Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.
Lipopolysaccharide (LPS) derived from the outer membrane of gram-negative bacteria induces acute lung injury (ALI) in mice. This injury is associated with lung edema, inflammation, diffuse alveolar damage, and severe respiratory insufficiency. We have previously reported that LPS-mediated nitric oxide synthase (NOS) uncoupling, through increases in asymmetric dimethylarginine (ADMA), plays an important role in the development of ALI through the generation of reactive oxygen and nitrogen species. Therefore, the focus of this study was to determine whether mice deficient in endothelial NOS (eNOS-/-) are protected against ALI. In both wild-type and eNOS-/- mice, ALI was induced by the intratracheal instillation of LPS (2 mg/kg). After 24 hours, we found that eNOS-/-mice were protected against the LPS mediated increase in inflammatory cell infiltration, inflammatory cytokine production, and lung injury. In addition, LPS exposed eNOS-/- mice had increased oxygen saturation and improved lung mechanics. The protection in eNOS-/- mice was associated with an attenuated production of NO, NOS derived superoxide, and peroxynitrite. Furthermore, we found that eNOS-/- mice had less RhoA activation that correlated with a reduction in RhoA nitration at Tyr34. Finally, we found that the reduction in NOS uncoupling in eNOS-/- mice was due to a preservation of dimethylarginine dimethylaminohydrolase (DDAH) activity that prevented the LPS-mediated increase in ADMA. Together our data suggest that eNOS derived reactive species play an important role in the development of LPS-mediated lung injury.
An analysis of records of 802 cases who were newly detected from 1983 to 1992 showed that 51 % were of the multi bacillary (MB) type, 33% had visible disabilities at detection, 5% were under 15 years of age while the average delay time was 2•6 years. Patients with disabilities reported a longer delay time, were more often men and had more often the MB type of leprosy. The data suggest that transmission of leprosy is low but that cases are not diagnosed early enough to prevent transmission altogether.
Brief Reports should be submitted online to www.editorialmanager.com/ amsurg. (See details online under ''Instructions for Authors''.) They should be no more than 4 double-spaced pages with no Abstract or sub-headings, with a maximum of four (4) references. If figures are included, they should be limited to two (2). The cost of printing color figures is the responsibility of the author.In general, authors of case reports should use the Brief Report format.
Surgeons frequently report frustration and loss of efficiency with electronic medical record (EMR) systems. Together, surgery residents and a programmer at Augusta University created a rounds report (RR) summarizing 24 hours of vitals, intake/output, labs, and other values for each inpatient that were previously transcribed by hand. The objective of this study was to evaluate the RR's effect on surgery residents. Surgery residents were queried to assess the RR's impact. Outcome measures were time spent preparing for rounds, direct patient care time, educational activity time, rates of incorrect/incomplete data on rounds, and rate of duty hour violations. Hospital wide, 17,200 RRs were generated in the 1-month study. Twenty-three surgery residents participated. Time spent preparing for rounds decreased per floor patient (15.6 ± 3.0 vs 6.0 ± 1.2, P < 0.0001) and per intensive care unit patient (19.9 ± 2.9 vs 7.5 ± 1.2 P < 0.0001). The work day spent in direct patient care increased from 45.1 ± 5.6 to 54.0 ± 5.7 per cent ( P = 0.0044). Educational activity time increased from 35.2 ± 5.4 to 54.7 ± 7.1 minutes per resident per day ( P = 0.0004). Reported duty hour violations decreased 58 per cent ( P < 0.0001). American Board of Surgery in Training exam scores trended up, and estimates of departmental annual financial savings range from $66,598 to $273,141 per year. Significant improvements occur with surgeon designed EMR tools like the RR. Hospitals and EMR companies should pair interested surgeons with health information technology developers to facilitate EMR enhancements. Improvements like RRs can have broad ranging, multidisciplinary impact and should be standard in all EMRs used for inpatient care at academic medical centers.
Brief Reports should be submitted online to www.editorialmanager.com/ amsurg. (See details online under ''Instructions for Authors''.) They should be no more than 4 double-spaced pages with no Abstract or sub-headings, with a maximum of four (4) references. If figures are included, they should be limited to two (2). The cost of printing color figures is the responsibility of the author.
Patients presenting with near-obstructing colon lesions requiring segmental colectomy may benefit from intraoperative colonoscopy (IOC) after primary anastomosis for a more timely and accurate diagnosis of synchronous lesions. The aim of this study is to demonstrate the feasibility and safety of this technique. A retrospective cohort study of patients undergoing single-stage segmental colectomy and anastomosis at a single tertiary care institution from 2011 to 2013 was performed. One Hundred and sixty-eight consecutive patients underwent segmental colectomy and primary anastomosis of which 78 (46%) were unable to receive preoperative colonoscopy (POC) because of near-obstructing lesions and received IOC after the anastomosis. IOC detected synchronous adenomatous polyps in 24.4 per cent, diverticular disease in 19 per cent, and colitis/proctitis in 2.5 per cent. The IOC group was not significantly different from the POC group with regard to overall morbidity (31% vs 39% P = 0.45), anastomotic leakage (1.3% vs 0%, P = 0.46), or wound infection (5.1% vs 1.1%, P = 0.18). Operation time was 19 minutes longer in the intra-operative group, but overall length of hospital stay was not significantly different (6.4 ± 2.9 days vs 7.3 ± 4.6 days). In patients unable to receive POC because of partial obstruction, IOC after primary anastomosis is both feasible and safe for detecting proximal synchronous lesions.
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