Family Chair Research Articles

Simple Maneuver to Improve TriClip Eligibility in Patients With Cardiac Implantable Electronic Device Leads.

HomeCirculation: Cardiovascular InterventionsVol. 16, No. 6Simple Maneuver to Improve TriClip Eligibility in Patients With Cardiac Implantable Electronic Device Leads No AccessCase ReportRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessCase ReportRequest AccessFull TextSimple Maneuver to Improve TriClip Eligibility in Patients With Cardiac Implantable Electronic Device Leads Paul Sorajja, Yashasvi Chugh, Marcus Burns, Nadira Hamid and Richard Bae Paul SorajjaPaul Sorajja Correspondence to: Paul Sorajja, MD, Roger and Lynn Headrick Family Chair, Valve Science Center, Minneapolis Heart Institute Foundation, 920 E 28th St, Ste 200, Minneapolis, MN, 55417. Email E-mail Address: [email protected] https://orcid.org/0000-0001-6401-854X Valve Science Center, Minneapolis Heart Institute Foundation, MN. Allina Health Minneapolis Heart Institute at AbbottNorthwestern Hospital, MN. Search for more papers by this author , Yashasvi ChughYashasvi Chugh https://orcid.org/0000-0001-9724-9088 Valve Science Center, Minneapolis Heart Institute Foundation, MN. Allina Health Minneapolis Heart Institute at AbbottNorthwestern Hospital, MN. Search for more papers by this author , Marcus BurnsMarcus Burns Valve Science Center, Minneapolis Heart Institute Foundation, MN. Allina Health Minneapolis Heart Institute at AbbottNorthwestern Hospital, MN. Search for more papers by this author , Nadira HamidNadira Hamid Valve Science Center, Minneapolis Heart Institute Foundation, MN. Allina Health Minneapolis Heart Institute at AbbottNorthwestern Hospital, MN. Search for more papers by this author and Richard BaeRichard Bae Valve Science Center, Minneapolis Heart Institute Foundation, MN. Allina Health Minneapolis Heart Institute at AbbottNorthwestern Hospital, MN. Search for more papers by this author Originally published20 Jun 2023https://doi.org/10.1161/CIRCINTERVENTIONS.123.012950Circulation: Cardiovascular Interventions. 2023;16FootnotesFor Sources of Funding and Disclosures, see page 400.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCINTERVENTIONS.123.012950.Correspondence to: Paul Sorajja, MD, Roger and Lynn Headrick Family Chair, Valve Science Center, Minneapolis Heart Institute Foundation, 920 E 28th St, Ste 200, Minneapolis, MN, 55417. Email paul.[email protected]com Previous Back to top Next FiguresReferencesRelatedDetails June 2023Vol 16, Issue 6 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.123.012950PMID: 37339235 Originally publishedJune 20, 2023 KeywordsinterferencecatheterheartfemaleelectronicsPDF download Advertisement SubjectsCatheter-Based Coronary and Valvular Interventions

High-intensity focused ultrasound ablation increases lymphocyte infiltration in mouse prostate tumor

Abstract Introduction and Objective: High-Intensity Focused Ultrasound (HIFU) is an FDA-approved procedure for the treatment of localized prostate cancer. HIFU destroys tumor tissue by noninvasively delivering ultrasonic energy, which rapidly heats the targeted tissue. Prostate cancer has few tumor-infiltrating lymphocytes, which are required for antitumor immunity. The objective of this study was to determine if HIFU activates antitumor immunity and increases lymphocyte infiltration into the tumor. Methods: RM1 tumors were grown on the flanks of syngeneic C57BL/6J mice and one tumor was treated with HIFU. Contralateral tumor growth was monitored, and tumors were collected at the end of the study to assess immune cell infiltration. Tumor infiltrating lymphocytes were assess by flow cytometry. Results: When one tumor was treated with HIFU, the growth of the contralateral (untreated) tumor decreased when the contralateral tumor was the same tumor type but not when it was a different tumor type. HIFU increased CD4 +and CD8 +lymphocyte infiltration into the contralateral (untreated) tumor. Depletion studies confirmed that the antitumor immune effect of HIFU is CD4 +and CD8 +lymphocyte dependent. Conclusions: In preclinical models, HIFU generates an antitumor immune response capable of suppressing the growth of mouse prostate tumors. The antitumor immune effect of HIFU is CD4 +and CD8 +lymphocyte dependent. Future studies should investigate mouse models of metastatic prostate cancer, where cytoreductive prostate tumor ablation can be combined with systemic immunotherapies to generate robust antitumor immunity. Homer and Gloria Harvey Family Chair Fund in urologic oncology in honor of Stuart Friedman, M.D.

Gut Microbiota of 13 Years Old Children Is Associated With BMI- and Height- For-Age Growth Patterns Since Birth

ObjectivesThe relationship between gut microbiota and growth during infancy has been substantiated, but whether this stands true in later childhood is under investigation. We used a new clustering methodology that improves interpretability of later childhood growth patterns. Three distinct patterns were identified (Increasing, Stable, Declining) for BMI-for-age (BMIZ) and height-for-age Z-scores (HAZ) in a birth cohort of 4231 Brazilian children. Here, we investigate the association between these growth patterns and gut microbiota diversity in late childhood. MethodsWe sampled 337 children from the 2004 Pelotas birth cohort (Brazil) grouped into Increasing (n = 78; 68), Stable (n = 161; 170), or Declining (n = 98; 99) patterns for BMIZ and HAZ, respectively. Feces and anthropometrics were collected at age 13 years. The fecal microbiota was analyzed via Illumina MiSeq (16S rRNA V3-V4 region) and the UNOISE pipeline. Alpha (Kruskal-Wallis) and beta (permutational multivariate analysis of variance) diversity were assessed in QIIME2. ResultsThe microbiota of children in the BMIZ Increasing pattern had lower richness and evenness compared to those in the Stable or Decreasing patterns (Chao1, q < 0.01; Shannon, q < 0.01). Beta diversity also differed between the Increasing vs Stable and Decreasing patterns (Jaccard, q < 0.03; Unweighted UNIFRAC, q < 0.009) but not if using abundance-normalized indices (Bray-Curtis and Weighted UNIFRAC). While alpha diversity did not differ with HAZ patterns, beta diversity did show differences between the Increasing vs Stable and Decreasing patterns (Jaccard, q < 0.006; Bray-Curtis, q < 0.01). ConclusionsIncreasing BMIZ and HAZ patterns during childhood are associated with a distinct microbiota structure at age 13, which is likely driven by less abundant organisms for BMIZ but not for HAZ. Overall, the gut microbiota seems to be related to markers of obesity in late childhood growth. Funding SourcesJoannah and Brian Lawson Centre for Child Nutrition, Lawson Family Chair in Microbiome Nutrition Research, CONACyT scholarship. The Wellcome Trust, World Health Organization, National Support Program for Centers of Excellence, Brazilian National Research Council, Brazilian Ministry of Health, and Children’s Pastorate.

Influence of Gestational Age Correction and Shape-Based Trajectories in the Identification of Children’s Growth Patterns From Birth to 11 Years

ObjectivesChildhood growth reflects nutritional status such as under- or overnutrition and is a determinant of life health. Thus, early detection of sub-optimal growth patterns can help identify modifiable risk factors. Current approaches rely on the trajectory intercept and struggle to capture differences in trajectory shape, which better reflects change over time. This study implemented a novel approach to identify shape-based growth patterns in children from birth to 11 years of age. MethodsWe used anthropometric measures from 3,945 children at postnatal age 3 months, 1, 2, 4, 6 and 11 years from the 2004 Pelotas Birth Cohort (Brazil). Weight-, height- and BMI-for-age Z-scores were calculated using INTERGROWTH21st and WHO growth standards. The impact of gestational age-correction (CA) in preterm-born children (n = 461) was tested, and trajectories were either baseline anchored at zero or not. This produced 4 analytical pipelines for pattern detection (k-means, Frechet’s distance): 1) no CA–no baseline anchoring; 2) no CA–with baseline anchoring; 3) with CA–no baseline anchoring; 4) with CA–with baseline anchoring. ResultsWe found 3 patterns for each Z-score, with “High” (increasing), “Middle” (stable) and “Low” (declining) trajectories. The use of both CA and baseline anchoring highlighted sub-groups of children with specific patterns related to early growth (first 3 months of life). In the non-anchored approach, CA influenced the mean trajectories detected by increasing the intercept and reducing the slope between birth and 3 months. Baseline anchoring identified mean trajectories with steeper slopes during this period, thus, capturing differential growth patterns in early life. ConclusionsDepending on the question, incorporating CA with or without baseline anchoring when analyzing growth patterns can better highlight aspects of early growth versus overall patterns across childhood and can improve growth analyses standardization in population-based studies. Funding SourcesJoannah and Brian Lawson Centre for Child Nutrition, Lawson Family Chair in Microbiome Nutrition Research, CONACyT scholarship, Wellcome Trust, World Health Organization, National Support Program for Centers of Excellence, Brazilian National Research Council, Brazilian Ministry of Health, and Children’s Pastorate.

Ralph L. Sacco, 65, Dies

![Graphic][1]</img> Ralph L. Sacco, MD, MS, FAAN, FAHA, the only physician to have served as both the president of the American Heart Association (AHA) and the American Academy of Neurology (AAN), the first neurologist to serve as president of the AHA, and an expert on stroke risk and prevention, died January 17, 2023, of a brain tumor at his home in Long Island, NY. The founder of the Northern Manhattan Study, a professor of neurology, public health sciences, human genetics, and neurosurgery at the University of Miami's Miller School of Medicine and the Olemberg Family Chair in Neurological Disorders, he was 65. For Dr. Sacco, who grew up in Margate City, NJ, 3 blocks from the Jersey shore, there was no more peaceful place than the beach. After settling in New York to do his residency in neurology in 1983 at Columbia Presbyterian Hospital, he began to spend his free time in the Hamptons where he developed a zeal for boating, interior design, and architecture. The eldest of 5 children, Dr. Sacco occasionally worked in the family business, Sack O′ Subs, cutting cold cuts and stacking steaks. “I didn't like working around food because I ate too much,” he would later confess, adding that he preferred his paper route, except when being chased by dogs. He set his sights on medicine after an aunt suggested that he would be well-suited for the career. Growing up in the disco era, he and his sister, Bess, 2 years his junior, would frequent the dance clubs in Atlantic City and Wildwood, NJ, along with mutual friends. Few people knew that he was skilled at freestyle—save those who later invited him to their weddings, and the close friends that he called his chosen family who accompanied him and his husband, Scott Dutcher, on coastal vacations … [1]: /embed/inline-graphic-1.gif

Ralph L. Sacco, 65, Dies: Stroke Expert With a Talent for Architectural Design.

Ralph L. Sacco, 65, Dies: Stroke Expert With a Talent for Architectural Design.

Ralph L. Sacco, 65, Dies: Stroke Expert With a Talent for Architectural Design.

Ralph L. Sacco, 65, Dies: Stroke Expert With a Talent for Architectural Design.

Symbolic Shareholder Democracy: Toward a Behavioral Understanding of the Role of Shareholder Voting in CEO Dismissals

We investigate the effect of expressive shareholder dissent voting, in which shareholders use their votes symbolically to express their discontent with management, on subsequent chief executive officer (CEO) dismissals. Using the routine but highly symbolic executive board discharge proposal voted on at the annual shareholder meetings of German firms, we argue that the board of directors understands these votes as a “vote of confidence in management” that challenges the CEO’s mandate to lead the firm. Arguing that board chairs are uniquely positioned to take up the stance of a steward of the firm and its leadership, we examine how independent and family board chairs moderate the board’s response to expressive voting dissent. Using a sample of German public firms over the period 2008–2015, we find that expressive voting dissent increases the chance of CEO dismissal increasingly with the level of dissent expressed. Contrary to prevailing agency theoretical expectations, we do not find that independent chairs are more responsive to expressive voting dissent, nor that this relationship is strengthened by the degree of minority institutional investor ownership of the firm. Consistent with the symbolic perspective on shareholder voting that we seek to develop, however, we find that family chairs are more likely to lead the board to dismiss the CEO due to the intrinsic disvalue they incur from symbolic leadership legitimacy challenges in their firms, and that the positive effect of having a family chair on the dissent induced chance of CEO dismissal is strengthened by the level of family ownership in the firm.Funding: A University of Illinois at Chicago Summer Research Grant is gratefully acknowledged for S. Sauerwald.

Editorial introductions

Editorial introductions

Maternal Administration Of Probiotic Lactobacilli Since Pre-Conception Programs Offspring Gut Microbiota Functions

ObjectivesProbiotics intake may be considered beneficial by prospective and pregnant mothers but their effects on offspring development are underexplored. The maternal gut microbiota is a determinant of early offspring gut microbial colonization patterns and pre-conception may be a critical period. Our aim was to assess the programming effects of a probiotic Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 mixture, which is known to support intestinal homeostasis in infancy, on the temporal dynamics of offspring gut microbiota functions.MethodsFemale C57BL/6 specific pathogen free mice received sterile or probiotic-supplemented water starting one week before mating and until weaning (postnatal day, PND, 21). Offspring remained on their respective mother's treatment from PND 21 to 36. Offspring cecal microbiota was profiled at PND 14, 21, and 36 by 16S rRNA (V3-V4) gene amplicon sequencing and metabolic pathways were inferred with PICRUSt2 and the MetaCyc database. Data analysis and clustering were conducted with DESeq2-Wald test and hclust in R.Results355 MetaCyc pathways were predicted and collapsed into 48 functional classes; 10 of these accounted for more than 80% of the total pathway relative abundance, including various biosynthetic as well as carbohydrate and protein degradation pathways. With time, 113 and 55 pathways were altered (q-values < 0.01) in the control and probiotic groups, respectively, but only control samples clustered by age. At PND 14 and 21,195 and 39 pathways were differentially represented in the probiotic group vs. controls, but none at PND 36. Age-dependent pathways altered by probiotic supplementation belonged to biosynthesis (Amino Acid, Nucleoside and Nucleotide, Cofactor, Electron Carrier, and Vitamin) and degradation (Carbohydrate, Nucleoside and Nucleotide, Secondary Metabolite Degradation, C1 Compound Utilization and Assimilation) functional classes.ConclusionsMaternal probiotic supplementation accelerates the establishment of gut microbiota metabolic functions necessary to process host diet as well as for the synthesis of metabolites relevant for host health in the juvenile offspring.Funding SourcesNSERC; Lallemand Health Solutions; Lawson Family Chair in Microbiome Research.

MP48-03 PREVALENCE AND NATURAL HISTORY OF NON-METASTATIC CASTRATE RESISTANT PROSTATE CANCER: A POPULATION-BASED ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP48-03 PREVALENCE AND NATURAL HISTORY OF NON-METASTATIC CASTRATE RESISTANT PROSTATE CANCER: A POPULATION-BASED ANALYSIS Amanda Hird, Erind Dvorani, Refik Saskin, Sender Herschorn, Ronald Kodama, Girish Kulkarni, and Robert Nam Amanda HirdAmanda Hird More articles by this author , Erind DvoraniErind Dvorani More articles by this author , Refik SaskinRefik Saskin More articles by this author , Sender HerschornSender Herschorn More articles by this author , Ronald KodamaRonald Kodama More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , and Robert NamRobert Nam More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The natural history of non-metastatic castrate resistant prostate cancer (nmCRPC) prior to the introduction of novel anti-androgen agents in a real-world setting is largely unknown. Our primary aim was to determine the prevalence and natural history of nmCRPC. METHODS: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada. Patients with a diagnosis of prostate cancer, castrate level of testosterone (<1.7 nmol/L) and a PSA >2.0 nmol/L with a subsequent rise >25% from the nadir, and without diagnostic or treatment codes for metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and death are presented as medians with interquartile range (IQR). Predictors of time from nmCRPC to prostate cancer death were compared using univariable and multivariable Fine and Gray subdistributional hazard models to account for the competing risk of non-prostate cancer death. RESULTS: From January 2007 until March 2018, we identified 2045 patients with nmCRPC. Median age was 79 years (IQR: 72-84). A total of 984 patients (48.1%) received upfront hormonal therapy while 584 (25.8%) received initial radiotherapy (RT) and 478 (23.4%) previously underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years (IQR: 3-10). PSA at the time of meeting nmCRPC criteria was a median of 3.0 ng/L. Patients were followed for a median 31.1 months (IQR: 19.8-47.9). The overall annual prevalence of nmCRPC ranged from 1,519-1,913 patients, representing 7-12% of men with prostate cancer prescribed androgen deprivation therapy each year. Crude median time from nmCRPC to all-cause death was 37.6 months (IQR: 22.1-55.4). Median time from nmCRPC to metastasis and metastasis to all-cause death was 20.0 and 8.3 months, respectively. On regression analysis, older patients, patients who had a higher PSA at the time of meeting nmCRPC criteria, and patients with grade group 4-5 disease had a shorter time from nmCRPC to prostate cancer death. CONCLUSIONS: This is the largest analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and advancements in systemic therapy for patients with nmCRPC impact prevalence estimates and disease trajectory over time. Source of Funding: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and Ministry of Long-Term Care (MLTC) (grant number not applicable). This study also received funding from the Ajmera Family Chair in Urologic Oncology awarded to RKN (grant number not applicable). We thank IQVIA Solutions Canada Inc. for use of their Drug Information File © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e821 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amanda Hird More articles by this author Erind Dvorani More articles by this author Refik Saskin More articles by this author Sender Herschorn More articles by this author Ronald Kodama More articles by this author Girish Kulkarni More articles by this author Robert Nam More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD03-04 SYSTEMATIC REVIEW OF THE IMPACT OF A PLANT-BASED DIET ON PROSTATE CANCER INCIDENCE AND OUTCOMES

You have accessJournal of UrologyCME1 May 2022PD03-04 SYSTEMATIC REVIEW OF THE IMPACT OF A PLANT-BASED DIET ON PROSTATE CANCER INCIDENCE AND OUTCOMES Natasha Gupta, Jacob Taylor, James Borin, Kenneth Jacobsohn, Stacey Kenfield, Scott Eggener, Hiten Patel, Carrie Price, Meena Davuluri, Nataliya Byrne, Trinity Bivalacqua, and Stacy Loeb Natasha GuptaNatasha Gupta More articles by this author , Jacob TaylorJacob Taylor More articles by this author , James BorinJames Borin More articles by this author , Kenneth JacobsohnKenneth Jacobsohn More articles by this author , Stacey KenfieldStacey Kenfield More articles by this author , Scott EggenerScott Eggener More articles by this author , Hiten PatelHiten Patel More articles by this author , Carrie PriceCarrie Price More articles by this author , Meena DavuluriMeena Davuluri More articles by this author , Nataliya ByrneNataliya Byrne More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , and Stacy LoebStacy Loeb More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002518.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Plant-based diets are increasingly popular and have many well-established benefits for health and environmental sustainability. Our objective was to perform a systematic review of plant-based diets and prostate cancer. METHODS: We performed a systematic search using PubMed, Embase, the Cochrane Library, Scopus, the Web of Science, AMED, Nursing and Allied Health, and CINAHL Plus in June 2020. A systematic citation search was also performed. Studies were included if they reported primary data on full plant-based dietary patterns (i.e., vegan, vegetarian, plant-based) and incidence among at-risk men for prostate cancer, or oncologic, general health/nutrition, or quality of life (QOL) outcomes among patients with prostate cancer or caregivers of patients with prostate cancer. RESULTS: A total of 31 publications were eligible for the qualitative synthesis, including 16 interventional (including 7 from the Prostate Cancer Lifestyle Trial) and 15 observational (including the EPIC-Oxford UK and Seventh Day Adventist cohorts) (Table 1). Interventional studies primarily focused on lifestyle modification including plant-based diets for men on active surveillance for localized prostate cancer or with biochemical recurrence after treatment, showing improvements in short-term oncologic outcomes alongside improvements in general health and nutritional parameters. Epidemiologic studies primarily focused on risk of prostate cancer, showing either protective or null associations for plant-based dietary patterns. Studies of the vegan diet consistently showed favorable associations with risk and/or outcomes. Gaps in the current literature include impact for long-term disease-specific outcomes. CONCLUSIONS: Interventional studies showed generally favorable results of lifestyle modifications incorporating a plant-based diet with prostate cancer outcomes as well as improvements in nutrition and general health. Epidemiologic studies have shown either a lower risk of total prostate cancer or no significant difference. These results are encouraging in light of the many benefits of plant-based diets for overall health, as well as environmental sustainability and animal welfare. Source of Funding: SAK is supported by the Helen Diller Family Chair in Population Science for Urologic Cancer, SL is supported by the Prostate Cancer Foundation, the New York State Department of Health Prostate Cancer Pilot Research Grant, and a generous donation from Patricia and Michael Berns. NG is supported by grant T32HS026120 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e42 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Natasha Gupta More articles by this author Jacob Taylor More articles by this author James Borin More articles by this author Kenneth Jacobsohn More articles by this author Stacey Kenfield More articles by this author Scott Eggener More articles by this author Hiten Patel More articles by this author Carrie Price More articles by this author Meena Davuluri More articles by this author Nataliya Byrne More articles by this author Trinity Bivalacqua More articles by this author Stacy Loeb More articles by this author Expand All Advertisement PDF DownloadLoading ...

A48 OPTIMIZATION OF TRYPTOPHAN-CONTAINING DIETS TO ACTIVATE THE ARYL HYDROCARBON RECEPTOR AND REDUCE SUSCEPTIBILITY TO COLITIS

BackgroundThe intestinal microbiota, diet, and the immune system have all been proposed to contribute to the development of inflammatory bowel disease (IBD). The aryl hydrocarbon receptor (AhR) is a critical regulator of intestinal immunity and mucosal barrier homeostasis that is activated by agonists such as diet-derived microbial tryptophan (Trp) metabolites. Increasing evidence suggests that IBD patients have reduced AhR agonists in intestinal content resulting in the downregulation of AhR-regulated genes. In mice, impaired Trp metabolism and AhR signaling translate to increased intestinal inflammation and injury during colitis. This finding highlights the utility of Trp dietary intervention to reduce the onset and progression of inflammation and injury in IBD.AimsTo optimize a Trp-enriched diet formulation to increase AhR activation and reduce intestinal inflammation and injury in mouse models of colitis.MethodsThree diet types with elevated Trp were explored: (1) free amino acid diet with added Trp, (2) purified protein diet with added Trp, and (3) purified high protein diet. Following three weeks of diet consumption by C57BL/6 mice, mucosal injury was induced with 2% dextran sulfate sodium in drinking water (DSS) before sacrifice. Susceptibility to colitis was assessed by analyzing stool consistency and blood, microscopic damage, immune infiltration by immunohistochemistry, and pro-inflammatory gene expression (NanoString). Activation of AhR was measured in feces using an in vitro AhR luciferase reporter assay. Colonic expression of AhR pathway genes Cyp1a1, Il22, Ahrr, and Il17 was evaluated by RT-qPCR. Fecal microbiota was analyzed by 16S rRNA gene sequencing (Illumina).ResultsAhR activation in vitro and colonic AhR pathway gene expression were elevated in mice fed diets containing added Trp (1 & 2) in comparison to mice fed a high protein diet (3). While all DSS-treated mice developed colitis, mice fed a purified protein diet with added Trp (2) were protected from severe colitis and developed less microscopic damage, immune cell infiltration, and pro-inflammatory gene signalling. Enriched Trp concentrations in the form of free amino acid (1) and high protein (3) diets were not associated with protection from inflammation and injury during colitis.ConclusionsOur findings suggest that the addition of Trp to a conventional diet (2) may increase microbial tryptophan metabolites to ameliorate colitis severity and intestinal homeostasis through AhR activation. Despite having similar Trp concentrations, a Trp-enriched free amino acid diet (1) and a high protein diet (3) do not improve colitis severity. Thus, both the diet formulation and the availability of Trp should be considered when designing dietary interventions for the treatment of colitis through AhR activation.Funding AgenciesCCC, CIHRFarncombe Family Digestive Health Research Institute, Douglas Family Chair in Gastroenterology Research, Biocodex Microbiota Foundation

The impact of lockdown timing on COVID-19 transmission across US counties.

BackgroundMany countries have implemented lockdowns to reduce COVID-19 transmission. However, there is no consensus on the optimal timing of these lockdowns to control community spread of the disease. Here we evaluated the relationship between timing of lockdowns, along with other risk factors, and the growth trajectories of COVID-19 across 3,112 counties in the US.MethodsWe ascertained dates for lockdowns and implementation of various non-pharmaceutical interventions at a county level and merged these data with those of US census and county-specific COVID-19 daily cumulative case counts. We then applied a Functional Principal Component (FPC) analysis on this dataset to generate FPC scores, which were used as a surrogate variable to describe the trajectory of daily cumulative case counts for each county. We used machine learning methods to identify risk factors including the timing of lockdown that significantly influenced the FPC scores.FindingsWe found that the first eigen-function accounted for most (>92%) of the variations in the daily cumulative case counts. The impact of lockdown timing on the total daily case count of a county became significant beginning approximately 7 days prior to that county reporting at least 5 cumulative cases of COVID-19. Delays in lockdown implementation after this date led to a rapid acceleration of COVID-19 spread in the county over the first ~50 days from the date with at least 5 cumulative cases, and higher case counts across the entirety of the follow-up period. Other factors such as total population, median family income, Gini index, median age, and within-county mobility also had a substantial effect. When adjusted for all these factors, the timing of lockdowns was the most significant risk factor associated with the county-specific daily cumulative case counts.InterpretationLockdowns are an effective way of controlling the spread of COVID-19 in communities. Significant delays in lockdown cause a dramatic increase in the cumulative case counts. Thus, the timing of the lockdown relative to the case count is an important consideration in controlling the pandemic in communities.FundingThe study period is from June 2020 to July 2021. Dr. Xuekui Zhang is a Tier 2 Canada Research Chairs (Grant No. 950231363) and funded by Natural Sciences and Engineering Research Council of Canada (Grant No. RGPIN201704722). Dr. Li Xing is funded by Natural Sciences and Engineering Research Council of Canada (Grant Number: RGPIN 202103530). This research was enabled in part by support provided by WestGrid (www.westgrid.ca) and Compute Canada (www.computecanada.ca). The computing resource is provided by Compute Canada Resource Allocation Competitions #3495 (PI: Xuekui Zhang) and #1551 (PI: Li Xing). Dr. Don Sin is a Tier 1 Canada Research Chair in COPD and holds the de Lazzari Family Chair at the Heart Lung Innovation, Vancouver, Canada.

"Anaya Fraizer, 16, Poet" from the series, "My Family Chair", 2018

Image Description: A photo of a Black teenage girl wearing a black shirt, green pants, and brown shoes sitting in a wicker chair in front of a draped pink cloth. Her hair is braided, and she is wearing a headband, Africa earrings, a necklace, and an anklet. Next to the wicker chair is a small wicker table. The chair and table are on a brown and white hide. She has one hand draped over the chair and one placed at her head. Her head is tilted upwards and to the side with her eyes looking forward.&#x0D;

Addressing Maternal Mental Health: Progress, Challenges, and Potential Solutions

Addressing Maternal Mental Health: Progress, Challenges, and Potential Solutions

The Impact of Early or Late Lockdowns on the Spread of COVID-19 in US Counties

Background: COVID-19 is a highly transmissible infectious disease that has infected over 122 million individuals worldwide. To combat this pandemic, governments around the world have imposed lockdowns. However, the impact of these lockdowns on the rates of COVID-19 transmission in communities is not well-known. Here, we used COVID-19 case counts from 3,000+ counties in the United States (US) to determine the relationship between lockdown as well as other county factors and the rate of COVID-19 spread in these communities.Methods: We merged county-specific COVID-19 case counts with US census data and the date of lockdown for each of the counties. We then applied a Functional Principal Component (FPC) analysis on this dataset to generate scores that described the trajectory of COVID-19 spread across the counties. We used machine learning methods to identify important factors in the county including the date of lockdown that significantly influenced the FPC scores.Findings: We found that the first FPC score accounted for up to 92.81% of the variations in the absolute rates and the topology of COVID-19 spread over time at a county level. The relation between incidence of COVID-19 and time at a county level demonstrated a hockey-stick appearance with an inflection point approximately 7 days prior to the county reporting at least 5 new cases of COVID-19; beyond this inflection point, there was an exponential increase in incidence. Among the risk factors, lockdown and total population were the two most significant features of the county that influenced the rate of COVID-19 infection, while the median family income, median age and within-county move also substantially affect COVID spread.Interpretation: Lockdowns are an effective way of controlling the COVID-19 spread in communities. However, significant delays in lockdown cause a dramatic increase in the case counts. Thus, the timing of the lockdown relative to the case count is an important consideration in controlling the pandemic in communities.Funding Statement: Dr. Xuekui Zhang is funded by Canada Research Chairs. Grant Number: 950-231363 and Natural Sciences and Engineering Research Council of Canada. Grant Number: RGPIN-2017-04722. This research was enabled in part by support provided by WestGrid (www.westgrid.ca) and Compute Canada (www.computecanada.ca). The computing resource is provided by Compute Canada Resource Allocation Competitions #3495 (PI: Xuekui Zhang) and #1551 (PI: Li Xing). Dr. Don Sin is a Tier 1 Canada Research Chair in COPD and holds the de Lazzari Family Chair at the Heart Lung Innovation, Vancouver, Canada.Declaration of Interests: Don Sin: Professor Sin reports grants from Merck, personal fees from Sanofi-Aventis, personal fees from Regeneron, grants and personal fees from Boehringer Ingelheim, grants and personal fees from AstraZeneca, personal fees from Novartis, outside the submitted work. Other coauthors have nothing to declare.

Perancangan dan Simulasi Tata Letak Pabrik Untuk Mengoptimalkan Biaya Material Handling Dengan Menggunakan Algoritma Craft dan Activity Relationship Chart pada Industri Kerajinan Bambu

CV. XYZ is one of small and medium entrepreneurship producing a wide range of bamboo handicrafts such as chairs, tables, partitions, etc. The company wants to increase profit by saving on production costs and optimizing transport material handling distances between the production process directly related to the layout of the factory. In research conducted in CV XYZ, there is an inefficient layout. This is indicated by irregular material flows, storage of the residual material production and a lot of material movement between operations. Type of layout used is process layout design, with the objective to minimize the total movement moment. The algorithm used is the CRAFT algorithm that requires data of transfer materials cost (multiplication of the distance with the frequency of movement). Besides methods used in this research is qualitative method that ' s using map relations activity diagram relations activity. Beside that simulation is performed to compare the existing layout with the proposed layout. Based on the research that has been done, the layout of the proposed methods can reduce the CRAFT movement of the moment of total material to 16.25% with yields as much as 21 Product Family Chair in one month while the layout of the proposed use of the ARC produces as many as 20 products only.

A23 DIETARY PROTEIN AND AMINO ACID COMPOSITIONS INFLUENCE MICROBIOTA, INTESTINAL PERMEABILITY, AND SUSCEPTIBILITY TO COLITIS

Abstract Background Environmental factors, such as alterations in diet and microbiota, have been linked to inflammatory bowel diseases (IBD). The incidence of IBD is rising, particularly in Canada and other industrialized nations that consume western-style diets high in fat and protein. While most dietary proteins and amino acids are absorbed in the small intestine, substantial amounts can enter the colon for microbial metabolism and to exert effects on intestinal tissue and immune cells. Prospective cohort studies suggest that diets high in protein are associated with an increased risk of IBD. However, the role of excess dietary protein and amino acids in IBD pathogenesis is not clear. Aims To study whether and how consumption of diets high in protein or amino acids influences intestinal inflammation, colitis severity, and intestinal microbiota. Methods To assess the influence of dietary protein composition on colitis severity, specific pathogen-free C57BL/6 mice were fed isocaloric casein-based purified diets containing low (7%), normal (14%), or high (35%) protein (HPD). Mice were also fed an amino acid-defined diet (AAD) with amino acid and ingredient composition matched to the normal protein diet. Following three weeks of diet consumption ad libitum, mice were continued on the same diet and mucosal injury was induced with 2% dextran sulfate sodium (DSS; 5 days) followed by water (2 days) before sacrifice. Mice were monitored daily for clinical signs of colitis. Susceptibility to colitis was assessed by analysing stool consistency and blood, microscopic scoring (Cooper score), and by immunohistochemistry of colon tissue. Fecal microbiota (16S rRNA Illumina), intestinal permeability (Ussing chambers), proinflammatory gene expression (NanoString and RT-qPCR), and bacterial translocation (plating) were analysed. Results Following DSS exposure, mice fed HPD and AAD experienced greater weight loss, bacterial translocation to the spleen, stool blood, and diarrhea compared to mice fed the normal protein control diet. While all DSS-treated mice developed colitis, HPD and AAD fed mice also developed greater histologic damage, intestinal permeability, and innate immune cell infiltration. Cytokine profiling revealed that AAD is associated with significant up-regulation of IL-18 during colitis. Principle coordinates analysis based on Bray-Curtis dissimilarities demonstrates distinct shifts in the fecal microbiota of mice fed HPD and AAD. Conclusions These results suggest that excess dietary protein and amino acids are associated with more severe colitis and microbiota alterations in the DSS model. Previous studies demonstrate that IL-18 is up-regulated in IBD patients. Its overexpression may incite inflammation by stimulating cytokine signalling through NFκB and modify microbial community structure by regulating antimicrobial peptides. Funding Agencies CIHRFarncombe Family Digestive Health Research Institute, Douglas Family Chair in Gastroenterology Research

Public Knowledge and Attitudes Concerning Palliative Care

Background: WHO recommends early integration of palliative care alongside usual care to improve quality of life; misunderstanding of palliative care may impede this. We aimed to compare the public’s perceived and actual knowledge of palliative care, and examine associations of this knowledge with attitudes concerning palliative care. Methods: We analyzed data from an online cross-sectional survey of a representative sample of the Canadian public, accessed through a survey panel in May-June, 2019. We compared high perceived knowledge (“know what palliative care is and could explain it”) with actual knowledge of the WHO definition (knew at least 5/8 components including that palliative care can be provided early in the illness and together with life-prolonging treatments), and examined their associations with attitudes to palliative care. Findings: Of 1518 eligible participants, 45% had high perceived knowledge, of whom 46% had high actual knowledge. Participants with high (vs. low) perceived knowledge were more likely to associate palliative care with end-of-life care (adjusted odds ratio, 2.15[95%CI, 1.66-2.79]) and less likely to believe it offered hope (0.62[0.47-0.81] ). Conversely, participants with high (vs. low) actual knowledge were less likely to associate palliative care with end-of-life care ( 0.59[0.46-0.76] ) , less likely to find palliative care fearful or depressing, and more likely to believe it offer ed hope (1.88[1.46-2.43]). Interpretation: Stigma regarding palliative care may be perpetuated by those who falsely believe they understand its meaning. Public health education is needed to increase knowledge about palliative care, promote its early integration, and counter false assumptions Funding Statement: This research was funded by the Canadian Institutes of Health Research (grant number 152996; CZ) and the Ontario Ministry of Health and Long-Term Care. Dr. Zimmermann is supported by the Rose Family Chair in Palliative Medicine and Supportive Care, Department of Medicine, University of Toronto. Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The study was approved by the University Health Network Research Ethics Board (#18-6039).