Hyper Acute Quadriplegia with Chronic Lead Toxicity; a Case Report

Industrial lead toxicity is more common among miners. This type of toxicity occurs in two forms: acute and chronic. Chronic toxicity is associated with different levels of brain dysfunction, motor impairment, cognitive dysfunction, and neuropsychiatric problems, including depression, anxiety, irritability, and emotional disorders. However, quadriplegia induced by chronic toxicity is very rare.  Here we report a 37-year-old male patient with a history of desert hunting, where he used to roll lead bullets in his mouth, who was admitted with sensory impairment, muscle weakness, and quadriplegia and final diagnosis of lead toxicity

An Approach to the Anthropological Theory of the Qur’an and Hadith and Their Roles in Reducing Environmental Degradation

Background: According to the Qur’an, man is the servant and the successor of Allah, the representative of prosperity on earth, and has the responsibility for the universe. This approach will create a constructive human interaction with the environment. Environmental degradation is against the will of Allah. It originates from ignorance, human selfishness, passions, and evil temptations, manifest in greed, arrogance, and extravagance. If humans control these abnormal factors and follow Qur’an teachings, they will enjoy a healthy environment that is a universal right. This paper seeks to study the anthropological theory of the Qur’an and its role in reducing environmental degradation.Methods: Based on the descriptive-analytical design, we explored 70 verses of the Holy Qur’an in which the words samā’, ‘ard, mas’ūl, khalīfah, shaytān, and those are cognate with the Arabic verbs sa-khkha-ra, ha-ra-sa, sa-ra-fa, ki-ba-ra, ha-wā, ‘a-ba-da, and ‘a-ma-ra, as well as the related articles, books, and philological and exegetical sources. We investigated the Qur’an to find the effect of awareness and more attention of human beings to the dimensions of man’s creation to reduce environmental degradation. These issues will be discussed in two parts: 1) the anthropology and the dimensions of human creation in the Qur’an, and 2) the causes of environmental degradation.Results: This study showed that the survival of life and human enjoyment of a healthy environment depends on enough knowledge of oneself, seeking help from Allah, and following the Qur’anic guidelines. These facts effectively control internal and external causes of environmental degradation, including ignorance, egoism, selfishness, and evil temptations. These actions destroy the roots of greed, arrogance, and extravagance in human beings. For this reason, Allah demands humans to develop earth, care for and rescue it from any destruction, avoid extravagance, and observe justice.Conclusion: Meditating in the Qur’an, the man knows his creative dimensions and environmental degradation factors that are incompatible with nature and are rooted in some of the inner and outer dimensions of human personality. Hence, he will consciously enjoy sustainable development and maintaining a healthy environment. This behavior will then reduce anomalies in the environment on his part

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Proteogenomics connects somatic mutations to signalling in breast cancer

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. We describe quantitative mass spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers of which 77 provided high-quality data. Integrated analyses allowed insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. The 5q trans effects were interrogated against the Library of Integrated Network-based Cellular Signatures, thereby connecting CETN3 and SKP1 loss to elevated expression of EGFR, and SKP1 loss also to increased SRC. Global proteomic data confirmed a stromal-enriched group in addition to basal and luminal clusters and pathway analysis of the phosphoproteome identified a G Protein-coupled receptor cluster that was not readily identified at the mRNA level. Besides ERBB2, other amplicon-associated, highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets

Statistical Design for Biospecimen Cohort Size in Proteomics-based Biomarker Discovery and Verification Studies

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC), with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance, and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step towards building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research

Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma

Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low µg/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma

Recommendations for the Generation, Quantification, Storage, and Handling of Peptides Used for Mass Spectrometry-Based Assays

BACKGROUND: For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope-labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays. CONTENT: The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials-in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry-is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care

Update on New Therapies of Diabetic Foot Ulcers: A Systematic Review

Diabetic foot ulcers (DFUs) are as a chronic wound with a serious and rampant complication of diabetes mellitus. Treatment of DFU remains often challenging and time-consuming due to consecutive uncomfortable outcomes. Therefore, this review helps to inform clinicians of the current status of new effective therapies for DFUs