Racial Disparities in Newborn Drug Testing After Implementation of Question-Based Screening for Prenatal Substance Use.

OBJECTIVE: To examine the association of universal question-based screening for prenatal substance use on racial inequities in prenatal and newborn drug testing. METHODS: We conducted a retrospective cohort study of 32,802 live births of patients receiving prenatal care at an academic medical center in the midwestern United States from 2014 to 2022, before and after implementation of question-based screening in 2018. Primary outcomes included prenatal and newborn drug test orders. Logistic regression models using a generalized estimating equation framework assessed associations with question-based screening and results, birthing parent age, race, ethnicity, marital status, and insurance type. Charts of patients who indicated difficulties stopping substance use were audited for guideline-directed care. RESULTS: A total of 12,725 of 14,992 pregnant people (85.3%) received question-based screening. Implementation of question-based screening was associated with a decrease in prenatal urine test orders (5.0% [95% CI, 4.6-5.3%] before implementation, 3.1% [95% CI, 2.8-3.4%] after implementation; P<.001), with Black birthing parents having the largest reduction in prenatal urine drug testing (10.3% [95% CI, 9.0-11.7%] before implementation, 4.9% [95% CI, 3.9-5.9%] after implementation). However, rates of newborn drug testing did not change (4.7% [95% CI, 4.4-5.0%] before implementation, 4.5% [95% CI, 4.2-4.8%] after implementation; P=.46), and clinicians continued to order significantly more newborn drug tests for newborns of Black birthing parents compared with other race and ethnicity groups. CONCLUSION: Implementation of question-based screening for substance use in pregnancy was associated with decreased prenatal urine drug testing but no change in overall newborn drug testing or racial inequities in newborn drug testing for Black birthing people. Further policy efforts are warranted to improve substance use treatment and to eliminate racial inequities in punitive policies such as newborn drug testing and subsequent child protective services reporting.

Perspectives of adolescents and young adults on cannabis use during pregnancy.

PURPOSE: Rates of cannabis use during pregnancy are highest for adolescents and young adults (AYAs). This study aims to understand AYA perspectives regarding the medical and legal consequences of prenatal and parental cannabis use. METHODS: This study delivered five open-ended survey questions regarding prenatal cannabis use in May/June 2022 via a text message polling platform to the MyVoice cohort, a cohort of AYA aged 14-24 throughout the United States recruited from social media to target national benchmarks set by the American Community Survey. We used qualitative content analysis to analyze open-ended responses and summarized code frequency and demographic data with descriptive statistics. RESULTS: Of 826 AYAs, 666 responded to at least one question (response rate = 80.6 %) and the mean age of respondents was 19.9 years (SD = 2.3). We identified four themes from responses: (1) AYA believe cannabis is harmful during pregnancy, (2) they are divided on whether prenatal cannabis exposure should be considered child abuse or neglect, (3) they have mixed attitudes about safe parenting and regular cannabis use, and (4) they support counseling from health care professionals about prenatal cannabis use. CONCLUSIONS: AYAs were concerned about potential risks of prenatal cannabis exposure and want clinicians to counsel about cannabis use during pregnancy. More than one in three AYAs surveyed felt prenatal cannabis use should be classified as child abuse or neglect, in contrast to the declining perception of risk among pregnant people.

Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

GraphT-T (V1.0Beta), a program for embedding and visualizing periodic graphs in 3D Euclidean space.

Following the work of Day & Hawthorne [Acta Cryst. (2022), A78, 212-233] and Day et al. [Acta Cryst. (2024), A80, 258-281], the program GraphT-T has been developed to embed graphical representations of observed and hypothetical chains of (SiO4)4- tetrahedra into 2D and 3D Euclidean space. During embedding, the distance between linked vertices (T-T distances) and the distance between unlinked vertices (T...T separations) in the resultant unit-distance graph are restrained to the average observed distance between linked Si tetrahedra (3.06±0.15 Å) and the minimum separation between unlinked vertices is restrained to be equal to or greater than the minimum distance between unlinked Si tetrahedra (3.713 Å) in silicate minerals. The notional interactions between vertices are described by a 3D spring-force algorithm in which the attractive forces between linked vertices behave according to Hooke's law and the repulsive forces between unlinked vertices behave according to Coulomb's law. Embedding parameters (i.e. spring coefficient, k, and Coulomb's constant, K) are iteratively refined during embedding to determine if it is possible to embed a given graph to produce a unit-distance graph with T-T distances and T...T separations that are compatible with the observed T-T distances and T...T separations in crystal structures. The resultant unit-distance graphs are denoted as compatible and may form crystal structures if and only if all distances between linked vertices (T-T distances) agree with the average observed distance between linked Si tetrahedra (3.06±0.15 Å) and the minimum separation between unlinked vertices is equal to or greater than the minimum distance between unlinked Si tetrahedra (3.713 Å) in silicate minerals. If the unit-distance graph does not satisfy these conditions, it is considered incompatible and the corresponding chain of tetrahedra is unlikely to form crystal structures. Using GraphT-T, Day et al. [Acta Cryst. (2024), A80, 258-281] have shown that several topological properties of chain graphs influence the flexibility (and rigidity) of the corresponding chains of Si tetrahedra and may explain why particular compatible chain arrangements (and the minerals in which they occur) are more common than others and/or why incompatible chain arrangements do not occur in crystals despite being topologically possible.

Bond topology of chain, ribbon and tube silicates. Part II. Geometrical analysis of infinite 1D arrangements of (TO4)n- tetrahedra.

In Part I of this series, all topologically possible 1-periodic infinite graphs (chain graphs) representing chains of tetrahedra with up to 6-8 vertices (tetrahedra) per repeat unit were generated. This paper examines possible restraints on embedding these chain graphs into Euclidean space such that they are compatible with the metrics of chains of tetrahedra in observed crystal structures. Chain-silicate minerals with T = Si4+ (plus P5+, V5+, As5+, Al3+, Fe3+, B3+, Be2+, Zn2+ and Mg2+) have a grand nearest-neighbour ⟨T-T⟩ distance of 3.06±0.15 Šand a minimum T...T separation of 3.71 Šbetween non-nearest-neighbour tetrahedra, and in order for embedded chain graphs (called unit-distance graphs) to be possible atomic arrangements in crystals, they must conform to these metrics, a process termed equalization. It is shown that equalization of all acyclic chain graphs is possible in 2D and 3D, and that equalization of most cyclic chain graphs is possible in 3D but not necessarily in 2D. All unique ways in which non-isomorphic vertices may be moved are designated modes of geometric modification. If a mode (m) is applied to an equalized unit-distance graph such that a new geometrically distinct unit-distance graph is produced without changing the lengths of any edges, the mode is designated as valid (mv); if a new geometrically distinct unit-distance graph cannot be produced, the mode is invalid (mi). The parameters mv and mi are used to define ranges of rigidity of the unit-distance graphs, and are related to the edge-to-vertex ratio, e/n, of the parent chain graph. The program GraphT-T was developed to embed any chain graph into Euclidean space subject to the metric restraints on T-T and T...T. Embedding a selection of chain graphs with differing e/n ratios shows that the principal reason why many topologically possible chains cannot occur in crystal structures is due to violation of the requirement that T...T > 3.71 Å. Such a restraint becomes increasingly restrictive as e/n increases and indicates why chains with stoichiometry TO<2.5 do not occur in crystal structures.

High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes.

Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto-Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (p < 0.05) reduced in Wistar diabetic rats and GK models fed on high-fat food. The co-localization study using immunofluorescence and TIEM techniques showed that HDL is detected alongside insulin within the secretory granules of ß-cells. HDL did not co-localize with glucagon. This observation implies that HDL may contribute to the metabolism of insulin.

Prescriptions for Buprenorphine in Michigan Following an Education Intervention.

Importance: Buprenorphine is an underused treatment for opioid use disorder (OUD) that can be prescribed in general medical settings. Founded in 2017, the Michigan Opioid Collaborative (MOC) is an outreach and educational program that aims to address clinician and community barriers to buprenorphine access; however, the association between the MOC and buprenorphine treatment is unknown. Objective: To evaluate the association between MOC service use and county-level temporal trends of density of buprenorphine prescribers and patients receiving buprenorphine. Design, Setting, and Participants: This cohort study exploited staggered implementation of MOC services across all Michigan counties. Difference-in-difference analyses were conducted by applying linear fixed-effects regression across all counties to estimate the overall association of MOC engagement with outcomes and linear regression for each MOC-engaged county separately to infer county-specific results using data from May 2015 to August 2020. Analyses were conducted from September 2021 to November 2023. Exposures: MOC engagement. Main Outcomes and Measures: County-level monthly numbers of buprenorphine prescribers and patients receiving buprenorphine (per 100 000 population). Results: Among 83 total counties, 57 counties (68.7%) in Michigan were engaged by MOC by 2020, with 3 (3.6%) initiating engagement in 2017, 19 (22.9%) in 2018, 27 (32.5%) in 2019, and 8 (9.6%) in 2020. Michigan is made up of 83 counties with a total population size of 9 990 000. A total of 5 070 000 (50.8%) were female, 1 410 000 (14.1%) were African American or Black, 530 000 (5.3%) were Hispanic or Latino, and 7 470 000 (74.7%) were non-Hispanic White. The mean (SD) value of median age across counties was 44.8 (6.4). The monthly increases in buprenorphine prescriber numbers in the preengagement (including all time points for nonengaged counties) and postengagement periods were 0.07 and 0.39 per 100 000 population, respectively, with the absolute difference being 0.33 (95% CI, 0.12-0.53) prescribers per 100 000 population (P = .002). The numbers of patients receiving buprenorphine increased by an average of 0.6 and 7.15 per 100 000 population per month in preengagement and postengagement periods, respectively, indicating an estimated additional 6.56 (95% CI, 2.09-11.02) patients receiving buprenorphine per 100 000 population (P = .004) monthly increase after engagement compared with before. Conclusions and Relevance: In this cohort study measuring buprenorphine prescriptions in Michigan over time, counties' engagement in OUD-focused outreach and clinician education services delivered by a multidisciplinary team was associated with a temporal increase in buprenorphine prescribers and patients receiving buprenorphine.

Social Determinants of Mental and Behavioral Health.

Both mental illness and overall mental health are determined by a complicated interplay of life experiences and genetic predisposition. While genetic predisposition is difficult to modify, many of the life experiences that worsen mental health and exacerbate serious mental illness are associated with social policies and cultural norms that are changeable. Now that we have identified these associations, it is time to rigorously test scalable interventions to address these risks. These interventions will need to focus on high-impact stages in life (like childhood) and will need to address risk beyond the individual by focusing on the family and community.

Programmable multispecific DNA-origami-based T-cell engagers.

Multispecific antibodies have emerged as versatile therapeutic agents, and therefore, approaches to optimize and streamline their design and assembly are needed. Here we report on the modular and programmable assembly of IgG antibodies, F(ab) and scFv fragments on DNA origami nanocarriers. We screened 105 distinct quadruplet antibody variants in vitro for the ability to activate T cells in the presence of target cells. T-cell engagers were identified, which in vitro showed the specific and efficient T-cell-mediated lysis of five distinct target cell lines. We used these T-cell engagers to target and lyse tumour cells in vivo in a xenograft mouse tumour model. Our approach enables the rapid generation, screening and testing of bi- and multispecific antibodies to facilitate preclinical pharmaceutical development from in vitro discovery to in vivo proof of concept.

Incidence of Newborn Drug Testing and Variations by Birthing Parent Race and Ethnicity Before and After Recreational Cannabis Legalization.

Importance: Thirty-seven US states and the District of Columbia mandate reporting newborns with suspected prenatal substance exposure to the state, and punitive policies that link prenatal substance exposure to newborn drug testing (NDT) may lead to disproportionate reporting of Black parents to Child Protective Services. The impact of recreational cannabis legalization on racial disproportionality in NDT is unknown. Objectives: To examine variations in the incidence and results of NDT by birthing parent race and ethnicity, variables associated with variation, and changes after statewide legalization of recreational cannabis. Design, Setting, and Participants: This retrospective cohort study was conducted from 2014 to 2020 with 26 366 live births to 21 648 birthing people who received prenatal care at an academic medical center in the Midwestern United States. Data were analyzed from June 2021 to August 2022. Exposures: Variables included birthing parent age, race, ethnicity, marital status, zip code, insurance type, prenatal and newborn diagnoses codes, and prenatal urine drug test orders and results. Main Outcome and Measures: The primary outcome was an NDT order. Secondary outcomes were substances detected. Results: Among 26 366 newborns of 21 648 birthing people (mean [SD] age at delivery, 30.5 [5.2] years), most birthing parents were White (15 338 [71.6%]), were non-Hispanic (20 125 [93.1%]), and had private insurance coverage (16 159 [74.8%]). The incidence of NDT ordering was 4.7% overall (1237 newborns). Clinicians ordered more NDTs for Black compared with White newborns (207 of 2870 [7.3%] vs 335 of 17 564 [1.9%]; P < .001) when the birthing parent had no prenatal urine drug test, a presumably low-risk group. Overall, 471 of 1090 NDTs (43.3%) were positive for only tetrahydrocannabinol (THC). NDTs were more likely to be positive for opioids in White compared with Black newborns (153 of 693 [22.2%] vs 29 of 308 [9.4%]; P < .001) and more likely to be positive for THC in Black compared with White newborns (207 of 308 [67.2%] vs 359 of 693 [51.8%]; P < .001). Differences remained consistent after state recreational cannabis legalization in 2018. Newborn drug tests were more likely to be positive for THC after legalization vs before legalization (248 of 360 [68.9%] vs 366 of 728 [50.3%]; P < .001) with no significant interaction with race and ethnicity groups. Conclusions and Relevance: In this study, clinicians ordered NDTs more frequently for Black newborns when no drug testing was done during pregnancy. These findings call for further exploration of how structural and institutional racism contribute to disproportionate testing and subsequent Child Protective Services investigation, surveillance, and criminalization of Black parents.

Exercise alleviates diabetic complications by inhibiting oxidative stress-mediated signaling cascade and mitochondrial metabolic stress in GK diabetic rat tissues.

Type 2 diabetes, obesity (referred to as "diabesity"), and metabolic syndrome associated with increased insulin resistance and/or decreased insulin sensitivity have been implicated with increased oxidative stress and inflammation, mitochondrial dysfunction, and alterations in energy metabolism. The precise molecular mechanisms of these complications, however, remain to be clarified. Owing to the limitations and off-target side effects of antidiabetic drugs, exercise-induced control of hyperglycemia and increased insulin sensitivity is a preferred strategy to manage "diabesity" associated complications. In this study, we have investigated the effects of moderate exercise (1 h/day, 5 days a week for 60 days) on mitochondrial, metabolic, and oxidative stress-related changes in the liver and kidney of type 2 diabetic Goto-Kakizaki (GK) rats. Our previous study, using the same exercise regimen, demonstrated improved energy metabolism and mitochondrial function in the pancreas of GK diabetic rats. Our current study demonstrates exercise-induced inhibition of ROS production and NADPH oxidase enzyme activity, as well as lipid peroxidation and protein carbonylation in the liver and kidney of GK rats. Interestingly, glutathione (GSH) content and GSH-peroxidase and GSH reductase enzymes as well as superoxide dismutase (SOD) activities were profoundly altered in diabetic rat tissues. Exercise helped in restoring the altered GSH metabolism and antioxidant homeostasis. An increase in cytosolic glycolytic enzyme, hexokinase, and a decrease in mitochondrial Kreb's cycle enzyme was observed in GK diabetic rat tissues. Exercise helped restore the altered energy metabolism. A significant decrease in the activities of mitochondrial complexes and ATP content was also observed in the GK rats and exercise regulated the activities of the respiratory complexes and improved energy utilization. Activation of cytochrome P450s, CYP 2E1, and CYP 3A4 was observed in the tissues of GK rats, which recovered after exercise. Altered expression of redox-responsive proteins and translocation of transcription factor NFκB-p65, accompanied by activation of AMP-activated protein kinase (AMPK), SIRT-1, Glut-4, and PPAR-γ suggests the induction of antioxidant defense responses and increased energy metabolism in GK diabetic rats after exercise.

Defining and supporting high-quality telehealth for patients with opioid use disorder: The promise and potential pitfalls of telehealth expansion.

Many patients with opioid use disorders do not receive evidence-based treatment. The COVID-19 pandemic expanded the use of telehealth for prescribing medications for opioid use disorder (OUD). The uptake of telehealth has been variable, and this uneven expansion has created natural experiments to test assumptions and answer key questions about what improves outcomes for patients with OUD. Many current quality of care measures are not patient centered and do not focus on the practical questions that clinicians face. What criteria should be met before prescribing buprenorphine? Are physical exams necessary? Does the frequency and type of drug testing predict clinical outcomes? Are short check-in visits by phone or video better than less frequent in-person visits? Answering these questions can help define the essential components of high-quality care for patients with OUD. Defining the features of high-quality care can help create guardrails that will help protect our patients from potentially exploitive and ineffective care. Telehealth will likely end up being one additional tool to deliver care, but the scientific questions that can be answered during this period of rapid change can help answer some of the fundamental questions about providing high-quality care-and that will help all our patients, no matter how care is delivered.

Capsaicin Inhibits Multiple Voltage-Gated Ion Channels in Rabbit Ventricular Cardiomyocytes in TRPV1-Independent Manner.

Capsaicin is a naturally occurring alkaloid derived from chili pepper which is responsible for its hot, pungent taste. It exerts multiple pharmacological actions, including pain-relieving, anti-cancer, anti-inflammatory, anti-obesity, and antioxidant effects. Previous studies have shown that capsaicin significantly affects the contractility and automaticity of the heart and alters cardiovascular functions. In this study, the effects of capsaicin were investigated on voltage-gated ion currents in rabbit ventricular myocytes. Capsaicin inhibited rapidly activated (IKr) and slowly activated (IKs) K+ currents and transient outward (Ito) K+ current with IC50 values of 3.4 µM,14.7 µM, and 9.6 µM, respectively. In addition, capsaicin, at higher concentrations, suppressed voltage-gated Na+ and Ca2+ currents and inward rectifier IK1 current with IC50 values of 42.7 µM, 34.9 µM, and 38.8 µM, respectively. Capsaicin inhibitions of INa, IL-Ca, IKr, IKs, Ito, and IK1 were not reversed in the presence of capsazepine (3 µM), a TRPV1 antagonist. The inhibitory effects of capsaicin on these currents developed gradually, reaching steady-state levels within 3 to 6 min, and the recoveries were usually incomplete during washout. In concentration-inhibition curves, apparent Hill coefficients higher than unity suggested multiple interaction sites of capsaicin on these channels. Collectively, these findings indicate that capsaicin affects cardiac electrophysiology by acting on a diverse range of ion channels and suggest that caution should be exercised when capsaicin is administered to carriers of cardiac channelopathies or to individuals with arrhythmia-prone conditions, such as ischemic heart diseases.

Effects of Isoprenaline on ventricular myocyte shortening and Ca2+ transport in the Zucker rat.

Obesity is an important risk factor for diabetes mellitus (DM) which is a major global health problem. Electro-mechanical dysfunction has been extensively described in diabetic heart and cardiovascular complications are an important cause of mortality and morbidity in diabetic patients. OBJECTIVES: To examine the effects of Isoprenaline (ISO) in obesity and diabesity on ventricular myocyte shortening and Ca2+ transport in Zucker fatty (ZF), Zucker diabetic fatty (ZDF) in comparison to Zucker lean (ZL) rats. METHODS: Myocyte shortening and intracellular Ca2+ were investigated with video imaging and fluorescence photometry, respectively. RESULTS: The amplitude of Isoprenaline stimulated shortening was significantly (p < 0.05) decreased in ZDF and ZF compared to ZL myocytes. The amplitude of Isoprenaline stimulated Ca2+ transient was also significantly (p < 0.05) reduced in ZF compared to ZL and modestly reduced in ZDF compared to ZL myocytes. Mean Isoprenaline stimulated time to peak along with time to half relaxation of shortening were unchanged in ZDF and ZF compared to ZL myocytes. Mean Isoprenaline stimulated time to peak Ca2+ transient was significantly shortened in ZF compared to ZL myocytes. Time to half decay of the Ca2+ transient was considerably prolonged in ZDF compared to ZL myocytes. Amplitude of Isoprenaline stimulated caffeine-evoked Ca2+ transients were significantly reduced in ZDF and ZF in comparison to ZL myocytes. CONCLUSION: Isoprenaline was less effective at generating an increase in the amplitude of shortening in ZDF and ZF in comparison to ZL myocytes and defects in Ca2+ signaling, and in particular SR Ca2+ transport, might partly underlie these abnormalities.

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat.

(1) Background: Cardiovascular complications are a leading cause of morbidity and mortality in diabetic patients. The effects of obesity and diabesity on the function and structure of ventricular myocytes in the Zucker fatty (ZF) rat and the Zucker diabetic fatty (ZDF) rat compared to Zucker lean (ZL) control rats have been investigated. (2) Methods: Shortening and intracellular Ca2+ were simultaneously measured with cell imaging and fluorescence photometry, respectively. Ventricular muscle protein expression and structure were investigated with Western blot and electron microscopy, respectively. (3) Results: The amplitude of shortening was increased in ZF compared to ZL but not compared to ZDF myocytes. Resting Ca2+ was increased in ZDF compared to ZL myocytes. Time to half decay of the Ca2+ transient was prolonged in ZDF compared to ZL and was reduced in ZF compared to ZL myocytes. Changes in expression of proteins associated with cardiac muscle contraction are presented. Structurally, there were reductions in sarcomere length in ZDF and ZF compared to ZL and reductions in mitochondria count in ZF compared to ZDF and ZL myocytes. (4) Conclusions: Alterations in ventricular muscle proteins and structure may partly underlie the defects observed in Ca2+ signaling in ZDF and ZF compared to ZL rat hearts.

Enabling Healthy Aging to AVOID Frailty in Community Dwelling Older Canadians.

The Canadian population is aging. With aging, biological and social changes occur increasing the risk of developing chronic conditions and functional loss leading to frailty. Older adults living with frailty are more vulnerable to minor stressors, take longer to recover from illness, and have difficulty participating in daily activities. The Canadian Frailty Network's (CFN) mission is to improve the lives of older adults living with frailty. In September 2019, CFN launched the Activity & Exercise, Vaccination, Optimization of medications, Interaction & Socialization, and Diet & Nutrition (AVOID) Frailty public health campaign to promote assessing and reducing risk factors leading to the development of frailty. As part of the campaign, CFN held an Enabling Healthy Aging Symposium with 36 stakeholders from across Canada. Stakeholders identified individual and community-level opportunities and challenges for the enablement of healthy aging and frailty mitigation, as part of a focused consultative process. Stakeholders ranked the three most important challenges and opportunities at the individual and community levels for implementing AVOID Frailty recommendations. Concrete actions, further research areas, policy changes, and existing resources/programs to enhance the AVOID Frailty campaign were identified. The results will help inform future priorities and behaviour change strategies for healthy aging in Canada.

Bond topology of chain, ribbon and tube silicates. Part I. Graph-theory generation of infinite one-dimensional arrangements of (TO4)n- tetrahedra.

Chain, ribbon and tube silicates are based on one-dimensional polymerizations of (TO4)n- tetrahedra, where T = Si4+ plus P5+, V5+, As5+, Al3+, Fe3+ and B3+. Such polymerizations may be represented by infinite graphs (designated chain graphs) in which vertices represent tetrahedra and edges represent linkages between tetrahedra. The valence-sum rule of bond-valence theory limits the maximum degree of any vertex to 4 and the number of edges linking two vertices to 1 (corner-sharing tetrahedra). The unit cell (or repeat unit) of the chain graph generates the chain graph through action of translational symmetry operators. The (infinite) chain graph is converted into a finite graph by wrapping edges that exit the unit cell such that they link to vertices within the unit cell that are translationally equivalent to the vertices to which they link in the chain graph, and the wrapped graph preserves all topological information of the chain graph. A symbolic algebra is developed that represents the degree of each vertex in the wrapped graph. The wrapped graph is represented by its adjacency matrix which is modified to indicate the direction of wrapped edges, up (+c) or down (-c) along the direction of polymerization. The symbolic algebra is used to generate all possible vertex connectivities for graphs with ≤8 vertices. This method of representing chain graphs by finite matrices may now be inverted to generate all non-isomorphic chain graphs with ≤8 vertices for all possible vertex connectivities. MatLabR2019b code is provided for computationally intensive steps of this method and ∼3000 finite graphs (and associated adjacency matrices) and ∼1500 chain graphs are generated.

Alterations in Energy Metabolism, Mitochondrial Function and Redox Homeostasis in GK Diabetic Rat Tissues Treated with Aspirin.

Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated the mechanism of action of aspirin in maintaining mitochondrial bioenergetics and redox metabolism in the liver and kidneys of GK rats. Aspirin reduced the production of reactive oxygen species (ROS) and oxidative stress-induced changes in GSH metabolism. Aspirin treatment also improved mitochondrial respiratory function and energy metabolism, in addition to regulating the expression of cell signaling proteins that were altered in diabetic animals. Ultrastructural electron microscopy studies revealed decreased accumulation of glycogen in the liver of aspirin-treated diabetic rats. Hypertrophic podocytes with irregular fusion of foot processes in the renal glomerulus and detached microvilli, condensed nuclei and degenerated mitochondria observed in the proximal convoluted tubules of GK rats were partially restored by aspirin. These results provide additional evidence to support our previous observation of moderation of diabetic complications by aspirin treatment in GK rats and may have implications for cautious use of aspirin in the therapeutic management of diabetes.