Fallacies of preoperative lymphoscintigraphy in detecting sentinel node in breast cancer

BACKGROUND: Preoperative lymphoscintigraphy is one of the three methods of evaluating sentinel nodes in patients with breast cancer; however, it has been reported to have a high false negative rate. CASE PRESENTATIONS: We report here two cases where the preoperative lymphoscintigraphy was found to be fallacious. A 44-year-old female with T2N0 breast cancer underwent preoperative lymphoscintigraphy with Tc(99 )sulfur colloid which failed to show any uptake in axilla or internal mammary chain. Intraoperative scintigraphy with blue dye and hand held gamma probe identified sentinel lymph node in axilla. Another patient with T2N0 lesion underwent preoperative lymphoscintigraphy which showed a sentinel lymph node in axilla and another in supraclevicular fossa. Intraoperative scintigraphy failed to show supraclevicular node however axillary node was correctly identified. CONCLUSION: These two cases further strengthen the need to carry out triple test in identification of sentinel lymph node in patients with breast cancer. It also demonstrates the fallacies of preoperative lymphoscintigraphy

Prevalence, distribution and correlates of tobacco smoking and chewing in Nepal: a secondary data analysis of Nepal Demographic and Health Survey-2006

<p>Abstract</p> <p>Background</p> <p>Nearly four-fifths of estimated 1.1 million smokers live in low or middle-income countries. We aimed to provide national estimates for Nepal on tobacco use prevalence, its distribution across demographic, socio-economic and spatial variables and correlates of tobacco use.</p> <p>Methods</p> <p>A secondary data analysis of 2006 Nepal Demographic and Health Survey (DHS) was done. A representative sample of 9,036 households was selected by two-stage stratified, probability proportional to size (PPS) technique. We constructed three outcome variables 'tobacco smoke', 'tobacco chewer' and 'any tobacco use' based on four questions about tobacco use that were asked in DHS questionnaires. Socio-economic, demographic and spatial predictor variables were used. We computed overall prevalence for 'tobacco smoking', 'tobacco chewing' and 'any tobacco use' i.e. point estimates of prevalence rates, 95% confidence intervals (CIs) after adjustment for strata and clustering at primary sampling unit (PSU) level. For correlates of tobacco use, we used multivariate analysis to calculate adjusted odds ratios (AORs) and their 95% CIs. A p-value < 0.05 was considered as significant.</p> <p>Results</p> <p>Total number of households, eligible women and men interviewed was 8707, 10793 and 4397 respectively. The overall prevalence for 'any tobacco use', 'tobacco smoking' and 'tobacco chewing' were 30.3% (95% CI 28.9, 31.7), 20.7% (95% CI 19.5, 22.0) and 14.6% (95% CI 13.5, 15.7) respectively. Prevalence among men was significantly higher than women for 'any tobacco use' (56.5% versus 19.6%), 'tobacco smoking' (32.8% versus 15.8%) and 'tobacco chewing' (38.0% versus 5.0%). By multivariate analysis, older adults, men, lesser educated and those with lower wealth quintiles were more likely to be using all forms of tobacco. Divorced, separated, and widowed were more likely to smoke (OR 1.49, 95% CI 1.14, 1.94) and chew tobacco (OR 1.36, 95% CI 0.97, 1.93) as compared to those who were currently married. Prevalence of 'tobacco chewing' was higher in eastern region (19.7%) and terai/plains (16.2%). 'Tobacco smoking' and 'any tobacco use' were higher in rural areas, mid-western and far western and mountainous areas.</p> <p>Conclusions</p> <p>Prevalence of tobacco use is considerably high among Nepalese people. Demographic and socioeconomic determinants and spatial distribution should be considered while planning tobacco control interventions.</p

Kinetic Pathway of Pyrophosphorolysis by a Retrotransposon Reverse Transcriptase

DNA and RNA polymerases use a common phosphoryl transfer mechanism for base addition that requires two or three acidic amino acid residues at their active sites. We previously showed, for the reverse transcriptase (RT) encoded by the yeast retrotransposon Ty1, that one of the three conserved active site aspartates (D211) can be substituted by asparagine and still retain in vitro polymerase activity, although in vivo transposition is lost. Transposition is partially restored by second site suppressor mutations in the RNAse H domain. The novel properties of this amino acid substitution led us to express the WT and D211N mutant enzymes, and study their pre-steady state kinetic parameters. We found that the kpol was reduced by a factor of 223 in the mutant, although the Kd for nucleotide binding was unaltered. Further, the mutant enzyme had a marked preference for Mn2+ over Mg2+. To better understand the functions of this residue within the Ty1 RT active site, we have now examined the in vitro properties of WT and D211N mutant Ty1 RTs in carrying out pyrophosphorolysis, the reverse reaction to polymerization, where pyrophosphate is the substrate and dNTPs are the product. We find that pyrophosphorolysis is efficient only when the base-paired primer template region is >14 bases, and that activity increases when the primer end is blunt-ended or recessed by only a few bases. Using pre-steady state kinetic analysis, we find that the rate of pyrophosphorolysis (kpyro) in the D211N mutant is nearly 320 fold lower than the WT enzyme, and that the mutant enzyme has an ∼170 fold lower apparent Kd for pyrophosphate. These findings indicate that subtle substrate differences can strongly affect the enzyme's ability to properly position the primer-end to carry out pyrophosphorolysis. Further the kinetic data suggests that the D211 residue has a role in pyrophosphate binding and release, which could affect polymerase translocation, and help explain the D211N mutant's transposition defect

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture

Abstract Background Neurons are highly polarized cells consisting of three distinct functional domains: the cell body (and associated dendrites), the axon and the synapse. Previously, it was believed that the clinical phenotypes of neurodegenerative diseases were caused by the loss of entire neurons, however it has recently become apparent that these neuronal sub-compartments can degenerate independently, with synapses being particularly vulnerable to a broad range of stimuli. Whilst the properties governing the differential degenerative mechanisms remain unknown, mitochondria consistently appear in the literature, suggesting these somewhat promiscuous organelles may play a role in affecting synaptic stability. Synaptic and non-synaptic mitochondrial subpools are known to have different enzymatic properties (first demonstrated by Lai et al., 1977). However, the molecular basis underpinning these alterations, and their effects on morphology, has not been well documented. Methods The current study has employed electron microscopy, label-free proteomics and in silico analyses to characterize the morphological and biochemical properties of discrete sub-populations of mitochondria. The physiological relevance of these findings was confirmed in-vivo using a molecular genetic approach at the Drosophila neuromuscular junction. Results Here, we demonstrate that mitochondria at the synaptic terminal are indeed morphologically different to non-synaptic mitochondria, in both rodents and human patients. Furthermore, generation of proteomic profiles reveals distinct molecular fingerprints – highlighting that the properties of complex I may represent an important specialisation of synaptic mitochondria. Evidence also suggests that at least 30% of the mitochondrial enzymatic activity differences previously reported can be accounted for by protein abundance. Finally, we demonstrate that the molecular differences between discrete mitochondrial sub-populations are capable of selectively influencing synaptic morphology in-vivo. We offer several novel mitochondrial candidates that have the propensity to significantly alter the synaptic architecture in-vivo. Conclusions Our study demonstrates discrete proteomic profiles exist dependent upon mitochondrial subcellular localization and selective alteration of intrinsic mitochondrial proteins alters synaptic morphology in-vivo

Harmful and beneficial aspects of Parthenium hysterophorus: an update

Parthenium hysterophorus is a noxious weed in America, Asia, Africa and Australia. This weed is considered to be a cause of allergic respiratory problems, contact dermatitis, mutagenicity in human and livestock. Crop production is drastically reduced owing to its allelopathy. Also aggressive dominance of this weed threatens biodiversity. Eradication of P. hysterophorus by burning, chemical herbicides, eucalyptus oil and biological control by leaf-feeding beetle, stem-galling moth, stem-boring weevil and fungi have been carried out with variable degrees of success. Recently many innovative uses of this hitherto notorious plant have been discovered. Parthenium hysterophorus confers many health benefits, viz remedy for skin inflammation, rheumatic pain, diarrhoea, urinary tract infections, dysentery, malaria and neuralgia. Its prospect as nano-medicine is being carried out with some preliminary success so far. Removal of heavy metals and dye from the environment, eradication of aquatic weeds, use as substrate for commercial enzyme production, additives in cattle manure for biogas production, as biopesticide, as green manure and compost are to name a few of some other potentials. The active compounds responsible for hazardous properties have been summarized. The aim of this review article is to explore the problem P. hysterophorus poses as a weed, the effective control measures that can be implemented as well as to unravel the latent beneficial prospects of this weed

Novel Crystalline SiO2 Nanoparticles via Annelids Bioprocessing of Agro-Industrial Wastes

The synthesis of nanoparticles silica oxide from rice husk, sugar cane bagasse and coffee husk, by employing vermicompost with annelids (Eisenia foetida) is reported. The product (humus) is calcinated and extracted to recover the crystalline nanoparticles. X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS) show that the biotransformation allows creating specific crystalline phases, since equivalent particles synthesized without biotransformation are bigger and with different crystalline structure

A Toxin–Antitoxin System Promotes the Maintenance of an Integrative Conjugative Element

SXT is an integrative and conjugative element (ICE) that confers resistance to multiple antibiotics upon many clinical isolates of Vibrio cholerae. In most cells, this ∼100 Kb element is integrated into the host genome in a site-specific fashion; however, SXT can excise to form an extrachromosomal circle that is thought to be the substrate for conjugative transfer. Daughter cells lacking SXT can theoretically arise if cell division occurs prior to the element's reintegration. Even though ∼2% of SXT-bearing cells contain the excised form of the ICE, cells that have lost the element have not been detected. Here, using a positive selection-based system, SXT loss was detected rarely at a frequency of ∼1×10−7. As expected, excision appears necessary for loss, and factors influencing the frequency of excision altered the frequency of SXT loss. We screened the entire 100 kb SXT genome and identified two genes within SXT, now designated mosA and mosT (for maintenance of SXT Antitoxin and Toxin), that promote SXT stability. These two genes, which lack similarity to any previously characterized genes, encode a novel toxin-antitoxin pair; expression of mosT greatly impaired cell growth and mosA expression ameliorated MosT toxicity. Factors that promote SXT excision upregulate mosAT expression. Thus, when the element is extrachromosomal and vulnerable to loss, SXT activates a TA module to minimize the formation of SXT-free cells