Information and Communication Technologies, eHealth and Homelessness: A bibliometric review

A bibliometric review was conducted to assess the available scientific knowledge regarding the use of Information and Communication Technologies (ICT) by Individuals Experiencing Homelessness (IEH) and reflect on the existing evidence that ICT use has on their health. A total of 50 published articles were selected after a process of systematic review from five databases containing record of publications up until 2016. All the studies were published in English, half of the works were published in the last three years and 48% of them included the description of ICT use as an objective. Despite the fact that experimental studies were rare, and sample sizes typically small, it was concluded that the studies analyzing the effect of ICT on health display benefits. ndeed, the use of such technology offers promising opportunities to explore new ways of intervention in prevention, harm reduction and health treatment of IEH

Mitochondial parts, pathways, and pathogenesis

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Cataloged from PDF version of thesis.Includes bibliographical references.In title on title page, the word "Mitochondrial" is spelled "Mitochondial."Mitochondria are cellular compartments that perform essential roles in energy metabolism, ion homeostasis, and apoptosis. Mitochondrial dysfunction causes disease in 1 in 5,000 live births and also has been associated with aging, neurodegeneration, cancer, and diabetes. To systematically explore the function of mitochondria in health and in disease, it is necessary to identify all of the proteins resident in this organelle and to understand how they integrate into pathways. However, traditional molecular and biochemistry methods have identified only half of the estimated 1200 mitochondrial proteins, including the 13 encoded by the tiny mitochondrial genome. Now, newly available genomic technologies make it possible to identify the remainder and explore their roles in cellular pathways and disease. Toward this goal, we performed mass spectrometry, GFP tagging, and machine learning on multiple genomic datasets to create a mitochondrial compendium of 1098 genes and their protein expression across 14 mouse tissues. We linked poorly characterized proteins in this inventory to known mitochondrial pathways by virtue of shared evolutionary history. We additionally used our matched mRNA and protein measurements to demonstrate a widespread role of upstream open reading frames (uORFs) in blunting translation of mitochondrial and other cellular proteins. Next we used the mitochondrial protein inventory to identify genes underlying inherited diseases of mitochondrial dysfunction. In collaboration with clinicians, we identified causal mutations in five genes underlying diseases including hepatocerebral mtDNA depletion syndrome, autosomal dominant mitochondrial myopathy, and several forms of inherited complex I deficiency. These discoveries have enabled the development of diagnostic tests now widely available. More broadly, the mitochondrial compendium provides a foundation for systematically exploring the organelle's contribution to both basic cellular biology and human disease.by Sarah E. Calvo.Ph.D

Mitochondrial Encephalomyopathy Due to a Novel Mutation in ACAD9

Importance Mendelian forms of complex I deficiency are usually associated with fatal infantile encephalomyopathy. Application of “MitoExome” sequencing (deep sequencing of the entire mitochondrial genome and the coding exons of >1000 nuclear genes encoding the mitochondrial proteome) allowed us to reveal an unusual clinical variant of complex I deficiency due to a novel homozygous mutation in ACAD9. The patient had an infantile-onset but slowly progressive encephalomyopathy and responded favorably to riboflavin therapy. Observation A 13-year-old boy had exercise intolerance, weakness, and mild psychomotor delay. Muscle histochemistry showed mitochondrial proliferation, and biochemical analysis revealed severe complex I deficiency (15% of normal). The level of complex I holoprotein was reduced as determined by use of Western blot both in muscle (54%) and in fibroblasts (57%). Conclusions and Relevance The clinical presentation of complex I deficiency due ACAD9 mutations spans from fatal infantile encephalocardiomyopathy to mild encephalomyopathy. Our data support the notion that ACAD9 functions as a complex I assembly protein. ACAD9 is a flavin adenine dinucleotide–containing flavoprotein, and treatment with riboflavin is advisable

Feline osteochondromatosis in a 12-year-old feline leukaemia virus-negative cat

Feline osteochondromatosis is a spontaneous osteocartilaginous exostosis associated with feline leukaemia virus (FeLV) infection or due to a frameshift variant in the exostosin glycosyltransferase 1 (EXT1) gene. Osteochondromatosis was diagnosed in an indoor-only, 12-year-old, neutered female, Russian Blue cat. Radiographs revealed bilateral calcified proliferations in the elbow, costochondral and sternochondral joints, which distorted the normal skeletal structure. Grossly, the proliferated joints presented with consistent, rounded masses, causing complete ankylosis. The main histopathological finding was an osteocartilaginous proliferation composed of multiple irregular islands of well-differentiated hyaline cartilage surrounded and delimited by osteoid tissue. Immunohistochemistry of the osteochondromas, bone marrow and mediastinal lymph nodes, using a primary anti-FeLV gp70 antibody, and FeLV proviral DNA real-time polymerase chain reaction on bone marrow were negative. Sequencing of exon 6 of the EXT1 gene was performed and nucleotide BLAST analysis demonstrated the absence of a frameshift variant. This study reports the only case of spontaneous feline osteochondromatosis in an animal more than 10 years old

Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency

Background: D-bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe, infantile-onset disorder of peroxisomal fatty acid oxidation. Few affected patients survive past two years of age. Compound heterozygous mutations in HSD17B4 have also been reported in two sisters diagnosed with Perrault syndrome (MIM # 233400), who presented in adolescence with ovarian dysgenesis, hearing loss, and ataxia. Case presentation: An adult male presented with cerebellar ataxia, peripheral neuropathy, hearing loss, and azoospermia. The clinical presentation, in combination with biochemical findings in serum, urine, and muscle biopsy, suggested a mitochondrial disorder. Commercial genetic testing of 18 ataxia and mitochondrial disease genes was negative. Targeted exome sequencing followed by analysis of single nucleotide variants and small insertions/deletions failed to reveal a genetic basis of disease. Application of a computational algorithm to infer copy number variants (CNVs) from exome data revealed a heterozygous 12 kb deletion of exons 10–13 of HSD17B4 that was compounded with a rare missense variant (p.A196V) at a highly conserved residue. Retrospective review of patient records revealed mildly elevated ratios of pristanic:phytanic acid and arachidonic:docosahexaenoic acid, consistent with dysfunctional peroxisomal fatty acid oxidation. Conclusion: Our case expands the phenotypic spectrum of HSD17B4-deficiency, representing the first male case reported with infertility. Furthermore, it points to crosstalk between mitochondria and peroxisomes in HSD17B4-deficiency and Perrault syndrome

Atypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Disease

Background: Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation: Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion: This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients

Comparative RNA editing in autistic and neurotypical cerebella

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene–environment interactions underlying complex behavior in health and disease. Synaptic function is a main target of A-to-I editing, which can selectively recode key amino acids in synaptic genes, directly altering synaptic strength and duration in response to environmental signals. Here, we performed a high-resolution survey of synaptic A-to-I RNA editing in a human population, and examined how it varies in autism, a neurodevelopmental disorder in which synaptic abnormalities are a common finding. Using ultra-deep (>1000 × ) sequencing, we quantified the levels of A-to-I editing of 10 synaptic genes in postmortem cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range of editing levels was detected across individuals and editing sites, from 99.6% to below detection limits. In most sites, the extreme ends of the population editing distributions were individuals with autism. Editing was correlated with isoform usage, clusters of correlated sites were identified, and differential editing patterns examined. Finally, a dysfunctional form of the editing enzyme adenosine deaminase acting on RNA B1 was found more commonly in postmortem cerebella from individuals with autism. These results provide a population-level, high-resolution view of A-to-I RNA editing in human cerebella and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism.Nancy Lurie Marks Family FoundationF. Hoffmann-La Roche & Co. (Applied Science Sequencing Grant Program)Autism Speaks (Organization)Simons FoundationNational Institutes of Health (U.S.) (Grant 1R01MH085143-01

Fate of pharmaceuticals and pesticides in fly larvae composting

A novel and efficient organic waste management strategy currently gaining great attention is fly larvae composting. High resource recovery efficiency can be achieved in this closed-looped system, but pharmaceuticals and pesticides in waste could potentially accumulate in every loop of the treatment system and spread to the environment. This study evaluated the fate of three pharmaceuticals (carbamazepine, roxithromycin, trimethoprim) and two pesticides (azoxystrobin, propiconazole) in a fly larvae composting system and in a control treatment with no larvae. It was found that the half-life of all five substances was shorter in the fly larvae compost (<10% of control) and no bioaccumulation was detected in the larvae. Fly larvae composting could thus impede the spread of pharmaceuticals and pesticides into the environment