Topical Flunixin Meglumine Effects on Pain Associated Biomarkers after Dehorning

Twenty-four calves were dehorned and treated with either topical flunixin meglumine formulated for systemic absorption or a placebo. Biomarkers associated with pain were evaluated for up to 72 hour after the dehorning procedure. Plasma cortisol concentrations, 90 minutes post-dehorning, and mechanical nociception threshold at the control site were the only tested biomarkers where a significant difference was demonstrated. No other differences of biomarkers between the two dehorned groups were observed for any time points. Although this product is easy to dose and dispense, its effects on pain biomarkers appears to be negligible

DNA Testing Reveals the Putative Identity of JB55, a 19th Century Vampire Buried in Griswold, Connecticut

In 1990 in Griswold, Connecticut, archaeologists excavated a burial found in a "skull and crossbones" orientation. The lid of the 19th century coffin had brass tacks that spelled "JB55", the initials of the person lying there and age at death. JB55 had evidence of chronic pulmonary infection, perhaps tuberculosis. It is possible that JB55 was deemed a vampire due to his disease, and therefore had to be "killed" by mutilating his corpse. In an attempt to reveal the identity of JB55, DNA testing was performed. Ancestry informative single nucleotide polymorphism (SNP) analysis using the Precision ID Ancestry Panel indicated European ancestry. A full Y-chromosomal short tandem repeat (Y-STR) profile was obtained, belonging to haplogroup R1b. When the Y-STR profile was searched in the publicly accessible FamilyTreeDNA R1b Project website, the two closest matches had the surname "Barber". A search of historical records led to a death notice mentioning John Barber, whose son Nathan Barber was buried in Griswold in 1826. The description of Nathan Barber closely fits the burial of "NB13," found near JB55. By applying modern forensic DNA tools to a historical mystery, the identity of JB55 as John Barber, the 19th century Connecticut vampire, has been revealed

Bacterial Community Profiling of Milk Samples as a Means to Understand Culture-Negative Bovine Clinical Mastitis

Inflammation and infection of bovine mammary glands, commonly known as mastitis, imposes significant losses each year in the dairy industry worldwide. While several different bacterial species have been identified as causative agents of mastitis, many clinical mastitis cases remain culture negative, even after enrichment for bacterial growth. To understand the basis for this increasingly common phenomenon, the composition of bacterial communities from milk samples was analyzed using culture independent pyrosequencing of amplicons of 16S ribosomal RNA genes (16S rDNA). Comparisons were made of the microbial community composition of culture negative milk samples from mastitic quarters with that of non-mastitic quarters from the same animals. Genomic DNA from culture-negative clinical and healthy quarter sample pairs was isolated, and amplicon libraries were prepared using indexed primers specific to the V1–V2 region of bacterial 16S rRNA genes and sequenced using the Roche 454 GS FLX with titanium chemistry. Evaluation of the taxonomic composition of these samples revealed significant differences in the microbiota in milk from mastitic and healthy quarters. Statistical analysis identified seven bacterial genera that may be mainly responsible for the observed microbial community differences between mastitic and healthy quarters. Collectively, these results provide evidence that cases of culture negative mastitis can be associated with bacterial species that may be present below culture detection thresholds used here. The application of culture-independent bacterial community profiling represents a powerful approach to understand long-standing questions in animal health and disease

Topical Flunixin Meglumine Effects on Pain Associated Biomarkers after Dehorning

Twenty-four calves were dehorned and treated with either topical flunixin meglumine formulated for systemic absorption or a placebo. Biomarkers associated with pain were evaluated for up to 72 hour after the dehorning procedure. Plasma cortisol concentrations, 90 minutes post-dehorning, and mechanical nociception threshold at the control site were the only tested biomarkers where a significant difference was demonstrated. No other differences of biomarkers between the two dehorned groups were observed for any time points. Although this product is easy to dose and dispense, its effects on pain biomarkers appears to be negligible.</p

BRAF Polymorphisms and Risk of Melanocytic Neoplasia

Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case–control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%. This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2%

Local administration of vancomycin powder in orthopaedic fracture surgery: current practice and trends

Abstract. Objectives:. Surgical site infections in orthopaedic trauma are a significant problem with meaningful patient and health care system–level consequences. Direct application of antibiotics to the surgical field has many potential benefits in reducing surgical site infections. However, to date, the data regarding the local administration of antibiotics have been mixed. This study reports on the variability of prophylactic vancomycin powder use in orthopaedic trauma cases across 28 centers. Methods:. Intrawound topical antibiotic powder use was prospectively collected within three multicenter fracture fixation trials. Fracture location, Gustilo classification, recruiting center, and surgeon information were collected. Differences in practice patterns across recruiting center and injury characteristics were tested using chi-square statistic and logistic regression. Additional stratified analyses by recruiting center and individual surgeon were performed. Results:. A total of 4941 fractures were treated, and vancomycin powder was used in 1547 patients (31%) overall. Local administration of vancomycin powder was more frequent in open fractures 38.8% (738/1901) compared with closed fractures 26.6% (809/3040) (P < 0.001). However, the severity of the open fracture type did not affect the rate at which vancomycin powder was used (P = 0.11). Vancomycin powder use varied substantially across the clinical sites (P < 0.001). At the surgeon level, 75.0% used vancomycin powder in less than one-quarter of their cases. Conclusions:. Prophylactic intrawound vancomycin powder remains controversial with varied support throughout the literature. This study demonstrates wide variability in its use across institutions, fracture types, and surgeons. This study highlights the opportunity for increased practice standardization for infection prophylaxis interventions. Level of Evidence:. Prognostic—III

CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies

OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin.

Item does not contain fulltextWe ascertained a multi-generation Malaysian family with Joubert syndrome (JS). The presence of asymptomatic obligate carrier females suggested an X-linked recessive inheritance pattern. Affected males presented with mental retardation accompanied by postaxial polydactyly and retinitis pigmentosa. Brain MRIs showed the presence of a "molar tooth sign," which classifies this syndrome as classic JS with retinal involvement. Linkage analysis showed linkage to Xpter-Xp22.2 and a maximum LOD score of 2.06 for marker DXS8022. Mutation analysis revealed a frameshift mutation, p.K948NfsX8, in exon 21 of OFD1. In an isolated male with JS, a second frameshift mutation, p.E923KfsX3, in the same exon was identified. OFD1 has previously been associated with oral-facial-digital type 1 (OFD1) syndrome, a male-lethal X-linked dominant condition, and with X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2). In a yeast two-hybrid screen of a retinal cDNA library, we identified OFD1 as an interacting partner of the LCA5-encoded ciliary protein lebercilin. We show that X-linked recessive mutations in OFD1 reduce, but do not eliminate, the interaction with lebercilin, whereas X-linked dominant OFD1 mutations completely abolish binding to lebercilin. In addition, recessive mutations in OFD1 did not affect the pericentriolar localization of the recombinant protein in hTERT-RPE1 cells, whereas this localization was lost for dominant mutations. These findings offer a molecular explanation for the phenotypic spectrum observed for OFD1 mutations; this spectrum now includes OFD1 syndrome, SGBS2, and JS