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1.
Curr Pharm Teach Learn ; 16(9): 102123, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38852207

ABSTRACT

INTRODUCTION: Herbal medicine has seen remarkable growth in consumption over the past few years. Community pharmacists are health care professionals who have an important role in the dispensing and counselling of these products. The aim of this study was to evaluate perceptions, professional practices and knowledge about herbal medicine among community pharmacists in Tenerife (Canary Islands, Spain). METHOD: A descriptive cross-sectional study was conducted in community pharmacies in Tenerife using a questionnaire that included demographic data, perceptions, professional practices and knowledge of herbal medicine. Data from 610 community pharmacists was analyzed using SPSS 26.0 software program. RESULTS: Most of the responders had a positive attitude towards herbal medicine, considering its products useful (80.9%), safe (64.2%) and those sold in pharmacies of high quality and standardized (84.6%). They thought that these products should only be sold in pharmacies (78.0%) and that it was their responsibility to provide information about them (95.5%). However, only 32.1% believed they are well prepared to provide herbal pharmaceutical care services and 36.1% that there are reliable and easily accessible sources of information. Moreover, 60.7% considered lack of training a barrier to recommending herbal medicinal products, being interested in updating their knowledge on it (96.9%). CONCLUSION: This study showed that community pharmacists have a positive perception of herbal medicines, considering them beneficial and safe. However, participants requested reliable sources of information, easy access, and more training to dispense, counsel, and safely label these products. Education and training programs in herbal medicine are needed to enhance their ability to provide herbal pharmaceutical care.

2.
Pediatr. (Asunción) ; 51(1)abr. 2024.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1558632

ABSTRACT

Introducción: Sulfato de magnesio (MgSO4) y aminofilina son broncodilatadores intravenosos utilizados en el tratamiento de niños con broncoobstrucción (BO). La evidencia disponible para recomendar su uso es escasa. Objetivo: Caracterizar el perfil de uso y la respuesta terapéutica al MgSO4 y aminofilina en el tratamiento de la BO en niños hospitalizados en un centro de referencia de Uruguay. Materiales y métodos: Estudio descriptivo de corte transversal mediante revisión de historias y entrevistas. Se incluyeron a todos los menores de 15 años que utilizaron estos fármacos. Se evaluó la respuesta terapéutica a la administración de ambos fármacos en forma exclusiva y concomitante y la presencia de efectos adversos. Resultados: Se incluyeron 102 niños, mediana de edad 4 años, ≤5 años 62%. Los principales diagnósticos fueron: crisis asmática 56% y neumonía viral 31%. Recibieron ambos fármacos 48%, únicamente aminofilina 28% y exclusiva de MgSO4 24%. Se observó buena respuesta terapéutica a la administración: exclusiva de MgSO4 67%, consecutiva de MgSO4 y aminofilina 45% y exclusiva de aminofilina en 34%. En 38,2% se registró al menos un efecto adverso, 64% eran menores de 5 años, riesgo aumentado en 1,5 veces. Conclusiones: Se registraron variadas indicaciones, la mayoría en niños asmáticos y en un porcentaje menor indicaciones fuera de prospecto. Menos de la mitad presentaron buena respuesta luego de la administración de MgSO4 y/o aminofilina. En un porcentaje no despreciable se registraron efectos adversos, predominaron en menores de 5 años. Son necesarios nuevos estudios para continuar caracterizando el perfil de uso y seguridad de estos fármacos.


Introduction: Magnesium sulfate (MgSO4) and aminophylline are intravenous bronchodilators used in the treatment of children with bronchoobstruction (BO). The evidence available to recommend their use is scarce. Objective: To characterize the use profile and therapeutic response to MgSO4 and aminophylline in the treatment of BO in children hospitalized in a reference center in Uruguay. Materials and methods: This was a descriptive cross-sectional study through review of clinical histories and interviews. All children under 15 years of age who used these drugs were included. The therapeutic response to the administration of both drugs exclusively and concomitantly and the presence of adverse effects were evaluated. Results: 102 children were included, median age was 4 years, 62% were ≤5 years. The main diagnoses were: asthmatic crisis, 56% and viral pneumonia, 31%. 48% received both drugs, 28% only aminophylline and 24% exclusively MgSO4. Good therapeutic response was observed to the administration: MgSO4 exclusively, 67%, MgSO4 followed by aminophylline, 45% and aminophylline exclusively in 34%. At least one adverse effect was recorded in 38.2%, of these, 64% were under 5 years of age, risk increased by 1.5 times. Conclusions: Various indications were recorded, the majority in asthmatic children and a smaller percentage off-label indications. Less than half had a good response after the administration of MgSO4 and/or aminophylline. Adverse effects were recorded in a non-negligible percentage, predominating in children under 5 years of age. New studies are necessary to continue characterizing the use and safety profile of these drugs.

3.
Nat Med ; 30(5): 1292-1299, 2024 May.
Article in English | MEDLINE | ID: mdl-38632391

ABSTRACT

Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.


Subject(s)
Hippocampus , Neurons , Animals , Hippocampus/pathology , Humans , Mice , Neurons/pathology , Epilepsy/pathology , Male , Optogenetics , Female , Seizures , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/pathology , Adult
4.
Cell Genom ; 3(11): 100418, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38020971

ABSTRACT

We describe construction of the synthetic yeast chromosome XI (synXI) and reveal the effects of redesign at non-coding DNA elements. The 660-kb synthetic yeast genome project (Sc2.0) chromosome was assembled from synthesized DNA fragments before CRISPR-based methods were used in a process of bug discovery, redesign, and chromosome repair, including precise compaction of 200 kb of repeat sequence. Repaired defects were related to poor centromere function and mitochondrial health and were associated with modifications to non-coding regions. As part of the Sc2.0 design, loxPsym sequences for Cre-mediated recombination are inserted between most genes. Using the GAP1 locus from chromosome XI, we show that these sites can facilitate induced extrachromosomal circular DNA (eccDNA) formation, allowing direct study of the effects and propagation of these important molecules. Construction and characterization of synXI contributes to our understanding of non-coding DNA elements, provides a useful tool for eccDNA study, and will inform future synthetic genome design.

5.
Rev. bras. oftalmol ; 82: e0063, 2023. graf
Article in English | LILACS | ID: biblio-1529926

ABSTRACT

ABSTRACT Ocular cysticercosis is a parasitic infection caused by Taenia solium. Its early diagnosis and treatment decreases the possibility of visual morbidity. It can either compromise the anterior chamber or the posterior segment, which translates into an very variable and interspecific presentation that changes depending on the site of the infection. It is important to report this case due to its low presentation rate and the fact that a high suspicion index is required to make an assertive and timely diagnosis. This is especially important in geographical areas that are endemic to this parasite due to the direct relationship between an early diagnosis and treatment and better visual outcomes. In this case report, we will discuss the multidisciplinary interventions of a pediatric patient in a high complexity hospital.


RESUMO A cisticercose ocular é uma infecção parasitária causada pela Taenia solium. O diagnóstico e tratamento precoces diminuem a possibilidade de morbidade visual. Ela pode comprometer a câmara anterior ou o segmento posterior, o que se traduz em uma apresentação muito variável e interespecífica, que muda dependendo do local da infecção. É importante relatar esse caso devido à sua baixa taxa de apresentação e ao fato de que é necessário um alto índice de suspeita para fazer um diagnóstico assertivo e oportuno. Isso é especialmente importante em áreas geográficas endêmicas para esse parasita, devido à relação direta entre diagnóstico e tratamento precoces e melhores resultados visuais. Neste relato de caso, discutiremos as intervenções multidisciplinares de um paciente pediátrico em um hospital de alta complexidade.


Subject(s)
Humans , Female , Child, Preschool , Cysticercosis/diagnosis , Eye Infections, Parasitic/diagnosis , Retinoblastoma/diagnosis , Vitrectomy , Vitreous Body/cytology , Magnetic Resonance Imaging , Ultrasonography , Taenia solium , Diagnosis, Differential
6.
Molecules ; 27(18)2022 Sep 18.
Article in English | MEDLINE | ID: mdl-36144833

ABSTRACT

In this work, we propose a general methodology to assess the bioactive potential (BP) of extracts in the quest of vegetable-based drugs. To exemplify the method, we studied the anticancer potential (AP) of four endemic species of genus Hypericum (Hypericum canariense L, Hypericum glandulosum Aiton, Hypericum grandifolium Choisy and Hypericum reflexum L.f) from the Canary Islands. Microextracts were obtained from the aerial parts of these species and were tested against six human tumor cell lines, A549 (non-small-cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small-cell lung), T-47D (breast) and WiDr (colon). The methanol-water microextracts were evaluated further for cell migration, autophagy and cell death. The most promising bioactive polar microextracts were analyzed by UHPLC-DAD-MS. The extraction yield, the bioactivity evaluation and the chemical profiling by LC-MS suggested that H. grandifolium was the species with the highest AP. Label-free live-cell imaging studies on HeLa cells exposed to the methanol-water microextract of H. grandifolium enabled observing cell death and several apoptotic hallmarks. Overall, this study allows us to select Hypericum grandifolium Choisy as a source of new chemical entities with a potential interest for cancer treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Hypericum , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Female , HeLa Cells , Humans , Lung Neoplasms/drug therapy , Methanol , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Spain , Water
9.
Ars pharm ; 63(2)abr.-jun. 2022.
Article in Spanish | IBECS | ID: ibc-202817

ABSTRACT

Introducción: Diversos estudios han puesto de manifiesto que los preparados a base de los rizomas y raíces de cimicífuga (Cimicifuga racemosa (L.) Nutt.) pueden ser útiles para aliviar los síntomas menopáusicos. El objetivo de este trabajo es realizar una revisión de la eficacia y seguridad de estos preparados en el tratamiento de los síntomas vasomotores de la menopausia. Método: Se realizó una búsqueda de los artículos publicados desde enero de 2005 a marzo de 2021 en el buscador de recursos de la Universidad de La Laguna, “el Punto Q”. Se seleccionaron los ensayos clínicos aleatorizados y controlados, que tuvieran las palabras claves en el resumen, texto o título, tanto en inglés como en español.Resultados:Se identificaron 13 ensayos clínicos que incluían los criterios de selección establecidos. Se encontró que los preparados de cimicífuga (principalmente extractos comerciales estandarizados en su contenido en principios activos) produjeron en la mayoría de los estudios una reducción significativa comparada con el placebo de los síntomas vegetativos (sofocos y sudores nocturnos) y psicológicos de la menopausia, así como una mejoría de la calidad de vida. No se observaron efectos adversos serios a las dosis utilizadas. Conclusiones: Los extractos de cimicífuga pueden ser eficaces y seguros para el tratamiento de los síntomas vegetativos y psicológicos de la menopausia, siendo bien tolerados. No obstante, son necesarios más ensayos clínicos con mayor número de pacientes, más extensos, uso de preparaciones estandarizadas, así como con criterios similares de inclusión y valoración de los síntomas, para obtener datos más concluyentes.(AU)


Introduction: Several studies have shown that preparations based on the rhizomes and roots of black cohosh (Cimicifuga racemosa (L.) Nutt.) can be useful in alleviating the menopausal symptoms. The aim of this study is to perform an update bibliographic review of the efficacy and safety of black cohosh in the treatment of the vasomotor symptoms of menopause. Method: A review of published articles from January 2005 to March 2021 in the resource search engine of the University of La Laguna, el punto Q”. Randomized and controlled clinical trials, which had the key words in the abstract, text or title, in both English and Spanish, were selected.Results:We found 13 trials which met the selection criteria. The studies reviewed showed that the black cohosh preparations (mainly commercial extracts standardized in their content of active ingredients) produced in most of the studies a significant reduction compared to placebo in the vegetative (hot flashes and night sweats) and psychological symptoms of menopause, as well as an improvement in the quality of life. No serious adverse effects were reported at the dose administered. Conclusions: Cimicifuga racemosa extracts can be effective and safe for the treatment of vegetative and psychological symptoms of menopause, being well tolerated. However, more clinical trials with a larger number of patients, more extensive, the use of standardized preparations, as well as similar criteria for inclusion and assessment of symptoms, are necessary to obtain more conclusive data.(AU)


Subject(s)
Humans , Female , Cimicifuga/chemistry , Plant Extracts/therapeutic use , Menopause , Hot Flashes/drug therapy , Hot Flashes/etiology
11.
Neurologia (Engl Ed) ; 36(8): 611-617, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34654536

ABSTRACT

BACKGROUND AND OBJECTIVE: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. METHODS: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. RESULTS: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P=.320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. CONCLUSION: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.


Subject(s)
COVID-19 , Migraine Disorders , Antibodies, Monoclonal/adverse effects , Calcitonin Gene-Related Peptide , Cross-Sectional Studies , Female , Humans , Middle Aged , Migraine Disorders/drug therapy , Pandemics , SARS-CoV-2
12.
Neurología (Barc., Ed. impr.) ; 36(8): 611-617, octubre 2021. tab
Article in English | IBECS | ID: ibc-220110

ABSTRACT

Background and objective: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus.MethodsThis is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms.ResultsWe recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P = .320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment.ConclusionAnti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19. (AU)


Antecedentes y objetivo: El péptido relacionado con el gen de la calcitonina (CGRP, por sus siglas en inglés), es un neuropéptido involucrado en la fisiopatología de la migraña, que también es conocido por participar en la regulación del sistema respiratorio y en algunas enfermedades inmunológicas como la sepsis. Hemos analizado el impacto del uso de los antagonistas de CGRP en pacientes con migraña durante la pandemia de COVID-19, causada por el coronavirus SARS-CoV-2.MétodosEstudio transversal multicéntrico desarrollado entre mayo y noviembre de 2020, en el que la Sociedad Española de Neurología distribuyó a nivel nacional una encuesta de la que recogimos datos sobre la presencia, las características y la gravedad de síntomas de COVID-19, entre los que se encontraba la cefalea, en pacientes con migraña tratados con anticuerpos monoclonales (AcM) anti-CGRP, y los comparamos con los de pacientes con migraña que no recibían dicho tratamiento. También realizamos un subanálisis de los pacientes con síntomas de COVID-19.ResultadosIdentificamos 300 pacientes con migraña: 51,7% (155/300) recibían AcM anti-CGRP; el 87,3% eran mujeres (262/300) y la edad media (desviación estándar) de la muestra fue de 47,1 (11,6) años. Un total de 41 pacientes (13,7%) cumplían los criterios diagnósticos de COVID-19, sin diferencias estadísticamente significativas entre los pacientes que recibían tratamiento con AcM anti-CGRP y los que no (16,1% y 11,0%, respectivamente; p = 0,320). De los pacientes con COVID-19, el 48,8% (20/41) acudieron a urgencias y el 12,2% (5/41) fueron hospitalizados. Igualmente, no se detectaron diferencias clínicas entre los pacientes que recibían dicho tratamiento y los que no.ConclusiónEl tratamiento con AcM anti-CGRP parece un recurso seguro en la práctica clínica, y no se asocia a un mayor riesgo de COVID-19. (AU)


Subject(s)
Humans , Antibodies, Monoclonal/adverse effects , Calcitonin Gene-Related Peptide , Severe acute respiratory syndrome-related coronavirus , Pandemics , Coronavirus Infections/epidemiology , Cross-Sectional Studies
13.
Elife ; 102021 08 20.
Article in English | MEDLINE | ID: mdl-34414886

ABSTRACT

The trafficking of specific protein cohorts to correct subcellular locations at correct times is essential for every signaling and regulatory process in biology. Gene perturbation screens could provide a powerful approach to probe the molecular mechanisms of protein trafficking, but only if protein localization or mislocalization can be tied to a simple and robust phenotype for cell selection, such as cell proliferation or fluorescence-activated cell sorting (FACS). To empower the study of protein trafficking processes with gene perturbation, we developed a genetically encoded molecular tool named HiLITR (High-throughput Localization Indicator with Transcriptional Readout). HiLITR converts protein colocalization into proteolytic release of a membrane-anchored transcription factor, which drives the expression of a chosen reporter gene. Using HiLITR in combination with FACS-based CRISPRi screening in human cell lines, we identified genes that influence the trafficking of mitochondrial and ER tail-anchored proteins. We show that loss of the SUMO E1 component SAE1 results in mislocalization and destabilization of many mitochondrial tail-anchored proteins. We also demonstrate a distinct regulatory role for EMC10 in the ER membrane complex, opposing the transmembrane-domain insertion activity of the complex. Through transcriptional integration of complex cellular functions, HiLITR expands the scope of biological processes that can be studied by genetic perturbation screening technologies.


Subject(s)
Endoplasmic Reticulum/metabolism , Membrane Proteins/metabolism , Mitochondria/metabolism , Ubiquitin-Activating Enzymes/metabolism , Clustered Regularly Interspaced Short Palindromic Repeats , Flow Cytometry , HEK293 Cells , HeLa Cells , Humans , K562 Cells , Membrane Proteins/genetics , Protein Transport , Signal Transduction/genetics , Ubiquitin-Activating Enzymes/genetics
14.
Neurologia (Engl Ed) ; 2021 Mar 19.
Article in English, Spanish | MEDLINE | ID: mdl-33832802

ABSTRACT

BACKGROUND AND OBJECTIVE: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. METHODS: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. RESULTS: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P=.320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. CONCLUSION: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.

15.
Cell ; 183(7): 2003-2019.e16, 2020 12 23.
Article in English | MEDLINE | ID: mdl-33308478

ABSTRACT

The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here, we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE's modular design, we expressed an optogenetic channel selectively in this cell type and showed that direct recruitment of this otherwise genetically inaccessible population elicits behavioral aversion. The specificity and minute resolution of FLiCRE enables molecularly informed characterization, manipulation, and reprogramming of activated cellular ensembles.


Subject(s)
Behavior, Animal , Calcium/metabolism , Corpus Striatum/metabolism , Animals , Female , HEK293 Cells , Humans , Kinetics , Male , Mice, Inbred C57BL , Neurons/metabolism , Optogenetics , Rats , Single-Cell Analysis , Transcriptome/genetics
16.
Proc Natl Acad Sci U S A ; 117(52): 33186-33196, 2020 Dec 29.
Article in English | MEDLINE | ID: mdl-33323488

ABSTRACT

Molecular integrators, in contrast to real-time indicators, convert transient cellular events into stable signals that can be exploited for imaging, selection, molecular characterization, or cellular manipulation. Many integrators, however, are designed as complex multicomponent circuits that have limited robustness, especially at high, low, or nonstoichiometric protein expression levels. Here, we report a simplified design of the calcium and light dual integrator FLARE. Single-chain FLARE (scFLARE) is a single polypeptide chain that incorporates a transcription factor, a LOV domain-caged protease cleavage site, and a calcium-activated TEV protease that we designed through structure-guided mutagenesis and screening. We show that scFLARE has greater dynamic range and robustness than first-generation FLARE and can be used in culture as well as in vivo to record patterns of neuronal activation with 10-min temporal resolution.

17.
Sensors (Basel) ; 20(19)2020 Sep 29.
Article in English | MEDLINE | ID: mdl-33003422

ABSTRACT

Merging is one of the most critical scenarios that can be found in road transport. In this maneuver, the driver is subjected to a high mental load due to the large amount of information he handles, while making decisions becomes a crucial issue for their safety and those in adjacent vehicles. In previous works, it was studied how the merging maneuver affected the cognitive load required for driving by means of an eye tracking system, justifying the proposal of a driver assistance system for the merging maneuver on highways. This paper presents a merging assistance system based on communications between vehicles, which allows vehicles to share internal variables of position and speed and is implemented on a mobile device located inside the vehicle. The system algorithm decides where and when the vehicle can start the merging maneuver in safe conditions and provides the appropriate information to the driver. Parameters and driving simulator tests are used for the interface definition to develop the less intrusive and demanding one. Afterward, the system prototype was installed in a real passenger car and tests in real scenarios were conducted with several drivers to assess usability and mental load. Comparisons among alternative solutions are shown and effectiveness is assessed.

18.
19.
Sci Rep ; 10(1): 3528, 2020 02 26.
Article in English | MEDLINE | ID: mdl-32103132

ABSTRACT

MitoBlue is a fluorescent bisamidine that can be used to easily monitor the changes in mitochondrial degradation processes in different cells and cellular conditions. MitoBlue staining pattern is exceptional among mitochondrial dyes and recombinant fluorescent probes, allowing the dynamic study of mitochondrial recycling in a variety of situations in living cells. MitoBlue is a unique tool for the study of these processes that will allow the detailed characterization of communication between mitochondria and lysosomes.


Subject(s)
2-Naphthylamine/analogs & derivatives , Amidines/pharmacology , Fibroblasts/metabolism , Lysosomes/metabolism , Mitochondria/metabolism , 2-Naphthylamine/pharmacology , Animals , Chick Embryo , Fibroblasts/cytology , Microscopy, Fluorescence
20.
PLoS One ; 15(1): e0227341, 2020.
Article in English | MEDLINE | ID: mdl-31923258

ABSTRACT

Clan CA cysteine proteases, also known as papain-like proteases, play important roles throughout the malaria parasite life cycle and are therefore potential drug targets to treat this disease and prevent its transmission. In order to study the biological function of these proteases and to chemically validate some of them as viable drug targets, highly specific inhibitors need to be developed. This is especially challenging given the large number of clan CA proteases present in Plasmodium species (ten in Plasmodium falciparum), and the difficulty of designing selective inhibitors that do not cross-react with other members of the same family. Additionally, any efforts to develop antimalarial drugs targeting these proteases will also have to take into account potential off-target effects against the 11 human cysteine cathepsins. Activity-based protein profiling has been a very useful tool to determine the specificity of inhibitors against all members of an enzyme family. However, current clan CA proteases broad-spectrum activity-based probes either target endopeptidases or dipeptidyl aminopeptidases, but not both subfamilies efficiently. In this study, we present a new series of dipeptydic vinyl sulfone probes containing a free N-terminal tryptophan and a fluorophore at the P1 position that are able to label both subfamilies efficiently, both in Plasmodium falciparum and in mammalian cells, thus making them better broad-spectrum activity-based probes. We also show that some of these probes are cell permeable and can therefore be used to determine the specificity of inhibitors in living cells. Interestingly, we show that the choice of fluorophore greatly influences the specificity of the probes as well as their cell permeability.


Subject(s)
Cysteine Proteases/metabolism , Cysteine Proteinase Inhibitors/chemistry , Malaria/enzymology , Animals , Antimalarials/chemistry , Cell Membrane Permeability , Humans , Malaria/diagnostic imaging , Malaria/drug therapy , Molecular Probes/chemistry , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Sulfones , Tryptophan
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