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Shlomo Yeshurun, Anthony J Hannan
In recent years, striking new evidence has demonstrated non-genetic inheritance of acquired traits associated with parental environmental exposures. In particular, this transgenerational modulation of phenotypic traits is of direct relevance to psychiatric disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. Here we review the recent progress in this field, with an emphasis on acquired traits of psychiatric illnesses transmitted epigenetically via the male lineage. We discuss the transgenerational effects of paternal exposure to stress vs...
March 8, 2018: Molecular Psychiatry
Edward L Hannan, Zaza Samadashvili, Kimberly Cozzens, Peter B Berger, Joanna Chikwe, Alice K Jacobs, Gary Walford, Frederick S K Ling, Ferdinand J Venditti, Jeffrey Gold, Spencer B King
OBJECTIVES: The purpose of this study is to revisit cases rated as "inappropriate" in the 2012 appropriate use criteria (AUC) using the 2017 AUC. BACKGROUND: AUC for coronary revascularization in patients with stable ischemic heart disease (SIHD) were released in January 2017. Earlier 2012 AUC identified a relatively high percentage of New York State patients for whom percutaneous coronary intervention (PCI) was rated as "inappropriate" versus optimal medical therapy alone...
March 12, 2018: JACC. Cardiovascular Interventions
Terence Y Pang, Anthony J Hannan, Andrew J Lawrence
Relapse remains the most prominent hurdle to successful rehabilitation from alcoholism. The neural mechanisms underlying relapse are complex, but our understanding of the brain regions involved, the anatomical circuitry and the modulation of specific nuclei in the context of stress and cue-induced relapse have improved significantly in recent years. In particular, stress is now recognised as a significant trigger for relapse, adding to the well-established impact of chronic stress to escalate alcohol consumption...
February 22, 2018: Neuropharmacology
Brita Kilburg-Basnyat, Sky W Reece, Miranda J Crouch, Bin Luo, Andria D Boone, Michael Yaeger, Myles Hodge, Christine Psaltis, Johanna L Hannan, Jonathan Manke, Michael L Armstrong, Nichole Reisdorph, Robert M Tighe, Saame Raza Shaikh, Kymberly M Gowdy
Exposure to ozone (O3) induces lung injury, pulmonary inflammation, and alters lipid metabolism. During tissue inflammation, specialized pro-resolving lipid mediators (SPMs) facilitate the resolution of inflammation. SPMs regulate the pulmonary immune response during infection and allergic asthma; however, the role of SPMs in O3-induced pulmonary injury and inflammation is unknown. We hypothesized that O3 exposure induces pulmonary inflammation by reducing SPMs. To evaluate this, male C57Bl/6J mice were exposed to filtered air (FA) or 1 ppm O3 for 3h and necropsied 24h after exposure...
February 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Eoghan T Hurley, Daren Lim Fat, Cathal J Moran, Hannan Mullett
BACKGROUND: Basic science studies suggest that platelet-rich therapies have a positive effect on tendon repair. However, the clinical evidence is conflicted on whether this translates to increased tendon healing and improved functional outcomes. PURPOSE: To perform a systematic review of randomized controlled trials (RCTs) in the literature to ascertain whether platelet-rich plasma (PRP) or platelet-rich fibrin (PRF) improved patient outcomes in arthroscopic rotator cuff repair...
February 1, 2018: American Journal of Sports Medicine
Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Sally Beard, Ping Cannon, Roxanne Hastie, Tuong V Nguyen, Natalie K Binder, Stephen Tong, Natalie J Hannan
INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG) are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. We recently identified metformin and esomeprazole as potential treatments for preeclampsia. Both reduce placental and endothelial secretion of sFlt-1 and soluble endoglin, and reduce endothelial dysfunction...
2018: PloS One
Caroline M Gorvin, Valerie N Babinsky, Tomas Malinauskas, Peter H Nissen, Anders J Schou, Aylin C Hanyaloglu, Christian Siebold, E Yvonne Jones, Fadil M Hannan, Rajesh V Thakker
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that signals through Gq/11 and Gi/o to stimulate cytosolic calcium (Ca2+ i ) and mitogen-activated protein kinase (MAPK) signaling to control extracellular calcium homeostasis. Studies of loss- and gain-of-function CASR mutations, which cause familial hypocalciuric hypercalcemia type 1 (FHH1) and autosomal dominant hypocalcemia type 1 (ADH1), respectively, have revealed that the CaSR signals in a biased manner. Thus, some mutations associated with FHH1 lead to signaling predominantly through the MAPK pathway, whereas mutations associated with ADH1 preferentially enhance Ca2+ i responses...
February 20, 2018: Science Signaling
Roxanne Hastie, Elgene Lim, Pavel Sluka, Lisa Campbell, Andrew W Horne, Lenore Ellett, Natalie J Hannan, Fiona Brownfoot, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice...
February 2, 2018: EBioMedicine
Anthony J Hannan
Accumulating evidence suggests that many classes of DNA repeats exhibit attributes that distinguish them from other genetic variants, including the fact that they are more liable to mutation; this enables them to mediate genetic plasticity. The expansion of tandem repeats, particularly of short tandem repeats, can cause a range of disorders (including Huntington disease, various ataxias, motor neuron disease, frontotemporal dementia, fragile X syndrome and other neurological disorders), and emerging data suggest that tandem repeat polymorphisms (TRPs) can also regulate gene expression in healthy individuals...
February 5, 2018: Nature Reviews. Genetics
Katharine Wickel Didericksen, Jerica M Berge, Peter J Hannan, Steven M Harris, Richard F MacLehose, Dianne Neumark-Sztainer
INTRODUCTION: This study utilizes triadic data to examine the association between mother-father-adolescent concordance (agreement) and discordance (disagreement) on home environment factors (i.e., parental encouragement of dieting, family functioning) and adolescent unhealthy weight control behaviors and binge eating. METHOD: A subsample of adolescent-mother-father triads (n = 833; adolescents ages 10-22) from two coordinated population-based studies (EAT 2010 and F-EAT) were used...
February 1, 2018: Families, Systems & Health: the Journal of Collaborative Family Healthcare
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
Iris Y Kim, Éilis J O'Reilly, Katherine C Hughes, Xiang Gao, Michael A Schwarzschild, Marjorie L McCullough, Marian T Hannan, Rebecca A Betensky, Alberto Ascherio
BACKGROUND: Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent. METHOD: We examined the interaction of caffeine intake with GRIN2A-rs4998386 and CYP1A2-rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort...
January 10, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Enda J Hannan, Donal P O'Leary, Stephen P MacNally, Elaine W Kay, Michael A Farrell, Patrick G Morris, Colm P Power, Arnold D K Hill
To compare BRAF V600E status of primary melanoma and brain metastases to assess for discordance by cross-sectional study, and to evaluate clinical implications on BRAF inhibitor therapy.Brain metastases are common in patients with advanced melanoma. Between 40% and 60% of melanomas demonstrate BRAF mutations, BRAF V600E being most common. Selective BRAF inhibitor therapy has shown improvement in outcome in patients with melanoma. It has been demonstrated that not all metastatic lesions carry the same BRAF mutation status as the primary, but the frequency in which discordance occurs remains unclear...
December 2017: Medicine (Baltimore)
Edward L Hannan, Ye Zhong, Peter B Berger, Alice K Jacobs, Gary Walford, Frederick S K Ling, Ferdinand J Venditti, Spencer B King
Importance: Many studies have compared outcomes for incomplete revascularization (IR) among patients undergoing percutaneous coronary interventions (PCI), but little is known about whether outcomes are related to the nature of the IR. Objective: To determine whether some coronary vessel characteristics are associated with worse outcomes in patients with PCI with IR. Design, Setting, and Participants: New York's PCI registry was used to examine mortality (median follow-up, 3...
February 1, 2018: JAMA Cardiology
Jake Rogers, Thibault Renoir, Anthony J Hannan
Gene-environment interactions drive experience-dependent changes in the brain that alter cognition, emotion and behaviour. Positive engagement with the environment, through novel experience and physical activity, can improve brain function, although the mechanisms mediating such experience-dependent plasticity remain to be fully elucidated. In this article, we discuss the therapeutic value of environmental stimuli, exercise and environmental enrichment (EE), for cognitive and affective disorders, with implications for the understanding and treatment of depression and anxiety disorders...
December 22, 2017: Neuropharmacology
Claire A Martin, Carleen Cullinane, Laura Kirby, Shatha Abuhammad, Emily J Lelliott, Kelly Waldeck, Richard J Young, Natalie Brajanovski, Donald P Cameron, Rachael Walker, Elaine Sanij, Gretchen Poortinga, Ross D Hannan, Richard B Pearson, Rodney J Hicks, Grant A McArthur, Karen E Sheppard
Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are currently in clinical trials for the treatment of melanoma. We hypothesize that the timing of the addition of CDK4/6 inhibitors to the current BRAF and MEK inhibitor regime will impact on the efficacy of this triplet drug combination. The efficacy of BRAF, MEK and CDK4/6 inhibitors as single agents and in combination were assessed in human BRAF mutant cell lines that were treatment naïve, BRAF inhibitor tolerant or had acquired resistance to BRAF inhibitors...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
Sarah A Marshall, Natalie J Hannan, Maria Jelinic, Thy P H Nguyen, Jane E Girling, Laura J Parry
Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia...
December 6, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Sarah J Kane, Eric Swanson, Elizabeth O Gordon, Savannah Rocha, Heather R Bender, Luke R Donius, Adriano Aguzzi, Jonathan P Hannan, Mark D Zabel
Complement receptors 1 and 2 (CR1/2 or CD35/CD21) recognize complement-opsonized antigens to initiate innate and adaptive immunity, respectively. CD35 stimulates phagocytosis on macrophages and antigen presentation on follicular dendritic cells (FDCs). CD21 helps activate B cells as part of the B cell coreceptor with CD19 and CD81. Differential splicing of transcripts from the mouse Cr2 gene generates isoforms with both shared and unique complement binding capacities and cell-type expression. In mouse models, genetic depletion of Cr2 causes either a delay or complete prevention of prion disease, but the relative importance of CD35 versus CD21 in promoting prion disease remains unknown...
November 2017: MSphere
Alexandra H Antonioli, Janice White, Frances Crawford, Brandon Renner, Kevin J Marchbank, Jonathan P Hannan, Joshua M Thurman, Philippa Marrack, V Michael Holers
Factor H (FH) is a key alternative pathway regulator that controls complement activation both in the fluid phase and on specific cell surfaces, thus allowing the innate immune response to discriminate between self and foreign pathogens. However, the interrelationships between FH and a group of closely related molecules, designated the FH-related (FHR) proteins, are currently not well understood. Whereas some studies have suggested that human FHR proteins possess complement regulatory abilities, recent studies have shown that FHR proteins are potent deregulators...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Steven C Schallhorn, David Teenan, Jan A Venter, Julie M Schallhorn, Keith A Hettinger, Stephen J Hannan, Martina Pelouskova
PURPOSE: To compare clinical and quality of life outcomes between patients who underwent monovision LASIK and refractive lens exchange. METHODS: The study comprised 590 patients with refractive lens exchange and 608 patients with monovision LASIK available for 3-month postoperative clinical visits. All patients with refractive lens exchange had a Tecnis Symfony lens (Johnson & Johnson Vision Care, Inc., Santa Ana, CA) in at least one eye. Patients were divided into four refractive categories: moderate to high myopia, low myopia, plano presbyopia, and hyperopia...
November 1, 2017: Journal of Refractive Surgery
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