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Background: Internationally, Indigenous Peoples experience worse surgical outcomes than non-Indigenous patients, but equity of surgical care is less well studied in Canada. This study compares outcomes after appendectomy in First Nations and non--First Nations patients. Methods: In this population-based study, we reviewed administrative data of patients who underwent appendectomy between Apr. 1, 2004, and Mar. 31, 2017, in Northern Alberta. Demographic variables and characteristics of surgical care for First Nations and non--First Nations patients were collected. We identified adverse outcomes by the presence of predefined administrative codes. We identified variables related to a complex postoperative course (at least 1 of wound dehiscence, surgical site infection, abscess, bowel obstruction, pneumonia, deep vein thrombosis, sepsis, emergency department visit, readmission or death within 30 d after appendectomy) through a logistic regression model, and those related to longer length of stay using a Cox proportional hazards model. Results: A total of 28453 patients met the selection criteria, of whom 1737 (6.1%) had First Nations status. Compared to non-First Nations patients, First Nations patients were younger, lived farther away from the hospital of their appendectomy, were in lower socioeconomic quintiles, and had higher rates of obesity and diabetes (all p < 0.001). After adjustment for age, sex, distance to hospital, socioeconomic deprivation and comorbidities, First Nations status remained independently associated with higher rates of adverse outcomes (odds ratio 1.548, 95% confidence interval [CI] 1.384-1.733) and longer lengths of stay (hazard ratio 0.877, 95% CI 0.832-0.924). Conclusion: Although rurality, comorbidities and socioeconomic status contributed to worse outcomes after appendectomy for First Nations patients, First Nations status remained independently associated with worse surgical outcomes. Surgical care, an integral component of health care delivery, must be improved for First Nations patients in order to achieve equitable health care. Contexte : Partout dans le monde, l'issue des interventions chirurgicales est moins bonne chez les personnes des peuples autochtones que chez les non-Autochtones, mais l'équité en chirurgie est moins bien étudiée au Canada. La présente étude compare l'issue de l'appendicectomie chez des malades des Premières Nations et non des Premières Nations. Méthodes : Lors de cette étude menée dans la population, nous avons passé en revue les données administratives des malades ayant subi une appendicectomie entre le 1er avril 2004 et le 31 mars 2017 dans le Nord de l'Alberta. Nous avons recueilli les variables démographiques et les caractéristiques des chirurgies pour les malades des Premières Nations et non des Premières Nations. Nous avons recensé les complications, indiquées par des codes administratifs prédéfinis. Nous avons analysé les variables liées à un postop compliqué (soit au moins 1 parmi les complications suivantes : déhiscence ou infection de la plaie opératoire, abcès, obstruction intestinale, pneumonie, thrombose veineuse profonde, septicémie, consultation dans un service des urgences, réadmission ou décès dans les 30 jours suivant l'appendicectomie) au moyen d'un modèle de régression logistique, et les variables liées à la prolongation du séjour hospitalier au moyen du modèle à risques proportionnels de Cox. Résultats : En tout, 28453 malades répondaient aux critères de sélection et 1737 d'entre eux (6,1%) étaient membres des Premières Nations. Comparativement aux malades non des Premières Nations, les malades des Premières Nations étaient plus jeunes, vivaient plus loin du centre hospitalier où ils ont subi leur appendicectomie, se trouvaient dans les quintiles socio-économiques inférieurs et présentaient des taux d'obésité et de diabète plus élevés (tous p < 0,001). Après ajustement pour tenir compte de l'âge, du sexe, de la distance de l'hôpital, de la précarité socio-économique et des comorbidités, le fait d'être membre des Premières Nations est demeuré un facteur indépendamment associé à des taux plus élevés de complications (rapport des cotes 1,548, intervalle de confiance [IC] de 95% 1,384-1,733) et à des séjours hospitaliers plus longs (rapport de risque 0,877, IC de 95% 0,832-0,924). Conclusion : Même si la ruralité, les comorbidités et le statut socio-économique ont été associés à une issue post-appendicectomie négative chez les malades membres des Premières Nations, en soi, leur statut de membre des Premières Nations est resté un facteur indépendamment associé aux complications de la chirurgie. Les soins chirurgicaux, qui font partie intégrante de la prestation des soins, doivent être améliorés pour que les malades des Premières Nations reçoivent des soins de santé équitables., Disparities between First Nations patients and non--First Nations patients exist in multiple health measures. (1-3) Internationally, Indigenous Peoples experience worse outcomes across several surgical disciplines than non-Indigenous patients, (4-6) and [...]

Evolution has converged on cation-π interactions for recognition of quaternary alkyl ammonium groups such as trimethyllysine (Kme3). While computational modelling indicates that Trp provides the strongest cation-π interaction of the native aromatic amino acids, there is limited corroborative data from measurements within proteins. Herein we investigate a Tyr to Trp mutation in the binding pocket of the HP1 chromodomain, a reader protein that recognizes Kme3. Binding studies demonstrate that the Trp-mediated cation-π interaction is about -5 kcal mol-1 stronger, and the Y24W crystal structure shows that the mutation is not perturbing. Quantum mechanical calculations indicate that greater enthalpic binding is predominantly due to increased cation-π interactions. NMR studies indicate that differences in the unbound state of the Y24W mutation lead to enthalpy-entropy compensation. These results provide direct experimental quantification of Trp versus Tyr in a cation-π interaction and afford insight into the conservation of aromatic cage residues in Kme3 reader domains.

In 2008, Madoff Investment Securities was closed by the SEC. Owner Bernie Madoff was charged and later convicted for operating the largest Ponzi scheme in U.S. history. Even though the SEC investigated Madoff Investment Securities multiple times over a 16-year period, and even though at least six outsiders tried to warn the SEC of a potential Madoff Ponzi scheme, it took the crippling financial landscape of the 'great recession' to bring down the Madoff empire. The following article revisits the SEC investigation of Madoff Investment Securities, pointing out lapses in the SEC investigation based on SEC Inspector General H. David Kotz's report, Investigation of Failure of the SEC to Uncover Bernard Madoff's Ponzi scheme (SEC Case No. -OIG-509). Based on a review of the SEC Inspector General's report, further analysis suggests the potential for internal collusion at the SEC. Due to a series of lapses in performance of investigative duties; the SEC internal investigation should be reopened. Keywords: Forensic accounting, Ponzi scheme, INTRODUCTION In 1960, Bernard Madoff founded Madoff Investment Securities LLC. The firm operated for the next 48 years, investing funds for individuals and groups of investors. Through a series of [...]

Background: Ultrasonography for thyroid nodules is one of the most common imaging tests performed in the general population. Details from ultrasound reports guide biopsies and surgery. This study quantifies the [...]

Amide−π interactions, in which an amide interacts with an aromatic group, are ubiquitous in biology, yet remain understudied relative to other noncovalent interactions. Recently, we demonstrated that an electrostatically tunable amide−π interaction is key to recognition of histone acyllysine by the AF9 YEATS domain, a reader protein which has emerged as a therapeutic target due to its dysregulation in cancer. Amide isosteres are commonly employed in drug discovery, often to prevent degradation by proteases, and have proven valuable in achieving selectivity when targeting epigenetic proteins. However, like amide−π interactions, interactions of amide isosteres with aromatic rings have not been thoroughly studied despite widespread use. Herein, we evaluate the recognition of a series of amide isosteres by the AF9 YEATS domain using genetic code expansion to evaluate the amide isostere−π interaction. We show that compared to the amide−π interaction with the native ligand, each isostere exhibits similar electrostatic tunability with an aromatic residue in the binding pocket, demonstrating that the isosteres maintain similar interactions with the aromatic residue. We identify a urea‐containing ligand that binds with enhanced affinity for the AF9 YEATS domain, offering a promising starting point for inhibitor development. Furthermore, we demonstrate that carbamate and urea isosteres of crotonyllysine are resistant to enzymatic removal by SIRT1, a protein that cleaves acyl post‐translational modifications, further indicating the potential of amide isosteres in YEATS domain inhibitor development. These results also provide experimental precedent for interactions of these common drug discovery moieties with aromatic rings that can inform computational methods. [ABSTRACT FROM AUTHOR]