Microglial activation is an invariant feature of Alzheimer's disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in ...vitro and in vivo. On the other hand, the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in different paradigms. In the present study, we compared the effects of CBD with those of other cannabinoids on microglial cell functions in vitro and on learning behavior and cytokine expression after Aβ intraventricular administration to mice. CBD, (R)-(+)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-1,2,3-d,e-1,4-benzoxazin-6-yl-1-naphthalenyl-methanone WIN 55,212-2 (WIN), a mixed CB(1)/CB(2) agonist, and 1,1-dimethylbutyl-1-deoxy-Δ(9)-tetrahydrocannabinol JWH-133 (JWH), a CB(2)-selective agonist, concentration-dependently decreased ATP-induced (400 μM) increase in intracellular calcium (Ca(2+)(i)) in cultured N13 microglial cells and in rat primary microglia. In contrast, 4-4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl-6,6-dimethyl-bicyclo3.1.1hept-2-ene-2-methanol HU-308 (HU), another CB(2) agonist, was without effect. Cannabinoid and adenosine A(2A) receptors may be involved in the CBD action. CBD- and WIN-promoted primary microglia migration was blocked by CB(1) and/or CB(2) antagonists. JWH and HU-induced migration was blocked by a CB(2) antagonist only. All of the cannabinoids decreased lipopolysaccharide-induced nitrite generation, which was insensitive to cannabinoid antagonism. Finally, both CBD and WIN, after subchronic administration for 3 weeks, were able to prevent learning of a spatial navigation task and cytokine gene expression in β-amyloid-injected mice. In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.
Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective ...and anti-inflammatory agents with therapeutic potential.
We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on ¹⁸F-fluoro-deoxyglucose (¹⁸FDG) uptake by positron emission tomography (PET).
Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased ¹⁸FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro.
In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.
During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled ...in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials.
In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons.
After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance.
The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries.
El Prácticum se concibe como una de las variables constructoras del eje vertebral de las profesiones, al abordar el desarrollo de las competencias generales y específicas desde miradas ...teórico-experienciales, incidiendo en la visibilización y el desarrollo de la profesión como tal. Se plantea la siguiente cuestión: ¿Qué tipo de trabajos de investigación se han publicado en cuanto al Prácticum y la Educación Social? Para dar respuesta se propone el objetivo de indagar sobre las investigaciones publicadas en las actas de los Symposium celebrados en Poio (España) (1987-2022) ligando el Prácticum, las Prácticas externas y la titulación. Esta revisión revela datos interesantes: los 151 trabajos analizados presentan un índice de coautoría del 74%, situando la participación de autoría femenina en un 72%; desde la universidad pública se ha publicado de forma constante y elevada, contribuyendo en un porcentaje del 89%. En conclusión, se destaca la importancia del carácter formativo del Prácticum.
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•Hepatitis C virus (HCV) is a major etiological agent of chronic hepatitis, and around 71 million people have chronic HCV infection worldwide. HCV core is a multifunctional and highly ...conserved protein that has a great potential for both diagnostic and therapeutic applications.•We have in vitro selected DNA and RNA aptamers that bind with high affinity (showing dissociation constants, Kd, as low as 0.4 nM) to different variants of HCV core protein of genotypes 1 to 4.•The performance of the selected aptamers as probe molecules for HCV core detection was confirmed using ELONA-based methods, and a Limit of Detection down to 2 pM was achieved.•In parallel, the two most prevalent and high affinity aptamers were assayed in cell culture. Both of them decreased the viral progeny titer and the extracellular viral RNA level, while concomitantly increasing the amount of non-encapsidated, intracellular viral RNA.•The selected anti-HCV core aptamers are good candidate molecules for hepatitis C diagnosis and treatment.
Hepatitis C virus (HCV) core is a highly conserved and multifunctional protein that forms the viral capsid, making it an attractive target for HCV detection and inhibition. Aptamers are in vitro selected, single-stranded nucleic acids (RNA or ssDNA) with growing applicability in viral diagnostics and therapy. We have carried out DNA and RNA in vitro selection against six different variants of HCV core protein: two versions of the full-length protein of genotype 1, and the hydrophilic domain of genotypes 1 to 4. The aptamer populations obtained were analyzed by means of Ultra-Deep Sequencing (UDS), the most abundant sequences were identified and a number of highly represented sequence motifs were unveiled. Affinity (measured as the dissociation constant, Kd) of the most abundant DNA and RNA aptamers were quantified using Enzyme-Linked OligoNucleotide Assay (ELONA)-based methods. Some aptamers with nanomolar or subnanomolar Kd values (as low as 0.4 nM) were the common outcome of DNA and RNA selections against different HCV core variants. They were tested in sandwich and competitive biosensor assays, reaching a limit of detection for HCV core of 2 pM. Additionally, the two most prevalent and high affinity aptamers were assayed in Huh-7.5 reporter cell lines infected with HCV, where they decreased both the viral progeny titer and the extracellular viral RNA level, while increasing the amount of intracellular viral RNA. Our results suggest that these aptamers inhibit HCV capsid assembly and virion formation, thus making them good candidate molecules for the design of novel therapeutic approaches for hepatitis C.
IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform ...a transcultural adaptation and validation for the Spanish context. Translation, back-translation, and evaluation of the questionnaires were performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett's sphericity test (p-value < 0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser's criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, and CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92).
The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families.
• IMPACT-III and parent-proxy IMPACT-III (IMPACT-III-P) are useful questionnaires for assessing health-related quality of life (HRQoL) in pediatric inflammatory bowel disease (p-IBD) patients and their parents/caregivers and have been translated and validated in several countries. • To date, no transcultural adaptation and validation of these questionnaires have been published for Spanish patients with p-IBD and their families.
• This is the first transcultural adaptation and validation of IMPACT-III and IMPACT-III-P for Spanish p-IBD families. • These are valid and reliable instruments for assessing HRQoL in Spanish families of patients with p-IBD.
Aims To assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain. Design Multicentric, mixed method concurrent study. ...Methods This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial Registration Identifier: NCT05249868 ClinicalTrials.gov .
Despite the epidemiological evidence about the relationship between diabetes, mortality and cardiovascular disease, information about the population impact of uncontrolled diabetes is scarce. We ...aimed to estimate the attributable risk associated with HbA1c levels for all-cause mortality and cardiovascular hospitalization.
Prospective study of subjects with diabetes mellitus using electronic health records from the universal public health system in the Valencian Community, Spain 2008-2012. We included 19,140 men and women aged 30 years or older with diabetes who underwent routine health examinations in primary care.
A total of 11,003 (57%) patients had uncontrolled diabetes defined as HbA1c ≥6.5%, and, among those, 5325 participants had HbA1c ≥7.5%. During an average follow-up time of 3.3 years, 499 deaths, 912 hospitalizations for coronary heart disease (CHD) and 786 hospitalizations for stroke were recorded. We observed a linear and increasingly positive dose-response of HbA1c levels and CHD hospitalization. The relative risk for all-cause mortality and CHD and stroke hospitalization comparing patients with and without uncontrolled diabetes was 1.29 (95 CI 1.08,1.55), 1.38 (95 CI 1.20,1.59) and 1.05 (95 CI 0.91, 1.21), respectively. The population attributable risk (PAR) associated with uncontrolled diabetes was 13.6% (95% CI; 4.0-23.9) for all-cause mortality, 17.9% (95% CI; 10.5-25.2) for CHD and 2.7% (95% CI; - 5.5-10.8) for stroke hospitalization.
In a large general-practice cohort of patients with diabetes, uncontrolled glucose levels were associated with a substantial mortality and cardiovascular disease burden.
Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of ...cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS.
Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF.
One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria.
The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria.
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