Isolation of single cells from human uterus in the third trimester of pregnancy: myometrium, decidua, amnion and chorion

During pregnancy, interactions between uterine immune cells and cells of the surrounding reproductive tissues are thought to be vital for regulating labour. The mechanism that specifically initiates spontaneous labour has not been determined, but distinct changes in uterine immune cell populations and their activation status have been observed during labour at term gestation. To understand the regulation of human labour by the immune system, the ability to isolate both immune cells and non-immune cells from the uterus is required. Here, we describe protocols developed in our laboratory to isolate single cells from uterine tissues, which preserve both immune and non-immune cell populations for further analysis. We provide detailed methods for isolating immune and non-immune cells from human myometrium, chorion, amnion and decidua, together with representative flow cytometry analysis of isolated cell populations present. The protocols can be completed in tandem and take approximately 4–5 h, resulting in single-cell suspensions that contain viable leucocytes, and non-immune cells in sufficient numbers for single-cell analysis approaches such as flow cytometry and single cell RNA sequencing (scRNAseq)

A UMLS-based spell checker for natural language processing in vaccine safety

BACKGROUND: The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. METHODS: We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. RESULTS: We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74–75), 100% (95% CI: 100–100), and 47% (95% CI: 46%–48%), respectively. CONCLUSION: We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the specificity was much superior. The slow processing speed may be improved by trimming it down to the most useful component algorithms. Other investigators may find the methods we developed useful for cleaning text using lexicons specific to their area of interest

Validation of the Chronic Pain Acceptance Questionnaire-8 in an Australian pain clinic sample

Background: Recently, an 8-item short-form version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) was developed predominantly in an internet sample. Further investigation of the factor structure in a multidisciplinary pain clinic sample is required. Investigation of the concurrent validity of the CPAQ-8 after accounting for the effects of variables commonly measured in the pain clinic setting is also necessary. Purpose: This study examines the factor structure and concurrent validity of the CPAQ-8 in a sample of treatmentseeking patients who attended a multidisciplinary pain clinic. Methods: Participants were 334 patients who attended an Australian multidisciplinary pain service. Participants completed the CPAQ, a demographic questionnaire, and measures of patient adjustment and functioning. Results: Confirmatory factor analysis identified a two-factor 8-item model consisting of Activity Engagement and Pain Willingness factors (SRMR=0.039, RMSEA=0.063, CFI=0.973, TLI=0.960) was superior to both the CPAQ and CPAQ with an item removed. The CPAQ and CPAQ-8 total scores were highly correlated (r=0.93). After accounting for pain intensity, the CPAQ-8 was a significant predictor of depression, anxiety, stress, and disability. The subscales of the CPAQ-8 were both unique contributors to depression and disability in regression analyses, after accounting for pain intensity and kinesiophobia, and after accounting for pain intensity and catastrophizing. Conclusions: The CPAQ-8 has a sound factor structure and similar psychometric properties to the CPAQ; it may have clinical utility as a measure of pain acceptance in treatmentseeking, chronic pain patients

Spatial Analysis of Land Cover Determinants of Malaria Incidence in the Ashanti Region, Ghana

Malaria belongs to the infectious diseases with the highest morbidity and mortality worldwide. As a vector-borne disease malaria distribution is strongly influenced by environmental factors. The aim of this study was to investigate the association between malaria risk and different land cover classes by using high-resolution multispectral Ikonos images and Poisson regression analyses. The association of malaria incidence with land cover around 12 villages in the Ashanti Region, Ghana, was assessed in 1,988 children <15 years of age. The median malaria incidence was 85.7 per 1,000 inhabitants and year (range 28.4–272.7). Swampy areas and banana/plantain production in the proximity of villages were strong predictors of a high malaria incidence. An increase of 10% of swampy area coverage in the 2 km radius around a village led to a 43% higher incidence (relative risk [RR] = 1.43, p<0.001). Each 10% increase of area with banana/plantain production around a village tripled the risk for malaria (RR = 3.25, p<0.001). An increase in forested area of 10% was associated with a 47% decrease of malaria incidence (RR = 0.53, p = 0.029)

Maternal Use of Antibiotics, Hospitalisation for Infection during Pregnancy, and Risk of Childhood Epilepsy: A Population-Based Cohort Study

BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs

Resistance training with soy vs whey protein supplements in hyperlipidemic males

<p>Abstract</p> <p>Background</p> <p>Most individuals at risk for developing cardiovascular disease (CVD) can reduce risk factors through diet and exercise before resorting to drug treatment. The effect of a combination of resistance training with vegetable-based (soy) versus animal-based (whey) protein supplementation on CVD risk reduction has received little study. The study's purpose was to examine the effects of 12 weeks of resistance exercise training with soy versus whey protein supplementation on strength gains, body composition and serum lipid changes in overweight, hyperlipidemic men.</p> <p>Methods</p> <p>Twenty-eight overweight, male subjects (BMI 25–30) with serum cholesterol >200 mg/dl were randomly divided into 3 groups (placebo (n = 9), and soy (n = 9) or whey (n = 10) supplementation) and participated in supervised resistance training for 12 weeks. Supplements were provided in a double blind fashion.</p> <p>Results</p> <p>All 3 groups had significant gains in strength, averaging 47% in all major muscle groups and significant increases in fat free mass (2.6%), with no difference among groups. Percent body fat and waist-to-hip ratio decreased significantly in all 3 groups an average of 8% and 2%, respectively, with no difference among groups. Total serum cholesterol decreased significantly, again with no difference among groups.</p> <p>Conclusion</p> <p>Participation in a 12 week resistance exercise training program significantly increased strength and improved both body composition and serum cholesterol in overweight, hypercholesterolemic men with no added benefit from protein supplementation.</p

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

BACKGROUND: In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. RESULTS: A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION: Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS

Tres medici, duo athei? The Physician as Atheist and the Medicalization of the Soul

Until recently, examinations of the ‘mind-body problem’ in historical context paid only cursory attention to its specifically medical dimension, if at all. At best, some ‘folk physiology’ was entertained, usually to laugh at it (the pineal gland, animal spirits). Conversely, historians of neuroscience or of artificial intelligence (Jeannerod 1985, Dupuy 2000) often present figures like La Mettrie as heroic early cases of ‘naturalization’, giving an experimental basis to materialism: their symmetrically inverse mistake is to take professions of medical authority too literally (although there are genuine cases where all of the above does coalesce – where ‘actors’ categories mysteriously transcend historiographic projections –, such as Hieronymus Gaub’s reflections on the ‘regimen of the mind’ in the mid-eighteenth century, or, more theoretically, Guillaume Lamy’s Epicurean-inflected Anatomical Discourses on the Soul, eighty years earlier). Contrary to the denial of the relevance of medicine in early modern philosophy, as regards issues such as the body-soul (then body-mind) relation among others, it seems patently difficult to separate medical theory, medically nourished philosophical speculation, and metaphysics. This is the case, whether in Descartes, Gaub, the ‘animist’ Georg-Ernest Stahl, or materialists such as Guillaume Lamy and La Mettrie: medicine, or rather ‘a certain idea of medicine’, is everywhere. Here I focus on the motif of a radical medicine – a medical precursor of the Radical Enlightenment (Israel 2001, 2006, 2007), symbolized negatively by the slogan, tres medici, duo athei, or ‘where there are three doctors, there are two atheists’, i.e. medicine as a basis for atheism. This theme runs through various works of medical or medico-theological propaganda: Thomas Browne’s 1643 De religio medici begins with Browne regretting rumors of doctors being atheists as the “general scandal of my Profession”; Germain de Bezançon’s 1677 Les médecins à la censure works hard at rebutting the saying, “Bon Physicien, mauvais chrétien.” But these are examples of the fear of a radical medicine – a medicine that denies the existence of an immortal soul, or even defends materialism and atheism. Are there positive statements of this doctrine? Indeed, attacks on it are much more common than statements identifying with it, like medical versions of natural theology in general. In fact, just as there were theologically motivated medical works, there were also medically motivated works of radical or heretical theology, like William Coward’s Second Thoughts on the Human Soul (Coward 1702, building on Overton 1644), which engaged in polemics concerning the nature of the soul – mortal or immortal? (Thomson 2008). Parallel to the mortalist trend, but flowing into a common genre of radical, medico-materialist texts (sometimes anonymous, such as L’Âme Matérielle, from the 1720s) are at least two other strands of radical medicine: a post-Cartesian focus on medicina mentis and the nature of the mind (Henricus Regius, Hieronymus Gaub, Antoine Le Camus), and an Epicurean medicine, in which mind and body are organismically united, with an additional hedonistic component, notably in Lamy, Mandeville and La Mettrie (Wright 1991, Wolfe and van Esveld 2014). The focus on a medicine of the mind (Corneanu, ms. 2013) is obviously connected to a ‘medicalization of the soul’: there was a body-soul problem in and for medicine, a sort of medicalized ‘pneumatology’. Radical medicine is located somewhere in between the early forms of ‘naturalization’ or ‘medicalization’ of the soul and the pose of scientific neutrality that is characteristic of early nineteenth-century medicine (as in Cabanis, Bichat or Bernard): it is a short-lived episode. I seek to reconstruct this intellectual figure, in which mortalist, post-Cartesian and Epicurean strands intersect and sometimes come together. I suggest that medically influenced materialism in the Radical Enlightenment (e.g. in the later French cases, La Mettrie, Ménuret and Diderot), is different from later, more experimentally focused and more quantitatively oriented forms of medical materialism, precisely because of its radical dimension. This radical medicine often insists on vitality, as opposed to “anatomie cadavérique”: it is vital and hedonistic, a medicine concerned with maintaining bodily pleasure.Until recently, examinations of the 'mind-body problem' in historical context paid only cursory attention to its specifically medical dimension, if at all. At best, some 'folk physiology' was entertained, usually to laugh at it (the pineal gland, animal spirits). Conversely, historians of neuroscience or of artificial intelligence (Jeannerod M, The brain machine. The development of neurophysiological thought, trans. D. Urion, Harvard University Press, Cambridge, 1985; Dupuy J-P, The mechanization of the mind: on the origins of cognitive science, trans. M.B. DeBevoise, Princeton University Press, Princeton, 2000) often present figures like La Mettrie as heroic early cases of 'naturalization', giving an experimental basis to materialism: their symmetrically inverse mistake is to take professions of medical authority too literally (although there are genuine cases where all of the above does coalesce where 'actors' categories mysteriously transcend historiographic projections -, such as Hieronymus Gaub's reflections on the 'regimen of the mind' in the mid-eighteenth century, or, more theoretically, Guillaume Lamy's Epicurean-inflected Anatomical Discourses on the Soul, eighty years earlier). Contrary to the denial of the relevance of medicine in early modern philosophy, as regards issues such as the body-soul (then body-mind) relation among others, it seems patently difficult to separate medical theory, medically nourished philosophical speculation, and metaphysics. This is the case, whether in Descartes, Gaub, the 'animist' Georg-Ernest Stahl, or materialists such as Guillaume Lamy and La Mettrie: medicine, or rather 'a certain idea of medicine', is everywhere.Here I focus on the motif of a radical medicine - a medical precursor of the Radical Enlightenment (Israel J, Radical enlightenment. Philosophy and the making of modernity, 1650-1750, Oxford University Press, Oxford, 2001; Israel J, Enlightenment contested. Oxford University Press, Oxford, 2006, Israel J, Enlightenment, radical enlightenment and the "medical revolution" of the late seventeenth and eighteenth centuries. In: Grell OP, Cunningham A (ed) Medicine and religion in enlightenment Europe. Ashgate, Aldershot, pp 5-28, 2007), symbolized negatively by the slogan, tres medici, duo athei, or 'where there are three doctors, there are two atheists', i.e. medicine as a basis for atheism. This theme runs through various works of medical or medico-theological propaganda: Thomas Browne's 1643 De religio medici begins with Browne regretting rumors of doctors being atheists as the "general scandal of my Profession"; Germain de Bezancon's 1677 Les medecins a la censure works hard at rebutting the saying, "Bon Physicien, mauvais chretien." But these are examples of the fear of a radical medicine - a medicine that denies the existence of an immortal soul, or even defends materialism and atheism. Are there positive statements of this doctrine? Indeed, attacks on it are much more common than statements identifying with it, like medical versions of natural theology in general.In fact, just as there were theologically motivated medical works, there were also medically motivated works of radical or heretical theology, like William Coward's Second Thoughts on the Human Soul (Coward W, Second thoughts on the human soul. R. Basset, London, 1702, building on Overton 1644), which engaged in polemics concerning the nature of the soul - mortal or immortal? (Thomson A, Bodies of thought: science, religion, and the soul in the early enlightenment. Oxford University Press, Oxford, 2008). Parallel to the mortalist trend, but flowing into a common genre of radical, medico-materialist texts (sometimes anonymous, such as L'Ame Materielle, from the 1720s) are at least two other strands of radical medicine: a post-Cartesian focus on medicina mentis and the nature of the mind (Henricus Regius, Hieronymus Gaub, Antoine Le Camus), and an Epicurean medicine, in which mind and body are organismically united, with an additional hedonistic component, notably in Lamy, Mandeville and La Mettrie (Wright JP, Locke, Willis, and the seventeenth-century epicurean soul. In: Osler MJ (ed) Atoms, Pneuma, and Tranquillity: Epicurean and stoic themes in European thought. Cambridge University Press, Cambridge, pp 239-258, 1991; Wolfe CT, van Esveld M, The material soul: strategies for naturalising the soul in an early modern epicurean context. In: Kambaskovic D (ed) Conjunctions: body, soul and mind from Plato to the enlightenment. Springer, Dordrecht, pp 371-421, 2014). The focus on a medicine of the mind (Corneanu, (ms. 2013), The care of the whole man: medicine and theology in the late renaissance, 2013) is obviously connected to a 'medicalization of the soul': there was a body-soul problem in and for medicine, a sort of medicalized 'pneumatology'. Radical medicine is located somewhere in between the early forms of 'naturalization' or 'medicalization' of the soul and the pose of scientific neutrality that is characteristic of early nineteenth-century medicine (as in Cabanis, Bichat or Bernard): it is a short-lived episode. I seek to reconstruct this intellectual figure, in which mortalist, post-Cartesian and Epicurean strands intersect and sometimes come together. I suggest that medically influenced materialism in the Radical Enlightenment (e.g. in the later French cases, La Mettrie, Menuret and Diderot), is different from later, more experimentally focused and more quantitatively oriented forms of medical materialism, precisely because of its radical dimension. This radical medicine often insists on vitality, as opposed to "anatomie cadaverique": it is vital and hedonistic, a medicine concerned with maintaining bodily pleasure

T Cells from Programmed Death-1 Deficient Mice Respond Poorly to Mycobacterium tuberculosis Infection

Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice