Relevance of tumor angiogenesis patterns as a diagnostic value and prognostic indicator in oral precancer and cancer

Tumor angiogenesis occurs by recruitment of endothelial cell precursors or by sprouting of existing capillaries, which differ from the normal vasculature by having an altered morphology that can be exploited for diagnosis and as a prognostic indicator. Improved technologies have propelled diagnosis into a new era. These technologies have to be used with great precision. The diagnosis of a dysplastic premalignant lesion of the oral mucosa cannot be based solely on clinical findings. Therefore histologic evaluation of a representative biopsy specimen is necessary. Accurate judgment of the proper site for biopsy is essential for reaching a correct diagnosis. The aim of this report is to analyze the vascular patterns with the help of direct oral microscopy and the technique of stereo-optical microscopy in the oral cavity to select biopsy sites, and compare the outcome of a directed biopsy with that of biopsy specimens obtained from sites selected solely on the basis of clinical criteria. The study sample comprised 50 oral mucosal lesions. A statistically significant difference was noted between samples judged to be microscopically representative sites. We conclude that this method would aid in early and better diagnosis and treatment planning of oral premalignant and malignant lesions by assessing the various vascular patterns in the mucosa

Double vitrification and warming of blastocysts does not affect IVF implantation rates, or birth outcomes

Research question: Does double blastocyst vitrification and warming affect pregnancy rates from embryos subjected to PGT-A testing? Design: This is a retrospective observational analysis of embryo transfers performed at a single Centre between January 2017 and August 2022. The double vitrification (DV) group included frozen blastocysts that were vitrified after 5-7 days of culture, warmed, biopsied (either once or twice) and re-vitrified. The single vitrification (SV) group included fresh blastocysts that were biopsied at 5-7 days, and then vitrified. Results: Comparison of the 84 DV blastocysts and 729 control SV blastocysts indicated that the DV embryos were frozen later in development and had expanded more than the SV embryos. Of the 813 embryo transfer procedures reported in this study, 452 resulted in the successful delivery of healthy infants (56%). There were however no significant differences between DV and SV embryos in the pregnancy rates achieved after single embryo transfer (55% vs 56%). Logistic regression indicated that while reduced pregnancy rates were associated with increasing maternal age at oocyte collection and at embryo transfer, and with longer culture prior to freezing, DV was not a significant predictor of outcome. Conclusions: Blastocyst DV was not shown to impact pregnancy rates. While caution is necessary due to the study size, no effects of DV on miscarriage rates, birth weight or gestation period were noted. These data offer reassurance given the absence of influence of DV on pregnancy rates after PGT-A

Trust Perceptions of Online Travel Information by Different Content Creators: Some Social and Legal Implications

Consumers are increasingly turning to the online environment to provide information to assist them in making purchase decisions related to travel products. They often rely on travel recommendations from different sources, such as sellers, independent experts and, increasingly, other consumers. A new type of online content, usergenerated content (UGC), provides a number of legal and social challenges to providers and users of that content, especially in relation to areas such as defamation, misrepresentation and social embarrassment. This paper reports research that examined the level of trustworthiness of online travel information from these different sources. The study used a survey of Australian travel consumers (n= 12,000) and results support the notion that there are differences in the level of trust for online travel information from different sources. Respondents ‘tended to agree’ that they trusted information provided by travel agents, information from commercial operators and comments made by travellers on third party websites. However, the highest level of trust was afforded to information provided on State government tourism websites. These results suggest that greater trust is placed in online travel comments when they are on a specific travel website than when they are on a more generic social networking website. However, respondents were ‘not sure’ that they trusted comments made by travellers on weblogs and on social networking sites. Some 88% of respondents that had not visited UGC websites (or were unsure if they had) indicated that they thought that UGC would be useful in the future – suggesting that they feel that any concerns they may have in relation to legal and social problems resulting from its use will be resolved

Genome-Wide Linkage Scan to Identify Loci Associated with Type 2 Diabetes and Blood Lipid Phenotypes in the Sikh Diabetes Study

In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using Sall statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance

Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in <it>NOD1 </it>gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of <it>NOD1 </it>gene in context to Indian population.</p> <p>Methods</p> <p>A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of <it>NOD1 </it>gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's χ²test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12.</p> <p>Results</p> <p>We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of <it>NOD1 </it>gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, <it>p </it>= 0.002; L349P, <it>p </it>= 0.002 and L370R, <it>p </it>= 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg²⁺binding sites. No significant association was observed within different sub phenotypes.</p> <p>Conclusion</p> <p>We propose that the location of mutations in the Exon 6 spanning the ATP and Mg²⁺binding site of NBD in <it>NOD1 </it>gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility.</p

A case for increased private sector involvement in Ireland's national animal health services

Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise) of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia). The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise) of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands)

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

<p>Abstract</p> <p>Background</p> <p>Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke <it>et al</it>., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance.</p> <p>Methods</p> <p>Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ², Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing.</p> <p>Results</p> <p>The rs5771069 (<it>IL17REL</it>) SNP was not associated with UC in the Danish panel. The rs5771069 (<it>IL17REL</it>) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 <it>(SMURF1/KPNA7) </it>and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 <it>(SMURF1/KPNA7) </it>in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.</p> <p>Statistically significant P_BDwas found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).</p> <p>No SNP reached genome-wide significance in the combined analyses of all the panels.</p> <p>Conclusions</p> <p>This replication study supports an important role for the studied rs5771069 (<it>IL17REL</it>) SNP, but not for rs7809799 (<it>SMURF1</it>/<it>KPNA7</it>), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (<it>TCP11</it>) in UC etiology between the Nordic and the other European populations.</p

Community-based directly observed therapy (DOT) versus clinic DOT for tuberculosis: a systematic review and meta-analysis of comparative effectiveness.

Background: Directly observed therapy (DOT), as recommended by the World Health Organization, is used in many countries to deliver tuberculosis (TB) treatment. The effectiveness of community-based (CB DOT) versus clinic DOT has not been adequately assessed to date. We compared TB treatment outcomes of CB DOT (delivered by community health workers or community volunteers), with those achieved through conventional clinic DOT. Methods: We performed a systematic review and meta-analysis of studies before 9 July 2014 comparing treatment outcomes of CB DOT and clinic DOT. The primary outcome was treatment success; the secondary outcome was loss to follow-up. Results: Eight studies were included comparing CB DOT to clinic DOT, one a randomised controlled trial. CB DOT outperformed clinic DOT treatment success (pooled odds ratio (OR) of 1.54, 95% confidence interval (CI) 1.01 – 2.36, p = 0.046, I2 heterogeneity 84%). No statistically significant difference was found between the two DOT modalities for loss to follow-up (pooled OR 0.86, 95% CI 0.48 to 1.55, p = 0.62, I2 83%). Conclusions: Based on this systematic review, CB DOT has a higher treatment success compared to clinic DOT. However, as only one study was a randomised controlled trial, the findings have to be interpreted with caution

B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE. Methods: We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice. Results: We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice. Conclusions: Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE