs during normal embryologic development of the coronary circulation. Even though it is classically described as an epicardial structure, the vascular pattern in our cases suggests that the peritruncal ring may have an intramural segment in some individuals.