Population incidence and associated mortality of urinary tract infection in people living with dementia.

OBJECTIVES: Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. METHODS: Data were extracted for n = 2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. RESULTS: UTIs in dementia (HR=2.18, 95 %CI [1.88-2.53], p < .0) and diabetes (1.21[1.01-1.45], p = .035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p < .0) compared to matched individuals with neither dementia nor diabetes. 5.4 % of untreated PLWD died within 60 days of GP diagnosis-increasing to 5.9 % in PLWD with diabetes. CONCLUSIONS: Incidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.

Patient and Public Involvement in Technology-Related Dementia Research: Scoping Review.

BACKGROUND: Technology-related research on people with dementia and their carers often aims to enable people to remain living at home for longer and prevent unnecessary hospital admissions. To develop person-centered, effective, and ethical research, patient and public involvement (PPI) is necessary, although it may be perceived as more difficult with this cohort. With recent and rapid expansions in health and care-related technology, this review explored how and with what impact collaborations between researchers and stakeholders such as people with dementia and their carers have taken place. OBJECTIVE: This review aims to describe approaches to PPI used to date in technology-related dementia research, along with the barriers and facilitators and impact of PPI in this area. METHODS: A scoping review of literature related to dementia, technology, and PPI was conducted using MEDLINE, PsycINFO, Embase, and CINAHL. Papers were screened for inclusion by 2 authors. Data were then extracted using a predesigned data extraction table by the same 2 authors. A third author supported the resolution of any conflicts at each stage. Barriers to and facilitators of undertaking PPI were then examined and themed. RESULTS: The search yielded 1694 papers, with 31 (1.83%) being analyzed after screening. Most (21/31, 68%) did not make clear distinctions between activities undertaken as PPI and those undertaken by research participants, and as such, their involvement did not fit easily into the National Institute for Health and Care Research definition of PPI. Most of this mixed involvement focused on reviewing or evaluating technology prototypes. A range of approaches were described, most typically using focus groups or co-design workshops. In total, 29% (9/31) described involvement at multiple stages throughout the research cycle, sometimes with evidence of sharing decision-making power. Some (23/31, 74%) commented on barriers to or facilitators of effective PPI. The challenges identified often regarded issues of working with people with significant cognitive impairments and pressures on time and resources. Where reported, the impact of PPI was largely reported as positive, including the experiences for patient and public partners, the impact on research quality, and the learning experience it provided for researchers. Only 4 (13%) papers used formal methods for evaluating impact. CONCLUSIONS: Researchers often involve people with dementia and other stakeholders in technology research. At present, involvement is often limited in scope despite aspirations for high levels of involvement and partnership working. Involving people with dementia, their carers, and other stakeholders can have a positive impact on research, patient and public partners, and researchers. Wider reporting of methods and facilitative strategies along with more formalized methods for recording and reporting on meaningful impact would be helpful so that all those involved-researchers, patients, and other stakeholders-can learn how we can best conduct research together.

The impact of study type and sleep measurement on oxygen desaturation index calculation.

STUDY OBJECTIVES: The oxygen desaturation index (ODI) is an important measure of sleep-disordered breathing during polysomnography (PSG); however, the AASM Manual (V3) does not specify whether to include oxygen desaturations occurring during wake epochs. Additionally, an ODI obtained from PSG can differ from an ODI using home sleep apnea tests (HSATs) that do not measure sleep, hampering diagnostic and treatment decision reliability. This study aimed to (1) compare an ODI that included all desaturations with an ODI that excluded desaturations occurring during wake epochs in PSG and (2) compare ODIs obtained from PSG with HSAT. METHODS: 100 consecutive PSGs for investigation of obstructive sleep apnea were compared. ODIs were calculated including all desaturations (ODIall) and by excluding desaturations entirely during wake epochs (ODIsleep). Additionally, we compared ODIall with an ODI calculated using monitoring time as the denominator (ODIHSAT). RESULTS: The median (interquartile range) 3% ODI for ODIall was 22.8 (13.1, 44.1) events/h and ODIsleep was 17.6 (11.5, 35.2) events/h (median difference: -3.9 events/h [-8.2, -0.9]; 21.0% [8.7%, 33.2%]). This discrepancy was larger with increasing ODI and decreasing sleep efficiency. The ODIHSAT was 17.4 (11.3, 35.2) events/h and the median reduction in ODIHSAT vs ODIall was -4.5 (-10.9, -2.0) events/h (21.6%; 11.1%, 33.8). CONCLUSIONS: ODI was significantly reduced when desaturations in wake epochs were excluded, and when ODI was based on monitoring time rather than sleep time, with the potential for underestimation of disease severity. Results suggest that ODI can differ substantially depending on the calculation and study type used, and that there is a need for standardization to ensure consistent diagnosis and treatment outcomes. CITATION: Whenn CB, Wilson DL, Ruehland WR, Churchward TJ, Worsnop C, Tolson J. The impact of study type and sleep measurement on oxygen desaturation index calculation. J Clin Sleep Med. 2024;20(5):709-717.

The I-STOP Program and Narcotic Prescriptions Following Facial Reconstructive Plastic Surgeries.

OBJECTIVES: To explore the effect of e-prescribing requirements on narcotic dispersion in New York State. Slicer Dicer was used to identify patient records based on CPT codes. METHODS: We investigated the influence of New York State e-prescribing requirements on narcotic dispersion following five common facial plastics procedures. Slicer Dicer was used to identify patient records based on CPT codes.We then looked at narcotic prescription rates following those surgeries between March 2014 and March 2018 at an academic institution. RESULTS: Overall, between March 2014 and March 2018, 76.1% of the sample received a narcotic prescription following a facial reconstructive plastic surgery. Patients who underwent rhinoplasty were most likely to receive a prescription for postoperative narcotics. The implementation of ISTOP, CPT code, use of non-narcotic adjuvant, and insurance type were each significantly associated with prescription of postoperative narcotics. Surgery time and age in years were significantly associated with prescription of postoperative narcotics. Ultimately, when controlling for the aforementioned clinical and sociodemographic variables included in the study, those who underwent surgery after the implementation of ISTOP were 42.8% less likely to receive a prescription for postoperative narcotics, aOR = 0.572, 95% CI 0.356, 0.919, p = 0.021. CONCLUSIONS: New York State's ISTOP program has succeeded in reducing the number of postoperative narcotic prescriptions following facial plastic reconstructive surgeries at this academic institution. However, opioid medications can still be utilized for postoperative analgesia when clinically appropriate. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1208-1213, 2024.

Character Traits Predict Health and Well-Being beyond Personality.

We examined the incremental validity of character in predicting health outcomes and well-being beyond personality traits and investigated the extent to which health-related behaviors mediate the relationship between character and well-being. Findings indicate that several character cores (e.g., transcendence, fortitude) predict well-being, health behaviors, and health outcomes beyond different measures of personality traits, indicating that character is discriminable from personality as indicated by incremental prediction. In particular, fortitude, temperance, transcendence, and sincerity appear to be key players. Implications for character research are discussed.

Maternal Circadian Disruption from Shift Work and the Impact on the Concentration of Melatonin in Breast Milk.

Background and Objective: Melatonin in breast milk exhibits a 24-hour circadian rhythm, present in nighttime breast milk but nearly undetectable in daytime breast milk. Shift work can disrupt the circadian timing of individuals, evident in changes in melatonin in saliva and urine samples. However, it is unknown whether these changes are also reflected in breast milk from a shift working mother. The aim of this study was to investigate whether maternal circadian rhythm disturbance from shift work impacts the melatonin concentration in breast milk. Materials and Methods: Breast milk and saliva samples were collected from 11 shift working mothers at four timepoints across five consecutive days. This included during their day shift or nonworkdays to act as a control, night shift, subsequent night shifts and postnight shift. Where possible, pre- and postfeed collections were also undertaken. Samples were grouped into four-time intervals: 12-6:30 am, 7-11:30 am, 12-6:30 pm, 7-11:30 pm, and melatonin levels (picogram per milliliter) in the breast milk and saliva samples were analyzed. Results: There was a significant decrease in breast milk melatonin (p = 0.026) at the 12-6:30 am time interval on subsequent night shifts, compared with control days. However, there was no overall time and shift type interaction effect (p = 0.70). In addition, no observed difference in melatonin levels was found in saliva samples, or when comparing pre- and postfeed breast milk. Breast milk melatonin however was found to be significantly higher compared with saliva (p > 0.001), at all but one time interval. Conclusion: The findings suggest that there is a potential effect of maternal circadian rhythm disruption from shift work on breast milk melatonin levels. This is an important step in exploring the role of maternal circadian timing and the effect on breast milk composition. Expansion of this research and exploration of other circadian rhythm misalignment sleep disorders on breast milk is highly recommended.

Longitudinally assessed maternal sleep position, measures of breathing during sleep, and fetal growth in high-risk pregnancies.

STUDY OBJECTIVES: Subjective recall of supine sleep during pregnancy has been linked to increased risk of stillbirth, but longitudinal, objective data are lacking. We aimed to examine how sleep position and breathing parameters change throughout pregnancy, and investigated associations between maternal supine sleep, assessed objectively in early and late gestation, and fetal growth velocity in high-risk women. METHODS: Women with singleton pregnancies and body mass index (BMI) ≥27 kg/m2 underwent level-III sleep apnea testing. Sleep position was assessed by accelerometry. We derived percentiles of estimated fetal weight and birthweight using FetalGPSR software, then calculated growth velocity as change in percentile/week between the second-trimester anatomy scan and birth. RESULTS: In total, 446 women were included, with N = 126 in the longitudinal sleep pattern analysis and N = 83 in the fetal growth analysis. Sleep-onset position and predominant sleep position were significantly correlated in both early (p = 0.001) and late (p < 0.01) pregnancy. However, supine going-to-bed position predicted predominant supine sleep in only 47% of women. Between early and late pregnancy there was a reduction in predominant supine sleepers (51.6% to 30.2%). Percent of sleep spent supine and oxygen desaturation index, in the third trimester, were significantly associated after BMI adjustment (B = 0.018, p = 0.04). Models did not suggest significant effects of early or late pregnancy supine sleep on growth velocity (p > 0.05). CONCLUSIONS: Going-to-bed position predicts predominant supine sleep in less than half of women with overweight and obesity. Time spent supine throughout pregnancy correlates with measures of sleep-disordered breathing. Maternal sleep position patterns did not affect fetal growth velocity in this high-risk population, but the study was not powered to detect differences.

Validation of Longitudinal Progression Examinations for Prediction of APPE Readiness.

OBJECTIVE: To study curricular outcomes for the purpose of holistic improvement of the curriculum. METHODS: A single-institution retrospective cohort study evaluated 3 cohorts of Doctor of Pharmacy students entering the program through performance in Advanced Pharmacy Practice Experience (APPE) rotations. Assessment scores and pass/fail outcomes were collected from the 3 examinations to use as predictors, and the numbers of "needs improvement" (NI) and "unsatisfactory" (U) ratings from preceptors during the APPE rotations served as outcome measures. RESULTS: Pharmacy mathematics competency and Milemarker 1 (MM1) examination first-time scores, but not those from Milemarker 2 (MM2), were significantly associated with NI or U scores on required APPE rotations. Significant correlations for all examinations (pharmacy mathematics competency, MM1, and MM2) were found for the Acute Care/Inpatient APPE rotation for each cohort and the combined cohorts. Significant correlations were also found between all examinations and the APPE rotation courses Advanced Hospital and Ambulatory Care, with the exception of the 2021 cohort. Performance in the Advanced Community rotation was not associated with any of the examinations. MM1 and MM2 are both reliable measures of competence in our didactic curriculum and predictive of scoring an NI or U rating in the APPE Acute Care/Inpatient rotation. CONCLUSION: The longitudinal milestone examinations used in our institution provide a mechanism to identify students likely to struggle in required APPE rotations and target them for remediation activities.

Rapid Versus Slow Cooling Pasteurization of Donor Breast Milk: Does the Cooling Rate Effect Melatonin Reduction?

Background and Objective: There is a question as to whether melatonin levels in breast milk are impacted by the cooling rate postpasteurization. Past research that has used in the Australian donor bank's breast milk Holder Pasteurization technique has reported varying findings regarding melatonin levels postpasteurization. Where breast milk was cooled slowly, a significant reduction in breast milk melatonin levels was observed. Conversely, where a rapid cooling method was used, there was no significant reduction in melatonin levels. The aim of this study was to investigate whether the cooling process between the different pasteurization techniques impact on melatonin levels in breast milk postpasteurization. Materials and Methods: Twenty-seven nighttime breast milk samples were collected, with each sample divided into three; one remained unpasteurized, one was pasteurized and rapidly cooled to 4°C, and the other was pasteurized and cooled slowly to 4°C. Results: Melatonin levels were significantly reduced in both the rapidly cooled and slow cooled breast milk samples when compared to their unpasteurized counterpart (p < 0.001). There was no significant difference in melatonin levels between the two cooling methods (p = 0.91). Conclusion: This study showed that both the rapid and cooling pasteurization processes had a similar reduction in melatonin levels in breast milk. However, even after pasteurization melatonin was still present. Therefore, it is recommended that donor banks still take into consideration circadian timing hormones such as melatonin and the time of day breast milk is expressed.

Ensuring No Death Is Ignored: Development of a Hospital Mortality Review and Notification System.

BACKGROUND AND OBJECTIVES: Standardized review of mortalities may identify potential system improvements. We designed a hospitalwide identification, review, and notification system for inpatient pediatric mortalities. METHODS: Key stakeholders constructed a future state process map for identification and review of deaths. An online mortality review form was modified through a series of Plan-Do-Study-Act cycles and spread to all pediatric services in January 2019. Mortalities occurring within 30 days of discharge were added in December 2019. Our primary outcome was percentage of mortalities reviewed, and the process measure was time to review completion. Additional Plan-Do-Study-Act cycles were used to refine 2 mechanisms for monthly notification of deaths. We surveyed monthly mortality notification e-mail recipients to elicit feedback to further improve notifications. RESULTS: After the pilot, 284 of 328 (86.6%) of mortalities were reviewed. Average time to review completion decreased by 49% compared with baseline after an increase during the first year of the pandemic. Qualitative analysis of a subset of these mortalities showed that 154 of 229 (67.2%) underwent further review. We added a summary of mortalities by unit to a monthly hospitalwide safety report and developed monthly mortality notification e-mails. The survey showed that 89% of respondents (70 of 79) learned about a death they did not know about, 58% (46 of 79) sought additional information through discussion with a colleague, and 76% (65 of 86) agreed that the notifications helped process grief. CONCLUSIONS: We describe an effective and well-received approach to the identification, review, and notification of mortalities at an academic pediatric hospital, which may be useful at other institutions.

Conceptualizing "positive attributes" across psychological perspectives.

BACKGROUND: The growth of positive psychology has birthed debate on the nature of what "positive" really means. Conceptualizations of positive attributes vary across psychological perspectives, and it appears these definitional differences stem from standards for "positive" espoused by three normative ethical frameworks: consequentialism, deontology, and virtue ethics. When definitions of "positive" do not align with one of these ethical schools, it appears researchers rely on preference to distinguish positive attributes. In either case, issues arise when researchers do not make their theoretical alignment explicit, leading to value-laden, often subjective criteria being smuggled into science as a description of what is positive. OBJECTIVE: To foster a deeper critical understanding of the different approaches, we examine how these conceptual definitions of positive attributes (mis)align with their ethical traditions or fail to align with an ethical school. METHOD: We review several positive attribute theories across psychological disciplines that serve as examples of the ethical and non-ethical sources of "positivity." Through this, we assess the conceptual criteria for what each approach considers "positive," note the degree of alignment between definition and ethical school, and draw attention to potential issues. CONCLUSION: We advance the conceptual assessment of positive attributes by considering the implications of failing to explicitly address the theoretical foundation from which a construct is defined.

Gender Disparities in General Surgery Resident Subspecialization.

BACKGROUND: There are an increasing number of women entering medical school and general surgery residency. Despite this, there remains an underrepresentation of women in some surgical specialties. The purpose of this study is to examine gender differences in fellowship subspecialization of recent general surgery graduates. METHODS: Graduating residents from general surgery residencies from 2016 to 2020 were identified. Referring to each residency's graduating resident website, we noted whether or not listed alumni were reported to have entered a fellowship. If applicants were listed as having completed a fellowship, the fellowship was noted along with each applicant's expressed gender. Differences across groups were analyzed using SPSS. RESULTS: The majority (82.4%) of graduates pursued a fellowship after residency training. Men were more likely to enter fellowships in Cardiothoracic Surgery, Plastic and Reconstructive Surgery, Vascular Surgery, and practice than women. Women were more likely to enter fellowships in Breast Surgery, Acute Care Surgery/Trauma Surgery, Pediatric Surgery, and Endocrine Surgery than men. CONCLUSIONS: The majority of general surgery residency graduates pursue fellowship training. Gender disparities continue for a minority of subspecialties for both men and women.

High-Temperature Pasteurization Used at Donor Breast Milk Banks Reduces Melatonin Levels in Breast Milk.

Background and Objective: Donor human milk banks are used when breast milk directly from mothers is unavailable or insufficient. Breast milk contains melatonin, which exhibits a 24-hour pattern. Melatonin promotes sleep onset and is barely detected in daytime milk but rises in the evening and peaks early in the morning. Melatonin supports the development of an infant's own circadian rhythm and is important for neurodevelopment. Currently, donor banks pasteurize breast milk using a Holder Pasteurization (HoP) technique where breast milk is treated at a high temperature (+62°) for 30 minutes before cooling to eliminate any pathogens before it is given to infants. It is not known how the pasteurization process affects the melatonin levels in breast milk. The aim of this study was to investigate whether the pasteurization process reduces melatonin levels in breast milk. Materials and Methods: Ten night-time breast milk samples were collected and each divided into two groups; one group remained unpasteurized and the other group was pasteurized using the HoP technique. Results: Melatonin levels between the unpasteurized and pasteurized groups were compared. Results showed that there was a significant reduction after pasteurization (mean ± standard deviation = 51.92 pg/mL ± 19.54 versus 39.66 pg/mL ± 13.05, p = 0.01). Conclusions: It is important to understand that pasteurization can reduce melatonin levels in breast milk because this hormone is considered important to support the neurodevelopment of infants, especially those born preterm. Further focus on the effect of pasteurization techniques on melatonin in donor breast milk is warranted.

Remote Monitoring of Physiology in People Living With Dementia: An Observational Cohort Study.

BACKGROUND: Internet of Things (IoT) technology enables physiological measurements to be recorded at home from people living with dementia and monitored remotely. However, measurements from people with dementia in this context have not been previously studied. We report on the distribution of physiological measurements from 82 people with dementia over approximately 2 years. OBJECTIVE: Our objective was to characterize the physiology of people with dementia when measured in the context of their own homes. We also wanted to explore the possible use of an alerts-based system for detecting health deterioration and discuss the potential applications and limitations of this kind of system. METHODS: We performed a longitudinal community-based cohort study of people with dementia using "Minder," our IoT remote monitoring platform. All people with dementia received a blood pressure machine for systolic and diastolic blood pressure, a pulse oximeter measuring oxygen saturation and heart rate, body weight scales, and a thermometer, and were asked to use each device once a day at any time. Timings, distributions, and abnormalities in measurements were examined, including the rate of significant abnormalities ("alerts") defined by various standardized criteria. We used our own study criteria for alerts and compared them with the National Early Warning Score 2 criteria. RESULTS: A total of 82 people with dementia, with a mean age of 80.4 (SD 7.8) years, recorded 147,203 measurements over 958,000 participant-hours. The median percentage of days when any participant took any measurements (ie, any device) was 56.2% (IQR 33.2%-83.7%, range 2.3%-100%). Reassuringly, engagement of people with dementia with the system did not wane with time, reflected in there being no change in the weekly number of measurements with respect to time (1-sample t-test on slopes of linear fit, P=.45). A total of 45% of people with dementia met criteria for hypertension. People with dementia with α-synuclein-related dementia had lower systolic blood pressure; 30% had clinically significant weight loss. Depending on the criteria used, 3.03%-9.46% of measurements generated alerts, at 0.066-0.233 per day per person with dementia. We also report 4 case studies, highlighting the potential benefits and challenges of remote physiological monitoring in people with dementia. These include case studies of people with dementia developing acute infections and one of a person with dementia developing symptomatic bradycardia while taking donepezil. CONCLUSIONS: We present findings from a study of the physiology of people with dementia recorded remotely on a large scale. People with dementia and their carers showed acceptable compliance throughout, supporting the feasibility of the system. Our findings inform the development of technologies, care pathways, and policies for IoT-based remote monitoring. We show how IoT-based monitoring could improve the management of acute and chronic comorbidities in this clinically vulnerable group. Future randomized trials are required to establish if a system like this has measurable long-term benefits on health and quality of life outcomes.

Sleep disordered breathing and the risk of severe maternal morbidity in women with preeclampsia: A population-based study.

OBJECTIVE: Obstructive sleep apnea (OSA) may exacerbate the widespread endothelial dysfunction seen in preeclampsia, potentially worsening clinical outcomes. We aimed to assess whether OSA is associated with an increased risk of severe maternal morbidity, cardiovascular morbidity, and healthcare utilization among women with preeclampsia. STUDY DESIGN: We performed a retrospective cohort study utilizing data from the National Perinatal Information Center (2010-2014) in the United States.The cohort comprised women with preeclampsia. We estimated the association between OSA and the outcomes using logistic regression analyses and determined odds ratio adjusted for demographic factors and comorbidities (ORadj) and associated 95% confidence intervals (CI). MAIN OUTCOME MEASURES: The primary outcome was a composite of mortality and severe maternal morbidity comprising intensive care unit (ICU) admission, acute renal failure, pulmonary edema, pulmonary embolism, congestive heart failure, cardiomyopathy, and stroke. Secondary outcomes comprised the subset of cardiovascular events, as well as increased healthcare utilization (including Cesarean delivery, preterm birth, ICU admission, and prolonged length of hospital stay). RESULTS: In total, 71,159 women had preeclampsia, including 270 (0.4 %) with OSA. Women with preeclampsia and OSA were more likely to experience severe maternal morbidity than women without OSA (ORadj 2.65, 95 % CI [1.94-3.61]). Moreover, women with concomitant OSA had more severe cardiovascular morbidity than women without OSA (ORadj 5.05, 95 % CI [2.28-11.17]). Accordingly, OSA was associated with increased healthcare utilization in women with preeclampsia (ORadj. 2.26, 95 % CI [1.45-3.52]). CONCLUSION: In women with preeclampsia, OSA increases the risk for severe maternal morbidity, cardiovascular morbidity, and healthcare utilization.

A Case Study of Co-production Within a Mental Health Recovery College Dementia Course: Perspectives of A Person With Dementia, Their Family Supporter and Mental Health Staff.

Background: Undertaking co-production as a power-sharing way to improve mental health dementia services remains uncommon, suggesting opportunities to apply knowledge from lived experience of people with dementia, may often be missed. One barrier is stigma, assuming people with progressive cognitive impairment cannot manage this level of participation, support peers nor offer a "valid" perspective. Purpose: This paper shares knowledge gained from a service evaluation that explored various experiences of a person with dementia, their family supporter and mental health staff, involved in co-producing a course about "living well" with dementia, within a mental health Recovery College. Design: A qualitative, case study approach used semi-structured interviewing and inductive thematic analysis. Findings: Co-production activities generated a shared sense of positivity, pride and privilege, highlighting positive effects in breaking down the "them and us" barriers common in traditional healthcare professional-service user relationships. Each individual had both something to offer and something to gain during the process. Staff identified challenges in the co-production process; in that balancing all the voices during meetings could be complex at times, and the process overall required considerable time commitment. Conclusion: Taking part in co-production at an appropriate level and with peer support is a relational activity seen to be valuable in powerfully, yet gently, challenging stigma and assumptions around dementia. Findings show that while the process of co-production requires time and dedication, there is overall value in involving people living with dementia both in co-production and in peer support. This provided a straightforward and beneficial means to inclusively improve post-diagnosis support and care quality within a memory service.

Regulation of body weight and food intake by AGRP neurons during opioid dependence and abstinence in mice.

Dysregulation of body weight maintenance and opioid dependence are often treated as independent disorders. Here, we assessed the effects of both acute and long-term administration of morphine with and without chemogenetic activation of agouti-related peptide (AGRP)-expressing neurons in the arcuate nucleus (ARCAGRP neurons) to elucidate whether morphine and neuronal activation affect feeding behavior and body weight. First, we characterized interactions of opioids and energy deficit in wild-type mice. We observed that opioid administration attenuated both fasting-induced refeeding and ghrelin-stimulated feeding. Moreover, antagonism of opioid receptors blocked fasting-induced refeeding behavior. Next, we interfaced chemogenetics with opioid dependence. For chemogenetic experiments of ARCAGRP neurons, we conducted a priori behavioral qualification and post-mortem FOS immunostaining verification of arcuate activation following ARCAGRP chemogenetic activation. We administered clozapine during short-term and long-term morphine administration paradigms to determine the effects of dependence on food intake and body weight. We found that morphine occluded feeding behavior characteristic of chemogenetic activation of ARCAGRP neurons. Notably, activation of ARCAGRP neurons attenuated opioid-induced weight loss but did not evoke weight gain during opioid dependence. Consistent with these findings, we observed that morphine administration did not block fasting-induced activation of the ARC. Together, these results highlight the strength of opioidergic effects on body weight maintenance and demonstrate the utility of ARCAGRP neuron manipulations as a lever to influence energy balance throughout the development of opioid dependence.

EXPANSE: A time-of-flight EXPanded Angle Neutron Spin Echo spectrometer at the Second Target Station of the Spallation Neutron Source.

EXPANSE, an EXPanded Angle Neutron Spin Echo instrument, has been proposed and selected as one of the first suite of instruments to be built at the Second Target Station of the Spallation Neutron Source at the Oak Ridge National Laboratory. This instrument is designed to address scientific problems that involve high-energy resolution (neV-µeV) of dynamic processes in a wide range of materials. The wide-angle detector banks of EXPANSE provide coverage of nearly two orders of magnitude in scattering wavenumbers, and the wide wavelength band affords approximately four orders of magnitude in Fourier times. This instrument will offer unique capabilities that are not available in the currently existing neutron scattering instruments in the United States. Specifically, EXPANSE will enable direct measurements of slow dynamics in the time domain over wide Q-ranges simultaneously and will also enable time-resolved spectroscopic studies. The instrument is expected to contribute to a diverse range of science areas, including soft matter, polymers, biological materials, liquids and glasses, energy materials, unconventional magnets, and quantum materials.

Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments.

BACKGROUND: Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating executive functions including the regulation of attention. Attention is affected early in Alzheimer's disease (AD), and this may relate to pathological changes within the locus coeruleus, the main source of noradrenergic pathways within the brain. Given that cholinergic pathways, also involved in attention, are disrupted in AD, the combination of noradrenergic and cholinergic treatments may have a synergistic effect on symptomatic AD. The primary objective of the NorAD trial is to evaluate the change in cognition with 12 weeks of treatment of extended-release guanfacine (GXR) against a placebo as a combination therapy with cholinesterase inhibitors in participants with mild to moderate Alzheimer's disease. METHODS/DESIGN: NorAD is a 3-month, single-centre, randomised, double-blind, placebo-controlled, phase III trial of extended-release guanfacine (GXR) in participants with mild to moderate Alzheimer's disease. A total of 160 participants will be randomised to receive either daily guanfacine or placebo in combination with approved cholinesterase treatment for 12 weeks. The primary outcome is the change in cognition, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), from baseline to follow-up in the treatment group compared to the placebo group. Secondary outcomes include the change in additional cognitive measures of attention (Tests of Attention: Trails A and B, digit-symbol substitution, Test of Everyday Attention and CANTAB-RVP), neuropsychiatric symptoms (Neuropsychiatric Inventory), caregiver burden (Zarit Burden Interview) and activities of daily living (Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory). From July 2020, observation of change following cessation of treatment is also being assessed. DISCUSSION: There is strong evidence for early noradrenergic dysfunction in Alzheimer's disease. The NorAD trial aims to determine whether guanfacine, a noradrenergic alpha-2 agonist, improves attention and cognition when used in addition to standard cholinergic treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03116126 . Registered on 14 April 2017 EudraCT: 2016-002598-36.