Intermolecular structure and hydrogen-bonding in liquid 1,2-propylene carbonate and 1,2-glycerol carbonate determined from neutron scattering

Neutron diffraction with isotopic substitution has been used to investigate the liquid structures of propylene carbonate and glycerol carbonate. C-H···O=C hydrogen-bonding motifs dominate the local structure of propylene carbonate, giving rise to the formation of head-to-tail correlated chains of molecules. In contrast, glycerol carbonate exhibits a more disordered structure with no overall dominant interactions in which the pendant hydroxyl function disrupts structure-making correlations present in propylene carbonate

Association and liquid structure of pyridine-acetic acid mixtures determined from neutron scattering using a ‘free proton’ EPSR simulation model

Hydrogen-bonded molecular acetic acid chains are observed in acid–base mixtures from small angle neutron diffraction.</p

Change in health literacy over a decade in a prospective cohort of community-dwelling older adults

BACKGROUND: Health literacy is often viewed as a static trait in longitudinal studies, which may over or underestimate an individual’s ability to manage one’s health. OBJECTIVES: We sought to examine health literacy over time among older adults using three widely used measures. DESIGN: A prospective cohort study. PARTICIPANTS: Community-dwelling adults ages 55 to 74 at baseline with at least one follow-up visit (N = 656) recruited from one academic internal medicine clinic and six community health centers in Chicago, IL. MEASURES: Health literacy was measured using the Test of Functional Health Literacy in Adults (TOFHLA), Newest Vital Sign (NVS), and Rapid Estimate of Adult Literacy in Medicine (REALM) at baseline and up to three follow-up time points. RESULTS: In unadjusted analyses, significant changes since baseline were found beginning at the second follow-up (mean (M) = 6.0 years, SD = 0.6) for the TOFHLA (M = − 0.9, SD = 0.95, p = 0.049) and the REALM (M = 0.3, SD = 2.5, p = 0.004) and at the last follow-up (M = 8.6 years, SD = 0.5) for the NVS (M = − 0.2, SD = 1.4, p = 0.02). There were non-linear effects of baseline age on TOFHLA and NVS scores over time (piecewise cubic spline p = 0.01 and p < 0.001, respectively) and no effect on REALM scores (B = 0.02, 95% CI − 0.01 to 0.04, p = 0.17) using multivariable mixed-effects linear regression models, controlling for race, education, income, and comorbidity. CONCLUSION: We found a negative relationship between age and health literacy over time as measured by the TOFHLA and NVS. Health literacy barriers appear to be more prevalent among individuals in later life, when self-care demands are similarly increasing. Clinicians might consider strategies to assess and respond to limited health literacy, particularly among patients 70 and older. REALM performance remained stable over 10 years of follow-up. This questions whether health literacy tools measure the same attribute. Prospective health literacy studies should carefully consider what measures to use, depending on their objective

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin

The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m−2and leucovorin 20 mgm−2both given as intravenous bolus injection on days 1–4, plus cisplatin 20 mgm−2administered as 90-min infusion on days 1–4. Treatment courses were repeated every 4 weeks × 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of ≥ 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3–32), and median overall survival was 14.0 months (range 3–45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted. © 2000 Cancer Research Campaig

DNA Targeting as a Likely Mechanism Underlying the Antibacterial Activity of Synthetic Bis-Indole Antibiotics

We previously reported the synthesis and biological activity of a series of cationic bis-indoles with potent, broad-spectrum antibacterial properties. Here, we describe mechanism of action studies to test the hypothesis that these compounds bind to DNA and that this target plays an important role in their antibacterial outcome. The results reported here indicate that the bis-indoles bind selectively to DNA at A/T-rich sites, which is correlated with the inhibition of DNA and RNA synthesis in representative Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) organisms. Further, exposure of E. coli and S. aureus to representative bis-indoles resulted in induction of the DNA damage-inducible SOS response. In addition, the bis-indoles were found to be potent inhibitors of cell wall biosynthesis; however, they do not induce the cell wall stress stimulon in S. aureus, suggesting that this pathway is inhibited by an indirect mechanism. In light of these findings, the most likely basis for the observed activities of these compounds is their ability to bind to the minor groove of DNA, resulting in the inhibition of DNA and RNA synthesis and other secondary effects

The Hydrogel Endovascular Aneurysm Treatment Trial (HEAT): A Randomized Controlled Trial of the Second-Generation Hydrogel Coil

© 2020 Congress of Neurological Surgeons 2020. BACKGROUND: Aneurysm recurrence after coiling has been associated with aneurysm growth, (re)hemorrhage, and a greater need for follow-up. The second-generation HydroCoil Embolic System (HES; MicroVention, Inc) consists of a platinum core with integrated hydrogel and was developed to reduce recurrence through enhancing packing density and healing within the aneurysm. OBJECTIVE: To compare recurrence between the second-generation HES and bare platinum coil (BPC) in the new-generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT). METHODS: HEAT is a randomized, controlled trial that enrolled subjects with ruptured or unruptured 3- to 14-mm intracranial aneurysms amenable to coiling. The primary endpoint was aneurysm recurrence using the Raymond-Roy scale. Secondary endpoints included minor and major recurrence, packing density, adverse events related to the procedure and/or device, mortality, initial complete occlusion, aneurysm retreatment, hemorrhage from target aneurysm during follow-up, aneurysm occlusion stability, and clinical outcome at final follow-up. RESULTS: A total of 600 patients were randomized (HES, n = 297 and BPC, n = 303), including 28% with ruptured aneurysms. Recurrence occurred in 11 (4.4%) subjects in the HES arm and 44 (15.4%) subjects in the BPC arm (P =. 002). While the initial occlusion rate was higher with BPC, the packing density and both major and minor recurrence rates were in favor of HES. Secondary endpoints including adverse events, retreatment, hemorrhage, mortality, and clinical outcome did not differ between arms. CONCLUSION: Coiling of small-to-medium aneurysms with second-generation HES resulted in less recurrence when compared to BPC, without increased harm. These data further support the use of the second-generation HES for the embolization of intracranial aneurysms. Video Abstract: 10.1093/neuros/nyaa006 nyaa006Media1 613226478400

The rate and associated risk factors for acute carpal tunnel syndrome complicating a fracture of the distal radius

BACKGROUND: Acute carpal tunnel syndrome (ACTS) is a known complication of distal radius fractures. This study aimed to document the demographics, range of presenting symptoms and risk factors of patients who develop ACTS following a fracture of the distal radius.METHODS: A retrospective review of 1189 patients with an acute distal radius fracture treated in the study centre over a one-year period were identified. Demographic and clinical variables were collected and compared between controls (did not develop ACTS) and those patients who did develop ACTS to identify factors associated with developing ACS.RESULTS: There were 51 (4.3%) distal radius fractures complicated by ACTS. The mean age of patients who developed ACTS was 56 years (range, 16-89) and 73% were female. The median time of onset post-injury was one week (range, 1-12). There was no association between patient background and comorbidities with the development of ACTS. AO-OTA Type C fractures had significantly increased rates of developing ACTS.CONCLUSION: Four percent of distal radius fractures were complicated by ACTS. There was no association between patient background and comorbidities with the development of ACTS. AO-OTA type C complete articular fractures had a significantly higher rate of ACTS. A suggested treatment algorithm for patients presenting with ACTS has been presented.LEVEL OF EVIDENCE: III.</p

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg m−2 on day 1 (arm A) or irinotecan 200 mg m−2 on day 1 plus raltitrexed 3 mg m−2 on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3–40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted