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Article ; Online: Deflection to Harm Reduction: Public Health and Public Safety Collaborative Responses to the Overdose Epidemic in the United States.

Diriba, Kabaye / Whitlock, Esther

Journal of public health management and practice : JPHMP

2022 Volume 28, Issue 3, Page(s) 321–323

MeSH term(s)	Drug Overdose/drug therapy ; Drug Overdose/epidemiology ; Drug Overdose/prevention & control ; Epidemics ; Harm Reduction ; Humans ; Public Health ; United States/epidemiology
Language	English
Publishing date	2022-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2027860-3
ISSN	1550-5022 ; 1078-4659
ISSN (online)	1550-5022
ISSN	1078-4659
DOI	10.1097/PHH.0000000000001531
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Zs.A 5302: Show issues

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Article ; Online: Insulin Regulation of Hepatic Lipid Homeostasis.

Uehara, Kahealani / Santoleri, Dominic / Whitlock, Anna E Garcia / Titchenell, Paul M

Comprehensive Physiology

2023 Volume 13, Issue 3, Page(s) 4785–4809

Abstract: The incidence of obesity, insulin resistance, and type II diabetes (T2DM) continues to rise worldwide. The liver is a central insulin-responsive metabolic organ that governs whole-body metabolic homeostasis. Therefore, defining the mechanisms underlying ... ...

Abstract	The incidence of obesity, insulin resistance, and type II diabetes (T2DM) continues to rise worldwide. The liver is a central insulin-responsive metabolic organ that governs whole-body metabolic homeostasis. Therefore, defining the mechanisms underlying insulin action in the liver is essential to our understanding of the pathogenesis of insulin resistance. During periods of fasting, the liver catabolizes fatty acids and stored glycogen to meet the metabolic demands of the body. In postprandial conditions, insulin signals to the liver to store excess nutrients into triglycerides, cholesterol, and glycogen. In insulin-resistant states, such as T2DM, hepatic insulin signaling continues to promote lipid synthesis but fails to suppress glucose production, leading to hypertriglyceridemia and hyperglycemia. Insulin resistance is associated with the development of metabolic disorders such as cardiovascular and kidney disease, atherosclerosis, stroke, and cancer. Of note, nonalcoholic fatty liver disease (NAFLD), a spectrum of diseases encompassing fatty liver, inflammation, fibrosis, and cirrhosis, is linked to abnormalities in insulin-mediated lipid metabolism. Therefore, understanding the role of insulin signaling under normal and pathologic states may provide insights into preventative and therapeutic opportunities for the treatment of metabolic diseases. Here, we provide a review of the field of hepatic insulin signaling and lipid regulation, including providing historical context, detailed molecular mechanisms, and address gaps in our understanding of hepatic lipid regulation and the derangements under insulin-resistant conditions. © 2023 American Physiological Society. Compr Physiol 13:4785-4809, 2023.
MeSH term(s)	Humans ; Insulin/metabolism ; Insulin Resistance/physiology ; Diabetes Mellitus, Type 2/metabolism ; Liver/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Lipid Metabolism ; Triglycerides/metabolism ; Glycogen/metabolism ; Homeostasis
Chemical Substances	Insulin ; Triglycerides ; Glycogen (9005-79-2)
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural
ISSN	2040-4603
ISSN (online)	2040-4603
DOI	10.1002/cphy.c220015
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Article ; Online: Hematogenous Routing of Exogenous Messenger RNA Delivered Into the Amniotic Fluid.

Moskowitzova, Kamila / Whitlock, Ashlyn E / Zurakowski, David / Fauza, Dario O

The Journal of surgical research

2023 Volume 289, Page(s) 116–120

Abstract: Introduction: Therapies based on exogenous messenger RNA (mRNA) administration have emerged as a powerful novel strategy for the actual or potential treatment of an assortment of diseases, including congenital surgical pathologies. We sought to ... ...

Abstract	Introduction: Therapies based on exogenous messenger RNA (mRNA) administration have emerged as a powerful novel strategy for the actual or potential treatment of an assortment of diseases, including congenital surgical pathologies. We sought to determine whether the minimally invasive transamniotic route could be an alternative for prenatal mRNA delivery. Methods: Pregnant Sprague-Dawley dams underwent laparotomy followed by volume-matched intra-amniotic injections in all their fetuses (n = 120) of either a suspension of a custom firefly luciferase mRNA encapsulated by a lipid- and synthetic cationic polymer-based composite, or of a suspension of the same encapsulation components without mRNA, on gestational day 17 (E17; term = E21-22). On E18, E19, E20, and E21, samples from 14 fetal anatomical sites and maternal serum were procured for the screening of mRNA incorporation by host cells by measurement of luciferase activity via microplate luminometry. Statistical analysis was by Mann-Whitney U-test, including Bonferroni-adjustment. Results: Overall survival was 87.5% (105/120). Controlled by the encapsulating composite without mRNA, luciferase activity was detected in the animals that received encapsulated mRNA in the following fetal annexes: amniotic fluid, amnion, chorion, umbilical cord, and placenta (P = 0.033 to <0.001), as well as in the following fetal sites: liver, stomach, intestines, and lungs (P = 0.043-0.002). Conclusions: Packaged exogenous mRNA can be incorporated by the fetus at least at select anatomical sites after simple intra-amniotic administration in a rodent model. The pattern and chronology of mRNA incorporation are compatible with transplacental hematogenous routing, as well as with fetal swallowing/aspiration. Further study of transamniotic mRNA administration is warranted.
MeSH term(s)	Pregnancy ; Animals ; Female ; Amniotic Fluid ; Amnion ; Placenta ; Mesenchymal Stem Cell Transplantation ; Luciferases
Chemical Substances	Luciferases (EC 1.13.12.-)
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80170-7
ISSN	1095-8673 ; 0022-4804
ISSN (online)	1095-8673
ISSN	0022-4804
DOI	10.1016/j.jss.2023.03.037
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Article ; Online: Dispersion of National Institute of Health Funding to Departments of Surgery Is Contracting.

Brlecic, Paige E / Whitlock, Richard S / Zhang, Qianzi / LeMaire, Scott A / Rosengart, Todd K

The Journal of surgical research

2023 Volume 289, Page(s) 8–15

Abstract: Introduction: NIH funding to departments of surgery reported as benchmark Blue Ridge Institute for Medical Research (BRIMR) rankings are unclear.: Methods: We analyzed inflation-adjusted BRIMR-reported NIH funding to departments of surgery and ... ...

Abstract	Introduction: NIH funding to departments of surgery reported as benchmark Blue Ridge Institute for Medical Research (BRIMR) rankings are unclear. Methods: We analyzed inflation-adjusted BRIMR-reported NIH funding to departments of surgery and medicine between 2011 and 2021. Results: NIH funding to departments of surgery and medicine both increased 40% from 2011 to 2021 ($325 million to $454 million; $3.8 billion to $5.3 billion, P < 0.001 for both). The number of BRIMR-ranked departments of surgery decreased 14% during this period while departments of medicine increased 5% (88 to 76 versus 111 to 116; P < 0.001). There was a greater increase in the total number of medicine PIs versus surgery PIs during this period (4377 to 5224 versus 557 to 649; P < 0.001). These trends translated to further concentration of NIH-funded PIs in medicine versus surgery departments (45 PIs/program versus 8.5 PIs/program; P < 0.001). NIH funding and PIs/program in 2021 were respectively 32 and 20 times greater for the top versus lowest 15 BRIMR-ranked surgery departments ($244 million versus $7.5 million [P < 0.01]; 20.5 versus 1.3 [P < 0.001]). Twelve (80%) of the top 15 surgery departments maintained this ranking over the 10-year study period. Conclusions: Although NIH funding to departments of surgery and medicine is growing at a similar rate, departments of medicine and top-funded surgery departments have greater funding and concentration of PIs/program versus surgery departments overall and lowest-funded surgery departments. Strategies used by top-performing departments to obtain and maintain funding may assist less well-funded departments in obtaining extramural research funding, thus broadening the access of surgeon-scientists to perform NIH-supported research.
MeSH term(s)	Humans ; Schools, Medical ; Medicine ; Surgeons ; Hospital Departments ; Biomedical Research
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80170-7
ISSN	1095-8673 ; 0022-4804
ISSN (online)	1095-8673
ISSN	0022-4804
DOI	10.1016/j.jss.2023.03.023
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Article ; Online: phoenixin(smim20), a gene coding for a novel reproductive ligand, is expressed in the brain of adult zebrafish.

Ceriani, R / Calfún, C / Whitlock, K E

Gene expression patterns : GEP

2020 Volume 39, Page(s) 119164

Abstract: Gonadotropin-releasing hormone (GnRH) is a highly conserved neuroendocrine decapeptide that is essential for the onset of puberty and the maintenance of the reproductive state. In addition to its role as hypothalamic releasing hormone, GnRH has multiple ... ...

Abstract	Gonadotropin-releasing hormone (GnRH) is a highly conserved neuroendocrine decapeptide that is essential for the onset of puberty and the maintenance of the reproductive state. In addition to its role as hypothalamic releasing hormone, GnRH has multiple functions including modulator of neural activity within the nervous system and of resulting behaviors. These multiple functions are reflected by the existence of multiple isoforms. Despite its importance as a critical hypothalamic releasing hormone, the gnrh1 gene has been lost in zebrafish, and its reproductive function is not compensated for by other GnRH isoforms (GnRH2 and GnRH3), suggesting that, surprisingly, zebrafish do not use any of the GnRH peptides to control reproduction and fertility. Previously we proposed that Phoenixin/SMIM20, a novel peptide identified in mammals and the ligand for the orphan GPR173, is a potential candidate to control the initiation of sexual development and fertility in the zebrafish. Here we confirm the sequence of the zebrafish phoenixin/smim20 gene and by RT-PCR show that it is expressed early in development through adulthood. Subsequently we show that phoenixin/smim20 is expressed in the adult brain including the regions of the hypothalamus important in the control of fertility and reproduction.
MeSH term(s)	Animals ; Brain/metabolism ; Female ; Gene Expression Regulation, Developmental ; Gonadotropin-Releasing Hormone/metabolism ; Male ; Membrane Proteins/genetics ; Mitochondrial Proteins/genetics ; Receptors, G-Protein-Coupled/metabolism ; Reproduction/genetics ; Zebrafish/genetics ; Zebrafish/growth & development ; Zebrafish/physiology ; Zebrafish Proteins/genetics
Chemical Substances	Membrane Proteins ; Mitochondrial Proteins ; Receptors, G-Protein-Coupled ; Zebrafish Proteins ; smim20 protein, zebrafish ; Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2020-12-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2058346-1
ISSN	1872-7298 ; 1567-133X
ISSN (online)	1872-7298
ISSN	1567-133X
DOI	10.1016/j.gep.2020.119164
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Zs.A 5515: Show issues

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Article ; Online: Evaluation of Telephone-Based Cardiac Rehabilitation Services Delivered to Adults 65 and Older During the Early Months of the COVID-19 Pandemic.

Ownbey, Nicholas / Soukup, Jeff / Fugate-Whitlock, Elizabeth / Newsham, Tina M K

Journal of applied gerontology : the official journal of the Southern Gerontological Society

2022 Volume 41, Issue 10, Page(s) 2226–2234

Abstract: This study was performed to evaluate the effectiveness of a hybrid, telephone-based cardiac rehabilitation (TBCR) program implemented early in the COVID-19 pandemic compared with in-person, center-based programming offered prior to the pandemic. The ... ...

Abstract	This study was performed to evaluate the effectiveness of a hybrid, telephone-based cardiac rehabilitation (TBCR) program implemented early in the COVID-19 pandemic compared with in-person, center-based programming offered prior to the pandemic. The focus was on older adults' engagement and outcomes. Matched groups of hybrid and in-person cardiac rehabilitation (CR) participants were created from existing data and compared using t-tests and repeated measures ANOVAs. Qualitative interviews were conducted with participating CR staff then transcribed, coded, and analyzed for key themes. There were significant differences in body mass index and weight from pre-to post-CR within both hybrid and in-person groups. Despite this, CR staff believed exercise adherence was reduced in the hybrid group when compared to those in the in-person program. In the future, TBCR should be considered as an adjunct to in-person CR. Reluctance to prescribe exercise needs to be addressed through CR staff training.
MeSH term(s)	Aged ; COVID-19 ; Cardiac Rehabilitation ; Exercise ; Humans ; Pandemics ; Telephone
Language	English
Publishing date	2022-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	155897-3
ISSN	1552-4523 ; 0733-4648
ISSN (online)	1552-4523
ISSN	0733-4648
DOI	10.1177/07334648221104380
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Zs.A 2901: Show issues

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Article ; Online: Fetal Alloimmune Hemolytic Anemia (AHA) as a Potential Target for Transamniotic Fetal Immunotherapy (TRAFIT).

Whitlock, Ashlyn E / Moskowitzova, Kamila / Kycia, Ina / Zurakowski, David / Fauza, Dario O

Journal of pediatric surgery

2023 Volume 58, Issue 6, Page(s) 1107–1110

Abstract: Purpose: Fetal alloimmune hemolytic anemia (AHA) resulting from maternal antibodies against fetal erythrocytes may require fetal administration of immunoglobulin-G (IgG) via invasive methods. IgG can reach the fetal circulation after transamniotic fetal ...

Abstract	Purpose: Fetal alloimmune hemolytic anemia (AHA) resulting from maternal antibodies against fetal erythrocytes may require fetal administration of immunoglobulin-G (IgG) via invasive methods. IgG can reach the fetal circulation after transamniotic fetal immunotherapy (TRAFIT). We sought to both develop a model of AHA and to test TRAFIT as a potential treatment. Methods: Sprague-Dawley fetuses (n = 113) received intra-amniotic injections on gestational-day 18 (E18, term = E21) of either saline (control; n = 40), anti-rat-erythrocyte antibodies (AHA; n = 37), or anti-rat-erythrocyte antibodies plus IgG (AHA + IgG; n = 36). At term, blood was procured for red blood count (RBC), hematocrit, or ELISA for inflammatory markers. Results: There was no difference in survival [95% (107/113)] across groups (p = 0.87). Both hematocrit and RBC were significantly lower in the AHA group than controls (p < 0.001). Although still significantly lower than controls (p < 0.001), both hematocrit and RBC significantly increased in AHA + IgG group compared to AHA alone (p < 0.001). Pro-inflammatory TNF-α and IL1-β were significantly elevated from controls in the AHA group, but not in AHA + IgG (p < 0.001-0.159). Conclusions: Intra-amniotic injection of anti-rat-erythrocyte antibodies can reproduce manifestations of fetal AHA, constituting a practical model of this disease. Transamniotic fetal immunotherapy with IgG reduces anemia in this model and may emerge as a new minimally invasive means of treatment. Type of study: Animal and laboratory study. Level of evidence: N/A (animal and laboratory study).
MeSH term(s)	Animals ; Humans ; Rats ; Amniotic Fluid ; Anemia, Hemolytic ; Fetal Diseases/therapy ; Immunoglobulin G ; Immunotherapy ; Rats, Sprague-Dawley
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2023.02.034
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Article ; Online: Bidirectional Feto-Maternal Traffic of Donor Mesenchymal Stem Cells Following Transamniotic Stem Cell Therapy (TRASCET).

Moskowitzova, Kamila / Whitlock, Ashlyn E / Kycia, Ina / Zurakowski, David / Fauza, Dario O

Journal of pediatric surgery

2023 Volume 59, Issue 2, Page(s) 290–294

Abstract: Purpose: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has emerged experimentally as a potential treatment for different congenital diseases and maternal diseases of pregnancy. The broad applicability of TRASCET is ... ...

Abstract	Purpose: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has emerged experimentally as a potential treatment for different congenital diseases and maternal diseases of pregnancy. The broad applicability of TRASCET is predicated on hematogenous routing of donor MSCs via the placenta. We investigated whether donor MSC kinetics includes bidirectional traffic between the fetus and mother. Methods: Eight time-dated dams had their fetuses (n = 96) divided in 4 groups on gestational day 17 (E17, term = E21). Groups populating one uterine horn received intra-amniotic injections (50 μL) of either donor amniotic fluid-derived MSCs (2×10 Results: Overall survival was 95 % (91/96). When controlled by the acellular injection, positive luciferase activity was observed in the placentas of all MSC-injected fetuses, confirming viability of the donor cells at term. When controlled by the acellular injection group, MSC-CL fetuses showed positive luciferase activity in the bone marrow, peripheral blood, brain and skin (p = <0.001-0.048). No luciferase activity was detected in any maternal blood sample. Conclusion: Amniotic fluid-derived MSCs can traffic between the fetus and mother in both directions after simple intra-amniotic injection, in a healthy rat model. This phenomenon must be considered in TRASCET performed in twin/multiple pregnancies. Level of evidence: N/A (animal and laboratory study).
MeSH term(s)	Pregnancy ; Female ; Rats ; Animals ; Mesenchymal Stem Cell Transplantation ; Amniotic Fluid ; Placenta ; Mesenchymal Stem Cells ; Luciferases
Chemical Substances	Luciferases (EC 1.13.12.-)
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2023.10.009
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Article ; Online: Morphometric, Developmental, and Anti-Inflammatory Effects of Transamniotic Stem Cell Therapy (TRASCET) on the Fetal Heart and Lungs in a Model of Intrauterine Growth Restriction.

Whitlock, Ashlyn E / Moskowitzova, Kamila / Kycia, Ina / Zurakowski, David / Fauza, Dario O

Stem cells and development

2023 Volume 32, Issue 15-16, Page(s) 484–490

Abstract: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary ... ...

Abstract	Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O
MeSH term(s)	Pregnancy ; Female ; Humans ; Placenta ; Mesenchymal Stem Cell Transplantation ; Fetal Growth Retardation/therapy ; Amniotic Fluid ; Fetal Heart ; Inflammation/therapy ; Lung ; Anti-Inflammatory Agents
Chemical Substances	Anti-Inflammatory Agents
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2142214-X
ISSN	1557-8534 ; 1547-3287
ISSN (online)	1557-8534
ISSN	1547-3287
DOI	10.1089/scd.2023.0040
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Article ; Online: Long-term cognitive outcome after elective hip or knee total joint arthroplasty: A population-based observational study.

Tang, Angelina B / Diaz-Ramirez, L Grisell / Boscardin, W John / Smith, Alexander K / Ward, Derek / Glymour, M Maria / Whitlock, Elizabeth L

Journal of the American Geriatrics Society

2024

Abstract: ... surgery without expected functional benefits (e.g., cholecystectomy; inguinal herniorrhaphy), between 1998 ...

Abstract	Background: One year after elective hip or knee total joint arthroplasty (TJA), >30% of older adults meet criteria for postoperative neurocognitive disorder. However, this is not contextualized with long-term cognitive outcomes in comparable surgical and nonsurgical controls. We analyzed population-based data to compare long-term cognitive outcomes in older adults after TJA, other surgeries, and with and without arthritis pain. Methods: This was a retrospective observational analysis of United States older adults in the Health and Retirement Study (HRS) who underwent elective TJA, or elective surgery without expected functional benefits (e.g., cholecystectomy; inguinal herniorrhaphy), between 1998 and 2018 at aged 65 or older. TJA recipients were also age- and sex-matched to nonsurgical controls who reported moderate-severe arthritic pain or denied pain, so that comparison groups included surgical and nonsurgical (pain-suffering and pain-free) controls. We modeled biennially-assessed memory performance, a measure of direct and proxy cognitive assessments, before and after surgery, normalized to the rate of memory decline ("cognitive aging") in controls to express effect size estimates as excess, or fewer, months of memory decline. We used linear mixed effects models adjusted for preoperative health and demographic factors, including frailty, flexibly capturing time before/after surgery (knots at -4, 0, 8 years; discontinuity at surgery). Results: There were 1947 TJA recipients (average age 74; 63% women; 1358 knee, 589 hip) and 1631 surgical controls (average age 76; 38% women). Memory decline 3 years after TJA was similar to surgical controls (5.2 [95% confidence interval, CI -1.2 to 11.5] months less memory decline in the TJA group, p = 0.11) and nonsurgical controls. At 5 years, TJA recipients experienced 5.0 [95% CI -0.9 to 10.9] months less memory decline than arthritic pain nonsurgical controls. Conclusion: There is no systematic accelerated memory decline at 3 years after TJA compared with surgical or nonsurgical controls.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	80363-7
ISSN	1532-5415 ; 0002-8614
ISSN (online)	1532-5415
ISSN	0002-8614
DOI	10.1111/jgs.18724
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