Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics.

Alveolar epithelial type II (AETII) cells are important for lung epithelium maintenance and function. We demonstrate that AETII cells from mouse lungs exposed to cigarette smoke (CS) increase the levels of the mitochondria-encoded non-coding RNA, mito-RNA-805, generated by the control region of the mitochondrial genome. The protective effects of mito-ncR-805 are associated with positive regulation of mitochondrial energy metabolism, and respiration. Levels of mito-ncR-805 do not relate to steady-state transcription or replication of the mitochondrial genome. Instead, CS-exposure causes the redistribution of mito-ncR-805 from mitochondria to the nucleus, which correlated with the increased expression of nuclear-encoded genes involved in mitochondrial function. These studies reveal an unrecognized mitochondria stress associated retrograde signaling, and put forward the idea that mito-ncRNA-805 represents a subtype of small non coding RNAs that are regulated in a tissue- or cell-type specific manner to protect cells under physiological stress.

Decision analysis supports the use of drain amylase-based enhanced recovery method after esophagectomy.

Postesophagectomy anastomotic leak is a common postsurgical complication. The current standard method of detecting leak is esophagram usually late in the postoperative period. Perianastomotic drain amylase level had shown promising results in early detection anastomosis leak. Previous studies have shown that postoperative day 4 amylase level is more specific and sensitive than esophagram. The purpose of this study is to determine if implementing a drain amylase-based screening method for anastomotic leak can reduce length of stay and hospital cost relative to a traditional esophagram-based pathway. The drain amylase protocol we propose uses postoperative day 4 drain amylase level to direct the initiation of PO intake and discharge. We designed a decision analysis tree using TreeAge Pro software to compare the drain amylase-based screening method to the standard of care, the esophagram. We performed a retrospective review of postesophagectomy patients from a tertiary academic medical center (University hospital Cleveland medical center) where amylase level was measured routinely postoperatively. The patients were separated into amylase-based pathway group and the standard of care group based on their postop management. The length of stay, costs, complications, and leak rate of these two groups were used to inform the decision analysis tree. In the base-case analysis, the decision analysis demonstrated that an amylase-based screening method can reduce the hospital stay by one day and reduced costs by ∼$3,000 compared to esophagram group. To take the variability of the data into consideration, we performed a Monte Carlo simulation. The result showed again a median saving of 0.71 days and ∼$2,500 per patient in hospital cost. A ballistic sensitivity analysis was performed to show that the sensitivity of postoperative day 4 amylase level in detecting a leak was the most important factor in the model. We conclude that implementing an amylase-based screening method for anastomotic leak in postesophagectomy patient can significantly reduce hospital cost and length of stay. This study demonstrates a novel protocol to improve postesophagectomy care. Based on this result, we believe a prospective multicenter study is appropriate.

Medium-term follow up of pulmonary autograft aortic valve replacement: technical advances and echocardiographic follow up.

BACKGROUND AND AIM OF THE STUDY: The Ross procedure (aortic valve replacement (AVR) with pulmonary autograft and pulmonary homograft replacement of pulmonary valve) was developed as a durable aortic valve substitute that avoids the need for anticoagulation and provides young patients with a long-lasting aortic valve substitute. Our seven-year follow up echocardiography data are reviewed. METHODS: Between May 1993 and March 2000, 40 adult patients (28 males, 12 females; mean age 33.3 years) underwent the Ross procedure at the Brigham and Women's Hospital for congenital aortic stenosis (n = 6), aortic insufficiency (n = 17) and mixed disease (n = 17). All patients had aortic root replacement with the pulmonary autograft and had no regurgitation after operation. Postoperative evaluation was conducted by transthoracic echocardiography, office visit and/or telephone interview. NYHA functional class, aortic and pulmonary valve function and aortic root dimensions were evaluated. RESULTS: One patient died postoperatively as a result of a low output state related to global left ventricular dysfunction. Four patients (10%) developed pulmonary homograft stenosis with a peak gradient >40mmHg; and six developed mild pulmonary stenosis. One patient had aortic insufficiency seven years postoperatively that required valve replacement. Eight patients developed mild dilatation (>37 mm) of the neoaortic root, and five of these had aortic insufficiency. One patient required transplantation at 40 months for restrictive cardiomyopathy. CONCLUSION: The Ross procedure is an effective means of AVR that can be accomplished with low perioperative morbidity and mortality if certain technical modifications are carried out. In this series of 40 patients with mid-term follow up, a significant number developed moderate pulmonary trunk stenosis, though echo characterization demonstrated good valve function.

Femtosecond dynamics of the forbidden carotenoid S1 state in light-harvesting complexes of purple bacteria observed after two-photon excitation.

Time-resolved excited-state absorption intensities after direct two-photon excitation of the carotenoid S(1) state are reported for light-harvesting complexes of purple bacteria. Direct excitation of the carotenoid S(1) state enables the measurement of subsequent dynamics on a fs time scale without interference from higher excited states, such as the optically allowed S(2) state or the recently discovered dark state situated between S(1) and S(2). The lifetimes of the carotenoid S(1) states in the B800-B850 complex and B800-B820 complex of Rhodopseudomonas acidophila are 7+/-0.5 ps and 6+/-0.5 ps, respectively, and in the light-harvesting complex 2 of Rhodobacter sphaeroides approximately 1.9+/-0.5 ps. These results explain the differences in the carotenoid to bacteriochlorophyll energy transfer efficiency after S(2) excitation. In Rps. acidophila the carotenoid S(1) to bacteriochlorophyll energy transfer is found to be quite inefficient (phi(ET1) <28%) whereas in Rb. sphaeroides this energy transfer is very efficient (phi(ET1) approximately 80%). The results are rationalized by calculations of the ensemble averaged time constants. We find that the Car S(1) --> B800 electronic energy transfer (EET) pathway ( approximately 85%) dominates over Car S(1) --> B850 EET ( approximately 15%) in Rb. sphaeroides, whereas in Rps. acidophila the Car S(1) --> B850 EET ( approximately 60%) is more efficient than the Car S(1) --> B800 EET ( approximately 40%). The individual electronic couplings for the Car S(1) --> BChl energy transfer are estimated to be approximately 5-26 cm(-1). A major contribution to the difference between the energy transfer efficiencies can be explained by different Car S(1) energy gaps in the two species.

Erythrocyte aging in the demented elderly: a fluctuating process?

Measurement of erythrocyte aging parameters in patients with dementia indicates that an Alzheimer-related disturbance of the erythrocyte aging process may not be detectable until in the more advanced stages of the disease. Also, a strong fluctuation in the values of erythrocyte aging parameters, over a period of 15 months, was observed in patients with dementia, but not in age-matched control donors. This fluctuation was independent of the type and stage of dementia, and its cause remains to be elucidated. Such variability hampers the use of erythrocyte aging characteristics for the diagnosis of dementia. On the other hand, the aging-related erythrocyte IgG content may be a sensitive biomarker for disturbed systemic homeostasis in the elderly.