Pathophysiology of hypoperfusion of the precuneus in early Alzheimer’s disease

The earliest decline in cerebral perfusion in Alzheimer's disease (AD) is in the medial parietal cortex (precuneus). We have analyzed precuneus in post‐mortem tissue from 70 AD and 37 control brains to explore the pathophysiology of the hypoperfusion: the contribution of arteriolosclerotic small vessel disease (SVD) and cerebral amyloid angiopathy (CAA), and of the vasoconstrictors endothelin‐1 (EDN1) and angiotensin II (Ang II), and the association with Aβ. The myelin‐associated glycoprotein:proteolipid protein‐1 ratio (MAG:PLP1) was used as an indicator of oxygenation of the precuneus prior to death. MAG:PLP1 was reduced ∼50% in early AD (Braak stage III–IV). Although MAG:PLP1 remained low in advanced AD (stage V–VI), the reduction was less pronounced, possibly reflecting falling oxygen demand. Reduction in cortical MAG:PLP1 correlated with elevation in vascular endothelial growth factor (VEGF), another marker of hypoperfusion. Cortical MAG:PLP1 declined nonsignificantly with increasing SVD and CAA, but significantly with the concentration of EDN1, which was elevated approximately 75% in AD. In contrast, with reduction in cortical MAG:PLP1, Ang II level and angiotensin‐converting enzyme (ACE) activity declined, showing a normal physiological response to hypoperfusion. MAG:PLP1 was reduced in the parietal white matter (WM) in AD but here the decline correlated positively (ie, physiologically) with WM EDN1. However, the decline of MAG:PLP1 in the WM was associated with increasing cortical EDN1 and perhaps reflected vasoconstriction of perforating arterioles, which traverse the cortex to perfuse the WM. EDN1 in the cortex correlated highly significantly with both soluble and insoluble Aβ42, shown previously to upregulate neuronal endothelin‐converting enzyme‐2 (ECE2), but not with Aβ40. Our findings demonstrate reduced oxygenation of the precuneus in early AD and suggest that elevated EDN1, resulting from Aβ42‐mediated upregulation of ECE2, is a contributor

Can the palatability of healthy, satiety-promoting foods increase with repeated exposure during weight loss?

Repeated exposure to sugary, fatty, and salty foods often enhances their appeal. However, it is unknown if exposure influences learned palatability of foods typically promoted as part of a healthy diet. We tested whether the palatability of pulse containing foods provided during a weight loss intervention which were particularly high in fiber and low in energy density would increase with repeated exposure. At weeks 0, 3, and 6, participants (n = 42; body mass index (BMI) 31.2 ± 4.3 kg/m²) were given a test battery of 28 foods, approximately half which had been provided as part of the intervention, while the remaining half were not foods provided as part of the intervention. In addition, about half of each of the foods (provided as part or not provided as part of the intervention) contained pulses. Participants rated the taste, appearance, odor, and texture pleasantness of each food, and an overall flavor pleasantness score was calculated as the mean of these four scores. Linear mixed model analyses showed an exposure type by week interaction effect for taste, texture and overall flavor pleasantness indicating statistically significant increases in ratings of provided foods in taste and texture from weeks 0 to 3 and 0 to 6, and overall flavor from weeks 0 to 6. Repeated exposure to these foods, whether they contained pulses or not, resulted in a ~4% increase in pleasantness ratings. The long-term clinical relevance of this small increase requires further study.T32 AT000815 - NCCIH NIH HH

Utilizing the Power of Continuous Process Improvement in Technical Services

Objective: Examine the efficiency of work processes in the Technical Services Department, with the goal of reducing the turnaround time by 50% or more for three specific processes: (1) acquiring books for requestors; (2) implementing serials title changes; and (3) handling of journal issues from receipt to binding. Method: In summer 2003 the Library initiated a Continuous Process Improvement project. The project’s goal is to reduce time and/or save money by examining and improving work processes. The charge for the Technical Services team is to (1) reduce the turnaround time by 50% or more for firm orders from when the book is ordered to when it reaches the requestor; (2) reduce the time it takes by 50% or more to implement a serials title change, which involves staff throughout the library; and (3) reduce the time it takes by 50% or more for a newly-received journal issue to reach the shelf and eventually be bound. The team is utilizing value-added flow analysis to examine the processes and will make recommendations to management for changes to be implemented in a pilot project. Results: The Team met weekly over four months to identify the specific steps involved in each process, review the time involved in completing each task, analyze whether or not the step added value, and suggest improvements to the process. Team members documented and timed current workflow in spreadsheets and flowcharts. The Team proposed a number of procedural changes and initiatives that were accepted by library management for a five-month pilot project which is now ongoing. Important components of the implementation are establishing procedures for better communication and additional staff training. Conclusion: Value-added flow analysis is a useful tool for continuous process improvement. The Library’s goal of reducing turnaround time by 50% or more for these three specific processes will be achieved, as demonstrated in the pilot project. Technical Services will be better able to serve its internal and external customers. Presented at the Medical Library Association Annual Meeting, Washington, DC, on May 25, 2004

Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure Validation Simulation Study

The Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure (ITP) Validation Simulation Study investigated the viability of an ITP designed to enable oceanic flight level changes that would not otherwise be possible. Twelve commercial airline pilots with current oceanic experience flew a series of simulated scenarios involving either standard or ITP flight level change maneuvers and provided subjective workload ratings, assessments of ITP validity and acceptability, and objective performance measures associated with the appropriate selection, request, and execution of ITP flight level change maneuvers. In the majority of scenarios, subject pilots correctly assessed the traffic situation, selected an appropriate response (i.e., either a standard flight level change request, an ITP request, or no request), and executed their selected flight level change procedure, if any, without error. Workload ratings for ITP maneuvers were acceptable and not substantially higher than for standard flight level change maneuvers, and, for the majority of scenarios and subject pilots, subjective acceptability ratings and comments for ITP were generally high and positive. Qualitatively, the ITP was found to be valid and acceptable. However, the error rates for ITP maneuvers were higher than for standard flight level changes, and these errors may have design implications for both the ITP and the study's prototype traffic display. These errors and their implications are discussed

Cultural/Interpersonal Values and Smoking in an Ethnically Diverse Sample of Southern California Adolescents

In ethnically diverse school contexts, values from multiple cultures might influence adolescents\u27 attitudes and behaviors. This study developed scales to assess cultural values among Southern California 6- grade adolescents (N=2281) and evaluated the associations between values and smoking. The scales assessed values salient in many Hispanic and Asian cultures: Respect for Adults (e.g., filial piety, respeto). Interpersonal Harmony (e.g., saving face, simpatia), and Differentiated Gender Roles (e.g., machismo). In cross-sectional and one-year longitudinal models. Respect for Adults and Interpersonal Harmony were associated with a lower risk of lifetime smoking. The associations were significant even after controlling for demographic characteristics, friends\u27 smoking, and parents\u27 smoking, indicating that values influence adolescents\u27 behavior over and above the effects of modeling and peer influence. Increased understanding of adolescents\u27 values could inform the creation of smoking prevention programs for ethnically diverse adolescents

Level of Care Preferences Among Nursing Home Residents With Advanced Dementia

Delivering goal-directed care is a hallmark of high-quality palliative care, but requires an understanding of preferences

Long distance airborne transmission of SARS-CoV-2:rapid systematic review

OBJECTIVES: To evaluate the potential for long distance airborne transmission of SARS-CoV-2 in indoor community settings and to investigate factors that might influence transmission. DESIGN: Rapid systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, medRxiv, Arxiv, and WHO COVID-19 Research Database for studies published from 27 July 2020 to 19 January 2022; existing relevant rapid systematic review for studies published from 1 January 2020 to 27 July 2020; and citation analysis in Web of Science and Cocites. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Observational studies reporting on transmission events in indoor community (non-healthcare) settings in which long distance airborne transmission of SARS-CoV-2 was the most likely route. Studies such as those of household transmission where the main transmission route was likely to be close contact or fomite transmission were excluded. DATA EXTRACTION AND SYNTHESIS: Data extraction was done by one reviewer and independently checked by a second reviewer. Primary outcomes were SARS-CoV-2 infections through long distance airborne transmission (>2 m) and any modifying factors. Methodological quality of included studies was rated using the quality criteria checklist, and certainty of primary outcomes was determined using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Narrative synthesis was themed by setting. RESULTS: 22 reports relating to 18 studies were identified (methodological quality was high in three, medium in five, and low in 10); all the studies were outbreak investigations. Long distance airborne transmission was likely to have occurred for some or all transmission events in 16 studies and was unclear in two studies (GRADE: very low certainty). In the 16 studies, one or more factors plausibly increased the likelihood of long distance airborne transmission, particularly insufficient air replacement (very low certainty), directional air flow (very low certainty), and activities associated with increased emission of aerosols, such as singing or speaking loudly (very low certainty). In 13 studies, the primary cases were reported as being asymptomatic, presymptomatic, or around symptom onset at the time of transmission. Although some of the included studies were well conducted outbreak investigations, they remain at risk of bias owing to study design and do not always provide the level of detail needed to fully assess transmission routes. CONCLUSION: This rapid systematic review found evidence suggesting that long distance airborne transmission of SARS-CoV-2 might occur in indoor settings such as restaurants, workplaces, and venues for choirs, and identified factors such as insufficient air replacement that probably contributed to transmission. These results strengthen the need for mitigation measures in indoor settings, particularly the use of adequate ventilation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021236762

Functional Allocation with Airborne Self-Separation Evaluated in a Piloted Simulation

A human-in-the-loop simulation experiment was designed and conducted to evaluate an airborne self-separation concept. The activity supports the National Aeronautics and Space Administration s (NASA) research focus on function allocation for separation assurance. The objectives of the experiment were twofold: (1) use experiment design features in common with a companion study of ground-based automated separation assurance to promote comparability, and (2) assess agility of self-separation operations in managing trajectory-changing events in high traffic density, en-route operations with arrival time constraints. This paper describes the experiment and presents initial results associated with subjective workload ratings and group discussion feedback obtained from the experiment s commercial transport pilot participants

Translational neurophysiology in sheep:Measuring sleep and neurological dysfunction in CLN5 affected Batten disease sheep

This is the final published version of a paper originally published in BRAIN 2015: 138; 862?874, DOI: http://dx.doi.org/10.1093/brain/awv026Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders.This work was funded by CHDI Inc. (AJM). Founding the\ud sheep flock, and costs in NZ relating to the rearing and\ud genotyping of the animals were funded by a series of grants\ud from the Neurological Foundation of NZ and the Batten\ud Disease Support and Research Association (DNP, NLM)

Internet Accessibility and Usage among Urban Adolescents in Southern California: Implications for Web-Based Health Research

The World Wide Web (WWW) poses a distinct capability to offer interventions tailored to the individual’s characteristics. To fine tune the tailoring process, studies are needed to explore how Internet accessibility and usage are related to demographic, psychosocial, behavioral, and other health related characteristics. This study was based on a cross-sectional survey conducted on 2373 7th grade students of various ethnic groups in Southern California. Measures of Internet use included Internet use at school or at home, Email use, chat-room use, and Internet favoring. Logistic regressions were conducted to assess the associations between Internet uses with selected demographic, psychosocial, behavioral variables and self-reported health statuses. The proportion of students who could access the Internet at school or home was 90% and 40%, separately. Nearly all (99%) of the respondents could access the Internet either at school or at home. Higher SES and Asian ethnicity were associated with higher internet use. Among those who could access the Internet and after adjusting for the selected demographic and psychosocial variables, depression was positively related with chat-room use and using the Internet longer than 1 hour per day at home, and hostility was positively related with Internet favoring (All ORs = 1.2 for +1 STD, p \u3c 0.05). Less parental monitoring and more unsupervised time were positively related to email use, chat-room use, and at home Internet use (ORs for +1 STD ranged from 1.2 to 2.0, all p \u3c 0.05), but not related to at school Internet use. Substance use was positively related to email use, chat-room use, and at home Internet use (OR for “used” vs. “not used” ranged from 1.2 to 4.0, p \u3c 0.05). Self-reported health problems were associated with higher levels of Internet use at home but lower levels of Internet use at school. More physical activity was related to more email use (OR = 1.3 for +1 STD), chat room use (OR = 1.2 for +1 STD), and at school ever Internet use (OR = 1.2 for +1 STD, all p \u3c 0.05). Body mass index was not related to any of the Internet use-related measures. In this ethnically diverse sample of Southern California 7th grade students, 99% could access the Internet at school and/or at home. This suggests that the Internet is already a potential venue for large scale health communication studies. Adolescents with more psychosocial risk factors or detrimental health behaviors were more likely to use the Internet. Therefore, if used properly, Internet interventions could effectively address the high risk populations. Additional research is needed to gain a more complete understanding of the positive and negative consequences of Internet use among adolescents