Risk of Breast Cancer With Long-Term Use of Calcium Channel Blockers or Angiotensin-Converting Enzyme Inhibitors Among Older Women

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Controversy exists about breast cancer risk associated with long-term use of calcium channel blockers (CCBs) or angiotensin-converting enzyme inhibitors (ACEis), respectively. Our objective in this study was to separately evaluate associations between duration of CCB or ACEi use and breast cancer in hypertensive women aged ≥55 years at 3 sites in the Kaiser Permanente health-care system (1997–2012). Exposures included CCB or ACEi use of 1–12 years' duration, determined from pharmacy dispensings. Outcomes included invasive lobular or ductal carcinoma. Statistical methods included discrete-time survival analyses. The cohort included 19,674 (17.9%) CCB users and 90,078 (82.1%) ACEi users. Two percent (<span style="font-style:italic;">n</span> = 397) of CCB users and 1.9% (<span style="font-style:italic;">n</span> = 1,733) of ACEi users developed breast cancer. Compared with 1–<2 years of use, in adjusted analysis, there was no association between CCB use for 2–<12 years and breast cancer: All 95% confidence intervals included 1. Increasing duration of ACEi use was associated with reduced breast cancer risk: Compared with 1–<2 years of use, the adjusted hazard ratio was 0.76 (95% confidence interval: 0.63, 0.92) for 5–<6 years of use and 0.63 (95% confidence interval: 0.43, 0.93) for 9–<10 years of use. We conclude that among older women with hypertension, long-term CCB use does not increase breast cancer risk and long-term treatment with ACEis may confer protection against breast cancer.</span>

http://ift.tt/2kcLwuP

Time-Course of Cause-Specific Hospital Admissions During Snowstorms: An Analysis of Electronic Medical Records From Major Hospitals in Boston, Massachusetts

<span class="paragraphSection"><div class="boxTitle">Abstract</div>With global climate change, more frequent severe snowstorms are expected; however, evidence regarding their health effects is very limited. We gathered detailed medical records on hospital admissions (<span style="font-style:italic;">n</span> = 433,037 admissions) from the 4 largest hospitals in Boston, Massachusetts, during the winters of 2010–2015. We estimated the percentage increase in hospitalizations for cardiovascular and cold-related diseases, falls, and injuries on the day of and for 6 days after a day with low (0.05–5.0 inches), moderate (5.1–10.0 inches), or high (>10.0 inches) snowfall using distributed lag regression models. We found that cardiovascular disease admissions decreased by 32% on high snowfall days (relative risk (RR) = 0.68, 95% confidence interval (CI): 0.54, 0.85) but increased by 23% 2 days after (RR = 1.23, 95% CI: 1.01, 1.49); cold-related admissions increased by 3.7% on high snowfall days (RR = 3.7, 95% CI: 1.6, 8.6) and remained high for 5 days after; and admissions for falls increased by 18% on average in the 6 days after a moderate snowfall day (RR = 1.18, 95% CI: 1.09, 1.27). We did not find a higher risk of hospitalizations for injuries. To our knowledge, this is the first study in which the time course of hospitalizations during and immediately after snowfall days has been examined. These findings can be translated into interventions that prevent hospitalizations and protect public health during harsh winter conditions.</span>

http://ift.tt/2kXbN4L

In-Work Poverty and Self-Rated Health in a Cohort of Working Germans: A Hybrid Approach for Decomposing Within-Person and Between-Persons Estimates of In-Work Poverty Status

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In this study, we investigated whether self-rated health (SRH) can be predicted by in-work poverty and how between-persons and within-person differences in the poverty status of people who are working contribute to this relationship. We used a logistic random-effects model designed to test within-person and between-persons differences with data from a nationally representative German sample with 19 waves of data collection (1995–2013) to estimate effects of between-persons and within-person differences in working poverty status on poor SRH. Interactions by age and sex were tested, and models controlled for sociodemographic, socioeconomic, and work-related characteristics. We found significant differences in SRH between individuals with different working poverty status but no evidence that within-person differences in working poverty status are associated with poor SRH. The association between in-work poverty and SRH was significantly stronger for women but did not differ significantly by age. All findings were robust when including sociodemographic, socioeconomic, and working characteristics. In this sample of German adults, we found a polarization of poor SRH between the working nonpoor and the working poor but no causal association of within-person differences in working poverty status with SRH.</span>

http://ift.tt/2kXaXVq

Giorgis-Allemand et al. Respond to “Ambient Environment and Preterm Birth”

http://ift.tt/2kcWeRP

The Influence of Meteorological Factors and Atmospheric Pollutants on the Risk of Preterm Birth

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994–2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the −5°C to 15°C range, with a plateau afterwards (spline coding, <span style="font-style:italic;">P</span> = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.</span>

http://ift.tt/2kXgs6B

Invited Commentary: Ambient Environment and the Risk of Preterm Birth

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Preterm birth is a common adverse birth outcome known to be associated with increased infant mortality, and it often results in a higher burden of offspring morbidity in both the short and long terms. The potential for environmental factors, particularly air pollution and meteorological parameters, to increase preterm birth risk has received significant attention worldwide, but the findings are generally inconsistent, with variations in study designs and methods across populations and geographic locations. In the current issue of the <span style="font-style:italic;">Journal</span>, Giorgis-Allemand et al. (<span style="font-style:italic;">Am J Epidemiol.</span> 2017;185(4):247–258) take the field a step further than most prior investigations of the ambient environment. They examined the associations of ambient air pollution and meteorological factors with preterm risk among 13 cohorts across 11 European countries. No association with air pollution was observed, but associations with increased preterm birth risk were found for both increased atmospheric pressure and ambient temperature exposures during the first trimester. The study is notable in attempting to address several important issues that challenge the field, including exposure misclassification and defining critical windows of exposure. Their comprehensive evaluation of ambient exposures is to be commended.</span>

http://ift.tt/2kcNzyZ

How Accurate Is a Single Cutpoint to Identify High Blood Pressure in Adolescents?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In 2007 the International Diabetes Federation (IDF) proposed single blood pressure (BP) cutpoints (systolic: ≥130 mm Hg and diastolic: ≥85 mm Hg) for the diagnosis of high blood pressure (HBP) in adolescents. Before this proposal, HBP had been defined as BP at or above the 95th percentile for age, sex, and height percentile (reference standard). In this study, we evaluated the risk for misclassification when using the IDF single-cutpoints criteria. We first applied the IDF criteria to a reconstructed population with the same age, sex, and height distribution as the population used to develop the reference standard. The proposed single cutpoints corresponded to percentiles from the 81.6th to 99.9th for systolic BP and from the 92.9th to 98.9th for diastolic BP in the reconstructed population. Using IDF criteria, there were high false-negative fractions for both systolic and diastolic BP (from 54% to 93%) in 10- to 12-year-olds and a false-positive fraction up to 35% in older subjects. We then applied the IDF criteria to 1,162 overweight/obese adolescents recruited during 1998–2000 from pediatric clinical centers in Milano, Varese, and Modena in Italy and in Zaragoza, Spain. Overall false-negative and false-positive fractions were 22% and 2%, respectively; negative predictive values were especially low for 10- to 12-year-old subjects. The use of IDF's single cutpoints carries a high risk of misclassification, mostly due to false negatives in younger subjects. The effort to simplify diagnosis could be overcome by the risk of undiagnosed HBP.</span>

http://ift.tt/2kX5fD6

Analyses of Sensitivity to the Missing-at-Random Assumption Using Multiple Imputation With Delta Adjustment: Application to a Tuberculosis/HIV Prevalence Survey With Incomplete HIV-Status Data

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Multiple imputation with delta adjustment provides a flexible and transparent means to impute univariate missing data under general missing-not-at-random mechanisms. This facilitates the conduct of analyses assessing sensitivity to the missing-at-random (MAR) assumption. We review the delta-adjustment procedure and demonstrate how it can be used to assess sensitivity to departures from MAR, both when estimating the prevalence of a partially observed outcome and when performing parametric causal mediation analyses with a partially observed mediator. We illustrate the approach using data from 34,446 respondents to a tuberculosis and human immunodeficiency virus (HIV) prevalence survey that was conducted as part of the Zambia–South Africa TB and AIDS Reduction Study (2006–2010). In this study, information on partially observed HIV serological values was supplemented by additional information on self-reported HIV status. We present results from 2 types of sensitivity analysis: The first assumed that the degree of departure from MAR was the same for all individuals with missing HIV serological values; the second assumed that the degree of departure from MAR varied according to an individual's self-reported HIV status. Our analyses demonstrate that multiple imputation offers a principled approach by which to incorporate auxiliary information on self-reported HIV status into analyses based on partially observed HIV serological values.</span>

http://ift.tt/2kcXzrV

Danggui Buxue Tang (Astragali Radix and Angelicae Sinensis Radix) for menopausal symptoms: A review

Publication date: 6 March 2017
Source:Journal of Ethnopharmacology, Volume 199
Author(s): Huang Q. Lin, Amy G.W. Gong, Huai Y. Wang, Ran Duan, Tina T.X. Dong, Kui J. Zhao, Karl W.K. Tsim
BackgroundTraditional Chinese medicine (TCM) has contributed greatly to human health in past several thousand years. Today, the development of TCM is facing two obstacles: (i) quality control of herbal extract; and (ii) action mechanisms not known.ObjectivesAmong thousands of complex TCM formulations, Danggui Buxue Tang (DBT) is the simplest one. DBT is used to treat ailments in women and contains only two herbs, Astragali Radix (Huangqi; AR) and Angelicae Sinensis Radix (Danggui; ASR). The weight ratio of AR to ASR in DBT must be 5:1, as stipulated in AD 1247. By using DBT as a model formula, we develop a strategy to reveal the complexity of a traditional TCM formula.ResultsThere are 3 levels of research directions: (i) the preparation of DBT and its rationale behind; (ii) the traditional theory of DBT is elucidated by chemical and biological determinations; and (iii) the action mechanisms of DBT are revealed.ConclusionThrough the chemical, biological, genomic and proteomic studies, a possible direction in resolving the preparation mythologies, pharmacological and mechanistic analyses of a TCM decoction is being proposed here.

Graphical abstract

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Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: a controlled before-and-after study.

Access to a demand-led evidence briefing service did not improve NHS commissioners' uptake and use of research evidence, compared with less intensive and less targeted alternatives

http://ift.tt/2kcIYN8

Tonsillectomy for Obstructive Sleep-Disordered Breathing or Recurrent Throat Infection in Children [Internet].

To systematically review evidence addressing tonsillectomy in children with obstructive sleep-disordered breathing (OSDB) or recurrent throat infections.

http://ift.tt/2kX6fHt

Modeling and Simulation in the Context of Health Technology Assessment: Review of Existing Guidance, Future Research Needs, and Validity Assessment [Internet].

Despite rigorous systematic reviews of efficacy and effectiveness of health care interventions, patients, providers and policymakers may remain in doubt about what they should do because of uncertainty, tradeoffs among benefits and harms, and conflicting preferences. Modeling and simulation studies in health care can supplement systematic reviews to increase the usefulness of the evidence summary. The aims of this report are four-fold: (1) to summarize evidence- and consensus-based guidance on the conduct and reporting of health care modeling and simulation; (2) to summarize guidance from Health Technology Assessment (HTA) groups for modeling; (3) to prioritize future research needs to improve models; and (4) to provide an overview of methods for model calibration and validation.

http://ift.tt/2kcKcrY

Effect of gonadotropin inhibitory hormone (GnIH) on luteinizing hormone secretion in humans

Abstract

Gonadotropin inhibitory hormone (GnIH, human homologue of RFRP-3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human.

Objective

We tested the hypotheses that exogenous GnIH inhibits LH secretion a) in postmenopausal women, and b) in men concurrently administered exogenous kisspeptin.

Design

Following in vitro and in vivo pre-clinical studies to functionally characterize the GnIH peptide, a dose-finding study (human GnIH 1.5 to 150 μg/kg/h, iv for 3h) was undertaken, and 50 μg/kg/h selected for further evaluation.

Five postmenopausal women were administered 50 μg/kg/h iv infusion for 3h or vehicle on two separate days.

Four men were administered kisspeptin-10 (0.3 μg/kg iv bolus) with simultaneous infusion of GnIH (50 μg/kg/h, iv for 3h) or vehicle.

Participants

Healthy postmenopausal women (mean age 58±2 years, LH: 30.8±2.9 IU/L, FSH: 78.7±6.4 IU/L, estradiol: <50 pmol/L) and men (39.8±2.1 years, mean total testosterone 12.1±1.8 nmol/L, LH 2.2±0.2 IU/L).

Primary Outcome

Change in area-under-curve of LH during GnIH vs. vehicle.

Results

During GnIH administration in postmenopausal women, LH secretion decreased (Δ AUC -9.9±1.8 IU/3h) vs. vehicle (Δ AUC -0.5±1.7 IU/3h) (P= 0.02). Kisspeptin-10 stimulated LH responses in men was not affected by GnIH co-administration (60-min AUC of LH 6.2±0.8 IU/h with kisspeptin-10 alone, 6.3±1.0 IU/h, kisspeptin-10 with GnIH, P = 0.72).

Exogenous GnIH was well tolerated, with no adverse events reported.

Conclusions

GnIH decreased LH secretion in postmenopausal women in this first-in-human study. Kisspeptin-stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.

This article is protected by copyright. All rights reserved.

http://ift.tt/2kWMEqF

Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475

Conditions:   ALK Gene Mutation;   BRAF Gene Mutation;   EGFR Gene Mutation;   Head and Neck Squamous Cell Carcinoma;   Metastatic Head and Neck Carcinoma;   Recurrent Head and Neck Carcinoma;   Recurrent Non-Small Cell Lung Carcinoma;   ROS1 Gene Mutation;   Stage III Non-Small Cell Lung Cancer;   Stage IIIA Non-Small Cell Lung Cancer;   Stage IIIB Non-Small Cell Lung Cancer;   Stage IV Non-Small Cell Lung Cancer
Interventions:   Other: Laboratory Biomarker Analysis;   Biological: Pembrolizumab;   Biological: Recombinant EphB4-HSA Fusion Protein
Sponsors:   University of Southern California;   National Cancer Institute (NCI)
Not yet recruiting - verified February 2017

http://ift.tt/2kQ7rd5

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

Conditions:   Stage 0 Nasopharyngeal Carcinoma;   Stage 0 Paranasal Sinus Cancer;   Stage I Nasopharyngeal Carcinoma;   Stage I Paranasal Sinus Cancer;   Stage II Nasopharyngeal Carcinoma;   Stage II Paranasal Sinus Cancer;   Stage IIA Nasopharyngeal Carcinoma;   Stage IIB Nasopharyngeal Carcinoma;   Stage III Nasopharyngeal Carcinoma;   Stage III Paranasal Sinus Cancer;   Stage IV Nasopharyngeal Carcinoma;   Stage IV Paranasal Sinus Cancer;   Stage IVA Nasopharyngeal Carcinoma;   Stage IVA Paranasal Sinus Cancer;   Stage IVB Nasopharyngeal Carcinoma;   Stage IVB Paranasal Sinus Cancer;   Stage IVC Nasopharyngeal Carcinoma;   Stage IVC Paranasal Sinus Cancer
Interventions:   Other: Physiologic Testing;   Other: Quality-of-Life Assessment;   Procedure: Sham Intervention;   Procedure: Therapeutic Procedure;   Other: rose essential oil;   Other: lemon essential oil;   Other: clove essential oil;   Other: eucalyptus essential oil;   Other: canola oil
Sponsor:   Stanford University
Not yet recruiting - verified February 2017

http://ift.tt/2l1cdXx

Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development

Publication date: Available online 9 February 2017
Source:Cell Stem Cell
Author(s): Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V. Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6.1+ stage, leading to impaired formation of glucose-responsive β-like cells. In addition to this GATA6 haploinsufficiency, we also identified dosage-sensitive requirements for GATA6 and GATA4 in the formation of both definitive endoderm and pancreatic progenitor cells. Our work expands the application of hPSCs from studying the impact of individual gene loci to investigation of multigenic human traits, and it establishes an approach for identifying genetic modifiers of human disease.

Graphical abstract

Teaser

Huangfu, Chen, and colleagues model human pancreatic disease by stepwise differentiation of genetically modified hPSCs to characterize the phenotypic effects of GATA6 haploinsufficiency not evident in mouse models and its genetic interaction with GATA4.


http://ift.tt/2kPT9Jw

Cholinergic Signals from the CNS Regulate G-CSF-Mediated HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay

Publication date: Available online 9 February 2017
Source:Cell Stem Cell
Author(s): Halley Pierce, Dachuan Zhang, Claire Magnon, Daniel Lucas, John R. Christin, Matthew Huggins, Gary J. Schwartz, Paul S. Frenette
Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis. Blockade of Chrm1 in the CNS, but not the periphery, reduces HSC mobilization. Mobilization is impaired in Chrm1^−∕− mice and rescued by parabiosis with wild-type mice, suggesting a relay by a blood-borne factor. We have identified the glucocorticoid (GC) hormones as critical for optimal mobilization. Physiological levels of corticosterone promote HSC migration via the GC receptor Nr3c1-dependent signaling and upregulation of actin-organizing molecules. These results uncover long-range regulation of HSC migration emerging from the brain.

Graphical abstract

Teaser

Pierce et al. show that the muscarinic receptor type-1 (Chrm1) expression in the brain regulates HSC mobilization from bone marrow via the hypothalamic-pituitary-adrenal axis, leading to glucocorticoid-mediated control of actin organization pathways.


http://ift.tt/2kPWpEA

American Board of Dermatology Examination Dates

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Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals

Publication date: Available online 9 February 2017
Source:Cell Metabolism
Author(s): Claudio Mauro, Joanne Smith, Danilo Cucchi, David Coe, Hongmei Fu, Fabrizia Bonacina, Andrea Baragetti, Gaia Cermenati, Donatella Caruso, Nico Mitro, Alberico L. Catapano, Enrico Ammirati, Maria P. Longhi, Klaus Okkenhaug, Giuseppe D. Norata, Federica M. Marelli-Berg
Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4⁺ T cells. Memory CD4⁺ T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4⁺ T cell differentiation into CD44^hi-CCR7^lo-CD62L^lo-CXCR3⁺-LFA1⁺ effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4⁺ T cells and dendritic cells and was mediated via direct exposure of CD4⁺ T cells to palmitate, leading to increased activation of a PI3K p110δ-Akt-dependent pathway upon priming.

Graphical abstract

Teaser

Lymphocyte infiltration of non-lymphoid tissues, including adipose and vascular tissues, is a prominent feature of chronic inflammation in diet obesity. Mauro et al. find that the saturated fatty-acid palmitate activates a PI3K p110δ-Akt pathway leading to CD4⁺ T cell differentiation into effector memory-like T cells upon priming in obese mice and humans.


http://ift.tt/2kWIlMe

DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons

Publication date: Available online 9 February 2017
Source:Cell Metabolism
Author(s): Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1^fl/fl-POMC-cre:ER^T2) resulted in improved leptin sensitivity and glucose responsiveness. In Drp1^fl/fl-POMC-cre:ER^T2 mice, POMC neurons showed increased mitochondrial size, ROS production, and neuronal activation with increased expression of Kcnj11 mRNA regulated by peroxisome proliferator-activated receptor (PPAR). Furthermore, deletion of DRP1 enhanced the glucoprivic stimulus in these neurons, causing their stronger inhibition and a greater activation of counter-regulatory responses to hypoglycemia that were PPAR dependent. Together, these data unmasked a role for mitochondrial fission in leptin sensitivity and glucose sensing of POMC neurons.

Graphical abstract

Teaser

Mitochondrial fission protein DRP1 is decreased in activated glucose-excited POMC neurons, resulting in increased leptin sensitivity and glucose responsiveness and enhanced hypoglycemic counter-regulatory response. Mechanistically, altered ROS levels affect PPARγ targets, such as the KATP channel Kcnj11, which affects POMC neuronal responsiveness to metabolic shifts.


http://ift.tt/2kWQyA4

Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease

Publication date: Available online 9 February 2017
Source:Cell Metabolism
Author(s): Annelie Falkevall, Annika Mehlem, Isolde Palombo, Benjamin Heller Sahlgren, Lwaki Ebarasi, Liqun He, A. Jimmy Ytterberg, Hannes Olauson, Jonas Axelsson, Birgitta Sundelin, Jaakko Patrakka, Pierre Scotney, Andrew Nash, Ulf Eriksson
Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD.

Graphical abstract

Teaser

Human studies have highlighted that hyperglycemia may not be the underlying cause of diabetic kidney disease (DKD). Falkevall et al. highlight a role for VEGF-B in renal lipotoxicity in mouse models and patients, offering a potential novel therapeutic approach to DKD.


http://ift.tt/2kWQvnX

Sex Differences: A Resultant of an Evolutionary Pressure?

Publication date: Available online 9 February 2017
Source:Cell Metabolism
Author(s): Sara Della Torre, Adriana Maggi
Spurred by current research policy, we are witnessing a significant growth in the number of studies that observe and describe sexual diversities in human physiology and sex prevalence in a large number of pathologies. Yet we are far from the comprehension of the mechanisms underpinning these differences, which are the result of a long evolutionary history. This Essay is meant to underline female reproductive function as a driver for the positive selection of the specific physiological features that explain male and female differential susceptibility to diseases and metabolic disturbances, in particular. A clear understanding of the causes underlying sexual dimorphisms in the physio-pathology is crucial for precision medicine.

Teaser

A growing number of studies describe sexual differences in human physiology and sex prevalence in many diseases, though the mechanisms underpinning these differences remain unclear. In this Essay, Della Torre and Maggi point to female reproductive functions as the main cause for this metabolic drift during evolution.


http://ift.tt/2kWXcGl

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice

Publication date: Available online 9 February 2017
Source:Cell Metabolism
Author(s): Jinxiu Rui, Songyan Deng, Arnon Arazi, Ana Luisa Perdigoto, Zongzhi Liu, Kevan C. Herold
Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclophosphamide. Human β cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long-term survival of β cells in some patients.

Graphical abstract

Teaser

Type 1 diabetes (T1D) is due to the immune-mediated destruction of β cells. Rui et al. identify a population of β cells that survives immune attack during T1D progression in non-obese diabetic mice, which may account for the long-term survival of some β cells in patients.


http://ift.tt/2kcmfRp

Sulforaphane improves outcomes and slows cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Chang Yu, Qi He, Jing Zheng, Ling Yu Li, Yang Hao Hou, Fang Zhou Song
Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague–Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18.



http://ift.tt/2kWLA6e

Novel lineage- and stage-selective effects of retinoic acid on mouse granulopoiesis: Blockade by dexamethasone or inducible NO synthase inactivation

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Pedro Xavier-Elsas, Bruno Marques Vieira, Daniela Masid-de-Brito, Juliana Santos, Monica Gomes Barradas, Bianca de Luca, Maria Ignez Gaspar-Elsas
Despite the close relationship of eosinophils and neutrophils, these granulocyte lineages respond to distinct cytokines and play unique roles in immune responses. They nevertheless respond to shared physiological/pharmacological regulators, including glucocorticoids and retinoids, and to ubiquitous mediators, including NO. Others showed that, in humans, all-trans retinoic acid (ATRA) suppresses eosinophil differentiation, but promotes neutrophil differentiation. Mechanisms of dual co-regulation of physiological granulopoiesis were here examined in murine bone-marrow, a model system suitable for exploration of immunopharmacological mechanisms, given the availability of experimental resources, including mutant/knockout mouse strains. We examined the effects of ATRA on mouse eosinophil and neutrophil production, using wild-type (BALB/c, C57BL/6) and mutant (iNOS-, CD95L-, or CD95-KO) bone-marrow cultures, further assessing the modification of ATRA activity by dexamethasone and iNOS blockade. ATRA (10⁻⁶–10⁻⁸M) significantly decreased eosinophil production relative to IL-5 controls. This effect was iNOS-independent, but CD95L- and caspase-dependent, and prevented by dexamethasone (10⁻⁷M in vitro; 1–20mg·kg⁻¹ in vivo). In myeloid colony formation assays, ATRA markedly suppressed GM-CSF-responsive progenitors, through an iNOS-dependent, CD95-independent, dexamethasone-sensitive mechanism. By contrast, ATRA potently enhanced GM-CSF-dependent neutropoiesis in liquid culture from BALB/c or C57BL/6 bone-marrow. This novel stimulatory effect was resistant to dexamethasone and abolished in iNOS-KO bone-marrow. ATRA injections also induced lineage- and stage-selective effects on granulopoiesis in vivo. ATRA therefore co-regulates eosinophil and neutrophil production in murine bone-marrow through multiple lineage- and stage-selective mechanisms.



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4-Methoxylonchocarpin attenuates inflammation by inhibiting lipopolysaccharide binding to Toll-like receptor of macrophages and M1 macrophage polarization

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Hyo-Min Jang, Geum-Dan Kang, Thi Kim Van Le, Su-Min Lim, Dae-Sik Jang, Dong-Hyun Kim
The roots of Abrus precatorius (AP, Fabaceae) have traditionally been used in Vietnam and China for the treatment of inflammatory diseases such as stomatitis, asthma, bronchitis, and hepatitis. Therefore, in this study, we isolated 4-methoxylonchocarpin (ML), an anti-inflammatory compound present in AP, and studied its anti-inflammatory effects in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. In lipopolysaccharide (LPS)-stimulated macrophages, ML was found to inhibit nuclear factor (NF)-κB activation and tumor necrosis factor (TNF) and interleukin (IL)-6 expression by inhibiting LPS binding to Toll-like receptor 4 (TLR4) in vitro. Oral administration of ML in mice with TNBS-induced colitis suppressed colon shortening and colonic myeloperoxidase activity. ML treatment significantly inhibited the activation of nuclear factor (NF)-κB and phosphorylation of transforming growth factor β-activated kinase 1 in the colon. Treatment with ML also inhibited TNBS-induced expression of IL-1β, IL-17A, and TNF. While ML reduced the TNBS-induced expression of M1 macrophage markers such as arginase-2 and TNF, it was found to increase the expression of M2 macrophage markers such as arginase-1 and IL-10. In conclusion, oral administration of ML attenuated colitis in mice by inhibiting the binding of LPS to TLR4 on immune cells and increasing the polarization of M1 macrophages to M2 macrophages.

Graphical abstract

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Effect of inhaled and systemic glucocorticoid treatment on CD4+ regulatory and effector T cells in a mouse model of allergic asthma

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Monika Zuśka-Prot, Tomasz Maślanka
To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4⁺ T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4⁺ effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4⁺ Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4⁺ Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4⁺ Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4⁺ T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4⁺ T cells.



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Clinical implementation of coverage probability planning for nodal boosting in locally advanced cervical cancer

Publication date: Available online 9 February 2017
Source:Radiotherapy and Oncology
Author(s): Anne Ramlov, Marianne S. Assenholt, Maria F. Jensen, Caroline Grønborg, Remi Nout, Markus Alber, Lars Fokdal, Kari Tanderup, Jacob Chr. Lindegaard
PurposeTo implement coverage probability (CovP) for dose planning of simultaneous integrated boost (SIB) of pathologic lymph nodes in locally advanced cervical cancer (LACC).Material and methodsCovP constraints for SIB of the pathological nodal target (PTV-N) with a central dose peak and a relaxed coverage at the perimeter were generated for use with the treatment planning system Eclipse: PTV-N D98 >90%, CTV-N D98 >100% and CTV-N D50 >101.5% of prescribed dose. Dose of EBRT was 45Gy/25 fx with a SIB of 55–57.5Gy depending on expected dose from brachytherapy (BT). Twenty-five previously treated patients with 47 boosted nodes were analysed. Nodes were contoured on cone beam CT (CBCT) and the accumulated dose in GTV-NCBCT and volume of body, pelvic bones and bowel receiving >50Gy (V50) were determined.ResultsNearly all nodes (89%) were visible on CBCT and showed considerable concentric regression during EBRT. Total EBRT and BT D98 was >57 GyEQD2 in 98% of the visible nodes. Compared to treatment plans aiming for full PTV-N coverage, CovP significantly reduced V50 of body, bones and bowel (p<0.001)ConclusionCovP is clinically feasible for SIB of pathological nodes and significantly decreases collateral SIB dose to nearby OAR.



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Revisiting the role of Wnt/β-catenin signaling in prostate cancer

Publication date: Available online 9 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Jeffrey A. Schneider, Susan K. Logan
The androgen receptor (AR) is a widely accepted therapeutic target in prostate cancer and multiple studies indicate that the AR and Wnt/β-catenin pathways intersect. Recent genome-wide analysis of prostate cancer metastases illustrate the importance of the Wnt/β-catenin pathway in prostate cancer and compel us to reexamine the interaction of the AR and Wnt/β-catenin signaling pathways. This review includes newer areas of interest such as non-canonical Wnt signaling and the role of Wnts in prostate cancer stem cells. The effort to develop Wnt modulating therapeutics, both biologics and small molecules, is also discussed.



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QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl

Publication date: Available online 9 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Amir Fallahsharoudi, Neil de Kock, Martin Johnsson, Lejla Bektic, S.J. Kumari A. Ubhayasekera, Jonas Bergquist, Dominic Wright, Per Jensen
Domestication of animals is associated with numerous alterations in physiology, morphology, and behavior. Lower reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and reduced fearfulness is seen in most studied domesticates, including chickens. Previously we have shown that the physiological stress response as well as expression levels of hundreds of genes in the hypothalamus and adrenal glands are different between domesticated White Leghorn and the progenitor of modern chickens, the Red Junglefowl. To map genetic loci associated with the transcription levels of genes involved in the physiological stress response, we conducted an eQTL analysis in the F12 generation of an inter-cross between White Leghorn and Red Junglefowl. We selected genes for further studies based on their known function in the regulation of the HPA axis or sympathoadrenal (SA) system, and measured their expression levels in the hypothalamus and the adrenal glands after a brief stress exposure (physical restraint). The expression values were treated as quantitative traits for the eQTL mapping. The plasma levels of corticosterone were also assessed. We analyzed the correlation between gene expression and corticosterone levels and mapped eQTL and their potential effects on corticosterone levels. The effects on gene transcription of a previously found QTL for corticosterone response were also investigated. The expression levels of the glucocorticosteroid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. We found several cis- and trans-acting eQTL for stress-related genes in both hypothalamus and adrenal. In the hypothalamus, one eQTL for c-FOS and one QTL for expression of GR were found. In the adrenal tissue, we identified eQTL for the genes NR0B1, RGS4, DBH, MAOA, GRIN1, GABRB2, GABRB3, and HSF1. None of the found eQTL were significant predictors of corticosterone levels. The previously found QTL for corticosterone was associated with GR expression in hypothalamus. Our data suggests that domestication related modification in the stress response is driven by changes in the transcription levels of several modulators of the HPA and SA systems in hypothalamus and adrenal glands and not by changes in the expression of the steroidogenic genes. The presence of eQTL for GR in hypothalamus combined with the negative correlation between GR expression and corticosterone response suggests GR as a candidate for further functional studies regarding modification of stress response during chicken domestication.



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Emerging aspects of microRNA interaction with TMPRSS2-ERG and endocrine therapy

Publication date: Available online 9 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Eugenio Zoni, Sofia Karkampouna, George N. Thalmann, Marianna Kruithof-de Julio, Martin Spahn
Prostate cancer (PCa) is the most common malignancy detected in males and the second most common cause of cancer death in western countries. The development of the prostate gland, is finely regulated by androgens which modulate also its growth and function. Importantly, androgens exert a major role in PCa formation and progression and one of the hypothesized mechanism proposed has been linked to the chromosomal rearrangement of the androgen regulated gene TMPRSS2 with ERG. Androgens have been therefore used as main target for therapies in the past. However, despite the development of endocrine therapies (e.g. androgen ablation), when PCa progress, tumors become resistant to this therapeutic castration and patients develop incurable metastases. A strategy to better understand how patients respond to therapy, in order to achieve a better patient stratification, consists in monitoring the levels of small noncoding RNAs (microRNAs). microRNAs are a class of small molecules that regulate protein abundance and their application as biomarkers to monitor disease progression has been intensely studied in the last years. In this review, we highlight the interactions between microRNAs and endocrine-related aspects of PCa in tissues. We focus on the modulation of TMPRSS2-ERG and Glucocorticoid Receptor (GR) by microRNAs and detail the influence of steroidal hormonal therapies on microRNAs expression.



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Neuromyelitis Optica Spectrum Disorders

Publication date: Available online 9 February 2017
Source:Neuroimaging Clinics of North America
Author(s): Tetsuya Akaishi, Ichiro Nakashima, Douglas Kazutoshi Sato, Toshiyuki Takahashi, Kazuo Fujihara

Teaser

Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis, but recent studies with anti-aquaporin-4-antibody specific to NMO have revealed that the clinical spectrum is wider than previously thought. International consensus diagnostic criteria propose NMO spectrum disorders (NMOSD) as the term to define the entire spectrum including typical NMO, optic neuritis, acute myelitis, brain syndrome, and their combinations. NMOSD is now divided into anti-aquaporin-4-antibody-seropositive NMOSD and -seronegative NMOSD (or unknown serostatus). MR imaging and optical coherence tomography are indispensable in the diagnosis and evaluation of NMOSD. This article reviews the clinical and MR imaging findings of anti-aquaporin-4-antibody-seropositive and anti-myelin oligodendrocyte glycoprotein-antibody-seropositive NMOSD.


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Comparative Transcriptomics Reveals Discrete Survival Responses of S. aureus and S. epidermidis to Sapienic Acid.

Related Articles

Comparative Transcriptomics Reveals Discrete Survival Responses of S. aureus and S. epidermidis to Sapienic Acid.

Front Microbiol. 2017;8:33

Authors: Moran JC, Alorabi JA, Horsburgh MJ

Abstract
Staphylococcal colonization of human skin is ubiquitous, with particular species more frequent at different body sites. Whereas Staphylococcus epidermidis can be isolated from the skin of every individual tested, Staphylococcus aureus is isolated from <5% of healthy individuals. The factors that drive staphylococcal speciation and niche selection on skin are incompletely defined. Here we show that S. aureus is inhibited to a greater extent than S. epidermidis by the sebaceous lipid sapienic acid, supporting a role for this skin antimicrobial in selection of skin staphylococci. We used RNA-Seq and comparative transcriptomics to identify the sapienic acid survival responses of S. aureus and S. epidermidis. Consistent with the membrane depolarization mode of action of sapienic acid, both species shared a common transcriptional response to counteract disruption of metabolism and transport. The species differed in their regulation of SaeRS and VraRS regulons. While S. aureus upregulated urease operon transcription, S. epidermidis upregulated arginine deiminase, the oxygen-responsive NreABC nitrogen regulation system and the nitrate and nitrite reduction pathways. The role of S. aureus ACME and chromosomal arginine deiminase pathways in sapienic acid resistance was determined through mutational studies. We speculate that ammonia production could contribute to sapienic acid resistance in staphylococci.

PMID: 28179897 [PubMed - in process]

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Treatment Adherence Intervention Studies in Dermatology and Guidance on How to Support Adherence

Abstract

Adequate adherence to prescribed treatment regimens can help to break the cycle of treatment failure, disease progression and subsequent treatment escalation. Unfortunately, adherence in the treatment of skin disorders such as acne, atopic dermatitis/eczema and psoriasis is often inadequate. A review of the literature identified a number of studies that tested an intervention to improve adherence in dermatology, including the following: electronic messages and/or reminders; more frequent or 'extra' clinic visits; audio-visual and internet-based interventions; and patient support programmes and/or self-management, educational training programmes. While there is no one solution or action for improving adherence, some interventions were more successful than others. We provide practical guidance on how to support adherence based on aspects of the successful interventions identified and on our collective opinion and clinical practice experience. Holding patients accountable, providing a caring and supportive environment, raising awareness of poor adherence and helping patients build a solid medication-taking habit can help to improve adherence so that patients can experience maximal treatment benefits and desired clinical outcomes.

http://ift.tt/2kPxy3Q

Paper-based microfluidic devices for electrochemical immunofiltration analysis of human chorionic gonadotropin

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Liangli Cao, Cheng Fang, Ruosheng Zeng, Xiongjie Zhao, Yuren Jiang, Zhencheng Chen
An electrochemical immunofiltration analysis was introduced into microfluidic paper-based analytical devices (μPADs) for the first time, which was based on photolithography and screen-printing technology. The hydrophilic test zones of the aldehyde-functionalized screen-printed electrodes (SPEs) were biofunctionalized with capture antibodies (Ab1). A sensitive immune detection method was developed by using primary signal antibody functionalized gold nanoparticles (GNPs/Ab2) and alkaline phosphatase conjugated secondary antibody (ALP-IgG). Differential pulse voltammetry (DPV) was performed to detect the electrochemical response. The microfluidic paper-based electrochemical immunosensor (μ-PEI) was optimized and characterized for the detection of human chorionic gonadotropin (HCG), a model analyte, in a linear range from 1.0mIUmL⁻¹ to 100.0 IU mL⁻¹ with a detection limit of 0.36mIUmL⁻¹. Additionally, the proposed μ-PEI was used to test HCG in real human serum and obtained satisfactory results. The disposable, efficient, sensitive and low-cost μ-PEI has exhibited great potential for the development of point-of-care testing (POCT) devices that can be applicated in healthcare monitoring.



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Highly selective optical and reversible dual-path chemosensor for cyanide detection and its application in live cells imaging

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Karunesh Keshav, Pritam Torawane, Mukesh Kumar Kumawat, Kundan Tayade, Suban K. Sahoo, Rohit Srivastava, Anil Kuwar
A new biocompatible fluorescent receptor 1 was synthesized by conjugating diaminomaleonitrile (DMN) with benzothiazole unit, and characterized by single X-ray. In DMF/water (1:1, v/v), the receptor 1 showed a selectivity turn-on fluorescence at 517nm in the presence of CN⁻. Receptor 1 showed a detection limit down to 0.16µM without any interference from other tested anions. The reversibility and reusability of 1 for the detection of CN⁻ ion was also tested for five cycles indicating the probe 1 could be used in a reversible manner. Importantly, the receptor 1 showed excellent cells viability and was successfully applied for the detection of CN⁻ in live mouse fibroblast cells L929 cells.

Graphical abstract

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Biochemical changes on the repair of surgical bone defects grafted with biphasic synthetic micro-granular HA + β-tricalcium phosphate induced by laser and LED phototherapies and assessed by Raman spectroscopy

Abstracts

This work aimed the assessment of biochemical changes induced by laser or LED irradiation during mineralization of a bone defect in an animal model using a spectral model based on Raman spectroscopy. Six groups were studied: clot, laser (λ = 780 nm; 70 mW), LED (λ = 850 ± 10 nm; 150 mW), biomaterial (biphasic synthetic micro-granular hydroxyapatite (HA) + β-tricalcium phosphate), biomaterial + laser, and biomaterial + LED. When indicated, defects were further irradiated at a 48-h interval during 2 weeks (20 J/cm² per session). At the 15th and 30th days, femurs were dissected and spectra of the defects were collected. Raman spectra were submitted to a model to estimate the relative amount of collagen, phosphate HA, and carbonate HA by using the spectra of pure collagen and biomaterials composed of phosphate and carbonate HA, respectively. The use of the biomaterial associated to phototherapy did not change the collagen formation at both 15 and 30 days. The amount of carbonate HA was not different in all groups at the 15th day. However, at the 30th day, there was a significant difference (ANOVA, p = 0.01), with lower carbonate HA for the group biomaterial + LED compared to biomaterial (p < 0.05). The phosphate HA was higher in the groups that received biomaterial grafts at the 15th day compared to clot (significant for the biomaterial; p < 0.01). At the 30th day, the phosphate HA was higher for the group biomaterial + laser, while this was lower for all the other groups. These results indicated that the use of laser phototherapy improved the repair of bone defects grafted with the biomaterial by increasing the deposition of phosphate HA.

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Older women may not be offered breast reconstruction after mastectomy

A national study from England indicates that older women are often not offered immediate breast reconstruction following a mastectomy, even though guidelines state that surgeons should discuss...

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Further evidence that d-glycerate kinase (GK) deficiency is a benign disorder

Publication date: Available online 9 February 2017
Source:Brain and Development
Author(s): Attia Kalim, Patricia Fitzsimons, Claudia Till, Malkanthi Fernando, Philip Mayne, Jorn Oliver Sass, Ellen Crushell
d-Glyceric aciduria is caused by deficiency in d-glycerate kinase (GK) due to recessive mutations in the GLYCTK gene. GK catalyzes the conversion of d-glycerate to 2-phosphoglycerate which is an intermediary reaction in the catabolism of serine and fructose. Deficiency of GK leads to accumulation of d-glycerate, which may be detected in urine organic acid analysis. Debate exists as to whether this is a benign or disease-causing disorder as the reported phenotypes vary significantly. We report two siblings from a consanguineous Pakistani family. The index case is a 5year old boy with severe autism and global developmental delay. His urine organic acid analysis showed markedly increased excretion of glycerate, determined as d-form by enantioselective gas chromatography. There was no oxalic aciduria. His younger sister (3years old) is asymptomatic and developmentally normal (already bilingual). Her urine showed similar amounts of d-glycerate. Both children are homozygous for the novel mutation c.767C>G in exon 5 of the GLYCTK gene, predicted to affect the enzyme by replacing the evolutionarily conserved Proline with Arginine (P256R). Both parents are heterozygous carriers.These cases support the view that d-glycerate kinase deficiency is a benign disorder. Long term follow-up studies with a greater number of individuals may be required for further confirmation.



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Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Veronica L. Peterson, Nicholas J. Jury, Raúl Cabrera-Rubio, Lorraine A. Draper, Fiona Crispie, Paul D. Cotter, Timothy G. Dinan, Andrew Holmes, John F. Cryan
The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.



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Behavioral characterization of the anterior injection model of subarachnoid hemorrhage

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): S. Boettinger, F. Kolk, G. Broessner, R. Helbok, B. Pfausler, E. Schmutzhard, R. Beer, P. Lackner
BackgroundThe applicability of various neurological scores has not been sufficiently characterized in the anterior injection model of subarachnoid hemorrhage (SAH). Therefore this study was performed to evaluate different behavioral tests for quantifying disease severity.MethodsDifferent volumes of autologous blood were injected stereotaxically into the prechiasmatic cistern of mice. Sham controls underwent the same procedure without blood injection. The following seven days after surgery, mice were evaluated for behavioral deficits by the SHIRPA score, beam balance and flex field analyses. Brains were further processed for histological analyses.ResultsFlex field analysis of SAH animals showed a significant reduction of locomotor activity compared to controls in the first two days after SAH. This reduction was more intense in animals with a higher amount of injected blood. The SHIRPA score revealed a significant reduction in motor behavior in SAH animals two days after surgery. A significant increase of GFAP expression, Fluoro Jade C and TUNEL positive cells as well as microthrombi was observed in SAH animals compared to sham controls in the early phase of SAH. There was a significant negative correlation between flex field righting and the number of degenerative neurons or microthrombi in the first two days after SAH.ConclusionThe results of flex field analysis and SHIRPA single test show behavioral and functional deficits in the first two days after SAH in parallel to histological alterations indicating neuronal damage. In summary these tests can be used as functional outcome parameters in the anterior injection model of SAH.



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Paracetamol − Effect of early exposure on neurotransmission, spatial memory and motor performance in rats

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Kamilla Blecharz-Klin, Agnieszka Piechal, Katarzyna Jawna-Zboińska, Justyna Pyrzanowska, Adriana Wawer, Ilona Joniec-Maciejak, Ewa Widy-Tyszkiewicz
In the present study we examined the effect of prenatal and early life paracetamol exposure on neurotransmission and its behavioural manifestation in rat male pups. In order to assess the ability of spatial learning and memory consolidation and the level of physical and exploratory activity we conducted a series of behavioural tests: Staircase Test, Hole Board Test and Water Maze. The concentrations of monoamines, metabolites and amino acids were determined using High Performance Liquid Chromatography in the prefrontal cortex, hippocampus and striatum. The effect on spatial memory and exploratory behaviour was most pronounced in animals treated with the lower dose of paracetamol. In this group we have observed a much lower motor activity and decreased head-dipping behaviour. Simultaneously, the number of crossings in the Water Maze under the previous platform position during the probe trial was significantly higher in rats treated with paracetamol at the dose of 5mg/kg. There was also a preference for a new location of a platform to the original position of the platform in the reversal probe trial of this group.These results indicate that early paracetamol exposure produces major changes in serotonergic and dopaminergic neurotransmission in the prefrontal cortex and striatum.At the same time, administration of the drug in early life results in the spectacular change in the amino acid level, in particular in the hippocampus and cortex. This has been reflected in the behaviour of animals in the Water Maze and Hole Board Test (without any noticeable impact on the Staircase Test).



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Evaluation of verruca plana by in vivo reflectance confocal microscopy and dermoscopy

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Retrieval of high-fidelity memory arises from distributed cortical networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Peter E. Wais, Sahar Jahanikia, Daniel Steiner, Craig E.L. Stark, Adam Gazzaley
Medial temporal lobe (MTL) function is well established as necessary for memory of facts and events. It is likely that lateral cortical regions critically guide cognitive control processes to tune in high-fidelity details that are most relevant for memory retrieval. Here, convergent results from functional and structural MRI show that retrieval of detailed episodic memory arises from lateral cortical—MTL networks, including regions of inferior frontal and angular gyrii. Results also suggest that recognition of items based on low-fidelity, generalized information, rather than memory arising from retrieval of relevant episodic details, is not associated with functional connectivity between MTL and lateral cortical regions. Additionally, individual differences in microstructural properties in white matter pathways, associated with distributed MTL-cortical networks, are positively correlated with better performance on a mnemonic discrimination task.

Graphical abstract

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Assessing uncertainty in dynamic functional connectivity

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Maria Kudela, Jaroslaw Harezlak, Martin A. Lindquist
Functional connectivity (FC) – the study of the statistical association between time series from anatomically distinct regions (Friston, 1994, 2011) – has become one of the primary areas of research in the field surrounding resting state functional magnetic resonance imaging (rs-fMRI). Although for many years researchers have implicitly assumed that FC was stationary across time in rs-fMRI, it has recently become increasingly clear that this is not the case and the ability to assess dynamic changes in FC is critical for better understanding of the inner workings of the human brain (Hutchison et al., 2013; Chang and Glover, 2010). Currently, the most common strategy for estimating these dynamic changes is to use the sliding-window technique. However, its greatest shortcoming is the inherent variation present in the estimate, even for null data, which is easily confused with true time-varying changes in connectivity (Lindquist et al., 2014). This can have serious consequences as even spurious fluctuations caused by noise can easily be confused with an important signal. For these reasons, assessment of uncertainty in the sliding-window correlation estimates is of critical importance. Here we propose a new approach that combines the multivariate linear process bootstrap (MLPB) method and a sliding-window technique to assess the uncertainty in a dynamic FC estimate by providing its confidence bands. Both numerical results and an application to rs-fMRI study are presented, showing the efficacy of the proposed method.



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Dissociated roles of the parietal and frontal cortices in the scope and control of attention during visual working memory

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Siyao Li, Ying Cai, Jing Liu, Dawei Li, Zifang Feng, Chuansheng Chen, Gui Xue
Mounting evidence suggests that multiple mechanisms underlie working memory capacity. Using transcranial direct current stimulation (tDCS), the current study aimed to provide causal evidence for the neural dissociation of two mechanisms underlying visual working memory (WM) capacity, namely, the scope and control of attention. A change detection task with distractors was used, where a number of colored bars (i.e., two red bars, four red bars, or two red plus two blue bars) were presented on both sides (Experiment 1) or the center (Experiment 2) of the screen for 100ms, and participants were instructed to remember the red bars and to ignore the blue bars (in both Experiments), as well as to ignore the stimuli on the un-cued side (Experiment 1 only). In both experiments, participants finished three sessions of the task after 15min of 1.5mA anodal tDCS administered on the right prefrontal cortex (PFC), the right posterior parietal cortex (PPC), and the primary visual cortex (VC), respectively. The VC stimulation served as an active control condition. We found that compared to stimulation on the VC, stimulation on the right PPC specifically increased the visual WM capacity under the no-distractor condition (i.e., 4 red bars), whereas stimulation on the right PFC specifically increased the visual WM capacity under the distractor condition (i.e., 2 red bars plus 2 blue bars). These results suggest that the PPC and PFC are involved in the scope and control of attention, respectively. We further showed that compared to central presentation of the stimuli (Experiment 2), bilateral presentation of the stimuli (on both sides of the fixation in Experiment 1) led to an additional demand for attention control. Our results emphasize the dissociated roles of the frontal and parietal lobes in visual WM capacity, and provide a deeper understanding of the neural mechanisms of WM.



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Altered regional connectivity reflecting effects of different anaesthesia protocols in the mouse brain

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Tong Wu, Joanes Grandjean, Simone C. Bosshard, Markus Rudin, David Reutens, Tianzi Jiang
Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs-fMRI studies on mice and the type of anaesthetic agent used, and will help to bridge observations between this burgeoning research field and ongoing human research across analytical scales.



http://ift.tt/2lvGuKV

Can responses to basic non-numerical visual features explain neural numerosity responses?

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Ben M. Harvey, Serge O. Dumoulin
Humans and many animals can distinguish between stimuli that differ in numerosity, the number of objects in a set. Human and macaque parietal lobes contain neurons that respond to changes in stimulus numerosity. However, basic non-numerical visual features can affect neural responses to and perception of numerosity, and visual features often co-vary with numerosity. Therefore, it is debated whether numerosity or co-varying low-level visual features underlie neural and behavioral responses to numerosity. To test the hypothesis that non-numerical visual features underlie neural numerosity responses in a human parietal numerosity map, we analyze responses to a group of numerosity stimulus configurations that have the same numerosity progression but vary considerably in their non-numerical visual features. Using ultra-high-field (7T) fMRI, we measure responses to these stimulus configurations in an area of posterior parietal cortex whose responses are believed to reflect numerosity-selective activity. We describe an fMRI analysis method to distinguish between alternative models of neural response functions, following a population receptive field (pRF) modeling approach. For each stimulus configuration, we first quantify the relationships between numerosity and several non-numerical visual features that have been proposed to underlie performance in numerosity discrimination tasks. We then determine how well responses to these non-numerical visual features predict the observed fMRI responses, and compare this to the predictions of responses to numerosity. We demonstrate that a numerosity response model predicts observed responses more accurately than models of responses to simple non-numerical visual features. As such, neural responses in cognitive processing need not reflect simpler properties of early sensory inputs.



http://ift.tt/2karp5r

Statistical power and prediction accuracy in multisite resting-state fMRI connectivity

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Christian Dansereau, Yassine Benhajali, Celine Risterucci, Emilio Merlo Pich, Pierre Orban, Douglas Arnold, Pierre Bellec
Connectivity studies using resting-state functional magnetic resonance imaging are increasingly pooling data acquired at multiple sites. While this may allow investigators to speed up recruitment or increase sample size, multisite studies also potentially introduce systematic biases in connectivity measures across sites. In this work, we measure the inter-site effect in connectivity and its impact on our ability to detect individual and group differences. Our study was based on real, as opposed to simulated, multisite fMRI datasets collected in N=345 young, healthy subjects across 8 scanning sites with 3T scanners and heterogeneous scanning protocols, drawn from the 1000 functional connectome project. We first empirically show that typical functional networks were reliably found at the group level in all sites, and that the amplitude of the inter-site effects was small to moderate, with a Cohen's effect size below 0.5 on average across brain connections. We then implemented a series of Monte-Carlo simulations, based on real data, to evaluate the impact of the multisite effects on detection power in statistical tests comparing two groups (with and without the effect) using a general linear model, as well as on the prediction of group labels with a support-vector machine. As a reference, we also implemented the same simulations with fMRI data collected at a single site using an identical sample size. Simulations revealed that using data from heterogeneous sites only slightly decreased our ability to detect changes compared to a monosite study with the GLM, and had a greater impact on prediction accuracy. However, the deleterious effect of multisite data pooling tended to decrease as the total sample size increased, to a point where differences between monosite and multisite simulations were small with N=120 subjects. Taken together, our results support the feasibility of multisite studies in rs-fMRI provided the sample size is large enough.



http://ift.tt/2kao9Hg

Investigation of the confounding effects of vasculature and metabolism on computational anatomy studies

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): C.L. Tardif, C.J. Steele, L. Lampe, P.-L. Bazin, P. Ragert, A. Villringer, C.J. Gauthier
Computational anatomy studies typically use T1-weighted magnetic resonance imaging contrast to look at local differences in cortical thickness or grey matter volume across time or subjects. This type of analysis is a powerful and non-invasive tool to probe anatomical changes associated with neurodevelopment, aging, disease or experience-induced plasticity. However, these comparisons could suffer from biases arising from vascular and metabolic subject- or time-dependent differences. Differences in blood flow and volume could be caused by vasodilation or differences in vascular density, and result in a larger signal contribution of the blood compartment within grey matter voxels. Metabolic changes could lead to differences in dissolved oxygen in brain tissue, leading to T1 shortening. Here, we analyze T1 maps and T1-weighted images acquired during different breathing conditions (ambient air, hypercapnia (increased CO2) and hyperoxia (increased O2)) to evaluate the effect size that can be expected from changes in blood flow, volume and dissolved O2 concentration in computational anatomy studies. Results show that increased blood volume from vasodilation during hypercapnia is associated with an overestimation of cortical thickness (1.85%) and grey matter volume (3.32%), and that both changes in O2 concentration and blood volume lead to changes in the T1 value of tissue. These results should be taken into consideration when interpreting existing morphometry studies and in future study design. Furthermore, this study highlights the overlap in structural and physiological MRI, which are conventionally interpreted as two independent modalities.



http://ift.tt/2lvGUBa

Automaticity of phonological and semantic processing during visual word recognition

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Chotiga Pattamadilok, Valérie Chanoine, Christophe Pallier, Jean-Luc Anton, Bruno Nazarian, Pascal Belin, Johannes C. Ziegler
Reading involves activation of phonological and semantic knowledge. Yet, the automaticity of the activation of these representations remains subject to debate. The present study addressed this issue by examining how different brain areas involved in language processing responded to a manipulation of bottom-up (level of visibility) and top-down information (task demands) applied to written words. The analyses showed that the same brain areas were activated in response to written words whether the task was symbol detection, rime detection, or semantic judgment. This network included posterior, temporal and prefrontal regions, which clearly suggests the involvement of orthographic, semantic and phonological/articulatory processing in all tasks. However, we also found interactions between task and stimulus visibility, which reflected the fact that the strength of the neural responses to written words in several high-level language areas varied across tasks. Together, our findings suggest that the involvement of phonological and semantic processing in reading is supported by two complementary mechanisms. First, an automatic mechanism that results from a task-independent spread of activation throughout a network in which orthography is linked to phonology and semantics. Second, a mechanism that further fine-tunes the sensitivity of high-level language areas to the sensory input in a task-dependent manner.



http://ift.tt/2kaqXnH

A variance components model for statistical inference on functional connectivity networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Mark Fiecas, Ivor Cribben, Reyhaneh Bahktiari, Jacqueline Cummine
We propose a variance components linear modeling framework to conduct statistical inference on functional connectivity networks that directly accounts for the temporal autocorrelation inherent in functional magnetic resonance imaging (fMRI) time series data and for the heterogeneity across subjects in the study. The novel method estimates the autocorrelation structure in a nonparametric and subject-specific manner, and estimates the variance due to the heterogeneity using iterative least squares. We apply the new model to a resting-state fMRI study to compare the functional connectivity networks in both typical and reading impaired young adults in order to characterize the resting state networks that are related to reading processes. We also compare the performance of our model to other methods of statistical inference on functional connectivity networks that do not account for the temporal autocorrelation or heterogeneity across the subjects using simulated data, and show that by accounting for these sources of variation and covariation results in more powerful tests for statistical inference.



http://ift.tt/2lvnkF0

Direct access: how is it working?

http://ift.tt/2lqXYfo

Introducing a new alcohol-free hand disinfectant foam

http://ift.tt/2kbmaNU

Patient safety: Needle breakage

http://ift.tt/2lqWTnU

What red means in waste management

http://ift.tt/2kbmXhI

Corporates – friend or foe?

http://ift.tt/2kbfQG6

Love is ... fresh breath and a white smile

http://ift.tt/2kbjsYM

Anticoagulants: Updates on idarucizumab

http://ift.tt/2lqXXrQ

Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study

http://ift.tt/2kbn50J

Antimicrobial resistance: The antibiotic cure-all myth

http://ift.tt/2lqSPEm

Gastrointestinal diseases and their oro-dental manifestations: Part 4: Peutz-Jeghers syndrome

http://ift.tt/2kbiZWA

The toolkit blah

http://ift.tt/2lqQnNV

Literature reviews: Patient-centred care

http://ift.tt/2lqVTQH

Restorative dentistry: Incredulous restorations

http://ift.tt/2lr1XJ3

The financial burden for the surgical management of osteoradionecrosis

http://ift.tt/2kbnP6e

Endodontics: No rubber dam, no root canal

http://ift.tt/2lra7Bl

Academic performance of undergraduate dental students with learning disabilities

http://ift.tt/2kbr39T

Prevention: Fluoride varnish flavours

http://ift.tt/2lr4VgH

Imagine a universal solution

http://ift.tt/2kbmMTG

Conference report: National Conference on Socially Inclusive Dentistry 2016

http://ift.tt/2lr0mTx

Save the date for the Digital Symposium

http://ift.tt/2kbjgbM

De-epithelialized dorsal digital turnover flap for coverage of volar digital lesions: a modified technique

Abstract

Volar digital injuries represent a challenge to hand surgeons. Anatomical studies demonstrate the existence of dorsal digital branches of the ulnar and radial arteries at predictable and regular distances from the PIP joint, bilaterally. Moreover, as there are also small veins that accompany the arterial branches, we designed a novel de-epithelialized dorsal finger turnover flap, which can be performed on the ulnar and radial sides of fingers where it is important to maintain the paratenon to support the dorsal skin flap. A 21-year-old female presented with traumatic injury to the middle phalanx of the third finger associated with loss of substance and damage to the flexor tendons in zone II. The dorsal part of the finger was used to provide coverage for a volar injury. There was no scar retraction or functional limitation of the reconstructed finger. This novel, de-epithelialized dorsal finger turnover flap can be safely used for coverage of volar finger lesions, due to a reliable and well-described arterial supply, with no skin necrosis of the donor site, post-surgical infection, or scarring complications. Level of Evidence: Level V, therapeutic study.

http://ift.tt/2kP6nXb

The effect of lignin on the reactivity of natural fibres towards molecular fluorine

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): M. Pouzet, M. Dubois, K. Charlet, A. Béakou
In this study, a range of natural fibres and their main components have been treated by direct fluorination using F2 gas. Fourier-Transform infrared spectroscopy, ¹⁹F solid state Nuclear Magnetic Resonance and tensiometry results underline the substitution of OH groups by fluorine atoms and thus the formation of CF covalent bonds. Fluorination induces a significant decrease in the hydrophilic properties in the case of lignocellulosic materials. The relationship between the chemical composition of the natural fibres and their reactivity during fluorination has been established. Indeed, on the one hand, the affinity for F2 is improved by the presence of lignin, leading to a better conversion of COH into CF bonds. On the other hand, a high cellulose content tends to inhibit the reaction. As a consequence, the cellulose and lignin contents of wood materials can be determined thanks to their reactivity during fluorination. However, for high-content cellulose materials, estimating the cellulose and lignin contents by this method is more difficult because of their low reactivity during fluorination. In this case, a thermal assisted fluorination is necessary to increase reactivity and thus classify samples according to their cellulose content.

Graphical abstract

http://ift.tt/2lvyqJY

The histopathological differentiation between palmar psoriasis and hand eczema: A retrospective review of 96 cases

Publication date: Available online 9 February 2017
Source:Journal of the American Academy of Dermatology
Author(s): Jun Yeong Park, Eun Byul Cho, Eun Joo Park, Hye Rim Park, Kwang Ho Kim, Kwang Joong Kim
BackgroundThe histopathologic differences among palmar psoriasis (PP), hand eczema (HE), and hyperkeratotic hand dermatitis (HHD) have been poorly described.ObjectivesWe sought to distinguish among PP, HE, and HHD on a histopathologic basis.MethodsWe retrospectively analyzed the histology of hematoxylin-eosin–stained sections obtained from 96 patients diagnosed with PP, HE, or HHD.ResultsThe patients were divided into 4 subgroups: PP (n = 16, group A), HE without atopic or nummular dermatitis (n = 41, group B), HE with atopic or nummular dermatitis (n = 14, group C), and HHD (n = 25, group D). Loss of the granular layer (group A 62.5%, group B 24.4%, group C 0%) was more consistent with a diagnosis of PP (P = .047) than HE (P = .002). Psoriasiform epidermal hyperplasia (group B 36.6%, group C 35.7%, group D 72.0%) favored a diagnosis of HHD (P = .01) over HE (P = .043).LimitationsLimitations of this study include its retrospective nature and small sample size.ConclusionOur study demonstrated that a significant difference exists in the thickness of the granular layer between PP and HE, which might be helpful in differentiating between these 2 conditions. There was no difference between PP and HHD.



http://ift.tt/2kVZyW9

Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age

Publication date: Available online 9 February 2017
Source:Journal of the American Academy of Dermatology
Author(s): Andre Vadimovich Moyakine, Saskia Spillekom-van Koulil, Catharina Joanna Maria van der Vleuten
BackgroundConcern has been raised about the potential long-term effects of propranolol treatment for infantile hemangioma (IH).ObjectivesWe sought to assess psychologic (social, emotional, behavioral, and executive) functioning in children treated with propranolol for IH.MethodsTwenty-seven patients with IH (6.1-7.6 years of age) treated with propranolol for ≥6 months during infancy, and without other developmental risk factors, were recruited. Parents completed the Behavior Rating Inventory of Executive Function, Social Emotional Questionnaire, Child Behavior Checklist, and Strengths and Difficulties Questionnaire. For each questionnaire, the number of patients with abnormal scores, based on established cutoff points, was calculated.ResultsOnly 1 child (3.7%) scored outside the normal range. The Hemangioma Severity Scale did not correlate with psychologic problems in these patients. Longer treatment duration was found to correlate with less attention-deficit hyperactivity disorder (ADHD) characteristics (ρ = −0.476; P = .012) and better executive functioning (ρ = −0.466; P = .014).LimitationsExclusion of children born at gestational age <36 weeks or small for gestational age, no reference group and relatively small study size.ConclusionWe found no increased risk for psychologic problems at age 7 in IH patients treated with propranolol.



http://ift.tt/2kbcC5m

Single Stage Augmentation Mastopexy with L-shaped Inferior Pedicle Combined with Dual Plane Implant Placement

No abstract available

http://ift.tt/2luZrgH

Partial Breast Reconstruction with Goldilocks Technique After Excision of Giant Fibroadenoma: A Case Report

Summary: Giant juvenile fibroadenomas are relatively rare, accounting for less than 1% fibroadenomas. Large breast tumors create significant asymmetry and provide unique reconstructive challenges after removal. In this case, we describe a 21-year-old female with delayed presentation of a giant fibroadenoma of the right breast. This represents an unusual presentation of benign breast disease requiring reduction of the skin envelope, extensive glandular resection, lower pole reconstruction, and free nipple grafting to achieve symmetry with the opposite breast. A novel modification of the Goldilocks mastectomy technique is described for partial breast reconstruction. Adaptation of the Goldilocks mastectomy technique provides adequate soft tissue for partial breast reconstruction. Using the lower pole deepithelialization breast skin flap provides autologous vascularized tissue to supplement volume loss after tumor and glandular excision. Benign breast disease can create significant breast deformities. Application and combination of the Goldilocks mastectomy technique allow for partial breast reconstruction without the need for an additional donor site or prosthetic devices.

http://ift.tt/2lv6MNj

Characteristics and source apportionment of black carbon aerosols over an urban site

Abstract

Aethalometer based source apportionment model using the measured aerosol absorption coefficients at different wavelengths is used to apportion the contribution of fossil fuel and wood burning sources to the total black carbon (BC) mass concentration. Temporal and seasonal variabilities in BC mass concentrations, equivalent BC from fossil fuel (BC_{f f} ), and wood burning (BC_{w b} ) are investigated over an urban location in western India during January 2014 to December 2015. BC, BC_{f f} , and BC_{w b} mass concentrations exhibit strong diurnal variation and are mainly influenced by atmospheric dynamics. BC_{f f} was higher by a factor of 2–4 than BC_{w b} and contributes maximum to BC mass throughout the day, confirming consistent anthropogenic activities. Diurnal contribution of BC_{f f} and BC_{w b} exhibits opposite variation due to differences in emission sources over Ahmedabad. Night time BC values are about a factor of 1.4 higher than day time BC values. The annual mean percentage contributions of day time and night time are 42 and 58 %, respectively. BC, BC_{f f} , and BC_{w b} mass concentrations exhibit large and significant variations during morning, afternoon, evening, and night time. During afternoon, mass concentration values are minimum throughout the year because of the fully evolved boundary layer and reduced anthropogenic activities. BC exhibits a strong seasonal variability with postmonsoon high (8.3 μg m ⁻³) and monsoon low (1.9 μg m ⁻³). Annual mean BC_{f f} and BC_{w b} contributions are 80 and 20 %, respectively, to total BC, which suggests that major contribution of BC in Ahmedabad comes from fossil fuel emissions. The results show that the study location is dominated by fossil fuel combustion as compared to the emissions from wood burning. The results obtained represent a regional value over an urban regime which can be used as inputs on source apportionment to model BC emissions in regional and global climate models.

http://ift.tt/2kaOgJ5

Spatiotemporal distribution and source apportionment of low molecular weight organic acids in wet precipitation at a coastal city, China

Abstract

To investigate the characteristics and sources of low molecular weight (LMW) organic acids in wet precipitation at a coastal city, Xiamen, a total of 313 rainwater samples were collected at seven different functional areas from September 2012 to August 2013. Spatiotemporal characteristics of LMW organic acids as well as pH and electrical conductivity were analyzed. Meanwhile, air mass clusters in different seasons and the positive matrix factorization (PMF) source apportion model were comprehensively used to identify the sources of organic acids. In conclusion, the volume-weighted mean (VWM) concentration of formic (3.20 μmol/L), acetic (1.84 μmol/L), lactic (0.44 μmol/L), and oxalic acid (0.53 μmol/L) were obtained, which jointly contributed to 4.33% of the total free acidity (TFA). At the same time, the highest wet deposition flux of LMW organic acids and contribution of that to TFA were achieved at the forest protection area during growing season in Xiamen. In addition, biogenic emissions (77.12%), sea salts (13.77%), regional agriculture activities (3.92%), soil emissions (2.56%), biomass burning (1.47%), and secondary aerosols (1.15%) were determined as the source of LMW organic acids. Besides, the dominancy of biomass burning via long-range transport in non-growing season (NGS) and the contribution of biogenic emission in growing season (GS) were recognized. Finally, the considerable influence of sea salts on the LMW organic acids (13.77%) in Xiamen was quantified, especially for oxalic acid.

http://ift.tt/2kVyZ3c

Thermal analysis and stability of commercially available endodontic obturation materials

Abstract

Objectives

The purpose of this study was to evaluate the thermal stability of 23 commercially-available endodontic obturation materials.

Materials and methods

Specimens (n = 10) were sealed in aluminum differential scanning calorimetry (DSC) crucibles and subjected to thermal scan series consisting of a 25 to 70 °C at 5 °C/min followed by a rapid increase to 230 °C, followed by a second scan from 25 to 70 °C at 5 °C/min. The first scan evaluated the materials as-received followed by a worse-case-scenario thermal challenge simulating temperatures involved with warm vertical condensation obturation techniques. The second thermal scan observed any phase changes from the high temperature challenge. This two-scan process was repeated twice to observe changes encountered by repeat high heat exposure during obturation. Mean thermal enthalpies were analyzed with Kruskal-Wallis and Games-Howell post-hoc test. (p = 0.05).

Results

Thermal behavior was material dependent. During the first thermal scan, materials typically demonstrated broad endothermic enthalpy curves suggesting either a gutta-percha phase mixture and/or an alpha crystalline phase. The first high-heat challenge produced definitive alpha/beta thermal phase signatures usually associated with gutta-percha. Changes in beta-phase enthalpies were noted with Therarmafil Plus and UltraFil Firmset while increase in alpha-phases was observed with GuttaCore, K3, Lexicon, and Schein Accessory Points.

Conclusions

Commercial endodontic gutta-percha obturation materials displayed thermal characteristics that were material dependent. However, all demonstrated stability at temperatures in excess to that experienced during warm vertical condensation techniques.

Clinical relevance

The gutta-percha obturation materials evaluated in this evaluation can be used successfully in warm vertical condensation techniques without fear of degradation.

http://ift.tt/2lv4Gxb

DATASET FOR AN ANALYSIS OF COMMUNICATIVE ASPECTS OF FINANCE

Publication date: Available online 9 February 2017
Source:Data in Brief
Author(s): Zavyalova Natalya
The article describes a step-by-step strategy for designing a universal comprehensive vision of a vast majority of financial research topics. The strategy is focused around the analysis of the retrieval results of the word processing system Serelex which is based on the semantic similarity measure. While designing a research topic, scientists usually employ their individual background. They rely in most cases on their individual assumptions and hypotheses. The strategy, introduced in the article, highlights the method of identifying components of semantic maps which can lead to a better coverage of any scientific topic under analysis. On the example of the research field of finance we show the practical and theoretical value of semantic similarity measurements, i.e., a better coverage of the problems which might be included in the scientific analysis of financial field. At the designing stage of any research scientists are not immune to an insufficient and, thus, erroneous spectrum of problems under analysis. According to the famous maxima of St. Augustine, 'Fallor ergo sum', the researchers' activities are driven along the way from one mistake to another. However, this might not be the case for the 21^st century science approach. Our strategy offers an innovative methodology, according to which the number of mistakes at the initial stage of any research may be significantly reduced. The data, obtained, was used in two articles [7], [8]. The second stage of our experiment was driven towards analyzing the correlation between the language and income level of the respondents. The article contains the information about data processing.



http://ift.tt/2kaMJml

Residential construction cost: An Italian survey

Publication date: Available online 9 February 2017
Source:Data in Brief
Author(s): Rubina Canesi, Giuliano Marella
This paper reports data describing development projects for new buildings according to construction costs in North-East Italy. A survey was carried out on local companies undertaking new residential development projects in two Italian regions (Veneto and Lombardy). The aim of this survey was to record new real estate construction projects, collecting both technical and socio-economic cost features. It is extremely difficult to collect such data for the Italian real estate construction sector, due to its lack of transparency, so that the novelty for the Italian scenario is the dataset itself. Another interest perspective of this survey is that socio-economic characteristics were also recorded; they are often studied in urban economics, but are usually related to property purchase prices and values, not to construction costs. The data come from an analysis of Canesi and Marella regarding the relationship between the trend of construction costs and the socio-economic conditions of the reference setting, such as the mean years of schooling of the workforce, housing market trends, and average per capita income.



http://ift.tt/2kVKRSL

DNA methylation data for identification of epigenetic targets of resveratrol in triple negative breast cancer cells

Publication date: Available online 9 February 2017
Source:Data in Brief
Author(s): Rubiceli Medina-Aguilar, Carlos Pérez-Plasencia, Patricio Gariglio, Laurence A. Marchat, Ali Flores-Pérez, César López-Camarillo, Jaime García Mena
Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24h and 48h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720K array. Our data were associated to corresponding changes in mRNA expression in a set of cancer-related genes. Using gene ontology analysis we also identify cancer-related cellular processes and pathways that can be epigenetically reprogramed by resveratrol. Data in this article are associated to the research articles "Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol". Medina Aguilar et al., PLoS ONE 11(6): e0157866. doi:10.1371/journal.pone.0157866 2016 [2]; and "Resveratrol inhibits cell cycle progression by targeting Aurora kinase A and Polo-like kinase 1 in breast cancer cells" in Oncology Reports. Medina Aguilar et al., 2016 Jun; 35(6):3696-704. doi: 10.3892/or.2016.4728 [3].



http://ift.tt/2kaPX9k

Dataset of proteomics analysis of aging C. elegans exposed to Pseudomonas aeruginosa strain PA01

Publication date: Available online 9 February 2017
Source:Data in Brief
Author(s): Christina D. King, Daljeet Singh, Kyle Holden, Annie B. Govan, Scott Keith, Arjumand Ghazi, Renã A.S. Robinson
Here, we present the proteomics dataset of young and middle-aged Caenorhabditis elegans (C. elegans) exposed to Pseudomonas aeruginosa (P. aeruginosa strain PA01), which is related to the article "Proteomic Identification of Virulence-Related Factors in Young and Aging C. elegans infected with Pseudomonas aeruginosa" (C. D. King et. al, in-revisions). This dataset was generated to better understand the effects of aging on molecular mechanisms involved in host response to pathogen exposure. Protein from C. elegans of different age and exposure to P. aeruginosa PA01 or control E. coli OP50 were extracted and tryptically digested. Peptides were labeled with the reagents tandem mass tag (TMT⁶-plex), separated, and detected by using offline strong-cation exchange and online liquid chromatography – mass spectrometry (SCX – LC – MS/MS & MS³). A separate mixture of peptides were labeled on N-terminal amines and lysines with dimethylation. Dimethylated peptides were analyzed using LC – MS/MS and a portion of the results were used to verify fold-change direction for TMT⁶-plex experiments. Raw data can be found online at http://ift.tt/2kaKakf, a cloud-based data repository (see specifications table for details).



http://ift.tt/2kVA2jO

Short- and long-term changes in sugarbeet (Beta vulgaris L.) gene expression due to postharvest jasmonic acid treatment - Data

Publication date: Available online 9 February 2017
Source:Data in Brief
Author(s): Lucilene Silva de Oliveira, Karen Klotz Fugate, Jocleita Perruzo Ferrareze, Melvin D. Bolton, Edward L. Deckard, Fernando L. Finger
Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L.) root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr), Swiss-Prot, Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) protein databases, and unigene annotations with Gene Ontology (GO) terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, "Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots" (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017) [1]. Public dissemination of this dataset will allow further analyses of the data.



http://ift.tt/2kVGjvH