Tau- and α-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases.

The use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer's and Parkinson's disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer's and Parkinson's disease, as well as recent research about their use in preclinical, clinical, and emerging research areas.

Adding vortexing to the Maki technique provides no benefit for the diagnosis of catheter colonization or catheter-related bacteremia.

BACKGROUND: A previous study compared vortexing and Maki techniques for the diagnosis of catheter-related bloodstream infection (CRBSI), and concluded that vortexing was not superior to Maki method. AIM: To determine whether the combined use of vortexing and Maki techniques provides profitability versus the Maki technique for the diagnosis of catheter tip colonization (CTC) and CRBSI. METHODS: Observational and prospective study carried out in an Intensive Care Unit. Patients with suspected catheter-related infection (CRI) and with one central venous catheter for at least 7 days were included. The area under the curve (AUC) of the Maki technique, the vortexing technique and the combination of both techniques for the diagnosis of CTC and CRBSI were compared. RESULTS: We included 136 episodes of suspected CRI. We found 21 cases of CTC of which 10 were also CRBSI cases. Of the 21 CTC episodes, 18 (85.7%) were diagnosed by Maki technique and vortexing technique, 3 (14.3%) only by the technique of Maki, and none only by technique of vortexing. Of the 10 CRBSI episodes, 9 (90.0%) were diagnosed by the techniques of Maki and vortexing, 1 (10.0%) was diagnosed only by the technique of Maki, and none only by the technique of vortexing. We no found differences in the comparison of AUC between the technique of Maki and the combination of Maki and vortexing techniques for the diagnosis of CTC (P = 0.99) and CRBSI (P = 0.99). CONCLUSION: The novel finding of our study was that the combined use of vortexing and Maki techniques did not provide profitability to the technique of Maki alone to CRBSI diagnosis of.

Buccal delivery of small molecules and biologics: Of mucoadhesive polymers, films, and nanoparticles - An update.

Buccal delivery of small and large molecules is an attractive route of administration that has been studied extensively over the past few decades. This route bypasses first-pass metabolism and can be used to deliver therapeutics directly to systemic circulation. Moreover, buccal films are efficient dosage forms for drug delivery due to their simplicity, portability, and patient comfort. Films have traditionally been formulated using conventional techniques, including hot-melt extrusion and solvent casting. However, newer methods are now being exploited to improve the delivery of small molecules and biologics. This review discusses recent advances in buccal film manufacturing, using the latest technologies, such as 2D and 3D printing, electrospraying, and electrospinning. This review also focuses on the excipients used in the preparation of these films, with emphasis on mucoadhesive polymers and plasticizers. Along with advances in manufacturing technology, newer analytical tools have also been used for the assessment of permeation of the active agents across the buccal mucosa, the most critical biological barrier and limiting factor of this route. Additionally, preclinical and clinical trial challenges are discussed, and some small molecule products already on the market are explored.

Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates.

The ß-amyloid (Aß) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of Aß species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of Aß in animal models in the near-infrared region (NIR). However, considering future applications in biomedicine, it is relevant to develop strategies to improve detection of amyloid aggregates using NIR probes. An innovative approach to increase the fluorescence signal of these fluorophores is the use of plasmonic gold nanoparticles (surface-enhanced fluorescence effect). In this work, we improved the detection of Aß aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods (GNRs-PEG-D1) with the fluorescent probes CRANAD-2 or CRANAD-58, which bind selectively to different amyloid species (soluble and insoluble). This work shows that GNRs improve the detection of Aß using NIR probes in vivo.

Lower ΔFosB expression in the dopaminergic system after stevia consumption in rats housed under environmental enrichment conditions.

Environmental enrichment (EE) has been proven to reduce drug seeking and the development of addiction-related behaviors in rodent models, but the effects of EE on natural reward acquisition in the form of sweet beverages are poorly understood. Accumulating evidence shows that the intake of sugar, the main ingredient of sweet beverages, alters the dopaminergic system, leading to addiction-related physiological and molecular changes. Sugar in sweet beverages has been replaced with natural sweeteners, such as stevia extract, which has greater sweetener potential but no energy content. Our research group found that sucralose consumption increased the expression of ΔFosB in reward-related nuclei, suggesting activation of the dopaminergic system. The present study assessed the effects of EE on stevia consumption and the expression of ΔFosB in the nucleus accumbens, caudate putamen, and prefrontal cortex. Sixteen male Wistar rats, 21 days old, were randomly assigned to an EE group (n = 8) or standard environment (SE) group (n = 8) and reared for 30 days. On postnatal day 52 (PND52), the brains of four animals in each housing condition were extracted to determine basal ΔFosB levels. Stevia consumption with intermittent access and ΔFosB immunoreactivity were measured for 21 days in the remainder of the rats. Compared with SE animals, EE animals exhibited a reduction of stevia consumption and alterations of ΔFosB immunoreactivity in the reward system. These results indicate that EE reduces stevia consumption and the stevia-induced ΔFosB expression, suggesting addiction-related changes in dopaminergic nuclei, which may be interpreted as a neuroprotective effect.

Acceso a servicios de salud en pacientes con tuberculosis en Cuba. La percepción de directivos / Access to health services in patients with tuberculosis in Cuba. The perception of managers

Resumen Objetivo: Indagar las percepciones de los directores sobre el acceso a los servicios de salud en pacientes con tuberculosis pulmonar. Materiales y métodos: Investigación descriptiva, en informantes claves seleccionados de forma intencional no aleatoria a partir de criterios de inclusión relevantes. Resultaron seleccionados 5 jefes de los Programa de Prevención y Control de la Tuberculosis pulmonar y VIH/sida, del nivel nacional y provincial. Se elaboró y validó por expertos una guía de entrevista, con los aspectos de acceso a los servicios de salud. La entrevista se realizó en óptimas condiciones y se solicitó su consentimiento para grabar. El análisis de contenido de la información, se organizó según la metodología de Bardin, preanálisis, exploración del material y tratamiento de los resultados e interpretación. Resultados: Las percepciones reportadas por los directivos fueron alteraciones en la dinámica de la atención, oportunidad y su continuidad, la educación a la comunidad y compañeros de trabajo, afectación de grupos poblacionales con indisciplina social, existencia de estigmas sociales hacia la enfermedad, poca participación de los sectores de la comunidad para resolver sus dificultades, imposibilidad de asumir siempre la alimentación y transportación, la calidad de los recursos humanos y gestión del programa. Conclusiones: Los directivos del programa de prevención y control de tuberculosis percibieron que existen dificultades en la disponibilidad, la accesibilidad, la aceptabilidad y la calidad de los servicios de salud en pacientes con tuberculosis pulmonar, estos elementos identificados pueden contribuir al rediseñó de la estrategia de eliminación de la enfermedad en La Habana.

Abstract Objective: to investigate direct perceptions of access to health services in patients with pulmonary tuberculosis. Methodo: descriptive, in key informants selected intentionally not randomly based on relevant inclusion criteria. The Heads of the Prevention and Control Program for Pulmonary Tuberculosis and HIV / AIDS, at the national and provincial level, were selected. An interview guide was developed and validated by experts, with aspects of access to health services. This was done in optimal conditions and your consent to record was requested. The analysis of information content was organized according to Bardin's methodology, pre-analysis, exploration of the material and treatment of the results and interpretation. Results: There were perceptions by managers of alterations in the dynamics of care, opportunity and its continuity, education to the community and coworkers, involvement of population groups with social indiscipline, existence of social stigmas towards the disease, low participation of the sectors of the community to solve their difficulties, impossibility of always assuming food and transportation, the quality of human resources and program management. Conclusions: The directors of the tuberculosis prevention and control program perceived that there are difficulties in the availability, accessibility, acceptability and quality of health services in patients with pulmonary tuberculosis, these identified elements can contribute to the redesign of the strategy of Elimination of the disease in Havana.

Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer's Disease.

Alzheimer's disease (AD), considered a common type of dementia, is mainly characterized by a progressive loss of memory and cognitive functions. Although its cause is multifactorial, it has been associated with the accumulation of toxic aggregates of the amyloid-ß peptide (Aß) and neurofibrillary tangles (NFTs) of tau protein. At present, the development of highly sensitive, high cost-effective, and non-invasive diagnostic tools for AD remains a challenge. In the last decades, nanomaterials have emerged as an interesting and useful tool in nanomedicine for diagnostics and therapy. In particular, plasmonic nanoparticles are well-known to display unique optical properties derived from their localized surface plasmon resonance (LSPR), allowing their use as transducers in various sensing configurations and enhancing detection sensitivity. Herein, this review focuses on current advances in in vitro sensing techniques such as Surface-enhanced Raman scattering (SERS), Surface-enhanced fluorescence (SEF), colorimetric, and LSPR using plasmonic nanoparticles for improving the sensitivity in the detection of main biomarkers related to AD in body fluids. Additionally, we refer to the use of plasmonic nanoparticles for in vivo imaging studies in AD.

Survey of Commercial Food Products for Detection of Walnut (Juglans regia) by Two ELISA Methods and Real Time PCR.

Labeling of food allergens in accordance with legal regulations is important to protect the health of allergic consumers. The requirements for detecting allergens in foods involve adequate specificity and sensitivity to identify very small amounts of the target allergens in complex food matrices and processed foods. In this work, one hundred commercial samples were analyzed for walnut detection using three different methods: a sandwich enzyme-linked immunosorbent assay (ELISA) kit based on polyclonal antibodies, a direct ELISA using a recombinant multimeric scFv, and a real time PCR. The most sensitive method was real time PCR followed by sandwich ELISA kit and multimeric scFv ELISA. There was agreement between the three methods for walnut detection in commercial products, except for some heat-treated samples or those that contained pecan. The walnut ELISA kit was less affected by sample processing than was the multimeric scFv ELISA, but there was cross-reactivity with pecan, producing some false positives that must be confirmed by real time PCR. According to the results obtained, 7.0 to 12.6% of samples (depending on the analytical method) contained walnut but did not declare it, confirming there is a risk for allergic consumers. Moreover, there was one sample (3.7%) labelled as containing walnut but that tested negative for this tree nut. Genetic and immunoenzymatic techniques offer complementary approaches to develop a reliable verification for walnut allergen labeling.

Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons.

Stress seems to contribute to Parkinson's disease (PD) neuropathology, probably by dysregulation of the hypothalamic-pituitary-adrenal axis. Key factors in this pathophysiology are oxidative stress and mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. The insulin-like growth factor II (IGF-II), a pleiotropic hormone, has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Our aim was to examine the protective effect of IGF-II on a dopaminergic cellular combined model of PD and mild to moderate stress measuring oxidative stress parameters, mitochondrial and neuronal markers, and signalling pathways. IGF-II counteracts the mitochondrial-oxidative damage produced by the toxic synergistic effect of corticosterone and 1-methyl-4-phenylpyridinium, protecting dopaminergic neurons from death and neurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. Thus, IGF-II is a potential therapeutic tool for treatment and prevention of disease progression in PD patients suffering mild to moderate emotional stress.

Cirugía de catarata senil en diabéticos tipo 2 / Senile cataract surgery in type 2 diabetics

RESUMEN Objetivo: Determinar los resultados visuales de la cirugía de catarata en pacientes diabéticos tipo 2 con y sin alteraciones en el fondo de ojo, posterior a la facoemulcificación. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo en 116 pacientes (232 ojos) diabéticos tipo 2 con catarata senil bilateral, en el Instituto Cubano Oftalmología "Ramón Pando Ferrer", de septiembre del año 2015 a septiembre de 2017. Se analizaron las variables sexo, edad, índice de masa corporal, tiempo de evolución de la diabetes tipo 2, tratamiento actual y agudeza visual sin corrección y mejor corregida. Se calcularon los valores absolutos, relativos, la media y la desviación estándar. Resultados: Predominaron el sexo femenino, con 70 años o más, y los pacientes entre los 5 a 9 años del debut de la diabetes. Más del 80 por ciento de los pacientes presentaban sobrepeso y obesidad, en la mayoría de los pacientes diabéticos tipo 2 operados de catarata mejoró la agudeza visual sin corrección y la mejor agudeza visual corregida a pesar del daño en el fondo de ojo. Conclusiones: La diabetes mellitus tipo 2 no es un factor determinante en la recuperación de la visión en pacientes operados de catarata(AU)

ABSTRACT Senile cataract surgery in type 2 diabetic patients, with or without funduscopy alterations, is a controversial issue. Objective: Determine the visual results of cataract surgery in type 2 diabetic patients with and without funduscopy alterations after phacoemulsification. Methods: A prospective longitudinal descriptive study was conducted of 116 type 2 diabetic patients (232 eyes) with bilateral senile cataract at Ramón Pando Ferrer Cuban Institute of Ophthalmology from September 2015 to September 2017. The variables analyzed were sex, age, body mass index, time of evolution of type 2 diabetes, current treatment and visual acuity without correction and best corrected. Estimation was performed of absolute and relative values and mean and standard deviation. Results: There was a predominance of the female sex, the 70 years and over age group, and patients with 5-9 years of diabetes evolution. More than 80 percent of the patients were overweight or obese. Most of the type 2 diabetic patients undergoing cataract surgery showed improvement in their visual acuity without correction and their best corrected visual acuity despite the damage revealed by the funduscopy. Conclusions: Type 2 diabetes mellitus is not a determining factor in sight recovery by patients undergoing cataract surgery(AU)