Do acetaminophen and an NSAID combined relieve osteoarthritis pain better than either alone?

Combining nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for short courses provides more relief of pain in osteoarthritis without an increase in side effects (strength of recommendation [SOR]=B). Combining acetaminophen at 4 g/d with an NSAID can also decrease the daily dose of NSAID required for pain relief, thus reducing the potential risk from higher-dose NSAID therapy (SOR=B). Over the long term, however, this combination may increase the risk of upper gastrointestinal (GI) bleeding more than that conferred by the NSAID alone (SOR=B). If combination therapy is necessary, limiting the dose of acetaminophen to ≤2 g/d minimizes gastrointestinal toxicity. Acetaminophen alone at the lowest dose to provide pain relief is the safest pharmacologic choice for patients with osteoarthritis

Fab Fridays: Fostering Elementary Teacher Candidate Preparation Through Informal STEM Events

Informal STEM learning opportunities offered outside of the structured school day have been gaining popularity in today’s STEM-oriented culture. These are venues where children and their families gather to engage and explore in science, technology, engineering, and math —together. For a number of years, faculty from the College of Education at Tennessee Tech University have been promoting these events for the local community, free of charge, to encourage and foster a love for STEM Education. Methods professors recognize these events as golden opportunities for teacher candidates enrolled to learn about STEM content while aiding in the development of their pedagogy. In addition to the experience gained from working with the materials at various STEM stations, teacher candidates have the opportunity to interact with children and families. Furthermore, teacher candidates interact with faculty and students from other academic areas such as nursing, engineering, biology and physics, as well as content specialists from the community. These interactions help to bolster preservice teachers’ skills and feelings of self-efficacy toward communicating with families and teaching STEM concepts. The informal STEM learning events offer a variety of experiences often unavailable during the school day and promote the social, emotional, and intellectual skills of our teacher candidates, as well as, those of the children and families who attend

Linkage disequilibrium compared between five populations of domestic sheep

<p>Abstract</p> <p>Background</p> <p>The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x^2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino × Border Leicester), along with an inbred Australian Merino museum flock were analysed.</p> <p>Results</p> <p>Short range LD (0 – 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x^2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino × Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 – 2.5 centimorgans, depending on the population used.</p> <p>Conclusion</p> <p>Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x^2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.</p

Diversity and Ecological Correlates of Red Fluorescence in Marine Fishes

Marine environments at depths below -10 to -25 m are almost devoid of ambient red sunlight because water quickly attenuates long wavelengths. This stenospectral light environment presents unique opportunities for organisms that can transform ambient blue-green light into red light by fluorescence. Numerous marine fish species display intricate patterns of fluorescence. Because color vision is a key component of fish sensory ecology, several putative visual functions of red fluorescence have been proposed but are difficult to test experimentally. Here, we follow a comparative approach to assess the consistency between the phylogenetic distribution of red fluorescence with its presumed functions. We collected and analyzed the largest data set of red fluorescence in fishes to date, consisting of confirmed cases in 272 primarily diurnal fish species from 49 out of 90 surveyed fish families and 12 out of 21 surveyed fish orders, contrasted to 393 fish species with confirmed absence of red fluorescence. Based on a priori hypotheses on adaptive function, we compare the prevalence of red fluorescence among pre-defined sets of species based on ecological or biological characteristics while controlling for shared ancestry. When comparing between species, we find no evidence that red fluorescence is more prevalent in deep-water species, contrasting with our recent finding that fluorescence brightness increases with depth within species. There is also no evidence for a role in group-driven communication. Phylogenetic patterns are consistent, however, with three other predictions. First, fluorescence with a rather patchy distribution across the body occurred significantly more often among sit-and-wait predators or otherwise sedentary fish than in more mobile species, consistent with background matching for camouflage. Second, small, predatory fishes tended to show red fluorescent irides disproportionally often consistent with a proposed function in prey localization. Finally, sexually dimorphic species showed fluorescent fins more often, as predicted if relevant in sexual communication. From these findings, we derive predictions for experimental investigations of the presumed functions of red fluorescence

Engaging All Mathematical Learners Through Project-Based Design

The authors describe a project-based activity using TI calculators or Desmos within a high schoolmathematics classroom. As students learn about functions with technology using a project-based approach, they make connections between school mathematics and topics of personal interest

Target gene selectivity of the myogenic basic helix–loop–helix transcription factor myogenin in embryonic muscle

AbstractThe myogenic regulatory factors MyoD and myogenin are crucial for skeletal muscle development. Despite their importance, the mechanisms by which these factors selectively regulate different target genes are unclear. The purpose of the present investigation was to compare embryonic skeletal muscle from myogenin+/+ and myogenin−/− mice to identify genes whose expression was dependent on the presence of myogenin but not MyoD and to determine whether myogenin-binding sites could be found within regulatory regions of myogenin-dependent genes independent of MyoD. We identified a set of 140 muscle-expressed genes whose expression in embryonic tongue muscle of myogenin−/− mice was downregulated in the absence of myogenin, but in the presence of MyoD. Myogenin bound within conserved regulatory regions of several of the downregulated genes, but MyoD bound only to a subset of these same regions, suggesting that many downregulated genes were selective targets of myogenin. The regulatory regions activated gene expression in cultured myoblasts and fibroblasts overexpressing myogenin or MyoD, indicating that expression from exogenously introduced DNA could not recapitulate the selectivity for myogenin observed in vivo. The results identify new target genes for myogenin and show that myogenin's target gene selectivity is not based solely on binding site sequences

Ovine Domestication and Diversity

Sheep are a highly versatile and adaptable domestic species. Dissection of the genetics responsible for the ovine domestic phenotype relies on an understanding of the genetic variability that resides within and between breeds and also knowledge regarding both the maternal and paternal origins of sheep. Mitochondrial DNA was investigated in the search for novel 'Ovis aries' matrilines and the complete mitogenome sequenced from a subset of domestic and wild sheep to resolve the phylogenetic relationships between these groups. A fifth domestic lineage was identified in sheep from the Near East, a proposed centre of domestication. Mitogenome analysis revealed no wild sheep introgression in the five 'O. aries' groups. To contrast this maternal picture, variation in the male-specific region of the ovine Y chromosome was investigated. Seven novel single nucleotide polymorphisms and a previously uncharacterised microsatellite from the ovine sex determining gene region were used to generate 17 paternal haplotypes. Analysis of these markers across wild and domestic sheep again failed to identify signatures of wild Ovis introgression in modern sheep. The emerging picture of male mediated domestication suggested that there are at least two patrilines present within 'O. aries'. One of these has a possible European origin and the other, a less restricted distribution. Genetic diversity and linkage disequilibrium (LD) was characterised using autosomal microsatellites. Five domestic populations were investigated, with the result that in genetically diverse breeds, LD extended for only short distances, whilst more homogeneous populations displayed extensive patterns of LD. This clearly illustrated the impact of population history on the extent LD and will inform subsequence gene mapping studies in sheep. The three classes of genetic variation investigated (autosomal, paternal and maternal), each reveal aspects of the genetic architecture present within domestic sheep and only by assaying each of these, will the true picture of ovine domestic and diversity be revealed

Системний підхід у соціальній адаптації студентів-іноземців

SUMMARY: High-throughput genotyping and sequencing technologies facilitate studies of complex genetic traits and provide new research opportunities. The increasing popularity of genome-wide association studies (GWAS) leads to the discovery of new associated loci and a better understanding of the genetic architecture underlying not only diseases, but also other monogenic and complex phenotypes. Several softwares are available for performing GWAS analyses, R environment being one of them. RESULTS: We present cgmisc, an R package that enables enhanced data analysis and visualisation of results from GWAS. The package contains several utilities and modules that complement and enhance the functionality of the existing software. It also provides several tools for advanced visualisation of genomic data and utilises the power of the R language to aid in preparation of publication-quality figures. Some of the package functions are specific for the domestic dog (Canis familiaris) data. AVAILABILITY: The package is operating system-independent and is available from: https://github.com/cgmisc-team/cgmisc CONTACT: [email protected]

Increasing the availability and utilization of reliable data on population micronutrient (MN) status globally: the MN Data Generation Initiative.

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support

Downregulation of hepatic stem cell factor by Vivo-Morpholino treatment inhibits mast cell migration and decreases biliary damage/senescence and liver fibrosis in Mdr2−/− mice

Introduction Primary sclerosing cholangitis (PSC) is characterized by increased mast cell (MC) infiltration, biliary damage and hepatic fibrosis. Cholangiocytes secrete stem cell factor (SCF), which is a chemoattractant for c-kit expressed on MCs. We aimed to determine if blocking SCF inhibits MC migration, biliary damage and hepatic fibrosis. Methods FVB/NJ and Mdr2−/− mice were treated with Mismatch or SCF Vivo-Morpholinos. We measured (i) SCF expression and secretion; (ii) hepatic damage; (iii) MC migration/activation and histamine signaling; (iv) ductular reaction and biliary senescence; and (v) hepatic fibrosis. In human PSC patients, SCF expression and secretion were measured. In vitro, cholangiocytes were evaluated for SCF expression and secretion. Biliary proliferation/senescence was measured in cholangiocytes pretreated with 0.1% BSA or the SCF inhibitor, ISK03. Cultured HSCs were stimulated with cholangiocyte supernatant and activation measured. MC migration was determined with cholangiocytes pretreated with BSA or ISK03 loaded into the bottom of Boyden chambers and MCs into top chamber. Results Biliary SCF expression and SCF serum levels increase in human PSC. Cholangiocytes, but not hepatocytes, from SCF Mismatch Mdr2−/− mice have increased SCF expression and secretion. Inhibition of SCF in Mdr2−/− mice reduced (i) hepatic damage; (ii) MC migration; (iii) histamine and SCF serum levels; and (iv) ductular reaction/biliary senescence/hepatic fibrosis. In vitro, cholangiocytes express and secrete SCF. Blocking biliary SCF decreased MC migration, biliary proliferation/senescence, and HSC activation. Conclusion Cholangiocytes secrete increased levels of SCF inducing MC migration, contributing to biliary damage/hepatic fibrosis. Targeting MC infiltration may be an option to ameliorate PSC progression