Partial Cholecystectomy Safe and Effective

Patients undergoing surgical treatment for calculous disease were considered to have had a partial cholecystectomy performed when a part of the gall bladder wall was retained for technical reasons. Forty patients underwent partial cholecystectomy: for chronic cholecystitis (20), acute cholecystitis (4), Mirizzi's syndrome (14), portal hypertension or partially accesible gall bladder (one patient each). Four patients (10%) developed infective complications and two patients had retained common bile duct stones. In a mean follow up period of 13 months (range 1–36 mths), only 3 patients have ongoing mild dyspeptic symptoms while the rest have remained asymptomatic. Partial cholecystectomy has been found to be a safe and effective procedure in difficult cholecystectomy situations, since it combines the merits of cholecystectomy and cholecystostomy

Correction due to finite speed of light in absolute gravimeters

Correction due to finite speed of light is among the most inconsistent ones in absolute gravimetry. Formulas reported by different authors yield corrections scattered up to 8 $\mu$Gal with no obvious reasons. The problem, though noted before, has never been studied, and nowadays the correction is rather postulated than rigorously proven. In this paper we make an attempt to revise the subject. Like other authors, we use physical models based on signal delays and the Doppler effect, however, in implementing the models we additionally introduce two scales of time associated with moving and resting reflectors, derive a set of rules to switch between the scales, and establish the equivalence of trajectory distortions as obtained from either time delay or distance progression. The obtained results enabled us to produce accurate correction formulas for different types of instruments, and to explain the differences in the results obtained by other authors. We found that the correction derived from the Doppler effect is accountable only for $\frac23$ of the total correction due to finite speed of light, if no signal delays are considered. Another major source of inconsistency was found in the tacit use of simplified trajectory models

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challeng- ing. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein— that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the bind- ing of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligo- methylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications intro- duced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors

Circular Economy Pathways for Municipal Wastewater Management in India: A Practitioner’s Guide

The 2030 Water Resources Group is a unique publicprivate- civil society partnership that helps governments to accelerate reforms that will ensure sustainable water resource management for the long term development and economic growth of their country. It does so by helping to change the “political economy” for water reform in the country through convening a wide range of actors and providing water resource analysis in ways that are digestible for politicians and business leaders. The 2030 WRG was launched in 2008 at the World Economic Forum and has been hosted by the International Finance Corporation (IFC) since 2012

Cytogenetics of human malignant melanoma

There has been a tremendous recent resurgence of interest in examining chromosomal abnormalities in human cancers (particularly solid tumors). This interest has been stimulated by the molecular examination of recurring chromosome abnormalities, and the recognition that they may pinpoint the location of growth regulatory sequences (e.g. cellular oncogenes). This finding coupled with the clear recognition that specific chromosome abnormalities can also have important diagnostic and prognostic implications, have caused this avenue of research to expand at a significant rate. The following brief review will summarize the current state of knowledge regarding recurring chromosome abnormalities in human malignant melanoma. A discussion of chromosome changes in pre-malignant skin lesions, primary melanoma, and metastatic melanoma is described. Brief descriptions of the potential clinical utility, and biologic relevance of chromosome abnormalities in this disorder are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44500/1/10555_2004_Article_BF00049408.pd