Attitudes of Mexican anesthesiologists to indicate preoperative fasting periods: A cross-sectional survey

BACKGROUND: In Mexico, guidelines for fasting periods, or any audits on this topic are unavailable, and therefore the attitudes of anesthesiologists for recommending preoperative fasting periods are unknown. MATERIAL AND METHODS: The study was a cross-sectional survey of anesthesiologists subscribed to the Annual Updated Course, organized by the Sociedad Mexicana de Anestesiologia in 2000. The response rate was 31.4%. RESULTS: Most respondents were general anesthesiologists, with 5 or more years experience in a clinical post, were working in both public and private hospitals, and were performing anesthetic procedures on both pediatric and adult patients and in both ambulatory and hospitalized patients. Approximately 23% of the respondents considered natural fruit juices to be clear liquids. For a pediatric patient ingesting breast milk 1 h before undergoing a surgical procedure, 45% thought that surgery should be delayed for 3h, followed by those delaying the surgical procedure for 6 to 8 h. Our results show that more than 50% of the anesthesiologists had better defined attitudes for fasting milk and clear liquids in patients of 6 month or under than for older children and adults. However, due to the poor definition or pre-operative fasting, using clear liquids, in all other patient groups, several patients are allowed to go without oral clear liquids administration for prolonged periods. CONCLUSION: Preoperative fasting periods recommended by Mexican anesthesiologists differ from international guidelines

Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline

Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility

Assessment of age-related changes in pediatric gastrointestinal solubility

PurposeCompound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.MethodsSolubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.ResultsFor six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).ConclusionDevelopmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.<br/