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1.
Inorg Chem ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39374176

RESUMEN

The present study outlines the synthesis of cadmium sulfide-metal-organic framework (CdS-MOF) MIL-101 (Fe) heterojunctions achieved via fast microwave-assisted reactions. Thus, different CdS-MOF MIL-101 (Fe) ratios were prepared to study their effectiveness as photocatalysts. These compounds were employed in the photocatalytic degradation of methylene blue (MB) under UV and visible irradiation. Structural, morphological, textural, compositional, and optical properties of the synthesized compounds determined by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy were utilized to characterize the structural, morphological, textural, compositional, and optical properties. Electrochemical impedance spectroscopy (EIS) was also employed to determine photovoltage and photocurrent densities. The resulting valence band offset (Vfb) and band gap energy values were utilized to construct an energy band scheme. Our research revealed that the CdS-MOF MIL-101 (Fe) heterojunction enhances the efficiency of electron-hole pair separation, thereby mitigating charge carrier recombination effects. Moreover, the type I electronic band structure established an efficient reaction mechanism, effectively suppressing the recombination of photogenerated electron-hole pairs. The photocatalytic system demonstrated exceptional behavior, achieving complete MB removal within 30 min of reaction time and exhibiting outstanding stability and reusability after four reaction cycles. These findings highlight the potential of the synthesized compounds in the field of wastewater treatment for organic pollutants, offering a promising alternative to current environmental issues.

2.
Transplantation ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39375895

RESUMEN

BACKGROUND: Intensive care to facilitate organ donation (ICOD) involves the initiation or continuation of intensive care for patients with devastating brain injury for donation purposes. In the Spanish system, relatives undergo an early interview to request consent for this procedure. If they consent, a waiting time is agreed upon in the expectation that death by neurological criteria occurs and donation after brain death takes place. Otherwise, relatives can decide on donation after circulatory determination of death or withdrawal of life support. This study analyzes how Spanish transplant coordinators interact with relatives in early interviews and follow-ups on potential donation pathways. METHODS: Semistructured interviews were conducted with a random stratified sample of 23 Spanish transplant coordination teams to explore strategies, practices, and perceptions of ICOD consent requests. The interviews were recorded, transcribed, and analyzed using content analysis. RESULTS: Previous coordination with other units and information retrieval regarding patient and relatives' situations is crucial. The development of early interviews includes an introduction to the family, identification of decision makers, empathizing with relatives and offering condolences, reaffirming the fatal prognosis, explaining the possibility of donating based on the patient's will, confirming the family's understanding and resolving doubts, and ensuring comfort and assessing family needs. CONCLUSIONS: Approaching families to obtain ICOD consent is a regular practice for Spanish coordination teams. It involves a highly professional and diversified set of strategies based on establishing a support relationship for relatives. Our study provides strategies that serve as a reference for obtaining ICOD consent from families in other settings.

4.
Antioxidants (Basel) ; 13(9)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39334705

RESUMEN

Lepidium meyenii Walp (LmW) or Maca, including its bioactive components such as macamides, among others, has demonstrated antioxidant effects. However, the effect size (ES) of LmW on oxidative stress has not been qualitatively described and calculated. The primary objective of this systematic review and meta-analysis was to review and qualitatively describe the studies published up to 2023 that supplemented LmW to control cellular oxidative stress; the secondary objective was to calculate the ES of the different interventions. The search was designed following the PRISMA® guidelines for systematic reviews and meta-analyses and performed in the Web of Science, Scopus, SPORTDiscus, PubMed, and MEDLINE until 2023. The selection of studies included randomized controlled trials, with tests and post-tests, both in vitro and in vivo in animals and humans. The methodological quality and risk of bias were evaluated with the CAMARADES tool. The main variables were reduced glutathione, glutathione peroxidase, superoxide dismutase, and malondialdehyde. The analysis was conducted with a pooled standardized mean difference (SMD) through Hedges' g test (95% CI). Eleven studies were included in the systematic review and eight in the meta-analysis. They revealed a small effect for reduced glutathione (SMD = 0.89), a large effect for glutathione peroxidase (SMD = 0.96), a moderate effect for superoxide dismutase (SMD = 0.68), and a moderate effect for malondialdehyde (SMD = -0.53). According to the results, the phytochemical compounds of LmW effectively controlled cellular oxidative stress, mainly macamides. It was also determined that a higher dose of LmW generated a greater antioxidant effect. However, information concerning humans is scarce.

5.
Obes Surg ; 34(10): 3755-3759, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39251568

RESUMEN

BACKGROUND: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context. METHODS: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m2) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention. RESULTS: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05). CONCLUSION: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Creatina , Suplementos Dietéticos , Músculo Esquelético , Entrenamiento de Fuerza , Humanos , Femenino , Creatina/administración & dosificación , Proyectos Piloto , Adulto , Entrenamiento de Fuerza/métodos , Músculo Esquelético/efectos de los fármacos , Pérdida de Peso , Obesidad Mórbida/cirugía , Fuerza de la Mano , Persona de Mediana Edad , Fuerza Muscular/fisiología , Fuerza Muscular/efectos de los fármacos
6.
Artículo en Inglés | MEDLINE | ID: mdl-39287796

RESUMEN

PURPOSE: Malaria keeps on being a serious global health threat, especially in many tropical countries, where it is endemic. Also in non-endemic countries, like Spain, malaria is an issue that requires attention due to the presence of imported cases. METHODS: This is a retrospective study, including all patients diagnosed with malaria at Severo Ochoa University Hospital from 2006 to 2022, being classified according to: (I) their type of stay in an endemic area as visiting friends and relatives (VFR), migrants of recent arrival (MRA), or tourism and business (T&B), and (II) the mode of presentation as microscopic (MM) or submicroscopic (SMM) malaria. RESULTS: In this study, 132 patients (23.7% of all suspected) were diagnosed with malaria. The PCR was the most sensitive technique (99.2%), followed by antigen detection (78.8%) and microscopy (75%), with Plasmodium falciparum being the predominant species (94.7%). VFR was the largest group infected with malaria (69.7%), mostly symptomatic (98.2%) and presenting MM (90.2%). Instead, MRA patients (25%) presented milder (47.4%) or no symptoms (31.6%) and higher cases of SMM (42.4%). Coinfection with another imported pathogen was present in 19 patients (14.4%), being MRA more frequently coinfected (30.3%) CONCLUSION: This study shows the need for establishing systems for VFRs to attend pre-travel consultations to reduce malaria imported risk. In the case of MRA, screening for imported diseases should be conducted upon their arrival. Finally, we highlight two cases of co-infection with imported viruses, showing that presence of symptoms resembling malaria from another imported pathogen does not exclude malaria.

7.
Gates Open Res ; 8: 5, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319308

RESUMEN

Background: Calcium intake is below recommendations in several parts of the world. Improving calcium intake has benefits not only for bone health but also helps to prevent pregnancy hypertension disorders. Calcium concentration of tap water is usually low The aim of the present study was to determine the maximum amount of calcium that can be added to tap water while complying with drinking water Argentine regulations. Methods: Tap water samples were collected from the Province of Buenos Aires (Argentina). Physicochemical properties and saturation index were measured. Different incremental concentrations of calcium chloride were added to the experimental aliquots. Results: Baseline water had a mean calcium concentration of 22.00 ± 2.54 mg/L, water hardness of 89.9 ± 6.4 mg/L CaCO 3, and a saturation index of -1.50 ± 0.11. After the addition of 0.4554 ± 0.0071 g of salt, water hard-ness reached 355.0 ± 7.1 mg/L CaCO 3, a calcium concentration of 140.50 ± 2.12 mg/L, and a saturation index -0.53 ± 0.02. Conclusions: This study shows that at laboratory level it is feasible to increase calcium concentration of drinking water by adding calcium chloride while complying with national standards. Calcium concentration of drinking tap water could be evaluated and minimum calcium concentration of tap water regulated so as to improve calcium intake in populations with low calcium intake.


Asunto(s)
Calcio , Agua Potable , Agua Potable/química , Agua Potable/normas , Humanos , Argentina , Calcio/análisis , Estudios de Factibilidad , Calcio de la Dieta/análisis , Calidad del Agua/normas , Abastecimiento de Agua/normas , Femenino
8.
Plant Cell Environ ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39253952

RESUMEN

Endoplasmic reticulum-plasma membrane contact sites (ER-PM CSs) are evolutionarily conserved membrane domains found in all eukaryotes, where the ER closely interfaces with the PM. This short distance is achieved in plants through the action of tether proteins such as synaptotagmins (SYTs). Arabidopsis comprises five SYT members (SYT1-SYT5), but whether they possess overlapping or distinct biological functions remains elusive. SYT1, the best-characterized member, plays an essential role in the resistance to abiotic stress. This study reveals that the functionally redundant SYT1 and SYT3 genes, but not SYT5, are involved in salt and cold stress resistance. We also show that, unlike SYT5, SYT1 and SYT3 are not required for Pseudomonas syringae resistance. Since SYT1 and SYT5 interact in vivo via their SMP domains, the distinct functions of these proteins cannot be caused by differences in their localization. Interestingly, structural phylogenetic analysis indicates that the SYT1 and SYT5 clades emerged early in the evolution of land plants. We also show that the SYT1 and SYT5 clades exhibit different structural features in their SMP and Ca2+ binding of their C2 domains, rationalizing their distinct biological roles.

9.
J Clin Med ; 13(16)2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39201109

RESUMEN

Background/Objectives: Radiography is an essential and low-cost diagnostic method in pulmonary medicine that is used for the early detection and monitoring of lung diseases. An adequate and consistent image quality (IQ) is crucial to ensure accurate diagnosis and effective patient management. This pilot study evaluates the feasibility and effectiveness of the International Atomic Energy Agency (IAEA)'s remote and automated quality control (QC) methodology, which has been tested in multiple imaging centers. Methods: The data, collected between April and December 2022, included 47 longitudinal data sets from 22 digital radiographic units. Participants submitted metadata on the radiography setup, exposure parameters, and imaging modes. The database comprised 968 exposures, each representing multiple image quality parameters and metadata of image acquisition parameters. Python scripts were developed to collate, analyze, and visualize image quality data. Results: The pilot survey identified several critical issues affecting the future implementation of the IAEA method, as follows: (1) difficulty in accessing raw images due to manufacturer restrictions, (2) variability in IQ parameters even among identical X-ray systems and image acquisitions, (3) inconsistencies in phantom construction affecting IQ values, (4) vendor-dependent DICOM tag reporting, and (5) large variability in SNR values compared to other IQ metrics, making SNR less reliable for image quality assessment. Conclusions: Cross-comparisons among radiography systems must be taken with cautious because of the dependence on phantom construction and acquisition mode variations. Awareness of these factors will generate reliable and standardized quality control programs, which are crucial for accurate and fair evaluations, especially in high-frequency chest imaging.

10.
Cell Rep Med ; 5(8): 101669, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39127040

RESUMEN

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid ß (Aß)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aß amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aß in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Encéfalo , Placa Amiloide , Proteómica , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Proteómica/métodos , Animales , Péptidos beta-Amiloides/metabolismo , Humanos , Placa Amiloide/metabolismo , Placa Amiloide/patología , Ratones , Encéfalo/metabolismo , Encéfalo/patología , Proteoma/metabolismo , Ratones Transgénicos , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Citocinas/metabolismo , Masculino
11.
Clin Transl Oncol ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158803

RESUMEN

PURPOSE: Concurrent chemoradiotherapy (cCRT) is the standard treatment for locally advanced and unresectable non-small-cell lung cancer. Population is aging, and Geriatric assessment (GA) has demonstrated its paper to select fit patients for active treatment and vulnerable, frail patients for interventions and/or palliative care in many histologies. Its role in locally advanced, unresectable non-small-cell lung cancer has been less explored. METHODS: To assess the capability of GA to detect frail patients not suitable for active treatment, we developed this exploratory non-interventional prospective study. All patients ≥ 70 years diagnosed with stage locally advanced and unresectable non-small-cell lung cancer were invited to undergo geriatric assessment. Secondary aims were description of population, exploring GA as prognostic factor, determination of toxicity profile and look for a frailty biomarker. RESULTS: From June 2017 to June 2020, 51 patients were included, of whom 35% (n:18) were classified as frail. Frail patients had less overall survival and more grade 3-4 toxicity. Exploratory results for frailty phenotype are described in the text. CONCLUSIONS: With the results of our study, we confirm that GA can detect frail patients unsuitable for treatment, with a higher risk of toxicity and less overall survival. A trend toward blood-test results for phenotype frailty can be hypothesis generation.

12.
Eur J Sport Sci ; 24(9): 1260-1269, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38949958

RESUMEN

Change of directions (COD) involves multidirectional and complex actions, with performance influenced by multiple factors. As lower limb strength is one of the most determinant of COD performance, the present study aimed to (a) explore the differences in strength outcomes across different lower limb muscle actions between faster and slower basketball players in COD actions at different angles and (b) analyse the relationship between isometric, concentric and eccentric strength outcomes and COD performance at different cutting angles. Twenty-five basketball players (44% female) completed a battery of tests, encompassing isokinetic and isometric squat strength assessments, along with COD tests at 45°, 90° and 180°. Players were categorised as 'low-performance' and 'high-performance' groups based on execution time in COD, facilitating a comparison between performance groups. Results indicated that concentric strength showed the greatest differences between performance groups at 45° COD (effect size ≥ 0.813; p ≤ 0.034). Isometric and eccentric strength demonstrated a moderate-to-large relationship with 90° COD performance (Rho ≥ 0.394; p ≤ 0.045), and all muscle actions exhibited a large relationship with 180° COD (Rho ≥ 0.445; p ≤ 0.030). Moreover, the fastest players showed higher levels of concentric strength relative to eccentric strength, regardless of the cutting angle. These findings hold practical applications, suggesting that basketball coaches should train a specific kind of muscle action depending on the individual players' COD demands, focusing on improving the rapid eccentric force application while striving to reduce the eccentric/concentric ratio.


Asunto(s)
Rendimiento Atlético , Baloncesto , Extremidad Inferior , Fuerza Muscular , Humanos , Baloncesto/fisiología , Fuerza Muscular/fisiología , Masculino , Femenino , Rendimiento Atlético/fisiología , Adulto Joven , Extremidad Inferior/fisiología , Músculo Esquelético/fisiología , Contracción Isométrica/fisiología , Adulto , Adolescente
13.
Artículo en Inglés | MEDLINE | ID: mdl-39042515

RESUMEN

Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in >90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity.

15.
NanoImpact ; 35: 100517, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38848992

RESUMEN

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.


Asunto(s)
Nanopartículas Magnéticas de Óxido de Hierro , Espermatozoides , Testículo , Masculino , Animales , Ratones , Testículo/efectos de los fármacos , Nanopartículas Magnéticas de Óxido de Hierro/toxicidad , Nanopartículas Magnéticas de Óxido de Hierro/química , Espermatozoides/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Citrato de Sodio , Células Cultivadas
16.
Sensors (Basel) ; 24(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38894200

RESUMEN

Chicken behavior recognition is crucial for a number of reasons, including promoting animal welfare, ensuring the early detection of health issues, optimizing farm management practices, and contributing to more sustainable and ethical poultry farming. In this paper, we introduce a technique for recognizing chicken behavior on edge computing devices based on video sensing mosaicing. Our method combines video sensing mosaicing with deep learning to accurately identify specific chicken behaviors from videos. It attains remarkable accuracy, achieving 79.61% with MobileNetV2 for chickens demonstrating three types of behavior. These findings underscore the efficacy and promise of our approach in chicken behavior recognition on edge computing devices, making it adaptable for diverse applications. The ongoing exploration and identification of various behavioral patterns will contribute to a more comprehensive understanding of chicken behavior, enhancing the scope and accuracy of behavior analysis within diverse contexts.


Asunto(s)
Crianza de Animales Domésticos , Conducta Animal , Pollos , Metodologías Computacionales , Crianza de Animales Domésticos/instrumentación , Crianza de Animales Domésticos/métodos , Grabación en Video , Animales , Aprendizaje Profundo
17.
Rev Soc Bras Med Trop ; 57: e004072024, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38896654

RESUMEN

BACKGROUND: Dengue is a disease that accounts for a major morbidity and mortality in Honduras. METHODS: This descriptive study used an analytical component based on the data from the National Virology Laboratory between 2016-2022. Ordinal logistic regression was used to identify the factors associated with the classification of dengue without warning signs (DWOS), dengue with warning signs (DWS), and severe dengue (SD). RESULTS: Overall, 14,687 dengue cases were included; 50.1% had DWOS, 36.5% had DWS, and 13.4% had SD. Patients that were more associated with a higher probability of DWS and SD were patients in the age groups 1-4 years (DWS OR 1.61; 95%CI:1.33-1.94), (SD OR 1.52; 95% CI:1.26-1.84), 5-9 years (DWS OR 2.01; 95% CI:1.68-2.40), (SD OR 2.00; 95% CI:1.67-2.40), and 10-19 years (DWS OR 1.55; 95% CI:1.30-1.85) (SD OR 1.57; 95% CI:1.31-1.88). The departments that were associated with a higher probability of DWS and SD were La Paz (OR 6.35; 95% CI:3.53-11.42), (OR 10.94; 95% CI:5.96-20.08), Copán (OR 6.94; 95% CI:5.05-9.53) (OR 7.33; 95% CI: 5.35-10.03), Valle (OR 5.22; 95% CI:1.25-21.82) (OR 10.71; 95% CI:2.21-51.88). CONCLUSIONS: During the study period, dengue presented endemic behavior, with peaks consistent with the last two epidemics in Honduras in 2015 and 2019. The main factors associated with dengue severity were age< 19 years, male sex, and being from La Paz, Copán, or Valle.


Asunto(s)
Dengue , Índice de Severidad de la Enfermedad , Humanos , Honduras/epidemiología , Masculino , Adolescente , Niño , Femenino , Dengue/epidemiología , Adulto , Adulto Joven , Preescolar , Lactante , Persona de Mediana Edad , Factores de Riesgo , Dengue Grave/epidemiología
18.
Angew Chem Int Ed Engl ; 63(34): e202405823, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38856634

RESUMEN

Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of ß-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.


Asunto(s)
Aspergillus fumigatus , Dominio Catalítico , Anticuerpos de Dominio Único , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/farmacología , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/enzimología , Cryptococcus neoformans/enzimología , Cryptococcus neoformans/inmunología , Antifúngicos/química , Antifúngicos/farmacología , Animales , Ratones , Glucano Endo-1,3-beta-D-Glucosidasa
19.
J Trace Elem Med Biol ; 85: 127473, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38795413

RESUMEN

INTRODUCTION: Zinc (Zn) deficiency has been described not only on general human health but also within the sports context -as negatively affecting performance-. Thus, Zn status assessment is of great interest for athletes, especially in order to correct deficiency states of this mineral. OBJECTIVE: The overall objective of this work was to assess Zn status in professional handball players during the competitive period (through plasma levels, dietary intake and gene expression of the Zn transporters), as well as to determine the effect of Zn supplementation. METHODS: A total of twenty-two participants were recruited, -twelve belonged to the Control Group (CG) and ten male handball players comprised the experimental group (ATH-G)-, being monitored over a 2-month period with 2 evaluation moments: baseline (i.e., initial conditions) and follow-up (i.e., after 8 weeks of training and competition). Zn intake, plasma Zn levels, and gene expression of Zn transporters were obtained. RESULTS: Plasma Zn levels were higher in ATH-G than in CG at the end of Zn intervention (p ≤ 0.010). Moreover, differences in the gene expression profile of Zn transporters were observed in ATH-G -with the down-regulation of several Zn transporters-, compared to the CG at baseline (p ≤ 0.05). Likewise, differences in the Zn transporters expression were observed in ATH-G at 8 weeks (all, p ≤ 0.001) -with ZnT2, ZnT5, ZIP3, ZIP5, ZIP11, ZIP13 and ZIP14 transporters being up-regulated-. CONCLUSION: Handball players seemed to have different nutritional needs for Zn, with differences in the gene expression of Zn transporters compared to controls. Zn intervention in our athletes may have influenced the expression of Zn transporters, indicating a potential increase in Zn transporters expression to mobilize Zn at the cellular level at 8 weeks of Zn intervention.


Asunto(s)
Atletas , Suplementos Dietéticos , Zinc , Humanos , Masculino , Zinc/sangre , Zinc/metabolismo , Adulto Joven , Adulto , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Deportes
20.
Fam Cancer ; 23(3): 383-392, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38753287

RESUMEN

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sistema de Registros , Humanos , Neoplasias Pancreáticas/genética , Persona de Mediana Edad , España , Femenino , Masculino , Adulto , Anciano , Estudios de Seguimiento , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico , Anciano de 80 o más Años , Predisposición Genética a la Enfermedad , Detección Precoz del Cáncer/métodos , Imagen por Resonancia Magnética , Endosonografía , Factores de Riesgo , Carcinoma
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