External urology consultation quality at a third-level public hospital in Mexico.

INTRODUCTION: Patient satisfaction is the degree of conformity with the healthcare they receive. It is real evidence and one of the most important factors in determining the effectiveness and quality of healthcare systems. OBJECTIVE: To identify the quality of care in the Urology outpatient department of a third-level hospital. MATERIALS AND METHODS: The NHS (National Health Service) 2018 quality of care questionnaire with 11 sections, 133 items, and duration of approximately 25min was randomly administered to 250 patients attending Urology outpatients at a third-level public hospital in Mexico. RESULTS: According to responses, 92% (n=230) knew the reason for the consultation. 64.8% (n=162) had a consultation with the same physician by whom they were initially seen. The longest reported hospital wait time before being seen was more than 2h in 29.6% (n=74). As for consultation time, 212 patients responded and the duration was 11-20min in 52.8% (n=112). Finally, 33.2% (n=83) considered the quality of service to be good. CONCLUSIONS: The use of the NHS 2018 survey in the Urology service at a third-level public hospital in Mexico is feasible, since we managed to obtain a significant and continuous improvement in all its indicators which is satisfactory for all.

Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.

Proapoptotic Effect and Molecular Docking Analysis of Curcumin-Resveratrol Hybrids in Colorectal Cancer Chemoprevention.

Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.

Correlation and agreement between the Mohindra and cycloplegic retinoscopy techniques in children.

PURPOSE: As an objective technique to assess refractive status, retinoscopy is particularly useful in children. The Mohindra technique (RM) is an alternative for those patients not good candidates for cycloplegic retinoscopy (RC). The aim of the present research was to compare both techniques and to determine the correlation and agreement of their measurements. MATERIAL AND METHODS: A total of 47 boys and girls of ages ranging from 3 to 11 years old were included in the study. Cycloplegic (cyclopentolate 1%) and Mohindra retinoscopy were conducted in both eyes, and refraction was also assessed with an autorefractometre (AR). The results from the three techniques were compared and a correction factor between RM and RC was calculated. RESULTS: Statistically significant differences were found between RM and RC (median of -0.42 D; p < 0.001) and between RM and AR (median of -0.42 D; p = 0.008), but not between RC and AR (median of 0.00 D; p = 0.758). A strong correlation was found between RM and RC (rho = 0.846; p < 0.001), although the Bland-Altman test revealed a larger difference between these techniques in patients with larger hyperopic refractive errors, with a correction factor of RC = 1.15 RM + 0.42. CONCLUSIONS: The Mohindra technique may be considered a valid alternative to cycloplegic retinoscopy in patients of young age, with a good correlation between both techniques, albeit less agreement in patients with high hyperopic refractions.

S-allylCysteine Ester/Caffeic Acid Amide Hybrids as Promising Antiprotozoal Candidates: Synthesis, Biological Evaluation and Molecular Modeling Studies

Abstract In order to overcome the challenges of discovering new antiprotozoal drugs, we synthesized a new class of hybrids based on S-allylCysteine Ester/Caffeic Acid Amide and evaluated four of them against Trypanosoma cruzi and Plasmodium falciparum. Hybrid 6 exhibited good activity on T. cruzi with an EC50 value of 5.45 µM, whereas hybrid 3 was active over P. falciparum with an EC50 of 18.08 µM. All hybrids displayed a good selectivity index on P. falciparum. Molecular docking computations indicated that several hybrids have good binding affinities towards the protozoa related enzymes (Cruzipain or Falcipain-2) when compared against current inhibitors. In silico studies showed that conjugates 1-3 and 6 fulfilled optimal ADME characteristics, suggesting them as safe alternatives for oral treatment of protozoal infections.

Promising Hybrids Derived from S-Allylcysteine and NSAIDs Fragments against Colorectal Cancer: Synthesis, In-vitro Evaluation, Drug-Likeness and In-silico ADME/tox Studies.

We synthesized twelve hybrids, S-allyl Cysteine methyl, ethyl and propyl ester-based non-steroidal anti-inflammatory drugs and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of all compounds was evaluated against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 10b-c, 11b and 12b displayed the best anticancer activity with IC50 values between 0.131-0.183 mM and selectivity indices higher than 1 after 48 h of treatment. Selectivity indices were comparable to those reported for the reference drug, 5-fluorouracil (SI > 1). The SAR analysis showed that compounds with two carbon atom alkylic chains displayed the best activity (10b, 11b and 12b). Modeling studies including drug-likeness, bioactivity score and ADME/tox studies using online tools like molinspiration and Osiris suggested that these designed hybrids have a good pharmacological profile and can be considered as promising scaffolds for further studies in the search for new therapeutic alternatives to treat colorectal cancer.

On the efficiency of perovskite solar cells with a back reflector: effect of a hole transport material.

Organometal halide perovskites are promising, high-performance absorbers in solar cells. However, the light-harvesting performance of these devices is still limited by excessive charge carrier recombination. Charge carrier management can be improved, taking into account the transport properties of layers surrounding the absorber. In particular, the choice of an appropriate hole-transport material (HTM) could provide a path towards increasing the device performance of perovskite solar cells (PSCs). The Lambertian reflection on the cell's back-surface reflector could increase the power conversion efficiency (PCE) of PSCs as well. Taking into account these facts, we analyse the absorptance and the PCE of a perovskite thin-film solar cell with the Lambertian reflection on the cell's back-surface reflector for various organic and inorganic HTMs. The analysis is done by means of the Monte-Carlo ray tracing simulations complemented by the transfer-matrix method to account for the interference phenomenon in the local generation rate G of carriers in a thin-film multilayer system. This function is employed further in the transport equations to calculate the current-voltage characteristics of the cell. We show that wide band gap HTMs, that possess negligible absorption, increase the photocurrent in the perovskite, passing reflected photons from the back reflector. In contrast, at the same perovskite thickness the PSC gains less photocurrent with narrow band gap HTMs, where an excessive non-radiative recombination takes place. Our analysis demonstrates that the optimal thickness of the solar cell with the typical absorber CH3NH3PbI3 is ∼300 nm, providing the maximal efficiency ∼18.8% for the wide band gap HTM (CuSCN) at the moderate absorber purity (the diffusion length D ∼ 1 µm).

Phytochemical Screening of Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) Latex, In Vitro Cytotoxicity and Incision Wound Repair in Mice.

Himatanthus sucuuba, also known as "Bellaco caspi", is a medicinal plant whose latex, stem bark, and leaves possess phenolic acids, lupeol, ß-dihydro-plumbericinic acid, plumericin, and plumeride, among other components. Some of these have been linked to such biological activities as antiulcer, anti-inflammatory, and wound healing. The aim of this study was to determine the phytochemical compounds of H. sucuuba latex, as well as its in vitro cytotoxicity and wound healing effect in mice. Latex was collected in the province of Iquitos, Peru. Phytochemical analysis was carried out with UPLC-ESI-MS/MS. The cytotoxicity was evaluated on two colon tumor cell lines (SW480 and SW620) and non-malignant cells (human keratinocytes, HaCaT, and Chinese hamster ovary, CHO-K1). The mice were distributed into two groups, as follows: Group I-control (n = 10; without treatment); II-(n = 10) H. sucuuba latex; wounds were induced with a scalpel in the dorsal-cervical area and treatments were applied topically twice a day on the incision for 10 days. Molecular docking was carried out on the glycogen synthase kinase 3ß protein. Twenty-four chemical compounds were determined, mainly flavonoid-type compounds. Latex did not have a cytotoxic effect on tumor cells with IC50 values of more than 500 µg/mL. The latex had a regenerative effect on wounds in mice. Acacetin-7-O-neohesperidoside had the best docking score of -9.9 kcal/mol. In conclusion, H. sucuuba latex had a wound healing effect in mice, as confirmed by histological study. However, a non-cytotoxic effect was observed on colon tumor cells SW480 and SW620.

In-vitro Chemopreventive Potential of a Chromone from Bomarea setacea (ALSTROEMERIACEAE) against Colorectal Cancer.

Chemoprevention with natural products may provide important alternatives in the search for new drugs to treat cancer. Thus, the ethanol extract of Bomarea setacea and its secondary metabolite (chromone) were evaluated in-vitro in SW480 and SW620 human adenocarcinoma colon cells to identify a possible effect on cell growth, antiproliferative and/or proapoptotic activity. The ethanol extract did not show growth inhibition of these cell lines 48 h after treatment; besides, it required higher concentration and time to have an antiproliferative effect. On the other hand, although the chromone was not as active as the reference drug (5-FU), it displayed a greater selectivity, being 156-fold more selective against SW480 cells (SI => 100) and 255-fold against SW620 cells (SI => 86,9). Additionally, the chromone caused an important arrest in G2/M (44.18%) with an important accumulation in subG0/G1 phase in SW620 cells, inducing loss in mitochondrial membrane potential and damage in the cell membrane of both cell lines, with activation of caspase 3, suggesting an apoptotic process independent of ROS production and p53 activation.

New Hybrids Based on Curcumin and Resveratrol: Synthesis, Cytotoxicity and Antiproliferative Activity against Colorectal Cancer Cells.

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 3e and 3i (for SW480) and 3a, 3e and 3k (for SW620) displayed the best cytotoxic activity with IC50 values ranging from 11.52 ± 2.78 to 29.33 ± 4.73 µM for both cell lines, with selectivity indices (SI) higher than 1, after 48 h of treatment. Selectivity indices were even higher than those reported for the reference drug, 5-fluorouracil (SI = 0.96), the starting compound resveratrol (SI = 0.45) and the equimolar mixture of curcumin plus resveratrol (SI = 0.77). The previous hybrids showed good antiproliferative activity.

Chemistry and Anticancer Activity of Hybrid Molecules and Derivatives based on 5-Fluorouracil.

Considering that cancer continues to be an important cause of death worldwide, several conventional anticancer treatments are widely used. However, most of them display low selectivity against malignant cells and induce many adverse side effects. Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the most efficient, with a broad-spectrum. Due to these circumstances, various modifications of 5-FU have been developed to improve drug delivery and reduce side effects. Among the optimization strategies, modifications of 5-FU at N1 or N3 position are made, usually including the incorporation of pharmacologically active compounds with anticancer activity (called hybrid molecule) and functionalization with other groups of compounds (called conjugates). Several studies have been conducted in the search for new alternative therapies against cancer. Many of them have evidenced that hybrid compounds exhibit good anticancer activity, which has emerged as a promising strategy in this field of drug discovery and development. Furthermore, the binding of 5-FU to amino acids, peptides, phospholipids, polymers, among others, improves metabolic stability and absorption. This review highlights the potential of hybrids and derivatives based on 5-FU as a scaffold for the development of antitumor agents. Besides, it also presents a detailed description of the different strategies employed to design and synthesized these compounds, together with their biological activities and structure-activity relationship (SAR) analysis.

Antileishmanial and cytotoxic activities of four Andean plant extracts from Colombia.

BACKGROUND AND AIM: Licania salicifolia (L.S) Cuatrec., Persea ferruginea (P.F) Kunth, Oreopanax floribundus (O.F), and Psychotria buchtienii (P.B) belong to the families Chrysobalanaceae, Lauraceae, Araliaceae, and Rubiaceae, respectively, which have been used as medicines by communities in the Andes. This study evaluated the leishmanicidal and cytotoxic activities of alcohol and non-alcohol extracts from four Andean plant extracts (L.S, O.F, P.F, and P.B). MATERIALS AND METHODS: Extracts were obtained by percolation with solvents of different polarities - hexane, dichloromethane, ethyl acetate, and ethanol. Phytochemical screening was conducted based on reported methods. All products were evaluated in vitro to determine the leishmanicidal activity against amastigotes of Leishmania panamensis and cytotoxicity against U937 cells. RESULTS: Flavonoids, triterpenes, and tannins were the main secondary metabolites found. From the results, dichloromethane extracts from O.F and P.B, ethanol extract from P.B, and ethyl acetate extracts of all plants were active, with EC50 <30 µg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 µg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extracts from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 µg/mL, respectively. Hexane and ethanol extracts from O.F, ethyl acetate, and ethanol extracts from L.S, and all extracts from P.F were not toxic. Alternatively, hexane and dichloromethane extracts from L.S and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high toxicity. CONCLUSION: Based on the activity we observed, ethyl acetate extract can continue in its usage in the search for new antileishmanial drugs, mainly ethyl acetate extract from L.S showed activity comparable to meglumine antimoniate and was not cytotoxic.

Double-Ring Epimerization in the Biosynthesis of Clavulanic Acid.

All reaction steps during the biosynthesis of suicidal clavulanic acid (coformulated with ß-lactam antibiotics and used to fight bacterial infections) are known, except for the crucial 3S,5S → 3R,5R double epimerization needed to produce a biologically active stereoisomer, for which mechanistic hypothesis is subject to debate. In this work, we provide evidence for a reaction channel for the double inversion of configuration that involves a total of six reaction steps. When mediated by an enzyme with a terminal S-H bond, this highly complex reaction is spontaneous in the absence of solvents. Polarizable continuum models introduce reaction barriers in aqueous environments because of the strong destabilization of the first transition state. Molecular geometries and electronic structures in both cases indicate that solvent-free spontaneity and aqueous medium barriers are both firmly rooted in a substantial reorganization of the electron density right at the onset of the reaction, mostly involving a cyclic evolution/involution of large regions of π delocalization used to stabilize the excess charge left after the initial proton abstraction.

Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat's Claw) against the Main Protease 3CLpro of SARS-CoV-2 by Molecular Modeling.

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease Mpro (also called 3CLpro) bound to a synthetic inhibitor, which represents a major druggable target. The druggability of Mpro could be used for discovering drugs to treat COVID-19. A multilevel computational study was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (Cat's claw), focusing on the inhibition of Mpro. The in silico approach starts with protein-ligand docking of 26 Cat's claw key components, followed by ligand pathway calculations, molecular dynamics simulations, and MM-GBSA calculation of the free energy of binding for the best docked candidates. The structural bioinformatics approaches led to identification of three bioactive compounds of Uncaria tomentosa (speciophylline, cadambine, and proanthocyanidin B2) with potential therapeutic effects by strong interaction with 3CLpro. Additionally, in silico drug-likeness indices for these components were calculated and showed good predicted therapeutic profiles of these phytochemicals. Our findings suggest the potential effectiveness of Cat's claw as complementary and/or alternative medicine for COVID-19 treatment.

Translation and cultural adaptation into Spanish of the Low Vision Quality of Life Questionnaire. / Traducción y adaptación cultural al español del cuestionario Low Vision Quality of Life (LVQOL).

OBJECTIVE: The purpose of the present study was to provide a translation into Spanish, as well as a cross-cultural adaptation, of the English version of the Low Vision Quality of Life Questionnaire (LVQOL). There are currently some questionnaires designed to assess vision related quality of life in Spanish, although none of them specifically examines the quality of life of patients with visual disability. METHOD: The LVQOL consists of 25 items and examines 4 different dimensions: distance vision; mobility and ilumination; adaptation, reading and precision work, and daily life activities. The process of translation and cross-cultural adaptation was conducted following the recommendations of the International Society for Pharmacoeconomics and Outcomes. This included, amongst other variables, a direct translation, a back-translation, and a cognitive debriefing with a small sample of patients with visual impairment. Work was supervised by an expert committee consisting of an ophthalmologist, a psychologist with expertise in Patient Reported Outcomes, and an optician-optometrist with experience in the field of low vision. RESULTS: A total of 46 phrases were considered for translation of which, 41 (89.1%) had excellent equivalence, 3 (6.5%) moderate equivalence, and 2 poor equivalence. The cognitive debriefing phase showed a high degree of acceptance of the questionnaire by the sample of participants with visual impairment. CONCLUSIONS: The results obtained suggest that the Spanish version of this tool is understandable for patients with visual impairment. Its properties as a measuring tool will be evaluated in a later study to determine its validity, reliability, and sensitivity to changes.

Virtual and experimental screening of phenylfuranchalcones as potential anti-Leishmania candidates.

Discovery of novel or repurposed chemical treatments for leishmaniasis is a priority given the limited number of therapeutic alternatives available. One way to accelerate the finding is by implementing virtual screening methodologies using structural information, with subsequent experimental validations. Here we tested a library of 48 phenylfuranchalcones as anti-Leishmania agents that can be associated to the potential inhibition of a protein target within the parasite. For that purpose, a list of 43 protein structures from different Leishmania species was prepared to dock the virtual compound library. The protein with the best predicted scores was used as reference to select a subset of previously synthesized compounds for in vitro validation of their cytotoxicity and anti-Leishmania activity. We found a set of active compounds (EC50 < 25 µM) that were compared with the computational results using Spearman correlations. The analysis allowed us to propose the inhibition of a phosphodiesterase enzyme as the potential mechanism of action.

Synthesis and in-vitro Evaluation of S-allyl Cysteine Ester - Caffeic Acid Amide Hybrids as Potential Anticancer Agents.

We have synthesized a series of S-allyl cysteine ester-caffeic acid amide hybrids and evaluated them in order to determine their possible anticancer activity and selectivity in colorectal cancer, which is still one of the leading causes of morbidity and mortality worldwide. All compounds were tested against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 6e, 9a, 9b, 9c, and 9e exhibited the highest effect on viability (IC50 SW480-48h= 0.18, 0.12, 0.12, 0.11, and 0.12 mM, respectively) and selectivity (SI = 10.3, 1.5, >83.33, >90.91 and >83.33, respectively) in a time- and concentration-dependent manner. Besides, our results were even better as regards lead compounds (S-allyl cysteine and caffeic acid) and the standard drug (5-FU). Additionally, these five compounds induced mitochondrial depolarization that could be related with an apoptotic process. Moreover, hybrids 6e, 9a, and 9e induced cell cycle arrest in G2/M phase, and compound 9c in S- phase, which suggests that these hybrid compounds could have also a cytostatic effect in SW480 cell line. The SAR analysis showed that hydroxyl groups increased the activity. Besides, there was not a clear relationship between the antitumor properties and the length of the alkyl chain. Since hybrid compounds were much more selective than the conventional drug (5-FU), this makes them promising candidates for further studies against colorectal cancer.

Hybrid Molecules: Promising Compounds for the Development of New Treatments Against Leishmaniasis and Chagas Disease.

Leishmaniasis and Chagas disease are endemic pathologies in tropical countries. These cause high morbidity and a public health problem. Current chemotherapies are based on conventional drugs with variable efficacy and toxicity related with the length of therapeutic schemes and high doses. When two pharmacological agents are combined into a single molecule, the result is the so-called hybrid molecule. In the search for new treatments against Chagas disease and leishmaniasis, several studies have shown that hybrid molecules display high antiprotozoal activity and this emerging strategy is quite promising in the field of new drug discovery and development. This review focuses on the antiprotozoal activity of different hybrids obtained from the hybridization of pharmacophores, showing that the most of the efforts have been concentrated in the molecular hybridization of quinoline, chalcone and hydrazone moieties.

Variability of Alt a 1 expression by different strains of Alternaria alternata.

BACKGROUND: While it is well known that there is significant intraspecific variation in the content an potency of Alternaria alternata allergens, little data has been published on intraspecific variability for individual allergens from moulds. OBJECTIVE: To assess the variability of Alt a 1 expression in different strains of A alternata. METHODS: Eleven strains of A alternata were cultured in a Czapek broth medium and culture filtrate extracts were obtained. A sensitive two-site enzyme-linked immunosorbent assay was used to measure Alt a 1 concentrations in medium following 3 weeks of culture and in culture filtrate extracts. RESULTS: Expression of Alt a 1 was highly variable in different strains ofA alternata (coefficient of variation > 135%). A good correlation was found between Alt a 1 concentrations at the beginning of the process and measurements at the end of extract production (r=0.940). CONCLUSIONS: The high variability of Alt a 1 expression in different A alternata strains makes it necessary to measure Alt a 1 concentrations during the first stage of allergenic extract production in order to be able to choose a suitable strain for producing extracts or purifying Alt a 1.