Publications by authors named "Jessica Adams"

77 Publications

GFRAL-expressing neurons suppress food intake via aversive pathways.

Proc Natl Acad Sci U S A 2021 Feb;118(8)

Department of Surgery, University of Michigan, Ann Arbor, MI 48109;

The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated and conditional mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRP) neurons. Silencing CGRP neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption.
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http://dx.doi.org/10.1073/pnas.2021357118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923658PMC
February 2021

Determining patient needs to enhance exercise program implementation and uptake in rural settings for women after a cancer diagnosis.

Support Care Cancer 2021 Jan 25. Epub 2021 Jan 25.

University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL, 35294, USA.

Purpose: To qualitatively explore exercise barriers and facilitators experienced by rural female cancer survivors from the program interventionist and recipient perspective for the purpose of enhancing exercise program implementation and uptake in rural settings.

Methods: A descriptive qualitative study design was utilized. Focus groups were conducted prior to implementation of an evidence-based exercise program by a rural non-research cancer clinical site. Nineteen rural female cancer survivors (mean age = 61.7 ± 10.9 years) and 11 potential interventionists (mean age = 42.3 ± 15.3 years) completed focus groups (stratified by participant role). Focus groups were audio recorded, transcribed, coded, and analyzed using inductive thematic analysis with NVivo 11.

Results: Cancer survivors identified 12 barrier themes (cancer specific adverse effects, lack of support, lack of knowledge, perceived negative aspects of exercise, cost, lack of resources, motivation, inconvenience, lack of program flexibility, time, weather, safety) and eight facilitator themes (knowledge, ease of access, resources, awareness, cost, options, organized, fun) related to exercise. Interventionists identified seven barrier themes (cost, transportation, lack of cancer survivor and interventionist knowledge, fear, motivation, lack of support, lack of resources) and four facilitator themes (resources, support, knowledge, motivation). Narratives revealed differing role-specific perspectives on shared themes between survivors and interventionists as well as potential implementation strategies for enhancing exercise participation and exercise program uptake among rural female cancer survivors.

Conclusion: Exploring multi-level stakeholder perspectives on cancer survivors' exercise needs and related strategies yields important information for organizations to consider when implementing exercise programs in rural contexts.
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http://dx.doi.org/10.1007/s00520-021-05990-8DOI Listing
January 2021

Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer.

PLoS One 2020 31;15(12):e0244793. Epub 2020 Dec 31.

Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus. Here we demonstrate that deletion of nPE1 produces mild obesity while knockout of nPE2 has no discernible metabolic phenotypes. Additionally, we show that acute leptin administration has significant effects on nPE1 knockout mice, with food intake and body weight change significantly impacted by peripheral leptin treatment. nPE1 knockout mice became less responsive to leptin treatment over time as percent body weight change increased over 2 week exposure to peripheral leptin. Both Pomc and Agrp mRNA were not differentially affected by chronic leptin treatment however we did see a decrease in Pomc and Agrp mRNA in both nPE1 and nPE2 knockout calorie restricted mice as compared to calorie restricted PBS-treated WT mice. Collectively, these data suggest dynamic regulation of Pomc by nPE1 such that mice with nPE1 knockout become less responsive to the anorectic effects of leptin treatment over time. Our results also support our earlier findings in which nPE2 may only be critical in adult mice that lack nPE1, indicating that these neural enhancers work synergistically to influence metabolism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775064PMC
March 2021

Changes in neurocognitive assessment scores after initiating dolutegravir- versus elvitegravir-based antiretroviral therapy.

AIDS Care 2020 Oct 26:1-7. Epub 2020 Oct 26.

Clinical Pharmacokinetics Research Lab, National Institutes of Health, Bethesda, MD, USA.

This prospective cohort study enrolled people living with HIV initiating antiretroviral therapy (ART) containing the integrase inhibitors, dolutegravir (DTG) or elvitegravir (EVG) and administered the Montreal Cognitive Assessment (MoCA) at baseline and again after approximately six months to compare changes in MoCA scores. The proportion of patients found to have cognitive impairment, as indicated by a MoCA score <26/30, on each agent were also compared and comparisons were made between changes in each domain assessed by the MoCA (visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation). Thirty-five evaluable participants were enrolled, 18 on DTG and 17 on EVG. The median [interquartile range(IQR)] age was 44 (32 to 54) years, 63% were male, 57% were African American. The median (IQR) MoCA score at baseline was 25 (23 to 27) with no difference between groups (=0.249). The median (IQR) change in MoCA score was 0 (-1 to 2) for DTG and 1 (0 to 3) for EVG ( = 0.183). Of those on DTG, 8 (44%) had MoCA scores <26 on follow-up compared to 11 (65%) on EVG ( = 0.229). There were no significant differences in changes in any of the individual MoCA domains.
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http://dx.doi.org/10.1080/09540121.2020.1837337DOI Listing
October 2020

Evaluation of pyrolysis chars derived from marine macroalgae silage as soil amendments.

Glob Change Biol Bioenergy 2020 Sep 24;12(9):706-727. Epub 2020 Jul 24.

Biorefining Group Institute of Biological, Environmental and Rural Sciences Aberystwyth University Aberystwyth UK.

Pyrolysis char residues from ensiled macroalgae were examined to determine their potential as growth promoters on germinating and transplanted seedlings. Macroalgae was harvested in May, July and August from beach collections, containing predominantly and ; naturally seeded mussel lines dominated by ; and lines seeded with cultivated . Material was ensiled, pressed to pellets and underwent pyrolysis using a thermo-catalytic reforming (TCR) process, with and without additional steam. The chars generated were then assessed through proximate and ultimate analysis. Seasonal changes had the prevalent impact on char composition, though using mixed beach-harvested material gave a greater variability in elements than when using the offshore collections. Applying the char at 5% (v/v)/2% (w/w) into germination or seedling soils was universally negative for the plants, inhibiting or delaying all parameters assessed with no clear advantage in harvesting date, species or TCR processing methodology. In germinating lettuce seeds, soil containing the pyrolysis chars caused a longer germination time, poorer germination, fewer true leaves to be produced, a lower average plant health score and a lower final biomass yield. For transplanted ryegrass seedlings, there were lower plant survival rates, with surviving plants producing fewer leaves and tillers, lower biomass yields when cut and less regrowth after cutting. As water from the char-contained plant pots inhibited the lettuce char control, one further observation was that run-off water from the pyrolysis char released compounds which detrimentally affected cultivated plant growth. This study clearly shows that pyrolysed macroalgae char does not fit the standard assumption that chars can be used as soil amendments at 2% (w/w) addition levels. As the bioeconomy expands in the future, the end use of residues and wastes from bioprocessing will become a genuine global issue, requiring consideration and demonstration rather than hypothesized use.
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http://dx.doi.org/10.1111/gcbb.12722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508059PMC
September 2020

The utilization of seawater for the hydrolysis of macroalgae and subsequent bioethanol fermentation.

Sci Rep 2020 06 16;10(1):9728. Epub 2020 Jun 16.

School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, United Kingdom.

A novel seawater-based pretreatment process was developed to improve the hydrolysis yield of brown (Laminaria digitata), green (Ulva linza) and red (Porphyra umbilicalis) macroalgae. Pre-treated with 5% sulphuric acid at 121 °C, 15 minutes, L. digitata, U. linza and P. umbilicalis liberated 64.63 ± 0.30%, 69.19 ± 0.11% and 63.03 ± 0.04% sugar in seawater compared with 52.82 ± 0.16%, 45.93 ± 0.37% and 48.60 ± 0.07% in reverse-osmosis water, respectively. Low hydrolysis yields (2.6-11.7%) were observed in alkali and hydrothermal pretreatment of macroalgae, although seawater led to relatively higher yields. SEM images of hydrolyzed macroalgae showed that reverse-osmosis water caused contortions in the remaining cell walls following acid and hydrothermal pre-treatments in the L. digitata and U. linza samples. Fed-batch fermentations using concentrated green seaweed hydrolysates and seawater with marine yeast Wickerhamomyces anomalus M15 produced 48.24 ± 0.01 g/L ethanol with an overall yield of 0.329 g/g available sugars. Overall, using seawater in hydrolysis of seaweed increased sugar hydrolysis yield and subsequent bioethanol production.
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http://dx.doi.org/10.1038/s41598-020-66610-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297732PMC
June 2020

Arthroscopic thermal stabilization for distal radioulnar joint instability: 3 to 19 years follow-up.

J Hand Surg Eur Vol 2020 Nov 9;45(9):916-922. Epub 2020 Jun 9.

Department of Orthopaedic Surgery, University of Kansas School of Medicine, Wichita, KS, USA.

This retrospective study investigated the clinical outcomes of patients treated for chronic distal radioulnar joint instability with arthroscopic thermal annealing of the superficial radioulnar ligaments, ulnar palmar wrist ligaments, and dorsoulnar wrist capsule using a radiofrequency probe. Sixty patients (62 wrists) were treated over an 18-year period. At mean follow-up of 10 years (range 3 to 19), 30 of 33 patients were satisfied with their surgical outcomes. There were statistically significant improvements in ulnar-sided wrist pain on a visual analogue scale and in distal radioulnar joint stability on the dorsopalmar stress test after surgery compared with preoperative status. The modified Mayo Wrist Score and Quick Disabilities of the Arm, Shoulder, and Hand score of the patients were favourable. Early failure occurred in 11 of 62 wrists. Nine of these 11 wrists needed a secondary procedure. We conclude that arthroscopic thermal shrinkage is effective for the majority of the patients with mild to moderate chronic distal radioulnar joint instability in long-term follow-up. Secondary open ligament reconstruction is an option in the case of early failure. IV.
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http://dx.doi.org/10.1177/1753193420927882DOI Listing
November 2020

A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine.

Clin Infect Dis 2020 05;70(11):2241-2246

Johns Hopkins School of Medicine, Baltimore, Maryland.

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists. To reduce the risk of medication-related errors, antiretroviral stewardship programs (ARVSPs) are needed to enhance patient safety. This call to action, endorsed by the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine, is modeled upon the success of antimicrobial stewardship programs now mandated by the Joint Commission. Herein, we propose definitions of ARVSPs, suggest resources for ARVSP leadership, and provide a summary of published, successful strategies for ARVSP that healthcare facilities may use to develop locally appropriate programs.
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http://dx.doi.org/10.1093/cid/ciz792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245143PMC
May 2020

Paraventricular, subparaventricular and periventricular hypothalamic IRS4-expressing neurons are required for normal energy balance.

Sci Rep 2020 03 26;10(1):5546. Epub 2020 Mar 26.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Understanding the neural components modulating feeding-related behavior and energy expenditure is crucial to combating obesity and its comorbidities. Neurons within the paraventricular nucleus of the hypothalamus (PVH) are a key component of the satiety response; activation of the PVH decreases feeding and increases energy expenditure, thereby promoting negative energy balance. In contrast, PVH ablation or silencing in both rodents and humans leads to substantial obesity. Recent studies have identified genetically-defined PVH subpopulations that control discrete aspects of energy balance (e.g. oxytocin (OXT), neuronal nitric oxide synthase 1 (NOS1), melanocortin 4-receptor (MC4R), prodynorphin (PDYN)). We previously demonstrated that non-OXT NOS1 neurons contribute to PVH-mediated feeding suppression. Here, we identify and characterize a non-OXT, non-NOS1 subpopulation of PVH and peri-PVH neurons expressing insulin-receptor substrate 4 (IRS4) involved in energy balance control. Using Cre-dependent viral tools to activate, trace and silence these neurons, we highlight the sufficiency and necessity of IRS4 neurons in normal feeding and energy expenditure regulation. Furthermore, we demonstrate that IRS4 neurons lie within a complex hypothalamic circuitry that engages distinct hindbrain regions and is innervated by discrete upstream hypothalamic sites. Overall, we reveal a requisite role for IRS4 neurons in PVH-mediated energy balance which raises the possibility of developing novel approaches targeting IRS4 neurons for anti-obesity therapies.
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http://dx.doi.org/10.1038/s41598-020-62468-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099088PMC
March 2020

Guide RNA Engineering Enables Dual Purpose CRISPR-Cpf1 for Simultaneous Gene Editing and Gene Regulation in .

ACS Synth Biol 2020 04 2;9(4):967-971. Epub 2020 Apr 2.

Chemical and Environmental Engineering, University of California Riverside, Riverside, California 92521, United States.

has fast become a biotechnologically significant yeast for its ability to accumulate lipids to high levels. While there exists a suite of synthetic biology tools for genetic engineering in this yeast, there is a need for multipurposed tools for rapid strain generation. Here, we describe a dual purpose CRISPR-Cpf1 system that is capable of simultaneous gene disruption and gene regulation. Truncating guide RNA spacer length to 16 nt inhibited nuclease activity but not binding to the target loci, enabling gene activation and repression with Cpf1-fused transcriptional regulators. Gene repression was demonstrated using a Cpf1-Mxi1 fusion achieving a 7-fold reduction in mRNA, while CRISPR-activation with Cpf1-VPR increased hrGFP expression by 10-fold. High efficiency disruptions were achieved with gRNAs 23-25 bp in length, and efficiency and repression levels were maintained with multiplexed expression of truncated and full-length gRNAs. The developed CRISPR-Cpf1 system should prove useful in metabolic engineering, genome wide screening, and functional genomics studies.
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http://dx.doi.org/10.1021/acssynbio.9b00498DOI Listing
April 2020

Delphi assessment of audit and research priorities in an emergency department.

Emerg Med Australas 2020 08 5;32(4):556-561. Epub 2020 Feb 5.

Emergency Department, The Royal Children's Hospital, Melbourne, Victoria, Australia.

Objective: Audit and research projects in the ED are important to improve patient care but can be time and resource consuming. We identified and prioritised audit and research topics among multidisciplinary ED staff to fill perceived knowledge gaps, encourage engagement, reduce duplication and facilitate translation of evidence into clinical practice.

Methods: A two-stage electronic Delphi survey process was undertaken by senior medical, nursing, education and social work staff at the Royal Children's Hospital, Victoria. Survey 1 collected demographic data and audit and research ideas following a series of open-ended questions. Priority themes were defined as those that had more than four responses. Survey 2 used a 7-point Likert ranking of these themes to generate a departmental audit and research prioritisation list.

Results: 72/89 (82%) available senior staff responded to survey 1 and 63/83 (76%) responded to survey 2. Survey 1 yielded 208 audit and 130 research topics. Survey 2 established a prioritised list of 17 audit and 14 research topics. Top audit themes were mental healthcare, patient flow, management of sepsis and delays in ED specialist referrals. Top research priorities were the management of sepsis, mental healthcare, management of patients with autism and the management of severe asthma.

Conclusions: This Delphi study has provided departmental audit and research priorities that are perceived to be of importance across the multidisciplinary ED team. This methodology allows strategic allocation of limited resources and may increase staff engagement.
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http://dx.doi.org/10.1111/1742-6723.13453DOI Listing
August 2020

Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.

Cell Metab 2020 02 16;31(2):301-312.e5. Epub 2020 Jan 16.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA; Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48105, USA. Electronic address:

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr neurons decreased food intake and body weight but (unlike neighboring Cck cells) failed to promote aversion, revealing that Calcr neurons mediate a non-aversive suppression of food intake. While both Calcr and Cck neurons decreased feeding via projections to the PBN, Cck cells activated aversive CGRP cells while Calcr cells activated distinct non-CGRP PBN cells. Hence, Calcr cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing Calcr cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, Calcr neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.
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http://dx.doi.org/10.1016/j.cmet.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104375PMC
February 2020

Comparison of psychiatric comorbidities and impact on quality of life in patients with epilepsy or psychogenic nonepileptic spells.

Epilepsy Behav 2020 01 20;102:106649. Epub 2019 Nov 20.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, TX 75390, USA. Electronic address:

Objectives: Psychiatric comorbidity is common in people with epilepsy (PWE) and psychogenic nonepileptic spells (PNES). These comorbidities can be detrimental to quality of life (QOL) and are often underdiagnosed and undertreated. Some types of epilepsy, such as focal temporal lobe epilepsy (TLE), have been associated with higher rates of psychiatric comorbidity. This study examined the impact of psychiatric comorbidity on QOL in patients admitted to two level 4 epilepsy monitoring units (EMUs).

Methods: In this prospective observational study, 200 patients admitted to two level 4 EMUs completed standardized surveys including the Quality of Life in Epilepsy (QOLIE-31-P), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Beck Depression Inventory-II (BDI-II). Hierarchal multiple regression was performed to assess impact on QOL.

Results: Of the 200 participants, 113 had a diagnosis of epilepsy, 36 had a diagnosis of PNES, and 51 were excluded for nondiagnostic evaluation or dual diagnosis. Of those with epilepsy, 65 had TLE, 28 had focal extratemporal lobe epilepsy (ETLE), and 20 had nonfocal epilepsy. Patients with PNES had higher self-reported anxiety and depression levels (GAD-7: p = 0.04, PHQ-9: p < 0.01; BDI-II: p < 0.01) but similar QOL to PWE (p = 0.78). Using hierarchal multiple regression, symptoms of anxiety and depression were significant predictors of lower QOL in PWE but not in patients with PNES. There was no difference in QOL in those with ETLE and TLE.

Conclusions: Our findings suggest that self-reported anxiety and depression symptoms are common in patients admitted to level 4 EMUs regardless of diagnosis and play an important role in predicting QOL in PWE. Our findings emphasize the importance of routinely screening all EMU patients for psychiatric comorbidity.
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http://dx.doi.org/10.1016/j.yebeh.2019.106649DOI Listing
January 2020

Diet, digestion and energy intake in captive common marmosets (Callithrix jacchus): research and management implications.

Sci Rep 2019 08 20;9(1):12134. Epub 2019 Aug 20.

Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.

Common marmosets (Callithrix jacchus) are susceptible to intestinal inflammation which leads to chronic diarrhea, weight loss, and vitamin D deficiency. We examined food intake and digestion in three mixed-sex groups of adult marmosets maintained on three commercial base diets. Animals underwent two consecutive 4-day digestion trials. Body mass stayed constant. Feces and diet were assayed for Mn, fat, and gross energy (GE). Apparent digestibility of dry matter (ADDM) was calculated by the total collection method and from dietary and fecal Mn; the methods produced correlated results (r = 0.658, p < 0.001). Apparent digestibility of energy (ADE) was calculated from ADDM and the GE of feces and diet; apparent digestibility of fat (ADfat) was calculated from ADDM and fecal fat. ADDM and ADE varied by diet (p < 0.001). We found poor digesters on all three diets. The concentration of fecal fat was inversely related to ADE (r = -0.729, p < 0.001). High fecal fat (>10%) was associated with ADfat of zero, consistent with lipid malabsorption. Mean digestible energy intake (DEI) was equal to 1.5 the estimated metabolic rate, but varied widely between individuals. The diet with the fewest animals with high fecal fat had the highest mean DEI and most animals above 450 g, suggesting it may be obesogenic.
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http://dx.doi.org/10.1038/s41598-019-48643-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702194PMC
August 2019

Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis.

Clin Infect Dis 2019 11;69(12):2201-2204

Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics.

Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP's active metabolites vs competing deoxynucleotides compared to cisgender women and men (P = .03) that inversely correlated with estradiol (ρ = -0.79; P < .05). Thus, FHT may negatively impact PrEP efficacy. Clinical Trials Registration . NCT02983110.
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http://dx.doi.org/10.1093/cid/ciz290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188232PMC
November 2019

Review of Real-World Implementation Data on Emtricitabine-Tenofovir Disoproxil Fumarate as HIV Pre-exposure Prophylaxis in the United States.

Pharmacotherapy 2019 04 1;39(4):486-500. Epub 2019 Apr 1.

University of Minnesota College of Pharmacy, Minneapolis, Minnesota.

The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012. Since then, Centers for Disease Control and Prevention guidelines for the use of PrEP have been published and implemented into clinical practice throughout the United States. A number of published open-label and PrEP demonstration projects have evaluated the real-world use of PrEP including analysis of the barriers to its use and addressing major concerns. Despite the approval of FTC/TDF for PrEP, its use for this indication relies on patient and provider acceptance, and its effectiveness requires patient adherence and retention in care during periods of high-risk behaviors. Concerns regarding the use of PrEP in healthy individuals persist and include medication adverse effects including renal dysfunction and bone mineral density loss; risk compensation leading to HIV infections, sexually transmitted infections, and unintended pregnancies; and the development of drug resistance in the event of seroconversion. The cost-effectiveness of PrEP continues to be assessed with the greatest cost-effectiveness remaining in those at highest risk of acquiring HIV. Additionally, cases of HIV acquisition in individuals who are adherent to PrEP highlight scenarios in which PrEP is not 100% effective including against the transmission of drug-resistant HIV strains. This review examines data on the implementation of PrEP outside the setting of clinical trials with the aim of providing clinicians with a summary of the current barriers and opportunities for PrEP use with a specific focus on the role of pharmacists in the optimization of PrEP implementation.
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http://dx.doi.org/10.1002/phar.2240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453722PMC
April 2019

Outcomes of ulnar nerve anterior transmuscular transposition and significance of ulnar nerve instability in cubital tunnel syndrome.

J Shoulder Elbow Surg 2019 Jun 13;28(6):1120-1129. Epub 2019 Feb 13.

Advanced Orthopaedics Associates, PA, Wichita, KS, USA; Department of Orthopaedic Surgery, University of Kansas School of Medicine-Wichita, Wichita, KS, USA. Electronic address:

Background: We investigated the experience of a single surgeon with ulnar nerve anterior transmuscular transposition with the patient in the lateral decubitus position for cubital tunnel syndrome.

Methods: The medical records of all patients who underwent primary or revision ulnar nerve anterior transmuscular transposition were screened to define a cohort of 156 patients (162 limbs) for further study of demographic and disease-specific data and retrospective assessment of short-term outcomes. Ulnar neuropathy severity was stratified by McGowan grade. A prospective cohort composed of 49 patients (51 limbs) with a minimum 2-year follow-up volunteered to complete patient outcome surveys, and some presented for an ulnar nerve-focused examination to assess long-term outcomes.

Results: The overall patient satisfaction rate was 92%, with statistically significant improvements in ulnar sensation and intrinsic strength at short- and long-term follow-up. Outcomes were better for lower McGowan grades than for higher grades and better in primary cases than in revision cases. Ulnar nerve instability was observed in 69 of 162 cases (43%) in this series. A major complication occurred in 7 cases (4.3%), but all were mitigated by contributory patient-related factors. Reoperation for recurrent ulnar paresthesia was required in 4 cases (2.5%). No operations or outcomes were compromised by the lateral decubitus position.

Discussion And Conclusion: Ulnar nerve anterior transmuscular transposition in the lateral decubitus position is a good surgical option for primary or recurrent cubital tunnel syndrome and remains our preferred procedure. The high prevalence of ulnar nerve instability observed in this study is a factor worthy of consideration by surgeons and patients weighing the surgical options for ulnar neuropathy at the elbow.
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http://dx.doi.org/10.1016/j.jse.2018.11.054DOI Listing
June 2019

Transcriptional and physiological roles for STAT proteins in leptin action.

Mol Metab 2019 04 24;22:121-131. Epub 2019 Jan 24.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Objectives: Leptin acts via its receptor LepRb on specialized neurons in the brain to modulate food intake, energy expenditure, and body weight. LepRb activates signal transducers and activators of transcription (STATs, including STAT1, STAT3, and STAT5) to control gene expression.

Methods: Because STAT3 is crucial for physiologic leptin action, we used TRAP-seq to examine gene expression in LepRb neurons of mice ablated for Stat3 in LepRb neurons (Stat3KO mice), revealing the STAT3-dependent transcriptional targets of leptin. To understand roles for STAT proteins in leptin action, we also ablated STAT1 or STAT5 from LepRb neurons and expressed a constitutively-active STAT3 (CASTAT3) in LepRb neurons.

Results: While we also found increased Stat1 expression and STAT1-mediated transcription of leptin-regulated genes in Stat3KO mice, ablating Stat1 in LepRb neurons failed to alter energy balance (even on the Stat3KO background); ablating Stat5 in LepRb neurons also failed to alter energy balance. Importantly, expression of a constitutively-active STAT3 (CASTAT3) in LepRb neurons decreased food intake and body weight and improved metabolic parameters in leptin-deficient (ob/ob) mice, as well as in wild-type animals.

Conclusions: Thus, STAT3 represents the unique STAT protein required for leptin action and STAT3 suffices to mediate important components of leptin action in the absence of other LepRb signals.
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http://dx.doi.org/10.1016/j.molmet.2019.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437596PMC
April 2019

Cross-sectional comparison of health-span phenotypes in young versus geriatric marmosets.

Am J Primatol 2019 02 21;81(2):e22952. Epub 2019 Jan 21.

Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas.

The development of the marmoset as a translational model for healthspan and lifespan studies relies on the characterization of health parameters in young and geriatric marmosets. This cross-sectional study examined health phenotypes in marmosets for five domains of interest for human health and aging: mobility, cognition, metabolism, homeostasis, and immune function. Geriatric marmosets were found to have significant executive function impairment when compared to young animals. While geriatric animals did not show gross abnormalities in mobility and measures of locomotion, their types of movement were altered from young animals. Geriatric marmosets had alterations in cardiac function, with significantly increased mean arterial pressures; metabolism, with significantly lower VO ; and suppressed immune function. Further, this study sought to characterize and describe histopathology for both young and geriatric healthy marmosets. Overall this study provides a characterization of health parameters for young and geriatric marmosets which will greatly enhance future aging and interventional testing in marmosets.
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http://dx.doi.org/10.1002/ajp.22952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036287PMC
February 2019

Age-related changes in myelin of axons of the corpus callosum and cognitive decline in common marmosets.

Am J Primatol 2019 02 8;81(2):e22949. Epub 2019 Jan 8.

Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas.

Executive control is a higher-level cognitive function that involves a range of different processes that are involved in the planning, coordination, execution, and inhibition of responses. Many of the processes associated with executive control, such as response inhibition and mental flexibility, decline with age. Degeneration of white matter architecture is considered to be the one of the key factors underlying cognitive decline associated with aging. Here we investigated how white matter changes of the corpus callosum were related to cognitive aging in common marmosets (Callithrix jacchus). We hypothesized that reduction in myelin thickness, myelin density, and myelin fraction of axonal fibers in the corpus callosum would be associated with performance on a task of executive function in a small sample of geriatric marmosets (n = 4) and young adult marmosets (n = 2). Our results indicated declines in myelin thickness, density, and myelin fraction with age. Considerable variability was detected on these characteristics of myelin and cognitive performance assessed via the detoured reach task. Age-related changes in myelin in Region II of the corpus callosum were predictive of cognitive performance on the detoured reach task. Thus the detoured reach task appears to also measure aspects of corticostriatal function in addition to prefrontal cortical function.
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http://dx.doi.org/10.1002/ajp.22949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685070PMC
February 2019

Hypothalamic POMC or MC4R deficiency impairs counterregulatory responses to hypoglycemia in mice.

Mol Metab 2019 02 20;20:194-204. Epub 2018 Nov 20.

Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address:

Objective: Life-threatening hypoglycemia is a major limiting factor in the management of diabetes. While it is known that counterregulatory responses to hypoglycemia are impaired in diabetes, molecular mechanisms underlying the reduced responses remain unclear. Given the established roles of the hypothalamic proopiomelanocortin (POMC)/melanocortin 4 receptor (MC4R) circuit in regulating sympathetic nervous system (SNS) activity and the SNS in stimulating counterregulatory responses to hypoglycemia, we hypothesized that hypothalamic POMC as well as MC4R, a receptor for POMC derived melanocyte stimulating hormones, is required for normal hypoglycemia counterregulation.

Methods: To test the hypothesis, we induced hypoglycemia or glucopenia in separate cohorts of mice deficient in either POMC or MC4R in the arcuate nucleus (ARC) or the paraventricular nucleus of the hypothalamus (PVH), respectively, and measured their circulating counterregulatory hormones. In addition, we performed a hyperinsulinemic-hypoglycemic clamp study to further validate the function of MC4R in hypoglycemia counterregulation. We also measured Pomc and Mc4r mRNA levels in the ARC and PVH, respectively, in the streptozotocin-induced type 1 diabetes mouse model and non-obese diabetic (NOD) mice to delineate molecular mechanisms by which diabetes deteriorates the defense systems against hypoglycemia. Finally, we treated diabetic mice with the MC4R agonist MTII, administered stereotaxically into the PVH, to determine its potential for restoring the counterregulatory response to hypoglycemia in diabetes.

Results: Stimulation of epinephrine and glucagon release in response to hypoglycemia or glucopenia was diminished in both POMC- and MC4R-deficient mice, relative to their littermate controls. Similarly, the counterregulatory response was impaired in association with decreased hypothalamic Pomc and Mc4r expression in the diabetic mice, a phenotype that was not reversed by insulin treatment which normalized glycemia. In contrast, infusion of an MC4R agonist in the PVH restored the counterregulatory response in diabetic mice.

Conclusion: In conclusion, hypothalamic Pomc as well as Mc4r, both of which are reduced in type 1 diabetic mice, are required for normal counterregulatory responses to hypoglycemia. Therefore, enhancing MC4R function may improve hypoglycemia counterregulation in diabetes.
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http://dx.doi.org/10.1016/j.molmet.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358536PMC
February 2019

Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast.

Cell Rep 2018 10;25(3):702-714.e6

Program in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Electronic address:

CDH1 and PIK3CA are the two most frequently mutated genes in invasive lobular carcinoma (ILC) of the breast. Transcription profiling has identified molecular subtypes for ILC, one of which, immune-related (IR), is associated with gene expression linked to lymphocyte and macrophage infiltration. Here, we report that deletion of Cdh1, together with activation of Pik3ca in mammary epithelium of genetically modified mice, leads to formation of IR-ILC-like tumors with immune cell infiltration, as well as gene expression linked to T-regulatory (Treg) cell signaling and activation of targetable immune checkpoint pathways. Interestingly, these tumors show enhanced Rac1- and Yap-dependent transcription and signaling, as well as sensitivity to PI3K, Rac1, and Yap inhibitors in culture. Finally, high-dimensional immunophenotyping in control mouse mammary gland and IR-ILC tumors by mass cytometry shows dramatic alterations in myeloid and lymphoid populations associated with immune suppression and exhaustion, highlighting the potential for therapeutic intervention via immune checkpoint regulators.
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http://dx.doi.org/10.1016/j.celrep.2018.09.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276789PMC
October 2018

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

PLoS Med 2018 09 24;15(9):e1002660. Epub 2018 Sep 24.

Neurology Department, Multimedica, Castellanza, Italy.

Background: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease.

Methods And Findings: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid.

Conclusions: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.

Trial Registration: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.
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http://dx.doi.org/10.1371/journal.pmed.1002660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152871PMC
September 2018

Describing pharmacy student participation in an international, interprofessional medical mission trip as part of an advanced pharmacy practice experience (APPE).

Curr Pharm Teach Learn 2018 07 27;10(7):940-945. Epub 2018 Apr 27.

Philadelphia College of Pharmacy at University of the Sciences, 600 S. 43rd St, Box 34, Philadelphia, PA 19104, United States. Electronic address:

Background And Purpose: Several schools of pharmacy across the United States have taken steps to incorporate international medical mission trips into the doctor of pharmacy (PharmD) curriculum. This study aims to describe the impact of advanced pharmacy practice experience (APPE)-level student pharmacists on an interprofessional team during an international medical mission trip to Jamaica.

Educational Activity And Setting: The Jamaica Medical Mission (JMM) trip is an annual event involving healthcare professionals from several disciplines across multiple universities and healthcare systems. At this institution, the JMM trip is included as part of a rural health elective APPE rotation. Students electing to participate in this rotation are provided with the opportunity to serve as active participants on an interprofessional healthcare team in underserved and under-resourced communities throughout Jamaica. The JMM trip that took place during June 2016 included healthcare professionals and students in the fields of medicine, dentistry, optometry, nursing, and pharmacy. A total of five pharmacist preceptors and 10 pharmacy students attended the JMM trip in June 2016. Approximately three to five clinic sites per day were conducted simultaneously on each of the seven clinic days at various locations throughout Jamaica. The interprofessional healthcare teams provided free medical care, including physical exams and access to prescription and non-prescription medications.

Findings: The interprofessional healthcare team saw a total of 1014 patients and dispensed 1879 prescriptions during the seven clinic days. A total of 811 clinical recommendations were made by student pharmacists and/or pharmacy preceptors. Of these recommendations, 561 (69%) were made by student pharmacists without pharmacy preceptor prompting, 103 (13%) were made by the student pharmacist with preceptor prompting, and 147 (18%) were made by pharmacy preceptors. Over 70% of recommendations made by student pharmacists without pharmacy preceptor prompting were accepted by prescribers.

Discussion And Summary: This study sought to describe the impact of APPE-level student pharmacists on an interprofessional team during an international medical mission trip. Our findings demonstrate that APPE-level student pharmacists were capable of making a substantial number of clinical recommendations without preceptor prompting. The number of recommendations made by students without preceptor prompting were consistently greater than the number of recommendations made with preceptor prompting throughout the trip. Future studies should address student competence in achieving learning objectives associated with international, interprofessional APPE rotations.
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http://dx.doi.org/10.1016/j.cptl.2018.04.009DOI Listing
July 2018

Species variation in the effects of dewatering treatment on macroalgae.

J Appl Phycol 2018 20;30(4):2305-2316. Epub 2018 Feb 20.

5Agricultural Centre for Sustainable Energy Systems, Harper Adams University, Newport, Shropshire TF10 8NB UK.

Seaweeds can be a valuable resource for biorefinery and biotechnology applications, but their high water content is a recurrent problem and one of the key bottlenecks for their sustainable use. Treatments to increase dry matter content of the kelp were recently described by the authors. However macroalgae are an extremely diverse group of organisms and compositional variation between species may influence the effects of particular treatments. In this study, potential dewatering treatments including drying, osmotic media, and the application of both organic and mineral acids all followed by screw-pressing have been tested on two other species of kelp ( and ) and a red seaweed (). Conditions that dewatered these species were identified and the data have been combined with the previous results for . There were significant differences between species across all the traits of interest. However dewatering was highly dependent on specific interactions with both treatment and season of collection. Nevertheless, the dry matter content of brown seaweeds was widely and successfully increased by air drying or acid treatment followed by screw-pressing. The results for were quite different, particularly with regard to juice production. For this species, acid treatment did not result in dewatering, but dry matter content could be increased by screw-pressing immediately after harvest. Together the data presented here demonstrate that dewatering pre-treatments need to be specific for the type of seaweed to be processed; important knowledge for the future use of this sustainable biomass resource.
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http://dx.doi.org/10.1007/s10811-018-1420-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096787PMC
February 2018

Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor-Expressing Glutamatergic Neurons.

Diabetes 2018 08 18;67(8):1538-1548. Epub 2018 May 18.

Department of Pediatrics, University of Michigan, Ann Arbor, MI

Glucagon-like peptide 1 receptor (GLP-1R) agonists are U.S. Food and Drug Administration-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) affect appetite and body weight are still not fully understood. We determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the short- and long-term effects of the GLP1RA liraglutide on food intake, visceral illness, body weight, and neural network activation. We found that mice lacking GLP-1Rs in -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding. Concomitantly, deletion of GLP-1Rs from glutamatergic neurons completely abolished the neural network activation observed after liraglutide administration. We conclude that liraglutide activates a dispersed but discrete neural network to mediate its physiological effects and that these effects require GLP-1R expression on glutamatergic but not GABAergic neurons.
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http://dx.doi.org/10.2337/db17-1385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054439PMC
August 2018

Essential Role for Hypothalamic Calcitonin Receptor‒Expressing Neurons in the Control of Food Intake by Leptin.

Endocrinology 2018 04;159(4):1860-1872

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

The adipocyte-derived hormone leptin acts via its receptor (LepRb) on central nervous system neurons to communicate the repletion of long-term energy stores, to decrease food intake, and to promote energy expenditure. We generated mice that express Cre recombinase from the calcitonin receptor (Calcr) locus (Calcrcre mice) to study Calcr-expressing LepRb (LepRbCalcr) neurons, which reside predominantly in the arcuate nucleus (ARC). Calcrcre-mediated ablation of LepRb in LepRbCalcrknockout (KO) mice caused hyperphagic obesity. Because LepRb-mediated transcriptional control plays a crucial role in leptin action, we used translating ribosome affinity purification followed by RNA sequencing to define the transcriptome of hypothalamic Calcr neurons, along with its alteration in LepRbCalcrKO mice. We found that ARC LepRbCalcr cells include neuropeptide Y (NPY)/agouti-related peptide (AgRP)/γ-aminobutyric acid (GABA) ("NAG") cells as well as non-NAG cells that are distinct from pro-opiomelanocortin cells. Furthermore, although LepRbCalcrKO mice exhibited dysregulated expression of several genes involved in energy balance, neither the expression of Agrp and Npy nor the activity of NAG cells was altered in vivo. Thus, although direct leptin action via LepRbCalcr cells plays an important role in leptin action, our data also suggest that leptin indirectly, as well as directly, regulates these cells.
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http://dx.doi.org/10.1210/en.2017-03259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888224PMC
April 2018

Reduced renal sympathetic nerve activity contributes to elevated glycosuria and improved glucose tolerance in hypothalamus-specific Pomc knockout mice.

Mol Metab 2017 10 17;6(10):1274-1285. Epub 2017 Jul 17.

Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address:

Objective: Hypothalamic arcuate nucleus-specific pro-opiomelanocortin deficient (ArcPomc) mice exhibit improved glucose tolerance despite massive obesity and insulin resistance. We demonstrated previously that their improved glucose tolerance is due to elevated glycosuria. However, the underlying mechanisms that link glucose reabsorption in the kidney with ArcPomc remain unclear. Given the function of the hypothalamic melanocortin system in controlling sympathetic outflow, we hypothesized that reduced renal sympathetic nerve activity (RSNA) in ArcPomc mice could explain their elevated glycosuria and consequent enhanced glucose tolerance.

Methods: We measured RSNA by multifiber recording directly from the nerves innervating the kidneys in ArcPomc mice. To further validate the function of RSNA in glucose reabsorption, we denervated the kidneys of WT and diabetic db/db mice before measuring their glucose tolerance and urine glucose levels. Moreover, we performed western blot and immunohistochemistry to determine kidney GLUT2 and SGLT2 levels in either ArcPomc mice or the renal-denervated mice.

Results: Consistent with our hypothesis, we found that basal RSNA was decreased in ArcPomc mice relative to their wild type (WT) littermates. Remarkably, both WT and db/db mice exhibited elevated glycosuria and improved glucose tolerance after renal denervation. The elevated glycosuria in obese ArcPomc, WT and db/db mice was due to reduced renal GLUT2 levels in the proximal tubules. Overall, we show that renal-denervated WT and diabetic mice recapitulate the phenotype of improved glucose tolerance and elevated glycosuria associated with reduced renal GLUT2 levels observed in obese ArcPomc mice.

Conclusion: Hence, we conclude that ArcPomc is essential in maintaining basal RSNA and that elevated glycosuria is a possible mechanism to explain improved glucose tolerance after renal denervation in drug resistant hypertensive patients.
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http://dx.doi.org/10.1016/j.molmet.2017.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641634PMC
October 2017

A Single-Center Retrospective Cohort Analysis of Maternal and Infant Outcomes in HIV-Infected Mothers Treated with Integrase Inhibitors During Pregnancy.

Infect Dis Ther 2017 Dec 13;6(4):531-544. Epub 2017 Sep 13.

Cooper University Hospital, Camden, NJ, USA.

Introduction: Integrase strand transfer inhibitors (INSTI) are currently being investigated for the treatment of HIV in pregnancy. The purpose of this study is to evaluate the differences in maternal and infant outcomes in HIV-positive mothers treated with INSTI-containing antiretroviral therapy (ART) during pregnancy compared to protease inhibitor (PI)-containing ART.

Methods: A retrospective, cohort study of INSTI- and PI-based ART used in pregnancy between 2007 and 2015 was performed. The primary objective was to evaluate the differences in viral load (VL) suppression prior to delivery. Secondary endpoints included time to and duration of VL suppression and safety parameters in both mothers and infants. For the primary analysis, the two arms were matched 1:2 INSTI to PI based on the presence or absence of viremia at the time of pregnancy determination. Additional analysis was performed on the entire matched and unmatched dataset.

Results: Twenty-one patients were matched (7 INSTI and 14 PI). There were no significant differences between groups with respect to the proportion of patients with VL suppression prior to delivery (71.4% INSTI vs. 92.9% PI, p = 0.247), and there were no significant differences in any of the secondary endpoints. Patients with documented adherence issues were statistically more likely to not be virologically suppressed prior to delivery (p = 0.002).

Conclusion: No differences in efficacy or safety were found between patients treated with INSTIs compared to PIs. This study supports the further investigation of the use of INSTIs during pregnancy to reduce HIV transmission.
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http://dx.doi.org/10.1007/s40121-017-0170-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700890PMC
December 2017

Using Community-Based Participatory Research and Human-Centered Design to Address Violence-Related Health Disparities Among Latino/a Youth.

Fam Community Health 2017 Apr/Jun;40(2):160-169

Department of Counseling, Clinical, and School Psychology, University of California, Santa Barbara (Dr Kia-Keating and Mss Santacrose and Liu); and Child Abuse Listening Mediation (CALM), Santa Barbara, California (Dr Adams).

High rates of exposure to violence and other adversities among Latino/a youth contribute to health disparities. The current article addresses the ways in which community-based participatory research (CBPR) and human-centered design (HCD) can help engage communities in dialogue and action. We present a project exemplifying how community forums, with researchers, practitioners, and key stakeholders, including youths and parents, integrated HCD strategies with a CBPR approach. Given the potential for power inequities among these groups, CBPR + HCD acted as a catalyst for reciprocal dialogue and generated potential opportunity areas for health promotion and change. Future directions are described.
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http://dx.doi.org/10.1097/FCH.0000000000000145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319705PMC
September 2017