Ricardo Montoya Monsalve, Sara Isabel Castaño Ocampo
Introducción: la inteligencia artificial (IA) ha emergido como una herramienta relevante en neuropsicología, con potencial para optimizar procesos clínicos, investigativos y educativos en el estudio de las funciones cognitivas.
Materiales y métodos: se realizó una revisión teórica mediante búsqueda en bases de datos como PubMed, Scopus, ScienceDirect, Scielo y Redalyc, empleando términos MeSH y operadores booleanos. Se incluyeron artículos en inglés y español, principalmente desde 2014. De 98 registros, se seleccionaron 52 tras aplicar criterios de inclusión y exclusión.
Resultados: se identificaron tres áreas de aplicación: clínica, investigativa y educativa. En el ámbito clínico, la IA alcanzó precisiones de hasta el 91?% en la predicción de demencia y apoyó el análisis de neuroimágenes y el tratamiento. En investigación, facilitó el análisis de grandes volúmenes de datos, la identificación de biomarcadores y el desarrollo de modelos predictivos. en educación, mostró beneficios en el aprendizaje personalizado, aunque con menor nivel de evidencia.
Discusión: persisten limitaciones como la baja interpretabilidad, problemas de generalización y desafíos éticos relacionados con sesgos y privacidad de datos.
Conclusiones: la IA representa un avance significativo en neuropsicología, pero requiere marcos ético-legales y debe complementar, no sustituir, la experiencia clínica.
ABSTRACT Background and Objectives A variety of observational studies suggest a possible connection between C‐X‐C Motif Chemokine Ligand 5 (CXCL5) and vascular dementia (VaD), though the exact causal relationship is still uncertain. This research aims to investigate the causal connection between CXCL5 and VaD risk through a Mendelian randomization (MR) method and to examine the phosphate‐to‐glucose ratio as a possible mediator. Methods Using summary‐level data from genome‐wide association studies (GWAS), we conducted a two‐sample MR analysis to investigate the genetic prediction of CXCL5 and VaD. Horizontal pleiotropy, heterogeneity, and sensitivity analyses were also performed on the MR findings. Additionally, a two‐step MR was utilized to quantify the proportion of the effect of CXCL5 on VaD mediated by the phosphate‐to‐glucose ratio. Results MR analysis identified that higher levels of CXCL5 (IVW: p = 0.022, OR = 1.265, 95% CI = 1.034–1.547) increase the risk of VaD. Tests for horizontal pleiotropy (p > 0.05), heterogeneity (p > 0.05), and sensitivity analyses supported these findings. There is insufficient robust evidence to suggest that genetic predispositions for VaD have any significant impact on CXCL5 (IVW: p = 0.254). The phosphate‐to‐glucose ratio accounted for 11.1% of increase in the risk of VaD associated with CXCL5 (95% CI = −12.3% to 34.5%). Conclusion To conclude, our research confirms a causal link between CXCL5 and VaD and shows that the ratio of phosphate‐to‐glucose plays a mediating role in a segment of the risk effect of CXCL5 on VaD. However, most of the effects of CXCL5 on VaD are still not well understood. Additional studies are necessary to explore other potential mediators as risk factors. In clinical settings, individuals with abnormally elevated CXCL5 may need to be monitored for an increased risk of developing VaD.
Abstract The persistence of drug memories accounts for the high risk of drug relapse, which is a major challenge in the treatment of substance use disorders. However, the neurobiological underpinnings, especially the dynamic changes of brain networks underlying long-term drug memories, remain unclear. Here we utilized cocaine conditioned place preference (CPP) in rats combined with c-Fos mapping in multiple brain regions and network analysis to assess dynamic patterns of neural activity and functional memory networks following the recall of short-term and long-term cocaine memory. Furthermore, we employed chemogenetic interventions to disrupt the core nodes within the long-term memory network. Our results showed that the recall of long-term cocaine memory is characterized by more extensive and stronger neuronal activation, greater interregional co-activation, and a more coordinated and stable brain network, compared to short-term cocaine memory. Within this reorganized network, the retrosplenial cortex (RSC) emerged as a key hub. Chronic inhibition of RSC disrupted the network and impaired the recall of the long-term memory. These findings demonstrate that the persistence of cocaine memory is encoded by a large-scale reorganization toward a more integrated and stable brain state, and identify the RSC as a critical cortical node orchestrating this process, offering a potential target for relapse prevention strategies.
MinJae Lee, Anna M Georgiopoulos, Raksha Jain
et al.
Introduction People with cystic fibrosis (CF) are living longer and healthier lives with a growing number considering and pursuing parenthood. The decision of whether to become a parent is complex for people with CF, and CF is a major factor in reproductive decision-making. Unfortunately, in people with CF who become parents, there are no prospective studies of disease trajectory, no data on the impact of parenthood on mental health, disease self-management, or quality of life, and no research regarding non-genetic parenthood.Methods and analysis Health Outcomes of Parents with CF (HOPeCF) is a prospective, multicentre observational cohort study which will enrol 146 new parents with CF of children less than 5 years of age. The primary aim of this 60-month study is to assess the rate of lung function decline as impacted by mental health, parental stress and responsibility, and the use of CF transmembrane conductance regulator modulators. In addition, we will conduct dyadic interviews with a subset of study participants and their key supports (partner/family/friend) to inform future interventions.Ethics and dissemination This longitudinal, observational multicentre study is a necessary and timely step in understanding parental health outcomes in CF and will provide data essential for care guidance to people with CF, their partners, and healthcare providers. The University of Pittsburgh Institutional Review Board approved this study (STUDY23080161). As people with a variety of paediatric-onset chronic diseases are living longer and considering parenthood, these results may have widespread applicability and will be distributed at international meetings and submitted to peer-reviewed journals.
Aims
Local protein synthesis at the synapse is a key determinant of learning and memory and is predicted to be severely disrupted in Alzheimer's disease (AD). Omics approaches have played a key role in deciphering molecular mechanisms underlying AD pathology. However, isolating the transcriptome may be biased due to inherent variations in transcript levels, or by transcription-on-demand models employed by several genes, whereas mass-spec based proteomics approaches fail to capture low abundance peptides. The translatome bypasses these inherent limitations of other omics methods by capturing actively translating mRNA species trapped inside ribosomes and subjecting them to unbiased RNA-seq analysis capturing even very low abundance transcripts.
Methods
Isolating the neuronal ribosomes from human post-mortem brains without interference from non-neuronal cells remains a challenge. We used frozen brain tissue from Alzheimer's patients and healthy controls obtained from the Cambridge Brain Biobank. Synaptoneurosomal fractions were prepared using sucrose gradients in non-denaturing buffers with RNAse inhibitors to preserve ribosomal composition and trapped mRNA. We isolated functional ribosomes on affinity columns following recombinant RNAse digestion. Finally, actively translating ribosome-trapped mRNAs were sequenced using RNA-seq, aligned to human genome using STAR alignment and analysed for differential expression using DeSeq2 followed by pathway analysis.
Results
We have successfully isolated ribosome-associated RNA transcripts in the dendritic spines from cortical neurons of postmortem Alzheimer's brains with little interference from glial and non-neuronal material. The novel AD translatome disruptions identified by isolating endogenous ribosome bound mRNA will help detect downstream molecular targets. We will also integrate targeted translatome data with published transcriptome and GWAS DNA variant data to identify novel biomarkers.
Conclusion
This is the first successful isolation of the dendritic translatome from human postmortem AD brains. Future studies will verify functional significance of key targets using gain- and loss-of-function studies in animal models of AD and human iPSCs.
Angélica Uscátegui Daccarett., J. Sebastián Ortiz De La Rosa., Laura Victoria Guío Mahecha.
Se presenta una revisión de la literatura acerca de la presencia de alteración del campo visual asociada al uso de vigabatrín como antiepiléptico. Considerando las precauciones de prescripción derivadas de los efectos visuales de vigabatrin, presentamos una revisión no sistemática que muestra los principales datos respecto a prevalencia, factores de riesgo, fisiopatología y seguimiento de esta alteración. La prevalencia de aparición de la retinopatía es variable según las series revisadas, y los factores de riesgo como uso de dosis máxima, dosis acumulada y edad no están claramente demostrados, por lo que se considera a éste un efecto idiosincrático. Se recomienda la vigilancia oftalmológica y campimétrica periódica.
Natalia Smith-Cortinez, Natalia Smith-Cortinez, Ferry G. J. Hendriksen
et al.
IntroductionThe leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is a tissue resident stem cell marker, which it is expressed in supporting cells (SCs) in the organ of Corti in the mammalian inner ear. These LGR5+ SCs can be used as an endogenous source of progenitor cells for regeneration of hair cells (HCs) to treat hearing loss and deafness. We have recently reported that LGR5+ SCs survive 1 week after ototoxic trauma. Here, we evaluated Lgr5 expression in the adult cochlea and long-term survival of LGR5+ SCs following severe hearing loss.MethodsLgr5GFP transgenic mice and wild type mice aged postnatal day 30 (P30) and P200 were used. P30 animals were deafened with a single dose of furosemide and kanamycin. Seven and 28 days after deafening, auditory brainstem responses (ABRs) were recorded. Cochleas were harvested to characterize mature HCs and LGR5+ SCs by immunofluorescence microscopy and quantitative reverse transcription PCR (q-RT-PCR).ResultsThere were no significant age-related changes in Lgr5 expression when comparing normal-hearing (NH) mice aged P200 with P30. Seven and 28 days after ototoxic trauma, there was severe outer HC loss and LGR5 was expressed in the third row of Deiters’ cells and in inner pillar cells. Seven days after induction of ototoxic trauma there was an up-regulation of the mRNA expression of Lgr5 compared to the NH condition; 28 days after ototoxic trauma Lgr5 expression was similar to NH levels.DiscussionThe presence of LGR5+ SCs in the adult mouse cochlea, which persists after severe HC loss, suggests potential regenerative capacity of endogenous cochlear progenitor cells in adulthood. To our knowledge, this is the first study showing not only long-term survival of LGR5+ SCs in the normal and ototoxically damaged cochlea, but also increased Lgr5 expression in the adult mouse cochlea after deafening, suggesting long-term availability of potential target cells for future regenerative therapies.
Fernando L. Pagan, Yasar Torres‐Yaghi, Michaeline L. Hebron
et al.
Abstract Introduction Bosutinib, a dual Abelson/Src inhibitor, was investigated in individuals with dementia with Lewy bodies (DLB). Methods A single site, randomized, double‐blind, placebo‐controlled study of the effects of oral bosutinib, 100 mg once daily for 12 weeks on primary safety and pharmacokinetics and secondary biomarker outcomes. Results Twenty‐six participants were randomized and included male and female (12:1) in the bosutinib arm and all male (13) in the placebo arm. The average age was 72.9 ± 8.1 (year ± standard deviation). There were no serious adverse events and no dropouts. Bosutinib was measured in the cerebrospinal fluid (CSF) and inhibited Abelson. Bosutinib reduced CSF alpha‐synuclein and dopamine catabolism. Discussion Bosutinib is safe and well tolerated and penetrates the blood–brain barrier to inhibit Abelson and reduce CSF alpha‐synuclein and dopamine catabolism, suggesting that bosutinib (100 mg) may be at or near the lowest effective dose in DLB. These results will guide adequately powered studies to determine the efficacy of a dose range of bosutinib and longer treatment in DLB. Highlights Bosutinib is a dual Abl/Src inhibitor that penetrates the blood brain barrier Bosutinib is safe and tolerated in individuals with dementia with Lewy bodies Bosutinib engages its target via inhibition of Abl and Src Bosutinib reduces CSF alpha‐synuclein and attenuates breakdown of dopamine Bosutinib improves activities of daily living in dementia with Lewy bodies
Neurology. Diseases of the nervous system, Geriatrics
Weronika Zwolińska, Maria Skibinska, Agnieszka Słopień
et al.
Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, pro–brain–derived neurotrophic factor (proBDNF), in the pathophysiology of mood disorders and the potential neurodegenerative role of calcium-binding protein B (S100B). Our objective was to compare BDNF, proBDNF, and S100B serum levels before and after the treatment of acute depressive episodes and to assess their correlation with the severity of symptoms and history of stress. We also aimed to investigate the differences in BDNF, proBDNF, and S100B levels between depression in the course of bipolar disorder (BD) and major depressive disorder (MDD). We recruited 31 female patients diagnosed with BD or MDD who were hospitalized due to current depressive episodes. The patients had their serum BDNF, proBDNF, and S100B levels evaluated using the ELISA method upon admission and after the symptoms improved, at discharge. We found that proBDNF levels decreased significantly with the treatment (<i>p</i> = 0.0478), while BDNF and S100B levels were not altered significantly. No differences in biochemical parameters between MDD and BD subjects were observed. Consequently, we concluded that a decrease in serum proBDNF levels could be considered a biomarker of recovery from depressive episodes.
Gut microbial alteration is closely associated with brain disorders including cognitive impairment (CI). Gut microbes have the potential to predicate the development of diseases. However, the gut microbial markers for CI remain to be elucidated. In this study, the gut microbial alterations were assessed using16S rRNA sequencing, and identified the gut microbial markers using a random forest model. The results showed that there were significant gut microbial differences between the control and CI groups based on beta diversity (p < 0.002). Patients with CI had higher abundances of Actinobacteria and Proteobacteria but lower proportions of Bcateroidetes and Firmicutes vs. that in the control group. Patients had 39 special genera and the control subjects had 11 special genera. Furthermore, 11 genera such as Blautia, Roseburia, and Lactococcus and 18 genera such as Lactobacillus, Ruminococcus 2, and Akkermansia were the differential taxa in the control and CI groups, respectively. Gene functions related to nutrient metabolisms were upregulated in patients with CI. This suggested that the huge differences in gut microbes between the two groups and gut microbiota had the potential to predicate the development of CI. Based on machine learning results, 15 genera such as Lactobacillus, Bifidobacterium, and Akkermansia were selected as the optimal marker set to predicate CI with an area under curve (AUC) value of 78.4%. The results revealed the gut microbial markers for CI and provided a potential diagnosis tool to prevent the development of CI in the elderly.
Rahul Pillai, Bijesh Ravindran Nair, Prasad Kanna Prabhakar
et al.
Context: The iliac crest (IC) is widely used as an autograft for bony fusion in spine surgeries. The pain after IC harvesting is severe enough to delay ambulation and thus hospital discharge. Aim: This study aimed to determine the effect of a transmuscular quadratus lumborum block (QLB) on postoperative ambulation in patients undergoing anterior IC bone graft harvesting. Settings and Design: This was a retrospective study of patients who underwent cervical corpectomy and fusion with anterior IC bone graft over a period of 3 years. Materials and Methods: Group A was patients who received QLB for anterior IC bone graft harvest site pain, and those who did not receive QLB were Group B. The primary outcome was the time taken for ambulation, and the secondary outcomes compared were the pain scores, hemodynamics, and the duration of hospital stay. Results: A total of 34 patients were studied, of which 17 patients received QLB (Group A) and the rest 17 did not receive QLB (Group B). The demographics, preoperative and intraoperative variables, and the pain score were comparable between the groups. The patients in the QLB group ambulated early as compared to Group B (1.5 ± 0.7 vs. 2.4 ± 0.9 days = 0.002). Further, the duration of postoperative hospitalization was shorter in the former as compared to the latter (3.8 ± 1.6 vs. 5.1 ± 2.1 days; P = 0.054). There were no complications related to the QLB. Conclusion: The administration of QLB resulted in earlier postoperative ambulation in patients undergoing cervical corpectomy with AIC bone graft. Although the length of hospitalization was shorter in the QLB group, it was not statistically significant.
Background.Given the range and reach of psychosocial support (PSS) interventions in humanitarian settings, within the continuum of mental health and psychosocial support services, evaluation of their impact is critical. Understanding stakeholders' perspectives on which PSS interventions of unknown effectiveness warrant rigorous evaluation is essential to identify research priorities. This project aimed to facilitate a process with stakeholders to reach consensus on PSS interventions that are of high priority for further research based on existing evidence and stakeholders' opinions.Methods.Interviews with 109 stakeholders working on PSS programming in humanitarian settings served as the foundation for two in-person regional meetings and four webinars. Nominal Group Technique (NGT) was used to develop a priority PSS program list. The top five priorities from each meeting were combined for a final online survey distributed globally.Results.Seventy participants across six meetings contributed to the prioritization process. Eighty-seven individuals completed the final online survey. ‘Community based PSS’ was the top-ranked research priority, followed by PSS integrated into basic services, providing PSS to caregivers to improve child wellbeing, PSS-focused gender-based violence programming, and classroom-based PSS interventions.Conclusions.NGT and online surveys were effective methods to engage stakeholders in a priority setting exercise to development a research agenda. Information from this stage of the project will be combined with findings from a concurrent systematic review to form the base of a second phase of work, which will include the development and implementation of a research strategy to strengthen the evidence base for those prioritized interventions.
The catechol-o-methyltransferase (COMT) gene has repeatedly been shown to change amygdala activity and amygdala-prefrontal connectivity during face processing. Although the COMT gene appears to induce a negativity bias during the neural processing of faces, it is currently unclear whether a similar negativity bias emerges during the behavioral processing of faces. To address this issue, we investigated differences in complex emotion recognition between participants (n = 181) that had been a priori genotyped for functional polymorphisms of the COMT (Val158Met) and serotonin transporter (5-HTTLPR) gene. We were, thus, able to analyze differences in face processing on basis of participants’ COMT genotype while controlling for participants’ 5-HTTLPR genotype. Variations of participants’ COMT but not 5-HTTLPR genotype accounted for differences in participants’ emotion recognition performance: Met/Met carriers and Met/Val carriers were more accurate in the recognition of negative, but not neutral or positive, expressions than Val/Val carriers. We, therefore, revealed a similar negativity bias during the behavioral processing of faces that has already been demonstrated during the neural processing of faces, indicating that genotype-dependent changes in catecholamine metabolism may affect face processing on the behavioral and neural level.
The psychoanalytical sections, as would be expected from a distinguished psychoanalyst, are at once the main strength of the book and the main weakness in that they are relatively so full as to make the whole work appear overbalanced towards this school of thought. Drugs, physical treatments and community therapies each merit five or six pages?much less than is devoted to recent changes in personality theory. The style of the book is somewhat ponderous and humourless. The general layout and production are good, while the full references and appendices will be useful. In sum, it is the best general historical survey available of the mid-century position of