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BACKGROUND: Invasive fungal disease (IFD) causes morbidity and mortality in immunocompromised hosts (ICH). Based on increasing recognition of the impact of IFD on human disease, a recent WHO priority list identified key areas of need. OBJECTIVES: This review examines changes in epidemiology of IFD, in particular emergence of antifungal resistant pathogens and current availability of rapid diagnostic tests and antifungal treatment options. SOURCES: Literature between 2000 and January 2024 regarding fungal epidemiology, diagnostic test, antifungal resistance, emerging fungal pathogens and novel antifungal agents in both adult and pediatric immunocompromised hosts (ICH) was reviewed. CONTENT: We describe the changing epidemiology and continued burden and mortality of IFD in ICH. Further we discuss the emergence of antifungal resistant organisms driven by new immunosuppressed populations, climate change and antifungal exposure in the individual and environment. We highlight novel antifungal agents and how they will address current unmet needs. IMPLICATIONS: The changing epidemiology and increased population at risk for IFD, lack of recognition of or quantification of risks for IFD with new therapies, current gaps in the availability of rapid diagnostic tests and the imminent availability of novel antifungals with distinct spectra of activity argue for improved availability of and access to rapid diagnostics, antifungal stewardship programs and global of access to antifungal agents.
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Introduction: Holter-SRA (Stroke Risk Analysis) is an automated analysis of ECG monitoring for Atrial Fibrillation (AF) detection. The aim of this study was to evaluate the rate of AF in undetermined TIA/Rapidly improving stroke symptoms (RISS) patients. Methods: Prospective study of undetermined TIA/RISS patients who presented to the emergency department. Early vascular studies (angio CT, transthoracic echocardiography and ECG) were performed in emergency department. The Holter-SRA device was placed for 2 h and the patients were classified into: confirmed AF, high risk of AF or low risk of AF. Prolonged ambulatory monitoring (7 days) was carried out every month for patients with a high-risk pattern. The results were evaluated until definitive detection of AF or low-risk pattern. The endpoints were rate of AF and vascular recurrence at 90 days. Results: Over a period of 24 months, 83 undetermined TIA/RISS patients were enrolled. The mean age was 70 ± 10 years and 61% were men. The median ABCD2 score was 4 points (1-7). After 2 h of monitoring in the emergency department, AF was detected in one patient (1.2%), 51 patients with a low-risk pattern and 31 patients (37.3%) showed a high-risk pattern of AF. During the ambulatory monitoring, of the 31 patients high risk pattern patients, AF was diagnosed to 17 cases and of the 51 patients with a low-risk pattern, one case experienced a recurrent vascular due to undetected AF (1.9% false negative). Three patients (3.6%) suffered a vascular recurrence within the first 90 days, before AF diagnosis. Conclusions: In our study, AF was detected in 22.9% of the 83 patients with indeterminate TIA/RISS. Holter-SRA has allowed us to increase the detection of AF, especially those patients with a high-risk pattern in the first 3 months.
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BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.
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Axila , Neoplasias de la Mama , Terapia Neoadyuvante , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Escisión del Ganglio Linfático , Pronóstico , Estudios de Seguimiento , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Metástasis Linfática , Quimioterapia AdyuvanteRESUMEN
Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.
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Complejo Nuclear Basolateral , Ratas , Masculino , Femenino , Animales , Incertidumbre , Complejo Nuclear Basolateral/fisiología , Ratas Long-Evans , Corteza Prefrontal/fisiología , Aprendizaje Inverso/fisiologíaRESUMEN
The Mauritania-Senegalese upwelling region (MSUR), the southernmost region of the Canary current upwelling system, is well-known for its coastal productivity and the key role it plays in enriching the oligotrophic open ocean through the offshore transport of the upwelled coastal waters. The great ecological and socio-economic importance makes it necessary to evaluate the impact of climate change on this region. Hence, our main objective is to examine the climate change signal over the MSUR with a high resolution regional climate system model (RCSM) forced by the Earth system model MPI-ESM-LR under RCP8.5 scenario. This RCSM has a regional atmosphere model (REMO) coupled to a global ocean model (MPIOM) with high-resolution in the MSUR, which allows us to evaluate the wind pattern, the ocean stratification, as well as the upwelling source water depth, while maintaining an ocean global domain. Under RCP8.5 scenario, our results show that the upwelling favourable winds of the northern MSUR are year-round intensified, while the southern MSUR presents a strengthening in winter and a weakening in March-April. Along with changes in the wind pattern, we found increased ocean stratification in the spring months. In those months southern MSUR presents a shallowing of the upwelling source water depth associated to changes in both mechanisms. However, in winter the whole MSUR shows a deepening of the upwelling source water depth due to the intensification of the upwelling favourable winds, with the increased ocean stratification playing a secondary role. Our results demonstrate the need to evaluate the future evolution of coastal upwelling systems taking into account their latitudinal and seasonal variability and the joint contribution of both mechanisms.
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We construct a simple field theory in which a sphaleron, i.e., a saddle-point particle-like solution, forms a semi-BPS state with a background defect that is an impurity. This means that there is no static force between the sphaleron and the impurity. Therefore, such a sphaleron-impurity system is very much like usual BPS multisolitons, however, still possessing an unstable direction allowing for its decay. We study dynamics of the sphaleron in such a system.
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INTRODUCTION: the COVID-19 pandemic had an impact on hospital admissions. The clinical profiles of patients referred to liaison psychiatry teams (LPT) remained stable over the last few decades. We postulate changes in patient profiles due to the COVID-19 pandemic. MATERIALS AND METHODS: a total of 384 patients admitted to a tertiary care University Hospital in Madrid (Spain) and referred to LPTs were recruited. Patients referred 5 months before and after the first admission for COVID-19 were included. Clinical and sociodemographic characteristics were collected, and non-parametric hypothesis contrast tests were used to study possible differences between both periods. RESULTS: patients referred during the pandemic were significantly older (U = 2.006; p = .045), most of them were admitted to medical hospitalization units (χ2 (2) = 5.962; p = 015), and with a different reason for admission. There was an increase in the rate of adjustment disorders (χ2 (1) =7.893; p = 005) and delirium (χ2 (1) =9.413; p = 002), as well as psychiatric comorbidity (χ2 (2) = 9.930; p = .007), and a reduction in the proportion of patients treated for substance misuse (χ2 (5) = 19.152; p = .002). The number of deaths increased significantly (χ2 (1) = 6.611; p = .010). In persons over 65 years inappropriate prescription was significantly lower (χ2 (1) = 8.200; p = .004). CONCLUSIONS: the pandemic had an impact on the activity of the LPTs due to the change in the clinical profile and evolution of referred patients, maintaining standards of care that are reflected through prescription.
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COVID-19 , Trastornos Mentales , Psiquiatría , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Trastornos Mentales/terapia , Pandemias , Derivación y ConsultaRESUMEN
The objective of this study is to determine the prevalence of Fasciola hepatica infection in cattle slaughterhouses, as well as its association with climatic/environmental factors (derived from satellite data), seasonality and climate regions in two states in Mexico. Condemned livers from slaughtered animals were obtained from three abattoirs in the states of Puebla and Veracruz. The overall prevalence of the parasite in cattle between January and December of 2017 was 20.6% (1407 out of 6834); the highest rate of condemnation was observed in Veracruz (26.3%; tropical climate), and the lowest rate was found in Puebla (15.5%; temperate climate). The seasonal prevalence of fluke infection was 18.6%, 14.8% and 28.4% during the wet season, and 17.1%, 12.4% and 22.8% during the dry season in the three abattoir sites, located in the districts of Zacatlán, Teziutlán and Ciudad Alemán, respectively. Liver condemnations due to bovine fasciolosis were prevalent in the Zacatlán, Teziutlán and Ciudad Alemán districts during summer, autumn and summer, respectively. Using generalized estimating equations analysis, we determined six variables - rainfall (wet/dry), land surface temperature day, land surface temperature night, normalized difference vegetation index, seasonality and climate regions (temperate/tropical) - to be significantly associated with the prevalence of condemned livers. Climate region was the variable most strongly associated with F. hepatica infection (odds ratio (OR) 266.59; 95% confidence interval (CI): 241.90-353.34), followed by wet and dry seasons (OR 25.56; 95% CI: 20.56-55.67).
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Enfermedades de los Bovinos , Fasciola hepatica , Fascioliasis , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Fascioliasis/epidemiología , Fascioliasis/veterinaria , México/epidemiología , Prevalencia , Estaciones del Año , Clima TropicalRESUMEN
This study focuses on the development of a new hybrid biological material to be applied in the production of electrical energy. These organo-metallic cells are constituted by cyanobacteria (Fischerella muscicola) and silver nanoparticles (AgNPs). AgNPs were obtained by green synthesis using the extract of the fruit of theBerberis halliiplant as reducing agent with two different concentrations of silver nitrate (AgNO3), 1 and 10 mM. The morphology, physicochemical and electrical properties of the cyanobacteria with and without AgNPs were evaluated. To verify the efficacy of this new material, and the effect of the medium used, Nitrofoska or BG-11, the growth kinetics was evaluated by UV-vis up tot= 63 d with and without renewal of the culture medium and O2/CO2exchange. Through morphological characterizations ofFischerella muscicolait was possible to identify the presence of an associated bacterium identified using molecular techniques asPseudomona guguanensithat could act as a supporting organism in the growth of this cyanobacteria. The studies carried out did not shown cell toxicity for the cultures that have AgNPs and on the other hand, it was observed that the hybrid cells (Cy-AgNPs) are electron carriers recording an increase of up to 57% and 18% in their electrical potential with BG-11 and Nitrofoska culture media, respectively and an increase in the anodic current peak of 6.5% of Cy-AgNPs respect to onlyF. musicola.
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PURPOSE: The diagnosis of a second primary cancer (SPC) is a major concern in the follow-up of survivors of a primary head and neck cancer (HNC), but the anatomic subsites in the head and neck area are close, making it difficult to distinguish a SPC of a recurrence and therefore register it correctly. METHODS: We performed a retrospective cohort study using data from two population-based cancer registries in Catalonia, Spain: the Tarragona Cancer Registry and the Girona Cancer Registry. All patients diagnosed with HNC during the period 1994-2013 were registered and followed-up to collect cases of SPC. We analysed the standardized incidence ratio (SIR) and the excess absolute risk (EAR) to determine the risk of second malignancies following a prior HNC. RESULTS: 923 SPC were found in a cohort of 5646 patients diagnosed of a first head and neck cancer. Men had an increased risk of a SPC with a SIR of 2.22 and an EAR of 216.76. Women also had an increased risk with a SIR of 2.02 and an EAR of 95.70. We show the risk for different tumour sites and discuss the difficulties of the analysis. CONCLUSION: The risks of a SPC following a prior HNC in Tarragona and Girona are similar to those previously found in other similar cohorts. It would appear to be advisable to make a revision of the international rules of classification of multiple tumours, grouping the sites of head and neck area with new aetiological criteria to better determine and interpret the risks of SPC obtained in these studies.
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Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Estudios de Cohortes , Femenino , Neoplasias de Cabeza y Cuello/clasificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias/etiología , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Factores Sexuales , España/epidemiología , Factores de TiempoRESUMEN
The present study evaluates the removal capacity of microalgae photobioreactors of environmental pollutants present in wastewater from the dry riverbed El Albujón, as a way to minimize the eutrophication process of the Mar Menor. Particularly, the capacity of four autochthonous microalgae consortia collected from different locations of the salty lagoon to remove emerging contaminants (simazine, atrazine, terbuthylazine, adenosine and ibuprofen), nitrates, and phosphates, was evaluated. Among the four microalgae consortia, consortium 1 was the best in terms of biomass productivity (0.11 g L-1 d-1) and specific growth rate (0.14 d-1), providing 100% removal of emerging contaminants (simazine, atrazine, terbuthylazine, adenosine and ibuprofen), and a maximal reduction and consumption of macronutrients, especially nitrates and phosphates, reaching levels below 28 mg L-1, that is, a decrease of 89.90 and 99.70% of nitrates and phosphates, respectively. Therefore, this consortium (Monoraphidium sp., Desmodesmus subspicatus, Nannochloris sp.) could be selected as a green filter for successful large-scale applications. This study is the first one that combines the successful removal of herbicides, ibuprofen and adenosine as emerging contaminants, and nitrate removal.
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Microalgas , Biomasa , Eutrofización , Fotobiorreactores , Aguas ResidualesRESUMEN
Mucor species are common soil fungi but also known as agents of human infections (mucormycosis) and used in food production and biotechnology. Mucor circinelloides is the Mucor species that is most frequently isolated from clinical sources. The taxonomy of Mucor circinelloides and its close relatives (Mucor circinelloides complex - MCC) is still based on morphology and mating behaviour. The aim of the present study was a revised taxonomy of the MCC using a polyphasic approach. Using a set of 100 strains molecular phylogenetic analysis of five markers (ITS, rpb1, tsr1, mcm7, and cfs, introduced here) were performed, combined with phenotypic studies, mating tests and the determination of the maximum growth temperatures. The multi-locus analyses revealed 16 phylogenetic species of which 14 showed distinct phenotypical traits and were recognised as discrete species. Five of these species are introduced as novel taxa: M. amethystinus sp. nov., M. atramentarius sp. nov., M. variicolumellatus sp. nov., M. pseudocircinelloides sp. nov., and M. pseudolusitanicus sp. nov. The former formae of M. circinelloides represent one or two separate species. In the MCC, the simple presence of well-shaped zygospores only indicates a close relation of both strains, but not necessarily conspecificity. Seven species of the MCC have been implemented in human infection: M. circinelloides, M. griseocyanus, M. janssenii, M. lusitanicus, M. ramosissimus, M. variicolumellatus, and M. velutinosus.
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Since March 2020, the world is involved in the COVID-19 pandemic, a disease caused by a novel virus called SARS-CoV-2. Some authors have described the ultrasonographic findings of COVID-19 pneumonia in adults and children, but data on neonates are lacking. Our objective was to describe the ultrasonographic lung pattern on newborns with SARS-CoV-2 infection during the COVID-19 pandemic. Newborns who tested positive for SARS-CoV-2 PCR in respiratory samples and were evaluated with point-of-care lung ultrasound (LU) from March to April 2020 were included. LU was performed bedside by a single investigator at the time of diagnosis and every 48 h during the first week following diagnosis. Six areas were studied. Three neonates were included. Infants' comorbidities included meconium aspiration syndrome, bronchopulmonary dysplasia, and Hirschsprung's disease. One required mechanical ventilation. No deaths occurred. LU showed B-lines, consolidation, and spared areas. No pneumothorax or pleural effusion was observedConclusions: LU could be of value when managing COVID-19 neonates. We describe the findings of lung ultrasound monitoring during the first week following diagnosis in three neonates with SARS-CoV-2 infection. What is known: ⢠Lung ultrasound (LU) is a useful tool in COVID-19 management in adults. To date, no report on LU and neonates with SARS-CoV-2 infection has been published. What is new: ⢠This study adds evidence about LU findings in neonates with SARS-CoV-2 infection.
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Betacoronavirus , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Sistemas de Atención de Punto , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Humanos , Recién Nacido , Masculino , Pandemias , Neumonía Viral/complicaciones , SARS-CoV-2 , UltrasonografíaRESUMEN
BACKGROUND: An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae. Among them, phytoprostanes (PhytoPs) and phytofurans (PhytoFs), both autoxidation products of α-linolenic acid, have been seen to exert immunomodulatory and antiinflammatory activities in vitro. The purpose of this study was to explore the bioaccesibility, bioavailability, and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima, and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells. METHODS: The PhytoPs and PhytoFs profile and concentration of G. longissima were determined by UHPLC-QqQ-MS/MS. Algal samples were processed following a standardised digestion method including gastric, intestinal, and gastrointestinal digestion. The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier. The inflammation response of these prostaglandin-like compounds in human endothelial cells, after intestinal absorption, was investigated in vitro. RESULTS: Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42 µg per 100 g, respectively, on average, although permeability through the Caco-2 cell monolayer was high (up to 88.2 and 97.7%, on average, respectively). PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers. The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins, suggesting pro- or anti-inflammatory activity on their part. In this aspect, the cross-reactivity of these compounds with diverse receptors, and their relative concentration could explain the diversity of the effects found in the current study. CONCLUSIONS: The results indicate that PhytoPs and PhytoFs display complex pharmacological profiles probably mediated through their different actions and affinities in the endothelium.
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Antiinflamatorios no Esteroideos/farmacología , Células Endoteliales/efectos de los fármacos , Furanos/farmacología , Gracilaria/química , Oxilipinas/farmacología , Fitoquímicos/farmacología , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/toxicidad , Disponibilidad Biológica , Células CACO-2 , Digestión , Células Endoteliales/metabolismo , Ácidos Grasos Insaturados/farmacocinética , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos Insaturados/toxicidad , Furanos/farmacocinética , Furanos/toxicidad , Humanos , Técnicas In Vitro , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Oxilipinas/farmacocinética , Oxilipinas/toxicidad , Fitoquímicos/farmacocinética , Fitoquímicos/toxicidad , Relación Estructura-ActividadRESUMEN
PURPOSE: To assess the use of external beam radiotherapy in Catalonia (Spain), overall and by health management area. METHODS: We assessed radiotherapy treatments in a cohort of patients diagnosed with cancer from 2009 to 2011, using the population-based cancer registries in Girona and Tarragona. Participants had to have a minimum follow-up of 5 years from the time the cancer registry database was linked to the catalan health service database for financing radiation oncology. Outcomes included the proportion of patients receiving radiotherapy within 1 and 5 years of diagnosis. A log-binomial model was used to assess age-related trends in the use of radiotherapy by tumour site. Finally, we calculated the standardized utilization rate and 95% confidence intervals by health management area covered by the radiation oncology services, using indirect methods. RESULTS: At 1 and 5 years from diagnosis, 21.4 and 24.4% of patients, respectively, had received external beam radiotherapy. Patients aged 40-64 years had the most indications for the treatment, and there was a negative correlation between the patients' age and the use of radiotherapy for most tumour sites (exceptions were cervical, thyroid, and uterine cancers). There were no statistically significant differences in the use of radiotherapy according to th health management area. CONCLUSIONS: Population-based data show that external beam radiotherapy is underutilized in Catalonia. This situation requires a careful analysis to understand the causes, as well as an improvement of the available resources, oriented toward achieving realistic targets for the optimal use of external beam radiotherapy in our country.
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Neoplasias/radioterapia , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Intervalos de Confianza , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Radioterapia/estadística & datos numéricos , España/epidemiología , Tiempo de TratamientoRESUMEN
Given the growing interest in phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in the fields of plant physiology, biotechnology, and biological function, the present study aims to optimize a method of enzymatic hydrolysis that utilizes bacterial and yeast esterases that allow the appropriate quantification of PhytoPs and PhytoFs. To obtain the highest concentration of PhytoPs and PhytoFs, a response surface methodology/Box-Behnken design was used to optimize the hydrolysis conditions. Based on the information available in the literature on the most critical parameters that influence the activity of esterases, the three variables selected for the study were temperature (°C), time (min), and enzyme concentration (%). The optimal hydrolysis conditions retrieved differed between PhytoPs (21.5 °C, 5.7 min, and 0.61 µg of enzyme per reaction) and PhytoFs (20.0 °C, 5.0 min, and 2.17 µg of enzyme per reaction) and provided up to 25.1- and 1.7-fold higher contents relative to nonhydrolyzed extracts. The models were validated by comparing theoretical and experimental values for PhytoP and PhytoF yields (1.01 and 1.06 theoretical/experimental rates, respectively). The optimal conditions were evaluated for their relative influence on the yield of individual nonesterified PhytoPs and PhytoFs to define the limitations of the models for obtaining the highest concentration of most considered compounds. In conclusion, the models developed provided valuable alternatives to the currently applied methods using unspecific alkaline hydrolysis to obtain free nonesterified PhytoPs and PhytoFs, which give rise to more specific hydrolysis of PhytoP and PhytoF esters, reducing the degradation of free compounds by classical chemical procedures.
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Furanos , Pisum sativum , Esterasas , Hidrólisis , Extractos VegetalesRESUMEN
Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood-brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.
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BACKGROUND: A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). METHODS: Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. RESULTS: In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200-350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. CONCLUSIONS: The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.