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Article: Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

De Sousa Rodrigues, Maria Elizabeth / Bolen, MacKenzie L / Blackmer-Raynolds, Lisa / Schwartz, Noah / Chang, Jianjun / Tansey, Malú Gámez / Sampson, Timothy Robert

bioRxiv : the preprint server for biology

2024

Abstract: Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly ... ...

Abstract	Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.28.582516
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Article ; Online: Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Rodrigues, Maria Elizabeth De Sousa / Bolen, MacKenzie L / Blackmer-Raynolds, Lisa / Schwartz, Noah / Chang, Jianjun / Tansey, Malú Gámez / Sampson, Timothy Robert

Neurobiology of disease

2024 , Page(s) 106511

Abstract	Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2024.106511
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Article ; Online: Evaluation of a Statewide Policy to Improve Post-Overdose Care in Emergency Departments and Subsequent Treatment Engagement.

Chambers, Laura C / Hallowell, Benjamin D / Samuels, Elizabeth A / Daly, Mackenzie / Baird, Janette / Beaudoin, Francesca L

Rhode Island medical journal (2013)

2023 Volume 106, Issue 2, Page(s) 34–39

Abstract: Objective: To evaluate the impact of a statewide treatment standards policy for post-overdose emergency department (ED) care on services provided and subsequent treatment engagement.: Methods: This pre-/post-study used electronic health record data ... ...

Abstract	Objective: To evaluate the impact of a statewide treatment standards policy for post-overdose emergency department (ED) care on services provided and subsequent treatment engagement. Methods: This pre-/post-study used electronic health record data and surveillance data from Rhode Island. Outcomes were compared for patients attending EDs for opioid overdose before (03/1/2015-02/28/2017) and after (04/01/2017-03/31/2021) policy release. Results: Overall, 2,134 patients attended 2,891 ED visits for opioid overdose. Compared to pre-policy, visits post-policy more often included initiation of buprenorphine in or from the ED (<1% vs. 3%, p<0.01), provision of a take-home naloxone kit or prescription (41% vs. 58%, p<0.01), and referral to treatment (0% vs. 34%, p<0.01). Provision of behavioral counseling in the ED and initiation of treatment within 30 days of the visit were similar during the two periods. Conclusions: Statewide post-overdose treatment standards may improve provision of some ED services. Additional strategies are needed to improve subsequent treatment engagement.
MeSH term(s)	Humans ; Opiate Overdose ; Drug Overdose/prevention & control ; Emergency Service, Hospital ; Emergency Medical Services ; Policy
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	419430-5
ISSN	2327-2228 ; 0363-7913
ISSN (online)	2327-2228
ISSN	0363-7913
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Article ; Online: Prevalence of food insecurity in NCAA Division III collegiate athletes.

Brown, Melissa L / Karpinski, Christine / Bragdon, Morgan / Mackenzie, Michelle / Abbey, Elizabeth

Journal of American college health : J of ACH

2021 Volume 71, Issue 5, Page(s) 1374–1380

Abstract: Objective: ...

Abstract	Objective:
MeSH term(s)	Humans ; Female ; Adolescent ; Young Adult ; Adult ; Male ; Prevalence ; Students ; Universities ; Athletes ; Food Insecurity ; Food Supply
Language	English
Publishing date	2021-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	604907-2
ISSN	1940-3208 ; 0744-8481
ISSN (online)	1940-3208
ISSN	0744-8481
DOI	10.1080/07448481.2021.1942886
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Article ; Online: An evaluation of the association between specific post‐overdose care services in emergency departments and subsequent treatment engagement

Laura C. Chambers / Benjamin D. Hallowell / Elizabeth A. Samuels / Mackenzie Daly / Janette Baird / Francesca L. Beaudoin

Journal of the American College of Emergency Physicians Open, Vol 4, Iss 1, Pp n/a-n/a (2023)

2023

Abstract: Abstract Objective The objective of this study was to estimate the association between receipt of specific post‐overdose care services in the emergency department (ED) and subsequent engagement in treatment for opioid use disorder (OUD) after discharge. ... ...

Abstract	Abstract Objective The objective of this study was to estimate the association between receipt of specific post‐overdose care services in the emergency department (ED) and subsequent engagement in treatment for opioid use disorder (OUD) after discharge. Methods This was a retrospective cohort study of Rhode Island residents treated at 1 of 4 EDs for opioid overdose who were not engaged in OUD treatment and were discharged home (May 2016–April 2021). Electronic health record data were used to identify ED services received, and state administrative data were used to define subsequent engagement in OUD treatment within 30 days. Multivariable conditional logistic regression was used to estimate the association between ED services received and subsequent treatment engagement. Results Overall, 1008 people not engaged in OUD treatment were treated at study EDs for opioid overdose and discharged home, of whom 146 (14%) subsequently engaged in OUD treatment within 30 days. Most patients were aged 25 to 44 years (59%) and non‐Hispanic White (69%). Receipt of behavioral counseling in the ED (adjusted odds ratio [aOR] = 1.79, 95% confidence interval [CI] = 1.18–2.71) and initiation of buprenorphine treatment in/from the ED (aOR = 5.86, 95% CI = 2.70–12.71) were associated with treatment engagement. Receipt of a take‐home naloxone kit or naloxone prescription and referral to treatment at discharge were not associated with treatment engagement. Overall, 49% of patients received behavioral counseling in the ED, and 3% initiated buprenorphine in/from the ED. Conclusion Strategies for increasing provision of behavioral counseling and initiation of buprenorphine in the ED may be useful for improving subsequent engagement in OUD treatment after discharge.
Keywords	emergency medicine ; medications for opioid use disorder ; opioid use disorder ; overdose ; behavioral counseling ; Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9
Subject code	360
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Peltier, MacKenzie R / Verplaetse, Terril L / Altemus, Margaret / Zakiniaeiz, Yasmin / Ralevski, Elizabeth A / Mineur, Yann S / Gueorguieva, Ralitza / Picciotto, Marina R / Cosgrove, Kelly P / Petrakis, Ismene / McKee, Sherry A

Frontiers in neuroendocrinology

2024 Volume 73, Page(s) 101119

Abstract: Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; ... ...

Abstract	Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption.
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390985-2
ISSN	1095-6808 ; 0532-7466 ; 0091-3022
ISSN (online)	1095-6808
ISSN	0532-7466 ; 0091-3022
DOI	10.1016/j.yfrne.2023.101119
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Zs.A 3423: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Collateral benefits from a school-readiness intervention on breastfeeding: A cross-domain impact evaluation.

Miller, Elizabeth B / Whipps, Mackenzie D M / Bogen, Debra L / Morris, Pamela A / Mendelsohn, Alan L / Shaw, Daniel S / Gross, Rachel S

Maternal & child nutrition

2022 Volume 19, Issue 1, Page(s) e13446

Abstract: This study evaluated the collateral, or unanticipated, impacts of Smart Beginnings (SB), a two-site, tiered intervention designed to promote responsive parenting and school readiness, on breastfeeding intensity in a low-income sample. Impact analyses for ...

Abstract	This study evaluated the collateral, or unanticipated, impacts of Smart Beginnings (SB), a two-site, tiered intervention designed to promote responsive parenting and school readiness, on breastfeeding intensity in a low-income sample. Impact analyses for the SB intervention were conducted using an intent-to-treat design leveraging a two-arm random assignment structure. Mothers assigned to the SB intervention group were more than three times more likely to give breastmilk as the only milk source at infant age 6 months than mothers assigned to the control group at one site, an effect not evident at the other study site. As development and growth are the two most salient domains of child health, understanding how interventions impact subsequent parenting practices across both domains is critical to address long-term economic and racial/ethnic disparities. Implications of the findings are discussed for improving the efficacy of interventions based on paediatric primary care.
MeSH term(s)	Infant ; Female ; Child ; Humans ; Breast Feeding ; Mothers ; Parenting ; Child Development ; Schools
Language	English
Publishing date	2022-10-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2175105-5
ISSN	1740-8709 ; 1740-8695
ISSN (online)	1740-8709
ISSN	1740-8695
DOI	10.1111/mcn.13446
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Article ; Online: Interventions to Facilitate Return to Work after Stroke: A Systematic Review.

Pearce, Gemma / O'Donnell, Joan / Pimentel, Rebecca / Blake, Elizabeth / Mackenzie, Lynette

International journal of environmental research and public health

2023 Volume 20, Issue 15

Abstract: Purpose: To gather knowledge about effective return to work interventions for survivors of stroke.: Methods: A database search was conducted in MEDLINE, CINAHL, PsycINFO, Scopus, and Web of Science using keywords and medical subject headings. Studies ...

Abstract	Purpose: To gather knowledge about effective return to work interventions for survivors of stroke. Methods: A database search was conducted in MEDLINE, CINAHL, PsycINFO, Scopus, and Web of Science using keywords and medical subject headings. Studies were included if they met the following criteria: (i) studies published in English since the year 2000; (ii) adult patients aged 18-65 with a primary diagnosis of stroke; (iii) working pre-stroke; and (iv) intervention in which one of the primary outcomes is return to work. The methodological quality of included studies was assessed and the evidence synthesised. Results: Twelve studies were included, of which three were randomised controlled trials, four were retrospective studies, one was a cohort study, one was an explorative longitudinal study, one was a pre-post treatment observation study and two were pilot studies. The employment rate at follow-up ranged from 7% to 75.6%. Overall, there was limited published evidence regarding the effectiveness of interventions to promote return to work for this population, and it was unclear if return to pre-stroke work was the goal. Conclusion: A lack of large, controlled trials, variations in follow-up time and the definitions of return to work accounted for the large range of employment rates at follow-up. There is limited published high-quality evidence regarding the effectiveness of interventions to promote return to work in working-age survivors of stroke.
MeSH term(s)	Adult ; Humans ; Return to Work ; Cohort Studies ; Retrospective Studies ; Longitudinal Studies ; Stroke/therapy ; Randomized Controlled Trials as Topic
Language	English
Publishing date	2023-07-28
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20156469
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Article ; Online: Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

Griffith, Garett / Lamotte, Guillaume / Mehta, Niyati / Fan, Peng / Nikolich, Juliana / Springman, Victoria / Suttman, Erin / Joslin, Elizabeth / Balfany, Katherine / Dunlap, MacKenzie / Kohrt, Wendy M / Christiansen, Cory L / Melanson, Edward L / Josbeno, Deborah / Chahine, Lana M / Patterson, Charity G / Corcos, Daniel M

Journal of Parkinson's disease

2024 Volume 14, Issue 1, Page(s) 121–133

Abstract: Background: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early ... ...

Abstract	Background: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. Objective: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. Methods: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). Results: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). Conclusions: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.
MeSH term(s)	Humans ; Male ; Female ; Exercise Test ; Parkinson Disease/complications ; Heart Failure ; Autonomic Nervous System Diseases/diagnosis ; Autonomic Nervous System Diseases/etiology ; Heart Rate/physiology
Language	English
Publishing date	2024-02-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-230006
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Article ; Online: Effects of tissue decomposition on stable isotope ratios and implications for use of stranded animals in research

Cloyed, Carl S. / Johnson, Che'Isha / DaCosta, Kayla P. / Clance, Lauren R. / Russell, Mackenzie L. / Díaz Clark, Cristina / Hieb, Elizabeth E. / Carmichael, Ruth H.

Ecosphere. 2023 Feb., v. 14, no. 2 p.e4385-

2023

Abstract: Stable isotope analysis (SIA) provides ecological data that can be safely and efficiently collected on endangered, threatened, and cryptic species. Marine mammals are an ecologically important group for which economical and logistical constraints can ... ...

Abstract	Stable isotope analysis (SIA) provides ecological data that can be safely and efficiently collected on endangered, threatened, and cryptic species. Marine mammals are an ecologically important group for which economical and logistical constraints can make data collection challenging. Stranded marine mammals are often used in research, but the causes of strandings and subsequent tissue decomposition could affect SIA. We conducted a three‐part study to test the validity of using δ¹³C and δ¹⁵N values from tissues of stranded bottlenose dolphins (Tursiops truncatus) and West Indian manatees (Trichechus manatus) for ecological studies. First, we quantified isotopic overlap using ellipses based on 95% of the data to compare isotope values in skin between stranded and live‐captured animals. Second, we compared stable isotope values from liver, skin, and muscle of animals that had stranded and were sampled at different decomposition stages. Third, we experimentally exposed each tissue to environmental conditions and sampled tissues as they decomposed. For both dolphins and manatees, isotopic ellipses from skin of stranded carcasses were similar to live‐captured individuals. Among individuals recovered at different decomposition stages, more advanced decomposition affected δ¹³C values in dolphin liver and skin but not in manatee tissues and had no effect on δ¹⁵N values in any tissue for either species. In the experimental manipulation, decomposition resulted in depleted δ¹³C values, enriched δ¹⁵N values, and increased C:N in liver for both species. Skin and muscle from stranded dolphins and manatees are representative of their corresponding live populations and can be used for SIA with appropriate caution. To facilitate the use of tissues from stranded animals, tissues should be dried or frozen for storage as soon as possible after sampling. We recommend liver from stranded animals only be used for SIA when researchers need tissues with short turnover times and can access fresh samples. Without consideration of decomposition effects on isotope values, ecologists may make inaccurate inferences about habitat use, diet, and community structure. Careful use of SIA on tissues from stranded animals can help researchers provide better quality information for managers and policy makers.
Keywords	Trichechus manatus ; Tursiops truncatus ; community structure ; cryptic species ; data collection ; diet ; dolphins ; habitat preferences ; issues and policy ; liver ; muscles ; stable isotopes
Language	English
Dates of publication	2023-02
Publishing place	John Wiley & Sons, Inc.
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2572257-8
ISSN	2150-8925
ISSN	2150-8925
DOI	10.1002/ecs2.4385
Database	NAL-Catalogue (AGRICOLA)

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