The authors describe a family group studied by the Centro de Biologìa Molecular y Biotecnologìa, and the Clìnica de la Memoria, las Demencias y el Envejecimiento (Universidad Tecnològica de Pereira, ...Colombia), and evaluate the association of depressive symptoms with Alzheimer’s disease (AD). This family presented a hereditary pattern for AD characterized by an early onset of dementia symptoms, a long preclinical depressive course, and, once the first symptoms of dementia appeared, a rapid progression to severe cognitive function impairment. The authors found a high prevalence of depressive symptoms in this family and propose that the symptoms could be an important risk factor for developing AD in the presence of other risk factors such as the APOE E4 allele.
This thesis describes research investigating the development of a model for the initial design of complex systems, with application to spacecraft design. The design model is called an atomic design ...process (ADP) and contains four fundamental stages (specifications, configurations, trade studies and drivers) that constitute the minimum steps of an iterative process that helps designers find a feasible solution. Representative design models from the aerospace industry are reviewed and are compared with the proposed model. The design model's relevance, adaptability and scalability features are evaluated through a focused design task exercise with two undergraduate teams and a long-term design exercise performed by a spacecraft payload team. The implementation of the design model is explained in the context in which the model has been researched. This context includes the organization (a student-run research laboratory at the University of Michigan), its culture (academically oriented), members that have used the design model and the description of the information technology elements meant to provide support while using the model. This support includes a custom-built information management system that consolidates relevant information that is currently being used in the organization. The information is divided in three domains: personnel development history, technical knowledge base and laboratory operations. The focused study with teams making use of the design model to complete an engineering design exercise consists of the conceptual design of an autonomous system, including a carrier and a deployable lander that form the payload of a rocket with an altitude range of over 1000 meters. Detailed results from each of the stages of the design process while implementing the model are presented, and an increase in awareness of good design practices in the teams while using the model are explained. A long-term investigation using the design model consisting of the successful characterization of an imaging system for a spacecraft is presented. The spacecraft is designed to take digital color images from low Earth orbit. The dominant drivers from each stage of the design process are indicated as they were identified, with the accompanying hardware development leading to the final configuration that comprises the flight spacecraft.
Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel ...cleanliness.
The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014. The validation cohort included 409 outpatients who underwent colonoscopy between October and December 2014. Cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). Bowel preparation was administered on the same day as the examination.
In the development cohort, BBPS was adequate in 541 patients (81.1 %). At multivariate analysis, antidepressants (odds ratio OR 4.25, 95 % confidence interval CI 1.91 - 9.47), co-morbidity (OR 3.35, 95 %CI 2.16 - 5.18), constipation (OR 2.09, 95 %CI 1.29 - 3.40), and abdominal/pelvic surgery (OR 1.60, 95 %CI 1.03 - 2.47) were independent predictors for inadequate cleansing. The model built with these variables showed an area under the curve of 0.72 in the development cohort and 0.70 in the validation cohort. A cutoff of 1.225 predicted inadequate bowel preparation with a sensitivity, specificity, positive predictive value, and negative predictive value of 60.3 % (95 %CI 51.6 - 68.4), 75.4 % (95 %CI 71.6 - 78.9), 36.4 % (95 %CI 30.1 - 43.1), and 89.1 % (95 %CI 85.9 - 91.6) in the development cohort, and 50.0 % (95 %CI 38.1 - 61.9), 80.0 % (95 %CI 75.3 - 84.2), 35.7 % (95 %CI 26.4 - 45.6), and 87.9 % (95 %CI 83.7 - 91.3) in the validation cohort.
A simple score may assist the clinician in predicting which patients are at high risk of inadequate bowel cleanliness. This may guide changes in bowel preparation strategy accordingly.
Abstract
Background
The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously ...explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19.
Methods
The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients.
Results
Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV.
Conclusions
Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.
Levels of soluble TNFR1 and TNFR2 were different according to the genotype of TNFRSF1Brs1061622, TNFrs1800629, and rs361525 in patients with COVID-19. Higher soluble TNF, TNFR1, and TNFR2 levels were detected in patients with a more severe disease.
An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been ...explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (P-Selectin, D-dimer, P-selectin glycoprotein ligand-1, tissue plasminogen activator tPA, plasminogen activator inhibitor-1, and Factor IX) were assessed by cytometric bead arrays in one- and two-time determinations. Accordingly, SERPINE1 rs6092, P-Selectin (GG 385 pg/mL vs. AG+AA 632 pg/mL, p = 0.0037), and tPA (GG 1858 pg/mL vs. AG+AA 2546 pg/mL, p = 0.0284) levels were different. Patients carrying the CT F5-rs6025 genotype exhibited lower levels of factor IX (CC 17,136 pg/mL vs. CT 10,247 pg/mL, p = 0.0355). Coagulation proteins were also different among IMV patients than non-IMV. PSGL-1 levels were significantly increased in the late stage of COVID-19 (>10 days). The frequencies of F5 rs6025 and SERPINE1 rs6092 variants were not different among IMV and non-IMV. The SERPINE1 rs6092 variant is related to the impaired coagulation process in patients with COVID-19 severe.
Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate ...bowel preparation.
Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%.
Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation.
After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552).
Cefazolin is a recommended treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections that has been successfully used in outpatient parenteral antibiotic therapy (OPAT) programs. ...The aim of this study was to assess the clinical outcomes of cefazolin delivered each day (Group 24) vs. every two days (Group 48) for MSSA infections in OPAT programs. It was a prospective observational study with retrospective analysis of a cohort of MSSA infections attended in OPAT. The primary outcome was treatment success, defined as completing the antimicrobial regimen without death, treatment discontinuation, or readmission during treatment and follow-up. A univariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Of the 149 MSSA infections treated with cefazolin 2 g/8 h in OPATs, 94 and 55 patients were included in the delivery Group 24 and Group 48, respectively. Treatment failure and unplanned readmission rates were similar in both groups (11.7% vs. 7.3% p = 0.752 and 8.5% vs. 5.5% p = 0.491). There was a significant increase in vascular access complications in Group 24 (33.0%) with respect to Group 48 (7.3%) (p < 0.001). Treating uncomplicated MSSA infection with cefazolin home-delivered every two days through an OPAT program is not associated with an increased risk of treatment failure and entails a significant reduction in resource consumption compared to daily delivery.
We aimed to identify clinical factors associated with recurrent infective endocarditis (IE) episodes. The clinical characteristics of 2816 consecutive patients with definite IE (January 2008-2018) ...were compared according to the development of a second episode of IE. A total of 2152 out of 2282 (94.3%) patients, who were discharged alive and followed-up for at least the first year, presented a single episode of IE, whereas 130 patients (5.7%) presented a recurrence; 70 cases (53.8%) were due to other microorganisms (reinfection), and 60 cases (46.2%) were due to the same microorganism causing the first episode. Thirty-eight patients (29.2%), whose recurrence was due to the same microorganism, were diagnosed during the first 6 months of follow-up and were considered relapses. Relapses were associated with nosocomial endocarditis (OR: 2.67 (95% CI: 1.37-5.29)), enterococci (OR: 3.01 (95% CI: 1.51-6.01)), persistent bacteremia (OR: 2.37 (95% CI: 1.05-5.36)), and surgical treatment (OR: 0.23 (0.1-0.53)). On the other hand, episodes of reinfection were more common in patients with chronic liver disease (OR: 3.1 (95% CI: 1.65-5.83)) and prosthetic endocarditis (OR: 1.71 (95% CI: 1.04-2.82)). The clinical factors associated with reinfection and relapse in patients with IE appear to be different. A better understanding of these factors would allow the development of more effective therapeutic strategies.
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•Both epimeric of 4,5-secocholest-3-yn-5-ols were prepared from cholesterol.•Reaction with terephthaloyl chloride led to crystalline dimeric terephthalates.•The configuration at C-5 ...plays an important role in the crystal packing.•Hydrophobic interactions promote multilayer or helicoidal self assemblies.
Two dimeric steroidal terephthalates derived from epimeric 4,5-seco-cholest-3-yn-5-ols were prepared starting from cholesterol in a five-step synthetic sequence. X-ray crystallography shows that the obtained compounds display novel supramolecular networks in the solid state in which the facial hydrophobicity of the steroidal skeletons plays an important role. Unambiguous NMR characterization of the obtained dimers is also provided.
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