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1.
Int J Urol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757476

RESUMO

OBJECTIVE: The study evaluated the anatomical and functional outcomes, as well as the safety data of laparoscopic sacrocolpopexy (LSC) for pelvic organ prolapse (POP) using a lightweight macroporous mesh. METHODS: A multicentric observational study was developed including five expert centers between March 2011 and December 2019. Inclusion criteria were female patients with symptomatic ≥stage II POP (POP-Q classification), who underwent a LSC. A lightweight and macroporous mesh device (Surelift Uplift) was used. Baseline anatomical positions were evaluated using POP-Q stage. The anatomical outcomes and procedural complications were assessed during the postoperative period. Primary outcomes were anatomical success, defined as POP-Q stage ≤I, and subjective success, defined as no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse. RESULTS: A total of 325 LSCs were analyzed with a median patient age of 66 (interquartile range [IQR] 61-73). After a median follow-up of 68 months (IQR 46.5-89), anatomical success was found in 88.9%, whereas subjective success was seen in 98.5% of the patients. Recurrent prolapse presented as cystocele (1.5%). Reported complications were bladder (4.6%) or rectum lesions (0.6%), de novo urinary incontinence (12.9%), and mesh extrusion (1.2%). CONCLUSIONS: LSC provides significant clinical improvement and excellent anatomical results, with a low risk of serious complications for women with ≥2 grade POP in a real clinical practice setting.

2.
ACS Omega ; 9(10): 11562-11573, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38497015

RESUMO

As the global urgency for effective antimicrobial agents intensifies, this work harnesses the widely demonstrated antimicrobial activity of silver nanoparticles (Ag-NPs) and proposes alternative synthesis approaches to metal-organic hybrid systems with antimicrobial activity. In this study, the proposed synthesis route involves decorating metallic nanoparticles into organic substrates without previous doping. The synthesis simultaneously uses polyethylene glycol for three crucial purposes: (1) acting as a mild reducing agent to generate Ag-NPs with a spherical shape and diameters ranging from 10 to just over 20 nm, (2) functioning as a dispersing agent for flakes of commercial nanostructured carbon supports, including reduced graphene oxide (rGO, ID-nano), and commercial carbon nanoplatelets from Sigma-Aldrich (GNPs, Sigma-Aldrich), and (3) serving as a promoter for the homogeneous anchoring of Ag-NPs in the carbon lattice without altering the conformation of the carbon lattice. This intricate interaction involves the π-orbitals from the sp2 hybridization honeycomb and the d-orbitals from the Ag-NPs, leading to the constructive rehybridization of rGO and GNPs. In our study, Ag-NPs/rGO are compared with a support lacking oxygenated groups in the lattice, such as commercial GNPs (Sigma-Aldrich), to produce Ag-NPs/GNPs. This comparison maintains constructive sp2 rehybridization, preserving the characteristic properties of rGO (ID-nano) and graphene nanoplatelets, including commercial GNPs (Sigma-Aldrich). Notably, oxygenated groups from rGO exhibit greater availability for exchanging oxo and hydroxy defects for Ag-NPs compared with GNPs (Sigma-Aldrich). The resulting Ag-NPs/rGO and Ag-NPs/GNP systems are thoroughly physicochemically characterized, employing techniques such as Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, and scanning transmission electron microscopy, revealing the successful integration of Ag-NPs with minimal alteration to the carbon lattice. Subsequent antimicrobial evaluation against Escherichia coli (E. coli) demonstrates significant activity, with Ag-NPs/rGO and Ag-NPs/GNPs registering similar minimum inhibitory concentrations of 50 µg mL-1. This study underscores the potential of our metal-organic hybrid systems as antimicrobial agents and provides insights into the constructive rehybridization process, paving the way for diverse applications in the biomedical and environmental fields.

5.
Int Urogynecol J ; 34(9): 2301-2306, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37154898

RESUMO

INTRODUCTION AND HYPOTHESIS: Laparoscopic sacrocolpopexy (LSC) is a functional reconstructive surgery used to treat pelvic organ prolapse (POP) in middle-aged women. Although LSC is widely used, its implementation is hindered by perceived technical difficulties and surgical learning curves. Surgeons require adequate experience with LSC prior to performing the procedure on patients to improve their quality of life. This study is aimed at demonstrating the effectiveness of the ovine model (OM) for training and research in LSC, while also comparing anatomical differences between ovine and human models during the procedure. METHODS: The animal model and training were provided by the Jesús Usón Minimally Invasive Surgery Centre. Urologists and gynecologists with experience in LSC participated in a course and their findings were recorded and documented. RESULTS: Differences in patient positioning, trocar placement, and reperitonealization were identified between the ovine and human models. Hysterectomy is always performed in the ovine model, whereas it is not mandatory in humans. There are also differences in the dissection of the levator ani muscle and attachment point of the posterior mesh to the uterus between the two models. Despite differences in some areas, the ovine pelvic structure and vagina are similar in size to those of humans. CONCLUSIONS: The ovine model is a valuable tool for surgeons in their learning curve for LSC, allowing for safe and effective practice prior to performing the procedure on patients. The use of the OM can help to improve the quality of life for women affected by pelvic organ prolapse.


Assuntos
Laparoscopia , Prolapso de Órgão Pélvico , Pessoa de Meia-Idade , Humanos , Feminino , Ovinos , Animais , Laparoscopia/métodos , Procedimentos Cirúrgicos em Ginecologia/métodos , Qualidade de Vida , Anatomia Comparada , Resultado do Tratamento , Vagina/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/etiologia , Diafragma da Pelve , Telas Cirúrgicas
6.
FEMS Yeast Res ; 22(1)2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36040324

RESUMO

The study of nitrogen assimilation in yeast is of interest from genetic, evolutionary, and biotechnological perspectives. Over the course of evolution, yeasts have developed sophisticated control mechanisms to regulate nitrogen metabolism, with domesticated lineages sometimes displaying particular specialisation. The focus of this study was on assimilation of asparagine, which is a significant nutritional source for some alcoholic fermentations. We were particularly interested in ASP3, which encodes a periplasmic asparaginase and that was proposed to have been acquired relatively recently in S. cerevisiae by horizontal gene transfer. We examined 1680 S. cerevisiae genome assemblies to evaluate the distribution and evolutionary trajectory of ASP3. Our findings suggest an alternative hypothesis that ASP3 is an ancient Saccharomyces gene that has generally been lost over the course of evolution but has been retained in certain fermentative environments. As asparagine is the major nitrogen source in apple juice, we explored whether the presence of ASP3 would confer a growth advantage. Interestingly, we found that although ASP3 enhances growth when asparagine is the sole nitrogen source, the same effect is not seen in apple juice. These data indicate that growth in pure culture may not reflect the original selective environment for ASP3+ strains and highlight the role that complex regulation may play in optimising nitrogen assimilation in yeasts.


Assuntos
Asparaginase , Saccharomyces cerevisiae , Asparaginase/genética , Asparaginase/metabolismo , Asparagina , Fermentação , Nitrogênio/metabolismo , Saccharomyces cerevisiae/metabolismo
7.
J Imaging ; 7(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34564101

RESUMO

In recent years, there has been an increasing demand to digitize and electronically access historical records. Optical character recognition (OCR) is typically applied to scanned historical archives to transcribe them from document images into machine-readable texts. Many libraries offer special stationary equipment for scanning historical documents. However, to digitize these records without removing them from where they are archived, portable devices that combine scanning and OCR capabilities are required. An existing end-to-end OCR software called anyOCR achieves high recognition accuracy for historical documents. However, it is unsuitable for portable devices, as it exhibits high computational complexity resulting in long runtime and high power consumption. Therefore, we have designed and implemented a configurable hardware-software programmable SoC called iDocChip that makes use of anyOCR techniques to achieve high accuracy. As a low-power and energy-efficient system with real-time capabilities, the iDocChip delivers the required portability. In this paper, we present the hybrid CPU-FPGA architecture of iDocChip along with the optimized software implementations of the anyOCR. We demonstrate our results on multiple platforms with respect to runtime and power consumption. The iDocChip system outperforms the existing anyOCR by 44× while achieving 2201× higher energy efficiency and a 3.8% increase in recognition accuracy.

8.
Arch Esp Urol ; 74(4): 369-382, 2021 May.
Artigo em Espanhol | MEDLINE | ID: mdl-33942728

RESUMO

OBJECTIVES: To study the possibility of classifying patients with BPS by UPOINT phenotypes and their correlation with the results of different BPS diagnostic tools. MATERIAL AND METHODS: Epidemiological, observational, longitudinal and multicentric study performed according to clinical practice. A total of 319 women with BPS were included, 79 with new diagnosis and 240 in follow-up. Sociodemographic and clinical data were collected together with results of cystoscopy, biopsy and physical examination. Patients completed a 3-day Bladder Diary (3dBD) and Patient Reported Outcomes (PROs). All the patients were classified according to the 6 UPOINT domains and their distribution was described according to the clinical history, diagnostic tests, urinary symptoms and PROs' scores. RESULTS: 92.8% of the patients had affectation in more than one phenotype, however, there were no remarkable differences in the clinical and sociodemographic variables according to the number of affected domains. The percentage of patients with 3C classification was higher in the urinary (8.2%), organ-specific (9.0%) and neurological (10.9%) phenotypes. Around 90% had high voiding frequency, regardless of the phenotype. The improvement reported by the PROs was superior in the neurological and tenderness phenotypes. The worst scores were associated with a greater number of affected domains. CONCLUSIONS: The present study is the first one carried out in Spain on a phenotypic classification of women with BPS, with data from routine clinical practice. The results point out that patients with several domains affected present more affectation on the BPS, worse HRQo Land higher anxiety.


OBJETIVOS: Estudiar la posibilidad de clasificar a las pacientes con SDV por los fenotipos UPOINT y su correlación con los resultados de otras herramientas diagnósticas para SDV. MATERIAL Y MÉTODOS: Estudio epidemiológico, observacional, longitudinal y multicéntrico realizado según la práctica clínica habitual. Se incluyeron 319 mujeres con SDV, 79 de nuevo diagnóstico y 240 en seguimiento. Se recogieron datos sociodemográficos y clínicos y resultados de la cistoscopia, biopsia y exploración física. Las pacientes cumplimentaron un diario miccional de 3 días y los Patient Reported Outcomes (PROs). Todas las pacientes fueron clasificadas según los 6 dominios UPOINT y se describió su distribución según la historia clínica, pruebas diagnósticas, síntomas urinarios y las puntuaciones de los PROs. RESULTADOS: El 92,8% de las pacientes tenían afectación en más de un fenotipo, sin embargo, no hubo diferencias destacables en las variables clínicas y sociodemográficas según el número de dominios afectados. El porcentaje de pacientes con clasificación 3C fue mayor en los fenotipos urológico (8,2%), órgano-específico (9,0%) y neurológico (10,9%). Alrededor del 90% presentaron frecuencia miccional elevada, independientemente del fenotipo. La mejoría reportada por los PROs fue superior en los fenotipos neurológico y tenderness. Las peores puntuaciones se asociaron a un mayor número de dominios afectados. CONCLUSIONES: El presente estudio es el primero realizado en España sobre una clasificación fenotípica de mujeres con SDV, basándose en datos de práctica clínica habitual. Los resultados obtenidos señalan una tendencia a que pacientes con afectación de varios dominios fenotípicos presentan mayor afectación por el SDV, peor CVRS y mayor ansiedad.


Assuntos
Cistite Intersticial , Cistoscopia , Feminino , Humanos , Fenótipo , Espanha
9.
Arch. esp. urol. (Ed. impr.) ; 74(4): 369-382, May 28, 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-218207

RESUMO

Objetivos: Estudiar la posibilidad declasificar a las pacientes con SDV por los fenotiposUPOINT y su correlación con los resultados de otrasherramientas diagnósticas para SDV.Material y métodos: Estudio epidemiológico, observacional, longitudinal y multicéntrico realizado segúnla práctica clínica habitual. Se incluyeron 319 mujerescon SDV, 79 de nuevo diagnóstico y 240 en seguimiento. Se recogieron datos sociodemográficos y clínicosy resultados de la cistoscopia, biopsia y exploraciónfísica. Las pacientes cumplimentaron un diario miccional de 3 días y los Patient Reported Outcomes (PROs).Todas las pacientes fueron clasificadas según los 6 dominios UPOINT y se describió su distribución según lahistoria clínica, pruebas diagnósticas, síntomas urinariosy las puntuaciones de los PROs. Resultados: El 92,8% de las pacientes tenían afectación en más de un fenotipo, sin embargo, no hubodiferencias destacables en las variables clínicas y sociodemográficas según el número de dominios afectados.El porcentaje de pacientes con clasificación 3C fue mayor en los fenotipos urológico (8,2%), órgano-específico(9,0%) y neurológico (10,9%). Alrededor del 90% presentaron frecuencia miccional elevada, independiente-mente del fenotipo. La mejoría reportada por los PROsfue superior en los fenotipos neurológico y tenderness.Las peores puntuaciones se asociaron a un mayor número de dominios afectados.Conclusiones: El presente estudio es el primerorealizado en España sobre una clasificación fenotípicade mujeres con SDV, basándose en datos de prácticaclínica habitual. Los resultados obtenidos señalan unatendencia a que pacientes con afectación de variosdominios fenotípicos presentan mayor afectación por elSDV, peor CVRS y mayor ansiedad.(AU)


Objetives: To study the possibility ofclassifying patients with BPS by UPOINT phenotypesand their correlation with the results of different BPS diagnostic tools.Materials and methods: Epidemiological, observational, longitudinal and multicentric study performed according to clinical practice. A total of 319 women withBPS were included, 79 with new diagnosis and 240in follow-up. Sociodemographic and clinical data werecollected together with results of cystoscopy, biopsyand physical examination. Patients completed a 3-dayBladder Diary (3dBD) and Patient Reported Outcomes(PROs). All the patients were classified according to the6 UPOINT domains and their distribution was describedaccording to the clinical history, diagnostic tests, urinarysymptoms and PROs’ scores.Results: 92.8% of the patients had affectation in morethan one phenotype, however, there were no remarkable differences in the clinical and sociodemographicvariables according to the number of affected domains.The percentage of patients with 3C classification washigher in the urinary (8.2%), organspecific (9.0%) andneurological (10.9%) phenotypes. Around 90% hadhigh voiding frequency, regardless of the phenotype.The improvement reported by the PROs was superior inthe neurological and tenderness phenotypes. The worstscores were associated with a greater number of affected domains. Conclusions: The present study is the first one carried out in Spain on a phenotypic classification of women with BPS, with data from routine clinical practice. Theresults point out that patients with several domains affected present more affectation on the BPS, worse HRQoLand higher anxiety.(AU)


Assuntos
Humanos , Feminino , Adulto , Bexiga Urinária , Dor , Fenótipo , Cistoscopia , Medição da Dor , Urologia , Doenças Urológicas , Estudos Longitudinais
10.
FEMS Yeast Res ; 21(4)2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33890624

RESUMO

The capacity of yeasts to assimilate xylose or arabinose is strongly dependent on plasma membrane transport proteins. Because pentoses comprise a substantial proportion of available sugars in lignocellulosic hydrolysates, their utilisation is centrally important for the development of second generation biorefineries. Relatively few native pentose transporters have been studied and there is intense interest in expanding the repertoire. To aid the identification of novel transporters, we developed a screening platform in the native pentose-utilising yeast Kluyveromyces marxianus. This involved the targeted deletion of twelve transporters of the major facilitator superfamily (MFS) and application of a synthetic biology pipeline for rapid testing of candidate pentose transporters. Using this K. marxianus ΔPT platform, we identified several K. marxianus putative xylose or arabinose transporter proteins that recovered a null strain's ability to growth on these pentoses. Four proteins of the HGT-family were able to support growth in media with high or low concentrations of either xylose or arabinose, while six HXT-like proteins displayed growth only at high xylose concentrations, indicating solely low affinity transport activity. The study offers new insights into the evolution of sugar transporters in yeast and expands the set of native pentose transporters for future functional and biotechnological studies.


Assuntos
Proteínas Fúngicas/metabolismo , Kluyveromyces/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Pentoses/metabolismo , Arabinose/metabolismo , Transporte Biológico , Xilose/metabolismo
11.
Curr Biol ; 31(7): 1393-1402.e5, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33548192

RESUMO

The green alga Ostreobium is an important coral holobiont member, playing key roles in skeletal decalcification and providing photosynthate to bleached corals that have lost their dinoflagellate endosymbionts. Ostreobium lives in the coral's skeleton, a low-light environment with variable pH and O2 availability. We present the Ostreobium nuclear genome and a metatranscriptomic analysis of healthy and bleached corals to improve our understanding of Ostreobium's adaptations to its extreme environment and its roles as a coral holobiont member. The Ostreobium genome has 10,663 predicted protein-coding genes and shows adaptations for life in low and variable light conditions and other stressors in the endolithic environment. This alga presents a rich repertoire of light-harvesting complex proteins but lacks many genes for photoprotection and photoreceptors. It also has a large arsenal of genes for oxidative stress response. An expansion of extracellular peptidases suggests that Ostreobium may supplement its energy needs by feeding on the organic skeletal matrix, and a diverse set of fermentation pathways allows it to live in the anoxic skeleton at night. Ostreobium depends on other holobiont members for vitamin B12, and our metatranscriptomes identify potential bacterial sources. Metatranscriptomes showed Ostreobium becoming a dominant agent of photosynthesis in bleached corals and provided evidence for variable responses among coral samples and different Ostreobium genotypes. Our work provides a comprehensive understanding of the adaptations of Ostreobium to its extreme environment and an important genomic resource to improve our comprehension of coral holobiont resilience, bleaching, and recovery.


Assuntos
Adaptação Biológica/genética , Antozoários , Clorófitas/genética , Genômica , Simbiose , Animais
12.
Transplantation ; 105(1): 138-150, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941394

RESUMO

BACKGROUND: The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. METHODS: Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. RESULTS: Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. CONCLUSIONS: In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.


Assuntos
COVID-19/complicações , Imunossupressores/uso terapêutico , Transplante de Órgãos/mortalidade , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Interações Medicamentosas , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantados , Tratamento Farmacológico da COVID-19
13.
Artigo em Inglês | MEDLINE | ID: mdl-33123676

RESUMO

BACKGROUND: Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile. OBJECTIVES: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation. METHODS: Fresh samples of female inflorescences from three stable Cannabis sativa phenotypes, collected at different time points during the end of the flowering period were analyzed. Chemical characterization of chloroform extracts was performed by 1H-NMR. The antioxidant properties of the cannabis sativa extracts, and pure cannabinoids, were measured in a Cu2+-induced LDL oxidation assay. RESULTS: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2-3.5 per µg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7-4.6 µg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 µg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 µg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per µg, while for the propagation phase showed an IC50 ≤ 1 µg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 µg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase. CONCLUSION: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of cannabis sativa whole extracts on the initial phase of atherosclerosis.

16.
Arch Pharm (Weinheim) ; 353(1): e1900213, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31709599

RESUMO

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.


Assuntos
Benzoquinonas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Benzoquinonas/química , Relação Dose-Resposta a Droga , Técnicas Eletroquímicas , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química
17.
Curr Biol ; 29(24): 4284-4290.e2, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31813610

RESUMO

Humans have used yeasts to make cheese and kefir for millennia, but the ability to ferment the milk sugar lactose is found in only a few yeast species, of which the foremost is Kluyveromyces lactis [1]. Two genes, LAC12 (lactose permease) and LAC4 (lactase), are sufficient for lactose uptake and hydrolysis to glucose and galactose [2]. Here, we show that these genes have a complex evolutionary history in the genus Kluyveromyces that is likely the result of human activity during domestication. We show that the ancestral Lac12 was bifunctional, able to import both lactose and cellobiose into the cell. These disaccharides were then hydrolyzed by Lac4 in the case of lactose or Cel2 in the case of cellobiose. A second cellobiose transporter, Cel1, was also present ancestrally. In the K. lactis lineage, the ancestral LAC12 and LAC4 were lost and a separate upheaval in the sister species K. marxianus resulted in loss of CEL1 and quadruplication of LAC12. One of these LAC12 genes became neofunctionalized to encode an efficient lactose transporter capable of supporting fermentation, specifically in dairy strains of K. marxianus, where it formed a LAC4-LAC12-CEL2 gene cluster, although another remained a cellobiose transporter. Then, the ability to ferment lactose was acquired very recently by K. lactis var. lactis by introgression of LAC12 and LAC4 on a 15-kb subtelomeric region from a dairy strain of K. marxianus. The genomic history of the LAC genes shows that strong selective pressures were imposed on yeasts by early dairy farmers.


Assuntos
Kluyveromyces/genética , Kluyveromyces/metabolismo , Lactose/genética , Celobiose/genética , Celobiose/metabolismo , Domesticação , Evolução Molecular , Fermentação/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Genoma Fúngico/genética , Genótipo , Lactose/metabolismo , Família Multigênica/genética , Fenótipo , Filogenia
18.
BMC Pharmacol Toxicol ; 20(Suppl 1): 76, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852548

RESUMO

BACKGROUND: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, Caenorhabditis elegans has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds. METHODS: Trypanocidal activity: Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of Trypanosoma cruzi (Tulahuen 2 strain) by inhibitory concentration 50% (IC50). Toxicity assays: Lethal dose 50% (LD50) and Body Area were determined by Caenorhabditis elegans N2 strain (wild type) after acute exposure. Structure-activity relationship: A classificatory model was built using 3D descriptors. RESULTS: Two of these coumarins demonstrated near equipotency to Nifurtimox (IC50 = 5.0 ± 1 µM), with values of: 11 h (LaSOM 266), (IC50 = 6.4 ± 1 µM) and 11 g (LaSOM 231), (IC50 = 8.2 ± 2.3 µM). In C. elegans it was possible to observe that Nfx showed greater toxicity in both the LD50 assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11 h and 11 g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the C. elegans model is efficient for screening potentially toxic compounds. CONCLUSION: Two coumarins (11 h and 11 g) showed activity against T. cruzi epimastigote similar to Nifurtimox, however with lower toxicity in both LD50 and development of C. elegans assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Cumarínicos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/toxicidade , Concentração Inibidora 50 , Dose Letal Mediana , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento
19.
Salud Publica Mex ; 61(5): 648-656, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31661742

RESUMO

OBJECTIVE: To know the characteristics of medical education and identify its strengths and weaknesses. MATERIALS AND METHODS: A transversal and quantitative study of the characteristics of medical education in 29 medical schools in Mexico was carried out, between April and September 2017. Questionnaire with Likert scale was applied to explore context, regulation, structure, process, results and impact of medical education. Bivariate analysis was performed with a Chi square test and the significance level was equal to or less than 0.05. RESULTS: The political context obtained 64%, economical context 10% and mechanisms of regulation 31%. The educational structure was 61% and the social impact was 93%. CONCLUSIONS: Public policies, regulatory mechanisms and public investment must be strengthened to improve the quality of medical education.


OBJETIVO: Conocer las características de la educación médica e identificar sus fortalezas y debilidades. MATERIAL Y MÉTODOS: Se realizó un estudio transversal y cuantitativo para conocer las características de la educación médica en 29 escuelas de medicina en México, entre abril y septiembre de 2017. Se utilizó un cuestionario con escala tipo Likert para explorar el contexto, la regulación, la estructura, el proceso, los resultados y el impacto de la educación médica. Se realizó un análisis bivariado con ji cuadrada y una significancia estadística de p igual o menor a 0.05. RESULTADOS: El contexto político obtuvo 64%, el contexto económico 10%, los mecanismos de regulación 31%, la estructura educativa 61% y el impacto social 93%. CONCLUSIONES: Se requiere fortalecer las políticas públicas, la regulación y la inversión pública, para mejorar la calidad de la educación médica.


Assuntos
Educação Médica/normas , Setor Privado/normas , Setor Público/normas , Faculdades de Medicina/normas , Distribuição de Qui-Quadrado , Estudos Transversais , Currículo , Educação Médica/economia , Educação Médica/legislação & jurisprudência , Educação Médica/organização & administração , México , Programas Nacionais de Saúde , Médicos/provisão & distribuição , Setor Privado/economia , Setor Privado/organização & administração , Probabilidade , Política Pública , Setor Público/economia , Setor Público/organização & administração , Inquéritos e Questionários
20.
Rev Panam Salud Publica ; 43: e83, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31636659

RESUMO

OBJECTIVE: To gather opinions from medical schools regarding the existence of public policies on the health workforce (human resources for health) and whether sufficient public financing and regulatory mechanisms are in place for undergraduate medical education; and to identify areas of opportunity to improve the availability of general practitioners in the Region of the Americas. METHODS: Cross-sectional, descriptive study conducted with 105 medical schools (51 public and 54 private) in 17 countries. A questionnaire with a Likert scale was used to explore three dimensions (political, economic, and regulatory contexts) composed of 4, 2, and 4 variables each, respectively, and validated with the Delphi method. Frequencies of responses to the questions were estimated. A frequency analysis was performed, as well as a bivariate analysis to identify differences between public and private schools, applying the Chi-square test to compare percentages. RESULTS: The political context was considered favorable by 64% of the schools; the economic context, by 37%; and the regulatory context, by 23%. The only significant differences between public and private schools were in the financial resources they administer. CONCLUSIONS: It is necessary to strengthen public policies, public investment, and the regulation of medical education in order to improve the education and availability of general practitioners in the countries of the Region.


OBJETIVO: Conhecer a opinião das faculdades de medicina sobre o volume de políticas públicas e financiamento público e mecanismos reguladores para graduação médica e identificar áreas que possibilitem aumentar o número de clínicos gerais na Região das Américas. MÉTODOS: Estudo transversal descritivo realizado com 105 faculdades de medicina (51 públicas e 54 particulares) em 17 países. Um questionário com uma escala tipo Likert foi usado para explorar três dimensões (contexto político, contexto econômico e regulamentação), contendo 4, 2 e 4 variáveis cada, e foi validado com o método Delphi. As frequências de respostas às perguntas do questionário foram calculadas e analisadas. A fim de identificar diferenças entre as faculdades públicas e particulares, uma análise bivariada com teste qui-quadrado foi realizada para comparar porcentagens. RESULTADOS: O contexto político foi considerado favorável por 64% das faculdades; o contexto econômico por 37%; e a regulamentação por 23%. Apenas foi observada diferença significativa entre as faculdades públicas e particulares na variável recursos financeiros geridos. CONCLUSÕES: É necessário fortalecer as políticas públicas, o investimento público e a regulamentação da educação médica para melhorar a formação e aumentar o número de clínicos gerais nos países da Região.

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