In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections

High-efficiency tooth bleaching using non-thermal atmospheric pressure plasma with low concentration of hydrogen peroxide

Light-activated tooth bleaching with a high hydrogen peroxide (HP; H(2)O(2)) concentration has risks and the actual role of the light source is doubtful. The use of conventional light might result in an increase in the temperature and cause thermal damage to the health of the tooth tissue. OBJECTIVE: This study investigated the efficacy of tooth bleaching using non-thermal atmospheric pressure plasma (NAPP) with 15% carbamide peroxide (CP; CH(6)N(2)O(3)) including 5.4% HP, as compared with conventional light sources. MATERIAL AND METHODS: Forty human teeth were randomly divided into four groups: Group I (CP+NAPP), Group II (CP+plasma arc lamp; PAC), Group III (CP+diode laser), and Group IV (CP alone). Color changes (ΔE ) of the tooth and tooth surface temperatures were measured. Data were evaluated by one-way analysis of variance (ANOVA) and post-hoc Tukey's tests. RESULTS: Group I showed the highest bleaching efficacy, with a ΔE value of 1.92-, 2.61 and 2.97-fold greater than those of Groups II, III and IV, respectively (P<0.05). The tooth surface temperature was maintained around 37ºC in Group I, but it reached 43ºC in Groups II and III. CONCLUSIONS: The NAPP has a greater capability for effective tooth bleaching than conventional light sources with a low concentration of HP without causing thermal damage. Tooth bleaching using NAPP can become a major technique for in-office bleaching in the near future

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function

Myc-regulated microRNAs attenuate embryonic stem cell differentiation

Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

The Role of Digital Rectal Examination for Diagnosis of Acute Appendicitis: A Systematic Review and Meta-Analysis

Background: Digital rectal examination (DRE) has been traditionally recommendedto evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No metaanalysis has examined DRE for diagnosis of acute appendicitis. Objectives: To assess the role of DRE for diagnosis of acute appendicitis. Data Sources: Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions. Study Selection: Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis. Data Extraction and Synthesis: Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI). Main Outcomes and Measures: The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis. Results: We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42-0.56) and 0.61 (95% CI 0.53-0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97-1.58) and 0.85 (95% CI 0.70-1.02), respectively. The DOR was 1.46 (0.95-2.26). Conclusion and Relevance: Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis