Automating Angle Measurements on Foot Radiographs in Young Children: Feasibility and Performance of a Convolutional Neural Network Model

Journal of Digital Imaging - Measurement of angles on foot radiographs is an important step in the evaluation of malalignment. The objective is to develop a CNN model to measure angles on...     

A Review on the History of Tympanoplasty

The history of myringoplasty and tympanoplasty is one of the most interesting in the history of ear surgery. The aims and ambitions of otologists have evolved along with time and experience. The objective of this article is to give an idea about the evolution of tympanoplasty, thus giving inspiration to future surgeons in their quest for a perfect technique which would be as good as a normal ear and its hearing. The history of otology starts from the early Egyptian healers. Hippocrates in his time observed that ear infections may be cause of death especially in young children. Early surgeries were performed mainly for drainage in order to save the life of the child having the ear disease. With time and scientific developments newer methods of treatment started to evolve. The invention of antimicrobials and their usage threw a new light into the treatment of otology infections. Then after the advent of microscope and with better understanding of the anatomy and physiology of ear and its diseases treatment strategies and surgical planning kept on advancing. Surgeons with time have become more interested in returning back the hearing along with curing infection from ear. But the quest is on for the perfect surgical technique which would give best results with minimal maneuvering. History of tympanoplasty nearly sums up the history of evolution of otology as a whole. The quest is still on to devise a way so as to give maximum post-operative hearing using minimal instrumentation.     

On the evolution of chaperones and cochaperones and the expansion of proteomes across the Tree of Life

Across the Tree of Life (ToL), the complexity of proteomes varies widely. Our systematic analysis depicts that from the simplest archaea to mammals, the total number of proteins per proteome expanded ∼200-fold. Individual proteins also became larger, and multidomain proteins expanded ∼50-fold. Apart from duplication and divergence of existing proteins, completely new proteins were born. Along the ToL, the number of different folds expanded ∼5-fold and fold combinations ∼20-fold. Proteins prone to misfolding and aggregation, such as repeat and beta-rich proteins, proliferated ∼600-fold and, accordingly, proteins predicted as aggregation-prone became 6-fold more frequent in mammalian compared with bacterial proteomes. To control the quality of these expanding proteomes, core chaperones, ranging from heat shock proteins 20 (HSP20s) that prevent aggregation to HSP60, HSP70, HSP90, and HSP100 acting as adenosine triphosphate (ATP)-fueled unfolding and refolding machines, also evolved. However, these core chaperones were already available in prokaryotes, and they comprise ∼0.3% of all genes from archaea to mammals. This challenge—roughly the same number of core chaperones supporting a massive expansion of proteomes—was met by 1) elevation of messenger RNA (mRNA) and protein abundances of the ancient generalist core chaperones in the cell, and 2) continuous emergence of new substrate-binding and nucleotide-exchange factor cochaperones that function cooperatively with core chaperones as a network.

All cellular life is thought to have stemmed from the last universal common ancestor (LUCA) (1, 2), that emerged more than 3.6 billion y ago. Two major kingdoms of life diverged from LUCA: bacteria and archaea, which about 2 billion y later merged into the eukaryotes (3). Since the beginning of biological evolution, life’s volume has increased on a grand scale: The average size of individual cells has increased ∼100-fold from prokaryotes to eukaryotes (4), the number of cell types has increased ∼200-fold from unicellular eukaryotes to humans (5), and average body size has increased ∼5,000-fold from the simplest sponges to blue whales (6).This expansion in organismal complexity and variability was accompanied by an expansion in life’s molecular workforce, proteomes in particular, which in turn presented a challenge of reaching and maintaining properly folded and functional proteomes. Most proteins must fold to their native structure in order to function, and their folding is largely imprinted in their primary amino acid sequence (7–9). However, many proteins, and especially large multidomain polypeptides, or certain protein types such as all-beta or repeat proteins, tend to misfold and aggregate into inactive species that may also be toxic (10). Life met this challenge by evolving molecular chaperones that can minimize protein misfolding and aggregation, even under stressful out-of-equilibrium conditions favoring aggregation (11, 12). Chaperones can be broadly divided into core and cochaperones. Core chaperones can function on their own, and include ATPases heat shock protein 60 (HSP60), HSP70, HSP100, and HSP90 and the adenosine triphosphate (ATP)-independent HSP20. The basal protein holding, unfolding, and refolding activities of the core chaperones are facilitated and modulated by a range of cochaperones such as J-domain proteins (13–15).Starting from LUCA, as proteomes expanded, so did the core chaperones and their respective cochaperones. Indeed, chaperones have been shown to facilitate the acquisition of destabilizing mutations and thereby accelerate protein evolution (16–18). However, the coexpansion of proteomes and of chaperones, underscoring a critical balance between evolutionary innovation and foldability, remains largely unexplored. We thus embarked on a systematic bioinformatics analysis that explores the evolution of both proteomes and chaperones, and of both core and their auxiliary cochaperones, along the Tree of Life.     

Increase in Temperature Induces the Malathion Toxicity in <Emphasis Type="Italic">Pangasianodon hypophthalmus</Emphasis>: A Short Term Acute Test

The study was conducted to evaluate the effect of higher temperature beyond optimum range on acute toxicity for malathion (effective concentration 50 %) in Pangasianodon hypophthalmus. A 2 days renewal bioassay system for 96 h was used to determine LC₅₀ value of malathion at three different regimes of temperature that is 30, 32 and 34 °C considering as T1, T2 and T3, respectively. The physico-chemical parameters of water of different treatment groups were estimated during pre and post-exposure of test chemical, following standard methods. The result of short term acute toxicity test at 96 h LC₅₀ values through probit analysis was found to be 7.76, 6.45 and 4.46 µL L^?1 for T1, T2, and T3, respectively. The 96 h LC₅₀ of malathion at 34 °C was found to be significantly (p < 0.01) lower as compared with estimated LC₅₀ for malathion at 30 and 32 °C. High temperature and free carbon dioxide coupled with low dissolved oxygen were significantly noticed in T3 group when compared to T1 and T2 groups. Lower LC₅₀ of malathion at 34 °C as compared to 30 and 32 °C showed that at a higher temperature, the toxicity of malathion increased, signifying diminished fish protective response to malathion toxicity. The current study reflects the impact of increased temperature on pesticide toxicity in the aquatic ecosystem, alarming the aqua farmers to judiciously use malathion in ponds.     

SYNTAX Score and Outcomes of Coronary Revascularization in Diabetic Patients

Purpose of Review

This review describes the dynamic relationship between diabetes mellitus (DM) and coronary artery disease (CAD) with respect to different revascularization strategies and how angiographic tools such as the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score can supplement clinical decision-making.

Recent Findings

The SYNTAX score characterizes the anatomical extent of CAD in terms of the number of lesions, functional importance, and complexity. Studies not limited to patients with DM suggest that percutaneous coronary intervention (PCI) is a reasonable alternative to coronary artery bypass grafting (CABG) in patients with low-medium SYNTAX scores, while patients with high SYNTAX scores should be revascularized with CABG if operable. Similar findings were also observed for diabetes patients with multivessel disease in retrospective pooled analysis. The SYNTAX II score combines anatomical and clinical risk to improve upon the decision regarding the optimal revascularization strategy. The SYNTAX II score can be applied to patients with DM.

Summary

The SYNTAX scores provide guidance to clinicians faced with determining the optimal revascularization strategy in patients with DM and advanced CAD. Using a heart team approach, the information can be considered along with other factors that influence PCI or CABG risk.

     

Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial fibrillation or heart failure

Dronedarone is a benzofuran derivative approved by the Food and Drug Administration to decrease the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) and associated cardiovascular risk factors who are in sinus rhythm or will undergo cardioversion. There has been recent evidence to suggest that dronedarone may not have a favorable safety profile. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 through 2011 comparing dronedarone to comparators in AF/heart failure. Intervention was dronedarone for AF for some studies and heart failure for others. Comparators included standard medical therapy and/or placebo and amiodarone for 1 study. Outcomes assessed were all-cause mortality, cardiovascular mortality, ventricular arrhythmias, embolic events, acute coronary syndrome, heart failure exacerbations, and hospitalization rates in the intervention versus comparator group at the end of ≥ 3 months of follow up with abstraction of data by 1 author. Seven randomized controlled trials were included in our analysis. Dronedarone use was associated with a trend toward worse all-cause and cardiovascular mortalities and increased heart failure exacerbations. It also showed numerically higher event rates for all other outcome events except acute coronary syndrome. Our pooled analysis showed increased all-cause and cardiovascular mortalities and increased heart failure exacerbations with use of dronedarone across a wide spectrum of populations. In conclusion, we recommend exercising caution using dronedarone, especially in patients with cardiovascular risk factors.