The association between white matter hyperintensities (WMH) and amyloid accumulation over time in cognitively normal, amyloid-negative elderly people remains largely unexplored. In order to study ...whether baseline WMH were associated with longitudinal subthreshold amyloid accumulation, 159 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative who were amyloid-negative at baseline were examined. All the participants underwent a T1 and a Fluid-Attenuated Inversion Recovery MRI scan at baseline. Amyloid PET imaging was performed at baseline and follow-up visits in 2-year intervals for up to 8 years. Partial volume correction was applied for quantifying cortical Standardised Uptake Value Ratios (SUVR). The associations between global and regional WMH burden and amyloid accumulation were assessed using linear mixed models adjusted by demographic characteristics and baseline SUVR. Partial volume correction increased the measured annual rate of change (+2.4%) compared to that obtained from non-corrected data (+0.5%). There were no significant correlations between baseline WMHs and baseline subthreshold cortical amyloid uptake. In a longitudinal analysis, increased baseline cortical SUVR and increased baseline burden of global (p = 0.006), frontal (p = 0.006), and parietal WMH (p = 0.003) were associated with faster amyloid accumulation. WMH-related amyloid accumulation occurred in parietal, frontal, and, to a lesser extent, cingulate cortices. These results remained unchanged after a sensitivity analysis excluding participants with the highest cortical SUVRs. This is the first study to identify a specific spatial distribution of WMH which is associated with future amyloid accumulation in cognitively normal elderly subjects without PET-detectable amyloid pathology. These findings may have important implications in prevention trials for the early identification of amyloid accumulation.
•The relation between white matter lesions and amyloid accumulation is unclear.•Longitudinal Aβ-PET scans in Aβ-negative, normal elderly for up to 8 years.•A spatial pattern of WMH relates to amyloid accrual in Aβ-negative, normal elderly.•WMH patterns might help identify amyloid “accumulators”.
Este artículo presenta el análisis de las vivencias de un grupo de jóvenes que han sido objeto de acoso escolar, a partir de la percepción de sí mismos, su historia familiar y su contexto ...socio-escolar, desde una perspectiva psicoanalítica. Participaron seis estudiantes del nivel medio superior a través de una entrevista semiestructurada y el Test de Apercepción Temática. Los hallazgos indican que estos jóvenes, al ocupar un lugar de desvalorización, complacencia y vulnerabilidad en la familia, son más proclives a mantener esa condición ante los pares escolares y las relaciones de noviazgo, se callan las agresiones recibidas y prevalece una la ley del silencio.
The purpose of our study was to evaluate the accuracy of sonography and sonographically guided biopsy in the preoperative diagnosis of metastatic invasion of the axilla in patients with breast ...carcinoma.
We performed a MEDLINE search (keywords, "sonography" OR "ultrasound" AND "axillary") and a manual search of the references of relevant studies and reviews of preoperative diagnosis on sonography of possible axillary metastases. The gold standard required was axillary lymph node dissection; we accepted sentinel node biopsy as an alternative gold standard. Considering the sonographic findings and the results of the sonographically guided biopsy, the sensitivity and specificity were calculated using metaanalysis. We also checked the existence of heterogeneity of the summary results.
Sixteen articles were selected. In sonography of axillae without palpable nodes, and using lymph node size as the criterion for positivity, sensitivity varied between 48.8% (95% confidence interval, 39.6-58%) and 87.1% (76.1-94.3%) and specificity, between 55.6% (44.7-66.3%) and 97.3% (86.1-99.9%). When lymph node morphology was used as the criterion for positivity, sensitivity ranged from 26.4% (15.3-40.3%) to 75.9% (56.4-89.7%) and specificity, from 88.4% (82.1-93.1%) to 98.1% (90.1-99.9%). The results are different if axillae with palpable nodes are included. The sonographically guided biopsy shows a sensitivity that varies between 30.6% (22.5-39.6%) and 62.9% (49.7-74.8%) and a specificity of 100% (94.8-100%). Many of the summary results obtained after meta-analysis show a heterogeneity that disappears, on occasion, on excluding the studies that use a double gold standard.
Axillary sonography is moderately sensitive and fairly specific in the diagnosis of axillary metastatic involvement. Sonographically guided biopsy of the sonographically suspicious nodes somewhat increases the specificity, which reaches 100%. Negative sonographic results do not exclude axillary lymph node metastases.
Abstract Background and purpose Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea (SA), although the evidence for improving chronic heart failure (CHF) is ...inconclusive. Our aim was to evaluate the effect of CPAP treatment on the left ventricle ejection fraction (LVEF) among other cardiological variables in a randomized, multicenter, placebo (sham-CPAP)-controlled study. Methods After the selection procedure, 60 patients with CHF with LVEF < 45% and SA with an apnea–hypopnea index (AHI) > 10/h were evaluated at baseline, and after 3 months of treatment with optimal CPAP or sham-CPAP. The assessment was based on the LVEF, hypertension, daytime sleepiness (Epworth sleepiness scale ESS), quality of life (SF-36), New York Heart Scale (NYHA score), dyspnea (by using the Borg scale) and exercise tolerance (6-min walk test). Results The mean AHI was normalized in the optimal CPAP group but not in the sham-CPAP group. The LVEF showed a significant improvement in the group of patients treated with CPAP (2.5; 95% CI: 0.6 to 4.3), which was not observed in the sham-CPAP group (0.0; 95% CI: −2.1 to 2.1). However, the change in the LVEF from baseline to 3 months was not significantly greater in the whole group (obstructive and Cheyne–Stokes events) treated with CPAP than in the control group ( p : 0.07). In patients with only obstructive sleep apnea (OSA), who account for 83% of the total population, there was a significant improvement in the LVEF in the group of patients treated with CPAP but no such improvement in the sham-CPAP group. In this OSA group, the change in the LVEF from baseline to 3 months was significantly greater in the group treated with CPAP than in the sham-CPAP group ( p : 0.03). The other variables studied were not modified. When the patients were divided according to the severity of the LVEF (a LVEF cut-off of 30%), improvement was observed in those with a LVEF > 30. No changes were found in the other cardiological variables. Conclusions CPAP therapy proved to be useful in patients with associated sleep-disordered breathing and CHF. The improvement was more marked in patients with a LVEF > 30%. However, the increased LVEF in the CPAP group was not accompanied by changes in the other cardiological variables.
Magnetic resonance imaging (MRI) volumetric measures have become a standard tool for the detection of incipient Alzheimer's Disease (AD) dementia in mild cognitive impairment (MCI). Focused on ...providing an earlier and more accurate diagnosis, sophisticated MRI machine learning algorithms have been developed over the recent years, most of them learning their non-disease patterns from MCI that remained stable over 2-3 years. In this work, we analyzed whether these stable MCI over short-term periods are actually appropriate training examples of non-disease patterns. To this aim, we compared the diagnosis of MCI patients at 2 and 5 years of follow-up and investigated its impact on the predictive performance of baseline volumetric MRI measures primarily involved in AD, i.e., hippocampal and entorhinal cortex volumes. Predictive power was evaluated in terms of the area under the ROC curve (AUC), sensitivity, and specificity in a trial sample of 248 MCI patients followed-up over 5 years. We further compared the sensitivity in those MCI that converted before 2 years and those that converted after 2 years. Our results indicate that 23% of the stable MCI at 2 years progressed in the next three years and that MRI volumetric measures are good predictors of conversion to AD dementia even at the mid-term, showing a better specificity and AUC as follow-up time increases. The combination of hippocampus and entorhinal cortex yielded an AUC that was significantly higher for the 5-year follow-up (AUC = 73% at 2 years vs. AUC = 84% at 5 years), as well as for specificity (56% vs. 71%). Sensitivity showed a non-significant slight decrease (81% vs. 78%). Remarkably, the performance of this model was comparable to machine learning models at the same follow-up times. MRI correctly identified most of the patients that converted after 2 years (with sensitivity >60%), and these patients showed a similar degree of abnormalities to those that converted before 2 years. This implies that most of the MCI patients that remained stable over short periods and subsequently progressed to AD dementia had evident atrophies at baseline. Therefore, machine learning models that use these patients to learn non-disease patterns are including an important fraction of patients with evident pathological changes related to the disease, something that might result in reduced performance and lack of biological interpretability.
The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the ...intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro, encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.
Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology ...has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.
The Household Life Cycle framework relates family demographic processes to land use-cover change, but also revealed limitations. We propose several modifications, featuring a focus on extended ...families instead of single households, to broaden the applicability to land use systems. In the process, we pay particular attention to temporal dynamics and the spatial distribution of families concerning demographic processes, going beyond fertility to focus on population distribution. To evaluate the extended family model’s explanatory value, we apply it to the Transamazon Highway region in Brazil. The analysis includes 330 families, which are often multi-generational and multi-sited, based on data from 402 lots (1997/8–2005). We present models for forest, secondary succession, annual crops, perennials and pasture. Explanatory variables feature nine demographic factors with five others controlling for exogenous forces. The findings show strong effects for family dynamics and spatial distribution variables in many equations. Time on lot (cohort effect), the complexity of family structure (age effect) and social integration into urban fabric (spatial effect) are demographic processes that deserve further attention in land use studies.
It is unclear whether episodic memory is an appropriate descriptor of the cognitive continuum in mild cognitive impairment (MCI). Here, we investigated the ability of episodic memory to track ...cognitive changes in patients with MCI with biomarker evidence of Alzheimer's disease (AD). We examined 387 MCI amyloid-positive subjects, cognitively staged as “early” or “late” on the basis of episodic memory impairment. Cross-sectional and longitudinal comparisons between these 2 groups were performed for each amyloid, tau, and neurodegeneration (AT(N)) profile. Cross-sectional analyses indicate that “early” MCI represents a transitional phase between normal cognition and “late” MCI in the AD biomarker pathway. After adjusting by confounders and levels of A, T, and (N), “late” MCI progressed significantly faster than “early” MCI only in profiles with both abnormal amyloid and tau markers (A+T+(N)− p < 0.05, A+T+(N)+ p < 0.001). Episodic memory staging is useful for describing symptoms in prodromal AD and complements the AT(N) profiles. Our findings might have implications for the Numeric Clinical staging scheme of the National Institute on Aging and Alzheimer's Association research framework.
•It is unclear whether episodic memory can track the prodromal cognitive continuum.•We studied episodic memory staging in patients with mild cognitive impairment with biomarker evidence of Alzheimer's disease.•This scheme tracks symptoms only in patients with mild cognitive impairment with abnormal amyloid and tau markers.•Episodic memory adds prognostic information to biomarker profiles in prodromal Alzheimer's disease.
Psiconeuroinmunología, su relación con las enfermedades Diana Esperanza Monet Alvarez; Virgen Yaneisi Gross Ochoa; Julia Tamara Alvarez Cortés
Anales de la Academia de Ciencias de Cuba,
05/2022, Letnik:
12, Številka:
2
Journal Article
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