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In this study we investigated the relationship between cognitive reserve (CR) proxies, such as education, physical activity (PA), and cognitive dysfunction (CD) in the presence or absence of frontotemporal disorders (FTD). Previous research has suggested that education and PA may delay the onset of CD and reduce the risk of developing dementia. However, it remains unclear whether these CR proxies can protect against CD when FTD is present. We aimed to explore this relationship and determine whether sustained CR may be evident regardless of FTD. We recruited 149 older adults (aged 65-99 years) from community centers where they were voluntarily participating in leisure activities. We used bioelectrical impedance to measure their body composition, and we administered the International PA Questionnaire and the Mini-Mental State Examination to measure their PA and cognitive function, respectively. We used the Frontal Assessment Battery to screen for frontotemporal dementia. Our results showed that people with FTD were older, had lower education, and engaged in less PA, relative to other participants. Regression models revealed that age, education, and PA were significant predictors of FTD. More specifically, FTD was negatively associated with cognitive functioning, and there were significant interaction effects between FTD and education and PA. PA and education were significant predictors of cognitive functioning, and, when values for PA and education were high, they offset the effects of FTD on cognitive function. These findings support impressions that PA and years of education provide an insulating or compensatory effect on cognitive functioning in older adults with executive dysfunction or frontotemporal dementia, highlighting the importance of encouraging both pursuits.
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Disfunción Cognitiva , Reserva Cognitiva , Escolaridad , Ejercicio Físico , Demencia Frontotemporal , Humanos , Anciano , Reserva Cognitiva/fisiología , Masculino , Femenino , Anciano de 80 o más Años , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Demencia Frontotemporal/psicologíaRESUMEN
The World Health Organization highlights the urgent need to address the global threat posed by antibiotic-resistant bacteria. Efficient and rapid detection of bacterial response to antibiotics and their virulence state is crucial for the effective treatment of bacterial infections. However, current methods for investigating bacterial antibiotic response and metabolic state are time-consuming and lack accuracy. To address these limitations, we propose a novel method for classifying bacterial virulence based on statistical analysis of nanomotion recordings. We demonstrated the method by classifying living Bordetella pertussis bacteria in the virulent or avirulence phase, and dead bacteria, based on their cellular nanomotion signal. Our method offers significant advantages over current approaches, as it is faster and more accurate. Additionally, its versatility allows for the analysis of cellular nanomotion in various applications beyond bacterial virulence classification.
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We present a novel optical nanomotion-based rapid antibiotic and antifungal susceptibility test. The technique consisted of studying the effects of antibiotics or antifungals on the nanometric scale displacements of bacteria or yeasts to assess their sensitivity or resistance to drugs. The technique relies on a traditional optical microscope, a video camera, and custom-made image analysis software. It provides reliable results in a time frame of 2-4 h and can be applied to motile, non-motile, fast, and slowly growing microorganisms. Due to its extreme simplicity and low cost, the technique can be easily implemented in laboratories and medical centers in developing countries.
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The emergence of antibiotic and antifungal resistant microorganisms represents nowadays a major public health issue that might push humanity into a post-antibiotic/antifungal era. One of the approaches to avoid such a catastrophe is to advance rapid antibiotic and antifungal susceptibility tests. In this study, we present a compact, optical fiber-based nanomotion sensor to achieve this goal by monitoring the dynamic nanoscale oscillation of a cantilever related to microorganism viability. High detection sensitivity was achieved that was attributed to the flexible two-photon polymerized cantilever with a spring constant of 0.3 N/m. This nanomotion device showed an excellent performance in the susceptibility tests of Escherichia coli and Candida albicans with a fast response in a time frame of minutes. As a proof-of-concept, with the simplicity of use and the potential of parallelization, our innovative sensor is anticipated to be an interesting candidate for future rapid antibiotic and antifungal susceptibility tests and other biomedical applications.
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Antibacterianos , Antifúngicos , Fibras Ópticas , Pruebas de Sensibilidad Microbiana , Candida albicans , Escherichia coliRESUMEN
Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.
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Cells of two molecular genetic types of breast cancer-hormone-dependent breast cancer (ZR-75 cell line) and triple-negative breast cancer (BT-20 cell line)-were studied using atomic force microscopy and an optical nanomotion detection method. Using the Peak Force QNM and Force Volume AFM modes, we revealed the unique patterns of the dependence of Young's modulus on the indentation depth for two cancer cell lines that correlate with the features of the spatial organization of the actin cytoskeleton. Within a 200-300 nm layer just under the cell membrane, BT-20 cells are stiffer than ZR-75 cells, whereas in deeper cell regions, Young's modulus of ZR-75 cells exceeds that of BT-20 cells. Two cancer cell lines also displayed a difference in cell nanomotion dynamics upon exposure to cytochalasin D, a potent actin polymerization inhibitor. The drug strongly modified the nanomotion pattern of BT-20 cells, whereas it had almost no effect on the ZR-75 cells. We are confident that nanomotion monitoring and measurement of the stiffness of cancer cells at various indentation depths deserve further studies to obtain effective predictive parameters for use in clinical practice.
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Citoesqueleto de Actina , Neoplasias de la Mama Triple Negativas , Humanos , Microscopía de Fuerza Atómica/métodos , Citoesqueleto de Actina/metabolismo , Módulo de Elasticidad , Línea Celular , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Nanometric scale size oscillations seem to be a fundamental feature of all living organisms on Earth. Their detection usually requires complex and very sensitive devices. However, some recent studies demonstrated that very simple optical microscopes and dedicated image processing software can also fulfill this task. This novel technique, termed as optical nanomotion detection (ONMD), was recently successfully used on yeast cells to conduct rapid antifungal sensitivity tests. In this study, we demonstrate that the ONMD method can monitor motile sub-cellular organelles, such as mitochondria. Here, mitochondrial isolates (from HEK 293 T and Jurkat cells) undergo predictable motility when viewed by ONMD and triggered by mitochondrial toxins, citric acid intermediates, and dietary and bacterial fermentation products (short-chain fatty acids) at various doses and durations. The technique has superior advantages compared to classical methods since it is rapid, possesses a single organelle sensitivity, and is label- and attachment-free.
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Introduction: Patients undergoing cancer treatment by radiation therapy commonly develop Candida albicans infections (candidiasis). Such infections are generally treated by antifungals that unfortunately also induce numerous secondary effects in the patient. Additional to the effect on the immune system, ionizing radiation influences the vital activity of C. albicans cells themselves; however, the reaction of C. albicans to ionizing radiation acting simultaneously with antifungals is much less well documented. In this study, we explored the effects of ionizing radiation and an antifungal drug and their combined effect on C. albicans. Methods: The study essentially relied on a novel technique, referred to as optical nanomotion detection (ONMD) that monitors the viability and metabolic activity of the yeast cells in a label and attachment-free manner. Results and discussion: Our findings demonstrate that after exposure to X-ray radiation alone or in combination with fluconazole, low-frequency nanoscale oscillations of whole cells are suppressed and the nanomotion rate depends on the phase of the cell cycle, absorbed dose, fluconazole concentration, and post-irradiation period. In a further development, the ONMD method can help in rapidly determining the sensitivity of C. albicans to antifungals and the individual concentration of antifungals in cancer patients undergoing radiation therapy.
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BACKGROUND: To learn about the experiences and opinions of adolescent non-consumers and regular cannabis users about cannabis use and the factors that determine its use, using the I-Change explanatory model as a basis. METHODS: Qualitative methodology with a content analysis was used. Focus groups were conducted with adolescents who were non-regular cannabis users (those who had not tried cannabis or had only experimented with it before) and semi-structured interviews were conducted with adolescent and young adult in recovery who were in a detoxification program. A deductive analysis of the audio-recorded and transcribed interviews was performed, using the domains of the I-Change Model as a reference. RESULTS: Personal problems, social problems or family problems can lead to cannabis use. There was a lack of knowledge and low risk perception about consumption of this drug. There are other factors that influence consumption, the perception of advantages, such as the feeling of freedom and the influence of the peer group. The consumption of this substance in girls is changing, becoming more and more equal to that of boys. The family has an important role to play in preventing drug use. CONCLUSION: Knowledge of these factors is of vital importance as a prior step to the development of efficient intervention measures adjusted to the needs identified and the characteristics of the population.
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Antibiotic resistance is nowadays a major public health issue. Rapid antimicrobial susceptibility tests (AST) are one of the options to fight this deadly threat. Performing AST with single-cell sensitivity that is rapid, cheap, and widely accessible, is challenging. Recent studies demonstrated that monitoring bacterial nanomotion by using atomic force microscopy (AFM) upon exposure to antibiotics constitutes a rapid and highly efficient AST. Here, we present a nanomotion detection method based on optical microscopy for testing bacterial viability. This novel technique only requires a very basic microfluidic analysis chamber, and an optical microscope equipped with a camera or a mobile phone. No attachment of the microorganisms is needed, nor are specific bacterial stains or markers. This single-cell technique was successfully tested to obtain AST for motile, nonmotile, gram-positive, and gram-negative bacteria. The simplicity and efficiency of the method make it a game-changer in the field of rapid AST.
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Antibacterianos , Bacterias , Viabilidad Microbiana , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Microscopía de Fuerza AtómicaRESUMEN
PURPOSE: We compared next generation sequencing multigene panels (NGS-MGP) from 5 commercial laboratories to inform ophthalmologists' decision making in diagnostic genetic testing for congenital anterior segment anomalies (CASAs). DESIGN: Comparison of commercial genetic testing panels. METHODS: This observational study gathered publicly available information on NGS-MGP from 5 commercial laboratories for the following: cataracts, glaucoma, anterior segment dysgenesis (ASD), microphthalmia-anophthalmia-coloboma (MAC), corneal dystrophies, and Axenfeld-Rieger syndrome (ARS). We compared gene panel composition, consensus rate (genes covered by all the panels per condition, "concurrent"), dissensus rate (genes covered by only 1 panel per condition, "standalone"), and intronic variant coverage. For individual genes, we compared publication history and association with systemic conditions. RESULTS: Altogether, cataract, glaucoma, corneal dystrophies, MAC, ASD, and ARS panels tested 239, 60, 36, 292, and 10 discrete genes, respectively. The consensus rate varied between 16% and 50%, and the dissensus rate varied between 14% and 74%. After pooling concurrent genes from all conditions, 20% of these genes were concurrent in 2 or more conditions. For both cataract and glaucoma, concurrent genes had significantly stronger correlation with the condition than standalone genes. CONCLUSIONS: The genetic testing of CASAs using NGS-MGPs is complicated, owing to their number, variety, and phenotypic and genetic overlap. Although the inclusion of additional genes, such as the standalone ones, might increase diagnostic yield, these genes are also less well studied, indicating uncertainty over their role in CASA pathogenesis. Rigorous prospective diagnostic yield studies of NGS-MGPs will aid in making decisions of panel selection for the diagnosis of CASAs.
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Catarata , Coloboma , Distrofias Hereditarias de la Córnea , Glaucoma , Microftalmía , Humanos , Estudios Prospectivos , Glaucoma/genéticaRESUMEN
The dual theory establishes that the decision-making process relies on two different systems, the affective system and the executive function (EF), developed during adolescence. This study analyzes the relationship between the decision-making and EF processes in a group of early adolescents (mean age = 12.51 years, SD = 0.61), where more affective impulse processes are developed, and in young adults (mean age = 19.38 years, SD = 1.97), where cognitive control processes have already matured. For this purpose, 140 participants in Spain completed the Iowa Gambling Task (IGT) to measure their risky decisions and the Wisconsin Card Sorting Task (WCST) to measure their EF. Performance on the IGT improves over blocks; however, adolescents received lower mean scores than young adults. However, controlling for age, perseverative errors were negatively associated with the mean net score on the risky blocks of IGT; thus, those who committed more perseverative errors in the WCST were more likely to take cards from the disadvantageous decks on the last blocks of the IGT. The current study shows that adolescents and adults solve ambiguous decisions by trial and error; however, adolescents are more likely to make risky decisions without attending to the long-term consequences. Following the dual theory hypothesis, the maturation of EF with age partly accounts for this difference in risky decision-making between adolescents and adults.
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The aim of this study is to analyze the effect of the type of habitation of older adults-with relatives or alone-on their health and well-being. The participants were 352 people over 65 years of age who collaborated with the research on a voluntary basis. The data indicated that those who live with family members have better social integration, well-being and happiness than those who live alone. A multiple regression analysis showed the positive effect of living with relatives on well-being and happiness. However, participation in social activities mitigates the effect of the type of cohabitation explaining better well-being and happiness in the older population. These findings support the idea of designing and implementing intervention policies focused on activities that promote social participation and social interactions to improve well-being and happiness in the older adults.
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Surveillance of hepatitis E virus (HEV) in risk groups is an important strategy to monitor its circulation pattern and to timely detect changes thereof. The aims of this cross-sectional study were to estimate the prevalence of HEV infections in pigs and humans from different regions of the country, to identify risk factors for increasing anti-HEV IgG prevalence and to characterize HEV strains. The presence of anti-HEV antibodies was assessed by commercial ELISA in serum samples from the general population, farm and slaughterhouse employees, as well as pigs sampled in the three regions of Cuba from February to September 2016. Overall, individuals with occupational exposure to swine or swine products (70/248, 28.2%) were 4 times more likely to be seropositive compared to the general population (25/285, 8.7%; OR: 4.18; p < .001). Within the risk group, risk factors included age, number of years working in a professional activity with direct exposure to swine, geographic region and distance between residence and closest professional swine setting, while wearing gloves had a protective effect. Prevalence of total anti-HEV antibodies in swine was 88.2% (165/187) and HEV RNA was detected by real-time RT-PCR in 9.2% (16/173) swine stools. All HEV strains sequenced clustered within genotype 3. Some strains clearly belonged to subtype 3a, while another group of strains was related with subtypes 3b and 3 k but partial HEV sequences did not allow unequivocal subtype assignment. These findings suggest that the high HEV exposure in Cuban individuals with swine-related occupations could be due to enzootic HEV in certain regions, direct contact with infectious animals or their products as well as environmental contamination.
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Virus de la Hepatitis E , Hepatitis E , Enfermedades de los Porcinos , Humanos , Porcinos , Animales , Virus de la Hepatitis E/genética , Estudios Transversales , Cuba/epidemiología , ARN Viral/genética , Enfermedades de los Porcinos/epidemiología , Filogenia , Genotipo , Hepatitis E/epidemiología , Hepatitis E/veterinaria , Anticuerpos AntihepatitisRESUMEN
BACKGROUND: Early-onset glaucoma is a potentially sight-threatening condition with high heritability. Next generation sequencing is a cost-effective alternative to individual gene screening that could expedite its diagnosis. However, the diagnostic yield of multigene panel assays for early-onset glaucoma varies according to the tested population. The purpose of this study was to ascertain the diagnostic yield of next generation sequencing panels in our cohort and to identify population characteristics that increase such yield. METHODS: We conducted a retrospective review of the medical records of consecutive patients from November 2016 to August 2021 who were evaluated at our clinics for early-onset glaucoma and had undergone next generation sequencing panels for molecular diagnosis. RESULTS: A total of 118 patients were included, in 22 of whom (19%) a causative variant was identified. Diagnostic yield varied by age of onset: of 60 patients with onset at <3 years of age, 19 (32%) had such variants identified. In contrast, of 58 patients with later-onset glaucoma, 3 (5%) had said variants identified (P = 0.0003). Other metrics that increased diagnostic yield were presence of additional ocular anomalies (P = 0.0092) and identifying ethnicity as White (compared with non-White, P = 0.0001). CONCLUSIONS: In childhood glaucoma, earlier age of onset is correlated with higher likelihood of pathogenic variant identification. The large proportion of unsolved cases indicates a robust opportunity for gene discovery and genetic therapy targets in early-onset glaucoma patients.
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Glaucoma , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Adulto Joven , Adulto , Preescolar , Mutación , Glaucoma/diagnóstico , Glaucoma/genética , Estudios Retrospectivos , Pruebas GenéticasRESUMEN
Lung cancer patients are diagnosed at late stages when curative treatments are no longer possible; thus, molecular biomarkers for noninvasive detection are urgently needed. In this sense, we previously identified and validated an epigenetic 4-gene signature that yielded a high diagnostic performance in tissue and invasive pulmonary fluids. We analyzed DNA methylation levels using the ultrasensitive digital droplet PCR in noninvasive samples in a cohort of 83 patients. We demonstrated that BCAT1 is the candidate that achieves high diagnostic efficacy in circulating DNA derived from plasma (area under the curve: 0.85). Impact of potentially confounding variables was also explored.
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Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , ADN , Metilación de ADN , Epigénesis Genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Transaminasas/genéticaRESUMEN
A 2-week-old girl presented with bilateral congenital corneal opacities. Additional systemic manifestations included microcephaly, patent foramen ovale, and poor feeding. Patient and parents underwent whole exome sequencing trio analysis that revealed a de novo pathogenic variant in POGZ (p.Val1150GlyfsX8), which is causative of the White-Sutton syndrome. This rare genetic condition is usually associated with intellectual and developmental delay, facial dysmorphism, strabismus, refractive error, and retinal changes. To our knowledge, this is the first reported case of White-Sutton syndrome presenting with congenital corneal opacities.
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Opacidad de la Córnea , Anomalías del Ojo , Discapacidad Intelectual , Microcefalia , Femenino , Humanos , Mutación , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Microcefalia/diagnóstico , Microcefalia/genética , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Transposasas/genéticaRESUMEN
RESUMEN Introducción: Los medios de colecta de muestras clínicas con capacidad de desnaturalizar virus reducen los riesgos de contagio durante el transporte y procesamiento. Objetivo: Emplear el medio de transporte de ácidos nucleicos (TAN) en muestras de exudado nasofaríngeo colectadas para el diagnóstico de SARS-CoV-2. Métodos: Se realizó un estudio experimental para demostrar la capacidad del medio de inactivar la infectividad viral. Se tomó como modelo de virus envuelto el virus Zika (VZk), cuyo nivel de bioseguridad es 2. Se evaluó el desempeño clínico del medio TAN para el diagnóstico de SARS-CoV-2. Se empleó una cepa del VZk propagada en la línea celular Vero y, previo a la infección de las células, el VZk se puso en contacto a intervalos de tiempo diferentes (2; 15 y 30 min) con el medio TAN puro; y luego se realizaron diluciones seriadas (10-1-10-4). La inactivación viral se evaluó por RT-PCR, en el sobrenadante y células colectadas, al culminar el periodo de propagación. El desempeño clínico del medio TAN se estimó tomando como referencia el CITOSWAB® VTM, en 30 exudados nasofaríngeos colectados para diagnóstico de la infección por SARS-CoV-2. Resultados: El VZk preservó su infectividad a diluciones del inóculo ≥ 10-2, independientemente del tiempo de contacto. La sensibilidad y especificidad clínica del medio TAN para el diagnóstico de SARS-CoV-2 fueron del 100 %, respectivamente. Conclusiones: Los resultados sugieren que muestras clínicas positivas a VZk en diluciones ≤ 10-1 del medio TAN pueden ser manipuladas de forma segura, lo que pudiera aplicarse potencialmente al diagnóstico molecular del SARS-CoV-2.
ABSTRACT Introduction: Collection media of clinical samples with the capacity to denature viruses reduce the risk of contagion during transportation and processing. Objective: To use the nucleic acids transport media (NATM) in nasopharyngeal swab samples collected for the diagnosis of SARS-CoV-2. Methods: An experimental study was conducted to demonstrate the medium capacity to inactivate viral infectivity. Zika virus (ZIKV), of biosafety level 2, was used as an enveloped virus model. The clinical performance of the NATM for the diagnosis of SARS-CoV-2 was evaluated. A ZIKV strain propagated in the Vero cell line was used and, prior to cells infection, ZIKV was in contact at different intervals (2; 15, and 30 min) with pure NATM; subsequently, serial dilutions (10-1-10-4) were performed. Viral inactivation was evaluated by RT-PCR in the supernatant and the collected cells when the propagation period was completed. CITOSWAB® VTM was used as reference to estimate the clinical performance of the NATM in 30 nasopharyngeal swabs collected for the diagnosis of SARS-CoV-2 infection. Results: ZIKV remained infectious at inoculum dilutions of ≥ 10-2, regardless of contact time. Clinical specificity and sensitivity of the NATM for the diagnosis of SARS-CoV-2 were 100%, respectively. Conclusions: Results suggest that ZIKV positive clinical samples at dilutions ≤ 10-1 of the NATM can be safely handled, which could potentially be applied to the molecular diagnosis of SARS-CoV-2.