bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic Cells in the Immune System—History, Lineages, Tissues, Tolerance, and Immunity
Authors: Austyn Jonathan M. 
Published: January 2017

ABSTRACTThe aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the “History” section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The “Lineages” section then focuses on five different populations of DCs: two subsets of “classical” DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells. It highlights some cellular and molecular specializations of each, and also notes other DC subsets that have been proposed. The following “Tissues” section discusses the distribution and behavior of different DC subsets within nonlymphoid and secondary lymphoid tissues that are connected by DC migration pathways between them. In the “Tolerance” section, the role of DCs in central and peripheral tolerance is considered, including their ability to drive the differentiation of different populations of regulatory T cells. In contrast, the “Immunity” section considers the roles of DCs in sensing of infection and tissue damage, the initiation of primary responses, the T-cell effector phase, and the induction of immunological memory. The concluding section provides some speculative ideas about the evolution of DCs. It also revisits earlier concepts of generation of diversity and clonal selection in terms of DCs driving the evolution of T-cell responses. Throughout, this review highlights certain areas of uncertainty and suggests some avenues for future investigation.
The Memory Immune Response to Tuberculosis
Authors: Kirman Joanna R. , Henao-Tamayo Marcela I. , Agger Else Marie 
Published: January 2017

ABSTRACTImmunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses toMycobacterium tuberculosiswill thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity. More recently, we have learned that the memory response required for effective control ofM. tuberculosisis much more complex, probably involving several phenotypically different CD4 T cell subsets as well as other cell types that are yet to be defined. Herein, we describe recent insights into memory immunity to TB in the context of both animal models and the human infection. With the increasing amount of data generated from clinical testing of novel TB vaccines, we also summarize recent knowledge of vaccine-induced memory immunity.
Innate Immune Responses to Tuberculosis
Authors: Schorey Jeffrey S. , Schlesinger Larry S. 
Published: January 2017

ABSTRACTTuberculosis remains one of the greatest threats to human health. The causative bacterium,Mycobacterium tuberculosis, is acquired by the respiratory route. It is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. However,M. tuberculosisbacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primary infection, most commonly a latently infected healthy human host, in whom the bacteria are held in check by the host immune response within the confines of tissue granuloma, the host histopathologic hallmark. Such individuals can develop active TB later in life with impairment in the immune system. In contrast, in a minority of infected individuals, the early host immune response fails to control bacterial growth, and progressive granulomatous disease develops, facilitating spread of the bacilli via infectious aerosols. The molecular details of theM. tuberculosis-host innate immune system interaction continue to be elucidated, particularly those occurring within the lung. However, it is clear that a number of complex processes are involved at the different stages of infection that may benefit either the bacterium or the host. In this article, we describe a contemporary view of the molecular events underlying the interaction betweenM. tuberculosisand a variety of cellular and soluble components and processes of the innate immune system.
Mycobacterium bovis
and Other Uncommon Members of the
Mycobacterium tuberculosis
Complex
Authors: Esteban Jaime , Muñoz-Egea Maria-Carmen 
Published: January 2017

ABSTRACT

Since its discovery by Theobald Smith,
Mycobacterium bovis
has been a human pathogen closely related to animal disease. At present,
M. bovis
tuberculosis is still a problem of importance in many countries and is considered the main cause of zoonotic tuberculosis throughout the world. Recent development of molecular epidemiological tools has helped us to improve our knowledge about transmission patterns of this organism, which causes a disease indistinguishable from that caused by
Mycobacterium tuberculosis
. Diagnosis and treatment of this mycobacterium are similar to those for conventional tuberculosis, with the important exceptions of constitutive resistance to pyrazinamide and the fact that multidrug-resistant and extremely drug-resistant
M. bovis
strains have been described. Among other members of this complex,
Mycobacterium africanum
is the cause of many cases of tuberculosis in West Africa and can be found in other areas mainly in association with immigration.
M. bovis
BCG is the currently available vaccine for tuberculosis, but it can cause disease in some patients. Other members of the
M. tuberculosis
complex are mainly animal pathogens with only exceptional cases of human disease, and there are even some strains, like “
Mycobacterium canettii
,” which is a rare human pathogen that could have an important role in the knowledge of the evolution of tuberculosis in the history.
Diagnosis, Treatment, and Prevention of Urinary Tract Infection
Authors: Pietrucha-Dilanchian Paula , Hooton Thomas M. 
Published: January 2017

ABSTRACT
UTI may involve the lower or upper urinary tract and may be uncomplicated or complicated. The emphasis of this chapter is uncomplicated UTI. The diagnosis of uncomplicated cystitis (bladder infection) and pyelonephritis (kidney infection) is usually easily made based on the clinical presentation, whereas the diagnosis in patients with complicated UTI is often more complex. Thus uncomplicated cystitis is usually manifested by dysuria, frequency and/or urgency without fever, and pyelonephritis is usually manifested by fever and back pain/costovertebral angle tenderness. However, pyuria is usually present with UTI, regardless of location, and its absence suggests that another condition may be causing the patient’s symptoms. Treatment of cystitis is usually straightforward with one of several effective short-course antimicrobial regimens, although antimicrobial resistance continues to increase and can complicate treatment choices in certain areas. Likewise, antimicrobial resistance has complicated our management of uncomplicated pyelonephritis since resistance of uropathogens to the fluoroquinolone class, the mainstay of oral treatment for pyelonephritis, is increasing worldwide, and some of the other agents used for cystitis are not recommended for pyelonephritis due to low tissue levels. The goal of prevention of recurrent cystitis is to minimize the use of antimicrobials and there are several research efforts in progress to develop effective and safe antimicrobial-sparing preventive approaches for this common condition.
Introducing rapid tests for malaria into the retail sector: what are the unintended consequences?
Authors: Hutchinson Eleanor , Hutchison Coll , Lal Sham , Hansen Kristian , Kayendeke Miriam , Nabirye Christine , Magnussen Pascal , Clarke Siân E , Mbonye Anthony , Chandler Clare I R 
Published: January 2017

The observation that many people in Africa seek care for febrile illness in the retail sector has led to a number of public health initiatives to try to improve the quality of care provided in these settings. The potential to support the introduction of rapid diagnostic tests for malaria (mRDTs) into drug shops is coming under increased scrutiny. Those in favour argue that it enables the harmonisation of policy around testing and treatment for malaria and maintains a focus on market-based solutions to healthcare. Despite the enthusiasm among many global health actors for this policy option, there is a limited understanding of the consequences of the introduction of mRDTs in the retail sector. We undertook an interpretive, mixed methods study with drug shop vendors (DSVs), their clients and local health workers to explore the uses and interpretations of mRDTs as they became part of daily practice in drug shops during a trial in Mukono District, Uganda. This paper reports the unintended consequences of their introduction. It describes how the test engendered trust in the professional competence of DSVs; was misconstrued by clients and providers as enabling a more definitive diagnosis of disease in general rather than malaria alone; that blood testing made drug shops more attractive places to seek care than they had previously been; was described as shifting treatment-seeking behaviour away from formal health centres and into drug shops; and influenced an increase in sales of medications, particularly antibiotics.Trial registration numberNCT01194557; Results.
Have health inequalities changed during childhood in the New Labour generation? Findings from the UK Millennium Cohort Study
Authors: Rougeaux Emeline , Hope Steven , Law Catherine , Pearce Anna 
Published: January 2017

ObjectivesTo examine how population-level socioeconomic health inequalities developed during childhood, for children born at the turn of the 21st century and who grew up with major initiatives to tackle health inequalities (under the New Labour Government).SettingThe UK.ParticipantsSingleton children in the Millennium Cohort Study at ages 3 (n=15 381), 5 (n=15 041), 7 (n=13 681) and 11 (n=13 112) years.Primary outcomesRelative (prevalence ratios (PR)) and absolute health inequalities (prevalence differences (PD)) were estimated in longitudinal models by socioeconomic circumstances (SEC; using highest maternalacademicattainment, ranging from ‘no academic qualifications’ to ‘degree’ (baseline)). Three health outcomes were examined: overweight (including obesity), limiting long-standing illness (LLSI), and socio-emotional difficulties (SED).ResultsRelative and absolute inequalities in overweight, across the social gradient, emerged by age 5 and increased with age. By age 11, children with mothers who had no academic qualifications were considerably more likely to be overweight as compared with those with degree-educated mothers (PR=1.6 (95% CI 1.4 to 1.8), PD=12.9% (9.1% to 16.8%)). For LLSI, inequalities emerged by age 7 and remained at 11, but only for children whose mothers had no academic qualifications (PR=1.7 (1.3 to 2.3), PD=4.8% (2% to 7.5%)). Inequalities in SED (observed across the social gradient and at all ages) declined between 3 and 11, although remained large at 11 (eg, PR=2.4 (1.9 to 2.9), PD=13.4% (10.2% to 16.7%) comparing children whose mothers had no academic qualifications with those of degree-educated mothers).ConclusionsAlthough health inequalities have been well documented in cross-sectional and trend data in the UK, it is less clear how they develop during childhood. We found that relative and absolute health inequalities persisted, and in some cases widened, for a cohort of children born at the turn of the century. Further research examining and comparing the pathways through which SECs influence health may further our understanding of how inequalities could be prevented in future generations of children.
Implementation of a consumer-focused eHealth intervention for people with moderate-to-high cardiovascular disease risk: protocol for a mixed-methods process evaluation
Authors: Coorey Genevieve M , Neubeck Lis , Usherwood Timothy , Peiris David , Parker Sharon , Lau Annie Y S , Chow Clara , Panaretto Kathryn , Harris Mark , Zwar Nicholas , Redfern Julie 
Published: January 2017

IntroductionTechnology-mediated strategies have potential to engage patients in modifying unhealthy behaviour and improving medication adherence to reduce morbidity and mortality from cardiovascular disease (CVD). Furthermore, electronic tools offer a medium by which consumers can more actively navigate personal healthcare information. Understanding how, why and among whom such strategies have an effect can help determine the requirements for implementing them at a scale. This paper aims to detail a process evaluation that will (1) assess implementation fidelity of a multicomponent eHealth intervention; (2) determine its effective features; (3) explore contextual factors influencing and maintaining user engagement; and (4) describe barriers, facilitators, preferences and acceptability of such interventions.Methods and analysisMixed-methods sequential design to derive, examine, triangulate and report data from multiple sources. Quantitative data from 3 sources will help to inform both sampling and content framework for the qualitative data collection: (1) surveys of patients and general practitioners (GPs); (2) software analytics; (3) programme delivery records. Qualitative data from interviews with patients and GPs, focus groups with patients and field notes taken by intervention delivery staff will be thematically analysed. Concurrent interview data collection and analysis will enable a thematic framework to evolve inductively and inform theory building, consistent with a realistic evaluation perspective. Eligible patients are those at moderate-to-high CVD risk who were randomised to the intervention arm of a randomised controlled trial of an eHealth intervention and are contactable at completion of the follow-up period; eligible GPs are the primary healthcare providers of these patients.Ethics and disseminationEthics approval has been received from the University of Sydney Human Research Ethics Committee and the Aboriginal Health and Medical Research Council (AH&MRC) of New South Wales. Results will be disseminated via scientific forums including peer-reviewed publications and national and international conferences.Trial registration numberANZCTR 12613000715774.
International multiphase mixed methods study protocol to develop a cross-cultural patient-reported outcome instrument for children and young adults with cleft lip and/or palate (CLEFT-Q)
Authors: Wong Riff Karen W Y , Tsangaris Elena , Goodacre Tim , Forrest Christopher R , Pusic Andrea L , Cano Stefan J , Klassen Anne F 
Published: January 2017

IntroductionPatient-reported outcome (PRO) instruments should be developed according to rigorous guidelines in order to provide clinically meaningful, scientifically sound measurement. Understanding the methodology behind instrument development informs the selection of the most appropriate tool. This mixed methods protocol describes the development of an internationally applicable PRO instrument, the CLEFT-Q, for evaluating outcomes of treatment for cleft lip and/or palate (CL/P).Methods and analysisThe study includes three main phases that occur iteratively and interactively. In phase I, we determine what concepts are important to patients regarding their outcome. A conceptual framework for the CLEFT-Q is formed through a systematic review and an extensive international qualitative study. The systematic review ascertains what concepts have previously been measured in patients with CL/P. The qualitative study employs interpretive description and involves in-depth interviews with patients in high-income and lower-middle income countries. Preliminary items are generated from the qualitative data. Preliminary scales are then created for each theme in the framework. Cognitive debriefing interviews and expert clinician input are used to refine the scales in an iterative process. In phase II, the preliminary scales are administered to a large international group of patients with CL/P. The modern psychometric method of Rasch Measurement Theory analysis is employed to define the measurement characteristics. The preliminary scales are shortened based on these results. In phase III, further tests assess reliability, validity and responsiveness of the instrument.Ethics and disseminationThe study is approved by Research Ethics Boards for each participating site. Findings from this study will be published in open access peer-reviewed journals and presented at national and international conferences. Integrated knowledge translation is employed to engage stakeholders from the outset of the study. Successful execution of the CLEFT-Q will result in an internationally applicable PRO instrument for children and young adults with CL/P.
Brachycephalic dogs and honesty with clients
Authors: Fawcett Anne 
Published: January 2017

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Brachycephalic dogs and honesty with clients’, was submitted and is discussed by Anne Fawcett. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It is hoped it will provide a framework that will help practitioners find solutions when facing similar dilemmas.
Radon dynamics in a dwelling with high radon levels in a karst area
Authors: Vaupotič J. , Brodar A. , Gregorič A. , Kobal I. 
Published: January 2017

Abstract

Year-long continuous radon monitoring was carried out (using Sarad Radon Scout devices) in a dwelling with high radon levels in the karst region of Slovenia. Two living rooms were selected: one on the ground floor with normal housework activities; and the second, on the first floor, closed and unattended. Meteorological data were also recorded. The following seasonal geometric means of radon activity concentration (kBq m
−3
) have been found: 6.28×/: 3.05 for spring, 1.25×/: 3.78 for summer, 5.17×/: 2.03 kBq m
−3
for autumn and 9.83×/: 1.48 for winter on the ground floor; and 1.43×/: 3.71 for spring, 0.168×/: 2.49 for summer, 1.08×/: 2.39 for autumn and 2.08×/: 2.14 for winter on the first floor. Results are supported by additional radon measurements in other rooms; and in water the results indicate a strong radon source associated with an underground karst shaft.
Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia
Authors: Jouett Noah P. , Moralez Gilbert , Raven Peter B. , Smith Michael L. 
Published: January 2017

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in 1) SNA discharge and 2) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mmHg, all P < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mmHg, all P > 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. NEW & NOTEWORTHY This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients.
Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study
Authors: Guertin Kristin A. , Li Xinmin S. , Graubard Barry I. , Albanes Demetrius , Weinstein Stephanie J. , Goedert James J. , Wang Zeneng , Hazen Stanley L. , Sinha Rashmi 
Published: January 2017

Abstract
Background: Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk.
Methods: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case–control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations.
Results: Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24–4.61; Ptrend &lt; 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P &lt; 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P = 0.25, 0.71, and 0.61, respectively).
Conclusions: Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer.
Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. Cancer Epidemiol Biomarkers Prev; 26(6); 945–52. ©2017 AACR.