tbuckley/cabot-search huggingface dataset:
Physicians and Medical Marijuana
Authors: Herbert D. Kleber, Robert L. Dupont
Journal: American Journal of Psychiatry (2012)

Psychiatrists may be asked by patients for referrals for medical marijuana under legislation in a number of states. There is no clinical scientific literature to support benefits. Risks to the patient include a supply whose purity and potency are not specified. Particularly problematic is breeding of marijuana to develop more potent strains in which components that limit potential harmful effects have been removed. Effects on brain development and increased liability for risk of other drug abuse are observed in adolescence. In addition, by sanctioning patients' consumption, psychiatrists may contribute to the adverse community impact of the culture surrounding marijuana dispensaries, including criminal behavior. It is advised that physicians assume their role of educating patients about risks and benefits, particularly when responding to requests for a nonbeneficial treatment.
Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance
Authors: Jodie L. Babitt, Franklin W. Huang, Yin Xia, Yisrael Sidis, Nancy C. Andrews, Herbert Y. Lin
Journal: Journal of Clinical Investigation (2007)

Systemic iron balance is regulated by hepcidin, a peptide hormone secreted by the liver. By decreasing cell surface expression of the iron exporter ferroportin, hepcidin decreases iron absorption from the intestine and iron release from reticuloendothelial stores. Hepcidin excess has been implicated in the pathogenesis of anemia of chronic disease, while hepcidin deficiency has a key role in the pathogenesis of the iron overload disorder hemochromatosis. We have recently shown that hemojuvelin is a coreceptor for bone morphogenetic protein (BMP) signaling and that BMP signaling positively regulates hepcidin expression in liver cells in vitro. Here we show that BMP-2 administration increases hepcidin expression and decreases serum iron levels in vivo. We also show that soluble hemojuvelin (HJV.Fc) selectively inhibits BMP induction of hepcidin expression in vitro and that administration of HJV.Fc decreases hepcidin expression, increases ferroportin expression, mobilizes splenic iron stores, and increases serum iron levels in vivo. These data support a role for modulators of the BMP signaling pathway in treating diseases of iron overload and anemia of chronic disease.
Raf and MEK Protein Kinases Are Direct Molecular Targets for the Chemopreventive Effect of Quercetin, a Major Flavonol in Red Wine
Authors: Ki Won Lee, Nam Joo Kang, Yong-Seok Heo, Evgeny A. Rogozin, Angelo Pugliese, Mun Kyung Hwang, G. Tim Bowden, Ann M. Bode, Hyong Joo Lee, Zigang Dong
Journal: Cancer Research (2008)

Abstract Considerable attention has focused on the health-promoting effects of red wine and its nonflavonoid polyphenol compound resveratrol. However, the underlying molecular mechanisms and molecular target(s) of red wine or other potentially active ingredients in red wine remain unknown. Here, we report that red wine extract (RWE) or the red wine flavonoid quercetin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 promotion-sensitive mouse skin epidermal (JB6 P+) cells. The activation of activator protein-1 and nuclear factor-κB induced by TPA was dose dependently inhibited by RWE or quercetin treatment. Western blot and kinase assay data revealed that RWE or quercetin inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and Raf1 kinase activities and subsequently attenuated TPA-induced phosphorylation of ERK/p90 ribosomal S6 kinase. Although either RWE or quercetin suppressed Raf1 kinase activity, they were more effective in inhibiting MEK1 activity. Importantly, quercetin exerted stronger inhibitory effects than PD098059, a well-known pharmacologic inhibitor of MEK. Resveratrol did not affect either MEK1 or Raf1 kinase activity. Pull-down assays revealed that RWE or quercetin (but not resveratrol) bound with either MEK1 or Raf1. RWE or quercetin also dose dependently suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are involved in the activation of MEK/ERK signaling. Docking data suggested that quercetin, but not resveratrol, formed a hydrogen bond with the backbone amide group of Ser212, which is the key interaction for stabilizing the inactive conformation of the activation loop of MEK1. [Cancer Res 2008;68(3):946–55]
US Republicans will attack individual provisions of health reform law as repeal is unlikely
Authors: M. McCarthy
Journal: BMJ (2015)

Republicans assume control of the US Senate and the House of Representatives on Tuesday 6 January and have vowed to dismantle President Barack Obama’s signature legislative accomplishment, the 2010 Affordable Care Act.

However, although Republicans hold large majorities in both chambers—234 to 201 in the House and 54 to 46 in the Senate—the party is still far short of the 67 votes in the Senate that it would need to over-ride the president’s veto, which any legislation would surely face if it seriously undermined the law.

In a recent interview on National Public Radio, Obama noted that he had made little use of the veto pen in the previous six years of his administration, largely because the Democratic controlled Senate had blocked legislation that he opposed. “Now I suspect there are going to be some times where I’ve got …
Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis
Authors: M Schaller
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> In K/BxN mice, anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are arthritogenic, and their transfer into naïve mice induces arthritis. Anti-GPI Abs develop in many human patients with RA and are associated with more severe forms of the disease. <b>Objective:</b> To elucidate the serum and synovial fluid (SF) anti-GPI IgG profiles among different patient groups with a variety of arthritides. <b>Methods:</b> Blood and SF obtained concomitantly from 91 patients with clinically well defined arthritis were tested for concentrations of total anti-GPI IgG, anti-GPI IgG subclasses, B lymphocyte stimulator (BLyS), and APRIL by ELISA. <b>Results:</b> Anti-GPI IgG was detected in sera and SF of patients with many arthritic diseases, but was preferentially associated with inflammatory arthritis, in general, and RA, in particular. The anti-GPI IgG subclass usage was skewed and varied among the different arthritic disease groups. Inverse correlations between serum levels of BLyS and anti-GPI IgG and positive correlations between serum levels of APRIL and anti-GPI IgG were seen among immune based arthritic patients and patients with RA but not among non-immune based patients. No correlations were found in SF from any group of arthritic patients. <b>Conclusion:</b> Raised circulating anti-GPI Abs are not unique to patients with RA but are present in many patients with inflammatory arthritis. The difference in anti-GPI IgG subclass usage among disease groups may influence effector function and disease outcome. The inverse correlation between serum BLyS and anti-GPI IgG levels suggests that anti-GPI B cells may be regulated differently from other autoantibody producing B cells. Anti-GPI Abs may serve a pathogenic function in humans by promoting the maintenance of existing disease.
Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?
Authors: A.M.M. de Vrankrijker, C.K. van der Ent, F.T. van Berkhout, R.K. Stellato, R.J.L. Willems, M.J.M. Bonten, T.F.W. Wolfs
Journal: Clinical Microbiology and Infection (2010)
Do neurodegenerative cascades in Parkinson's disease really reflect bottom-up processing?
Authors: Christopher A. Shaw
Journal: Behavioral and Brain Sciences (2002)

The target article suggests that the neurological disorders catatonia and Parkinson's disease share similar behavioral features that nevertheless reflect different forms of abnormal information processing. However, emerging research on Parkinson's disease and related age-dependent neurodegenerative disorders suggests that no simplistic notions about processing will be correct for all stages of the disease.
Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues.
Authors: J H Gong, I Clark-Lewis
Journal: The Journal of Experimental Medicine (1995)

Monocyte chemoattractant protein (MCP)-1 analogues were designed to determine the role of the NH2-terminal region in structure and function. The NH2-terminal residue was important for function and receptor binding, as it could not be deleted or extended. However the NH2-terminal pyroglutamate residue of the wild type was not essential as it could be replaced by several other noncyclic amino acids without loss of activity. Residues 7-10 were essential for receptor desensitization, but were not sufficient for function, and the integrity of residues 1-6 were required for functional activity. A peptide corresponding to MCP-1, 1-10 lacked detectable receptor-binding activities, indicating that residues 1-10 are essential for MCP-1 function, but that other residues are also involved. Several truncated analogues, including 8-76, 9-76, and 10-76, desensitized MCP-1-induced Ca2+ induction, but were not significantly active. These analogues were antagonists of MCP-1 activity with the most potent being the 9-76 analogue (IC50 = 20 nM) The 9-76 specifically bound to MCP-1 receptors with a Kd of 8.3 nM, which was three-fold higher than MCP-1 (Kd 2.8 nM). The 9-76 analogue desensitized the Ca2+ response to MCP-1 and MCP-3, but not to other CC chemokines, suggesting that it is MCP receptor specific. The availability of these compounds will be helpful in evaluating MCP receptor antagonists as anti-inflammatory therapeutics.
International Health: Purpose, Value, Challenges
Authors: Kayvon Modjarrad
Journal: JAMA (2002)

AT THE 2002 INTERNATIONAL CONFERENCE ON FINANCING FOR DEVELopment, the United States pledged an increase in foreign assistance to developing countries for the first time in several decades. This policy shift reflects a trend of international engagement that has pervaded the economic, political, and health sectors of American life in the past year. Recent health threats of international origin have raised concerns about the implications of globalization for US public health. Threats of bioterrorism and surges in the incidence of emerging pathogens such as West Nile virus have helped underscore the domestic dangers of diseases from abroad. Prior to this new swell of attention on health problems of global reach, however, industrialized nations were already allocating resources toward the control of pandemics such as HIV/AIDS, tuberculosis, and malaria. The urgency with which the commitments were made came in response to the devastation wrought by these diseases. The impact of HIV, in particular, is reflected by the grim fact that a 15-year-old living in a country with a 15% prevalence of HIV infection has a one-third lifetime risk of dying of AIDS. Although statistics such as these have made the mandate for global collaborations in international health clear, the path to stabilizing and improving the health of the world’s populations remains obscured. In order to engage in the ongoing debates about US involvement in global health initiatives, it is necessary first to understand the reasons and aims for international health endeavors. This issue of MSJAMA examines the purpose, value, and challenges of conducting research and practicing medicine across continents. Robert Luo discusses the destabilizing influence of the HIV/AIDS pandemic on national infrastructures as well as family units. Paula Braveman addresses the inadequacy of current health statistics to gauge and ultimately eliminate health inequities both between and within nations. Jeffrey Greenberg and Rebecca Mazar argue for more international training opportunities for US medical students in order to meet the increasing demand for global health professionals. Jennifer Singler and Paul Farmer describe a sustainable program to provide HIV treatment in Haiti, the poorest nation in the Western hemisphere. Policymakers recently met in Johannesburg for the UN World Summit on Sustainable Development. Leaders in medicine, politics, and economics all echoed previous calls for affluent nations to make good on their past declarations to implement plans to improve the livelihood of all members of the global community. Action requires political will and financial commitment. But comprehension of the rationale for and barriers to the control of disease at an international level will be equally vital to the improvement of global health and stability.
Transfusion-Associated Babesiosis in the United States: A Description of Cases
Authors: Barbara L. Herwaldt, Jeanne V. Linden, Elizabeth Bosserman, Carolyn Young, Danuta Olkowska, Marianna Wilson
Journal: Annals of Internal Medicine (2011)

Babesiosis is a potentially life-threatening disease caused by intraerythrocytic parasites, which usually are tickborne but also are transmissible by transfusion. Tickborne transmission of Babesia microti mainly occurs in 7 states in the Northeast and the upper Midwest of the United States. No Babesia test for screening blood donors has been licensed.To ascertain and summarize data on U.S. transfusion-associated Babesia cases identified since the first described case in 1979.Case series.United States.Case patients were transfused during 1979-2009 and had posttransfusion Babesia infection diagnosed by 2010, without reported evidence that another transmission route was more likely than transfusion. Implicated donors had laboratory evidence of infection. Potential cases were excluded if all pertinent donors tested negative.Distributions of ascertained cases according to Babesia species and period and state of transfusion.159 transfusion-associated B. microti cases were included; donors were implicated for 136 (86%). The case patients' median age was 65 years (range, <1 to 94 years). Most cases were associated with red blood cell components; 4 were linked to whole blood-derived platelets. Cases occurred in all 4 seasons and in 22 (of 31) years, but 77% (122 cases) occurred during 2000-2009. Cases occurred in 19 states, but 87% (138 cases) were in the 7 main B. microti-endemic states. In addition, 3 B. duncani cases were documented in western states.The extent to which cases were not diagnosed, investigated, reported, or ascertained is unknown.Donor-screening strategies that mitigate the risk for transfusion transmission are needed. Babesiosis should be included in the differential diagnosis of unexplained posttransfusion hemolytic anemia or fever, regardless of the season or U.S. region.None.
Burden of Diabetic Foot Ulcers for Medicare and Private Insurers
Authors: J. Bradford Rice, Urvi Desai, Alice Kate G. Cummings, Howard G. Birnbaum, Michelle Skornicki, Nathan B. Parsons
Journal: Diabetes Care (2013)

To estimate the annual, per-patient incremental burden of diabetic foot ulcers (DFUs).DFU patients and non-DFU patients with diabetes (controls) were selected using two de-identified databases: ages 65+ years from a 5% random sample of Medicare beneficiaries (Standard Analytical Files, January 2007-December 2010) and ages 18-64 years from a privately insured population (OptumInsight, January 2007-September 2011). Demographics, comorbidities, resource use, and costs from the payer perspective incurred during the 12 months prior to a DFU episode were identified. DFU patients were matched to controls with similar pre-DFU characteristics using a propensity score methodology. Per-patient incremental clinical outcomes (e.g., amputation and medical resource utilization) and health care costs (2012 U.S. dollars) during the 12-month follow-up period were measured among the matched cohorts.Data for 27,878 matched pairs of Medicare and 4,536 matched pairs of privately insured patients were analyzed. During the 12-month follow-up period, DFU patients had more days hospitalized (+138.2% Medicare, +173.5% private), days requiring home health care (+85.4% Medicare, +230.0% private), emergency department visits (+40.6% Medicare, +109.0% private), and outpatient/physician office visits (+35.1% Medicare, +42.5% private) than matched controls. Among matched patients, 3.8% of Medicare and 5.0% of privately insured DFU patients received lower limb amputations. Increased utilization resulted in DFU patients having $11,710 in incremental annual health care costs for Medicare, and $16,883 for private insurance, compared with matched controls. Privately insured matched DFU patients incurred excess work-loss costs of $3,259.These findings document that DFU imposes substantial burden on public and private payers, ranging from $9-13 billion in addition to the costs associated with diabetes itself.
Gene by Environment Interaction in Asthma
Authors: Stephanie J. London, Isabelle Romieu
Journal: Annual Review of Public Health (2008)

Marked international differences in rates of asthma and allergies and the importance of family history highlight the primacy of interactions between genetic variation and the environment in asthma etiology. Environmental tobacco smoke (or secondhand smoke), ambient air pollutants, and endotoxin and/or other pathogen-associated molecular patterns are the ambient exposures studied most frequently for interactions with genetic polymorphisms in asthma. To date, results from the literature remain inconclusive. Most published studies are underpowered to study interactions between genetic polymorphisms and ambient exposures, each with weak effects. Strategies to increase power include cooperation across studies to increase sample sizes and improve measures of both exposure and asthma phenotypes. Genome-wide association studies hold promise for identifying unexpected gene environment interactions, but given the statistical power issues, candidate gene association studies will remain important. New tools are enabling the study of epigenetic mechanisms for environmental interactions.
GENETIC CORRELATION OF A MOUSE LIGHT CHAIN VARIABLE REGION MARKER WITH A THYMOCYTE SURFACE ANTIGEN
Authors: Paul D. Gottlieb
Journal: The Journal of Experimental Medicine (1974)

The inbred and congenic strain distribution of the I(H)-peptide marker in the variable region of mouse immunoglobulin light chains has been compared with other known genetic markers. A positive correlation was noted between the I(H)-peptide marker and expression of the Ly-3.1 thymocyte cell surface antigen. This suggests that the locus responsible for I(H)-peptide expression is genetically linked to the Ly-2 and Ly-3 loci in linkage group XI on chromsome 6 of the mouse.
Patterns of IgE sensitization in house dust mite‐allergic patients: implications for allergen immunotherapy
Authors: T. Batard, V. Baron‐Bodo, A. Martelet, M. Le Mignon, P. Lemoine, K. Jain, S. Mariano, S. Horiot, H. Chabre, C. Harwanegg, C. A. Marquette, B. P. Corgier, W. T. Soh, P. Satitsuksanoa, A. Jacquet, F. T. Chew, E. Nony, P. Moingeon
Journal: Allergy (2015)

Understanding patterns of IgE sensitization in Dermatophagoides-allergic patients living in various geographical areas is necessary to design a product suitable for worldwide allergen immunotherapy (AIT).Using a HIFI Allergy customized microarray assay, IgEs specific for 12 purified allergens from Dermatophagoides pteronyssinus or D. farinae were assessed in sera from 1302 house dust mite (HDM)-allergic patients living in various areas. Comprehensive mass spectrometric (MS) analyses were conducted to characterize HDM extracts, as well as purified bodies and feces.Patterns of IgE reactivity to HDM allergens are comparable in all cohorts of patients analyzed, encompassing adults and 5- to 17-year-old children, as well as American, Canadian, European, and Japanese patients. Overall, >70% and >80% of HDM-allergic patients are sensitized to group 1 and group 2 allergens, respectively, from D. pteronyssinus and/or D. farinae species. Furthermore, 20-47% of patients also have IgEs to allergens from groups 4, 5, 7, 13, 15, 21, and 23. All patients have IgEs to allergens present in mite bodies and feces. MS-based analyses confirmed the presence of mite allergens recorded by IUIS in D. pteronyssinus and D. farinae extracts, with groups 2, 8, 10, 11, 14, and 20 prominent in bodies and groups 1, 6, 18, and 23 well represented in feces.Mite-specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination is appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America.
Screening for Narrow Angles in the Singapore Population: Evaluation of New Noncontact Screening Methods
Authors: Raghavan Lavanya, Paul J. Foster, Lisandro M. Sakata, David S. Friedman, Kenji Kashiwagi, Tien-Yin Wong, Han T. Aung, Tamuno Alfred, Hong Gao, Adrian G. Ee, Steve K. Seah, Tin Aung
Journal: Ophthalmology (2008)
Survey of rotavirus surveillance, laboratory capacity and disease burden in the eastern part of the WHO European Region
Authors: C  J Williams, J J Gray, R  G Pebody, A Lobanov
Journal: Eurosurveillance (2008)

Following the licensure of two rotavirus vaccines in Europe, we aimed to assess factors, such as surveillance, disease burden and laboratory capacity, which will be relevant for making decisions about rotavirus vaccine introduction in the different countries. We conducted an email-based survey of the national public health bodies in the World Health Organization (WHO) European Region in 2006 and report here the results from the 23 countries in the eastern part of the region. The survey included questions on rotavirus surveillance, laboratory capacity, burden (in children under the age of five years) and intention to introduce rotavirus vaccination. Countries were grouped into the four per-capita income categories defined by the World Bank. Fourteen of the 23 countries responded to the survey. All except one country reported that less than a quarter of their laboratories had rotavirus diagnostic capacity. Four countries had some form of specific rotavirus surveillance, but half were of very limited coverage. Ten countries did not report data on the incidence of rotavirus hospital admissions, although nine were able to report some data on rotavirus burden. Six of the responding countries said they were likely to introduce universal rotavirus vaccination. Rotavirus surveillance and laboratory capacity in the eastern part of the WHO European Region is limited but most countries had some estimate of rotavirus burden, often from special studies. The reported mortality rates were lower than those from a WHO mortality data source. Many countries in the eastern part of WHO European Region face a number of challenges before vaccine implementation, including strengthening surveillance, improving laboratory capacity and addressing financial barriers.