Validation of SmartRank: A likelihood ratio software for searching national DNA databases with complex DNA profiles.

Searching a national DNA database with complex and incomplete profiles usually yields very large numbers of possible matches that can present many candidate suspects to be further investigated by the forensic scientist and/or police. Current practice in most forensic laboratories consists of ordering these 'hits' based on the number of matching alleles with the searched profile. Thus, candidate profiles that share the same number of matching alleles are not differentiated and due to the lack of other ranking criteria for the candidate list it may be difficult to discern a true match from the false positives or notice that all candidates are in fact false positives. SmartRank was developed to put forward only relevant candidates and rank them accordingly. The SmartRank software computes a likelihood ratio (LR) for the searched profile and each profile in the DNA database and ranks database entries above a defined LR threshold according to the calculated LR. In this study, we examined for mixed DNA profiles of variable complexity whether the true donors are retrieved, what the number of false positives above an LR threshold is and the ranking position of the true donors. Using 343 mixed DNA profiles over 750 SmartRank searches were performed. In addition, the performance of SmartRank and CODIS were compared regarding DNA database searches and SmartRank was found complementary to CODIS. We also describe the applicable domain of SmartRank and provide guidelines. The SmartRank software is open-source and freely available. Using the best practice guidelines, SmartRank enables obtaining investigative leads in criminal cases lacking a suspect.

Methylation of LOXL1 Promoter by DNMT3A in Aged Human Skin Fibroblasts.

Lysyl oxidase-like 1 (LOXL1) is an amino-oxidase involved in maturation of elastic fibers. Its downregulation has been associated with elastic fibers repair loss in aging aorta, lung, ligament, and skin. Several evidences of LOXL1 epigenetic silencing by promoter methylation were reported in cancer and cutis laxa syndrome. We hypothesized that this mechanism could be implicated in skin aging process, as far as elastic fibers are also concerned. Anti-DNMT3A chromatin immunoprecipitation was conducted with nuclear extracts from skin fibroblasts isolated from young and elderly individuals, and showed a higher level of DNMT3A protein binding to the LOXL1 promoter in older cells concomitantly to the decrease of LOXL1 mRNA expression and the increase of LOXL1 promoter methylation. Using luciferase reporter assay driven by LOXL1 promoter in HEK293 cells, we demonstrated that LOXL1 transcriptional activity was dramatically reduced when a recombinant DNMT3A was concomitantly overexpressed. LOXL1 promoter transcriptional activity was restored in the presence of a broad-spectrum inhibitor of DNMT activity, 5-aza-2'-deoxycytidine. Finally, to assess whether the interplay between DNMT3A and LOXL1 promoter could be targeted to increase LOXL1 mRNA expression level, an Origanum majorana extract was selected among 43 plant extracts as a new inhibitor of human DNMT3A activity to restore LOXL1 secretion without cytotoxicity in aged skin fibroblasts.

Predictors of desaturation during patient transport to the postoperative anesthesia care unit: an observational study.

BACKGROUND: The transport of postoperative patients to the postoperative anesthesia care unit (PACU) is a high-risk period for hypoxemia. The aim of this study was to determine risk factors for hypoxemia during transfers to the PACU. METHODS: An observational, prospective, monocentric, and noninterventional study was conducted in the University Hospital of Toulouse in 2015 during a 5-week period. All patients who were transferred to PACU were included. Twenty-eight variables related to patient, surgery, and anesthesia were recorded. Hypoxemia during transfer was defined as Spo2 <90%. RESULTS: Five hundred five patients were included. The incidence of hypoxemia during transfer was 13%. After logistic regression analysis, 3 risk factors for desaturation were identified: sedation score >2, Spo2 <96% before exiting the operating room (OR), and body mass index >30 kg/m2. The 72% of patients were transferred without oxygen. Most of the hypoxemia appears in these patients. CONCLUSION: The development of hypoxemia during transfer from the OR to the PACU was greater in patients who were obese, were more sedated, or had lower oxygen saturations upon leaving the OR. The rates of hypoxemia were greater among patients in whom supplemental oxygen was not administered. Supplemental oxygen should be considered in higher risk patients.