Alzheimer's disease is the most common form of dementia, characterized by a persistent and progressive impairment of cognitive functions. Alzheimer's disease is typically associated with ...extracellular deposits of amyloid-β peptide and accumulation of abnormally phosphorylated tau protein inside neurons (amyloid-β and neurofibrillary pathologies). It has been proposed that these pathologies cause neuronal degeneration and synaptic alterations, which are thought to constitute the major neurobiological basis of cognitive dysfunction in Alzheimer's disease. The hippocampal formation is especially vulnerable in the early stages of Alzheimer's disease. However, the vast majority of electron microscopy studies have been performed in animal models. In the present study, we performed an extensive 3D study of the neuropil to investigate the synaptic organization in the stratum pyramidale and radiatum in the CA1 field of Alzheimer's disease cases with different stages of the disease, using focused ion beam/scanning electron microscopy (FIB/SEM). In cases with early stages of Alzheimer's disease, the synapse morphology looks normal and we observed no significant differences between control and Alzheimer's disease cases regarding the synaptic density, the ratio of excitatory and inhibitory synapses, or the spatial distribution of synapses. However, differences in the distribution of postsynaptic targets and synaptic shapes were found. Furthermore, a lower proportion of larger excitatory synapses in both strata were found in Alzheimer's disease cases. Individuals in late stages of the disease suffered the most severe synaptic alterations, including a decrease in synaptic density and morphological alterations of the remaining synapses. Since Alzheimer's disease cases show cortical atrophy, our data indicate a reduction in the total number (but not the density) of synapses at early stages of the disease, with this reduction being much more accentuated in subjects with late stages of Alzheimer's disease. The observed synaptic alterations may represent a structural basis for the progressive learning and memory dysfunctions seen in Alzheimer's disease cases.
ObjectivesSeveral studies have reported the role of immune-related adverse events as a predictor of clinical benefit, but few have properly described these findings in advanced or metastatic ...non-small cell lung cancer treated with pembrolizumab. This study aimed to evaluate the association between immune-related adverse events development and clinical outcomes in the aforementioned group of patients.MethodsWe conducted a retrospective study in patients with advanced or metastatic non-small cell lung cancer treated with pembrolizumab. Overall response rate, progression-free survival and overall survival were evaluated according to the appearance, subtype and number of immune-related adverse events developed. We report the results of the immune-related adverse events analysis and the potential correlation between immune-related adverse events and clinical outcomes. Univariate and multivariate analyses were performed to evaluate this relationship.ResultsA total of 94 patients were analysed; 60 of them developed immune-related adverse events. Patients with immune-related adverse events had a significantly higher overall response rate compared with the non-immune-related adverse events group (34% vs 8.5%, χ2=0.005). Median progression-free survival was statistically significant in favour of patients with at least one immune-related adverse event (p=0.015). Median overall survival was not reached in patients with ≥1 immune-related adverse events, compared with 8 months (95% CI 0.6 to 15.4 months) in those without immune-related adverse events. Patients who developed ≥2 immune-related adverse events had longer median progression-free survival (11 vs 4 months, not statistically significant) and overall survival (not reached vs 11, p=0.022) compared with those with ≤1 immune-related adverse events.ConclusionsObtained data showed that patients with immune-related adverse events occurrence had significantly better overall response rate and longer progression-free survival and overall survival. This study highlights the role of immune-related adverse events as a predictor of survival in a real-life setting.
Pdp11 is a strain described as a probiotic for use in aquaculture. However,
includes strains reported to be pathogenic or saprophytic to fish. Although the probiotic trait has been related to the ...presence of a group of genes in its genome, the existence of plasmids that could determine the probiotic or pathogenic character of this bacterium is unknown. In the present work, we searched for plasmids in several strains of
that differ in their pathogenic and probiotic character. Under the different conditions tested, plasmids were only found in two of the five pathogenic strains, but not in the probiotic strain nor in the two saprophytic strains tested. Using a workflow integrating Sanger and Illumina reads, the complete consensus sequences of the plasmids were obtained. Plasmids differed in one ORF and encoded a putative replication initiator protein of the repB family, as well as proteins related to plasmid stability and a toxin-antitoxin system. Phylogenetic analysis showed some similarity to functional repB proteins of other
species. The implication of these plasmids in the probiotic or pathogenic nature of
is discussed.
Low self-efficacy has been identified as one of the factors that could hinder the prescribing competence of nurses. No valid and reliable existing instruments assess Galician nurses' confidence to ...prescribe. The aim of this study was to determine the reliability and validity of the Galician version of the Nurse Prescribing Self-Efficacy Scale (G-NP-SES, 19 items). The study was conducted in two phases: the translation and adaptation to the Galician version of the NP-SES, and the assessment of its psychometric properties. G-NP-SES was sent to nurses working in primary healthcare centers in Galicia (Spain) between March and June of 2022. Its content, construct and discriminant validity, and internal consistency reliability were examined. A total of 193 people participated in the study. As the original scale, G-NP-SES also had three dimensions (% of cumulative variance = 80.82%). It showed good internal consistency (Cronbach's alpha coefficient (α) = 0.90, with each factor ranging from 0.86 to 0.89), high content validity (scale's content validity index = 0.92, with item-content validity index ranged from 0.87 to 1), and good discriminant validity. G-NP-SES is an instrument with good psychometric properties which could be used to accurately assess Galician nurses' self-efficacy to prescribe and consequently to improve their job performance.
Ice creams produced with unsaturated fats rich in oleic (OO, 70.7% of oleic) and linoleic (LO, 49.0% of linoleic) fatty acids, were compared to ice cream based on saturated coconut oil (CO, 50% of ...lauric acid). The globule size distribution of OO mix during aging (72 h at 4°C) followed a similar trend to CO mix, being stable after 48 h; whereas LO mix destabilized after 24 h. CO mix showed higher destabilization during ice cream production, but no significant differences among fats were observed in the particle size of the ice cream produced. The overrun was also lower for OO and LO ice creams (34.19 and 27.12%, respectively) compared to CO based ice cream (45.06%). However, an improved melting behavior, which gradually decreased from 88.69% for CO to 66.09% for LO ice cream, was observed.
Practical applications: This work evaluates the use of high unsaturated fats in the production of ice cream as alternative to highly saturated coconut oil. Common unsaturated fats normally lead to ice cream with low quality in terms of overrun and melting points. Nevertheless, the results obtained in this study indicated that the two fats assayed, rich in oleic and linoleic acids, are adequate for the production of ice cream. Therefore, these highly unsaturated fats are a promising alternative for the development of healthier ice creams.
Unsaturated fats are introduced in ice cream and compared to saturated coconut oil. Similar fat globule size and viscosity are found, while melting behavior is improved.
Unsaturated fats are introduced in ice cream and compared to saturated coconut oil. Similar fat globule size and viscosity are found, while melting behavior is improved.
The Ex Utero Intrapartum Treatment (EXIT) procedure has long been an invaluable tool in managing complex fetal conditions requiring airway interventions during the transition from intrauterine to ...extrauterine life. This technical note offers an in-depth examination of the EXIT procedure, emphasizing the refinements and innovations introduced at our center. The technique focuses on meticulous preoperative assessment and uses distinctive techniques and anesthetic methodologies. A multidisciplinary team assembles to plan the EXIT procedure, emphasizing patient communication and risk discussion. Our technique involves atraumatic access to the uterine cavity, achieved through the application of a uterine progressive distractor developed for this purpose. Following the use of this distractor, vascular clamps and a stapling device (Premium Poly Cs-57 Autosuture®, Medtronic) are employed. Our anesthetic approach employs general anesthesia with epidural catheter placement. Maternal operation involves low transverse laparotomy and intraoperative ultrasonography-guided hysterotomy. Fetal exposure includes gentle extraction or external version, ensuring airway access. After securing fetal airway access, umbilical cord clamping and maternal abdominal closure conclude the procedure. By revisiting the core principles of EXIT and incorporating center-specific advancements, we enhance our understanding and technical expertise. To our knowledge, this is the first time a detailed description of the technique has been published.
Introduction
This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease ...activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment.
Methods
Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures
t
-test.
Results
A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (
p
value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (
p
value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit.
Conclusions
The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.
Introduction: Trunk function assessment is considered a key factor for the development of evidence-based classification process in wheelchair athletes. Thus, the aim of this study was to determine ...the intra-session reliability of two kinematic analysis tools (2D video analysis measure and an inclinometer mobile application) that could be used by classifiers to detect trunk range of movement (ROM) impairment in wheelchair athletes. Material and methods: Sixteen wheelchair athletes and six non-disabled participants (CG) were recruited for this study. Wheelchair athletes were dividing according to the origin of their eligible physical impairment in a neurological impairment group (ANI, n=7) and an impaired muscle power group (IMP, n=9). ROM was assessed in sagittal and coronal plane movements. Results: High-excellent relative intra-session reliability scores were found for trunk ROM measures for all participants (0.87 < ICC < 0.99). Significantly lower ROM values were observed in wheelchair athletes compared to CG, with the exception of the trunk flexion tilt movement measured by the 2D video analysis in the IMP group and the trunk extension tilt movement measured by the inclinometer app in the ANI group. Conclusion: 2D video analysis showed good intra-session reliability in the assessment of trunk ROM, while high intra-subject variability was observed when using the inclinometer app. The proposed tools may help classifiers to detect trunk ROM impairment at different levels in wheelchair athletes with different health conditions being the inclinometer app more interesting to detect lower back trunk impairment.
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