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Arthropod herbivory poses a serious threat to crop yield, prompting plants to employ intricate defense mechanisms against pest feeding. The generalist pest 2-spotted spider mite (Tetranychus urticae) inflicts rapid damage and remains challenging due to its broad target range. In this study, we explored the Arabidopsis (Arabidopsis thaliana) response to T. urticae infestation, revealing the induction of abscisic acid (ABA), a hormone typically associated with abiotic stress adaptation, and stomatal closure during water stress. Leveraging a Forster resonance energy transfer (FRET)-based ABA biosensor (nlsABACUS2-400n), we observed elevated ABA levels in various leaf cell types postmite feeding. While ABA's role in pest resistance or susceptibility has been debated, an ABA-deficient mutant exhibited increased mite infestation alongside intact canonical biotic stress signaling, indicating an independent function of ABA in mite defense. We established that ABA-triggered stomatal closure effectively hinders mite feeding and minimizes leaf cell damage through genetic and pharmacological interventions targeting ABA levels, ABA signaling, stomatal aperture, and density. This study underscores the critical interplay between biotic and abiotic stresses in plants, highlighting how the vulnerability to mite infestation arising from open stomata, crucial for transpiration and photosynthesis, reinforces the intricate relationship between these stress types.
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Ácido Abscísico , Arabidopsis , Herbivoria , Estomas de Plantas , Tetranychidae , Animales , Ácido Abscísico/metabolismo , Tetranychidae/fisiología , Estomas de Plantas/fisiología , Arabidopsis/fisiología , Arabidopsis/genética , Arabidopsis/parasitología , Transducción de Señal , Hojas de la Planta/parasitología , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismoRESUMEN
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.
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BACKGROUND: HIV stigma and discrimination are drivers of adverse HIV outcomes because they deter individuals from engaging in the HIV care continuum. We estimate the prevalence of public stigma towards people with HIV, investigate individuals' sociodemographic determinants for reporting stigmatizing attitudes, and test the impact of HIV stigma on HIV testing uptake. METHODS: This was an observational study based on an analysis of cross-sectional surveys from 64 low- and middle-income countries. We used nationally representative survey data for the population aged 15-49 years from 2015 to 2021, which was the latest available data. HIV public stigma was measured using an index of two questions about attitudes towards people with HIV. First, prevalence estimates of HIV stigma were calculated by country, across countries, and by sociodemographic characteristics. Second, country fixed-effects multivariable logistic regression models were fit to assess sociodemographic determinants of holding stigmatizing attitudes towards people with HIV. Additional logistic regression models assessed country-level income and HIV prevalence as determinants of stigma and assessed the role of HIV public stigma as a driver of testing uptake. RESULTS: A total of 1 172 841 participants were included in the study. HIV stigma was prevalent in all countries, ranging from 12.87% in Rwanda to 90.58% in Samoa. There was an inverse dose-response association between HIV stigma and educational level, wealth quintile, and age group, whereby higher levels of each were associated with lower odds of holding stigmatized attitudes towards people with HIV. The odds of stigmatized attitudes were lower among men and individuals with adequate knowledge of HIV. HIV stigma was lower in countries with greater gross domestic product per capita and HIV prevalence. Holding stigmatized attitudes towards people with HIV was associated with lower testing uptake, including having ever tested or having tested in the last year. CONCLUSION: HIV stigma is present to a highly varying degree in all countries studied, so different approaches to reducing stigma towards people with HIV are required across settings. Action to eliminate HIV stigma is crucial if we are to progress towards ending HIV because holding stigmatized attitudes towards people with HIV was associated with reduced testing.
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Infecciones por VIH , Masculino , Humanos , Estudios Transversales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prevalencia , Países en Desarrollo , Estigma Social , Prueba de VIHRESUMEN
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown etiology characterized by infiltration of encephalitogenic cells in the central nervous system (CNS) resulting in the presence of multifocal areas of demyelination leading to neurodegeneration. The infiltrated immune cells population is composed mainly of effector CD4+ and CD8+ T lymphocytes, B cells, macrophages, and dendritic cells that secrete pro-inflammatory factors that eventually damage myelin leading to axonal damage. The most common clinical form of MS is relapsing-remitting (RR), characterized by neuroinflammatory episodes followed by partial or total recovery of neurological deficits. The first-line treatment for RRMS relapses is a high dose of glucocorticoids, especially methylprednisolone, for three to five consecutive days. Several studies have reported the beneficial effects of melatonin in the context of neuroinflammation associated with MS or experimental autoimmune encephalomyelitis (EAE), the preclinical model for MS. Therefore, the objective of this study was to evaluate the effect of the combined treatment of melatonin and methylprednisolone on the neuroinflammatory response associated with the EAE development. This study shows for the first time the protective synergistic effect of co-treatment with melatonin and methylprednisolone on reducing the severity of EAE by decreasing CD4 lymphocytes, B cells, macrophages and dendritic cells in the CNS, as well as modulating the population of infiltrated T and B cells toward regulatory phenotypes to the detriment of pro-inflammatory effector functions. In addition to the potentiation of the protective role of methylprednisolone, treatment with melatonin from the clinical onset of EAE improves the natural course of the EAE and the response to a subsequent treatment with methylprednisolone in a later relapse of the disease, pointing melatonin as potential therapeutic tool in combination with methylprednisolone for the treatment of relapses in MS.
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We report the cases of two Spanish pediatric patients with hypotonia, muscle weakness and feeding difficulties at birth. Whole-exome sequencing (WES) uncovered two new homozygous VAMP1 (Vesicle Associated Membrane Protein 1) splicing variants, NM_014231.5:c.129+5 G > A in the boy patient (P1) and c.341-24_341-16delinsAGAAAA in the girl patient (P2). This gene encodes the vesicle-associated membrane protein 1 (VAMP1) that is a component of a protein complex involved in the fusion of synaptic vesicles with the presynaptic membrane. VAMP1 has a highly variable C-terminus generated by alternative splicing that gives rise to three main isoforms (A, B and D), being VAMP1A the only isoform expressed in the nervous system. In order to assess the pathogenicity of these variants, expression experiments of RNA for VAMP1 were carried out. The c.129+5 G > A and c.341-24_341-16delinsAGAAAA variants induced aberrant splicing events resulting in the deletion of exon 2 (r.5_131del; p.Ser2TrpfsTer7) in the three isoforms in the first case, and the retention of the last 14 nucleotides of the 3' of intron 4 (r.340_341ins341-14_341-1; p.Ile114AsnfsTer77) in the VAMP1A isoform in the second case. Pathogenic VAMP1 variants have been associated with autosomal dominant spastic ataxia 1 (SPAX1) and with autosomal recessive presynaptic congenital myasthenic syndrome (CMS). Our patients share the clinical manifestations of CMS patients with two important differences: they do not show the typical electrophysiological pattern that suggests pathology of pre-synaptic neuromuscular junction, and their muscular biopsies present hypertrophic fibers type 1. In conclusion, our data expand both genetic and phenotypic spectrum associated with VAMP1 variants.
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Homocigoto , Síndromes Miasténicos Congénitos , Fenotipo , Proteína 1 de Membrana Asociada a Vesículas , Femenino , Humanos , Masculino , Empalme Alternativo/genética , Secuenciación del Exoma , Mutación , Síndromes Miasténicos Congénitos/genética , Síndromes Miasténicos Congénitos/patología , Isoformas de Proteínas/genética , Empalme del ARN/genética , Proteína 1 de Membrana Asociada a Vesículas/genética , Lactante , PreescolarRESUMEN
Pseudomonas aeruginosa infections have become a serious threat to public health due to the increasing emergence of extensively antibiotic-resistant strains and high mortality rates. Therefore, the search for new therapeutic alternatives has become crucial. In this study, the antivirulence and antibacterial activity of methyl gallate was evaluated against six clinical isolates of extensively antibiotic-resistant P. aeruginosa. Methyl gallate exhibited minimal inhibitory concentrations of 256 to 384 µg/mL; moreover, the use of subinhibitory concentrations of the compound inhibited biofilm formation, swimming, swarming, proteolytic activity, and pyocyanin production. Methyl gallate plus antipseudomonal antibiotics showed a synergistic effect by reduced the MICs of ceftazidime, gentamicin and meropenem. Furthermore, the potential therapeutic effect of methyl gallate was demonstrated in an infection model. This study evidenced the antivirulence and antimicrobial activity of methyl gallate as a therapeutic alternative against P. aeruginosa.
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Comparative extinction risk analysis-which predicts species extinction risk from correlation with traits or geographical characteristics-has gained research attention as a promising tool to support extinction risk assessment in the IUCN Red List of Threatened Species. However, its uptake has been very limited so far, possibly because existing models only predict a species' Red List category, without indicating which Red List criteria may be triggered. This prevents such approaches to be integrated into Red List assessments. We overcome this implementation gap by developing models that predict the probability of species meeting individual Red List criteria. Using data on the world's birds, we evaluated the predictive performance of our criterion-specific models and compared it with the typical criterion-blind modelling approach. We compiled data on biological traits (e.g. range size, clutch size) and external drivers (e.g. change in canopy cover) often associated with extinction risk. For each specific criterion, we modelled the relationship between extinction risk predictors and species' Red List category under that criterion using ordinal regression models. We found criterion-specific models were better at identifying threatened species compared to a criterion-blind model (higher sensitivity), but less good at identifying not threatened species (lower specificity). As expected, different covariates were important for predicting extinction risk under different criteria. Change in annual temperature was important for criteria related to population trends, while high forest dependency was important for criteria related to restricted area of occupancy or small population size. Our criteria-specific method can support Red List assessors by producing outputs that identify species likely to meet specific criteria, and which are the most important predictors. These species can then be prioritised for re-evaluation. We expect this new approach to increase the uptake of extinction risk models in Red List assessments, bridging a long-standing research-implementation gap.
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Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Conservación de los Recursos Naturales/métodos , Extinción Biológica , Bosques , Medición de Riesgo , BiodiversidadRESUMEN
BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.
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Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10-93 years, body mass index: 14-41 kg/m2 ) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hbmass ), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kgBM ) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kgLBM ). Hbmass /BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kgBM ) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kgLBM )/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R2 = .72, p < .001) and Hbmass (R2 = .81, p < .001). These data may only be valid for BV/Hbmass when assessed by CO re-breathing. Hbmass /LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis.
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Ejercicio Físico , Hemoglobinas , Masculino , Humanos , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Valores de Referencia , Índice de Masa Corporal , Hemoglobinas/análisis , Volumen SanguíneoRESUMEN
DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case-control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score.
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Bacteriemia , Cultivo de Sangre , Endocarditis Bacteriana , Enterococcus faecalis , Infecciones por Bacterias Grampositivas , Humanos , Enterococcus faecalis/aislamiento & purificación , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Estudios Retrospectivos , Cultivo de Sangre/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Estudios de Casos y Controles , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/sangre , Factores de Tiempo , Adulto , Anciano de 80 o más Años , Sensibilidad y Especificidad , Valor Predictivo de las PruebasRESUMEN
Complex IrH5(PiPr3)2 (1) activates two different σ-bonds of 3-phenoxy-1-phenylisoquinoline, 2-(1H-benzimidazol-2-yl)-6-phenylpyridine, 2-(1H-indol-2-yl)-6-phenylpyridine, 2-(2-hydroxyphenyl)-6-phenylpyridine, N-(2-hydroxyphenyl)-N'-phenylimidazolylidene, and 1,3-di(2-pyridyl)-4,6-dimethylbenzene to give IrH{κ3-C,N,C-[C6H4-isoqui-O-C6H4]}(PiPr3)2 (2), IrH{κ3-N,N,C-[NBzim-py-C6H4]}(PiPr3)2 (3), IrH{κ3-N,N,C-[Ind-py-C6H4]}(PiPr3)2 (4), IrH{κ3-C,N,O-[C6H4-py-C6H4O]}(PiPr3)2 (5), IrH{κ3-C,C,O-[C6H4-Im-C6H4O]}(PiPr3)2 (6), and IrH{κ3-N,C,C-[py-C6HMe2-C5H3N]}(PiPr3)2 (7), respectively. The activations are sequential, with the second generally being the slowest. Accordingly, dihydride intermediates IrH2{κ2-C,N-[C6H4-isoqui-O-C6H5]}(PiPr3)2 (2d), IrH2{κ2-N,N-[NBzim-py-C6H5]}(PiPr3)2 (3d), IrH2{κ2-N,N-[Ind-py-C6H5]}(PiPr3)2 (4d), and IrH2{κ2-N,C-[py-C6HMe2-py]}(PiPr3)2 (7d) were characterized spectroscopically. Complexes 3 and 5 are green phosphorescent emitters upon photoexcitation, exhibiting good absorption over a wide range of wavelengths, emission quantum yields about 0.70 in solution, long enough lifetimes (10-17 µs), and reversible electrochemical behavior. In agreement with these features, complex 3 promotes the photocatalytic α-amino C(sp3)-H arylation of N,N-dimethylaniline and N-phenylpiperidine with 1,4-dicyanobenzene and 4-cyanopyridine under blue LED light irradiation. The C-C coupling products are isolated in high yields with only 2 mol % of photocatalyst after 24 h.
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PURPOSE OF REVIEW: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. RECENT FINDINGS: Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.
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Terapias Complementarias , Medicina Integrativa , Oncología Integrativa , Neoplasias , Humanos , Calidad de Vida , Desarrollo de Programa , Neoplasias/terapiaRESUMEN
BACKGROUND: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving ANKRD11 cause KBG syndrome, but no genotype-phenotype correlation has been reported. METHODS: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in >50% of the patients and a 'phenotypical score' were used to perform a genotype-phenotype correlation in 340 patients from our cohort and the literature. RESULTS: Neurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions. CONCLUSION: We present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype-phenotype correlation between some KBG features and specific ANKRD11 variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.
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Anomalías Múltiples , Trastorno del Espectro Autista , Enfermedades del Desarrollo Óseo , Discapacidad Intelectual , Anomalías Dentarias , Masculino , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/genética , Anomalías Múltiples/diagnóstico , Enfermedades del Desarrollo Óseo/genética , Anomalías Dentarias/genética , Facies , Trastorno del Espectro Autista/genética , Variaciones en el Número de Copia de ADN , Proteínas Represoras/genética , Deleción Cromosómica , Fenotipo , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: The i-gel® Plus is a modified version of the i-gel® supraglottic airway device. It contains a wider drainage port; a longer tip; ramps inside the breathing channel; and an additional port for oxygen delivery. There has been no prospective evaluation of this device in clinical practice. METHODS: This international, multicentre, prospective cohort study aimed to evaluate the performance of the i-gel Plus in adult patients undergoing elective procedures under general anaesthesia. The primary outcome was overall insertion success rate, defined as the ability to provide effective airway management through the device from insertion until the end of the surgical procedure. Secondary outcomes included device performance and incidence of postoperative adverse events. Data from the first 1000 patients are reported. RESULTS: In total, 1012 patients were enrolled; 12 forms were excluded from the final analysis due to incomplete data leaving 1000 included patients (545 female). Overall insertion success rate was 98.6%, with a first-attempt success rate of insertion of 88.2%. A significant difference between females and males was seen for the overall success rate (97.4% vs. 99.6% respectively) but not for first-attempt successful insertion. Mean (SD) oropharyngeal seal pressure was 32 (7) cmH2O. The only independent factor that increased the risk of first-attempt failure was low operator experience. Complications included desaturation < 85% in 0.6%; traces of blood on the device in 7.4%; laryngospasm in 0.5%; and gastric contents inside the bowl in 0.2% of patients. CONCLUSIONS: The i-gel Plus appears to be an effective supraglottic airway device that is associated with a high insertion success rate and a reasonably low incidence of complications.
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Aspergillus fumigatus and Fusarium solani infections have become severe health threat; both pathogens are considered a priority due to the increasing emergence of antifungal-resistant strains and high mortality rates. Therefore, the discovery of new therapeutic strategies has become crucial. In this study, we evaluated the antifungal and antivirulence effects of vanillin and tannic acid against Aspergillus fumigatus and Fusarium solani. The minimum inhibitory concentrations of the compounds were determined by the microdilution method in RPMI broth in 96-well microplates according to CLSI. Conidial germination, protease production, biofilm formation, and in vivo therapeutic efficacy assays were performed. The results demonstrated that vanillin and tannic acid had antifungal activity against Aspergillus fumigatus, while tannic acid only exhibited antifungal activity against Fusarium solani. We found that vanillin and tannic acid inhibited conidial germination and secreted protease production and biofilm formation of the fungal pathogens using sub-inhibitory concentrations. Besides, vanillin and tannic acid altered the fungal membrane permeability, and both compounds showed therapeutic effect against aspergillosis and fusariosis in an infection model in Galleria mellonella larvae. Our results highlight the antivirulence effect of vanillin and tannic acid against priority pathogenic fungi as a possible therapeutic alternative for human fungal infections.
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Antifúngicos , Aspergillus fumigatus , Benzaldehídos , Biopelículas , Fusarium , Pruebas de Sensibilidad Microbiana , Polifenoles , Taninos , Benzaldehídos/farmacología , Fusarium/efectos de los fármacos , Taninos/farmacología , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Aspergillus fumigatus/efectos de los fármacos , Animales , Aspergilosis/microbiología , Aspergilosis/tratamiento farmacológico , Virulencia/efectos de los fármacos , Larva/microbiología , Larva/efectos de los fármacos , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Esporas Fúngicas/efectos de los fármacos , Mariposas Nocturnas/microbiología , Mariposas Nocturnas/efectos de los fármacosRESUMEN
BACKGROUND: Chronicity and lack of motivation often go together during the upper limb rehabilitation process in stroke. Virtual reality is a useful tool in this context, providing safe, intensive, individualised treatments in a playful environment. B-cost, easy-to-use devices with personalised and motivating games for a specific population seem to be the most effective option in the treatment of the upper limbs. METHODS: A randomised clinical study with follow-up was carried out to assess the effectiveness of the Leap Motion Controller® device in improving the functionality of the upper limb in patients with chronic stroke. Patients (n = 36) were randomised into a control group that performed conventional therapy and an experimental group that combined the virtual reality protocol with conventional therapy. The outcome measures used were grip strength; the Block and Box Test; the Action Research Arm Test; the Disabilities of the Arm, Shoulder and Hand; as well as a Technology Satisfaction Questionnaire and adherence to treatment. RESULTS: Inter-group statistical analysis showed no significant differences except in subsection D of the Action Research Arm Test. Intra-group analysis showed significant differences in both groups, but the experimental group reached significance in all long-term variables. Satisfaction and adherence levels were very high. CONCLUSIONS: The Leap Motion Controller® system, as a complementary tool, produces improvements in grip strength, dexterity and motor function in patients with chronic stroke. It is perceived as a safe, motivating, and easy-to-use device. CLINICAL REGISTRATION: NCT04166617 Clinical Trials.
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Accidente Cerebrovascular , Realidad Virtual , Humanos , Extremidad Superior , Mano , Accidente Cerebrovascular/terapia , Fuerza de la ManoRESUMEN
BACKGROUND: Stroke is a leading cause of disability, especially due to an increased fall risk and postural instability. The objective of this study was to analyze the impact of motor impairment in the hemiparetic UE on static balance in standing, in subject with chronic stroke. METHODS: Seventy adults with chronic stroke, capable of independent standing and walking, participated in this cross-sectional study. The exclusion criteria included vestibular, cerebellar, or posterior cord lesions. The participants were classified based on their UE impairment using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA-UE). A posturographic evaluation (mCTSIB) was performed in the standing position to analyze the center of pressure (COP) displacement in the mediolateral (ML) and anteroposterior (AP) axes and its mean speed with eyes open (OE) and closed (EC) on stable and unstable surfaces. RESULTS: A strong and significant correlation (r = -0.53; p < 0.001) was observed between the mediolateral (ML) center of pressure (COP) oscillation and the FMA-UE, which was particularly strong with eyes closed [r(EO) = 0.5; r(EC) = 0.54]. The results of the multiple linear regression analysis indicated that the ML oscillation is influenced significantly by the FMA-Motor, and specifically by the sections on UE, wrist, coordination/speed, and sensation. CONCLUSIONS: The hemiparetic UE motor capacity is strongly related to the ML COP oscillation during standing in individuals with chronic stroke, with a lower motor capacity associated with a greater instability. Understanding these relationships underpins the interventions to improve balance and reduce falls in people who have had a stroke.
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Equilibrio Postural , Accidente Cerebrovascular , Extremidad Superior , Humanos , Equilibrio Postural/fisiología , Accidente Cerebrovascular/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Anciano , Extremidad Superior/fisiopatología , Enfermedad Crónica , Adulto , Rehabilitación de Accidente Cerebrovascular/métodosRESUMEN
Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cells.
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Nanotubos , Paladio , Aleaciones , Paclitaxel , CatálisisRESUMEN
The temporomandibular joint (TMJ) is one of the most complex joints in the human anatomy. In advanced degenerative stages, conservative or minimally invasive surgical therapies have failed to restore joint function, and joint replacement with prostheses has been required. Stock prostheses, compared to custom-made prostheses, are much less expensive and require less pre-operative preparation time. Four patients followed for years for temporomandibular dysfunction and previously operated on by arthroscopy or open joint surgery that have been reconstructed with stock TMJ prostheses (STMJP) through virtual surgical planning (VSP) and an STL model with surgical and positioning guides were included. The median follow-up was 15 months; the median number of previous TMJ surgeries was 2. The mean preoperative MIO was 24.6 mm and at longest follow-up was 36.4 mm. The median preoperative TMJ pain score was 8, and the median postoperative TMJ pain was 3. All patients have improved their mandibular function with a clear improvement of their initial situation. In conclusion, we believe that stock TMJ prostheses with virtual surgical planning and surgical guides are a good alternative for TMJ reconstruction at the present time. Nonetheless, prospective and randomized trials are required with long-term follow up to assess their performance and safety.
Asunto(s)
Prótesis Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Proyectos Piloto , Trastornos de la Articulación Temporomandibular/cirugía , Estudios Prospectivos , Resultado del Tratamiento , Articulación Temporomandibular/cirugía , DolorRESUMEN
Hydrogen peroxide (H2O2) not only is an oxidant but also is an important signaling molecule in vascular biology, mediating several physiological functions. Red blood cells (RBCs) have been proposed to be the primary sink of H2O2 in the vasculature because they are the main cellular component of blood with a robust antioxidant defense and a high membrane permeability. However, the exact permeability of human RBC to H2O2 is neither known nor is it known if the mechanism of permeation involves the lipid fraction or protein channels. To gain insight into the permeability process, we measured the partition constant of H2O2 between water and octanol or hexadecane using a novel double-partition method. Our results indicated that there is a large thermodynamic barrier to H2O2 permeation. The permeability coefficient of H2O2 through phospholipid membranes containing cholesterol with saturated or unsaturated acyl chains was determined to be 4 × 10-4 and 5 × 10-3 cm s-1, respectively, at 37 °C. The permeability coefficient of human RBC membranes to H2O2 at 37 °C, on the other hand, was 1.6 × 10-3 cm s-1. Different aquaporin-1 and aquaporin-3 inhibitors proved to have no effect on the permeation of H2O2. Moreover, human RBCs devoid of either aquaporin-1 or aquaporin-3 were equally permeable to H2O2 as normal human RBCs. Therefore, these results indicate that H2O2 does not diffuse into RBCs through aquaporins but rather through the lipid fraction or a still unidentified membrane protein.