"Just Join Them": Improv and Dementia Care.

Improvisational (improv) theatre skill development holds promise for improving the dementia capability of care partners. In this report, we present analysis of data from an ongoing study on meaningful engagement and quality of life among assisted living (AL) residents with dementia. Using ethnographic methods, we collected data from persons with dementia (n = 59) and their care partners (n = 165) in six diverse AL communities each studied for one year. Building cumulatively on past work and existing literature, we demonstrate the potential benefits of training care partners to use improv skills. We discuss implications, including the need for intervention research.

Use of Mechanical Ventilation Across 3 Countries.

Importance: The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. Objective: To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. Design, Setting, and Participants: This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. Exposure: The country in which IMV was received. Main Outcomes and Measures: The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. Results: The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). Conclusions and Relevance: This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource.

Understanding Capacity and Optimizing Meaningful Engagement among Persons Living with Dementia.

Meaningful engagement is a key dimension of quality of life among persons living with dementia, yet little is known about how to best to promote it. Guided by grounded theory methods, we present analysis of data collected over a 1-year period in four diverse assisted living (AL) communities as part of the study, "Meaningful Engagement and Quality of Life among Assisted Living Residents with Dementia." Our aims are to: (a) learn how meaningful engagement is negotiated among AL residents with dementia and their care partners; and (b) identify how to create these positive encounters. Researchers followed 33 residents and 100 care partners (formal and informal) and used participant observation, resident record review, and semi-structured interviews. Data analysis identified "engagement capacity" as central to the negotiation of meaningful engagement. We conclude that understanding and optimizing the engagement capacities of residents, care partners, care convoys, and settings, are essential to creating and enhancing meaningful engagement among persons living with dementia.

Discovery and Enzymatic Screening of Genome-Mined Microbial Levanases to Produce Second-Generation ß-(2,6)-Fructooligosaccharides: Catalytic Properties.

Evidence suggests that ß-(2,6)-levan-type fructooligosaccharides (FOSs) possess higher prebiotic potential and selectivity than their ß-(2,1)-inulin-type counterparts. The focus of the present work was to develop an enzymatic approach for the synthesis of levan-type FOSs, employing levanases (EC 3.2.1.65), specifically those performing endo-hydrolysis on levans. To identify new levanases, a selection of candidates was obtained via in silico exploration of the levanase family biodiversity through a sequence-driven approach. A collection of 113 candidates was screened according to their specific activities on low- and high-molecular-weight (MW) levan as well as thermal stability. The most active levanases were able to hydrolyze both types of levan with similar efficiency. This ultimately revealed 10 active, highly evolutionary distant and diverse candidate levanases, which demonstrated preferential hydrolysis of levan over inulin. The end-product profile differed significantly depending on levanase with levanbiose, levantriose, and levantetraose being the major FOSs. Among them, the catalytic properties of 5 selected potential new levanases (LEV9 from Belliella Baltica, LEV36 from Dyadobacter fermentans, LEV37 from Capnocytophaga ochracea, LEV79 from Vibrio natriegens, LEV91 from Paenarthrobacter aurescens) were characterized, especially in terms of pH and temperature profiles, thermal stability, and kinetic parameters. The identification of these novel levanases is expected to contribute to the production of levan-type FOSs with properties surpassing those of commercial preparations.

New and Persistent Sedative Prescriptions Among Older Adults Following a Critical Illness: A Population-Based Cohort Study.

BACKGROUND: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use posthospitalization. RESEARCH QUESTION: For sedative-naive, older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt? STUDY DESIGN AND METHODS: This population-based cohort study included ICU survivors aged ≥ 66 years who had not filled sedative prescriptions within ≤ 6 months before hospitalization (sedative-naive) in Ontario, Canada (2003-2019). Using multilevel logistic regression, demographic, clinical, and hospital characteristics and their association with new sedative prescription within ≤ 7 days of discharge are described. Variation between hospitals was quantified by using the adjusted median OR. Factors associated with persistent prescriptions (≤ 6 months) were examined with a multivariable proportional hazards model. RESULTS: A total of 250,428 patients were included (mean age, 76 years; 61% male). A total of 15,277 (6.1%) filled a new sedative prescription, with variation noted across hospitals (2% [95% CI, 1-3] to 44% [95% CI, 3-57]); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (adjusted OR [aOR], 4.00; 95% CI, 3.72-4.31), receipt of inpatient geriatric (aOR, 1.95; 95% CI, 1.80-2.10) or psychiatry (aOR, 2.76; 95% CI, 2.62-2.91) consultation, invasive ventilation (aOR, 1.59; 95% CI, 1.53-1.66), and ICU length of stay ≥ 7 days (aOR, 1.50; 95% CI, 1.42-1.58). The residual heterogeneity between hospitals (adjusted median OR, 1.43; 95% CI, 1.35-1.49) had a stronger association with new sedative prescriptions than the Charlson Comorbidity Index score or sepsis. Factors associated with persistent sedative use were similar with the addition of female subjects (subdistribution hazard ratio, 1.07; 95% CI, 1.02-1.13) and pre-existing polypharmacy (subdistribution hazard ratio, 0.88; 95% CI, 0.80-0.93). INTERPRETATION: One in 15 sedative-naive, older adult ICU survivors filled a new sedative within ≤ 7 days of discharge; more than one-half of these survivors filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation.

Acute high-fat diet impairs macrophage-supported intestinal damage resolution.

Chronic exposure to high-fat diets (HFD) worsens intestinal disease pathology, but acute effects of HFD in tissue damage remain unclear. Here, we used short-term HFD feeding in a model of intestinal injury and found sustained damage with increased cecal dead neutrophil accumulation, along with dietary lipid accumulation. Neutrophil depletion rescued enhanced pathology. Macrophages from HFD-treated mice showed reduced capacity to engulf dead neutrophils. Macrophage clearance of dead neutrophils activates critical barrier repair and antiinflammatory pathways, including IL-10, which was lost after acute HFD feeding and intestinal injury. IL-10 overexpression restored intestinal repair after HFD feeding and intestinal injury. Macrophage exposure to lipids from the HFD prevented tethering and uptake of apoptotic cells and Il10 induction. Milk fat globule-EGF factor 8 (MFGE8) is a bridging molecule that facilitates macrophage uptake of dead cells. MFGE8 also facilitates lipid uptake, and we demonstrate that dietary lipids interfere with MFGE8-mediated macrophage apoptotic neutrophil uptake and subsequent Il10 production. Our findings demonstrate that HFD promotes intestinal pathology by interfering with macrophage clearance of dead neutrophils, leading to unresolved tissue damage.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

Nonopioid Analgesic Prescriptions Filled after Surgery among Older Adults in Ontario, Canada: A Population-based Cohort Study.

BACKGROUND: The objective was to assess changes over time in prescriptions filled for nonopioid analgesics for older postoperative patients in the immediate postdischarge period. The authors hypothesized that the number of patients who filled a nonopioid analgesic prescription increased during the study period. METHODS: The authors performed a population-based cohort study using linked health administrative data of 278,366 admissions aged 66 yr or older undergoing surgery between fiscal year 2013 and 2019 in Ontario, Canada. The primary outcome was the percentage of patients with new filled prescriptions for nonopioid analgesics within 7 days of discharge, and the secondary outcome was the analgesic class. The authors assessed whether patients filled prescriptions for a nonopioid only, an opioid only, both opioid and nonopioid prescriptions, or a combination opioid/nonopioid. RESULTS: Overall, 22% (n = 60,181) of patients filled no opioid prescription, 2% (n = 5,534) filled a nonopioid only, 21% (n = 59,608) filled an opioid only, and 55% (n = 153,043) filled some combination of opioid and nonopioid. The percentage of patients who filled a nonopioid prescription within 7 days postoperatively increased from 9% (n = 2,119) in 2013 to 28% (n = 13,090) in 2019, with the greatest increase for acetaminophen: 3% (n = 701) to 20% (n = 9,559). The percentage of patients who filled a combination analgesic prescription decreased from 53% (n = 12,939) in 2013 to 28% (n = 13,453) in 2019. However, the percentage who filled both an opioid and nonopioid prescription increased: 4% (n = 938) to 21% (n = 9,880) so that the overall percentage of patients who received both an opioid and a nonopioid remained constant over time 76% (n = 18,642) in 2013 to 75% (n = 35,391) in 2019. CONCLUSIONS: The proportion of postoperative patients who fill prescriptions for nonopioid analgesics has increased. However, rather than a move to use of nonopioids alone for analgesia, this represents a shift away from combination medications toward separate prescriptions for opioids and nonopioids.

Surgeon Postoperative Opioid Prescribing Intensity and Risk of Persistent Opioid Use Among Opioid-naive Adult Patients: A Population-based Cohort Study.

OBJECTIVE: The aim of this study was to determine the relationship between surgeon opioid prescribing intensity and subsequent persistent opioid use among patients undergoing surgery. SUMMARY BACKGROUND DATA: The extent to which different postoperative prescribing practices lead to persistent opioid use among surgical patients is poorly understood. METHODS: Retrospective population-based cohort study assessing opioid-naive adults who underwent 1 of 4 common surgeries. For each surgical procedure, the surgeons' opioid prescribing intensity was categorized into quartiles based on the median daily dose of morphine equivalents of opioids dispensed within 7 days of the surgical visit for all the surgeons' patients. The primary outcome was persistent opioid use in the year after surgery, defined as 180 days or more of opioids supplied within the year after the index date excluding prescriptions filled within 30 days of the index date. Secondary outcomes included a refill for an opioid within 30 days and emergency department visits and hospitalizations within 1 year. RESULTS: Among 112,744 surgical patients, patients with surgeons in the highest intensity quartile (Q4) were more likely to fill an opioid prescription within 7 days after surgery compared with those in the lowest quartile (Q1) (83.3% Q4 vs 65.4% Q1). In the primary analysis, the incidence of persistent opioid use in the year after surgery was rare in both highest and lowest quartiles (0.3% Q4 vs 0.3% Q1), adjusted odds ratio (AOR) of 1.18, 95% CI 0.83-1.66). However, multiple analyses using stricter definitions of persistent use that included the requirement of a prescription filled within 7 days of discharge after surgery showed a significant association with surgeon quartile (up to an AOR 1.36, 95% CI 1.25, 1.47). Patients in Q4 were more likely to refill a prescription within 30 days (4.8% Q4 vs 4.0% Q1, AOR 1.14, 95% CI 1.04-1.24). CONCLUSIONS: Surgeons' overall prescribing practices may contribute to persistent opioid use and represent a target for quality improvement. However, the association was highly sensitive to the definition of persistent use used.

The effects of acute care hospitalization on health and cost trajectories for nursing home residents: A matched cohort study.

Thirty five percent to sixty seven percent of admissions to acute care hospitals from nursing homes are potentially preventable. Limited data exist regarding clinical and cost trajectories post an acute care hospitalization. To describe clinical impact and post-hospitalization costs associated with acute care admissions for nursing home residents. Analysis of population-based data. The 65,996 nursing home residents from a total of 645 nursing homes. Clinical outcomes assessed with the Changes in Health, End-stage disease and Symptoms and Signs (CHESS) scores, and monthly costs. Post-index date, hospitalized residents worsened their clinical conditions, with increases in CHESS scores (CHESS 3 + 24.5% vs 7.6%, SD 0.46), more limitations in activities of daily living (ADL) (86.1% vs 76.0%, SD 0.23), more prescriptions (+1.64 95% CI 1.43-1.86, P < .001), falls (30.9% vs 18.1%, SD 0.16), pressure ulcers (16.4% vs 8.6%, SD 0.37), and bowel incontinence (47.3% vs 39.3%, SD 0.35). Acute care hospitalizations for nursing home residents had a significant impact on their clinical and cost trajectories upon return to the nursing home. Investments in preventive strategies at the nursing home level, and to mitigate functional decline of hospitalized frail elderly residents may lead to improved quality of care and reduced costs for this population. Pre-hospitalization costs were not different between the hospitalized and control groups but showed an immediate increase post-hospitalization (CAD 1882.60 per month, P < .001).

Location and outcomes of rehospitalizations after critical illness in a single-payer healthcare system.

PURPOSE: Unplanned rehospitalization at a hospital other than the initial hospital may contribute to poor outcomes. We examined the location of rehospitalizations and assessed outcomes following critical illness in a single-payer healthcare system. MATERIALS AND METHODS: Population-based retrospective cohort study using linked datasets (2012-2017) from Ontario, Canada including adults (≥18 years) with an unplanned rehospitalization within 30-days after an index hospitalization that included an ICU stay with mechanical ventilation. Outcomes were the percentage of 30-day rehospitalizations at non-index hospitals, mortality and costs. We employed logistic regression and generalized linear models to assess associations. RESULTS: There were 14,997 (16.4%) 30-day rehospitalizations. Of these 2765 (18.4%) occurred in a non-index hospital. Distance of home residence from the index hospital was the strongest predictor of a non-index rehospitalization (adjusted odds ratio (aOR) 8.40, 95%CI 7.05-10.01, highest vs. lowest distance quintile). Within 30-days of rehospitalization, deaths (aOR 0.91, 95%CI (0.80-1.04)) and total healthcare costs (adjusted relative risk 1.03 (1.00-1.06)), were similar for patients readmitted to the index or a non-index hospital. CONCLUSION: Non-index rehospitalization within 30-days of initial discharge is common following critical illness. These rehospitalizations were not significantly associated with an increased risk of harm or higher costs in a single-payer healthcare system.

First-Line Vasopressor Use in Septic Shock and Route of Administration: An Epidemiologic Study.

Rationale: Norepinephrine is a first-line agent for the treatment of hypotension in septic shock. However, its frequency of use and potential barriers to its use are unclear. Objectives: To evaluate the frequency of use of norepinephrine in septic shock, to identify potential barriers to its use, and to evaluate trends in use of vasopressors over time. Methods: We conducted a retrospective population-based cohort study of patients with septic shock in Alberta, Canada, between July 1, 2012, and December 31, 2018. The primary outcome was receipt of a first-line vasopressor other than norepinephrine ("nonnorepinephrine vasopressor"). Predictors of receiving a nonnorepinephrine vasopressor were assessed using a multivariable-adjusted, multilevel logistic regression model with intensive care unit as a random effect. Results: Among 6,343 patients with septic shock, the proportion of patients receiving nonnorepinephrine vasopressors as first-line treatment decreased steadily from 11.5% in 2012 to 3.0% in 2018. Two factors most strongly associated with their receipt were having peripheral intravenous access only (adjusted odds ratio [aOR], 6.15; 95% confidence interval [CI], 4.58-8.26; P < 0.001) and year of admission (aOR, 0.74 per year after 2012; 95% CI, 0.69-0.80; P < 0.001). Other factors that had associations after adjustment included admission to a nonteaching hospital (aOR, 2.19; 95% CI, 1.23-3.89; P = 0.007), admission to a coronary care unit (aOR, 2.56; 95% CI, 1.001-6.54; P = 0.05), Sequential Organ Failure Assessment score (aOR, 0.92 per unit increase; 95% CI, 0.88-0.96; P < 0.001), and heart rate (aOR, 0.92 per 10-beat per minute increase; 95% CI, 0.87-0.97; P = 0.002). Conclusions: In a large cohort of patients in Alberta, Canada, we found a steady decrease in use of first-line vasopressors other than norepinephrine in septic shock. The strongest factor associated with their use was the presence of only peripheral venous access, suggesting that this may still be considered a barrier to administration of norepinephrine.

Trends in postoperative opioid prescribing in Ontario between 2013 and 2019: a population-based cohort study.

PURPOSE: Many hospital and provincial-level recommendations now advise a tailored approach to postoperative opioid prescribing; recent trends in postoperative prescribing at the population level have not been well described. METHODS: This population-based cohort study included opioid-naïve patients ≥ 18 yr of age who underwent one of 16 surgical procedures with varying anticipated postoperative pain between July 2013 and March 2020. We evaluated the rate of filled opioid prescriptions within seven days postoperatively, the total morphine milligram equivalent (MME) dose, duration, and type of the first opioid prescription. We then compared the MMEs in initial opioid prescriptions with available procedure-specific recommendations. RESULTS: The sample included 900,989 opioid-naïve patients (mean [standard deviation (SD)] age of 50 [17] 31 yr; 66% women). The percentage of patients filling an opioid prescription within 7 days postoperatively increased from 65% in 2013 to 69% in 2016, and returned to the baseline (65%) in 2019. The mean (SD) MMEs dispensed increased until 2015/2016 and then declined (226 [176] MMEs in 2013, 240 [202] MMEs in 2016, and 175 [175] MMEs in 2019). The most frequently prescribed opioid in 2013 was oxycodone compared with hydromorphone in 2019. Among patients who filled an opioid prescription in 2013, 67% were prescribed an opioid dose higher than those in one set of available prescribing recommendations, while in 2019, 41% were prescribed doses above those stated in recommendations. CONCLUSION: While the proportion of patients filling an opioid prescription postoperatively remained s during the study period, MMEs decreased after 2016. Opioid prescribing remained significantly higher than available prescribing recommendations, particularly among low pain procedures. These findings highlight the need to identify strategies that improve adherence to surgery-specific prescribing guidelines in North America.

RéSUMé: OBJECTIF: De nombreuses recommandations à l'échelle hospitalière et provinciale préconisent aujourd'hui une approche personnalisée de la prescription d'opioïdes postopératoires; les tendances récentes de la prescription postopératoire au niveau de la population n'ont pas été bien décrites. MéTHODE: Cette étude de cohorte basée sur la population englobait des patients naïfs aux opioïdes et âgés de ≥ 18 ans ayant bénéficié de l'une de 16 interventions chirurgicales entraînant une douleur postopératoire anticipée variable entre juillet 2013 et mars 2020. Nous avons évalué le taux d'ordonnances d'opioïdes remplies dans les sept jours suivant l'opération, la dose totale d'équivalent en milligrammes de morphine (EMM), ainsi que la durée et le type de la première ordonnance d'opioïdes. Nous avons ensuite comparé les EMM des ordonnances initiales d'opioïdes avec les recommandations spécifiques à l'intervention disponibles. RéSULTATS: L'échantillon comprenait 900 989 patients naïfs aux opioïdes (âge moyen [écart type (ET)] de 50 [17] ans; 66 % de femmes). La proportion de patients remplissant une ordonnance d'opioïdes dans les 7 jours suivant l'opération est passée de 65 % en 2013 à 69 % en 2016, et est revenue à la valeur de référence (65 %) en 2019. Les EMM moyens (ET) administrés ont augmenté jusqu'en 2015-2016, puis ont diminué (226 [176] EMM en 2013, 240 [202] EMM en 2016 et 175 [175] EMM en 2019). L'opioïde le plus fréquemment prescrit en 2013 était l'oxycodone par rapport à l'hydromorphone en 2019. Parmi les patients qui ont rempli une ordonnance d'opioïdes en 2013, 67 % se sont vu prescrire une dose d'opioïdes supérieure à celle d'un ensemble de recommandations de prescription disponibles, tandis qu'en 2019, 41 % se sont vu prescrire des doses supérieures à celles indiquées dans les recommandations. CONCLUSION: Alors que la proportion de patients remplissant une ordonnance d'opioïdes en période postopératoire est restée stable au cours de la période d'étude, les EMM ont diminué après 2016. La prescription d'opioïdes est demeurée beaucoup plus élevée que les recommandations de prescription disponibles, en particulier dans le cas d'interventions à faible douleur. Ces résultats soulignent la nécessité d'identifier des stratégies pour améliorer l'adhérence aux recommandations de prescription spécifiques au type de chirurgie en Amérique du Nord.

Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice.

With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. They are also more prone to substance use disorder in adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence (Experiment 1) and during emerging adulthood (Experiment 2). The present set of experiments were divided into four stages: (1) adolescent intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using intermittent vapor inhalation from postnatal day (PND) 28-42. Following this, mice underwent short-term abstinence from PND 43-49 (Experiment 1) or protracted abstinence from PND 43-69 (Experiment 2). Beginning on PND 50-76 or PND 70-97, mice were assessed for intermittent voluntary ethanol consumption using a two-bottle choice drinking procedure over 28 days. Male adolescent ethanol-exposed mice showed increased ethanol consumption following short-term abstinence and following protracted abstinence. In contrast, female mice showed no changes in ethanol consumption following short-term abstinence and decreased ethanol consumption following protracted abstinence. There were modest changes in open field behavior following voluntary ethanol consumption in both experiments. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These results highlight sex-dependent vulnerability to developing substance use disorders in adulthood.

In vitro development of mechanically and enzymatically isolated cat ovarian follicles.

Isolation of ovarian follicles is a key step in culture systems for large mammalian species to promote the continued growth of follicles beyond the preantral stage in fertility preservation efforts. Still, mechanical isolation methods are user-skill dependent and time-consuming, whereas enzymatic strategies carry increased risk of damaging theca cell layers and the basement membranes. Here, we sought to determine an optimal method to rescue domestic cat (Felis catus) early antral and antral stage follicles from ovarian tissue and to evaluate the influence of isolation strategy on follicle development, survival, and gene expression during 14 days of in vitro culture in alginate hydrogel. Mechanical isolation was compared with 90 min digestion in 0.7 and 1.4 Wünsch units/mL Liberase blendzyme (0.7L and 1.4L, respectively). Mechanical isolation resulted in improved follicle growth and survival, and better antral cavity and theca cell maintenance in vitro, compared with 1.4L (P < 0.05) but displayed higher levels of apoptosis after incubation compared with enzymatically isolated follicles. However, differences in follicle growth and survival were not apparent until 7+ days in vitro. Expressions of CYP19A1, GDF9, LHR, or VEGFA were similar among isolation-strategies. Cultured follicles from all isolation methods displayed reduced STAR expression compared with freshly isolated follicles obtained mechanically or via 0.7L, suggesting that prolonged culture resulted in loss of theca cell presence and/or function. In sum, early antral and antral stage follicle development in vitro is significantly influenced by isolation strategy but not necessarily observable in the absence of extended culture. These results indicate that additional care must be taken in follicle isolation optimizations for genome rescue and fertility preservation efforts.

Acute healthcare resource utilization by age: A cohort study.

BACKGROUND: Granular data related to the likelihood of individuals of different ages accessing acute and critical care services over time is lacking. METHODS: We used population-based, administrative data from Ontario to identify residents of specific ages (20, 30, 40, etc. to 100) on January 1st every year from 1995-2019. We assessed rates of emergency department (ED) visits (2003-19), hospitalizations, intensive care unit (ICU) admissions (2003-19), and mechanical ventilation. FINDINGS: Overall the 25-year study period, ED were the most common acute healthcare encounter with 100-year-olds having the lowest rate (138.7/1,000) and 90-year-olds the highest (378.5/1,000). Rates of hospitalization ranged from 24.2/1,000 for those age 20 up to 224.9/1,000 for those age 90. Rates of ICU admission and mechanical ventilation were lowest for those age 20 (1.0 and 0.4/1,000), more than tripled by age 50 (3.3 and 1.7/1,000) and peaked at age 80 (20.3 and 10.1/1,000). Over time rates of ED visits increased (164.3 /1,000 in 2003 vs 199.1 /1,000 in 2019) as did rates of invasive mechanical ventilation (2.0/1,000 in 1995 vs 2.9/1,000 in 2019), whereas rates of ICU admission remained stable (4.8/1,000 in 2003 vs 4.9/1,000 in 2019) and hospitalization declined (66.8/1,000 in 1995 vs 51.5/1,000 in 2019). Age stratified analysis demonstrated that rates of ED presentation increased for those age 70 and younger while hospitalization decreased for all age groups; ICU admission and mechanical ventilation rates changed variably by age, with increasing rates demonstrated primarily among people under the age of 50. INTERPRETATION: Rates of hospitalizations have decreased over time across all age groups, whereas rates of ED presentation, ICU admissions, and mechanical ventilation have increased, primarily driven by younger adults. These findings suggest that although the delivery of healthcare may be moving away from inpatient medicine, there is a growing population of young adults requiring significant healthcare resources.

Thymic development of gut-microbiota-specific T cells.

Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3-5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.

Meaningful Engagement Among Assisted Living Residents With Dementia: Successful Approaches.

Meaningful engagement is an important dimension of quality of life and care for persons living with dementia, including the growing number who reside in assisted living communities. This report presents preliminary findings from an ongoing qualitative study aimed at identifying best care practices to create and maintain meaningful engagement among persons with dementia. Over a 1-year period, we conducted interviews, residents' record review, and participant observations in four diverse care communities. Our analysis identified four approaches that successfully promote meaningful engagement: (a) knowing the person, (b) connecting with and meeting people where they are, (c) being in the moment, and (d) viewing all encounters as opportunity. Incorporation of these approaches in care routines and adoption by all care partners can promote meaningful engagement, including during crises such as COVID-19.

Effect of Anti-seizure Medications on Functional Anatomy of Language: A Perspective From Language Functional Magnetic Resonance Imaging.

Background: In epilepsy, cognitive difficulties are common, partly a consequence of anti-seizure medications (ASM), and cognitive side-effects are often considered to be more disabling than seizures and significantly affect quality of life. Functional MRI during verbal fluency tasks demonstrated impaired frontal activation patterns and failed default mode network deactivation in people taking ASM with unfavourable cognitive profiles. The cognitive effect of ASMs given at different dosages in monotherapy, or in different combinations, remains to be determined. Methods: Here, we compared the effects of different drug loads on verbal fluency functional MRI (fMRI) in people (i) taking dual therapy of ASMs either considered to be associated with moderate (levetiracetam, lamotrigine, lacosamide, carbamazepine/oxcarbazepine, eslicarbazepine, valproic acid; n = 119, 56 females) or severe (topiramate, zonisamide) side-effects; n = 119, 56 females), (ii) taking moderate ASMs in either mono-, dual- or triple-therapy (60 subjects in each group), or (iii) taking different dosages of ASMs with moderate side-effect profiles (n = 180). "Drug load" was defined as a composite value of numbers and dosages of medications, normalised to account for the highest and lowest dose of each specific prescribed medication. Results: In people taking "moderate" ASMs (n = 119), we observed higher verbal-fluency related to left inferior frontal gyrus and right inferior parietal fMRI activations than in people taking "severe" ASMs (n = 119). Irrespective of the specific ASM, people on monotherapy (n = 60), showed greater frontal activations than people taking two (n = 60), or three ASMs (n = 60). People on two ASMs showed less default mode (precuneus) deactivation than those on monotherapy. In people treated with "moderate" ASMs (n = 180), increased drug load correlated with reduced activation of language-related regions and the right piriform cortex. Conclusion: Our study delineates the effects of polytherapy and high doses of ASMs when given in monotherapy on the functional anatomy of language. Irrespective of the cognitive profile of individual ASMs, each additional ASM results in additional alterations of cognitive activation patterns. Selection of ASMs with moderate cognitive side effects, and low doses of ASMs when given in polytherapy, could reduce the cognitive effect.