Acyldepsipeptide activated ClpP1P2 macromolecule of Leptospira,an ideal Achilles’ heel to hamper the cell survival and deregulate ClpP proteolytic activity

Antibiotic acyldepsipeptide (ADEP) targets the bacterial ClpP serine protease and can inhibit the growth of numerous bacterial species by activating/dysregulating the protease activity within the cell. The spirochete Leptospira interrogans harbors two ClpP isoforms (LepClpP1 and LepClpP2). Supplementation of ADEP in the Leptospira growth medium resulted in the inhibition of bacterial growth. The ADEP mediated activation of the LepClpP mixture was dependent on the time allowed for the self-assembly of LepClpP1 and LepClpP2. The dynamic light scattering of the LepClpP mixture in the presence of the ADEP indicated a conformational transformation of the LepClpP machinery. Serine 98, a catalytic triad residue of the LepClpP1 in the LepClpP1P2 heterocomplex, was critical for the ADEP mediated activation. The computational prototype of the LepClpP1P2 structure suggested that the hydrophobic pockets wherein the ADEPs or the physiological chaperone ClpX predominantly dock are exclusively present in the LepClpP2 heptamer. Using the ADEP as a tool, this investigation provides an insight into the molecular function of the LepClpP1P2 in a coalition with its ATPase chaperone LepClpX. The shreds of the evidence illustrated in this investigation verify that ADEP1 possesses the ability to control the LepClpP system in an unconventional approach than the other organisms.     

Tracheal Stenosis after Tracheostomy

INTRODUCTIONTracheal stenosis is a late and usually non-life threatening complication of surgical and percutaneous tracheostomies (PDT) as well as delayed endotracheal extubation.METHODSWe undertook a retrospective review of all patients who underwent a surgical tracheostomy over a 10 year period. Patients were included in the study if they had CT or MRI imaging of the tracheostomy site both pre-operatively and six or more weeks post operatively. Patients whose imaging was not available were excluded (n = 3) as were those patients who still had a tracheostomy in situ (n = 8). In total 91 patients were included in the study. In the same period 1170 surgical tracheostomies were performed by the maxillofacial surgeons. The images were analysed by a radiologist and the degree of stenosis reported.RESULTSAll 91 patients underwent a tracheostomy with a window. 83 patients did not demonstrate any stenosis. Looking at the remaining 8 patients with stenosis: 6 patients had stenosis of less than 25%, 1 patient had stenosis between 25-50% and 1 patient had stenosis greater than 50%. Both patients with stenosis greater than 25% had more than one surgical tracheostomy.CONCULSIONWe have shown that the risk of stenosis is 8.8%, lower than often quoted in literature, and when it occurs it is likely to be symptomatic only in severe stenosis. Our main risk of stenosis was repeat surgical tracheostomies which also seems to be linked to a greater degree of stenosis.     

Droplet fluid infusion into a dust layer in relation to self-cleaning

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets. Influence of droplet hydrostatic pressure on the fluid infusion into dust layer is also investigated towards exploring the dust removal mechanisms. Environmental dust characteristics are evaluated and their interface with the droplet fluid is assessed. Sets of experiments are carried out to examine: (i) droplet fluid infusion into the dust layer, (ii) droplet fluid cloaking of dust, and (iii) evaluate the weight gain of the dust particles during cloaking. The findings reveal that droplet fluid (water) spreads onto the dusty surface and infuses on the dust particles. Cloaking velocity decays sharply with time and the weight gain of the dust particles is about 17% of the original dust weight after cloaking. The dust particles have a large area of nano-size open-pores-sites on the surface; however, capillary diffusion through these sites is limited with shallow depths and the weight gain of a dust particle via capillary diffusion is about 1% of the particle weight. The maximum infusion depth of the droplet fluid in the dust layer is about 74 μm, which is slightly less than the dust layer thickness on the surface. The rolling droplet picks up all the dust from the 150 μm thick dust layer on the surface.

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets.     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.