tbuckley/cabot-search huggingface dataset:
The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month
Authors: Amy L. Salisbury, Kevin E. O’Grady, Cynthia L. Battle, Katherine L. Wisner, George M. Anderson, Laura R. Stroud, Cynthia L. Miller-Loncar, Marion E. Young, Barry M. Lester
Journal: American Journal of Psychiatry (2015)

Objective: The purpose of this article was to systematically compare the developmental trajectory of neurobehavior over the first postnatal month for infants with prenatal exposure to pharmacologically untreated maternal depression, selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors (collectively: SSRIs), SSRIs with concomitant benzodiazepines (SSRI plus benzodiazepine), and no maternal depression or drug treatment (no exposure). Method: Women (N=184) were assessed at two prenatal time points to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined with a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at multiple time points across the first postnatal month. SSRI exposure was confirmed in a subset of participants with plasma SSRI levels. General linear-mixed models were used to examine group differences in neurobehavioral scores over time with adjustment for demographic variables and depression severity. Results: Infants in the SSRI and SSRI plus benzodiazepine groups had lower motor scores and more CNS stress signs across the first postnatal month, as well as lower self-regulation and higher arousal at day 14. Infants in the depression group had low arousal throughout the newborn period. Infants in all three clinical groups had a widening gap in scores from the no-exposure group at day 30 in their response to visual and auditory stimuli while asleep and awake. Infants in the SSRI plus benzodiazepine group had the least favorable scores on the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Conclusions: Neonatal adaptation syndrome was not limited to the first 2 weeks postbirth. The profile of neurobehavioral development was different for SSRI exposure than depression alone. Concomitant benzodiazepine use may exacerbate adverse behavioral effects.
Real friends:<i>Faecalibacterium prausnitzii</i>supports mucosal immune homeostasis
Authors: Mathias W Hornef, Oliver Pabst
Journal: Gut (2015)

IBD is commonly considered as an exaggerated immune response to the microbiota in a genetically susceptible host. This statement recognises the central role of the enteric microbiota in the pathogenesis of IBD. Consistently, in animal models of IBD, inflammation is not observed in the absence of live bacteria and distinct members of the microbiota differ in their potential to trigger disease. Patients with IBD present substantial changes of their microbiota commonly described as dysbiosis.1–4 However, intestinal bacteria not only drive disease but quite the contrary, individual commensal members also dampen inflammatory responses and might thereby contribute to maintain host–microbial homeostasis (figure 1). This aspect seems of particular interest since it may provide the opportunity to develop therapeutic anti-inflammatory strategies.



Figure 1 
Immunomodulatory effects of the microbiota and specific commensal bacteria. Tryptophan metabolites via the aryl hydrocarbon receptor (AhR) modulate intraepithelial lymphocytes (IELs) and stimulate RAR-related orphan receptor ((ROR)γt+) type 3 innate lymphocytes (ILCs) to promote cryptopatch and isolated lymphoid follicles (ILFs) as well as interleukin 22 (IL-22) secretion. IL-22 in turn stimulates the expression of the antibacterial c-type lectin Reg3γ. Also, short-chain fatty acids (SCFAs) resulting from bacterial degradation of dietary fibres induce the expression of an antimicrobial peptide, the cathelicidin LL37. SCFAs additionally activate the G-coupled protein receptors 43 and 109a inducing K+ release and stimulation of the inflammasome leading to barrier reinforcement. SCFAs also induce differentiation and proliferation of T regulatory (TREG) cells. Examples of specific effects are the microbial anti-inflammatory molecules (MAM) secreted from Faecalibacterium prausnitzii that inhibit cellular NF-κB signalling and inflammation. Polysaccharide A (PSA) produced by Bacteroides fragilis stimulates via Toll-like receptor (TLR)2 interleukin 10 (IL-10) secretion and the differentiation of TREG cells. Lactocepin released …
The role of multinuclear macrophages for diagnosing pulmonary tuberculosis with application of cytospine-preparation - Review of 152 cases
Authors: Tinatin Mamaladze, Marina Kikvidze, Lali Mikiashvili, Natia Gujabidze, Rusudan Aspindzelashvili
Journal: European Respiratory Journal (2013)

Introduction: Despite recent advances in bacteriological diagnostics of pulmonary tuberculosis (PTB), in many smear negative cases establishing diagnosis remains problem. Macrophages, have long been thought of as the primary intracellular niche for M. tuberculosis  Aim: The aim of this study was: to assess the utility of Cytospin-preparation for the recognition of macrophages in bronchial washing and definition of it’s the diagnostic value; gaining a better understanding of the cellular processes that protect the lung during infection.  Methods: Bronchial washings of 152 PTB-suspected patients were studied in National Center for Tuberculosis and Lung Diseases in 2009-10years for multinuclear macrophages, which was cytological confirmation of PTB. These data were compared to bacteriological results - “gold standard”.  Results: Among 152 PTB-suspects’ bronchial washings multinuclear macrophages was found in 34 patient. From them cultural confirmation of PTB was in 24 cases. 118 bronchial washings didn’t contained macrophages, but in 14 cases culture was positive. Specificity of cytological method - Cytospin-preparation was 91,23% and sensitivity 63,16%. +PV was 70,6% and –PV=11,89%; +LR=7,20 and –LR=0,40.  Conclusion: Cytospin-preparation showed high specificity and mild sensitivity for diagnosis PTB and can be thought as one of the most valuable diagnostic tool. Multinuclear macrophages may be defined as diagnostic criteria for tuberculosis, though further similar researches are needed.
The Science of CPR: Just Scratching the Surface
Authors: Thomas D. Rea
Journal: Circulation (2015)

CPR involving external chest compression and positive-pressure ventilation was first described over 50 years ago in a landmark publication that launched the fundamental approach to present-day CPR 1 . Since this initial description, modern-day CPR has given rise to initiatives related to CPR research, education and training, advocacy, and industry.
Long-term survival is linked to serum LDH normalization in SCLC
Authors: Cheng Chen, Jianan Huang
Journal: European Respiratory Journal (2013)

Background: High serum LDH level is linked to many malignancies with poorer survival, but tumour LDH has not been well investigated in small cell lung cancer (SCLC).

Methods: Chemotherapy was performed in 157 cases of confirmed SCLC. The evaluation of treatment response was based on CT imaging. The relationship between LDH level change and chemotherapeutic efficiency was analyzed. Impact on long-term survival and correlation was analyzed.

Results: At diagnosis, the median LDH level in our 157 SCLC patients was 246 U/l (range 101–1254 U/l). Significant differences in LDH levels were found in limited and expanding groups (186 U/l VS 242 U/L, P <0.05). After first-line chemotherapy, the remissive group showed decreased level of LDH, the progressive group showed increased LDH. In refractory patients, the LDH level will be increased compared to that of remissive period. In the follow-up, we found that prolonging of serum LDH normalization co-related to TTP and OS. In patients who die, LDH levels were significantly higher in the two 3-month period preceding progression compared with the initial two 3-month period ( P < 0.005). An increase in LDH by at least 145 U/l was found to be associated to a significantly higher probability of disease progression and a significantly reduced probability of survival compared to patients without increasing LDH( P < 0.05). In multivariate analyses, the LDH increase was found to be an independent prognostic variable.

Conclusions The LDH is a useful biological mark in finding out recurrence and reflecting the therapeutic effect. LDH is an interesting follow-up parameter in SCLC, which may assist in early recognition of disease progression and thus help in risk stratification.
The DLNO/DLCO ratio is not dependent on breath holding time in healthy subjects
Authors: Ivo van der Lee, Sjaak Dijkman, Frans Krouwels
Journal: European Respiratory Journal (2013)

Introduction: The nitric oxide diffusion capacity (DLNO) has been found to be dependant on breath holding time (BHT) [1], a phenomenon that has not been confirmed by other researchers [2]. The aim of this study was to measure the effect of BHT on the DLNO, DLCO (diffusion capacity of carbon monoxide) and the DLNO/DLCO ratio.  Methods: Measurements of the DLNO and DLCO were performed in 15 healthy subjects (11 female and 4 male). The inhalation gas mixture (9% He, 0,25% CO, 50 ppm NO, balance air) was prepared in a Douglas bag, immediately before the test. Measurements were performed in random order with 4 and 10 sec BHT according to Meade and Jones. The tests were performed twice for each BHT, with variability for DLCO and DLNO of less than 10% in all cases. Between the tests subjects rested for at least 4 min.  Results: The mean DLCO at 4 sec was 9.1 mmol/min/kPa (SD 1.7) and at 10 sec 8.5 (SD 1.5), (p  Conclusion: a statistically significant difference between both DLNO and DLCO has been found at 4 and 10 sec BHT, but no significant difference was found of the DLNO/DLCO ratio between 4 and 10 sec BHT. Therefore using the DLNO/DLCO ratio in the assessment of disorders of gas transfer has a great advantage by being independent of BHT.  References  1. Dressel et al., Chest 2008;133:1149-1154  2. Hughes et al., Eur Respir J. 2013 Feb;41:453-61.
Hepatic DNA deposition drives drug‐induced liver injury and inflammation in mice
Authors: Pedro Elias Marques, André Gustavo Oliveira, Rafaela Vaz Pereira, Bruna Araújo David, Lindisley Ferreira Gomides, Adriana Machado Saraiva, Daniele Araújo Pires, Júlia Tosta Novaes, Daniel O. Patricio, Daniel Cisalpino, Zélia Menezes‐Garcia, W. Matthew Leevy, Sarah Ellen Chapman, GermánArturo Mahecha, Rafael Elias Marques, Rodrigo Guabiraba, Vicente Paulo Martins, Danielle Gloria Souza, Daniel Santos Mansur, Mauro Martins Teixeira, M. Fatima Leite, Gustavo Batista Menezes
Journal: Hepatology (2014)

Drug‐induced liver injury (DILI) is an important cause of acute liver failure, with limited therapeutic options. During DILI, oncotic necrosis with concomitant release and recognition of intracellular content amplifies liver inflammation and injury. Among these molecules, self‐DNA has been widely shown to trigger inflammatory and autoimmune diseases; however, whether DNA released from damaged hepatocytes accumulates into necrotic liver and the impact of its recognition by the immune system remains elusive. Here we show that treatment with two different hepatotoxic compounds (acetaminophen and thioacetamide) caused DNA release into the hepatocyte cytoplasm, which occurred in parallel with cell death in vitro . Administration of these compounds in vivo caused massive DNA deposition within liver necrotic areas, together with an intravascular DNA coating. Using confocal intravital microscopy, we revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA‐rich areas, where they exhibit an active patrolling behavior. DNA removal by intravenous DNASE1 injection or ablation of Toll‐like receptor 9 (TLR9)‐mediated sensing significantly reduced systemic inflammation, liver neutrophil recruitment, and hepatotoxicity. Analysis of liver leukocytes by flow cytometry revealed that emigrated neutrophils up‐regulated TLR9 expression during acetaminophen‐mediated necrosis, and these cells sensed and reacted to extracellular DNA by activating the TLR9/NF‐κB pathway. Likewise, adoptive transfer of wild‐type neutrophils to TLR9 −/− mice reversed the hepatoprotective phenotype otherwise observed in TLR9 absence. Conclusion : Hepatic DNA accumulation is a novel feature of DILI pathogenesis. Blockage of DNA recognition by the innate immune system may constitute a promising therapeutic venue. (H epatology 2015;61:348–360)
Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities
Authors: Anne Wanquet, Thomas Prebet, Céline Berthon, Marie Sebert, Clémence Roux, Austin Kulasekararaj, Jean‐Baptiste Micol, Benjamin Esterni, Raphael Itzykson, Sylvain Thepot, Christian Recher, Jacques Delaunay, François Dreyfus, Ghulam Mufti, Pierre Fenaux, Norbert Vey
Journal: American Journal of Hematology (2015)

Acute Myeloid Leukemia (AML) and myelodysplasia (MDS) with chromosome 3q abnormalities have a dismal outcome either untreated or with conventional treatments. Azacitidine (AZA) is now considered as the standard of care in high-risk MDS and oligoblastic AML patients. The objective of this study was to evaluate the impact of azacitine treatment in this cytogenetic subgroup. We report here a multicentre retrospective study of 157 patients treated with AZA for AML/MDS with chromosome 3q abnormalities and 27 patients with isolated EVI-1 overexpression. Median age was 65 years, 40 patients (25%) had inv(3)(q21q26.2) or t(3;3)(q21;q26.2), 36 patients (23%) had other balanced 3q26 rearrangements, 8 patients (5%) had balanced 3q21 rearrangements and 73 patients (46%) had other 3q abnormalities. The overall response rate was 50% (29% CR). Median overall survival was 10.6 months. By multivariate analysis, patients with lower bone marrow blast counts, higher platelet counts, non-complex cytogenetics, and absence of prior treatment with intensive chemotherapy had a better outcome. 27 patients were allo-transplanted and achieved a 21-month median OS. Balanced 3q21 translocations were associated with a better response rate and overall survival. Outcome of patients with isolated EVI-1 overexpression was comparable to that of patients with chromosome 3q lesions. Thus, AML/MDS patients with 3q abnormalities appear to be a heterogeneous group in their response to AZA, and AZA may represent a suitable option in particular as a bridge to allogeneic transplantation.
Tumor-Associated Antigens in H-2 Hemizygous Isoantigenic Variants of a Somatic Cell Hybrid, Derived From the Fusion of a 3-Methylcholanthrene-lnduced Sarcoma and a Mammary Carcinoma
Authors: George Klein
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Tumor-Associated Antigens in H-2 Hemizygous Isoantigenic Variants of a Somatic Cell Hybrid, Derived From the Fusion of a 3-Methylcholanthrene-lnduced Sarcoma and a Mammary Carcinoma Get access George Klein George Klein Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 383–386, https://doi.org/10.1093/jnci/58.2.383 Published: 01 February 1977 Article history Received: 13 April 1976 Accepted: 13 July 1976 Published: 01 February 1977
Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo
Authors: Cristian Taccioli, Michela Garofalo, Hongping Chen, Yubao Jiang, Guidantonio Malagoli Tagliazucchi, Gianpiero Di Leva, Hansjuerg Alder, Paolo Fadda, Justin Middleton, Karl J. Smalley, Tommaso Selmi, Srivatsava Naidu, John L. Farber, Carlo M. Croce, Louise Y. Fong
Journal: JNCI Journal of the National Cancer Institute (2015)

Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined. To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12–20 per group), locked nucleic acid–modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter assay. Cellular proliferation, apoptosis, and expression of inflammation genes were determined by immunoblotting, caspase assays, and immunohistochemistry. The miR-31 promoter in Zn-deficient esophagus was identified by ChIP-seq using an antibody for histone mark H3K4me3. Data were analyzed with t test and analysis of variance. All statistical tests were two-sided. In vivo, anti-miR-31 reduced miR-31 overexpression (P = .002) and suppressed the esophageal preneoplasia in Zn-deficient rats. At the same time, the miR-31 target Stk40 was derepressed, thereby inhibiting the STK40-NF-κΒ–controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis (caspase 3/7 activities, fold change = 10.7, P = .005). This same connection between miR-31 overexpression and STK40/NF-κΒ expression was also documented in human ESCC cell lines. In Zn-deficient esophagus, the miR-31 promoter region and NF-κΒ binding site were activated. Zn replenishment restored the regulation of this genomic region and a normal esophageal phenotype. The data define the in vivo signaling pathway underlying interaction of Zn deficiency and miR-31 overexpression in esophageal neoplasia and provide a mechanistic rationale for miR-31 as a therapeutic target for ESCC.
Susceptibility of Fetal Lung to Transplacental 1-Ethyl-1-nitrosourea: Its Relation to Epithelial Proliferation 2
Authors: Shirley L. Kauffman
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Susceptibility of Fetal Lung to Transplacental 1-Ethyl-1-nitrosourea: Its Relation to Epithelial Proliferation Get access Shirley L. Kauffman, M.D. Shirley L. Kauffman, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 4, October 1976, Pages 821–825, https://doi.org/10.1093/jnci/57.4.821 Published: 01 October 1976 Article history Received: 06 October 1975 Accepted: 02 April 1976 Published: 01 October 1976
Effect of Low-Energy Diets Differing in Fiber, Red Meat, and Coffee Intake on Cardiac Autonomic Function in Obese Individuals With Type 2 Diabetes
Authors: Dan Ziegler, Alexander Strom, Bettina Nowotny, Lejla Zahiragic, Peter J. Nowotny, Maren Carstensen-Kirberg, Christian Herder, Michael Roden
Journal: Diabetes Care (2015)

OBJECTIVE The autonomic nervous system (ANS) regulates both the cardiovascular system and energy balance and is disturbed in diabetes and obesity. The effect of different approaches of caloric restriction on ANS function has not been assessed in individuals with diabetes. Thus, we sought to determine whether low-energy diets differing in fiber, red meat, and coffee intake exert differential effects on cardiac autonomic function. RESEARCH DESIGN AND METHODS In this randomized parallel-group pilot trial, obese patients with type 2 diabetes were randomly allocated to consume either a diet high in cereal fiber, free of red meat, and high in coffee (n = 13) or a diet low in fiber, high in red meat, and coffee free (n = 15) over 8 weeks. Eight measures of heart rate variability (HRV) indicating vagal and/or sympathetic modulation over 3 h and inflammatory markers were determined during a hyperinsulinemic-euglycemic clamp. RESULTS After 8 weeks, both dietary interventions resulted in a mean weight loss of 5–6 kg, a mean decline in heart rate of 4–6 bpm, and improvement in vagally mediated HRV. However, the changes in HRV parameters from baseline to 8 weeks did not differ between the groups. In the entire study cohort, incremental HRV from baseline to 8 weeks was associated with enhanced oxidative glucose utilization (P &amp;lt; 0.05), but not with insulin sensitivity and inflammatory markers. CONCLUSIONS In obese patients with type 2 diabetes, energy restriction per se over 8 weeks contributed to improved cardiac vagal function in relation to improved oxidative glucose utilization. This preliminary finding should be verified in a confirmatory trial.
Nitric oxide as a protector from nonalcoholic fatty liver disease
Authors: Manlio Vinciguerra
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Gu et al. in which the authors demonstrate by knockout and knock‐down approaches, the existence of a nitric oxide (NO)‐signaling pathway that is crucial for the control of hepatic fatty acid oxidation in zebrafish, mice, and cultured human hepatocytes, which is, in turn, under the control of SLC7A3, an essential membrane transporter for cationic amino acids, such as arginine, a commonly used, over‐the‐counter supplement recommended to treat nonalcoholic fatty liver disease (NAFLD).1 Removing totally or partially SLC7A3 leads to lipid accumulation during the fasted state because of inhibition of fatty acid synthesis and promotion of lipogenesis.1 The role of NO as a protector from NAFLD proposed by Gu et al. is debatable. It has been reported that an increase, rather than a decrease, of NO production accompanies NAFLD onset.2 Accordingly, in the pathogenesis of NAFLD, NO potentiates cytotoxicity by reacting with superoxide anions to form peroxynitrite, a strong oxidant that promotes nitration of tyrosine to form nitrotyrosine.3 This is consistent with the fact that nitrosative stress developed upon an excess in NO content correlates with NAFLD severity: NO‐mediated nitration of hepatocellular proteins is markedly induced in the inflamed liver tissue from patients with chronic liver disease.4 How to reconcile that inhibition or depletion of intracellular NO production by blockage of the import from the extracellular space of its precursor, arginine, by SCL7A3 and, on the opposite, enzymatic NO overproduction could both lead to aggravating lipid accumulation as in NAFLD? Gu et al. used powerful inhibition approaches in their study, including chemical inhibitors, genetic knockout, small interfering RNA, and adenoviral‐mediated gene silencing. Overexpression or ectopic approaches for SLC7A3 protein in model organisms and hepatocytes in fed and fasted states may add important pieces to the puzzle.