The pulsatile brain, pulse pressure, cognition, and antihypertensive treatments in older adults: a functional NIRS study
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Advancements in ultrafast photonics: confluence of nonlinear optics and intelligent strategies
Automatic mode-locking techniques, the integration of intelligent technologies with nonlinear optics offers the promise of on-demand intelligent control, potentially overcoming the inherent limitations of traditional ultrafast pulse generation that have predominantly suffered from the instability and suboptimality of open-loop manual tuning. The advancements in intelligent algorithm-driven automatic mode-locking techniques primarily are explored in this review, which also revisits the fundamental principles of nonlinear optical absorption, and examines the evolution and categorization of conventional mode-locking techniques. The convergence of ultrafast pulse nonlinear interactions with intelligent technologies has intricately expanded the scope of ultrafast photonics, unveiling considerable potential for innovation and catalyzing new waves of research breakthroughs in ultrafast photonics and nonlinear optics characters.
Blood pressure elevations post-lenvatinib treatment in hepatocellular carcinoma: a potential marker for better prognosis
Lenvatinib is a tyrosine kinase inhibitor that effectively inhibits vascular endothelial growth factor signaling and is used for treating hepatocellular carcinoma. However, angiogenesis inhibitors often cause hypertension. Although lenvatinib-induced hypertension has been proposed as a potential surrogate marker for better prognosis, studies on blood pressure elevations and outcomes following lenvatinib initiation are limited. This study included 67 patients who underwent lenvatinib therapy at the Department of Gastroenterology, Kagoshima University Hospital, between May 2018 and December 2023. The median age of the cohort was 71 years, and 82.1% of the patients were male. The median blood pressure at admission was 128/73 mmHg, which significantly increased to 136/76 mmHg the day after lenvatinib administration. Grade 3 hypertension (≥160/100 mmHg) occurred in 37.3% of patients during hospitalization. The median increase in systolic blood pressure from admission to its peak during hospitalization was 26 mmHg. Patients who experienced an increase in blood pressure of ≥26 mmHg were classified into the blood pressure elevation group, which showed a significantly lower mortality rate than that of the blood pressure non-elevation group (35.3% vs. 81.8%, log-rank p = 0.007), even after adjusting for age, sex, disease stage, performance status, and liver reserve function. This study demonstrated that patients who experienced earlier blood pressure elevation after lenvatinib administration had lower overall mortality rates. These findings suggest that blood pressure elevations after lenvatinib initiation may serve as valuable prognostic indicators in patients with cancer undergoing lenvatinib therapy.
Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson’s disease
Parkinson’s disease (PD) is primarily diagnosed through its characteristic motor deficits, yet it also encompasses progressive cognitive impairments that profoundly affect quality of life. While dopaminergic medications are routinely prescribed to manage motor symptoms in PD, their influence extends to cognitive functions as well. Here we investigate how dopaminergic medication influences aberrant brain circuit dynamics associated with encoding, maintenance and retrieval working memory (WM) task-phases processes. PD participants, both on and off dopaminergic medication, and healthy controls, performed a Sternberg WM task during fMRI scanning. We employ a Bayesian state-space computational model to delineate brain state dynamics related to different task phases. Importantly, a within-subject design allows us to examine individual differences in the effects of dopaminergic medication on brain circuit dynamics and task performance. We find that dopaminergic medication alters connectivity within prefrontal-basal ganglia-thalamic circuits, with changes correlating with enhanced task performance. Dopaminergic medication also restores engagement of task-phase-specific brain states, enhancing task performance. Critically, we identify an “inverted-U-shaped” relationship between medication dosage, brain state dynamics, and task performance. Our study provides valuable insights into the dynamic neural mechanisms underlying individual differences in dopamine treatment response in PD, paving the way for more personalized therapeutic strategies.
Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels
The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate neurons to millimeter depth with sub-cellular specificity and millisecond temporal resolution, it can also cause heating of the targeted tissue. On the other hand, sonogenetics can non-invasively modulate the cellular activity of neurons expressed with mechano-sensitive proteins in deeper areas of the brain with less spatial selectivity. We present a theoretical analysis of a synergistic sono-optogenetic method to overcome these limitations by co-expressing a mechano-sensitive (MscL-I92L) ion-channel with a light-sensitive (CoChR/ChroME2s/ChRmine) ion-channel in hippocampal neurons. It is shown that in the presence of low-amplitude subthreshold ultrasound pulses, the two-photon excitation threshold for neural spiking reduces drastically by 73% with MscL-I92L-CoChR (0.021 mW/µm2), 66% with MscL-I92L-ChroME2s (0.029 mW/µm2), and 64% with MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. It allows deeper excitation of up to 1.2 cm with MscL-I92L-ChRmine combination. The method is useful to design new experiments for low-power deep excitation of neurons and multimodal neuroprosthetic devices and circuits.
Office and home blood pressure and their difference according to frailty status among community-dwelling older adults: the NOSE study
The relationship between frailty and blood pressure (BP) is inconsistent, and limited research has compared BP by frailty status using long-term home BP measurements. We aimed to identify office and home BP and determine differences according to frailty status, stratified by taking antihypertensives in community-dwelling older adults. This cross-sectional study was part of the ongoing non-randomized intervention NOSE study. Participants were aged ≥ 64 years. Frailty was categorized robust, pre-frailty, or frailty using the revised Japanese version of the Cardiovascular Health Study criteria. Office BP was measured in survey settings, and each participant was instructed to take home BP. We used the average home BP for 4 weeks post-survey. An analysis of covariance analyzed the relationship between frailty and office and home BP, and their differences stratified by antihypertensive use. We included 418 older participants (mean age: 72.8 years); 39.5% were male, 40.4% were taking antihypertensives, and 6.7% had frailty. Individuals with frailty taking antihypertensives had higher home morning systolic BP (SBP) than those with robust (134.2 vs. 145.7 mmHg, P = 0.018) and pre-frailty (135.6 vs. 145.7 mmHg, P = 0.024). The difference between office and morning home SBP in treated participants was 7.1 mmHg (robust), 4.7 mmHg (pre-frailty), and −5.1 mmHg (frailty), showing significant differences (robust vs. frailty: P = 0.005, pre-frailty vs. frailty: P = 0.016). Home morning SBP was higher in individuals with frailty taking antihypertensives compared to those without frailty, and it may be higher than office BP. Individuals with frailty should measure home BP for good BP control.
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