tbuckley/cabot-search huggingface dataset:
Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens
Authors: J G Fox, Y Feng, E J Theve, A R Raczynski, J L A Fiala, A L Doernte, M Williams, J L McFaline, J M Essigmann, D B Schauer, S R Tannenbaum, P C Dedon, S A Weinman, S M Lemon, R C Fry, A B Rogers
Journal: Gut (2009)

<h3>Background and aims:</h3> Hepatocellular carcinoma (HCC) frequently results from synergism between chemical and infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for the foodborne contaminant aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models. <h3>Methods:</h3> <i>Helicobacter</i>-free C3H/HeN mice were inoculated with AFB1 and/or <i>Helicobacter hepaticus</i>. The incidence, multiplicity and surface area of liver tumours were quantitated at 40 weeks. Molecular pathways involved in tumourigenesis were analysed by microarray, quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA, western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35 mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with C3H/HeN mice and cancer rates compared between offspring with and without <i>H hepaticus</i>. <h3>Results:</h3> Intestinal colonisation by <i>H hepaticus</i> was sufficient to promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation to the liver nor induction of hepatitis was necessary. From its preferred niche in the intestinal mucus layer, <i>H hepaticus</i> activated nuclear factor-κB (NF-κB)-regulated networks associated with innate and T helper 1 (Th1)-type adaptive immunity both in the lower bowel and liver. Biomarkers indicative of tumour progression included hepatocyte turnover, Wnt/β-catenin activation and oxidative injury with decreased phagocytic clearance of damaged cells. <h3>Conclusions:</h3> Enteric microbiota define HCC risk in mice exposed to carcinogenic chemicals or hepatitis virus transgenes. These results have implications for human liver cancer risk assessment and prevention.
Mapping Millikan's conceptual work onto (empirical) work by psychologists
Authors: Lloyd K. Komatsu
Journal: Behavioral and Brain Sciences (1998)

There are three points of difference between psychologists' assumptions and those that Millikan suggests: (1) concepts as representations versus concepts as reflecting a capacity; (2) concepts having a role in categorization and inference versus a role in reidentification; and (3) the “basic level” as an aspect of the “vertical” dimension of categories versus being a kind of category, on a par with natural kinds.
Polyps Wrap Mast Cells and Treg within Tumorigenic Tentacles
Authors: Mario P. Colombo, Silvia Piconese
Journal: Cancer Research (2009)

Gounaris and colleagues describe a previously unrecognized cross-talk between mast cells and Treg in colon adenomatous polyposis (Gounaris et al., Cancer Res 2009;69:5490-7). Adoptively transferred Treg suppress the focal mastocytosis that fosters tumor initiation and progression. In contrast, endogenous Treg, which abundantly infiltrate polyps, show proinflammatory activity under unknown microenvironmental cues that promote mast cell differentiation and expansion. Compartmentalized Treg plasticity seems to be a key factor in establishing the optimal milieu for cancer development in the intestines. Treg partnership with mast cells recapitulates the complexity of innate-adaptive networks characterizing gut inflammation and represents a novel target for cancer immunotherapy.
Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome
Authors: Rosa Vargas-Poussou, Chunfa Huang, Philippe Hulin, Pascal Houillier, Xavier Jeunemaître, Michel Paillard, Gabrielle Planelles, Michèle Déchaux, R Tyler Miller, Corinne Antignac
Journal: Journal of the American Society of Nephrology (2002)

The extracellular Ca2+-sensing receptor (CaSR) plays an essential role in extracellular Ca2+ homeostasis by regulating the rate of parathyroid hormone (PTH) secretion and the rate of calcium reabsorption by the kidney. Activation of the renal CaSR is thought to inhibit paracellular divalent cation reabsorption in the cortical ascending limb (cTAL) both directly and indirectly via a decrease in NaCl transport. However, in patients with autosomal dominant hypocalcemia (ADH), caused by CaSR gain-of-function mutations, a defect in tubular NaCl reabsorption with renal loss of NaCl has not been described so far. This article describes a patient with ADH due to a gain-of-function mutation in the CaSR, L125P, associated with a Bartter-like syndrome that is characterized by a decrease in distal tubular fractional chloride reabsorption rate and negative NaCl balance with secondary hyperaldosteronism and hypokalemia. The kinetics of activation of the L125P mutant receptor expressed in HEK-293 cells, assessed by measuring CaSR-stimulated changes in intracellular Ca2+ and ERK activity, showed a dramatic reduction in the EC50 for extracellular Ca2+ compared with the wild-type and a loss-of-function mutant CaSR (I40F). This study describes the first case of ADH associated with a Bartter-like syndrome. It is herein proposed that the L125P mutation of the CaSR, which represents the most potent gain-of-function mutation reported so far, may reduce NaCl reabsorption in the cTAL sufficiently to result in renal loss of NaCl with secondary hyperaldosteronism and hypokalemia.
Transmission Stages Dominate Trypanosome Within-Host Dynamics during Chronic Infections
Authors: Paula MacGregor, Nicholas J. Savill, Deborah Hall, Keith R. Matthews
Journal: Cell Host & Microbe (2011)

Sleeping sickness is characterized by waves of the extracellular parasite Trypanosoma brucei in host blood, with infections continuing for months or years until inevitable host death. These waves reflect the dynamic conflict between the outgrowth of a succession of parasite antigenic variants and their control by the host immune system. Although a contributor to these dynamics is the density-dependent differentiation from proliferative "slender forms" to transmissible "stumpy forms," an absence of markers discriminating stumpy forms has prevented accurate parameterization of this component. Here, we exploit the stumpy-specific PAD1 marker, which functionally defines transmission competence, to quantitatively monitor stumpy formation during chronic infections. This allows reconstruction of the temporal events early in infection. Mathematical modeling of these data describes the parameters controlling trypanosome within-host dynamics and provides strong support for a quorum-sensing-like mechanism. Our data reveal the dominance of transmission stages throughout infection, a consequence being austere use of the parasite's antigen repertoire.
The PROactive innovative conceptual framework on physical activity
Authors: Fabienne Dobbels, Corina de Jong, Ellen Drost, Janneke Elberse, Chryssoula Feridou, Laura Jacobs, Roberto Rabinovich, Anja Frei, Milo A. Puhan, Willem I. de Boer, Thys van der Molen, Kate Williams, Hillary Pinnock, Thierry Troosters, Niklas Karlsson, Karoly Kulich, Katja Rüdell
Journal: European Respiratory Journal (2014)

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what "physical activity" means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients' perspective. The PROactive PRO instruments' content validity represents the pivotal basis for empirically based item reduction and validation.
Effects of theophylline and S 9795 on hyperoxic and hypoxic pulmonary vascular tone in intact dogs
Authors: P Lejeune, M Leeman, C Melot, R Naeije
Journal: European Respiratory Journal (1989)

In the literature, it remains uncertain whether methylxanthines inhibit hypoxic pulmonary vasoconstriction. We examined the effects of theophylline and of S 9795, a new methylxanthine derivative, on multipoint mean pulmonary arterial pressure (Ppa)/cardiac index (Q) relationships in 31 intact dogs, ventilated alternately in hyperoxia (fraction of inspired oxygen, FIO2 0.4) and in hypoxia (FIO2 0.1). A sequence of two 5-point Ppa/Q plots at FIO2 0.4 and at FIO2 0.1, consecutively, was performed before and after i.v. administrations of theophylline 10 mg.kg-1 (n = 8) and 25 mg.kg-1 (n = 7), of S 9795 10 mg.kg-1 (n = 8) and of placebo (n = 8). The Ppa/Q plots were rectilinear in all experimental conditions. Over the entire range of Q studied, 2-5 l.min-1.m-2, hypoxia increased Ppa in all animals. Placebo had no effect on these Ppa/Q plots. Theophylline at the lowest dose (plasma levels from 8.4-13.6 micrograms.ml-1) and S 9795 (plasma levels from 3.0-11.2 micrograms.ml-1) did not affect Ppa/Q in hyperoxia or in hypoxia. Theophylline at the highest dose (plasma levels from 17.8-40.4 micrograms.ml-1) reduced hypoxic Ppa at all levels of Q and hyperoxic Ppa at the highest Q, from 3-5 l.min-1.m-2, and inhibited hypoxia-induced increases in Ppa. We conclude that pulmonary vasoconstriction may be preserved after the lowest doses of methylxanthines recommended for the treatment of increased bronchial tone.
The role of intervening hospital admissions on trajectories of disability in the last year of life: prospective cohort study of older people
Authors: T. M. Gill, E. A. Gahbauer, L. Han, H. G. Allore
Journal: BMJ (2015)

<b>Objective</b> To evaluate the role of intervening hospital admissions on trajectories of disability in the last year of life. <b>Design</b> Prospective cohort study. <b>Setting</b> Greater New Haven, Connecticut, United States, from March 1998 to June 2013. <b>Participants</b> 552 decedents from a cohort of 754 community living people, aged 70 years or older, who were initially non-disabled in four essential activities of daily living: bathing, dressing, walking, and transferring. <b>Main outcome measure</b> Occurrence of admissions to hospital and severity of disability (range 0-4), ascertained during monthly interviews for more than 15 years. <b>Results</b> In the last year of life, six distinct trajectories of disability were identified, from least disabled to most disabled: 95 participants (17.2%) had no disability, 61 (11.1%) had catastrophic disability, 53 (9.6%) had accelerated disability, 61 (11.1%) had progressively mild disability, 127 (23.0%) had progressively severe disability, and 155 (28.1%) had persistently severe disability. 392 (71.0%) participants had at least one hospital admission and 248 (44.9%) had multiple hospital admissions. For each trajectory the course of disability closely tracked the monthly prevalence of hospital admission. In a set of multivariable models that included several potential confounders, hospital admission in a given month had a strong independent effect on the severity of disability, in both relative and absolute terms. The largest absolute effect was observed for catastrophic disability, with a mean increase in disability score of 1.9 (95% confidence interval 1.5 to 2.4) in the setting of a hospital admission, corresponding to a rate ratio (or relative effect) of 2.0 (95% confidence interval 1.5 to 2.7). <b>Conclusions</b> In the last year of life, acute hospital admissions play an important role in the disabling process. Knowledge about the course of disability before these intervening events may facilitate clinical decision making at the end of life. For older patients admitted to hospital with progressive or persistent levels of severe disability, representing more than half of the decedents, clinicians might consider a palliative care approach to facilitate discussions about advance care planning and to better deal with personal care needs.
Developments in the Epidemiology of Drug Use and Drug Use Disorders
Authors: Wilson M Compton, Yonette F Thomas, Kevin P Conway, James D Colliver
Journal: American Journal of Psychiatry (2005)

The past 30 years of research on the epidemiology of drug use, drug use disorders, and related conditions, such as HIV, has provided major insight into these conditions. Drug use peaked in the late 1970s, decreased across the 1980s, increased in the 1990s, and has remained stable during the past few years. Within this broad pattern, specific epidemics of crack cocaine, amphetamines, club drugs (such as Ecstasy), heroin, and prescription opioids and associated epidemics of HIV and other infectious diseases have been identified and tracked. Besides major accomplishments in surveillance, the epidemiology of drug use and drug use disorders has traditionally focused on identifying risk factors at the individual (genetic factors, high-risk behaviors), family (child abuse), neighborhood (high availability of drugs), and societal (policies and laws) levels as domains of influence, not as components of interrelated processes. Research includes careful cross-sectional and longitudinal observational studies as well as clinical epidemiological experiments in which prevention interventions test specific etiological theories. Building on this background, the next challenges for the epidemiology of drug use and drug use disorders will be to link individual vulnerabilities with specific environmental factors by using multilevel methodological approaches. For example, what are the environmental factors that interact with individual vulnerabilities to produce drug addictions and drug consequences such as HIV? Research in genetic epidemiology has demonstrated the potential for studies of interactions of genetic and environmental factors. The field needs to focus on linking science with epidemiology to make progress in understanding these complex health conditions.
Eosinophilic bronchiolitis: is it a new syndrome?
Authors: Venerino Poletti
Journal: European Respiratory Journal (2013)

Identification of new diseases or a cluster (syndrome) of disorders with very similar pathological, radiological and clinical aspects, even sharing common pathogenic steps, is an important fact to build up the scientific soul of the complex and intriguing art called medicine. In this issue of the European Respiratory Journal , a new distinct syndrome, hypereosinophilic obliterative bronchiolitis, is described by Cordier et al. [1]. This syndrome is defined by: 1) a blood eosinophil cell count >1 G·L−1 and/or a bronchoalveolar lavage (BAL) eosinophil differential cell count >25%; 2) persistent airflow obstruction on lung function tests not modifiable after 4–6 weeks of inhaled corticosteroid therapy (2000 μg·day−1 of beclometasone or equivalent); and 3) a lung biopsy showing inflammatory bronchiolitis with prominent bronchiolar wall infiltration by eosinophils and/or characteristic direct high-resolution computed tomography (HRCT) features of bronchiolitis (poorly defined centrilobular nodules, branching opacities and tree-in-bud pattern). The first impression that a cursory clinician and/or pathologist may have, going swiftly through this list of criteria, is that “we are dealing with a severe and persistent form of asthma”. In chronic asthma the obstructive impairment becomes fixed and not modifiable, at least not easily, with steroids or bronchodilators. In chronic asthma eosinophils in lung tissue and blood may be constantly increased and HRCT scans show abnormalities in between 68% and 90% of patients (bronchial wall thickening and narrowing …
Hyperbaric oxygen. Association raises awareness.
Authors: M R Hamilton-Farrell
Journal: BMJ (1993)

Heart Association issued a press release last year about a controlled study showing the benefit of adjunctive hyperbaric oxygen after coronary thrombolysis.Similar studies are urgently needed in stroke.Facilities in Britain are grossly inadequate, even for the acute indications for hyperbaric oxygen.Treatment of problem wounds requires a simple chamber in every hospital.This would save the NHS millions ofpounds a year.
Transitioning From Pediatric to Adult Care
Authors: Jill Weissberg-Benchell, Howard Wolpert, Barbara J. Anderson
Journal: Diabetes Care (2007)

Diabetes research and health care have traditionally been divided into two distinct areas for receiving medical care: pediatric and adult. We propose a fresh approach to providing care in which we consider the period of development after high school as a period of “emerging adulthood” for youth with diabetes. We argue that the traditional conceptualization of only two distinct groups of patients misses the unique personal needs of individuals immediately post–high school. We frame this discussion about the needs of these post–high school patients (∼18–30 years of age) within the context of a contemporary theory of post-adolescent development. With this developmental context in hand, we then review psychosocial research on youth with type 1 diabetes. Next we discuss current clinical perspectives and knowledge about the natural course of diabetes during these years. Armed with an understanding of development, psychosocial functioning, and overall health, we then consider the literature regarding transition programs for youth with chronic diseases—both diabetes and other illnesses. We conclude by presenting specific strategies and recommendations to help both pediatric and adult providers care for the transition needs of this vulnerable population of individuals with diabetes.

Over the past century, traditional developmental psychology defined the time immediately after adolescence as the “young adult period” (3,4). In contrast, a leading contemporary developmental theorist (1,2) has argued that young adulthood does not begin until youth are in their late twenties or thirties and that the developmental stage between ∼l8 and 25 years defines a period called “emerging adulthood.” Recent cultural trends in America for young people in their twenties lead to delays in assuming adult roles with respect to marriage, parenting, and work. Arnett (2) suggests that today's young people “explore the possibilities available to them in love and work, and move gradually toward making enduring …
A Review of Collaborative Partnerships as a Strategy for Improving Community Health
Authors: Stergios Tsai Roussos, Stephen B. Fawcett
Journal: Annual Review of Public Health (2000)

▪ Abstract Collaborative partnerships (people and organizations from multiple sectors working together in common purpose) are a prominent strategy for community health improvement. This review examines evidence about the effects of collaborative partnerships on (a) community and systems change (environmental changes), (b) community-wide behavior change, and (c) more distant population-level health outcomes. We also consider the conditions and factors that may determine whether collaborative partnerships are effective. The review concludes with specific recommendations designed to enhance research and practice and to set conditions for promoting community health.
Distinct phenotypic changes between the superficial and deep component of giant congenital melanocytic naevi: a rationale for curettage
Authors: L.E. De Raeve, A. Claes, D.J. Ruiter, G.N.P. van Muijen, D. Roseeuw, L.C.L.T. Van Kempen
Journal: British Journal of Dermatology (2005)

Background Giant congenital melanocytic naevi (GCMN) convey a 14‐fold increased melanoma risk. In contrast, medium congenital melanocytic naevi (MCMN) are rarely associated with malignant transformation. Management of patients with GCMN is challenging and there is no consensus on the most appropriate strategy for treating these patients. Objectives To provide a rationale for performing curettage of GCMN in the neonatal period in order to reduce the risk of malignant transformation to melanoma. Methods Twenty‐six infants with GCMN who underwent biopsies before excisional surgery (n = 7) or curettage (n = 19) during the past 14 years (Academic Hospital, Vrije Universiteit Brussel) and 10 MCMN patients who underwent excision biopsies (Radboud University Nijmegen Medical Centre) were included in this study. Using these biopsies, we performed genetic and detailed immunohistochemical evaluations of changes that are associated with malignant transformation. Variables of interest included melanoma‐associated BRAF mutations, proliferative activity, vascularity, cellular context and extracellular matrix architecture. Results GCMN and MCMN did not show oncogenic BRAF mutation and displayed similar features with respect to the amount of nonmelanocytic cells within the naevus and matrix architecture. Naevus cells in the superficial component of the GCMN, however, were more proliferative, and this component was more vascular compared with its deep component and with MCMN. In this study, none of the 19 newborn patients who underwent curettage developed a melanoma within a mean follow‐up time of 7 years. Conclusions The data presented here support the idea that curettage of GCMN in neonates has the potential for lowering the risk of developing cutaneous melanoma by not only obtaining an important numerical reduction of naevus cells but also removing the 'active' melanocytes.
E<scp>PIDEMIOLOGY OF</scp>N<scp>EURODEGENERATION</scp>
Authors: Richard Mayeux
Journal: Annual Review of Neuroscience (2003)

▪ Abstract Alzheimer's disease, Parkinson's disease, and motor neuron disease share a propensity to occur with increasing age and as either a sporadic or a familial disorder. A number of behavioral and environmental risk factors have been proposed for each disorder, but most associations lack consistency and specificity. Over the last decade the remarkable frequency of these disorders has become apparent, and the identification of mutations in genes has provided the means to understand their pathogenesis. Better and more accurate means to characterize and diagnose these diseases has greatly facilitated analytic epidemiology. The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders.