Mirror Motor Activity During Right-Hand Contractions and Its Relation to White Matter in the Posterior Midbody of the Corpus Callosum

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Cortical activity during simple unimanual actions is typically lateralized to contralateral sensorimotor areas, while a more bilateral pattern is observed with an increase in task demands. In parallel, increasing task demands are associated with subtle mirror muscle activity in the resting hand, implying a relative loss in motor selectivity. The corpus callosum (CC) is crucially involved in unimanual tasks by mediating both facilitatory and inhibitory interactions between bilateral motor cortical systems, but its association with mirror motor activity is yet unknown. Here, we used diffusion-weighted imaging and bilateral electromyographic (EMG) measurements during a unimanual task to investigate potential relationships between white matter microstructure of the CC and mirror EMG activity. Participants performed an unimanual pinch force task with both hands alternatively. Four parametrically increasing force levels were exerted while EMG activity was recorded bilaterally from first dorsal interosseus muscles. Consistent with previous findings, mirror EMG activity increased as a function of force. Additionally, there was a significant relationship between the slope of increasing mirror EMG during right-hand contractions and fractional anisotropy in transcallosal fibers connecting both M1. No significant relationships were found for fibers connecting dorsal premotor cortices or supplementary motor area, indicating the local specificity of the observed brain–physiology relationship.</span>

http://ift.tt/2eO2vFL

Distinct Spatiotemporal Response Properties of Excitatory Versus Inhibitory Neurons in the Mouse Auditory Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In the auditory system, early neural stations such as brain stem are characterized by strict tonotopy, which is used to deconstruct sounds to their basic frequencies. But higher along the auditory hierarchy, as early as primary auditory cortex (A1), tonotopy starts breaking down at local circuits. Here, we studied the response properties of both excitatory and inhibitory neurons in the auditory cortex of anesthetized mice. We used in vivo two photon-targeted cell-attached recordings from identified parvalbumin-positive neurons (PVNs) and their excitatory pyramidal neighbors (PyrNs). We show that PyrNs are locally heterogeneous as characterized by diverse best frequencies, pairwise signal correlations, and response timing. In marked contrast, neighboring PVNs exhibited homogenous response properties in pairwise signal correlations and temporal responses. The distinct physiological microarchitecture of different cell types is maintained qualitatively in response to natural sounds. Excitatory heterogeneity and inhibitory homogeneity within the same circuit suggest different roles for each population in coding natural stimuli.</span>

http://ift.tt/2foqgk2

Unstable Maternal Environment Affects Stress Response in Adult Mice in a Genotype-Dependent Manner

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Early postnatal events exert powerful effects on development, inducing persistent functional alterations in different brain network, such as the catecholamine prefrontal–accumbal system, and increasing the risk of developing psychiatric disorders later in life. However, a vast body of literature shows that the interaction between genetic factors and early environmental conditions is crucial for expression of psychopathologies in adulthood. We evaluated the long-lasting effects of a repeated cross-fostering (RCF) procedure in 2 inbred strains of mice (C57BL/6J, DBA/2), known to show a different susceptibility to the development and expression of stress-induced psychopathologies. Coping behavior (forced swimming test) and preference for a natural reinforcing stimulus (saccharine preference test) were assessed in adult female mice of both genotypes. Moreover, c-Fos stress-induced activity was assessed in different brain regions involved in stress response. In addition, we evaluated the enduring effects of RCF on catecholamine prefrontal–accumbal response to acute stress (restraint) using, for the first time, a new "dual probes" in vivo microdialysis procedure in mouse. RCF experience affects behavioral and neurochemical responses to acute stress in adulthood in opposite direction in the 2 genotypes, leading DBA mice toward an "anhedonic-like" phenotype and C57 mice toward an increased sensitivity for a natural reinforcing stimulus.</span>

http://ift.tt/2eNTJrC

Deubiquitination and Stabilization of PD-L1 by CSN5

Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Seung-Oe Lim, Chia-Wei Li, Weiya Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-Chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu, Taewan Kim, Wei-Chao Chang, Jennifer L. Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung-Hsuan Chen, Aysegul A. Sahin, Dihua Yu, Gabriel N. Hortobagyi, Mien-Chie Hung
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.

Graphical abstract

Teaser

Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.


http://ift.tt/2gnDTEz

Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy

Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Anna Rita Cantelmo, Lena-Christin Conradi, Aleksandra Brajic, Jermaine Goveia, Joanna Kalucka, Andreas Pircher, Pallavi Chaturvedi, Johanna Hol, Bernard Thienpont, Laure-Anne Teuwen, Sandra Schoors, Bram Boeckx, Joris Vriens, Anna Kuchnio, Koen Veys, Bert Cruys, Lise Finotto, Lucas Treps, Tor Espen Stav-Noraas, Francesco Bifari, Peter Stapor, Ilaria Decimo, Kim Kampen, Katrien De Bock, Guttorm Haraldsen, Luc Schoonjans, Ton Rabelink, Guy Eelen, Bart Ghesquière, Jalees Rehman, Diether Lambrechts, Asrar B. Malik, Mieke Dewerchin, Peter Carmeliet
Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show that tumor endothelial cells (ECs) have a hyper-glycolytic metabolism, shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors.

Graphical abstract

Teaser

Cantelmo et al. show that tumor endothelial cells have hyperglycolytic metabolism. Inactivation of the glycolytic activator PFKFB3 normalizes tumor vessels and improves vessel perfusion via tightening the vascular barrier, which reduces cancer cell intravasation and metastasis and improves chemotherapy response.


http://ift.tt/2gnzeCx

Corrigendum to “Review of Amyotrophic Lateral Sclerosis, Parkinson’s and Alzheimer’s diseases helps further define proteomic events of the novel paradigm for Alzheimer’s with metals as primary disease cause” [Med. Hypotheses 85 (2015) 779–790]

Publication date: January 2017
Source:Medical Hypotheses, Volume 98
Author(s): Franco Cavaleri




http://ift.tt/2g2vFgO

Senses make sense: An individualized multisensory stimulation for dementia

Publication date: Available online 17 November 2016
Source:Medical Hypotheses
Author(s): Yuanwu Cui, Minxue Shen, Yan Ma, Shi Wu Wen
Nonpharmacologic interventions have been recommended as first-line treatments for dementia, and multisensory stimulation environment has been used as a non-pharmacological treatment to dementia patients in the last decade. However, the clinical effect of multisensory stimulation environment remains temporary and uncertain. Individualized medicine has been suggested to hold great promise in medicine, and it should be equally important for dementia. Reminiscence integrating individual experiences into therapeutic schemes has shown potential in the field of improving cognitive functions and depressive symptoms for dementia patients, and interactive music also demonstrated a positive outcome by using individualized music for the hearing aspect. We therefore hypothesize that an individualized multisensory stimulation in a natural and realistic environment integrating personal experience may be an effective intervention for patients suffering from dementia.



http://ift.tt/2fbBlY1

Orbital autoimmune inflammatory disorders - Protein regional variability might explain specific lesion location

Publication date: Available online 17 November 2016
Source:Medical Hypotheses
Author(s): Margo S. Clarke, Alexandre Plouznikoff, Jean Deschenes
In ophthalmology, inflammatory diseases target different highly specific regions within the small confine of the orbit. Some entities even prefer a particular location or depth within the same tissue (ex. anterior, intermediate or posterior uveitides, chorioretinitides with unique topographic presentations). Though the location of a lesion strongly influences and helps us in our differential diagnosis, we still don't understand why specific anatomic sites are susceptible to a disease while other areas are spared. We postulate that regional variability in tissue protein expression can sway the immune system's capacity to trigger an autoimmune response. In addition to this site-specific quantitative and qualitative variability in potential antigen expression, we believe that other proteins implicated in the immune cascade, as well as geographic areas of relative resistance, tolerance and susceptibility, may be unequally distributed within the orbit. To illustrate our hypotheses, we review three major types of ocular myositis and describe how the extraocular muscles different embryologic origins and protein disparities might explain the fundamental clinical differences between these orbital inflammatory diseases. We hope that future differential genomics, proteinomics, epigenomics and analysis of RNA species of affected tissues, compared to their non-affected, yet microscopically similar, counterparts, will help us understand why diseases occur where they do. Hopefully, understanding these immune triggers will pave the way to new treatment options for ocular inflammatory diseases and for other auto-inflammatory conditions with a marked predilection for any given site.



http://ift.tt/2g2A6bl

Evaluation of knee range of motion: Correlation between measurements using a universal goniometer and a smartphone goniometric application

Publication date: Available online 17 November 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Rafael Aparecido Dos Santos, Viviane Derhon, Michelle Brandalize, Danielle Brandalize, Luciano Pavan Rossi
BackgroundGoniometers are commonly used to measure range of motion in the musculoskeletal system. Recently smartphone goniometry applications have become available to clinicians.ObjectiveCompare angular measures using a universal goniometer and a smartphone application.MethodsThirty four healthy women with at least 20° of limited range of motion regarding knee extension were recruited. Knee flexion angles of the dominant limb were measured with a universal goniometer and the ROM^© goniometric application for the smartphone. Three trained examiners compared the two assessment tools.ResultsStrong correlations were found between the measures of the universal goniometer and smartphone application (Pearson's correlation and interclass correlation coefficient > 0.93). The measurements with both devices demonstrated low dispersion and little variation.ConclusionMeasurements obtained using the smartphone goniometric application analyzed are as reliable as those of a universal goniometer. This application is therefore a useful tool for the evaluation of knee range of motion.



http://ift.tt/2foaPsp

Unrealistic self-overconfidence in schizophrenia is associated with left presubiculum atrophy and impaired episodic memory

Publication date: Available online 17 November 2016
Source:Cortex
Author(s): Maria Donata Orfei, Fabrizio Piras, Nerisa Banaj, Giorgio Di Lorenzo, Alberto Siracusano, Carlo Caltagirone, Pier Luca Bandinelli, Giuseppe Ducci, Gianfranco Spalletta
The study aimed at investigating the role of the hippocampal subfields in cognitive insight and the clinical and neuropsychological underpinnings of the related two sub-dimensions, Self-Reflectiveness (SR), i.e., openness to external feedback, and Self-Certainty (SC), i.e., unrealistic overconfidence in one's opinions. In order to do this, 45 patients with a diagnosis of schizophrenia and 45 age- and gender-matched healthy control subjects (HC) were administered the Beck Cognitive Insight Scale (BCIS), along with neuropsychological, clinical and psychopathological assessment, and underwent an MRI investigation. Hippocampal segmentation was carried out. Regression analyses were performed for BCIS indexes, volumetric parameters of hippocampal subfields and clinical and neuropsychological variables. Results highlighted that in the schizophrenia group, higher levels of SC were related to reduced volume of the left presubiculum, and worse episodic memory. No significant relationship emerged for the SR index. There was no significant relationship between any of the BCIS indexes and volumetric data of the hippocampal subfields in the HC group. Our data support the hypothesis that unrealistic self-overconfidence in schizophrenia is related to the hippocampal presubiculum atrophy, which is involved in episodic memory and cognitive control and is supposed to be underpinned by difficulty in integrating new memories and thus in generating new hypotheses about the self.



http://ift.tt/2fD1wr8

Comorbidities that cause pain and the contributors to pain in individuals with chronic obstructive pulmonary disease

Publication date: Available online 17 November 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yi-Wen Chen, Pat G. Camp, Harvey O. Coxson, Jeremy D. Road, Jordan A. Guenette, Michael A. Hunt, W. Darlene Reid
ObjectiveTo determine comorbidities that cause pain and the potential contributors to pain in individuals with COPD.DesignProspective cross-sectional survey study.SettingPulmonary rehabilitation programs of six centers.ParticipantsA convenience sample of individuals with COPD who attended pulmonary rehabilitation programs (n=137). In total, 100 (73%) returned the survey packages. Of those responders, 96 (70%) participants were included in the analyses.InterventionsNot applicable.Main Outcome MeasuresPain was measured using the Brief Pain Inventory (BPI). The "health conditions that might contribute to pain and medication record" form asked about comorbidities that cause pain stated in lay terms. The health conditions that cause pain were then validated by health professionals. Demographics, fatigue, dyspnea, quality of life, and self-efficacy were also measured using questionnaires.ResultsPain was reported in 71% of participants (68 of 96). Low back pain was the most common location (41%). Arthritis (75%), back problems (47%) and muscle cramps (46%) were the most common comorbidities that cause pain. Lower self-efficacy, renting rather than home ownership increased the likelihood of pain (p < 0.05). Pain severity and BFI scores contributed to pain interference scores (p < 0.05).ConclusionPain was highly prevalent in pulmonary rehabilitation program participants with COPD. The most common causes of pain were musculoskeletal conditions. Pain severity and higher levels of fatigue contributed to how pain interfered with daily aspects of living. The assessment and management of pain needs to be addressed within the overall care of individuals with COPD.



http://ift.tt/2fbjVuB

How In Vitro Assays Contribute to Allergy Diagnosis

Abstract

Diagnosis of allergic disorders is based upon the clinical history of the disease, the immunoglobulin E (IgE) antibody response, and the allergen exposure. During the last decade, many changes have occurred in the in vitro diagnostic tests used in daily practice. The most important one is the use of allergenic molecules, which helps to define severe profile of allergy and/or to better understand cross-reactivity. The correlation between IgE sensitization and bronchial or nasal response in provocation tests is not so clear, which implies that such tests are still helpful in allergy diagnosis. In order to strengthen the link between a real allergen exposure and allergic symptoms, environmental allergen load assessment can be performed. For clinicians, it appears obvious to know the pollen count to treat their patients; however, they rarely measure the allergen load in the indoor environment, while nowadays home-tests (semi-quantitative or quantitative) make the assessment very easy. In the future, assessment of the environmental exposure (preferably with an indoor technician) of an allergic patient should take into account not only the allergens but also the other indoor pollutants, which could enhance respiratory symptoms in allergic patients.

http://ift.tt/2fbsQfz

How In Vitro Assays Contribute to Allergy Diagnosis

Abstract

Diagnosis of allergic disorders is based upon the clinical history of the disease, the immunoglobulin E (IgE) antibody response, and the allergen exposure. During the last decade, many changes have occurred in the in vitro diagnostic tests used in daily practice. The most important one is the use of allergenic molecules, which helps to define severe profile of allergy and/or to better understand cross-reactivity. The correlation between IgE sensitization and bronchial or nasal response in provocation tests is not so clear, which implies that such tests are still helpful in allergy diagnosis. In order to strengthen the link between a real allergen exposure and allergic symptoms, environmental allergen load assessment can be performed. For clinicians, it appears obvious to know the pollen count to treat their patients; however, they rarely measure the allergen load in the indoor environment, while nowadays home-tests (semi-quantitative or quantitative) make the assessment very easy. In the future, assessment of the environmental exposure (preferably with an indoor technician) of an allergic patient should take into account not only the allergens but also the other indoor pollutants, which could enhance respiratory symptoms in allergic patients.

http://ift.tt/2fbsQfz

Disk displacement, eccentric condylar position, osteoarthrosis – misnomers for variations of normality? Results and interpretations from an MRI study in two age cohorts

Abstract

Background

Clinical decision-making and prognostic statements in individuals with manifest or suspected temporomandibular disorders (TMDs) may involve assessment of (a) the position of articular disc relative to the mandibular condyle, (b) the location of the condyle relative to the temporal joint surfaces, and (c) the depth of the glenoid fossa of the temporomandibular joints (TMJs). The aim of this study was twofold: (1) Determination of the prevalence of these variables in two representative population-based birth cohorts. (2) Reinterpretation of the clinical significance of the findings.

Methods

From existing magnetic resonance imaging (MRI) scans of the TMJs that had been taken in 2005 and 2006 from 72 subjects born between 1930 and 1932 and between 1950 and 1952, respectively, the condylar position at closed jaw was calculated as percentage displacement of the condyle from absolute centricity. By using the criteria introduced by Orsini et al. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:489-97, 1998), a textbook-like disc position at closed jaw was distinguished from an anterior location. TMJ morphology of the temporal joint surfaces was assessed at open jaw by measuring the depth of the glenoid fossa, using the method proposed by Muto et al. (J Oral Maxillofac Surg 52:1269-72, 1994).

Frequency distributions were recorded for the condylar and disc positions at closed jaw.

Student's t-test with independent samples was used as test of significance to detect differences of condylar positions between the age cohorts (1930 vs. 1950) and the sexes. The significance levels were set at 5%. First, the results from the measurement of the age cohorts were compared without differentiation of sexes, i.e., age cohort 1930–1932 versus age cohort 1950–1952. Subsequently, the age cohorts were compared by sex, i.e., men in cohort 1930–1932 versus men in cohort 1950–1952, and women in cohort 1930–1932 women men in cohort 1950–1952.

Results

In both cohorts, condylar position was characterized by great variability. About 50% of the condyles were located centrically, while the other half was either in an anterior or in a posterior position. In both female cohorts, a posterior position predominated, whereas a centric position prevailed among men. Around 75% of the discs were positioned textbook-like, while the remaining forth was located anteriorly. Age had no statistically significant influence on condylar or on disc position. Conversely, comparison between the age groups revealed a statistically significant decrease of the depth of the glenoid fossa in both older cohorts. This age-dependent changes may be interpreted as flattening of the temporal joint surfaces.

Conclusions

We call for a re-interpretation of imaging findings because they may insinuate pathology which usually is not present. Instead, anterior or posterior positions of the mandibular condyle as well as an anterior location of the articular disc should be construed as a variation of normalcy. Likewise, flattening of articular surfaces of the TMJs may be considered as normal adaptive responses to increased loading, rather than pathological degenerative changes.

Trial registration

Not applicable.

http://ift.tt/2gqo1So

Supportive Therapie Teil 2

Zusammenfassung

Hintergrund

Unverändert besteht ein großes Interesse von Tumorpatienten an der zusätzlichen Einnahme von Mikronährstoffen zwecks Immunstabilisierung während der onkologischen Therapie. Im Gegensatz dazu bestehen gerade in Deutschland trotz Zunahme seriöser Daten diesbezüglich weiterhin Bedenken. Dieses Update liefert weitere Daten, den zusätzlichen Einsatz von ausgewählten Mikronährstoffen während der Tumortherapie in Erwägung zu ziehen.

Methoden

Es erfolgte eine Literaturrecherche hinsichtlich des Einsatzes von ausgewählten Mikronährstoffen in der Onkologie, die von 2013 bis 2016 in zitierfähigen Journalen erschienen sind.

Ergebnisse

Es werden Daten zu Vitamin D, Selen, Vitamin C, Glutamin und L‑Carnitin präsentiert, die sowohl hinsichtlich der Lebensqualität als auch der Prognose einen Nutzen für onkologische Patienten bringen.

Schlussfolgerung

Onkologisch tätige Ärzte sollten Kenntnisse über die wichtigsten Mikronährstoffe haben, um diese an die Patienten weiterzugeben und sie auch gezielt zum Nutzen der Patienten einzusetzen.

http://ift.tt/2g3oetp

Molybdenum-99 for Medical Imaging.

The decay product of the medical isotope molybdenum-99 (Mo-99), technetium-99m (Tc-99m), and associated medical isotopes iodine-131 (I-131) and xenon-133 (Xe-133) are used worldwide for medical diagnostic imaging or therapy. The United States consumes about half of the world's supply of Mo-99, but there has been no domestic (i.e., U.S.-based) production of this isotope since the late 1980s. The United States imports Mo-99 for domestic use from Australia, Canada, Europe, and South Africa.

http://ift.tt/2fbs8il

Nachsorge, Fertilität, Langzeittoxizität und Survivorship bei Keimzelltumoren

Zusammenfassung

Hintergrund

Keimzelltumoren sind heute auch in metastasierten Stadien bei der Mehrheit der Patienten heilbar. Das frühzeitige Erkennen eines Rezidivs durch konsequente Nachsorge, die aber zusätzliche Toxizitäten durch unnötig häufige Bildgebungen hervorrufen können, ist dabei essenziell. Da die Patienten meist jung erkranken, sind die Prävention und Therapie von Spättoxizitäten entscheidend für ihre Lebensqualität.

Ziel der Arbeit

Ziel ist eine Übersicht über die aktuelle Studien- und Datenlage zur Nachsorge von Keimzelltumorpatienten zur frühzeitigen Diagnose eines Rezidivs, aber auch zur Prävention und Therapie möglicher physischer und psychosozialer Spättoxizitäten.

Ergebnisse

Es liegen evidenzbasierte Empfehlungen zur Nachsorge, abhängig von der Krankheitsausbreitung und der durchgeführten Therapie, vor. Diese fokussieren auf eine lebenslange Nachsorge hinsichtlich Fertilität sowie Erkrankungen im Rahmen eines metabolischen Syndroms. Außerdem besteht ein erhöhtes Risiko für Zweitmalignome, anhaltende pulmonale bzw. nephrologische Toxizitäten und Polyneuropathie. Patienten beklagen zudem häufig Fatigue und kognitive Einschränkungen. Studien zeigen auch vermehrte psychische Störungen wie Angststörungen, Depression oder posttraumatische Belastungsstörungen. Zunehmend werden auch die Zusammenhänge zwischen körperlichen Spättoxizitäten, psychischen Störungen und sozialen wie beruflichen Langzeitfolgen deutlich. Mit Survivorship-Programmen wird versucht, den komplexen Bedürfnissen der Patienten gerecht zu werden.

Schlussfolgerungen

Eine leitliniengerechte Nachsorge hat das Ziel, ein langfristiges Überleben bei guter Gesundheit nach Keimzelltumorerkrankung zu erreichen. Die Prävention und Therapie von körperlichen sowie psychosozialen Spätfolgen sind entscheidend, um eine möglichst hohe Lebensqualität zu erreichen.

http://ift.tt/2fM3uDc

Primary Care Interventions to Support Breastfeeding: Updated Systematic Review for the U.S. Preventive Services Task Force [Internet].

We conducted this systematic review to support the U.S. Preventive Services Task Force (USPSTF) in updating its 2008 recommendation on counseling to promote and support breastfeeding. Our review addressed three questions: 1) What are the effects of prenatal, peripartum, and postpartum individual- and health care system-level interventions to promote and support breastfeeding on child and maternal health outcomes? 2) What are the effects of interventions on the initiation, duration, and exclusivity of breastfeeding? 3) Are there adverse events associated with interventions to promote and support breastfeeding?

http://ift.tt/2g2pWaE

The Use of Delamanid in the Treatment of Multidrug-Resistant Tuberculosis in Children and Adolescents: Interim Policy Guidance.

Multidrug-resistant tuberculosis (MDR-TB) is a public health challenge of growing concern. Approximately 580 000 people acquired MDR-TB in 2015, with children accounting for close to 30 000 of MDR-TB cases.

http://ift.tt/2fbo2a8

Science Literacy: Concepts, Contexts, and Consequences.

Science is a way of knowing about the world. At once a process, a product, and an institution, science enables people to both engage in the construction of new knowledge as well as use information to achieve desired ends. Access to science—whether using knowledge or creating it—necessitates some level of familiarity with the enterprise and practice of science: we refer to this as science literacy.

http://ift.tt/2g2rlhn

Hormonal Contraception and Post-menopausal Hormonal Therapy.

This monograph evaluates evidence for an increased risk of cancer in women using combined oral contraceptives, progestogen-only hormonal contraceptives, post-menopausal oestrogen therapy, and post-menopausal oestrogen-progestogen therapy. Although the carcinogenicity of these preparations has been extensively investigated, the book stresses the many complex methodological issues that must be considered when interpreting findings and weighing results. Evidence of an association between use of these preparations and positive effects on health, including a reduced risk of some cancers, is also critically assessed.

http://ift.tt/2fbplWs

Risky Repair: DNA-protein Crosslinks Formed by Mitochondrial Base Excision DNA Repair Enzymes Acting on Free Radical Lesions

Publication date: Available online 17 November 2016
Source:Free Radical Biology and Medicine
Author(s): Rachel Audrey Caston, Bruce Demple
Oxygen is both necessary and dangerous for the aerobic cell function. ATP is most efficiently made by the electron transport chain, which requires oxygen as an electron acceptor. However, the presence of oxygen, and to some extent the respiratory chain itself, poses a danger to cellular components. Mitochondria, the sites of oxidative phosphorylation, have defense and repair pathways to cope with oxidative damage. For mitochondrial DNA, an essential pathway is base excision repair, which acts on a variety of small lesions. There are instances, however, in which attempted DNA repair results in more damage, such as the formation of a DNA-protein crosslink trapping the repair enzyme on the DNA. That is the case for mitochondrial DNA polymerase γ acting on abasic sites oxidized at the 1-carbon of 2-deoxyribose. Such DNA-protein crosslinks presumably must be removed in order to restore function. In nuclear DNA, ubiquitylation of the crosslinked protein and digestion by the proteasome are essential first processing steps. How and whether such mechanisms operate on DNA-protein crosslinks in mitochondria remains to be seen.



http://ift.tt/2fCSmv0

Mitochondrial remodeling in the liver following chronic alcohol feeding to rats

Publication date: Available online 17 November 2016
Source:Free Radical Biology and Medicine
Author(s): Derick Han, Heather S Johnson, Madhuri P Rao, Gary Martin, Harsh Sancheti, Kai H Silkwood, Carl W Decker, Kim Tho Nguyen, Joseph G Casian, Enrique Cadenas, Neil Kaplowitz
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver. In this study, we examined the mitochondrial alterations that occur in rats fed alcohol both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate-, acetaldehyde- and succinate-driven state III respiration, RCR, and expression of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with previous results. IG alcohol feeding, on the other hand, caused a slight increase in glutamate/malate-driven respiration, and significantly increased acetaldehyde-driven respiration in liver mitochondria. IG feeding also caused liver mitochondria to experience a decline in succinate-driven respiration, but these decreases were smaller than those observed with oral alcohol feeding. Surprisingly, oral and IG alcohol feeding to rats increased mitochondrial respiration using other substrates, including glycerol-3-phosphate (which delivers electrons from cytoplasmic NADH to mitochondria) and octanoate (a substrate for beta-oxidation). The enhancement of glycerol-3-phosphate- and octanoate-driven respiration suggests that liver mitochondria remodeled in response to alcohol feeding. In support of this notion, we observed IG alcohol feeding also increased expression of mitochondrial glycerol phosphate dehydrogenase-2 (GPD2), transcription factor A (TFAM), and increased mitochondrial NAD⁺-NADH and NADP⁺-NADPH levels in the liver. Our findings suggest that mitochondrial dysfunction represents an incomplete picture of mitochondrial dynamics that occur in the liver following alcohol feeding. While alcohol feeding causes some mitochondrial dysfunction (i.e. succinate-driven respiration), our work suggests that the major consequence of alcohol feeding is mitochondrial remodeling in the liver as an adaptation. This mitochondrial remodeling may play an important role in the enhanced alcohol metabolism and other adaptations in the liver that develop with alcohol intake.

Graphical abstract

http://ift.tt/2fCPLRz

Ptgr1 expression is regulated by NRF2 in rat hepatocarcinogenesis and promotes cell proliferation and resistance to oxidative stress

Publication date: Available online 18 November 2016
Source:Free Radical Biology and Medicine
Author(s): Ricardo Sánchez-Rodríguez, Julia Esperanza Torres-Mena, Valeria Quintanar-Jurado, Victoria Chagoya-Hazas, Emilio Rojas del Castillo, Luis del Pozo Yauner, Saul Villa-Treviño, Julio Isael. Pérez-Carreón
Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is involved in the catabolism of eicosanoids and lipid peroxidation such as 4-hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in human clinical and experimentally induced samples of hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated and its role in carcinogenesis are not yet known. Here, we studied parameters associated with antioxidant responses and the mechanisms underlying the induction of Ptgr1 expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2 (NRF2). For these experiments, we used two protocols of induced hepatocarcinogenesis in rats. Furthermore, we determined the effect of PTGR1 on cell proliferation and resistance to oxidative stress in cell cultures of the epithelial liver cell line, C9. Ptgr1 was overexpressed during the early phase in altered hepatocyte foci, and this high level of expression was maintained in persistent nodules until tumors developed. Ptgr1 expression was regulated by NRF2, which bound to an antioxidant response element at -653 bp in the rat Ptgr1 gene. The activation of NRF2 induced the activation of an antioxidant response that included effects on proteins such as glutamate-cysteine ligase, catalytic subunit, NAD(P)H dehydrogenase quinone-1 (NQO1) and glutathione-S-transferase-P (GSTP1). These effects may have produced a reduced status that was associated with a high proliferation rate in experimental tumors. Indeed, when Ptgr1 was stably expressed, we observed a reduction in the time required for proliferation and a protective effect against hydrogen peroxide- and 4-HNE-induced cell death. These data were consistent with data showing colocalization between PTGR1 and 4-HNE protein adducts in liver nodules. These findings suggest that Ptgr1 and antioxidant responses act as a metabolic adaptation and could contribute to proliferation and cell-death evasion in liver tumor cells. Furthermore, these data indicate that Ptgr1 could be used to design early diagnostic tools or targeted therapies for HCC.

Graphical abstract

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Ammonia Promotes Endothelial Cell Survival via the Heme Oxygenase-1-Mediated Release of Carbon Monoxide

Publication date: Available online 17 November 2016
Source:Free Radical Biology and Medicine
Author(s): Xiao-Ming Liu, Kelly J. Peyton, William Durante
Although endothelial cells produce substantial quantities of ammonia during cell metabolism, the physiologic role of this gas in these cells is not known. In this study, we investigated if ammonia regulates the expression of heme oxygenase-1 (HO-1), and if this enzyme influences the biological actions of ammonia on endothelial cells. Exogenously administered ammonia, given as ammonium chloride or ammonium hydroxide, or endogenously generated ammonia stimulated HO-1 protein expression in cultured human and murine endothelial cells. Dietary supplementation of ammonia also induced HO-1 protein expression in murine arteries. The increase in HO-1 protein by ammonia in endothelial cells was first detected 4 hours after ammonia exposure and was associated with the induction of HO-1 mRNA, enhanced production of reactive oxygen species (ROS), and increased expression and activity of NF-E2-related factor-2 (Nrf2). Ammonia also activated the HO-1 promoter and this was blocked by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. The induction of HO-1 expression by ammonia was dependent on ROS formation and prevented by N-acetylcysteine or rotenone. Finally, prior treatment of endothelial cells with ammonia inhibited tumor necrosis factor-α -stimulated cell death. However, silencing HO-1 expression abrogated the protective action of ammonia and this was reversed by the administration of carbon monoxide but not bilirubin or iron. In conclusion, this study demonstrates that ammonia stimulates the expression of HO-1 in endothelial cells via the ROS-Nrf2 pathway, and that the induction of HO-1 contributes to the cytoprotective action of ammonia by generating carbon monoxide. Moreover, it identifies ammonia as a potentially important signaling gas in the vasculature that promotes endothelial cell survival.

Graphical abstract

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From POEM to POET: Applications and perspectives for submucosal tunnel endoscopy.

Related Articles

From POEM to POET: Applications and perspectives for submucosal tunnel endoscopy.

Endoscopy. 2016 Nov 17;

Authors: Chiu PW, Inoue H, Rösch T

Abstract
Recent advances in submucosal endoscopy have unlocked a new horizon for potential development in diagnostic and therapeutic endoscopy. Increasing evidence has demonstrated that peroral endoscopic myotomy (POEM) is not only clinically feasible and safe, but also has excellent results in symptomatic relief of achalasia. The success of submucosal endoscopy in performance of tumor resection has confirmed the potential of this new area in diagnostic and therapeutic endoscopy. This article reviews the current applications and evidence, from POEM to peroral endoscopic tunnel resection (POET), while exploring the possible future clinical applications in this field.

PMID: 27855465 [PubMed - as supplied by publisher]

http://ift.tt/2eNvB8d

Challenges in the use of immunotherapy in metastatic melanoma

A 65-year-old man with metastatic melanoma was started on immunotherapy, switched to alternative targeted therapy and developed disseminated intravascular coagulation. This case underscores the complexity of interpreting and managing side effects of novel therapies in cancer care, identification of progression versus pseudoprogression and challenges in sequencing treatments in metastatic melanoma.

http://ift.tt/2g2gcgC

Oral and gastrointestinal symptomatic metastases as initial presentation of lung cancer

Metastasis to the tongue, duodenum or pancreas from primary lung cancer is uncommon. Primary lung cancer presenting with symptoms related to metastases at these sites, at initial presentation is extremely rare. We report a 45-year-old man with disseminated lung malignancy who presented with dyspepsia, melena, symptoms due to anaemia and swelling in the tongue. Oral examination revealed a hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of metastasis from lung primary. CT revealed lung primary with disseminated metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum and intra-abdominal lymph nodes. The patient was treated with palliative chemotherapy. The unusual presentation and diagnostic details are discussed.

http://ift.tt/2fbjsJ1

Bacteraemia due to Parvimonas micra, a commensal pathogen, in a patient with an oesophageal tumour

A man aged 53 years was admitted to our hospital due to general malaise, fever and chills for the past 24 hours. He had a history of chronic alcoholic liver disease. The blood tests showed leucocytosis with neutrophilia, lactic acidosis and acute-phase reactants. The blood cultures were positive for Parvimonas micra, an anaerobic pathogen which is part of the flora of the oral cavity. There was no evidence of abscess formation in either the examination or the imaging tests, but in the work-up that followed, a gastroscopy showed a stenotic oesophageal mass that turned out to be an invasive squamous cell carcinoma.

http://ift.tt/2fblw3D

Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear Entry

Publication date: Available online 17 November 2016
Source:Cell Host & Microbe
Author(s): Gary Z. Wang, Ying Wang, Stephen P. Goff
Chromosomal structure of nuclear DNA is usually maintained by insertion of nucleosomes into preexisting chromatin, both on newly synthesized DNA at replication forks and at sites of DNA damage. But during retrovirus infection, a histone-free DNA copy of the viral genome is synthesized that must be loaded with nucleosomes de novo. Here, we show that core histones are rapidly loaded onto unintegrated Moloney murine leukemia virus DNAs. Loading of nucleosomes requires nuclear entry, but does not require viral DNA integration. The histones associated with unintegrated DNAs become marked by covalent modifications, with a delay relative to the time of core histone loading. Expression from unintegrated DNA can be enhanced by modulation of the histone-modifying machinery. The data show that histone loading onto unintegrated DNAs occurs very rapidly after nuclear entry and does not require prior establishment of an integrated provirus.

Graphical abstract

Teaser

Wang et al. show that histones are rapidly loaded onto newly synthesized retroviral DNAs soon after entry into the nucleus, but before integration into the host genome. Histone marks are added after a delay, and inhibition of histone modifiers enhances transcription from unintegrated viral DNA.


http://ift.tt/2f7pUxh

A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced Activation

Publication date: Available online 17 November 2016
Source:Cell Host & Microbe
Author(s): Jun Zhao, Yi Zeng, Simin Xu, Jie Chen, Guobo Shen, Caiqun Yu, David Knipe, Weiming Yuan, Jian Peng, Wenqing Xu, Chao Zhang, Zanxian Xia, Pinghui Feng
RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA-induced activation. Mass spectrometry analysis identified two asparagine residues in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus blocking its ability to trigger antiviral immune responses and restrict viral replication. Purified full-length UL37 and its carboxyl-terminal fragment were sufficient to deamidate RIG-I in vitro. Uncoupling RIG-I deamidation from HSV-1 infection, by engineering deamidation-resistant RIG-I or introducing deamidase-deficient UL37 into the HSV-1 genome, restored RIG-I activation and antiviral immune signaling. Our work identifies a viral deamidase and extends the paradigm of deamidation-mediated suppression of innate immunity by microbial pathogens.

Graphical abstract

Teaser

Herpes simplex virus 1 (HSV-1) blocks innate immune signaling. Here, Zhao et al. report that the HSV-1 UL37 protein deamidates the RNA sensor RIG-I to prevent RNA-induced activation. Uncoupling RIG-I deamidation from its activation restored RIG-I-dependent antiviral immune response and impaired HSV-1 replication.


http://ift.tt/2f7pTtd

Effectiveness of oxalic acid treatments for the protection of marble surfaces

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): A. Burgos-Cara, E. Ruiz-Agudo, C. Rodriguez-Navarro
Naturally formed rims of calcium oxalates developed on calcareous stones have been recognized as effective protective coatings. Inspired in nature, it has been recently proposed the use of oxalate salts for the protection of stone surfaces via dissolution of the calcitic substrate and the subsequent precipitation of oxalate phases. In contrast, the application of an oxalic acid solution on carbonate stones has been generally avoided due to assumed hazards associated with enhanced substrate dissolution. Nonetheless, it has been reported that coherent oxalate layers and preservation of textural features only occurs at low pH, which could be beneficial from a conservation point of view. Here, the application of oxalic acid treatments on two calcitic and dolomitic Spanish marbles from Macael area has been studied as a means to develop effective oxalate protective coatings. Morphological and compositional analyses show that reacted marble surfaces develop μm-thick calcium or calcium and magnesium oxalate rims on calcitic and dolomitic marble, respectively. The presence of such oxalate layers strongly reduces chemical weathering due to acid dissolution and sulfation, without altering the color of the marble substrates. This protection methodology overcomes the limitations of previous oxalate treatments and may represent a highly efficient conservation methodology.

Graphical abstract

http://ift.tt/2gqefzI

Antimicrobial and wear performance of Cu-Zr-Al metallic glass composites

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Victor M. Villapún, H. Zhang, C. Howden, L. Cheung Chow, F. Esat, P. Pérez, J. Sort, S. Bull, J. Stach, S. González
The antimicrobial and wear behaviour of metallic glass composites corresponding to the Cu50+x(Zr44Al6)50−x system with x=(0, 3 and 6) has been studied. The three compositions consist of crystalline phases embedded in an amorphous matrix and they exhibit crystallinity increase with increasing Cu content, i.e., decrease of the glass-forming ability. The wear resistance also increases with the addition of Cu as indirectly assessed from H/Er and H³/Er² parameters obtained from nanoindentation tests. These results are in agreement with scratch tests since for the alloy with highest Cu content, i.e., Cu56Zr38.7Al5.3, reveals a crack increase, lower pile-up, prone adhesion wear in dry sliding and higher scratch groove volume to pile-up volume. Samples with higher Cu content revealed higher hydrophilicity. Time-kill studies revealed higher reduction in colony-forming units for E. coli (gram-negative) and B. subtilis (gram-positive) after 60min of contact time for the Cu56Zr38.7Al5.3 alloy and all the samples achieved a complete elimination of bacteria in 250min.

Graphical abstract

http://ift.tt/2gqcX7V

Synthesis of tin oxide (SnO & SnO2) micro/nanostructures with novel distribution characteristic and superior photocatalytic performance

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Junxia Wang, Can Lu, Xinchuan Liu, Yongqian Wang, Zhengxin Zhu, Dawei Meng
SnO micro/nanostructures with novel distribution characteristic of concentric annulus were successfully synthesized by electrochemical anodization of tin foils in sodium hydroxide electrolyte. The SnO structures near the central fracture region were uniform and well-defined octahedron-like. The SnO structures away from the fracture region gathered together and presented petal-like and flower-like patterns. The effects of anodizing parameters and annealing temperatures on the structure features of tin oxide micro/nanostructures were systematically investigated. We found that as-anodized SnO micro/nanostructures can be transformed to tetragonal phase SnO2 micro/nanostructures by a thermal annealing process, which still maintained its original structure features as well as distribution characteristic. The optical property and photocatalytic performance of the annealed samples were also analyzed. The high photocatalytic property of the sample annealed at 400°C was attributed to the strong light absorption and efficient interfacial charge separation. Additionally, a synthesis mechanism was discussed to illustrate the evolution process of anodized SnO micro/nanostructures with the distribution characteristic of concentric annulus.

Graphical abstract

http://ift.tt/2gqbFtF

Effect of crystallographic texture on ratcheting response of commercially pure titanium

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Atasi Ghosh, N.P. Gurao
The effect of crystallographic texture on ratcheting behavior of cold rolled and annealed plate of commercially pure titanium has been investigated. Flat fatigue test specimens of two different orientations along rolling and transverse direction have been machined to obtain distinct texture with crystallographic direction close to 〈101¯0〉–〈112¯0〉 and 〈0001〉 ║ loading direction for sample A and B respectively. The microstructure, texture and grain boundary characteristics of tested specimens have been analyzed using electron backscatter diffraction data. The significant anisotropy in strain hardening for monotonic loading is not manifested in anisotropy in ratcheting response and shows only 20% lower fatigue life in orientation B compared to A under same stress cycle condition. The anisotropy in ratcheting response has been attributed to the unique combination of dislocation activity and twin variant selection in orientation A and B. Orientation A with higher Schmid factor for prism slip efficiently partitions the accumulated backstress by activating prism slip and detwinning of thin multiple twin variants which causes slow accumulation of ratcheting strain for higher number of cycle. While in orientation B prism slip is restricted and detwinning is difficult due to formation of thick single variant extension twins that causes its early failure.

Graphical abstract

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Epitaxial formation of cubic and trigonal Ge-Sb-Te thin films with heterogeneous vacancy structures

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Isom Hilmi, Andriy Lotnyk, Jürgen W. Gerlach, Philipp Schumacher, Bernd Rauschenbach
Preparation of epitaxial Ge-Sb-Te (GST) thin films with heterogeneous vacancy structures is of special interest for data storage applications such as non-volatile random access memory. In this work, epitaxial Ge2Sb2Te5 (GST225) thin films grown on Si(111) using pulsed laser deposition technique are reported. Structure analysis utilizing X-ray diffraction and high-resolution aberration-corrected scanning transmission electron microscopy revealed that the as-deposited GST225 films consist of both the cubic (c-GST225) and trigonal (t-GST225) phase. As-grown c-GST225 films exhibit crystalline grains with randomly distributed vacancies (cubic phase I) and with highly-ordered vacancy layers (cubic phase II). The formation of pure epitaxial t-GST225 films with micrometer grain size was achieved by post-annealing of as-grown GST225 films. The GST225 growth is initialized by the formation of a surface passivation Sb/Te layer on the Si(111) substrate surface. The layer is van-der-Waals bonded to the adjacent Te layer of a GST building block. The results of this work shed new insight into the crystal structure of the cubic modifications of the GST225 phase and may promote a better understanding of the switching mechanism of phase change materials as well as they might be beneficial for the future application in multi-level data storage.

Graphical abstract

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Effect of Al-Ti-C master alloy addition on microstructures and mechanical properties of cast eutectic Al-Si-Fe-Cu alloy

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Peng Tang, Wenfang Li, Kang Wang, Jun Du, Xiyong Chen, Yanjun Zhao, Weizhou Li
The microstructure and mechanical properties of cast eutectic Al-Si-Fe-Cu alloy influenced by different additions of Al-Ti-C master alloys (viz. 0, 0.2, 0.6, 1.0 and 2.0wt.%) were investigated. The phases and their morphologies in these alloys were identified by XRD and SEM equipped with EDS. In order to estimate the apparent size of the phases in these alloys, morphological identification technique based on the digital OM image was carried out. The results indicated that the Al-Ti-C could effectively refine the coarse phases. The mean apparent lengths of coarse secondary phases were decreased to a minimum value when the Al-Ti-C addition reached 0.6wt.%. The mechanical properties of the samples with various additions of Al-Ti-C were investigated by tensile and hardness tests. It was found that the UTS, % elongation and HB values were related to the mean perimeters of the phases in these alloys.

Graphical abstract

http://ift.tt/2gqcO4h

Thank you to all Reviewers of “Strahlentherapie und Onkologie” 2016

http://ift.tt/2g50cfz

Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

Abstract

Introduction

The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT).

Method

In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared.

Results

Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5‑year Kaplan–Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5–99.2), EBRT 9 events (81.7%, 95%CI 67.6–90.1), hazard ratio (HR) 0.19 (0.04–0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3–95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5–98.4), EBRT 12 events (69.0%, 49.1–82.4), HR 0.23 (0.06–0.80), log rank p = 0.012.

Conclusion

IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.

http://ift.tt/2fCMotZ

The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances

Publication date: Available online 17 November 2016
Source:Developmental Cell
Author(s): Orsolya Symmons, Leslie Pan, Silvia Remeseiro, Tugce Aktas, Felix Klein, Wolfgang Huber, François Spitz
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression. In contrast, inversions disrupting the TAD altered global folding of the region and prevented regulatory contacts in a distance-dependent manner. Our data indicate that the Shh TAD promotes distance-independent contacts between distant regions that would otherwise interact only sporadically, enabling functional communication between them. In large genomes where genomic distances per se can limit regulatory interactions, this function of TADs could be as essential for gene expression as the formation of insulated neighborhoods.

Graphical abstract

Teaser

Using systematic genomic rearrangements at the Shh locus, Symmons et al. demonstrate that the topologically associating domain overlapping the locus acts as a functional regulatory mold by promoting contacts between elements that would otherwise be too rare to yield a functional outcome due to the dampening effects of large genomic distances.


http://ift.tt/2gn996t

Deciphering Pro-Lymphangiogenic Programs during Mammary Involution and Postpartum Breast Cancer.

Deciphering Pro-Lymphangiogenic Programs during Mammary Involution and Postpartum Breast Cancer.

Front Oncol. 2016;6:227

Authors: Borges VF, Elder AM, Lyons TR

Abstract
Postpartum breast cancers are a highly metastatic subset of young women's breast cancers defined as breast cancers diagnosed in the postpartum period or within 5 years of last child birth. Women diagnosed with postpartum breast cancer are nearly twice as likely to develop metastasis and to die from breast cancer when compared with nulliparous women. Additionally, epidemiological studies utilizing multiple cohorts also suggest that nearly half of all breast cancers in women aged <45 qualify as postpartum cases. Understanding the biology that underlies this increased risk for metastasis and death may lead to identification of targeted interventions that will benefit the large number of young women with breast cancer who fall into this subset. Preclinical mouse models of postpartum breast cancer have revealed that breast tumor cells become more aggressive if they are present during the normal physiologic process of postpartum mammary gland involution in mice. As involution appears to be a period of lymphatic growth and remodeling, and human postpartum breast cancers have high peritumor lymphatic vessel density (LVD) and increased incidence of lymph node metastasis (1, 2), we propose that novel insight into is to be gained through the study of the biological mechanisms driving normal postpartum mammary lymphangiogenesis as well as in the microenvironment of postpartum tumors.

PMID: 27853703 [PubMed - in process]

http://ift.tt/2fbb6RD

Long-term results of hearing preservation cochlear implant surgery in patients with residual low frequency hearing.

Long-term results of hearing preservation cochlear implant surgery in patients with residual low frequency hearing.

Acta Otolaryngol. 2016 Nov 17;:1-6

Authors: Moteki H, Nishio SY, Miyagawa M, Tsukada K, Iwasaki S, Usami SI

Abstract
CONCLUSION: Differences were found between patients with stable hearing and those with progressive hearing loss in the lower frequencies with respect to the rate of progression in the contralateral ear. It is suggested that the electric acoustic stimulation (EAS) can provide improvement in hearing ability over the long-term if residual hearing might be lost to some extent.
OBJECTIVE: To evaluate the long-term threshold changes in the low frequency hearing of the implanted ear as compared with the non-implanted ear, and the hearing abilities with EAS along with the extent of residual hearing.
METHODS: Seventeen individuals were enrolled and received the EAS implant with a 24-mm FLEXeas electrode array. Hearing thresholds and speech perception were measured pre- and post-operatively for 1-5 years. Post-operative hearing preservation (HP) rates were calculated using the preservation numerical scale.
RESULTS: The average linear regression coefficient for the decline in hearing preservation score was -6.9 for the implanted ear and the patients were subsequently categorized into two groups: those with better than average, stable hearing; and those with worse than average, progressive hearing loss. EAS showed better results than electric stimulation alone, in spite of an absence of speech perception with acoustic stimulation.

PMID: 27852135 [PubMed - as supplied by publisher]

http://ift.tt/2faYaLC

Expression of cyclooxygenase-2 has no impact on survival in adenocarcinoma of the esophagogastric junction but is associated with favourable clinicopathologic features.

Expression of cyclooxygenase-2 has no impact on survival in adenocarcinoma of the esophagogastric junction but is associated with favourable clinicopathologic features.

Histol Histopathol. 2016 Nov 17;:11843

Authors: Knief J, Reddemann K, Petrova E, Herhahn T, Wellner U, Thorns C

Abstract
Background COX-2 expression induces carcinogenesis and is thought to be an adverse prognostic factor in gastric carcinomas while the prognostic value of DNA mismatch repair (MMR) is still controversial. Concerning adenocarcinomas of the esophagogastric junction, no comprehensive data regarding either factors are available as of yet. Objective We assessed expression of COX-2, MLH1 and MSH2 in adenocarcinoma of the esophagogastric junction in relation to patients' survival and various clinicopathologic features. Design Immunohistochemical studies (using antibodies against COX-2, MLH1 and MSH2) were performed in a study population of 228 tumours. Follow-up data was available for all patients with a mean follow-up time of 42.8 months. Results 78 (34.2%) tumours were COX-2 negative, 148 (64.9%) showed COX-2 positivity. Assessment of COX-2 expression and clinicopathologic features revealed an inverse correlation with depth of tumour invasion and number of metastatic lymph nodes (p=0,021 and p=0,004, respectively). No correlation with other features could be demonstrated. 62 cases (27.2%) showed loss of DNA repair enzymes MLH1 and/or MSH2. MMR differed significantly between COX-2 positive and negative cases (p=0,028). Kaplan-Meier survival analyses revealed no impact on patients' survival for COX-2 expression or MMR status (p=0.837 and p=0.972, respectively).
CONCLUSIONS: Expression of COX-2 in adenocarcinomas of the esophagogastric junction seems to have no prognostic effect or impact on patients' survival but is associated with favourable clinicopathologic factors. MMR deficiency was more frequent in COX-2 negative tumours, but MMR status had no impact on survival and patients' outcome whatsoever.

PMID: 27854106 [PubMed - as supplied by publisher]

http://ift.tt/2fLCOT4

Role of Low-Level Laser Therapy as an Adjunct to Initial Periodontal Treatment in Type 2 Diabetic Patients: A Split-Mouth, Randomized, Controlled Clinical Trial.

Role of Low-Level Laser Therapy as an Adjunct to Initial Periodontal Treatment in Type 2 Diabetic Patients: A Split-Mouth, Randomized, Controlled Clinical Trial.

Photomed Laser Surg. 2016 Nov 17;

Authors: Demirturk-Gocgun O, Baser U, Aykol-Sahin G, Dinccag N, Issever H, Yalcin F

Abstract
OBJECTIVE: In this split-mouth clinical trial, we evaluated the clinical benefits of low-level laser therapy (LLLT) as an adjunct to nonsurgical periodontal treatment in patients with type 2 diabetes mellitus (DM).
BACKGROUND DATA: The impaired wound healing seen in diabetic patients may affect the results of periodontal treatment and may require an additional approach.
MATERIALS AND METHODS: In total, 22 chronic periodontitis patients with type 2 DM were included. Applying a split-mouth design, two quadrants were treated with only scaling and root planing (SRP) as the control and those in the other two were treated with SRP + LLLT as the test sites in each patient. An 808 nm GaAlAs diode laser was performed in the test sites at the energy density of 4.46 J/cm(2) on days 1, 2, and 7 after SRP. Plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level were measured at baseline and again at 1 and 3 months after treatment. Deep periodontal pockets (PD ≥4 mm) were evaluated separately.
RESULTS: Test sites showed significant improvement in PI and BOP in deep pockets at the 1-month follow-up period (p < 0.001 and <0.001, respectively), whereas no difference was found between the control and the test sites in other periodontal parameters.
CONCLUSIONS: LLLT during periodontal treatment offered minimal short-term additional benefit in deep pocket healing in patients with type 2 DM.

PMID: 27855270 [PubMed - as supplied by publisher]

http://ift.tt/2gq1Trp

Acute Effects of Near Infrared Light Therapy on Brain State in Healthy Subjects as Quantified by qEEG Measures.

Acute Effects of Near Infrared Light Therapy on Brain State in Healthy Subjects as Quantified by qEEG Measures.

Photomed Laser Surg. 2016 Nov 17;

Authors: Grover F, Weston J, Weston M

Abstract
OBJECTIVE: Recent investigation suggests that near infrared (NIR) light may improve symptoms from mild traumatic brain injury. In addition, quantitative electroencephalography (qEEG) has shown measures correlating with concussion: P300, reaction time, and amplitude. The objective of this study was to determine whether NIR light treatment has an acute effect on brain state in healthy patients as measured by EEG.
METHODS: A total of 31 healthy volunteers, between the ages of 14 and 65, underwent qEEG event-related response tests before and after a 20-min NIR light head treatment. The treatment device is composed of 784 NIR GaAIAs LEDs covering 360 cm(2) on the head in a cap covering occipital, left temporal, right temporal frontal, and parietal lobes. The fluence rate was 1 J/cm(2)·min for a power density of 16.67 mW/cm(2). Peak spectral wavelength at steady-state temperature (42.2°C) is 903 nm. The device delivered a total dose of 20 J/cm(2). Two to four months later, 18 subjects returned for a second round of qEEG measurements, with a 20-min rest period in place of the NIR light treatment as a control arm.
RESULTS: Change in reaction time significantly differed between treated and control, with a mean of 23.8 msec improvement compared with controls (p = 0.035). Amplitude increased an average of 0.81 μV in treatment versus 0.22 μV in controls and did not reach significance. However, subanalysis of 14 treated subjects and 8 controls displaying initially low amplitude showed a mean increase in amplitude of 1.83 μV (30%) in treated subjects versus 0 μV in controls (p = 0.08). P300 measures did not show significant differences between groups.
CONCLUSIONS: The data suggest that NIR light may have an acute effect on reaction time and amplitude in certain subject subsets. There were no adverse events registered across the 31 subjects in the treatment group, nor in the 18 evaluable control group subjects.

PMID: 27855264 [PubMed - as supplied by publisher]

http://ift.tt/2g3kRQJ

"English Disease": Historical Notes on Rickets, the Bone-Lung Link and Child Neglect Issues.

"English Disease": Historical Notes on Rickets, the Bone-Lung Link and Child Neglect Issues.

Nutrients. 2016 Nov 15;8(11):

Authors: Zhang M, Shen F, Petryk A, Tang J, Chen X, Sergi C

Abstract
Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region.

PMID: 27854286 [PubMed - in process]

http://ift.tt/2fb4wuu

Beneficial therapeutic effects of vitamin C on recurrent respiratory tract infections in children: preliminary data.

Beneficial therapeutic effects of vitamin C on recurrent respiratory tract infections in children: preliminary data.

Minerva Pediatr. 2016 Nov 17;

Authors: Ferrara P, Ianniello F, Bianchi V, Quintarelli F, Cammerata M, Quattrocchi E, Terranova GM, Miggiano GA, Casale M

Abstract
BACKGROUND: To demonstrate whether supplementation of vitamin C has a beneficial effect in the prevention of recurrent respiratory tract infections (RTIs) in children. Moreover, we evaluate the main risk factors that predispose to the development of this disease.
METHODS: Sixty children have been enrolled in the study and randomized into two groups: the control group (G1 n = 33) and the group at risk of recurrent RTIs (G2 n = 27). To G2 group was administered every day 100% orange juice with the content of vitamin C 70 mg.
RESULTS: Significant reduction in the incidence rate of RTIs (episodes pre-treatment: 182-6.75 episodes/child, after-treatment: 71-2.62 episodes/child, P <0.05), were observed in G2 group.
CONCLUSIONS: The administration of vitamin C had a beneficial effect in our group of children with recurrent RTIs, reducing the number of infective episodes.

PMID: 27854116 [PubMed - as supplied by publisher]

http://ift.tt/2g26Wcx

Smoke-free legislation and child health.

Smoke-free legislation and child health.

NPJ Prim Care Respir Med. 2016 Nov 17;26:16067

Authors: Faber T, Been JV, Reiss IK, Mackenbach JP, Sheikh A

Abstract
In this paper, we aim to present an overview of the scientific literature on the link between smoke-free legislation and early-life health outcomes. Exposure to second-hand smoke is responsible for an estimated 166 ,000 child deaths each year worldwide. To protect people from tobacco smoke, the World Health Organization recommends the implementation of comprehensive smoke-free legislation that prohibits smoking in all public indoor spaces, including workplaces, bars and restaurants. The implementation of such legislation has been found to reduce tobacco smoke exposure, encourage people to quit smoking and improve adult health outcomes. There is an increasing body of evidence that shows that children also experience health benefits after implementation of smoke-free legislation. In addition to protecting children from tobacco smoke in public, the link between smoke-free legislation and improved child health is likely to be mediated via a decline in smoking during pregnancy and reduced exposure in the home environment. Recent studies have found that the implementation of smoke-free legislation is associated with a substantial decrease in the number of perinatal deaths, preterm births and hospital attendance for respiratory tract infections and asthma in children, although such benefits are not found in each study. With over 80% of the world's population currently unprotected by comprehensive smoke-free laws, protecting (unborn) children from the adverse impact of tobacco smoking and SHS exposure holds great potential to benefit public health and should therefore be a key priority for policymakers and health workers alike.

PMID: 27853176 [PubMed - in process]

http://ift.tt/2fb8aUZ

The Potential for Low Pathogenic Avian H7 Influenza A Viruses to Replicate and Cause Disease in a Mammalian Model.

The Potential for Low Pathogenic Avian H7 Influenza A Viruses to Replicate and Cause Disease in a Mammalian Model.

J Virol. 2016 Nov 16;:

Authors: Zanin M, Koçer ZA, Poulson RL, Gabbard JD, Howerth EW, Jones CA, Friedman K, Seiler J, Danner A, Kercher L, McBride R, Paulson JC, Wentworth DE, Krauss S, Tompkins SM, Stallknecht DE, Webster RG

Abstract
H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. Our objective was to assess the disease causing potential of 30 LP H7 viruses isolated from wild avian species in the USA and Canada, using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. Of these, 17 (56.7%) caused 100% mortality and 24 were of similar pathogenicity to A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck-origin were more pathogenic than those of shorebird-origin, as 13 of 18 (72.2%) duck-origin viruses caused 100% mortality whilst 4 of 12 (33.3%) shorebird-origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between these groups. Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids, however, binding to mammalian-type α2,6-linked sialic acids was also detected. These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk.
IMPORTANCE: Low pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. To address this we studied 30 LP avian H7 viruses isolated from wild avian species in the USA and Canada using the DBA/2J mouse model. Surprisingly, the majority of these viruses, 90%, caused mortality in mice without prior mammalian adaptation and 56.7% caused 100% mortality. There was also evidence of spread beyond the respiratory tract and fecal shedding. Therefore, the disease-causing potential of LP avian H7 influenza A viruses in mammals may be underestimated and these viruses therefore pose a potential public health risk.

PMID: 27852855 [PubMed - as supplied by publisher]

http://ift.tt/2g29Huc

A retrospective study of the prevalence of calcium oxalate crystals in veterinary Aspergillus cases.

A retrospective study of the prevalence of calcium oxalate crystals in veterinary Aspergillus cases.

J Vet Diagn Invest. 2016 Nov 15;:

Authors: Payne CL, Dark MJ, Conway JA, Farina LL

Abstract
Fungi in the genus Aspergillus are some of the most common fungal pathogens in veterinary species, primarily affecting the respiratory tract. In both human and veterinary cases, calcium oxalate crystals have been documented in sites of Aspergillus infection. Cases in multiple species (16 birds, 15 horses, 5 dogs, 1 ox, and 1 dolphin) were identified that had either positive cultures for Aspergillus sp., or had conidiophores present that could be identified as belonging to the genus Aspergillus Histologic slides were examined to confirm the presence of oxalate crystals and how often they were identified on the original report. Calcium oxalate deposition was detected in 14 of 38 cases examined, including A. fumigatus, A. versicolor, A. niger, and unspecified Aspergillus sp. infections. Calcium oxalate crystals were identified in 11 of 16 avian cases, as well as in 1 of 1 bovine, 1 of 15 equine, and 1 of 5 canine cases. Crystals were described in only 3 of the 14 original pathology reports of these cases, indicating that identification and reporting of crystals in histologic specimens could be improved. All the tissues with crystals were respiratory tissues with air interfaces, including nasal sinus, trachea, syrinx, lung, and air sac. In cases with crystals identified on H&E-stained sections, crystals were frequently not present or were fewer in number in tissue sections stained with Gomori methenamine silver and periodic acid-Schiff. Routine polarization of slides of fungal infections, especially in the respiratory tract, should be considered to check for calcium oxalate crystals.

PMID: 27852812 [PubMed - as supplied by publisher]

http://ift.tt/2fb73or