Noise characterization of “effective quiet” areas on a U.S. Navy aircraft carrier

The purpose of this investigation was to characterize noise levels in spaces designated as “effective quiet” areas on a U.S. Navy aircraft carrier. Noise dosimetry samples were collected in 15 designated spaces, representing 15 noise measurements, while at-sea during airwing carrier qualifications. Equivalent sound level (L_eq) measurements were collected during flight operations (L_{eq (flt ops)}), non-flight operations (L_{eq (non-flt ops)}), and over 24-hr periods (L_{eq (24-hr)}). These data were compared to the 70 dBA American Conference of Governmental Industrial Hygienists (ACGIH^®) Threshold Limit Value (TLV^®) for “effective quiet” areas intended for temporary threshold shift recovery when personnel live and work in a potentially noise hazardous environment for periods greater than 24?hr. The monitored areas were selected based on personnel occupancy/use during off-duty time periods. Areas were classified by either (1) leisure areas that included mess (eating areas), gyms, lounges, an internet cafe, and the fantail social area or (2) berthing (sleeping) areas. The L_eq measurements in decibels “A” weighted (dBA) were compared to determine significant differences between L_{eq (flt ops)}, L_{eq (non-flt ops)}, and L_{eq (24-hr)} and were compared between leisure area and berthing area. Measured noise levels according to time period ranged as follows: (1) L_{eq (24-hr)}: 70.8–105.4 dBA; (2) L_{eq (flt ops)}: 70–101.2 dBA; and (3) L_{eq (non-flt ops)}: 39.4–104.6 dBA. All area measurements over the 24-hr period and during flight operations and 46.7% of the areas during the non-flight operation time period exceeded the “effective quiet” 70 dBA ACGIH TLV. Mean L_eqs were 15 dBA higher during flight operations compared to non-flight operations in “effective quiet” areas (p?=?0.001). The L_eqs in leisure areas were significantly higher than berthing areas by approximately 21 dBA during non-flight operation periods (p?=?0.001). Results suggest noise levels in “effective quiet” areas frequented by aircraft carrier personnel during off-duty hours when at-sea may inhibit auditory recovery from occupational noise exposures that occur on-duty.     

The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Off pump coronary artery bypass (OPCAB) in critical left mainstem stenosis—Our experience

Background Beating heart surgery has now become the commonest technique of doing Coronary Artery Bypass Graft Surgery (CABG) in our country. It is being used even in such high risk situations like diffuse coronary disease and Critical Left Main stem Stenosis (LMCS) with good results. The aim of this study is to retrospectively review our results in Off-Pump Coronary Artery Bypass Surgery (OPCAB) in patients with critical left main stem stenosis. Methods This study is a retrospective analysis of the data of patients who underwent primary coronary artery bypass surgery. During the period from April 2003 to September 2005 a total of 64 patients underwent OPCAB procedure for critical LMCS. During the same period 10 patients underwent CABG on Cardio Pulmonary Bypass (CPB). The age range was 36–77yrs. The sex distribution was M: F 53∶10. Ten patients were done as emergency. 2 of them were on Intra Aortic Balloon Pump (IABP) support preoperatively. 10 patients were high risk with a Euro score of ≥5. Results Left Internal Mammary Artery (LIMA) was used in 78% of cases. Average grafts per patient was 2.96. The median ventilation time was 5.91 hrs. New IABP insertion in postoperative period was required in 1 patient. One patient was reexplored for bleeding. There was one perioperative myocardial infarction. 57% of patients did not need any blood transfusion. There was no conversion to CPB. There was no operative mortality. Inotropes were used in ten cases. Conclusions OPCAB is a safe method of revascularization in patients with critical LMCS. Preoperative IABP is useful in patients with cardiogenic shock. However, there is a place for CPB in patients needing additional procedures like Mitral Valve repair (MV repair) or Dor's procedure or when the vessels are very diffusely diseased. Those patients who are unstable despite IABP support may be managed by Beating heart On Pump (BHOP) technique.     

Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.