Abstract Introduction Ambulatory blood pressure (BP) monitoring encapsulates 24-h BP patterns across the sleep-wake cycle and provides a comprehensive assessment of BP regulation with certain features, such as sleep-time dipping, that can better predict health outcomes than traditional office BP measurements. However, 24-h BP patterns remain understudied in Latino populations, especially older adults. This pilot study investigated the feasibility of continuously ambulatory BP monitoring blood pressure with portable devices in Latinos with dementia. Methods Eight participants (4 with Alzheimer’s disease, 1 with Frontotemporal dementia, 3 controls; age range 45.8-80.3 years) from the ReDLat cohort (Multi-Partner Consortium to Expand Dementia Research in Latin America) were enrolled for a 48-h ambulatory BP assessment with hourly measurements using a portable arm-cuff device. Participants also answered six questions to evaluate: (1) device adaption, (2) measurement frequency tolerability, (3) study duration acceptability, (4) perceived value of the assessment, (5) willingness to perform the assessment again, and (6) likelihood of recommending the assessment to others. Results The study yielded high-quality recordings with minimal missing BP measurements (range: 0%-14.1%; mean: 8.9%). Device adaptation improved over time, with 75% (6/8) reporting better tolerance on the second day and 25% (2/8) reporting consistently good tolerance across both days. All participants reported that hourly BP measurement was tolerable, and majority (7/8, 87.5%) found 48-h monitoring acceptable. Seven participants (87.5%) believed that the assessment was valuable, were willing to participate again, and likely recommend to others the assessment. Conclusion Our findings demonstrate that 48-hour ambulatory BP monitoring is feasible and well-tolerated among older Latino adults with mild to moderate dementia in Latin American settings. Further feasibility testing should be performed in large samples and other populations, including individuals at later stages of dementia and in different countries.

Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.

In this work, we use a mathematical model of the property listing task dynamics and test its ability to predict processing time in semantic and lexical decision tasks. The study aims at exploring the temporal dynamics of semantic access in these tasks and showing that the mathematical model captures essential aspects of semantic access, beyond the original task for which it was developed. In two studies using the semantic and lexical decision tasks, we used the mathematical model’s coefficients to predict reaction times. Results showed that the model was able to predict processing time in both tasks, accounting for an independent portion of the total variance, relative to variance predicted by traditional psycholinguistic variables (i.e., frequency, familiarity, concreteness imageability). Overall, this study provides evidence of the mathematical model’s validity and generality, and offers insights regarding the characterization of concrete and abstract words.

Dementia is a syndrome characterized by cognitive and neuropsychiatric symptoms associated with progressive functional decline (FD). FD is a core diagnostic criterion for dementia, setting the threshold between its prodromal stages and the full-blown disease. The operationalization of FD continues to generate a great deal of controversy. For instance, the threshold of FD for the diagnosis of dementia varies across diagnostic criteria, supporting the need for standardization of this construct. Moreover, there is a need to reconsider how we are measuring FD to set boundaries between normal aging, mild cognitive impairment, and dementia. In this paper, we propose a multidimensional framework that addresses outstanding issues in the assessment of FD: i) What activities of daily living (ADLs) are necessary to sustain an independent living in aging? ii) How to assess FD in individuals with suspected neurocognitive disorders? iii) To whom is the assessment directed? and iv) How much does FD differentiate healthy aging from mild and major neurocognitive disorders? Importantly, the To Whom Question introduces a person-centered approach that regards patients and caregivers as active agents in the assessment process of FD. Thus, once impaired ADLs have been identified, patients can indicate how significant such impairments are for them in daily life. We envisage that this new framework will guide future strategies to enhance functional assessment and treatment of patients with dementia and their caregivers.

Abstract Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

Kindler Epidermolysis bullosa (KEB; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by bullous poikiloderma and photosensitivity. Additional presentations include blistering, poor wound healing, skin atrophy, and increased risk of skin cancer. Most cases of KEB result from aberrations in the FERMT1 (Fermitin family member 1) gene encoding kindlin-1 and include nonsense, frameshift, splicing, and missense variants. Large deletion variants have been reported in nine cases to date. Most variants are predicted to lead to premature termination of translation and to loss of kindlin-1 function. In this study, we report on a 33-year-old male patient who presented with typical clinical manifestations of KEB. As routine molecular testing failed to obtain a diagnosis, Next Generation Sequencing (NGS) of an Epidermolysis Bullosa (EB)-specific panel was carried out followed by the determination of the deletion breakpoints and verification at the mRNA and protein levels. This approach revealed a new large homozygous deletion of ~9.4 kb in the FERMT1 gene involving exons 7 to 9. Finally, we performed a literature review on large FERMT1 deletions. The deletion is predicted to skip exons 7 to 9 within the mRNA, which results in a frameshift. The patient’s phenotype is likely caused by the resulting truncated and non-functioning protein. Our report further enriches the spectrum of FERMT1 gene variants to improve genotype–phenotype correlations.