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Introduction: Vascular risk factors in midlife have been associated with accelerated age-related cognitive decline. However, associations with old-age cardiovascular health are less clear cut and sometimes opposite associations have been observed. The objective of this study was to examine whether change in cardiovascular health, measured using the Life's Simple 7 (LS7) score, is associated with rate of cognitive change in older adults. Methods: We included 1133 participants aged ≥60 years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, assessed at baseline and at the 6-year follow-up, was composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure). Change in LS7 was calculated as the difference between baseline and 6 years (range -5 to +8 points). Individuals were categorized into “worse” (-5 to 2 points), “same” (-1 to 1 point), or “improve” (2 to 8 points). Linear mixed-effect models were used to examine change in cognitive performance as a function of LS7 change categories. Results: On average, participants slightly improved (M = 0.3, SD = 1.6) their cardiovascular health from baseline to the 6-year follow-up. Participants were classified as “same” (67.1 %), “improve” (21.0 %), and “worse” (11.8 %). The proportion of those who improved their LS7 individual items was higher for total cholesterol and diet, while the largest deterioration was observed in glucose and physical activity. Both the worse and improve categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥ 78 years), whereas improvement tended to be associated with faster cognitive decline in the young-old (< 78 years) group. Discussion: Change in cardiovascular health in old age may lead to faster cognitive decline. The results stress the importance of monitoring and maintaining good cardiovascular health also in very old adults and to, above all, avoid worsening of vascular risk factors.

Objectives: The implementation of disease‐modifying treatments for Alzheimer's Disease (AD) will require cost‐effective diagnostic processes. As part of The Precision Medicine In AD consortium (PMI‐AD) project, the aim is to analyze the baseline costs of diagnosing early AD at memory clinics in Norway, Slovenia, and the Netherlands. Methods: The costs of cognitive testing and a clinical examination, apolipoprotein E, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), positron emission tomography and blood‐based biomarkers (BBM), which are used in different combinations in the three countries, were analyzed. Standardized unit costs, adjusted for GDP per capita and based on Swedish conditions were applied. The costs were expressed in euros (€) as of 2019. A diagnostic set comprising clinical examination, cognitive testing, MRI and CSF was defined as the gold standard, with MRI mainly used as an exclusion filter. Results: Cost data were available for 994 persons in Norway, 169 in Slovenia and 1015 in the Netherlands. The mean diagnostic costs were 1478 (95% confidence interval 1433–1523) € in Norway, 851 (731–970) € in Slovenia and 1184 (1135–1232) € in the Netherlands. Norway had the highest unit costs but also the greatest use of tests. With a uniform diagnostic test set applied, the diagnostic costs were 1264 (1238–1291) €, in Norway, 843 (771–914) € in Slovenia and 1184 (1156–1213) € in the Netherlands. There were no major cost differences between the final set of diagnoses. Conclusions: The total costs for setting a diagnosis of AD varied somewhat in the three countries, depending on unit costs and use of tests. These costs are relatively low in comparison to the societal costs of AD. Key points: The introduction of blood‐based biomarkers for detecting Alzheimer's Disease (AD) can change the diagnostic process.Given the expected demands for treatment of cognitive disorders such as AD, the costs and capacity of the diagnostic work‐up are of great importance for care funders and planners.Our study incorporating diagnostic costs from three distinct European regions provides valuable inputs for cost‐effectiveness studies. [ABSTRACT FROM AUTHOR]

Slovenia, situated in Central Europe with a population of 2.1 million, has an estimated 44,278 individuals with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia, rendering them potential candidates for disease-modifying treatment (DMT), such as lecanemab. We identified 114 potential candidates whose real-life expenses for diagnostic process surmount to more than €80,000. Treating all potential candidates nationwide would amount to €1.06 billion, surpassing Slovenia's entire annual medication expenditure for 2022 (€743 million). The introduction of DMTs and the associated logistics, along with potential complications, will significantly change societal, professional, and patient approach to treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild‐, moderate‐, severe dementia, and institutionalization until death. METHODS: Multistate modeling with Cox regression was used to obtain the sojourn time. Covariates were age at baseline, sex, amyloid status, and Alzheimer's disease (AD) or other dementia diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Cohort and Memento). RESULTS: Using 80,543 patients, the sojourn time from clinically identified MCI to death across all patient groups ranged from 6.20 (95% confidence interval [CI]: 5.57–6.98) to 10.08 (8.94–12.18) years. DISCUSSION: Generally, sojourn time was inversely associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis. [ABSTRACT FROM AUTHOR]

Challenges faced by companies while handling product returns are discussed. Effective product returns strategies to enhance the levels of customer service are presented.

The transcriptional repressor REST (RE1 silencing transcription factor) regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression.

Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure.Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals.Methods: This cohort study included 1,950 participants aged≥60 years (M = 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models.Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (β= 0.21, 95%CI 0.12-0.29), verbal fluency (β= 0.08, 0.00-0.16), and global cognition (β= 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals.Conclusion: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults. [ABSTRACT FROM AUTHOR]

In this paper we consider the restriction of a unitary irreducible representation of type A_q(λ) of GL(4,R) to reductive subgroups H which are the fixpoint sets of an involution. We obtain a formula for the restriction to the symplectic group and to GL(2,C), and as an application we construct in the last section some representations in the cuspidal spectrum of the symplectic and the complex general linear group. In addition to working directly with the cohmologically induced module to obtain the branching law, we also introduce the useful concept of pseudo dual pairs of subgroups in a reductive Lie group.

Background: A common concern for patients with dementia is the time until severe stages and mortality. Current literature is sparce and often features small sample sizes. We aim to determine the time spent in mild cognitive impairment (MCI), mild‐, moderate‐, or severe dementia, institutionalization, and death. Method: Multistate modeling was used to obtain the time in each state. Covariates were age at study baseline, sex, amyloid status, and Alzheimer's disease (AD) diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Center and Memento). Result: Based on 80,972 patients, the full disease course from MCI to institutionalized‐severe dementia lasted between 7.91 (95% CI: 7.07‐9.02) years for males aged 87 at baseline and 11.70 (9.96–14.44) years for females aged 71. Conclusion: Generally, rapid progression was associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis. [ABSTRACT FROM AUTHOR]

Shcherbatko, Anatoly D., Christopher M. Davenport, Joan C. Speh, Simon R. Levinson, Gail Mandel, and Paul Brehm. Progesterone treatment abolishes exogenously expressed ionic currents in Xenopus oocytes. Am J Physiol Cell Physiol 280: C677-C688, 2001.--Fully grown oocytes of Xenopus laevis undergo resumption of the meiotic cycle when treated with the steroid hormone progesterone. Previous studies have shown that meiotic maturation results in profound downregulation of specific endogenous membrane proteins in oocytes. To determine whether the maturation impacts the functional properties of exogenously expressed membrane proteins, we used cut-open recordings from Xenopus oocytes expressing several types of [Na.sup.+] and [K.sup.+] channels. Treatment of oocytes with progesterone resulted in a downregulation of heterologously expressed [Na.sup.+] and [K.sup.+] channels without a change in the kinetics of the currents. The time course of progesterone-induced ion channel inhibition was concentration dependent. Complete elimination of [Na.sup.+] currents temporally coincided with development of germinal vesicle breakdown, while elimination of [K.sup.+] currents was delayed by ~2 h. Coexpression of human [[Beta].sub.1]-subunit with rat skeletal muscle [Alpha]-subunit in Xenopus oocytes did not prevent progesterone-induced downregulation of [Na.sup.+] channels. Addition of 8-bromo-cAMP to oocytes or injection of heparin before progesterone treatment prevented the loss of expressed currents. Pharmacological studies suggest that the inhibitory effects of progesterone on expressed [Na.sup.+] and [K.sup.+] channels occur downstream of the activation of cdc2 kinase. The loss of channels is correlated with a reduction in [Na.sup.+] channel immunofluorescence, pointing to a disappearance of the ion channel-forming proteins from the surface membrane. sodium channels; potassium channels; maturation; internalization; cdc2 protein kinase

Three main business strategies must be changed to turn the returned products operation from a money loosing to a money making part of a company. These points are discussed here.

Nimodipine is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome and less delayed ischemic neurological deficits. Animal and clinical trials show neuroprotective efficacy following nerve injuries. We showed a neuroprotective effect on Neuro2a cells. Subsequent microarray analysis revealed—among others—fatty acid 2-hydroxylase (FA2H) upregulated by nimodipine in vitro, which is a component of myelin synthesis. Differentiated Neuro2a cells were analyzed for nimodipine-mediated survival considering stress treatment in comparison to nifedipine-treatment. Cell survival was determined by measurement of LDH activity in the culture medium. Nimodipine decreased surgery-like stress-induced cell death of differentiated Neuro2a cells. Neuro2a cell culture was analyzed for changes in FA2H expression induced by nimodipine or nifedipine in surgery-like stress conditions. We analyzed expression levels of FA2H mRNA and protein by qPCR using fa2h specific primers or a FA2H-specific antibody in nimodipine or nifedipine non- and pre-treated Neuro2a cell culture, respectively. Nimodipine but not nifedipine increases FA2H protein levels and also significantly increases mRNA levels of FA2H in both undifferentiated and differentiated Neuro2a cells. Our findings indicate that higher expression of FA2H induced by nimodipine may cause higher survival of Neuro2a cells stressed with surgery-like stressors. [ABSTRACT FROM AUTHOR]

Thank you for 'Social Media for Authors: Forever in Search of Buzz' by Lauren Cerand (May/June 2011). I have recently deactivated my Facebook page because I found it too restrictive: [...]