233,912 results match your criteria Harvard heart letter : from Harvard Medical School[Journal]


On the 80th Birthday of Jan van Bemmel.

Yearb Med Inform 2019 Apr 25. Epub 2019 Apr 25.

Dept. of Medical informatics, Erasmus University, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1055/s-0039-1677893DOI Listing

CD160 Stimulates CD8 T Cell Responses and Is Required for Optimal Protective Immunity to .

Immunohorizons 2018 Aug 27;2(7):238-250. Epub 2018 Aug 27.

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

CD160 promotes NK cell cytotoxicity and IFN-γ production, but the function of CD160 on CD8 T cells remains unclear with some studies supporting a coinhibitory role and others a costimulatory role. In this study, we demonstrate that CD160 has a costimulatory role in promoting CD8 T cell effector functions needed for optimal clearance of oral infection. CD160 mice did not clear oral as efficiently as wild type (WT) littermates. Read More

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http://dx.doi.org/10.4049/immunohorizons.1800039DOI Listing

Recent Advances in the Discovery and Delivery of TLR7/8 Agonists as Vaccine Adjuvants.

Authors:
David J Dowling

Immunohorizons 2018 Jul 2;2(6):185-197. Epub 2018 Jul 2.

Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115

The need for new adjuvants is absolutely cardinal to the development of new vaccines and to further optimizing current immunization approaches. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of TLR agonists as vaccine adjuvants have begun to open up a new toolbox for vaccinologists. Read More

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http://dx.doi.org/10.4049/immunohorizons.1700063DOI Listing

Micro-geographic targeting for precision public policy: Analysis of child sex ratio across 587,043 census villages in India, 2011.

Health Place 2019 Apr 22;57:92-100. Epub 2019 Apr 22.

Harvard Center for Population and Development Studies, Cambridge, MA, USA; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address:

Child sex ratio (CSR) is a marker of disproportionate sex ratio at birth and discriminatory practices that lead to differential survival in early childhood by sex. We used the 2011 Census on rural India to present the first local analysis of CSR across 587,043 villages. In our multilevel analysis considering villages, tehsils, districts, and states/union territories, we found 96% of the total variation in CSR to be attributed to villages. Read More

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http://dx.doi.org/10.1016/j.healthplace.2019.02.005DOI Listing

Bioinspired aerogel based on konjac glucomannan and functionalized carbon nanotube for controlled drug release.

Int J Biol Macromol 2019 Apr 22. Epub 2019 Apr 22.

College of food science, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

In this study, a facile marine bioinspired surface modification approach for carboxyl-functionalized multiwalled carbon nanotube (CCNT) and enhanced interfacial adhesion with the konjac glucomannan (KGM) matrix were illustrated to develop aerogels. Combined with FT-IR, XRD, Raman, TGA, XPS and SEM results, it was indicated that functionalized CCNT (PCCNT) is a reinforcer through hydrogen bond interactions in the aerogel formation process, which could be the main reason for the enhancement. The swelling and vitro release behavior of KGM/PCCNT aerogels were studied under two conditions using the drug 5-fluorouracil (5-FU). Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2019.04.148DOI Listing

Acute Myeloid Leukemia Driven by the CALM-AF10 Fusion Gene is Dependent on BMI1.

Exp Hematol 2019 Apr 22. Epub 2019 Apr 22.

Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address:

A subset of acute myeloid and lymphoid leukemia cases harbor a t(10;11)(p13;q14) translocation resulting in the CALM-AF10 fusion gene. Standard chemotherapeutic strategies are often ineffective in treating patients with CALM-AF10 fusions. Hence, there is an urgent need to identify molecular pathways dysregulated in CALM-AF10-positive leukemias which may lay the foundation for novel targeted therapies. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.04.003DOI Listing
April 2019
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Fostering the Future of Cardiac Surgery Around the World.

Ann Thorac Surg 2019 Apr 22. Epub 2019 Apr 22.

Division of Cardiovascular Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.athoracsur.2019.03.061DOI Listing

More than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea.

Am J Respir Crit Care Med 2019 Apr 25. Epub 2019 Apr 25.

University of California, San Diego, Division of Pulmonary and Critical Care Medicine, San Diego, California, United States.

Traditionally, the presence and severity of obstructive sleep apnea (OSA) has been defined by the apnea-hypopnea index (AHI). Continuous positive airway pressure (CPAP) is generally first line therapy despite low adherence as it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiologies (i. Read More

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http://dx.doi.org/10.1164/rccm.201901-0014TRDOI Listing

Safety and reliability of a handheld stimulator for neural monitoring during thyroid surgery.

Laryngoscope 2019 Apr 25. Epub 2019 Apr 25.

Division of Thyroid and Parathyroid Surgery, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston, Massachusetts, U.S.A.

Objective: The Checkpoint nerve stimulator (Checkpoint Surgical, Cleveland, OH) is a U.S. Food and Drug Administration-approved device for neural localization and monitoring during surgery. Read More

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http://dx.doi.org/10.1002/lary.28027DOI Listing

InflammAging at Ocular Surface: Clinical and Biomolecular Analyses in Healthy Volunteers.

Invest Ophthalmol Vis Sci 2019 Apr;60(5):1769-1775

Ophthalmology Complex Operative Unit, University Campus Bio-Medico, Rome, Italy.

Purpose: To assess the ocular surface in volunteers who consider themselves as healthy, in order to evaluate how para-inflammatory mechanisms fail with age, and thus investigate the phenomenon of "InflammAging."

Methods: In this observational prospective cohort study, volunteers were categorized into three groups according to age: young (19-40 years), middle-aged (41-60 years), and older adults (61-93 years). Clinical assessments included tear breakup time (T-BUT) and Schirmer test type I. Read More

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http://dx.doi.org/10.1167/iovs.18-25822DOI Listing

Playground lead levels in rubber, soil, sand, and mulch surfaces in Boston.

PLoS One 2019 25;14(4):e0216156. Epub 2019 Apr 25.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Rubber surfacing is often used in playgrounds due to its potential injury prevention benefits and as a way to recycle waste tires. Available research on chemicals in recycled rubber has focused on synthetic turf applications, but is limited for playground rubber surfacing. Potential lead contamination from vulcanizing agents used in rubber surfacing are a possible concern; however this has not been researched. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216156PLOS
April 2019
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Sugar sweetened beverage consumption during pregnancy is associated with lower diet quality and greater total energy intake.

PLoS One 2019 25;14(4):e0215686. Epub 2019 Apr 25.

Division of Community Health and Human Development, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.

Objective: Identify the socio-economic correlates of sugar sweetened beverage (SSB) consumption among pregnant women and analyze to what extent SSB consumption is associated with diet quality and total energy intake. Additionally, we aim to predict how diet quality scores and totally energy intakes would change if SSB consumption was artificially set to 0.

Design: Repeated Cross Sectional Study. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215686PLOS

Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study.

PLoS One 2019 25;14(4):e0214364. Epub 2019 Apr 25.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

Parkinson disease (PD) is associated with cognitive impairment. We aimed to determine the effects of intranasal insulin (INI) on cognition and motor performance in PD. This was a proof of concept, randomized, double-blinded, placebo-controlled trial evaluating the effects of 40 international units (IU) of insulin or saline once daily for four weeks on cognitive and functional performance. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214364PLOS

Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians.

PLoS Genet 2019 Apr 25;15(4):e1008092. Epub 2019 Apr 25.

Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008092DOI Listing

Third trimester vitamin D status is associated with birth outcomes and linear growth of HIV-exposed uninfected infants in the United States.

J Acquir Immune Defic Syndr 2019 Apr 1. Epub 2019 Apr 1.

Frontier Science Technology Research Foundation INC, Amherst Office, NY.

Background: Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth but few studies have examined the relationship among pregnant women living with HIV.

Methods: We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 Nutrition sub-study of the Surveillance Monitoring for ART Toxicities (SMARTT) Study. HIV-infected pregnant women had serum 25-hydroxyvitamin D (25(OH)D) assessed in the third trimester of pregnancy and their infants' growth and neurodevelopment were evaluated at birth and approximately one year of age. Read More

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http://dx.doi.org/10.1097/QAI.0000000000002041DOI Listing
April 2019
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Performance Measures in Dermatologic Surgery: A Review of the Literature and Future Directions.

Dermatol Surg 2019 Apr 23. Epub 2019 Apr 23.

Department of Dermatology, University of California San Francisco, San Francisco, California.

Background: In recent years, health care reform initiatives have aimed to assess quality of care through the use of performance measures. Multiple specialties, including dermatology, have implemented registries to track and report health care quality.

Objective: The authors review the history and rationale for assessing quality in dermatologic surgery. Read More

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http://dx.doi.org/10.1097/DSS.0000000000001938DOI Listing

Tenofovir concentrations in hair strongly predict virologic suppression in breastfeeding women.

AIDS 2019 Apr 22. Epub 2019 Apr 22.

Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA.

Background: Antiretroviral treatment (ART) adherence is often suboptimal in the perinatal period. We measured hair tenofovir (TFV) concentrations as a metric of adherence in postpartum women to understand patterns and predictors of adherence throughout this critical period. Additionally, we examined the association between hair TFV concentrations and virologic outcomes. Read More

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http://dx.doi.org/10.1097/QAD.0000000000002237DOI Listing
April 2019
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Letter by Morrell et al Regarding Article, "Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension".

Circ Res 2019 Apr;124(9):e81

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1161/CIRCRESAHA.119.314962DOI Listing

Johann Sebastian Bach.

Authors:
Peter Libby

Circ Res 2019 Apr;124(9):1303-1308

From the Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1161/CIRCRESAHA.119.315025DOI Listing

In vitro characterization and preclinical immunogenicity of Typhax, a typhoid fever protein capsular matrix vaccine candidate.

Hum Vaccin Immunother 2019 Apr 25. Epub 2019 Apr 25.

a Matrivax Research & Development Corporation , Boston , MA , USA.

Typhax is an investigational typhoid fever vaccine candidate that was GMP manufactured applying Protein Capsular Matrix Vaccine (PCMV) technology. It consists of Vi polysaccharide antigen, derived from S. Typhi, non-covalently entrapped in a glutaraldehyde catalyzed cross-linked α-poly-L-lysine and CRM197 protein matrix. Read More

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http://dx.doi.org/10.1080/21645515.2019.1599674DOI Listing

Associations between pain catastrophizing and clinical characteristics in adults with substance use disorders and co-occurring chronic pain.

Am J Drug Alcohol Abuse 2019 Apr 25:1-7. Epub 2019 Apr 25.

a Division of Alcohol and Drug Abuse , McLean Hospital , Belmont , MA , USA.

Background: Pain catastrophizing refers to the tendency to interpret pain as harmful, intolerable, or uncontrollable. Greater pain catastrophizing is associated with more pain-related negative phenomena, such as pain reactivity, pain disability, and emotional distress related to pain. Several studies of patients seeking chronic pain treatment have identified an association between pain catastrophizing and misuse of opioids and alcohol; however, it is unknown whether this association would be similarly present in patients with chronic pain seeking substance use disorder treatment. Read More

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http://dx.doi.org/10.1080/00952990.2019.1581793DOI Listing

Adipose Tissue Distribution and Survival Among Women with Nonmetastatic Breast Cancer.

Obesity (Silver Spring) 2019 Apr 25. Epub 2019 Apr 25.

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.

Objective: Previous studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).

Methods: This study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1. Read More

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http://dx.doi.org/10.1002/oby.22458DOI Listing

Human T-Cell Lymphotrophic Virus in Solid Organ Transplant Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Clin Transplant 2019 Apr 25:e13575. Epub 2019 Apr 25.

Department of Pediatrics, Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of Human T-cell lymphotrophic virus 1 (HTLV)-1 in the pre- and post-transplant period. HTLV-1 is an oncogenic human retrovirus rare in North America but endemic in the Caribbean and parts of Africa, South America, Asia, and Oceania. While most infected persons do not develop disease, <5% will develop adult T cell leukemia/lymphoma or neurological disease. Read More

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http://dx.doi.org/10.1111/ctr.13575DOI Listing
April 2019
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A report from a workshop of the International Stem Cell Banking Initiative, held in collaboration GAiT and the Harvard Stem Cell Institute, Boston 2017.

Stem Cells 2019 Apr 25. Epub 2019 Apr 25.

International Stem Cell Banking Initiative, 2 High St, Barley, Hertfordshire, SG88HZ, UK.

This report summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at Harvard Stem Cell Institute, Boston, USA, on 18th Jun 2017. In this meeting, we aimed to find consensus on ongoing issues of quality control (QC), safety and efficacy of human pluripotent stem cell (hPSC) banks and their derivative cell therapy products for the global harmonization. In particular, assays for the QC testing such as pluripotency assays test and general QC testing criteria was intensively discussed. Read More

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http://dx.doi.org/10.1002/stem.3003DOI Listing

Lysosome activates AKT inducing cancer and metastasis.

J Cell Biochem 2019 Apr 25. Epub 2019 Apr 25.

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Hyperactivated lysosome causes cancer and induces metastasis or cancer relapse. Such activation occurs during excessive, intense, and protracted oxidative burst in the lysosome. The burst induces the formation of the constitutively active (permanently active) AKT locus generating cancer complexity and robustness. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.28752
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http://dx.doi.org/10.1002/jcb.28752DOI Listing
April 2019
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The spectrum of facial palsy: The MEEI facial palsy photo and video standard set.

Laryngoscope 2019 Apr 25. Epub 2019 Apr 25.

Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.

Objectives: Facial palsy causes variable facial disfigurement ranging from subtle asymmetry to crippling deformity. There is no existing standard database to serve as a resource for facial palsy education and research. We present a standardized set of facial photographs and videos representing the entire spectrum of flaccid and nonflaccid (aberrantly regenerated or synkinetic) facial palsy. Read More

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http://dx.doi.org/10.1002/lary.27986DOI Listing

Persistent Pain and Gingival Swelling in a Middle-aged Woman.

JAMA Otolaryngol Head Neck Surg 2019 Apr 25. Epub 2019 Apr 25.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaoto.2019.0606DOI Listing

SHERLOCK and DETECTR Open a New Frontier in Molecular Diagnostics.

CRISPR J 2018 Jun;1:209-211

1 Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts.

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http://dx.doi.org/10.1089/crispr.2018.29018.kpeDOI Listing

Impact of Genetic Variation on CRISPR-Cas Targeting.

CRISPR J 2018 Apr;1:159-170

1 Molecular Pathology Unit, Massachusetts General Hospital , Charlestown, Massachusetts.

The CRISPR-CRISPR-associated (Cas) nuclease system offers the ability to perform unprecedented functional genetic experiments and the promise of therapy for a variety of genetic disorders. The understanding of factors contributing to CRISPR targeting efficacy and specificity continues to evolve. As CRISPR systems rely on Watson-Crick base pairing to ultimately mediate genomic cleavage, it logically follows that genetic variation would affect CRISPR targeting by increasing or decreasing sequence homology at on-target and off-target sites or by altering protospacer adjacent motifs. Read More

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http://dx.doi.org/10.1089/crispr.2017.0016DOI Listing

Earlier age at menarche as a transdiagnostic mechanism linking childhood trauma with multiple forms of psychopathology in adolescent girls.

Psychol Med 2019 Apr 25:1-9. Epub 2019 Apr 25.

Department of Psychology,Harvard University,Cambridge, MA,USA.

Background: Although early life adversity (ELA) increases risk for psychopathology, mechanisms linking ELA with the onset of psychopathology remain poorly understood. Conceptual models have argued that ELA accelerates development. It is unknown whether all forms of ELA are associated with accelerated development or whether early maturation is a potential mechanism linking ELA with psychopathology. Read More

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http://dx.doi.org/10.1017/S0033291719000953DOI Listing

Cancer Incidence and Mortality in 260,000 Nordic Twins With 30,000 Prospective Cancers.

Twin Res Hum Genet 2019 Apr 25:1-9. Epub 2019 Apr 25.

Department of Social Sciences,University of Tampere,Tampere,Finland.

The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Read More

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http://dx.doi.org/10.1017/thg.2019.10DOI Listing

Role of Perivascular Oligodendrocyte Precursor Cells in Angiogenesis After Brain Ischemia.

J Am Heart Assoc 2019 May;8(9):e011824

1 Department of Neurology Graduate School of Medicine Kyoto University Kyoto Japan.

Background Oligodendrocyte precursor cells ( OPC s) regulate neuronal, glial, and vascular systems in diverse ways and display phenotypic heterogeneity beyond their established role as a reservoir for mature oligodendrocytes. However, the detailed phenotypic changes of OPC s after cerebral ischemia remain largely unknown. Here, we aimed to investigate the roles of reactive OPC s in the ischemic brain. Read More

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https://www.ahajournals.org/doi/10.1161/JAHA.118.011824
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http://dx.doi.org/10.1161/JAHA.118.011824DOI Listing
May 2019
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Biomarker of Collagen Turnover (C-Terminal Telopeptide) and Prognosis in Patients With Non- ST -Elevation Acute Coronary Syndromes.

J Am Heart Assoc 2019 May;8(9):e011444

1 TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA.

Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure ( HF ). We examined C-terminal telopeptide (beta- CT x) and the risk of cardiovascular death or new or worsening HF in non- ST -elevation acute coronary syndrome. Methods and Results We measured baseline serum beta- CT x, NT -pro BNP (N-terminal pro-B-type natriuretic peptide), hsTnT (high-sensitivity cardiac troponin T) and hs CRP (high-sensitivity C-reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non- ST -elevation acute coronary syndrome. Read More

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http://dx.doi.org/10.1161/JAHA.118.011444DOI Listing

Evaluating the use of bootstrapping in cohort studies conducted with 1:1 propensity score matching-A plasmode simulation study.

Pharmacoepidemiol Drug Saf 2019 Apr 24. Epub 2019 Apr 24.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Purpose: Bootstrapping can account for uncertainty in propensity score (PS) estimation and matching processes in 1:1 PS-matched cohort studies. While theory suggests that the classical bootstrap can fail to produce proper coverage, practical impact of this theoretical limitation in settings typical to pharmacoepidemiology is not well studied.

Methods: In a plasmode-based simulation study, we compared performance of the standard parametric approach, which ignores uncertainty in PS estimation and matching, with two bootstrapping methods. Read More

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http://dx.doi.org/10.1002/pds.4784DOI Listing

Calcitonin Gene-Related Peptide Modulators - The History and Renaissance of a New Migraine Drug Class.

Headache 2019 Apr 25. Epub 2019 Apr 25.

Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark.

Several lines of evidence pointed to an important role for CGRP in migraine. These included the anatomic colocalization of CGRP and its receptor in sensory fibers innervating pain-producing meningeal blood vessels, its release by trigeminal stimulation, the observation of elevated CGRP in the cranial circulation during migraine with normalization concomitant with headache relief by sumatriptan, and translational studies with intravenous (IV) CGRP that evoked migraine only in migraineurs. The development of small molecule CGRP receptor antagonists (CGRP-RAs) that showed clinical antimigraine efficacy acutely and prophylactically in randomized placebo-controlled clinical trials subsequently gave definitive pharmacological proof of the importance of CGRP in migraine. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/head.13510
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http://dx.doi.org/10.1111/head.13510DOI Listing
April 2019
1 Read

Phase Ib study of the MEK inhibitor cobimetinib (GDC-0973) in combination with the PI3K inhibitor pictilisib (GDC-0941) in patients with advanced solid tumors.

Invest New Drugs 2019 Apr 24. Epub 2019 Apr 24.

Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA.

Purpose We investigated the combination of the MEK inhibitor, cobimetinib, and the pan-PI3K inhibitor, pictilisib, in an open-label, phase Ib study. Experimental Design Patients with advanced solid tumors were enrolled in 3 dose escalation schedules: (1) both agents once-daily for 21-days-on 7-days-off ("21/7"); (2) intermittent cobimetinib and 21/7 pictilisib ("intermittent"); or (3) both agents once-daily for 7-days-on 7-days-off ("7/7"). Starting doses for the 21/7, intermittent, and 7/7 schedules were 20/80, 100/130, and 40/130 mg of cobimetinib/pictilisib, respectively. Read More

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http://dx.doi.org/10.1007/s10637-019-00776-6DOI Listing

The effect of endometriosis on the antimüllerian hormone level in the infertile population.

J Assist Reprod Genet 2019 Apr 16. Epub 2019 Apr 16.

Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA.

Purpose: To determine whether the presence of endometriosis in infertile women without prior ovarian surgery influences markers of ovarian reserve, AMH and FSH.

Methods: A retrospective cohort study included three groups of women who presented for IVF treatment at our tertiary care center from 04/27/2015 to 05/31/2017: women with endometriosis and prior ovarian surgery (EnSx), women with endometriosis without prior ovarian surgery (En), and women with a primary diagnosis of male factor infertility (MF; reference group).

Results: There were 671 patients that met inclusion criteria (78 EnSx, 60 En, and 533 MF). Read More

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http://dx.doi.org/10.1007/s10815-019-01450-9DOI Listing

Detrimental impact of symptom-detected colorectal cancer.

Surg Endosc 2019 Apr 24. Epub 2019 Apr 24.

Division of General and Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Background: The incidence and mortality rates of colorectal cancer (CRC) have been steadily decreasing, largely attributable to screening colonoscopies that either remove precancerous lesions or identify CRC earlier. We aimed to assess the prognostic difference between colorectal cancers diagnosed by screening (SC), diagnostic (DC), or surveillance (SU) colonoscopies.

Methods: All 1809 surgically treated patients with primary CRC diagnosed through colonoscopy at our tertiary center (2004-2015) were extracted from a prospectively maintained database. Read More

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http://dx.doi.org/10.1007/s00464-019-06798-8DOI Listing

Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma.

J Cancer Res Clin Oncol 2019 Apr 24. Epub 2019 Apr 24.

Department of Hematology, The First Hospital, Harbin Medical University, Harbin, 150001, China.

Background: Hypercoagulability is a major cancer-associated complication linked to poor patient prognosis. The production of neutrophil extracellular traps (NETs) is increasingly found to be linked with the development and metastasis of cancer, as well as with thrombi formation in cancer patients. We hypothesized that the neutrophil NET release may be triggered by specific cytokines in oral squamous cell carcinoma (OSCC) patients, thereby predisposing them to a hypercoagulable state. Read More

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http://dx.doi.org/10.1007/s00432-019-02922-2DOI Listing

Genome-wide Kdm4 histone demethylase transcriptional regulation in Drosophila.

Mol Genet Genomics 2019 Apr 24. Epub 2019 Apr 24.

Department of Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.

The histone lysine demethylase 4 (Kdm4/Jmjd2/Jhdm3) family is highly conserved across species and reverses di- and tri-methylation of histone H3 lysine 9 (H3K9) and lysine 36 (H3K36) at the N-terminal tail of the core histone H3 in various metazoan species including Drosophila, C.elegans, zebrafish, mice and humans. Previous studies have shown that the Kdm4 family plays a wide variety of important biological roles in different species, including development, oncogenesis and longevity by regulating transcription, DNA damage response and apoptosis. Read More

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http://dx.doi.org/10.1007/s00438-019-01561-zDOI Listing

Spontaneous coronary artery dissection masquerading as Takotsubo cardiomyopathy: a case report.

Eur Heart J Case Rep 2018 Dec 11;2(4):yty102. Epub 2018 Oct 11.

Department of Medicine, Massachusetts General Hospital, 55 Fruit Street Gray 730, Boston, MA, USA.

Background: Although obstructive coronary artery disease (CAD) is the most likely cause of acute coronary syndromes (ACS), nearly one in 20 individuals with clinical myocardial infarction (MI) do not have obstructive CAD. For many such individuals, presentation of Takotsubo cardiomyopathy frequently mimics presentation of MI, though spontaneous coronary artery dissection (SCAD) is an increasingly recognized aetiology of MI in women.

Case Summary: This case report describes a woman with chest pain, found to have non-obstructive CAD on angiogram and left ventricular apical dysfunction on echocardiogram raising suspicion for Takotsubo cardiomyopathy. Read More

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http://dx.doi.org/10.1093/ehjcr/yty102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426097PMC
December 2018

Payer type does not impact patient-reported outcomes after primary total knee arthroplasty.

Arthroplast Today 2019 Mar 3;5(1):113-118. Epub 2019 Jan 3.

NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY, USA.

Background: There is a paucity of literature assessing whether payer type has an impact on postoperative patient-reported outcomes (PROs) after total knee arthroplasty (TKA). The aim of this study was to comparatively evaluate TKA PROs among patients with commercial and Medicare insurance.

Methods: We conducted a single-center, retrospective review of patients operated between January 2017 and March 2018. Read More

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http://dx.doi.org/10.1016/j.artd.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470348PMC

Immunotherapy with ponezumab for probable cerebral amyloid angiopathy.

Ann Clin Transl Neurol 2019 Apr 18;6(4):795-806. Epub 2019 Mar 18.

Massachusetts General Hospital Harvard Medical School Boston Massachusetts.

Objective: Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of -amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double-blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against A.

Methods: Thirty-six participants aged 55-80 years with probable CAA received intravenous placebo ( = 12) or ponezumab ( = 24). Read More

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http://dx.doi.org/10.1002/acn3.761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469253PMC

Ketamine's Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice.

Mol Neuropsychiatry 2019 Mar 15;5(1):42-51. Epub 2018 Nov 15.

Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany.

Ketamine, a noncompetitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect and is used for patients experiencing treatment-resistant depression. We carried out a time-dependent targeted mass spectrometry-based metabolomics profiling analysis combined with a quantitative based on in vivo N metabolic labeling proteome comparison of ketamine- and vehicle-treated mice. The metabolomics and proteomics datasets were used to further elucidate ketamine's mode of action on the gamma-aminobutyric acid (GABA)ergic and glutamatergic systems. Read More

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http://dx.doi.org/10.1159/000493425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465744PMC

Evaluating strategies and outcomes following rotator cuff tears.

Shoulder Elbow 2019 May 26;11(1 Suppl):4-18. Epub 2018 Apr 26.

Department of Orthopaedics, Beth Israel Deaconess Medical Center, Boston, USA.

Introduction: Rotator cuff tear surgical repair techniques have significantly progressed. However, tendon retear following primary repair persistently occurs at high rates. Rehabilitation protocols, surgical fixation techniques, biologic therapy with scaffolds, platelet-rich plasma, and even stem cell applications are under study to promote adequate tendon healing. Read More

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http://dx.doi.org/10.1177/1758573218768099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463377PMC

White Matter Changes in Cervical Dystonia Relate to Clinical Effectiveness of Botulinum Toxin Treatment.

Front Neurol 2019 4;10:265. Epub 2019 Apr 4.

Department of Neurology, Massachusetts General Hospital, Boston, MA, United States.

In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients ( = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. Read More

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http://dx.doi.org/10.3389/fneur.2019.00265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459077PMC

Response of Mouse Visual Cortical Neurons to Electric Stimulation of the Retina.

Front Neurosci 2019 4;13:324. Epub 2019 Apr 4.

Boston VA Healthcare System, Boston, MA, United States.

Retinal prostheses strive to restore vision to the blind by electrically stimulating the neurons that survive the disease process. Clinical effectiveness has been limited however, and much ongoing effort is devoted toward the development of improved stimulation strategies, especially ones that better replicate physiological patterns of neural signaling. Here, to better understand the potential effectiveness of different stimulation strategies, we explore the responses of neurons in the primary visual cortex to electric stimulation of the retina. Read More

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http://dx.doi.org/10.3389/fnins.2019.00324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459047PMC