Inhibition of cyclooxygenase-2 (COX-2) has been extensively studied as an approach to reduce proinflammatory markers in acute brain diseases, but the anti-neuroinflammatory role of cyclooxygenase-1 ...(COX-1) inhibition has been rather neglected. We report that
-terphenylamine derivatives are selective COX-1 inhibitors, able to block microglia inflammatory response and elicit a neuroprotective effect. These compounds were synthesized via a three-component reaction of chalcones, β-ketoesters, and primary amines, followed by hydrolysis/decarboxylation of the ester group. Together with their synthetic intermediates and some urea derivatives, they were studied as inhibitors of COX-1 and COX-2. The
-terphenylamine derivatives, which were selective COX-1 inhibitors, were also analyzed for their ability to block microglia inflammatory and oxidative response. Compound
presented an interesting anti-inflammatory and neuroprotective profile by reducing nitrite release, ROS overproduction, and cell death in organotypic hippocampal cultures subjected to LPS. We thus show that COX-1 inhibition is a promising approach to provide enhanced neuroprotection against acute inflammatory processes, which are crucial in the development of a plethora of acute neurodegenerative injuries.
Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α ...granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in platelet releasates. ADAM17 cuts TLT-1, suggesting that S136 is the C-terminal amino acid in sTLT-1. Our results revealed that for CAD patients, sTLT-1 levels did not differ significantly according to primary outcomes of death or major cardiac event; however, patients with left ventricular (LV) dysfunction had significantly lower plasma sTLT-1 levels as compared to those with normal LV function (981.62 ± 1141 pg/mL vs. 1247.48 ± 1589 pg/mL; p = 0.003). When patients were stratified based on sTLT-1 peak frequency distribution (544 pg/mL), a significant association with congestive heart failure was identified (OR = 2.94; 1.040–8.282; p = 0.042), which could be explained by LV dysfunction.
Major coastal storms, associated with strong winds, high waves and intensified currents, and occasionally with heavy rains and flash floods, are mostly known because of the serious damage they can ...cause along the shoreline and the threats they pose to navigation. However, there is a profound lack of knowledge on the deep-sea impacts of severe coastal storms. Concurrent measurements of key parameters along the coast and in the deep-sea are extremely rare. Here we present a unique data set showing how one of the most extreme coastal storms of the last decades lashing the Western Mediterranean Sea rapidly impacted the deep-sea ecosystem. The storm peaked the 26(th) of December 2008 leading to the remobilization of a shallow-water reservoir of marine organic carbon associated with fine particles and resulting in its redistribution across the deep basin. The storm also initiated the movement of large amounts of coarse shelf sediment, which abraded and buried benthic communities. Our findings demonstrate, first, that severe coastal storms are highly efficient in transporting organic carbon from shallow water to deep water, thus contributing to its sequestration and, second, that natural, intermittent atmospheric drivers sensitive to global climate change have the potential to tremendously impact the largest and least known ecosystem on Earth, the deep-sea ecosystem.
The effect of water over the performance of the Methanol-to-Olefins process was studied in a conventional fluidized bed reactor (CFBR) and a two-zone fluidized bed reactor (TZFBR). Both of them ...contained the same SAPO-34-based catalyst, prepared by agglomeration with bentonite and alumina. In the first section of this paper, the performance was studied in the TZFBR for a wide range of temperatures (350–600 °C, ΔT = 50 °C), and two oxygen concentrations fed to the lower zone (7.5 and 10.8% for 500, 550, and 600 °C). In the second section, a comparison between the performance over the two previously mentioned reactors is presented, followed by a comparison between feeding water or not doing so to the TZFBR. Results showed that the TZFBR increased the initial yield to olefins and the production time of them, an effect that was increased by feeding a mixture of methanol–water (1:1 molar ratio) instead of pure methanol.
Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to ...provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years 49·6–50·4, 48·2 years 47·3–49·2, 46·8 years 46·6–48·1, and 55·5 years 54·9–56·1, respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Marató de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.
Methanol can be obtained through CO2 hydrogenation in a membrane reactor with higher yield or lower pressure than in a conventional packed bed reactor. In this study, we explore a new kind of ...membrane with the potential suitability for such membrane reactors. Silicone–ceramic composite membranes are synthetized and characterized for their capability to selectively remove water from a mixture containing hydrogen, CO2, and water at temperatures typical for methanol synthesis. We show that this membrane can achieve selective permeation of water under such harsh conditions, and thus is an alternative candidate for use in membrane reactors for processes where water is one of the products and the yield is limited by thermodynamic equilibrium.
In order to explore the possible contribution of the motor system to the representation of verbs, we studied the relative preservation of the capacity of Parkinson disease patients to name matched ...sets of object and action pictures. The performance of this group of participants was compared with that of a group of healthy seniors, and a group of Alzheimer disease patients. Generalized linear mixed-effects analyses showed that, whereas the two control groups had similar accuracy scores in response to objects and actions, Parkinson disease patients presented a significant impairment in their capacity to name actions compared to objects. The results of this study support the idea that verb representations are grounded in neural networks to which brain areas involved in motor control contribute.
IntroductionSpain is one of the countries with the lowest rates of revascularisation and highest ratio of percutaneous coronary intervention (PCI) to coronary artery bypass grafting ...(CABG).ObjectivesTo investigate the changes and trends in the two revascularisation procedures between 1998 and 2017 in Spain.DesignRetrospective cohort study. Analysis of in-hospital outcomes.SettingMinimum basic data set from the Spanish National Department of Health: mandatory database collecting information of patients who are attended in the Spanish public National Health System.Participants603 976 patients who underwent isolated CABG or PCI in the Spanish National Health System. The study period was divided in four 5-year intervals. Patients with acute myocardial infarction on admission were excluded.Primary and secondary outcomesWe investigated the volume of procedures nationwide, the changes of the risk profile of patients and in-hospital mortality of both techniques.ResultsWe observed a 2.2-fold increase in the rate of any type of myocardial revascularisation per million inhabitants-year: 357 (1998) to 776 (2017). 93 682 (15.5%) had a coronary surgery. PCI to CABG ratio rose from 2.2 (1998–2002) to 8.1 (2013–2017). Charlson’s index increased by 0.8 for CABG and 1 for PCI. The median annual volume of PCI/hospital augmented from 136 to 232, while the volume of CABG was reduced from 137 to 74. In the two decades, we detected a significant reduction of CABG in-hospital mortality (6.5% vs 2.6%, p<0.001) and a small increase in PCI (1.2% vs 1.5%, p<0.001). Risk adjusted mortality rate was reduced for both CABG (1.51 vs 0.48, p<0.001), and PCI (1.42 vs 1.05, p<0.001).ConclusionWe detected a significant increase in the volume of revascularisations (particularly PCI) in Spain. Risk-adjusted in-hospital mortality was significantly reduced.
Minimal Clinically Important Difference (MCID) and Patient-Acceptable Symptomatic State (PASS) have emerged as patient-based treatment assessments. However, these have not been investigated in ...patients undergoing arthroscopic isolated subscapularis repair (AISR). The primary purpose of this study was to determine the MCID and PASS for commonly used patient-reported outcomes in individuals who underwent AISR. The secondary purpose was to assess potential associations between preoperative and intraoperative patient characteristics and the MCID and PASS.
A retrospective analysis was conducted on prospectively collected data for patients who underwent primary AISR between 2011 and 2021 at a single institution, with minimum 2-year postoperative follow-up. Functional outcomes were assessed using the American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV), and Visual Analog Scale (VAS) pain scale. The MCID was determined using the distribution-based method, while PASS was evaluated using area under the curve analysis. To investigate the relationship between preoperative variables and the achievement of MCID and PASS thresholds, Pearson and Spearman coefficient analyses were employed for continuous and noncontinuous variables, respectively.
A total of 77 patients with a mean follow-up of 58.1 months were included in the study. The calculated MCID values for VAS pain, ASES, and SSV were 1.2, 10.2, and 13.2, respectively. The PASS values for VAS pain, ASES, and SSV were 2.1, 68.8, and 68, respectively. There was no significant correlation between tear characteristics and the likelihood of achieving a MCID or PASS. Female sex, worker’s compensation status, baseline VAS pain score, and baseline ASES score, exhibited weak negative correlations for achieving PASS for VAS pain and ASES.
This study defined the MCID and PASS values for commonly used outcome measures at short-term follow-up in patients undergoing AISR. Tear characteristics do not appear to impact the ability to achieve a MCID or PASS after AISR. Female sex, worker’s compensation claim, and low baseline functional scores have weak negative correlations with the achievement of PASS for VAS pain and ASES scores.
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