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A (FeII)6-coordinated triply interlocked (“Star of David”) [2]catenane (612 link) and a (FeII)5-coordinated pentafoil (51) knot are found to selectively transport anions across phospholipid bilayers. Allostery, topology, and building block stoichiometry all play important roles in the efficacy of the ionophoric activity. Multiple FeII cation coordination by the interlocked molecules is crucial: the demetalated catenane exhibits no anion binding in solution nor any transmembrane ion transport properties. However, the topologically trivial, Lehn-type cyclic hexameric FeII helicates—which have similar anion binding affinities to the metalated Star of David catenane in solution—also display no ion transport properties. The unanticipated difference in behavior between the open- and closed-loop structures may arise from conformational restrictions in the linking groups that likely enhances the rigidity of the channel-forming topologically complex molecules. The (FeII)6-coordinated Star of David catenane, derived from a hexameric cyclic helicate, is 2 orders of magnitude more potent in terms of ion transport than the (FeII)5-coordinated pentafoil knot, derived from a cyclic pentamer of the same building block. The reduced efficacy is reminiscent of multisubunit protein ion channels assembled with incorrect monomer stoichiometries.

BACKGROUND: Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex. METHODS: We conducted a retrospective cohort study using 2010–2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12–5 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region. RESULTS: After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. No interaction was found in adjusted sampling-weighted model between sex and race/ethnicity on the odds of receiving opioids (P = .74). There was no difference in opioid administration to males as compared to females (odds ratio [OR] = 0.96, 95% CI, 0.87–1.06; P = .42) or to non-Caucasians as compared to Caucasians (OR = 0.99, 95% CI, 0.89–1.10; P = .84). In adjusted weighted models, non-Caucasian males, 123,12½39,457 (51.4%) did not differ from Caucasian non-Hispanic males, 317,427/525,434 (60.4%), on odds of receiving opioids, aOR = 0.88, 95% CI, 0.39–1.99; P = .75. Non-Caucasian females, 547,709/847,675 (64.6%) also did not differ from Caucasian females, 621,638/1,010,360 (61.5%), on odds of receiving opioids, aOR = 1.01, 95% CI, 0.53–1.90; P = .98. Across both sexes, non-Caucasians did not differ from Caucasians on receipt of nonopioid analgesics or antiemetics. Neither wait time to see a provider nor the length of the hospital visit was significantly different between sexes or race/ethnicities. CONCLUSIONS: Based on National Hospital Ambulatory Medical Care Survey data from 2010 to 2014, there is no statistically significant interaction between race/ethnicity and sex for administration of opioid analgesia to people presenting to the ED with appendicitis or gallbladder disease. These results suggest that the joint effect of patient race/ethnicity and sex may not manifest in disparities in opioid management. (Anesth Analg 2019;128:1005–12)

We report the two-step synthesis of a molecular trefoil knot in 90 % overall yield through the self-assembly of a twelve-component trimeric circular zinc helicate followed by ring closing metathesis of six pendant alkene chains. Both the trimeric circular helicate intermediate and the resulting trefoil knot were characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography.

Guest encapsulation underpins the functional properties of self-assembled capsules yet identifying systems capable of strongly binding small organic molecules in solution remains a challenge. Most coordination capsules rely on the hydrophobic effect to ensure effective solution-phase association. In contrast, we show that using non-interacting anions in apolar solvents can maximize favorable interactions between a cationic Pd2L4 host and charge-neutral guests resulting in a dramatic increase in binding strength. With quinone-type guests, association constants in excess of 108 m−1 were observed, comparable to the highest previously recorded constant for a metallosupramolecular capsule. Modulation of optoelectronic properties of the guests was also observed, with encapsulation either changing or switching-on luminescence not present in the bulk phase.

Radical depolymerisation is the method of choice for the depolymerisation of glycosaminoglycans (GAGs), especially when enzymatic depolymerisation cannot be performed due to the lack of suitable enzymes. The established Fenton type free radical depolymerisation generates radicals from a solution of H2O2 in the presence of Cu(2+) or Fe(2+). When applied to dermatan sulfate (DS), the Fenton type depolymerisation of DS (Panagos, Thomson, Bavington, & Uhrin, 2012) produced exclusively oligosaccharides with reducing end GalNAc, which was partially oxidised to acetylgalactosaminic acid. We report here the results of the TiO2 catalysed photochemical depolymerisation of DS. NMR analysis of these DS oligosaccharides revealed the presence of reducing end IdoA, observed for the first time. The reducing end acetylgalactosaminic acid was also detected. The photochemical depolymerisation method thus enables preparation of new types of GAG oligosaccharides suitable for further biochemical and biological investigation.

Esophagectomy is associated with significant morbidity. Optimizing perioperative fluid administration is one potential strategy to mitigate morbidity. We sought to investigate the relationship of intraoperative fluid (IOF) administration to outcomes in patients undergoing transhiatal esophagectomy with particular attention to malnourished patients, who may be more susceptible to the effects of fluid overload.Patients who underwent transhiatal esophagectomy from 2000-2013 were identified from a retrospective database. IOF rates (mL/kg/hr) were determined and their relationship to outcomes compared. To examine the impact of malnutrition, we stratified patients based on median preoperative serum albumin and compared outcomes.211 patients comprised the cohort. 74% of patients underwent esophagectomy for esophageal adenocarcinoma. Linear regression analyses were performed comparing independent perioperative variables to four outcomes variables: length of stay, complications per patient, major complications, and Clavien-Dindo classification. IOF rate was significantly associated with three of four outcomes on univariate analysis. Significantly more patients with a preoperative albumin level ≤3.7 g/dL who received more than the median IOF rate experienced more severe complications.Increased intraoperative fluid administration is associated with perioperative morbidity in patients undergoing transhiatal esophagectomy. Patients with lower preoperative albumin levels may be particularly sensitive to the effects of volume overload.

Objective Standard postoperative therapy for pancreatic cancer consists of both chemotherapy alone and chemoradiation. We sought to investigate whether the sequence of chemotherapy and chemoradiation and overall time to initiation of adjuvant therapy would impact local vs. distant recurrence. Methods After Institutional Review Board approval, resected pancreas cancer patient charts were evaluated for medical background, surgical, pathological, chemoradiation (CRT), and follow-up. Local recurrence (LR) was defined as failures occurring in the postoperative bed and regional lymph nodes. Early vs. late CRT was defined by whether CRT was given early (within 1-2 cycles of adjuvant chemotherapy) or late in the course of adjuvant chemotherapy (after the 3rd cycle of chemotherapy). The postoperative interval variance was compared to LR factors such as progression-free survival (PFS) and overall survival (OS). Results Of the 34 eligible patients, 47% (n=16) underwent early CRT and 41% (n=14) underwent late CRT. 12% (n=14) did not undergo any induction chemotherapy. At median follow-up of 22 months, 53% (n=18) had metastases, 24% (n=8) had LR, and 24% (n=8) were disease free. Kaplan-Meier curves revealed that early vs. late CRT did not appear to significantly impact OS (p=0.63), PFS (p=0.085) or LR (p=0.19). Postoperative interval did not affect PFS (p=0.42) or OS (p=0.93). Conclusions Early vs. late CRT and the time to initiation of adjuvant therapy were not significantly associated with LR in patients with resected pancreatic cancer. Future prospective studies are required to determine if sequencing of chemotherapy, CRT, or the postoperative interval impact survival and patterns of recurrence.

Cobalt(III) tetrahedral capsules have been prepared using an assembly-followed-by-oxidation protocol from a cobalt(II) precursor and a readily derivatizable pyridyl-triazole ligand system. Experiments designed to probe the constitutional dynamics show that these architectures are in a non-equilibrium state. A preliminary investigation into the host-guest chemistry of a water-soluble derivative shows it can bind and differentiate a range of different neutral organic molecules. The stability of this ensemble also permits the study of guest-binding at high salt concentrations.

STUDY OBJECTIVE—To illustrate the concept of "individualised fallacy", the result of improper interpretation and inference about aggregate level associations on the basis of associations at the individual level, in epidemiology. DESIGN—Cohort study. SETTING—Canadian province of Ontario. PATIENTS—All patients who underwent primary appendicectomy in 175 Ontario hospitals from 1989 to 1992. The association between rate of normal appendix removal and time to surgery was analysed at two levels: (1) at individual patient level, in which, for each patient, the exact number of days to surgery was derived, and (2) at hospital level, in which hospital specific proportions of time to surgery was calculated. MAIN RESULTS—Measured at individual level, compared with patients who had an operation on the same day of admission, the odds ratio was 2.41 (95% confidence intervals 2.28, 2.56) for patients who had an operation > 1 day after admission. Measured at hospital level, each 10% increase in the proportion of patients who had an operation > 1 day after admission resulted in a 15% reduction in the odds of normal appendix removal (odds ratio 0.85, 95% confidence intervals 0.82, 0.88) CONCLUSIONS—In this case study, hospital level measure correctly predicted a reduction in the rate of normal appendix removal by delaying surgery, whereas individual level measure biased the direction of the relation to the opposite. This example illustrates that bias in across level inference can occur either at individual or ecological level. The preferred level of analysis is the one that minimises confounding; often, it must be selected on the basis of a priori knowledge of the subject area. Keywords: epidemiological method; ecological fallacy; individualised fallacy

BackgroundOver recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques.MethodsOne hundred and forty‐eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri‐operative outcomes were compared.ResultsVascular intra‐operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra‐operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73.ConclusionLigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD.

Background Given their frequency of occurrence in the United States, cancer and heart disease often coexist. For patients requiring open-heart surgery, this raises concern that the use of cardiopulmonary bypass (CPB) may cause a transient immunosuppression with the potential to promote the spread and growth of coexisting cancer cells. This study examined the association of cardiopulmonary bypass with cancer progression in a large population-based setting using linked data from several state-wide registries. Methods A retrospective cohort study of cancer risk, stage, and mortality in 43,347 patients who underwent coronary artery bypass graft (CABG) surgery with and without CPB in New Jersey between 1998–2004 was conducted. A competing risk analogue of the Cox proportional hazards model with propensity score adjustment and regression on the cause-specific hazard was used to compute relative risk ratios (95% confidence intervals [CIs]) for patients undergoing CABG surgery with and without CPB. Results An increased risk for overall cancer incidence (17%) and cancer-specific mortality (16% overall, 12% case fatality) was observed; yet these results did not reach statistical significance. Of 11 tumor-specific analyses, an increased risk of skin melanoma (1.66 [95% CI, 1.08-2.55: p=0.02]) and lung cancer (1.36 [95% CI, 1.02-1.81: p=0.03]) was observed for patients with pump versus off-pump open-heart surgery. No association was found with cancer stage. Conclusions These results suggest that there may be a relationship between CPB and cancer progression. However, if real, the effect is likely modest at most. Further research may still be warranted with particular focus on skin melanoma and lung cancer which had the strongest association with CPB.