La utilización de las partes de la bóveda de arista en la arquitectura islámica y mudéjar en Al-Andalus, norte de África y Sicilia.

This article studies the use of sections of the groin vault as supporting architectural elements, particularly as squinches, its origin and development across the territories of Western Islam, particularly in the Iberian Peninsula. It includes a typological study supported on a broad catalogue of examples.Este artículo aborda el estudio de la utilización de las partes de la bóveda de arista como elementos arquitectónicos de soporte, especialmente como trompas, su origen y desarrollo en territorios del Islam occidental, particularmente la península Ibérica. Cuenta con un estudio tipológico apoyado en un amplio catálogo de ejemplos

Design, Synthesis, Characterization and In-Vitro Kinetic Study of Novel Antibacterials Prodrugs

A number of marketed antibacterial drugs suffer several problems, such as bitter sensation and low stability which lead to patient incompliance. The prodrug approach is considered the most promising and extremely exciting method to overcome such problems. Based on our previously reported density functional theory (DFT) calculations, amoxicillin ProD 1-2 and cephalexin ProD 1-2 were designed, synthesized and fully characterized. The intraconversion kinetics for amoxicillin ProD 1-2 and cephalexin ProD 1-2 were carried out in different aqueous media and the kobs and t1/2 values for the four prodrugs were calculated from a linear regression equation obtained from the plot of log concentration of the residual prodrug versus time. Kinetic studies in 1N HCl, pH 2.5 and pH 5 were selected to examine the intraconversion for the prodrugs to their active parent drugs. The intraconversion of the prodrugs to their active parent drugs was found to be much higher in 1N HCl than in pH 2.5 and pH 5. The experimental t1/2 values of amoxicillin ProD 1 in 1N HCl, pH 2.5 and pH 5 were 2.5, 7 and 81 hours, respectively, and for cephalexin ProD 1 in 1 N HCl and pH 2.5 were 2 and 14 hours, respectively. On the other hand, the t1/2 values of amoxicillin ProD 2 in 1N HCl and pH 2.5 were 8 and 44 hours, respectively, and for cephalexin ProD 2 in 1 N HCl was 6 hours. At pH 7.4, the four prodrugs were quite stable and no release of the parent drugs was observed. At pH 5 the hydrolysis of the prodrugs was too slow. In vitro binding test revealed that the four antibacterial prodrugs were bitterless and it is believed that the lack of the bitter sensation is due to the disability of the prodrugs to interact with the active sites of the tested bitter taste receptors

Synthesis, Characterization and In Vitro Kinetics of Amoxicillin and Cephalexin Antibacterial Prodrugs

Marketed antibacterial drugs suffer several problems, such as bitter taste and low stability which lead to patient incompliance. Prodrug technology for solving such problems is extremely exciting. Based on previously reported density functional theory calculations, amoxicillin ProD 1-2 and cephalexin ProD 1-2 were designed and synthesized. For the intraconversion of both antibacterial prodrugs the kobs and t1/2 values in different media were calculated from the linear regression equation obtained from the correlation of log concentration of the residual prodrug versus time. At constant temperature and pH the hydrolysis reaction for the above mentioned prodrugs displayed strict first order kinetics as the kobs was quite constant and a straight line was obtained. Kinetic studies in 1N HCl, pH 2.5 and pH 5 were selected to examine the intraconversion of both prodrugs to their parent drugs. The acid-catalyzed hydrolysis of the prodrugs was found to be much higher in 1N HCl than in pH 2.5 and pH 5. The experimental t1/2 values of amoxicillin ProD 1 in 1N HCl, pH 2.5 and pH 5 were 2.5, 7 and 81 hours respectively and for cephalexin ProD 1 in 1 N HCl and pH 2.5 were 2 and 14 hours respectively. In contrast, t1/2 values of amoxicillin ProD 2 in 1N HCl and pH 2.5 were 8 and 44 hours respectively and for cephalexin ProD 2 in 1 N HCl was 6 hours. On the other hand, at pH 7.4, the four prodrugs were quite stable and no release of the parent drugs was observed. At pH 5 the hydrolysis of the prodrugs was too slow. The four antibacterial prodrugs were found to be bitterless. The bitter taste masking by the prodrugs is believed to be via altering the ability of the drug to interact with bitter taste receptors

Prodrugs of fumarate esters for the treatment of psoriasis and multiple sclerosis—a computational approach

Density functional theory (DFT) calculations at B3LYP/6-31 G (d,p) and B3LYP/6-311+G(d,p) levels for the substituted pyridine-catalyzed isomerization of monomethyl maleate revealed that isomerization proceeds via four steps, with the rate-limiting step being proton transfer from the substituted pyridinium ion to the C0C double bond in INT1. In addition, it was found that the isomerization rate (maleate to fumarate) is solvent dependent. Polar solvents, such as water, tend to accelerate the isomerization rate, whereas apolar solvents, such as chloroform, act to slow down the reaction. A linear correlation was obtained between the isomerization activation energy and the dielectric constant of the solvent. Furthermore, linearity was achieved when the activation energy was plotted against the pKa value of the catalyst. Substitutedpyridine derivatives with high pKa values were able to catalyze isomerization more efficiently than those with low pKa values. The calculated relative rates for prodrugs 1–6 were: 1 (406.7), 2 (7.6×106), 3 (1.0), 4 (20.7), 5 (13.5) and 6 (2.2×103). This result indicates that isomerizations of prodrugs 1 and 3–5 are expected to be slow and that of prodrugs 2 and 6 are expected to be relatively fast. Hence, prodrugs 2 and 3–5 have the potential to be utilized as prodrugs for the slow release of monomethylfumarate in the treatment of psoriasis and multiple sclerosis

Prodrugs of fumarate esters for the treatment of psoriasis and multiple sclerosis—a computational approach

Density functional theory (DFT) calculations at B3LYP/6-31 G (d,p) and B3LYP/6-311+G(d,p) levels for the substituted pyridine-catalyzed isomerization of monomethyl maleate revealed that isomerization proceeds via four steps, with the rate-limiting step being proton transfer from the substituted pyridinium ion to the C0C double bond in INT1. In addition, it was found that the isomerization rate (maleate to fumarate) is solvent dependent. Polar solvents, such as water, tend to accelerate the isomerization rate, whereas apolar solvents, such as chloroform, act to slow down the reaction. A linear correlation was obtained between the isomerization activation energy and the dielectric constant of the solvent. Furthermore, linearity was achieved when the activation energy was plotted against the pKa value of the catalyst. Substitutedpyridine derivatives with high pKa values were able to catalyze isomerization more efficiently than those with low pKa values. The calculated relative rates for prodrugs 1–6 were: 1 (406.7), 2 (7.6×106), 3 (1.0), 4 (20.7), 5 (13.5) and 6 (2.2×103). This result indicates that isomerizations of prodrugs 1 and 3–5 are expected to be slow and tha

Organ-focused mutual information for nonrigid multimodal registration of liver CT and Gd–EOB–DTPA-enhanced MRI

Accurate detection of liver lesions is of great importance in hepatic surgery planning. Recent studies have shown that the detection rate of liver lesions is significantly higher in gadoxetic acid-enhanced magnetic resonance imaging (Gd–EOB–DTPA-enhanced MRI) than in contrast-enhanced portal-phase computed tomography (CT); however, the latter remains essential because of its high specificity, good performance in estimating liver volumes and better vessel visibility. To characterize liver lesions using both the above image modalities, we propose a multimodal nonrigid registration framework using organ-focused mutual information (OF-MI). This proposal tries to improve mutual information (MI) based registration by adding spatial information, benefiting from the availability of expert liver segmentation in clinical protocols. The incorporation of an additional information channel containing liver segmentation information was studied. A dataset of real clinical images and simulated images was used in the validation process. A Gd–EOB–DTPA-enhanced MRI simulation framework is presented. To evaluate results, warping index errors were calculated for the simulated data, and landmark-based and surface-based errors were calculated for the real data. An improvement of the registration accuracy for OF-MI as compared with MI was found for both simulated and real datasets. Statistical significance of the difference was tested and confirmed in the simulated dataset (p < 0.01)

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods

Benchmarking; PancreatectomyBenchmarking; PancreatectomiaBenchmarking; PancreatectomíaBackground Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. Methods Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006–2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. Results Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. Conclusion Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently

A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits

Présentation oraleInternational audiencen.

Impact of patient age on outcome of minimally invasive versus open pancreatoduodenectomy:a propensity score matched study

Background: Pancreatoduodenectomy in elderly patients may be associated with increased postoperative mortality, but studies in minimally invasive pancreatoduodenectomy (MIPD) are scarce. Methods: International multicenter retrospective study including patients aged &gt;60 years undergoing MIPD (robot-assisted and laparoscopic) and open pancreatoduodenectomy (OPD), were categorized by age: 60–69, 70–79, and 80+ years. In each category, propensity score matching (PSM) was performed (1:1 ratio) between MIPD and OPD. Primary outcome was 30-day/in-hospital mortality. Results: Among 3820 patients, we matched 1468 patients aged 60–69, 1154 patients aged 70–79, and 196 patients aged 80+ years. In patients aged 60–69 and 70–79 years, MIPD was associated with longer operative time, less blood loss and a longer length of stay. Major morbidity was higher after MIPD with similar 30-day/in-hospital mortality. The R0 resection rate was higher after MIPD. In patients aged 80+ years, besides a longer operative time in MIPD, outcomes were comparable between both groups. Conclusion: This study found no evidence that increasing age worsens mortality of MIPD. MIPD was associated with longer operative time, higher rate of major morbidity, prolonged length of stay versus less blood loss and a higher R0 resection in patients aged 60–69 and 70–79 years. These differences continue in patients aged 80+ years, but became less evident.</p