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BackgroundIt has been suggested that diabetes mellitus (DM) and the apolipoprotein E (APOE) ε4 allele (APOE4) increase the risk for Alzheimer’s disease (AD) and cognitive decline. However, the evidence is sparse. We explored whether APOE4 status modulated the effects of midlife and late-life DM on global cognition of non-demented older adults.MethodsIn all, 176 non-demented adults (age 65–90 years) were enrolled. All the participants underwent comprehensive clinical assessments including midlife and late-life DM evaluation and APOE genotyping. The global cognitive performance index was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery.ResultsWe found a significant midlife DM × APOE4 interaction effect on the global cognitive performance. Subgroup analyses indicated that an association between midlife DM and decreased global cognitive performance was apparent only in older adults who were APOE4-positive, and not in those with APOE4-negative.ConclusionOur findings from non-demented older adults suggest that midlife DM increases the risk for AD and cognitive decline, and this risk is modulated by APOE4 status. To prevent AD and cognitive decline, physicians should check for the possible coexistence of midlife DM and APOE4-positive status.

BackgroundAtrial fibrillation (AF) is occasionally diagnosed in individuals with Graves’ disease. Definite treatments, including radioactive iodine therapy (RAIT) or surgery might lower the risk of AF in the literature. However, no studies have compared the effects of anti-thyroid drugs (ATDs), RAIT, and surgery on the risk of AF.MethodsThis retrospective cohort study included 94,060 newly diagnosed Graves’ disease patients and 470,300 controls from the Korean National Health Insurance database. The incidence of AF was evaluated in patients and controls. Patients were categorized based on treatment method into ATD (95.6%), RAIT (3.5%), and surgery (0.9%) groups. In the ATD group, the dose and duration of ATDs were calculated for each patient. In the RAIT and surgery groups, remission was defined as levothyroxine prescription.ResultsGraves’ disease patients had a 2.2-fold higher risk of developing AF than controls. Regardless of demographic factors, the patient group had a consistently higher risk of AF than controls, with the highest risk of AF (HR, 5.49) in the younger patient group. The surgery group had a similar risk of AF compared with controls, whereas the ATD (HR, 2.23) and RAIT (HR, 2.00) groups had increased risks of AF, even in patients reaching hypothyroid status after RAIT. Patients with higher dose or longer treatment duration of ATDs were at greater risk of AF.ConclusionWe observed differing risks of AF according to methods of treatment for Graves’ disease, and that definite treatment can be an option for subjects needing sustained medical treatment considering the risk of AF.

BackgroundThe association between types of subjective memory complaint (SMC), poor objective cognitive performance, and brain Aβ deposition have been poorly understood. We investigated the association between types of SMC and objective global cognitive performance, then assessed whether this association is mediated by the brain amyloid prediction index (API).MethodsIn total, 173 non-demented older adults [63 cognitively normal (CN) and 110 mild cognitive impairment (MCI)] underwent comprehensive clinical assessments. Objective global cognitive performance and brain amyloid index were measured using the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery and API, respectively. In total, four items of SMC from the subjective memory complaints questionnaire (SMCQ) (SMCQ1: a feeling of memory problem; SMCQ2: the feeling of worse memory than 10 years ago; SMCQ3: the feeling of worse memory than others of similar age; or SMCQ4: the feeling of difficulty in everyday life) in global memory function were assessed.ResultsIn non-demented and participants with MCI, SMCQ3-positive and SMCQ4-positive groups were associated with decreased TS. In participants with MCI, the SMCQ3-positive group was associated with increased API, and API was associated with decreased TS, but the SMCQ4-positive group did not. In addition, the association between the SMCQ3-positive group and poor TS disappeared when API was controlled as a covariate, indicating that API has a mediation effect.ConclusionThe present findings suggest that SMC, a feeling of worse memory performance than others in a similar age group, in the older adults without dementia is associated with poor objective cognitive performance via increased brain amyloid index.

Objective: A beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP. Method: This study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient's whole blood (WB) and PRP by utilizing a commercial screening kit. Results: The live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB. Conclusion: Intrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement. [ABSTRACT FROM AUTHOR]

Up-to-date, accurate information on the disease burden of motor neuron disease (MND) is the cornerstone for evidence-based resource allocation and healthcare planning. We aimed to estimate the burden of MND globally from 1990 to 2019, as part of the Global Burden of Disease, Injuries and Risk Factor (GBD) study. Amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, pseudobulbar palsy, spinal muscular atrophy and hereditary spastic paraplegia- were included for analysis as MNDs. We measured age-standardized incidence, prevalence, death, and disability-adjusted life-years (DALYs) in 204 countries and territories worldwide from 1990 to 2019 using spatial Bayesian analyses. The effects of age, sex, and the sociodemographic index (measures of income per capita, education, and fertility) on incidence, prevalence, death, and disability-adjusted life-years due to MNDs were explored. According to 2019 GBD estimates, there were ~268,673 [95% uncertainty interval (UI), 213,893–310,663] prevalent cases and 63,700 (95% UI, 57,295–71,343) incident cases of MND worldwide. In 2019, MND caused 1,034,606 (95% UI, 979,910–1,085,401) DALYs and 39,081 (95% UI, 36,566–41,129) deaths worldwide. The age-standardized rates of prevalence, incidence, death, and DALYs for MNDs in 2019 were 3.37 (95% UI, 2.9–3.87) per 100,000 people, 0.79 (95% UI, 0.72–0.88) per 100,000 people, 0.48 (95% UI, 0.45–0.51) per 100,000 people, and 12.66 (95% UI, 11.98–13.29) per 100,000 people, respectively. The global prevalence and deaths due to MND in 2019 were increased (1.91% [95% UI, 0.61–3.42] and 12.39% [95% UI, 5.81–19.27], respectively) compared to 1990, without significant change in incidence. More than half of the prevalence and deaths due to MND occurred in three high-income regions (North America, Western Europe, and Australasia). In most cases, the prevalence, incidence, and DALYs of MNDs were high in regions with high sociodemographic index; however, in high-income East Asia, these were relatively low compared to similar sociodemographic index groups elsewhere. The burden of MND increased between 1990 and 2019. Its expected increase in the future highlights the importance of global and national healthcare planning using more objective evidence. Geographical heterogeneity in the MND burden might suggest the influences of sociodemographic status and genetic background in various regions.

Vancomycin-associated acute kidney injury (AKI) remains a major challenge for patients and clinicians. This study aimed to construct a risk scoring system for vancomycin-associated AKI. We retrospectively reviewed medical records of patients who underwent therapeutic drug monitoring for vancomycin from June 2018 to July 2019. We selected possible risk factors for AKI by univariate and multivariable logistic regression analyses and developed a scoring system for vancomycin-associated AKI. Machine learning methods were utilized to predict risk factors for the occurrence of AKI. The incidence of vancomycin-associated AKI was 31.7% among 104 patients included in this study. A bodyweight ≤60 kg (two points), a Charlson comorbidity index ≥3 (two points), a vancomycin trough serum level >15 μg/ml (one point), and concomitant use of ≥6 nephrotoxic agents (two points) were included to construct a risk scoring system based on the coefficient from the logistic regression model. The area under the receiver operating characteristic curve (AUROC) (mean, 95% confidence interval (CI)) across 10 random iterations using five-fold cross-validated multivariate logistic regression, elastic net, random forest, support vector machine (SVM)-linear kernel, and SVM-radial kernel models was 0.735 (0.638–0.833), 0.737 (0.638–0.835), 0.721 (0.610–0.833), 0.739 (0.648–0.829), and 0.733 (0.640–0.826), respectively. For total scores of 0–1, 2–3, 4–5, 6–7, the risk of vancomycin-associated AKI was 5, 25, 45, and 65%, respectively. Our scoring system can be applied to clinical settings in which several nephrotoxic agents are used along with vancomycin therapy.

BackgroundMaintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated.ObjectiveTo determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS).MethodsAge matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined.ResultsPlasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC0-120); 655±24 versus 849±13 mmol.l-1.min; G19 vs virgin; P

BackgroundAmidst growing concern about an increased risk of Guillain–Barré syndrome (GBS) following COVID-19 vaccination, clinical and electrodiagnostic features have not been fully characterized.MethodsWe retrospectively reviewed medical records of the patients diagnosed with GBS and its variants following COVID-19 vaccination at four referral hospitals during the period of the mass vaccination program in South Korea (February to October 2021).ResultsWe identified 13 patients with GBS and variants post COVID-19 vaccination: AstraZeneca vaccine (Vaxzevria) in 8, and Pfizer-BioNTech vaccine (Comirnaty) in 5. The mean time interval from vaccination to symptom onset was 15.6 days (range 4–30 days). Electrodiagnostic classification was demyelinating in 7, axonal in 4 and normal in 2 cases. Clinical manifestations were diverse with varying severity: classical GBS in 8 cases, paraparetic variant in 3, Miller-Fisher syndrome in 1 and acute cervicobrachial weakness in 1. Four patients developed respiratory failure, and 2 of them showed treatment-related fluctuations.ConclusionOur observations suggest that COVID-19 vaccines may be associated with GBS of distinctive clinical features characterized by severe quadriplegia, disproportionately frequent bilateral facial palsy or atypical incomplete variants. Continuous surveillance and further studies using robust study designs are warranted to fully assess the significance of the association.

Adolescence marks a particularly vulnerable period to developing substance use disorders. Human and rodent studies suggest that hypersensitivity to reward may contribute towards such vulnerability when adolescents are exposed to casual drug use. Methamphetamine is a popular illicit substance used by male and female youths. However, age- and sex-specific research in methamphetamine is scarce. The present study therefore aimed to examine potential sex differences in methamphetamine-conditioned place preference in adolescent and adult mice. Mice (n = 16–24/group) were conditioned to methamphetamine (0.1 mg/kg). We observed that regardless of age, females were more hyperactive compared to males. Individually normalized score against baseline preference indicated that on average, adolescents formed stronger preference compared to adults in both sexes. This suggests that adolescents are more sensitive to the rewarding effects of methamphetamine compared to adults. Surprisingly, individual data showed that some mice formed a conditioned place aversion instead of preference, with females less likely to form an aversion compared to males. These results suggest that adolescents may be hypersensitive to methamphetamine’s rewarding effects. In addition, female resistance to the aversive effects of methamphetamine may relate to the sex-specific findings in humans, including quicker transition to regular methamphetamine use observed in females compared to males.

For over 40 years, in vivo microdialysis techniques have been at the forefront in measuring the effects of illicit substances on brain tonic extracellular levels of dopamine that underlie many aspects of drug addiction. However, the size of microdialysis probes and sampling rate may limit this technique’s ability to provide an accurate assessment of drug effects in microneural environments. A novel electrochemical method known as multiple-cyclic square wave voltammetry (M-CSWV), was recently developed to measure second-to-second changes in tonic dopamine levels at microelectrodes, providing spatiotemporal resolution superior to microdialysis. Here, we utilized M-CSWV and fast-scan cyclic voltammetry (FSCV) to measure changes in tonic or phasic dopamine release in the nucleus accumbens core (NAcc) after acute cocaine administration. Carbon-fiber microelectrodes (CFM) and stimulating electrodes were implanted into the NAcc and medial forebrain bundle (MFB) of urethane anesthetized (1.5 g/kg i.p.) Sprague-Dawley rats, respectively. Using FSCV, depths of each electrode were optimized by determining maximal MFB electrical stimulation-evoked phasic dopamine release. Changes in phasic responses were measured after a single dose of intravenous saline or cocaine hydrochloride (3 mg/kg; n = 4). In a separate group, changes in tonic dopamine levels were measured using M-CSWV after intravenous saline and after cocaine hydrochloride (3 mg/kg; n = 5). Both the phasic and tonic dopamine responses in the NAcc were augmented by the injection of cocaine compared to saline control. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. These increases were largely consistent with previous studies using FSCV and microdialysis. However, the minimal disruption/disturbance of neuronal tissue by the CFM may explain why the baseline tonic dopamine values (134 ± 32 nM) measured by M-CSWV were found to be 10-fold higher when compared to conventional microdialysis. In this study, we demonstrated phasic dopamine dynamics in the NAcc with acute cocaine administration. M-CSWV was able to record rapid changes in tonic levels of dopamine, which cannot be achieved with other current voltammetric techniques. Taken together, M-CSWV has the potential to provide an unprecedented level of physiologic insight into dopamine signaling, both in vitro and in vivo, which will significantly enhance our understanding of neurochemical mechanisms underlying psychiatric conditions.

Background: This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer's disease (AD) assessment battery. Methods: The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers. Results: Our stepwise logistic regression analysis highlighted the 'helplessness item' (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating 'helplessness item + MMSE' demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = -5.300, SE = 1.899, ß = -0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels. Conclusion: Our findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness. [ABSTRACT FROM AUTHOR]

BackgroundThe trastuzumab biosimilar CT-P6 has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). Here, we present the first real-world comparison of CT-P6 versus RTZ with dual HER2-targeted therapy for the neoadjuvant and palliative first-line treatment with HER2-positive EBC and metastatic breast cancer (MBC) patients in two tertiary hospitals in Korea.MethodsWe retrospectively investigated medical records in the Severance Breast Cancer Registry in Korea. We identified patients with HER2-positive EBC (n=254) who had received neoadjuvant chemotherapy with RTZ or CT-P6, plus pertuzumab, carboplatin and docetaxel (TCHP) and untreated stage IV MBC (n=103) who had received palliative first-line treatment with RTZ or CT-P6, plus pertuzumab and docetaxel (THP) between May 2014 and December 2019. The primary endpoints were pathologic complete response (pCR) in the EBC and progression-free survival (PFS) in the MBC cohort. Overall survival (OS), overall response rate (ORR), disease control rate (DCR), and cardiac safety were secondary endpoints.ResultsA similar percentage of EBC patients achieved a pCR with CT-P6 versus RTZ (74.4% [93/125]) vs 69.8% [90/129], p=0.411). For patients with MBC, median follow-up duration was 23.0 and 41.0 months for CT-P6 and RTZ groups, respectively; median PFS did not differ significantly between two groups (13.0 vs 18.0 months, 95% confidence intervals (CIs) 0.0-26.6 vs 11.3-24.7, p=0.976). The ORR, DCR, and cardiac safety profiles did not also show significant difference efficacy outcomes between two groups.ConclusionsThese real-world data suggest that biosimilar trastuzumab CT-P6 has similar effectiveness and cardiac safety to RTZ in HER2-positive EBC and MBC patients, when administered as part of dual HER2-targeted therapy with pertuzumab plus chemotherapy in the neoadjuvant or palliative setting.

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies.Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured.Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect.Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.

PurposeThis study is to directly compare surgical outcomes between conventional nipple-sparing mastectomy (CNSM) and robot-assisted nipple-sparing mastectomy (RNSM).Materials and MethodFor this case–control study, 369 cases of 333 patients who underwent CNSM or RNSM with immediate reconstruction between November 2016 and January 2019 at Severance Hospital in Seoul, Republic of Korea were reviewed. Patients with stage IV breast cancer (n = 1), receiving neoadjuvant chemotherapy (n = 43), or subjected to previous operations (n = 14) or radiotherapy on the breasts were excluded. The main outcomes were comparing rates of post-operative complications, of high-grade post-operative complications as defined by the Clavien-Dindo classification, and nipple necrosis between the CNSM and the RNSM groups.ResultsA total of 311 cases, including 270 CNSMs and 41 RNSMs, were analyzed. The rates of post-operative nipple necrosis (p = 0.026, 2.4 vs. 15.2%) and of high-grade post-operative complications (p = 0.031, 34.8 vs. 17.1%) in the RNSM group were significantly lower than those in the CNSM group.ConclusionRNSM was associated with lower rates of high-grade post-operative complications and nipple necrosis than CNSM for patients with small breast volumes and less ptotic breasts.

Purpose: Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status. Methods: We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype. Results: During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS andOS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for bothDFS andOS.No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer. Conclusion: LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status andmolecular subtype. Therefore, the LVI status should be consideredwhenmaking treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Rationale: While the immune system plays a crucial role in the development of hypertension, the specific contributions of distinct immune cell populations remain incompletely understood. The emergence of single-cell RNAsequencing (scRNA-seq) technology enables us to analyze the transcriptomes of individual immune cells and to assess the significance of each immune cell type in hypertension development. Objective: We aimed to investigate the hypothesis that B cells play a crucial role in the development of fructose-induced hypertension. Methods and Results: Eight-week-old Dahl salt-sensitive (SS) male rats were divided into two groups and given either tap water (TW) or a 20% fructose solution (HFS) for 4 weeks. Systolic blood pressure was measured using the tailcuff method. ScRNA-seq analysis was performed on lamina propria cells (LPs) and peripheral blood mononuclear cells (PBMCs) obtained from SS rats subjected to either TW or HFS. The HFS treatment induced hypertension in the SS rats. The analysis revealed 27 clusters in LPs and 28 clusters in PBMCs, allowing for the identification and characterization of various immune cell types within each cluster. Specifically, B cells and follicular helper T (Tfh) cells were prominent in LPs, while B cells and M1 macrophages dominated PBMCs in the HFS group. Moreover, the HFS treatment triggered an increase in the number of B cells in both LPs and PBMCs, accompanied by activation of the interferon pathway. Conclusions: The significant involvement of B cells in intestinal and PBMC responses indicates their pivotal contribution to the development of hypertension. This finding suggests that targeting B cells could be a potential strategy to mitigate high blood pressure in fructose-induced hypertension. Moreover, the simultaneous increase in follicular B cells and Tfh cells in LPs, along with the upregulation of interferon pathway genes in B cells, underscores a potential autoimmune factor contributing to the pathogenesis of fructoseinduced hypertension in the intestine. [ABSTRACT FROM AUTHOR]

Background: An abundance of evidence indicates that physical activity may protect against Alzheimer's disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) +4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults. Methods: We enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: We found significant physical activity x age and physical activity x APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects. Conclusion: Our findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline. [ABSTRACT FROM AUTHOR]

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone. Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.). Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min-1 vs. 67.9 ± 8.3 min-1; pre- vs. postoxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min-1 vs. 105.2 ± 4.1 min-1; pre- vs. post-oxycodone; p = 0.072). Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction. [ABSTRACT FROM AUTHOR]

Background: The probable association among ginseng intake, Alzheimer's disease (AD)-specific cognition, and apolipoprotein ε4 (APOE4) remains poorly investigated. Hence, we examined the association between ginseng intake and AD-specific cognition in older adults under the moderating effect of APOE4 status. Methods: This study enrolled 160 adults aged 65-90 years without dementia. All participants underwent comprehensive dietary and clinical assessments including ginseng intake, AD-related cognition (i.e., delayed episodic memory, as the earliest cognitive change in AD), and non-memory cognition for comparative purposes. Results: Ginseng intake was associated with higher delayed episodic memory, but not non-memory cognition, compared to no ginseng intake. The interaction between ginseng intake and APOE4 status had a significant effect on delayed episodic memory. Subgroup analyses showed that ginseng intake was associated with higher delayed episodic memory in the APOE4-negative but not the APOE4-positive subgroup. The benefits of ginseng intake on delayed episodic memory were prominent in the high duration (≥5 years) and midlife onset (<65 years) groups. Conclusion: Our study of older adults with no dementia suggests that ginseng intake (with high duration and midlife onset) had a beneficial effect on AD-specific cognitive decline, i.e., the delayed episodic memory. In addition, APOE4 status moderates the association between ginseng intake status and AD-specific cognitive decline. [ABSTRACT FROM AUTHOR]

Environmental cues regulate the transition of many plants from vegetative to flowering development. Day length, or photoperiod, is one cue that synchronizes flowering by changing seasons. Consequently, the molecular mechanism of flowering control is prominent in Arabidopsis and rice, where essential genes like FLOWERING LOCUS T (FT) homolog, HEADING DATE 3a (Hd3a), have been connected to flowering regulation. Perilla is a nutrient-rich leaf vegetable, and the flowering mechanism remains largely elusive. We identified flowering-related genes under short-day conditions using RNA sequencing to develop an enhanced leaf production trait using the flowering mechanism in the perilla. Initially, an Hd3a-like gene was cloned from the perilla and defined as PfHd3a. Furthermore, PfHd3a is highly rhythmically expressed in mature leaves under short-day and long-day conditions. Ectopic expression of PfHd3a in Atft-1 mutant plants has been shown to complement Arabidopsis FT function, resulting in early flowering. In addition, our genetic approaches revealed that overexpression of PfHd3a in perilla caused early flowering. In contrast, the CRISPR/Cas9 generated PfHd3a-mutant perilla showed significantly late flowering, resulting in approximately 50% leaf production enhancement compared to the control. Our results suggest that PfHd3a plays a vital role in regulating flowering in the perilla and is a potential target for molecular breeding in the perilla. [ABSTRACT FROM AUTHOR]

Background: A post-marketing surveillance study was conducted to assess the real-world safety and effectiveness of vortioxetine for the treatment of major depressive disorder (MDD) in South Korea. Methods: Adult patients aged 19–94 years receiving vortioxetine for MDD at 72 hospitals and clinics in South Korea between 19th August 2014 and 18th August 2020 were included. Patients were followed for up to 24±2 weeks, at up to three visits. Adverse events (AEs) and effectiveness, assessed by both clinician and patient-reported measures, were analyzed. Results: A total of 3,263 patients (mean age: 51.28 years) were included in the safety set; 1,095 were aged ≥65 years. The majority of the safety set (61.97%) were female. The overall rate of any AEs and serious AEs were 17.13 and 1.56%, respectively. The majority of AEs were mild (88.32%). The rates of AEs did not differ statistically by age (≥65 years: 16.89% [185/1,095] versus <65 years: 17.25% [374/2,168)], p=0.7989), sex (male: 15.95% [198/1,241] versus female: 17.85% [361/2,022], p=0.1623), or liver impairment (with liver impairment: 20.90% [14/67] versus without liver impairment: 17.05% [545/3,196], p=0.4087). Effectiveness was assessed in 1,918 patients. By 24±2 weeks, there were significant clinical improvements from baseline, assessed by change in Montgomery-Asberg Depression Rating Scale total score (mean±standard deviation [SD]: -10.49±9.42 points, p <0.0001), the proportion of patients with improved symptoms using the Clinical Global Impression - Improvement scores (79.29%), and in both patient-reported measures, with a significant improvement in the Korean Version of the Perceived Deficits Questionnaire-Depression (mean±SD: -6.06±13.23, p <0.0001) and Digit Symbol Substitution Test (mean±SD: 4.83±9.81, p <0.0001) total scores from baseline. Similar to the safety profiles, the proportions of patients with improved symptoms compared with baseline using the Clinical Global Impression – Improvement scores did not differ by age (≥65 years: 82.09% versus <65 years: 78.32%, p=0.0511), sex (male: 77.45% versus female: 81.01%, p=0.0587), or liver impairment (with liver impairment: 67.57% versus without liver impairment: 79.85%, p=0.0663). Conclusion: Vortioxetine appears to be well-tolerated and effective for treating MDD patients in the real-world setting in South Korea, irrespective of age, sex, and liver impairment, reflecting the known profile of vortioxetine based on studies worldwide. [ABSTRACT FROM AUTHOR]

Cocaine's addictive properties stem from its capacity to increase tonic extracellular dopamine levels in the nucleus accumbens (NAc). The ventral tegmental area (VTA) is a principal source of NAc dopamine. To investigate how high frequency stimulation (HFS) of the rodent VTA or nucleus accumbens core (NAcc) modulates the acute effects of cocaine administration on NAcc tonic dopamine levels multiple-cyclic square wave voltammetry (M-CSWV) was used. VTA HFS alone decreased NAcc tonic dopamine levels by 42%. NAcc HFS alone resulted in an initial decrease in tonic dopamine levels followed by a return to baseline. VTA or NAcc HFS following cocaine administration prevented the cocaine-induced increase in NAcc tonic dopamine. The present results suggest a possible underlying mechanism of NAc deep brain stimulation (DBS) in the treatment of substance use disorders (SUDs) and the possibility of treating SUD by abolishing dopamine release elicited by cocaine and other drugs of abuse by DBS in VTA, although further studies with chronic addiction models are required to confirm that. Furthermore, we demonstrated the use of M-CSWV can reliably measure tonic dopamine levels in vivo with both drug administration and DBS with minimal artifacts. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that diabetes mellitus (DM) and the apolipoprotein E (APOE) +4 allele (APOE4) increase the risk for Alzheimer's disease (AD) and cognitive decline. However, the evidence is sparse. We explored whether APOE4 status modulated the effects of midlife and late-life DM on global cognition of non-demented older adults. Methods: In all, 176 non-demented adults (age 65-90 years) were enrolled. All the participants underwent comprehensive clinical assessments including midlife and late-life DM evaluation and APOE genotyping. The global cognitive performance index was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: We found a significant midlife DM × APOE4 interaction effect on the global cognitive performance. Subgroup analyses indicated that an association between midlife DM and decreased global cognitive performance was apparent only in older adults who were APOE4-positive, and not in those with APOE4-negative. Conclusion: Our findings from non-demented older adults suggest that midlife DM increases the risk for AD and cognitive decline, and this risk is modulated by APOE4 status. To prevent AD and cognitive decline, physicians should check for the possible coexistence of midlife DM and APOE4-positive status. [ABSTRACT FROM AUTHOR]

Background: Korean society has faced challenges in communicating with cancer patients about false information related to complementary alternative medicine. As the situation has become severewith the 2020 fenbendazole scandal, the demand for reliable information from health authorities has increased. Objectives: This study aimed to examine patients' acquisition patterns and perception of false information by presenting empirical evidence to help health authorities enable effective preemptive responses in the cancer communication context. Method: We conducted a focus group interview with 21 lung cancer patients who were informed about fenbendazole based on a semi-structured questionnaire with three categories: 1) acquisition channel of the general cancer information and the false information, 2) quality of obtained information, and 3) perception toward it. The interviewees, comprising 13 men and eight women, were aged 50 or older. Participants' current stages of cancer were stages one, three, and four and there were seven people in each stage. Results: 1) Acquisition channel: Participants had their first encounter with false information through the TV, while the channels to obtain general cancer information were through Internet communities or portal sites. YouTube was a second channel to actively search for information regardless of the information type. 2) Information quality: participants had only fragmented information through media. 3) Perception: Most patients had a negative attitude toward complementary and alternative medicine information such as fenbendazole. They perceive that it needs to be verified by experts and filtered according to their arbitrary criteria. They had vague expectations based on a hope for "what if" at the same time. Conclusions: Despite the complex media environment, traditional or legacy media is an important channel to encounter information. YouTube is independent of other media as an "active" information-seeking channel. Patients required the appropriate intervention of experts and governments because they perceived that they had obtained irrational and unreliable information from the media. Suggestions are made about how health authorities can construct an effective communication system focusing on the user to prevent patients from getting false cancer information. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Behavioral Neuroscience. It discusses the state of research on learning and memory and highlights recent developments and challenges in the field. The editorial includes articles that cover various topics such as fear extinction, food-seeking behavior, and the assessment of learning and memory in mice. The authors emphasize the importance of considering factors like sex, age, and lifestyle in learning and memory processes, as well as the role of technology and artificial intelligence in experimental design and analysis. [Extracted from the article]

The retinal structural changes after subretinal implantation of threedimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain–optical coherence tomography (SD–OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD–OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue. [ABSTRACT FROM AUTHOR]

Background: A robotic deep inferior epigastric perforator (DIEP) flap created through a totally extraperitoneal approach minimizes violation of the donor site, which may lead to postoperative pain reduction and rapid recovery. The authors compared the clinical outcomes of robotic and conventional DIEP flap breast reconstructions. Methods: Data from consecutive patients who underwent mastectomy with DIEP flaps for breast reconstruction between July 2017 and January 2021 were retrospectively reviewed. Patients were divided into robotic and conventional DIEP groups, and the two groups were matched using the inverse probability of treatment weighting method. They were compared based on the reconstruction time, drainage amount, postoperative pain, rescue analgesics, hospital stay, complications, and BREAST-Q scores. Results: After matching, a dataset of 207 patients was formed, including 21 patients in the robotic DIEP group and 186 patients in the conventional DIEP group. The mean reconstruction time was longer in the robotic DIEP group than in the conventional DIEP group (P<0.001). In the robotic group, pain intensity during the postoperative 6-24 hours was significantly reduced (P=0.001) with less use of fentanyl (P=0.003) compared to the conventional DIEP group. The mean length of hospital stay for the robotic DIEP group was shorter than that for conventional DIEP (P=0.002). BREAST-Q scores indicated a higher level of the abdominal physical well-being domain in the robotic group (P=0.020). Complication rates were comparable between the two groups. Conclusions: This study suggests that a robotic DIEP flap offers enhanced postoperative recovery, accompanied by a reduction in postoperative pain and hospital stay. [ABSTRACT FROM AUTHOR]

While deficits in fear extinction recall have been suggested to underlie vulnerability to anxiety disorders in adolescents, the neurobiology of these deficits remain underexplored. Here we investigate the functional connectivity (FC) of the ventromedial prefrontal cortex (vmPFC) and dorsolateral PFC (dlPFC) underlying extinction recall in healthy adolescents, and assess associations between FC and state/trait anxiety. Adolescents (17) and adults (14, for comparison) completed a fear-learning paradigm involving extinction and extinction recall during a functional magnetic resonance imaging session, in which skin conductance response (SCR) was recorded. Psychophysiological interaction analyses revealed that during extinction recall there was significant negative connectivity between the vmPFC and amygdala in adults, but not adolescents. vmPFC-amygdala connectivity was positively correlated with SCR. Adolescents showed significant negative FC between the dlPFC and the left and right hippocampus, and the amygdala, which was positively correlated with state anxiety. Recall was also associated with negative connectivity between the dlPFC and thalamus, posterior cingulate cortex, fusiform gyrus, and pallidum in adolescents. These results demonstrate that fear extinction recall in healthy adolescents is associated with FC between prefrontal and limbic brain regions, and suggest that alterations in connectivity may be associated with vulnerability to anxiety in adolescence. [ABSTRACT FROM AUTHOR]

Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (AbilifyTM), and examine the behavioral and neural outcomes. Adolescent rats were conditioned to fear a tone. The next day, rats received extinction 30 min after a systemic injection of either 5 mg/kg aripiprazole or vehicle, and then were tested the following day. For the immunohistochemistry experiment, naïve and "no extinction" conditions were added and rats were perfused either on the extinction day or test day. To assess the activation of neurons receiving dopaminergic input, c-Fos, and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) labeled neurons were quantified in the amygdala and the medial prefrontal cortex (mPFC). Systemic treatment with aripiprazole at the time of extinction significantly reduced freezing at test the next day. This effect was not observed in rats that were fear conditioned but did not receive any extinction. Aripiprazole's facilitation of extinction was accompanied by increased activation of neurons in the mPFC. Taken together, aripiprazole represents a novel pharmacological adjunct to exposure therapy worthy of further examination. The effect of aripiprazole is related to enhanced activation of mPFC neurons receiving dopaminergic innervation. [ABSTRACT FROM AUTHOR]

Adolescents with anxiety disorders attain poorer outcomes following extinction-based treatment compared to adults. Extinction deficit during adolescence has been identified to involve immaturity in the medial prefrontal cortex (mPFC). Findings from adult rodents suggest extinction involves dopamine signaling in the mPFC. This system changes dramatically during adolescence, but its role in adolescent extinction is unknown. Therefore, we investigated the role of prefrontal dopamine in extinction using Pavlovian fear conditioning in adolescent and adult rats. Using quantitative PCR (qPCR) analyses, we measured changes in dopamine receptor gene expression in the mPFC before and after extinction. We then enhanced dopamine 1 receptor (D1R) or dopamine 2 receptor (D2R) signaling in the infralimbic cortex (IL) of the mPFC using agonists at the time of extinction. Adolescent rats displayed a deficit in extinction retention compared to adults. Extinction induced a reduction in D1R compared to D2R gene expression in adolescent rats, whereas an increase of D1R compared to D2R gene expression was observed in adult rats. Acutely enhancing IL D1R signaling using SKF-81297 had no effect on extinction at either age. In contrast, acutely enhancing IL D2R signaling with quinpirole significantly enhanced long-term extinction in adolescents, and impaired within-session extinction in adults. Our results suggest a dissociated role for prefrontal dopamine in fear extinction during adolescence compared to adulthood. Findings highlight the dopamine system as a potential pharmacological target to improve extinction-based treatments for adolescents. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is a pre-clinical stage of Alzheimer's disease afflicting a large number of the elderly throughout the world. However, modifiable risk factors for the onset and progression of MCI remain unclear. A cross-sectional study was performed to explore whether and how daily dietary nutrients intake and lifestyle impacted the risk of MCI in the Chinese elderly. We examined 2,892 elderly subjects, including 768 MCI patients and 2,124 subjects with normal cognition in three different Provinces of China. Dietary intake of nutrients were collected by using a 33-item food frequency questionnaire and calculated based on the Chinese Food Composition database. The MCI patients were first screened by Montreal Cognitive Assessment and then diagnosed by medical neurologists. Multivariate logistic regression and exploratory factor analyses were applied to identify and rank the risk factors. Three dietary nutrient intake combination patterns were identified as the major protective factors of MCI, with eigenvalues of 14.11, 2.26, and 1.51 and adjusted odds ratios (OR) of 0.77, 0.81, and 0.83 (P < 0.05), respectively. The most protective combination was featured with eight vitamins and six minerals, and OR for the third and fourth quartiles of these nutrients intake ranged from 0.48 to 0.74 (P < 0.05). Carotenoids, vitamin C, and vitamin B6 exhibited the highest protective factor loadings of 0.97, 0.95, and 0.92 (P < 0.05), respectively. Education, computer use, reading, and drinking represented the most protective lifestyle factors (OR D 0.25 to 0.85, P < 0.05), whereas smoking and peripheral vascular diseases were associated with higher (OR D 1.40 and 1.76, P < 0.05) risk of MCI. Adequate dietary intake of monounsaturated fatty acids and cholesterol were significantly associated with decreased risk of MCI. In conclusion, adequate or enhanced intake of micronutrients seemed to lower the risk of MCI in the Chinese elderly. In addition, improving education and lifestyle such as reading, computer use and moderate drinking might also help to decrease the risk of MCI. [ABSTRACT FROM AUTHOR]

Devaluation is the key experimental paradigm used to demonstrate the presence of instrumental behaviors guided by goals in mammals. We propose a neural system-level computational model to address the question of which brain mechanisms allow the current value of rewards to control instrumental actions. The model pivots on and shows the computational soundness of the hypothesis for which the internal representation of instrumental manipulanda (e.g., levers) activate the representation of rewards (or "action-outcomes", e.g., foods) while attributing to them a value which depends on the current internal state of the animal (e.g., satiation for some but not all foods). The model also proposes an initial hypothesis of the integrated system of key brain components supporting this process and allowing the recalled outcomes to bias action selection: (a) the sub-system formed by the basolateral amygdala and insular cortex acquiring the manipulanda-outcomes associations and attributing the current value to the outcomes; (b) three basal ganglia-cortical loops selecting respectively goals, associative sensory representations, and actions; (c) the cortico-cortical and striato-nigro-striatal neural pathways supporting the selection, and selection learning, of actions based on habits and goals. The model reproduces and explains the results of several devaluation experiments carried out with control rats and rats with pre- and post-training lesions of the basolateral amygdala, the nucleus accumbens core, the prelimbic cortex, and the dorso-medial striatum. The results support the soundness of the hypotheses of the model and show its capacity to integrate, at the system-level, the operations of the key brain structures underlying devaluation. Based on its hypotheses and predictions, the model also represents an operational framework to support the design and analysis of new experiments on the motivational aspects of goal-directed behavior. [ABSTRACT FROM AUTHOR]

Canopy photosynthesis has typically been estimated using mathematical models that have the following assumptions: the light interception inside the canopy exponentially declines with the canopy depth, and the photosynthetic capacity is affected by light interception as a result of acclimation. However, in actual situations, light interception in the canopy is quite heterogenous depending on environmental factors such as the location, microclimate, leaf area index, and canopy architecture. It is important to apply these factors in an analysis. The objective of the current study is to estimate the canopy photosynthesis of paprika (Capsicum annuum L.) with an analysis of by simulating the intercepted irradiation of the canopy using a 3D ray-tracing and photosynthetic capacity in each layer. By inputting the structural data of an actual plant, the 3D architecture of paprika was reconstructed using graphic software (Houdini FX, FX, Canada). The light curves and A/Ci curve of each layer were measured to parameterize the Farquhar, von Caemmerer, and Berry (FvCB) model. The difference in photosynthetic capacity within the canopy was observed. With the intercepted irradiation data and photosynthetic parameters of each layer, the values of an entire plant's photosynthesis rate were estimated by integrating the calculated photosynthesis rate at each layer. The estimated photosynthesis rate of an entire plant showed good agreement with the measured plant using a closed chamber for validation. From the results, this method was considered as a reliable tool to predict canopy photosynthesis using light interception, and can be extended to analyze the canopy photosynthesis in actual greenhouse conditions. [ABSTRACT FROM AUTHOR]

We tested (1) whether the PQRST method, involving Preview (P), Question (Q), Read (R), State (S), and Test (T) phases, is effective in enhancing long-term memory in patients with mild memory problems due to prefrontal cortex lesions, and (2) whether patients also benefit from a more self-initiated version of the PQRST. Seven patients with prefrontal lesions encoded new texts under three different conditions: the Standard condition, requiring to read texts repeatedly, the PQRST-Other condition, in which the experimenter formulated questions about the text (Q phase), and the PQRST-Self condition, in which patients formulated the relevant questions on their own. Compared to the Standard condition, both the PQRST-Other and the PQRST-Self condition resulted in higher immediate and delayed recall rates, as well as a higher ability to answer questions about the texts. Importantly, the two PQRST conditions did not differ in efficacy. These results confirm that the PQRST method is effective in improving learning of new material in brain-injured populations with mild memory problems. Moreover, they indicate that the PQRST proves effective even under conditions with higher demands on patients' autonomy and self-initiation, which encourages its application to real-life situations. [ABSTRACT FROM AUTHOR]

This paper describes the R package crqa to perform cross-recurrence quantification analysis of two time series of either a categorical or continuous nature. Streams of behavioral information, from eye movements to linguistic elements, unfold over time. When two people interact, such as in conversation, they often adapt to each other, leading these behavioral levels to exhibit recurrent states. In dialog, for example, interlocutors adapt to each other by exchanging interactive cues: smiles, nods, gestures, choice of words, and so on. In order for us to capture closely the goings-on of dynamic interaction, and uncover the extent of coupling between two individuals, we need to quantify how much recurrence is taking place at these levels. Methods available in crqa would allow researchers in cognitive science to pose such questions as how much are two people recurrent at some level of analysis, what is the characteristic lag time for one person to maximally match another, or whether one person is leading another. First, we set the theoretical ground to understand the difference between "correlation" and "co-visitation" when comparing two time series, using an aggregative or cross-recurrence approach. Then, we describe more formally the principles of cross-recurrence, and show with the current package how to carry out analyses applying them. We end the paper by comparing computational efficiency, and results' consistency, of crqa R package, with the benchmark MATLAB toolbox crptoolbox (Marwan, 2013). We show perfect comparability between the two libraries on both levels. [ABSTRACT FROM AUTHOR]

BackgroundExcessive consumption of ultra-processed foods (UPFs) has been linked to an increased risk of cardiovascular disease. We aimed to investigate the association between the percentage of energy intake from UPFs and the American Heart Association’s cardiovascular health (CVH) metrics in Korean adults.MethodsThis study analyzed adults aged 40 years and older using data from the Korean National Health and Nutrition Examination Survey 2016–2018 (n = 9,351). All foods or beverages reported in a 24-h dietary recall were categorized using the NOVA system, and the percentage of energy from UPFs was calculated. Each CVH metric was scored 0–2 (poor, intermediate, ideal). The sum of six component scores was classified as inadequate, average, or optimum. Multinomial logistic regression models were used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for inadequate and average CVH versus optimum CVH.ResultsThe mean percentage of energy from UPFs was 24.2%. After adjusting for covariates, participants in the highest UPF quartile had 26% higher odds of having inadequate CVH than those in the lowest quartile (OR 1.26, 95% CI 0.94–1.69, P-trend = 0.03). The percentage of energy from UPFs was positively associated with current smoking, physical inactivity, body mass index, and total cholesterol and was inversely associated with blood pressure and fasting glucose.ConclusionThe percentage of energy from UPFs accounted for one-fourth of total calorie intake in Korean adults aged 40 years and older. Higher UPF consumption was associated with poorer CVH, underscoring the potential of limiting UPF consumption as a preventative measure for cardiovascular diseases.

Ice algae thriving within sea ice play a crucial role in transferring energy to higher trophic levels and influencing biogeochemical processes in polar oceans; however, the distribution of organic matter within the ice interior is not well understood. This study aimed to investigate the vertical distribution of organic matter, including chlorophyll a (Chl-a), particulate organic carbon and nitrogen (POC and PON), carbohydrates (CHO), proteins (PRT), lipids (LIP), and food material (FM), within the sea ice. Samples were collected from the bottom, middle, and top sections of the sea ice column near Cambridge Bay during the spring of 2018. Based on the δ13C signature, biochemical composition, and POC contribution of biopolymeric carbon (BPC), the organic substances within the sea ice were predominantly attributed to marine autotrophs. While the highest concentrations of each parameter were observed at the sea ice bottom, notable concentrations were also found in the upper sections. The average sea ice column-integrated Chl-a concentration was 5.05 ± 2.26 mg m−2, with the bottom ice section contributing 59% (S.D. = ± 10%) to the total integration. The column-integrated concentrations of FM, BPC, POC, and PON were 2.05 ± 0.39, 1.10 ± 0.20, 1.47 ± 0.25, and 0.09 ± 0.03 g m−2, respectively. Contributions of the bottom ice section to these column-integrated concentrations varied for each parameter, with values of 20 ± 6, 21 ± 7, 19 ± 5, and 28 ± 7%, respectively. While the bottom ice section exhibited a substantial Chl-a contribution in line with previous studies, significantly higher contributions of the other parameters were observed in the upper sea ice sections. This suggests that the particulate matter within the interior of the sea ice could potentially serve as an additional food source for higher trophic grazers or act as a seeding material for a phytoplankton bloom during the ice melting season. Our findings highlight the importance of comprehensive field measurements encompassing the entire sea ice section to better understand the distribution of organic carbon pools within the sea ice in the Arctic Ocean.

BackgroundAn abundance of evidence indicates that physical activity may protect against Alzheimer’s disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults.MethodsWe enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery.ResultsWe found significant physical activity × age and physical activity × APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects.ConclusionOur findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline.

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone.Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.).Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min−1 vs. 67.9 ± 8.3 min−1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min−1 vs. 105.2 ± 4.1 min−1; pre- vs. post-oxycodone; p = 0.072).Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.