Isolation of alkaline-tolerant bacteria from primary infected root canals.

Introduction: Alkaline-tolerant bacteria in primary infected root canals could have enhanced survival capacity against antimicrobials commonly used in root canal treatment. The aims of this study were to isolate and characterize alkaline-tolerant bacteria before endodontic treatment (S1), after chemomechanical root canal preparation (S2), and after calcium hydroxide dressing (S3).

Methods: Bacteriologic samples were obtained from 43 primary infected root canals.

Biological interpretation of genome-wide association studies using predicted gene functions.

The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.

Chemodenervation for treatment of limb spasticity following spinal cord injury: a systematic review.

Study Design: Systematic review.

Objectives: To systematically review the literature on chemodenervation with botulinum toxin (BoNT) or phenol/alcohol for treatment of limb spasticity following spinal cord injury (SCI).

Setting: British Columbia, Canada.

PAX3 and ETS1 synergistically activate MET expression in melanoma cells.

Melanoma is a highly aggressive disease that is difficult to treat owing to rapid tumor growth, apoptotic resistance and high metastatic potential. The MET proto-oncogene (MET) tyrosine kinase receptor promotes many of these cellular processes, but while MET is often overexpressed in melanoma, the mechanism driving this overexpression is unknown. As the MET gene is rarely mutated or amplified in melanoma, MET overexpression may be driven to increased activation through promoter elements.

Spatial regulation of gene expression during growth of articular cartilage in juvenile mice.

Background: In juvenile mammals, the epiphyses of long bones grow by chondrogenesis within the articular cartilage. A better understanding of the molecular mechanisms that regulate the growth of articular cartilage may give insight into the antecedents of joint disease, such as osteoarthritis.

Methods: We used laser capture microdissection to isolate chondrocytes from the superficial, middle, and deep zones of growing tibial articular cartilage in the 1-wk-old mouse and then investigated expression patterns by microarray.

Granules harboring translationally active mRNAs provide a platform for P-body formation following stress.

The localization of mRNA to defined cytoplasmic sites in eukaryotic cells not only allows localized protein production but also determines the fate of mRNAs. For instance, translationally repressed mRNAs localize to P-bodies and stress granules where their decay and storage, respectively, are directed. Here, we find that several mRNAs are localized to granules in unstressed, actively growing cells.

Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.

Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG.

Systematic review of the quality of economic evaluations in the otolaryngology literature.

Objective: To evaluate the quality of economic evaluations published in the otolaryngology--head and neck surgery literature, which will identify methodologic weaknesses that can be improved on in future studies. A secondary objective is to identify factors that may be associated with higher quality economic evaluations.

Data Sources: Ovid Medline (including PubMed), Embase, and the National Health Services Economic Evaluation databases.

Copy number variants in short children born small for gestational age.

Background/aims: In addition to genome-wide association studies (GWAS), height-associated genes may be uncovered by studying individuals with extreme short or tall stature.

Methods: Genome-wide analysis for copy number variants (CNVs), using single nucleotide polymorphism (SNP) arrays, was performed in 49 index cases born small for gestational age with persistent short stature. Segregation analysis was performed, and genes in CNVs were compared with information from GWAS, gene expression in rodents' growth plates, and published information.

Defining the role of common variation in the genomic and biological architecture of adult human height.

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability.

Opposing effects of CTLA4 insufficiency on regulatory versus conventional T cells in autoimmunity converge on effector memory in target tissue.

Quantitative variations in CTLA4 expression, because of genetic polymorphisms, are associated with various human autoimmune conditions, including type 1 diabetes (T1D). Extensive studies have demonstrated that CTLA4 is not only essential for the suppressive role of regulatory T cells (T(reg)) but also required for intrinsic control of conventional T (T(conv)) cells. We report that a modest insufficiency of CTLA4 in mice, which mimics the effect of some human CTLA4 genetic polymorphisms, accompanied by a T1D-permissive MHC locus, was sufficient to induce juvenile-onset diabetes on an otherwise T1D-resistant genetic background.

Control of outer radial glial stem cell mitosis in the human brain.

Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG). oRG cells display a characteristic division mode, mitotic somal translocation (MST), in which the soma rapidly translocates toward the cortical plate immediately prior to cytokinesis. MST may be essential for progenitor zone expansion, but the mechanism of MST is unknown, hindering exploration of its function in development and disease.

Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex.

Large-scale surveys of single-cell gene expression have the potential to reveal rare cell populations and lineage relationships but require efficient methods for cell capture and mRNA sequencing. Although cellular barcoding strategies allow parallel sequencing of single cells at ultra-low depths, the limitations of shallow sequencing have not been investigated directly. By capturing 301 single cells from 11 populations using microfluidics and analyzing single-cell transcriptomes across downsampled sequencing depths, we demonstrate that shallow single-cell mRNA sequencing (~50,000 reads per cell) is sufficient for unbiased cell-type classification and biomarker identification.

Reducing the preoperative ecological footprint in otolaryngology.

Objectives: To (1) evaluate the potential for recycling uncontaminated preoperative waste and (2) identify recycling differences within otolaryngology-head and neck surgery subspecialties.

Study Design: Prospective study.

Setting: Three university-affiliated tertiary level hospitals.

Prognostic factors relating to the outcome of endodontic microsurgery.

Introduction: The aim of this retrospective study was to evaluate the outcome of endodontic microsurgery and to examine prognostic factors related to healing.

Methods: The clinical records of all patients who had undergone endodontic microsurgery from 1997-2003 at the National Dental Centre of Singapore were examined. Teeth with a recall period of 1-2 years were selected.

Gene expression profiling reveals similarities between the spatial architectures of postnatal articular and growth plate cartilage.

Articular and growth plate cartilage are discrete tissues but arise from a common cartilaginous condensation and have comparable spatial architectures consisting of distinct layers of chondrocytes. To investigate similarities and differences between articular and growth plate cartilage and to explore transcriptional changes that occur during the onset of their divergence, we performed manual microdissection of 10-day-old rat proximal tibias, microarray analysis, bioinformatics, and real-time PCR to compare gene expression profiles in individual cartilage layers. We found that many genes that were spatially upregulated in the intermediate/deep zone of articular cartilage were also spatially upregulated in the resting zone of growth plate cartilage (overlap greater than expected by chance, P<0.

Famotidine, a Histamine H Receptor Antagonist, Does Not Reduce Levodopa-Induced Dyskinesia in Parkinson's Disease: A Proof-of-Concept Study.

The neural mechanisms underlying levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) may involve histamine (H) receptors on striatopallidal pathways. We recently demonstrated that the clinically available oral histamine H receptor antagonist (H RA), famotidine, can reduce l-dopa-induced chorea in MPTP-lesioned macaques. We hypothesized that famotidine may be useful in the treatment of LID in PD patients.

Primary squamous cell of the thyroid-an abbreviated clinical presentation.

Background: Lacking any squamous epithelium, thyroid gland with primary squamous cell carcinoma (PSCC) proves to be an etiopathophysiological quandary. Two major theories do exist, though few cases have been documented to support either. We present a case that supports the "metaplasia" theory, which serves to enhance our understanding of a disease that carries with it a very poor prognosis.

[Astragalus polysaccharides improved the cardiac function in Sjögren's syndrome model rats based on keap 1-Nrf2/ARE signaling pathway: a mechanism exploration].

Objective: To explore the mechanism of Astragalus polysaccharides (APS) for improving the cardiac function of Sjogren's syndrome (SS) model rats based on Keapl-Nrf2/ARE signaling pathway.

Methods: Totally 48 male Wistar rats were randomly divided into four groups by random digit table, i.e.

Novel ANO5 homozygous microdeletion causing myalgia and unprovoked rhabdomyolysis in an Arabic man.

Introduction: Recessive mutations in the anoctamin-5 gene (ANO5) cause a spectrum of clinical phenotypes, including limb-girdle muscular dystrophy (LGMD 2L), distal myopathy, and asymptomatic hyperCKemia.

Methods: In this report we describe our clinical, electrophysiological, pathological, and molecular findings in a subject with anoctaminopathy-5.

Results: A 49-year-old Arabic man from a consanguineous family presented with a 5-year history of myalgias, hyperCKemia and an episode of unprovoked rhabdomyolysis.

Evolutionary conservation and modulation of a juvenile growth-regulating genetic program.

Body size varies enormously among mammalian species. In small mammals, body growth is typically suppressed rapidly, within weeks, whereas in large mammals, growth is suppressed slowly, over years, allowing for a greater adult size. We recently reported evidence that body growth suppression in rodents is caused in part by a juvenile genetic program that occurs in multiple tissues simultaneously and involves the downregulation of a large set of growth-promoting genes.

Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations.

Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common.

Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age.

The effect of glass fiber-reinforced epoxy resin dowel diameter on the fracture resistance of endodontically treated teeth.

Purpose: To determine the effect of glass fiber-reinforced epoxy resin (FRC) dowels of different diameters on the failure load of endodontically treated teeth with different remaining dentine and reinforcing resin composite (RRC) thicknesses and the mode of failure in each group.

Materials And Methods: Fifty extracted intact human maxillary central incisors were decoronated 2 mm incisal to the buccal cementoenamel junction and endodontically treated. The teeth were randomly assigned to one of five groups (n = 10): group B, dowel space prepared with size 0 dowel drill/size 0 FRC dowel/no RRC; group W, size 1 dowel space/size 1 FRC dowel/no RRC; group R, size 3 dowel space/size 3 FRC dowel/no RRC; group WR, size 3 dowel space/size 1 FRC dowel/RRC; group BR, size 3 dowel space/size 0 FRC dowel/RRC.