Interplay of hydrogen bonding and other molecular interactions in determining the crystal packing of a series of anti-[beta]-ketoarylhydrazones

Publisher's version/PDFThe crystal structures of six anti-[beta]-ketoarylhydrazones are reported: (a1) (E)-2-(4-cyanophenylhydrazono)-3- oxobutanenitrile; (a2) (E)-2-(4-methylphenylhydrazono)-3-oxobutanenitrile; (a3) (E)-2-(4-acetylphenylhydrazono)-3-oxobutanenitrile; (a4) (E)-2-(2-methoxyphenylhydrazono)-3-oxobutanenitrile; (a5) (E)-2-(2-acetylphenylhydrazono)-3-oxobutanenitrile; (a6) (E)-2-(2-nitrophenylhydrazono)-3-oxobutanenitrile. All compounds contain the [pi]-conjugated heterodienic group HN--N==C--C==O and could form, at least in principle, chains of intermolecular N--H...O hydrogen bonds assisted by resonance (RAHB-inter). Compounds (a1) and (a2) form this kind of hydrogen bond though with rather long N...O distances of 2.948 (3) and 2.980 (2) [Angstrom], and compound (a6) undergoes the same interaction but even more weakened [N...O 3.150 (1) [Angstrom]] by the intramolecular bifurcation of the hydrogen bond donated by the N--H group. The intrinsic weakness of the intermolecular RAHB makes possible the setting up of alternative packing arrangements that are controlled by an antiparallel dipole-dipole (DD) interaction between two C==O groups of the [beta]-ketohydrazone moiety [compounds (a4) and (a5)]. The critical factors that cause the switching between the different packings turn out to be the presence of hydrogen bonding accepting substituents on the phenyl and, most frequently, the intramolecular N--H...O bond with the O atom of the phenyl o-substituent. The crystal packing is widely determined by RAHB-inter (three cases) or DD (two cases) interactions. Only compound (a3) displays a different packing arrangement, where the DD interaction is complemented by a non-resonant hydrogen bond between a p-acetyl phenyl substituent and the hydrazone N--H group [N...O 2.907 (2) [Angstrom]]. Crystal densities range from 1.24 to 1.44 Mg m[superscript -3] and are shown to increase with the number of intermolecular hydrogen bonds and other non-van der Waals interactions

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes

The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.Fil: Palma, Sabina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Raffa, Carlos Ignacio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Garcia Fabiani, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Ferretti, Valeria. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Zwenger, Ariel. Grupo Oncologico Cooperativo del Sur; Argentina. Provincia del Neuquén. Hospital Provincial Neuquén "Dr. E. Castro Rendón"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perez Verdera, P. V.. No especifíca;Fil: Llontop, A.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Rojas Bilbao, E.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cuartero, V.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Clinical effects of use polymyxin B fixed on fibers in liver transplant patients with severe sepsis or septic shock

Abstract: Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component exclusively found in gram-negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound to the surface of an insoluble carrier material to inactivate endotoxin in blood without exerting toxicity on the brain or the kidney. The aim of this study was to evaluate the efficacy, safety, and clinical effects of direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) among liver transplant patients with severe sepsis or septic shock. Methods. From June 2004 to May 2005, 10 patients (6 men and 4 women) of overall mean age of 55 years (46-65 range) underwent orthotopic liver transplantation (OLT) and developed severe sepsis or septic shock according to The Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all treated patients who received conventional antibiotic therapy, vasopressor or inotropic agents, and ventilatory support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters and dosages of vasopressor or inotropic drugs were assessed at baseline and after each treatment. Results. No adverse events occurred. From baseline to the third treatment the mean arterial pressure increased from 64 +/- 5 mm Hg to 89 +/- 4 rum Hg; while the dosages of dobutamine and norepinephrine were reduced: 6.4 to 1 mcg/kg/min and 1.3 to 0.001 mcg/kg per min, respectively. The PaO2/FiO(2) ratio increased: 214 to 291 mm Fig. Conclusion. The use of DHP-PMX may be an important aid in patients with sepsis in association with conventional therapy