Impact of ingredients on the elemental content of baby foods

Publication date: 15 September 2017
Source:Food Chemistry, Volume 231
Author(s): Judith Adikinyi Khamoni, Toby Hamshaw, Philip H.E. Gardiner
The levels of the minerals: Ca, K, Mg, Na, P, and the trace elements: Cd, Cu, Fe, Mn, Ni, Pb, Se, Zn were determined in foods for 4–6, 7+ and 10+ months old babies in a brand available on the UK market. The mineral contents in the vegetarian meals for all the age groups were similar, in contrast, when compared to the non-vegetarian options, the Ca, Na and P levels were higher in the former. Both the trace elements and minerals levels in the 4–6months vegetarian meal were the lowest of all the products analysed. The Cu, Se and Zn levels in all the meals were comparable to those in mature human breast milk. Calculations of the following molar ratios: Zn:Cu, Fe:Zn, and Fe:Mn, pairs of elements that have been shown to interaction antagonistically, were higher in the vegetarian meals.



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Clinical and cross-sectional imaging features of spontaneous pancreatic pseudocyst-portal vein fistula

Publication date: Available online 1 April 2017
Source:Clinical Imaging
Author(s): Francesco Alessandrino, Corinne Strickland, Amirkasra Mojtahed, Steven C. Eberhardt, Koenraad J. Mortele
PurposeTo evaluate clinical and imaging features of pancreatic pseudocyst-portal vein fistula (PPVF).MethodsPatients with evidence of PPVF on CT/MRI were included. Clinical presentation, outcomes, imaging appearance of the portal vein were recorded.Results75% of patients developed portal hypertension, 62% cavernous transformation of the portal vein and 25% portal biliopathy. PPVF presented on CT as fluid-attenuated portal vein, and on MRI as T2-weighted hyperintense fluid-filled portal vein. PPVF was misdiagnosed as portal vein thrombosis in all patients who underwent CT as initial examination.ConclusionsWhenever PPVF is suspected on CT, MRI can be helpful to achieve accurate diagnosis and avoid unnecessary interventions.



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Antipsychotic activity of embelin isolated from Embelia ribes: A preliminary study

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Sharanbasappa Durg, Naveen Kumar B., Ravichandra Vandal, Shivsharan B. Dhadde, B.S. Thippeswamy, Veeresh P. Veerapur, Shrishailappa Badami
BackgroundEmbelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats.MethodsTwo doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine. On the concluding day of pre-treatment, after apomorphine-injection, the rodents were assessed for climbing and stereotyped behaviours according to the published scoring system. Thereafter, neurotransmitters (dopamine, noradrenaline and serotonin) levels were estimated in rodent brains.ResultsEmbelin pre-treatment significantly inhibited apomorphine-induced climbing and stereotyped behaviours in mice and rats, respectively. Further, embelin also statistically reversed elevated levels of dopamine, noradrenaline and serotonin neurotransmitters in the brain of mice and rats. Embelin showed more significant results at high dose (10mg/kg) than low dose (5mg/kg) in both the tested models.ConclusionConsidering the present pharmacological profile of embelin, it is suggested that embelin possesses antipsychotic activity in the treatment of psychotic disorders. However, further research is warranted for evaluating its exact mechanism of action.



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Wip1 inhibition leads to severe pro-inflammatory phenotype in skin in response to chemical irritation

Publication date: Available online 1 April 2017
Source:Journal of Dermatological Science
Author(s): Grigorash B. Bogdan, Uyanik Burhan, Kochetkova Y. Elena, Goloudina R. Anastasia, Demidov N. Oleg




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Real-time detection of organic contamination events in water distribution systems by principal components analysis of ultraviolet spectral data

Abstract

The detection of organic contaminants in water distribution systems is essential to protect public health from potential harmful compounds resulting from accidental spills or intentional releases. Existing methods for detecting organic contaminants are based on quantitative analyses such as chemical testing and gas/liquid chromatography, which are time- and reagent-consuming and involve costly maintenance. This study proposes a novel procedure based on discrete wavelet transform and principal component analysis for detecting organic contamination events from ultraviolet spectral data. Firstly, the spectrum of each observation is transformed using discrete wavelet with a coiflet mother wavelet to capture the abrupt change along the wavelength. Principal component analysis is then employed to approximate the spectra based on capture and fusion features. The significant value of Hotelling's T² statistics is calculated and used to detect outliers. An alarm of contamination event is triggered by sequential Bayesian analysis when the outliers appear continuously in several observations. The effectiveness of the proposed procedure is tested on-line using a pilot-scale setup and experimental data.

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Characteristics and impacts of trace elements in atmospheric deposition at a high-elevation site, southern China

Abstract

To investigate the regional background trace element (TE) level in atmospheric deposition (dry and wet), TEs (Fe, Al, V, Cr, Mn, Ni, Cu, Zn, As, Se, Mo, Cd, Ba, and Pb) in 52 rainwater samples and 73 total suspended particles (TSP) samples collected in Mt. Lushan, Southern China, were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that TEs in wet and dry deposition of the target area were significantly elevated compared within and outside China and the volume weight mean pH of rainwater was 4.43. The relative contributions of wet and dry depositions of TEs vary significantly among elements. The wet deposition fluxes of V, As, Cr, Se, Zn, and Cd exceeded considerably their dry deposition fluxes while dry deposition dominated the removal of pollution elements such as Mo, Cu, Ni, Mn, and Al. The summed dry deposition flux was four times higher than the summed wet deposition flux. Prediction results based on a simple accumulation model found that the content of seven toxic elements (Cr, Ni, Cu, Zn, As, Cd, and Pb) in soils could increase rapidly due to the impact of annual atmospheric deposition, and the increasing amounts of them reached 0.063, 0.012, 0.026, 0.459, 0.076, 0.004, and 0.145 mg kg⁻¹, respectively. In addition, the annual increasing rates ranged from 0.05% (Cr and Ni) to 2.08% (Cd). It was also predicted that atmospheric deposition induced the accumulation of Cr and Cd in surface soils. Cd was the critical element with the greatest potential ecological risk among all the elements in atmospheric deposition.

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Sleep disturbances in obsessive-compulsive disorder: Association with non-response to repetitive transcranial magnetic stimulation (rTMS)

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Lana Donse, Alexander T. Sack, Paul B. Fitzgerald, Martijn Arns
Background Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation strategy for treatment-refractory OCD. However, a substantial group still fails to respond. Sleep disorders, e.g. circadian rhythm sleep disorders (CRSD), are highly prevalent in OCD and might mediate treatment response. The aims of the current study were to compare sleep disturbances between OCD patients and healthy subjects as well as between rTMS responders and non-responders, and most importantly to determine sleep-related predictors of rTMS non-response.Methods 22 OCD patients received at least 10 sessions rTMS combined with psychotherapy. Sleep disturbances were measured using questionnaires and actigraphy. Sleep in patients was compared to healthy subjects. Treatment response was defined as >35% reduction on YBOCS. Treatment response prediction models were based on measures of CRSD and insomnia.Results Sleep disturbances were more prevalent in OCD patients than healthy subjects. The OCD group consisted of 12 responders and 10 non-responders. The CRSD model could accurately predict non-response with 83% sensitivity and 63% specificity, whereas the insomnia model could not.Conclusions CRSD is more prevalent in OCD patients than healthy subjects, specifically in rTMS non-responders. Therefore, CRSD may serve as a biomarker for different subtypes of OCD corresponding with response to specific treatment approaches.



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The Affective Tie That Binds: Examining the Contribution of Positive Emotions and Anxiety to Relationship Formation in Social Anxiety Disorder

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Charles T. Taylor, Sarah Pearlstein, Murray B. Stein
Individuals with social anxiety disorder (SAD) have difficulty forming social relationships. The prevailing clinical perspective is that negative emotions such as anxiety inhibit one's capacity to develop satisfying social connections. However, empirical findings from social psychology and affective neuroscience suggest that positive emotional experiences are fundamental to establishing new social bonds. To reconcile these perspectives, we collected repeated measurements of anxiety, positive emotions (pleasantness), and connectedness over the course of a controlled relationship formation encounter in 56 participants diagnosed with SAD (64% female; Mage=23.3, SD=4.7). Participants experienced both increases in positive emotions and decreases in anxiety throughout the interaction. Change in positive emotions was the most robust predictor of subsequent increases in connectedness, as well as a greater desire to engage one's partner in future social activities, above and beyond reductions in anxiety (medium to large sized effects). Those findings suggest that anxiety-based models alone may not fully explain difficulties in relationship formation in SAD, and underscore the potential value of considering positive emotional experiences in conceptual and treatment models of SAD.



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Harm expectancy violation during exposure therapy for posttraumatic stress disorder

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Rianne A. de Kleine, Lotte Hendriks, Eni S. Becker, Theo G. Broekman, Agnes van Minnen
Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of harm expectancies is a crucial mechanism of action in exposure therapy. But to date, changes in harm expectancies have not been examined during exposure therapy in PTSD. The goal of the current study was to examine harm expectancy violation as mechanism of change in exposure therapy for posttraumatic stress disorder (PTSD). Patients (N=50, 44 female) with a primary diagnosis of chronic PTSD received intensive exposure therapy. Harm expectancies, harm experiences and subjective units of distress (SUDs) were assessed at each imaginal exposure session, and PTSD symptoms were assessed pre- and posttreatment with the Clinician Administered PTSD Scale (CAPS). Results showed that harm expectancies were violated within and strongly declined in-between exposure therapy sessions. However, expectancy violation was not related to PTSD symptom change. Fear habituation measures were moderately related to PTSD symptom reductions. In line with theory, exposure therapy promotes expectancy violation in PTSD patients, but this is not related to exposure therapy outcome. More work is warranted to investigate mechanisms of change during exposure therapy in PTSD.



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ACKNOWLEDGEMENT

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Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (<span style="font-style:italic;">Sert</span>^−/−) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as <span style="font-style:italic;">Sert</span>^−/− rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.</span>

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Different Effects of Sleep Deprivation and Torpor on EEG Slow-Wave Characteristics in Djungarian Hamsters

<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been shown previously in Djungarian hamsters that the initial electroencephalography (EEG) slow-wave activity (power in the 0.5–4.0 Hz band; SWA) in non-rapid eye movement (NREM) sleep following an episode of daily torpor is consistently enhanced, similar to the SWA increase after sleep deprivation (SD). However, it is unknown whether the network mechanisms underlying the SWA increase after torpor and SD are similar. EEG slow waves recorded in the neocortex during sleep reflect synchronized transitions between periods of activity and silence among large neuronal populations. We therefore set out to investigate characteristics of individual cortical EEG slow waves recorded during NREM sleep after 4 h SD and during sleep after emergence from an episode of daily torpor in adult male Djungarian hamsters. We found that during the first hour after both SD and torpor, the SWA increase was associated with an increase in slow-wave incidence and amplitude. However, the slopes of single slow waves during NREM sleep were steeper in the first hour after SD but not after torpor, and, in contrast to sleep after SD, the magnitude of change in slopes after torpor was unrelated to the changes in SWA. Furthermore, slow-wave slopes decreased progressively within the first 2 h after SD, while a progressive increase in slow-wave slopes was apparent during the first 2 h after torpor. The data suggest that prolonged waking and torpor have different effects on cortical network activity underlying slow-wave characteristics, while resulting in a similar homeostatic sleep response of SWA. We suggest that sleep plays an important role in network homeostasis after both waking and torpor, consistent with a recovery function for both states.</span>

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Positive and Negative Somatotopic BOLD Responses in Contralateral Versus Ipsilateral Penfield Homunculus

<span class="paragraphSection"><div class="boxTitle">Abstract</div>One of the basic properties of sensory cortices is their topographical organization. Most imaging studies explored this organization using the positive blood oxygenation level-dependent (BOLD) signal. Here, we studied the topographical organization of both positive and negative BOLD in contralateral and ipsilateral primary somatosensory cortex (S1). Using phase-locking mapping methods, we verified the topographical organization of contralateral S1, and further showed that different body segments elicit pronounced negative BOLD responses in both hemispheres. In the contralateral hemisphere, we found a sharpening mechanism in which stimulation of a given body segment triggered a gradient of activation with a significant deactivation in more remote areas. In the ipsilateral cortex, deactivation was not only located in the homolog area of the stimulated parts but rather was widespread across many parts of S1. Additionally, analysis of resting-state functional magnetic resonance imaging signal showed a gradient of connectivity to the neighboring contralateral body parts as well as to the ipsilateral homologous area for each body part. Taken together, our results indicate a complex pattern of baseline and activity-dependent responses in the contralateral and ipsilateral sides. Both primary sensory areas were characterized by unique negative BOLD responses, suggesting that they are an important component in topographic organization of sensory cortices.</span>

http://ift.tt/2oLUSAt

ADAM10-Initiated Release of Notch Intracellular Domain Regulates Microtubule Stability and Radial Migration of Cortical Neurons

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Proper neuronal migration is orchestrated by combined membrane signal paradigms, whereas the role and mechanism of regulated intramembrane proteolysis (RIP) remain to be illustrated. We show here that the disintegrin and metalloprotease-domain containing protein 10 (ADAM10) regulates cortical neurons migration by initiating the RIP of Notch. We found that Notch intracellular domain (NICD) significantly rescued the migration defect of ADAM10-deficient neurons. Moreover, ADAM10 deficiency led to reduced neuronal motility and disrupted microtubule (MT) structure, which were associated with downregulated expression of acetylated tubulin and MT-associated proteins. Specifically, the NICD/RBPJ complex bound directly to the promoter, and regulated the neuronal expression level of doublecortin (DCX), a modulator of the MT cytoskeleton. Functionally, DCX overexpression largely restored neuron motility and reversed migration defect caused by ADAM10 knockout. Taken together, these findings demonstrate the direct requirement of ADAM10 in cortical radial migration and reveal the underlying mechanism by linking ADAM10-initiated RIP of Notch to the regulation of MT cytoskeleton through transcriptional control of <span style="font-style:italic;">Dcx</span> expression.</span>

http://ift.tt/2ooiRte

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3–CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca²⁺ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning.</span>

http://ift.tt/2oLXFcM

In Vivo Evidence of Reduced Integrity of the Gray–White Matter Boundary in Autism Spectrum Disorder

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atypical cortical organization and reduced integrity of the gray–white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray–white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, <span style="font-style:italic;">P</span> < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray–white matter interface, which indicates a less distinct gray–white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray–white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies.</span>

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Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.</span>

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Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 and Ldb2 exhibit dynamic and inversely correlated expression patterns during cerebral cortical development. <span style="font-style:italic;">Ldb1</span>-deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of <span style="font-style:italic;">Lhx</span> mutants. <span style="font-style:italic;">Ldb2</span>-deficient brains, on the other hand, exhibit striking phenotypes affecting layer 5 pyramidal neurons: Immature neurons have an impaired capacity to segregate into mature callosal and subcerebral projection neurons. The analysis of <span style="font-style:italic;">Ldb2</span> single-mutant mice reveals a compensatory role of <span style="font-style:italic;">Ldb1</span> for <span style="font-style:italic;">Ldb2</span> during corticospinal motor neuron (CSMN) differentiation. Animals lacking both <span style="font-style:italic;">Ldb1</span> and <span style="font-style:italic;">Ldb2</span> uncover the requirement for <span style="font-style:italic;">Ldb2</span> during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract.</span>

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Hippocampus and Prefrontal Cortex Predict Distinct Timescales of Activation in the Human Ventral Tegmental Area

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The mesolimbic dopamine system contributes to a remarkable variety of behaviors at multiple timescales. Midbrain neurons have fast and slow signaling components, and specific afferent systems, such as the hippocampus (HPC) and prefrontal cortex (PFC), have been demonstrated to drive these components in anesthetized animals. Whether these interactions exist during behavior, however, is unknown. To address this question, we developed a novel analysis of human functional magnetic resonance imaging data that fits models of network excitation and inhibition on ventral tegmental area (VTA) activation. We show that specific afferent systems predict distinct temporal components of midbrain VTA signal. We found that PFC, but not HPC, positively predicted transient, event-evoked VTA activation. In contrast, HPC, but not PFC, positively predicted slow shifts in VTA baseline variability. Thus, unique functional contributions of afferent systems to VTA physiology are detectable at the network level in behaving humans. The findings support models of dopamine function in which dissociable neural circuits support different aspects of motivated behavior via active regulation of tonic and phasic signals.</span>

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Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Loss-of-function (LOF) mutations in <span style="font-style:italic;">CC2D1A</span> cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in <span style="font-style:italic;">Cc2d1a</span>-deficient mice. To overcome this challenge, we generated a floxed <span style="font-style:italic;">Cc2d1a</span> allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the <span style="font-style:italic;">Nestin</span> promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (<span style="font-style:italic;">CamKIIa</span>) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human <span style="font-style:italic;">CC2D1A</span> mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders.</span>

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NKCC1-Mediated GABAergic Signaling Promotes Postnatal Cell Death in Neocortical Cajal–Retzius Cells

<span class="paragraphSection"><div class="boxTitle">Abstract</div>During early development, a substantial proportion of central neurons undergoes programmed cell death. This activity-dependent process is essential for the proper structural and functional development of the brain. To uncover cell type-specific differences in the regulation of neuronal survival versus apoptosis, we studied activity-regulated cell death in Cajal–Retzius neurons (CRNs) and the overall neuronal population in the developing mouse cerebral cortex. CRNs in the upper neocortical layer represent an early-born neuronal population, which is important for cortical development and largely disappears by apoptosis during neonatal stages. In contrast to the overall neuronal population, activity blockade with tetrodotoxin improved survival of CRNs in culture. Activation of GABA_A receptors also blocked spontaneous activity and caused overall cell death including apoptosis of CRNs. Blockade of the Na–K–Cl transporter NKCC1 in vitro or its genetic deletion in vivo rescued CRNs from apoptosis. This effect was mediated by blockade of the p75^NTR receptor signaling pathway. In summary, we discovered a novel developmental death pathway mediated by NKCC1, via GABA_A receptor-mediated membrane depolarization and p75^NTR signaling in CRNs. This pathway controls apoptosis of CRNs and may be critically involved in neurodevelopmental disorders such as autism and schizophrenia.</span>

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Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of <span style="font-style:italic;">COUP-TFI</span> mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function.</span>

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Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect.</span>

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cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ∼30 s. These intermittent oscillations i) depended on type 2 inositol 1,4,5-trisphosphate receptors; ii) consisted of a complex reverberatory interaction between the soma and processes of individual astrocytes; iii) did not synchronize with those of other astrocytes; iv) did not require neuronal firing; v) were modulated through cAMP-protein kinase A signaling; vi) were facilitated under pathological conditions, such as energy deprivation and epileptiform hyperexcitation; and vii) were associated with enhanced hypertrophy in astrocytic processes, an early hallmark of reactive gliosis, which is observed in ischemia and epilepsy. Therefore, calcium oscillations appear to be associated with a pathological state in astrocytes.</span>

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Regulation of Cognitive Processing by Hippocampal Cholinergic Tone

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone in genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), a protein required for acetylcholine release. We measured long-term potentiation of Schaffer collateral-CA1 synapses in vivo and assessed information processing by using a mouse touchscreen version of paired associates learning task (PAL). Acquisition of information in the mouse PAL task correlated to levels of hippocampal VAChT, suggesting a critical role for cholinergic tone. Accordingly, synaptic plasticity in the hippocampus in vivo was disturbed, but not completely abolished, by decreased hippocampal cholinergic signaling. Disrupted forebrain cholinergic signaling also affected working memory, a result reproduced by selectively decreasing VAChT in the hippocampus. In contrast, spatial memory was relatively preserved, whereas reversal spatial memory was sensitive to decreased hippocampal cholinergic signaling. This work provides a refined roadmap of how synaptically secreted acetylcholine influences distinct behaviors and suggests that distinct forms of cognitive processing may be regulated in different ways by cholinergic activity.</span>

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Direct Recordings from Human Anterior Insula Reveal its Leading Role within the Error-Monitoring Network

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error-monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop-signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.</span>

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Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin-associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real-time RT–qPCR. In addition, we found that the density of myelin basic protein mRNA-expressing oligodendrocytes and of 2′,3′-cyclic nucleotide 3′-phosphodiesterase-positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high-resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.</span>

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Asc-1 Transporter Regulation of Synaptic Activity via the Tonic Release of d -Serine in the Forebrain

<span class="paragraphSection"><div class="boxTitle">Abstract</div><span style="text-transform:lowercase;font-variant:small-caps;">d</span>-Serine is a co-agonist of NMDA receptors (NMDARs) whose activity is potentially regulated by Asc-1 (SLC7A10), a transporter that displays high affinity for <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine and glycine. Asc-1 operates as a facilitative transporter and as an antiporter, though the preferred direction of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine transport is uncertain. We developed a selective Asc-1 blocker, Lu AE00527, that blocks <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine release mediated by all the transport modes of Asc-1 in primary cultures and neocortical slices. Furthermore, <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine release is reduced in slices from Asc-1 knockout (KO) mice, indicating that <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine efflux is the preferred direction of Asc-1. The selectivity of Lu AE00527 is assured by the lack of effect on slices from Asc-1-KO mice, and the lack of interaction with the co-agonist site of NMDARs. Moreover, in vivo injection of Lu AE00527 in P-glycoprotein-deficient mice recapitulates a hyperekplexia-like phenotype similar to that in Asc-1-KO mice. In slices, Lu AE00527 decreases the long-term potentiation at the Schaffer collateral-CA1 synapses, but does not affect the long-term depression. Lu AE00527 blocks NMDAR synaptic potentials when typical Asc-1 extracellular substrates are present, but it does not affect AMPAR transmission. Our data demonstrate that Asc-1 mediates tonic co-agonist release, which is required for optimal NMDAR activation and synaptic plasticity.</span>

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Common Neural Representations for Visually Guided Reorientation and Spatial Imagery

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Spatial knowledge about an environment can be cued from memory by perception of a visual scene during active navigation or by imagination of the relationships between nonvisible landmarks, such as when providing directions. It is not known whether these different ways of accessing spatial knowledge elicit the same representations in the brain. To address this issue, we scanned participants with fMRI, while they performed a judgment of relative direction (JRD) task that required them to retrieve real-world spatial relationships in response to either pictorial or verbal cues. Multivoxel pattern analyses revealed several brain regions that exhibited representations that were independent of the cues to access spatial memory. Specifically, entorhinal cortex in the medial temporal lobe and the retrosplenial complex (RSC) in the medial parietal lobe coded for the heading assumed on a particular trial, whereas the parahippocampal place area (PPA) contained information about the starting location of the JRD. These results demonstrate the existence of spatial representations in RSC, ERC, and PPA that are common to visually guided navigation and spatial imagery.</span>

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Social attention and autism symptoms in high functioning women with autism spectrum disorders

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Mieke P. Ketelaars, Anne In't Velt, Audrey Mol, Hanna Swaab, Fenne Bodrij, Sophie van Rijn
BackgroundResearch has suggested a different, less visible, clinical manifestation of Autism Spectrum Disorders (ASD) in females. There is, however, limited research into possible underlying mechanisms explaining the female phenotype.AimsThis study investigates social attention in females with ASD.Methods and procedures26 women diagnosed with ASD and 26 typical female controls were shown three video clips containing intense emotions. Social attention was assessed by measuring eye fixation patterns during the video clips. Autism symptoms were assessed using the informant reported Social Responsiveness Scale (SRS).Outcome and resultsResults show normal time to first fixation to the face, but lower fixation duration to the face in women with ASD. Analyzing the visual patterns further, there were similar impairments in fixation to mouth, eyes and other facial areas. Relating social attention to autism symptoms revealed several significant correlations within the ASD group.Conclusions and implicationsWomen with ASD show abnormalities in social attention and these abnormalities are related to level of autism symptoms. In contrast to other studies which investigate male dominated ASD samples, a hyperfocus to the mouth area could not be found.



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Masters et al. Respond

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Correction of Selection Bias in Survey Data: Is the Statistical Cure Worse Than the Bias?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In previous articles in the <span style="font-style:italic;">American Journal of Epidemiology</span> (<span style="font-style:italic;">Am J Epidemiol</span>. 2013;177(5):431–442) and <span style="font-style:italic;">American Journal of Public Health</span> (<span style="font-style:italic;">Am J Public Health</span>. 2013;103(10):1895–1901), Masters et al. reported age-specific hazard ratios for the contrasts in mortality rates between obesity categories. They corrected the observed hazard ratios for selection bias caused by what they postulated was the nonrepresentativeness of the participants in the National Health Interview Study that increased with age, obesity, and ill health. However, it is possible that their regression approach to remove the alleged bias has not produced, and in general cannot produce, sensible hazard ratio estimates. First, one must consider how many nonparticipants there might have been in each category of obesity and of age at entry and how much higher the mortality rates would have to be in nonparticipants than in participants in these same categories. What plausible set of numerical values would convert the ("biased") decreasing-with-age hazard ratios seen in the data into the ("unbiased") increasing-with-age ratios that they computed? Can these values be encapsulated in (and can sensible values be recovered from) 1 additional internal variable in a regression model? Second, one must examine the age pattern of the hazard ratios that have been adjusted for selection. Without the correction, the hazard ratios are attenuated with increasing age. With it, the hazard ratios at older ages are considerably higher, but those at younger ages are well below 1. Third, one must test whether the regression approach suggested by Masters et al. would correct the nonrepresentativeness that increased with age and ill health that I introduced into real and hypothetical data sets. I found that the approach did not recover the hazard ratio patterns present in the unselected data sets: The corrections overshot the target at older ages and undershot it at lower ages.</span>

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Editorial: Note About Inaccurate Results Published in the American Journal of Epidemiology and the American Journal of Public Health

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Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The ability to classify people according to their underlying genetic susceptibility to a disease is increasing with new knowledge, better family data, and more sophisticated risk prediction models, allowing for more effective prevention and screening. To do so, however, we need to know whether risk associations are the same for people with different genetic susceptibilities. To illustrate one way to estimate such gene-environment interactions, we used prospective data from 3 Australian family cancer cohort studies, 2 enriched for familial risk of breast cancer. There were 288 incident breast cancers in 9,126 participants from 3,222 families. We used Cox proportional hazards models to investigate whether associations of breast cancer with body mass index (BMI; weight (kg)/height (m)²) at age 18–21 years, BMI at baseline, and change in BMI differed according to genetic risk based on lifetime breast cancer risk from birth, as estimated by BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) software, adjusted for age at baseline data collection. Although no interactions were statistically significant, we have demonstrated the power with which gene-environment interactions can be investigated using a cohort enriched for persons with increased genetic risk and a continuous measure of genetic risk based on family history.</span>

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Assessment of Confounders in Comparative Effectiveness Studies From Secondary Databases

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Secondary clinical databases are an important and growing source of data for comparative effectiveness research (CER) studies. However, measurement of confounders, such as biomarker values or patient-reported health status, in secondary clinical databases may not align with the initiation of a new treatment. In many published CER analyses of registry data, investigators assessed confounders based on the first questionnaire in which the new exposure was recorded. However, it is known that adjustment for confounders measured after the start of exposure can lead to biased treatment effect estimates. In the present study, we conducted simulations to compare assessment strategies for a dynamic clinical confounder in a registry-based comparative effectiveness study of 2 therapies. As expected, we found that adjustment for the confounder value at the time of the first questionnaire after the start of exposure creates a biased estimate the total effect of exposure choice on outcome when the confounder mediates part of the effect. However, adjustment for the prior value can also be badly biased when measured long before exposure initiation. Thus, investigators should carefully consider the timing of confounder measurements relative to exposure initiation and the rate of change in the confounder in order to choose the most relevant measure for each patient.</span>

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RE: “AGE AND SEX DIFFERENCES IN BODY MASS INDEX AS A PREDICTOR OF HIP FRACTURE: A NOREPOS STUDY”

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THE AUTHORS REPLY

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Mode of Delivery and Asthma at School Age in 9 European Birth Cohorts

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5–9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohort-specific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.</span>

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Chronic Noncommunicable Diseases in 6 Low- and Middle-Income Countries: Findings From Wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (SAGE)

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In this paper, we examine patterns of self-reported diagnosis of noncommunicable diseases (NCDs) and prevalences of algorithm/measured test-based, undiagnosed, and untreated NCDs in China, Ghana, India, Mexico, Russia, and South Africa. Nationally representative samples of older adults aged ≥50 years were analyzed from wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (2007–2010; <span style="font-style:italic;">n</span> = 34,149). Analyses focused on 6 conditions: angina, arthritis, asthma, chronic lung disease, depression, and hypertension. Outcomes for these NCDs were: 1) self-reported disease, 2) algorithm/measured test-based disease, 3) undiagnosed disease, and 4) untreated disease. Algorithm/measured test-based prevalence of NCDs was much higher than self-reported prevalence in all 6 countries, indicating underestimation of NCD prevalence in low- and middle-income countries. Undiagnosed prevalence of NCDs was highest for hypertension, ranging from 19.7% (95% confidence interval (CI): 18.1, 21.3) in India to 49.6% (95% CI: 46.2, 53.0) in South Africa. The proportion untreated among all diseases was highest for depression, ranging from 69.5% (95% CI: 57.1, 81.9) in South Africa to 93.2% (95% CI: 90.1, 95.7) in India. Higher levels of education and wealth significantly reduced the odds of an undiagnosed condition and untreated morbidity. A high prevalence of undiagnosed NCDs and an even higher proportion of untreated NCDs highlights the inadequacies in diagnosis and management of NCDs in local health-care systems.</span>

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Interactions Between Genome-Wide Significant Genetic Variants and Circulating Concentrations of 25-Hydroxyvitamin D in Relation to Prostate Cancer Risk in the National Cancer Institute BPC3

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls—from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP–prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (<span style="font-style:italic;">P</span> ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.</span>

http://ift.tt/2oLMK31

Conducting Privacy-Preserving Multivariable Propensity Score Analysis When Patient Covariate Information Is Stored in Separate Locations

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Distributed networks of health-care data sources are increasingly being utilized to conduct pharmacoepidemiologic database studies. Such networks may contain data that are not physically pooled but instead are distributed horizontally (separate patients within each data source) or vertically (separate measures within each data source) in order to preserve patient privacy. While multivariable methods for the analysis of horizontally distributed data are frequently employed, few practical approaches have been put forth to deal with vertically distributed health-care databases. In this paper, we propose 2 propensity score–based approaches to vertically distributed data analysis and test their performance using 5 example studies. We found that these approaches produced point estimates close to what could be achieved without partitioning. We further found a performance benefit (i.e., lower mean squared error) for sequentially passing a propensity score through each data domain (called the "sequential approach") as compared with fitting separate domain-specific propensity scores (called the "parallel approach"). These results were validated in a small simulation study. This proof-of-concept study suggests a new multivariable analysis approach to vertically distributed health-care databases that is practical, preserves patient privacy, and warrants further investigation for use in clinical research applications that rely on health-care databases.</span>

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Invited Commentary: Foreclosures and Health in a Neighborhood Context

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Recent systematic reviews link foreclosure to worse health at both the individual and population levels. In this issue of the <span style="font-style:italic;">Journal</span>, Downing et al. (<span style="font-style:italic;">Am J Epidemiol</span>. 2017;185(6):429–435) add to what is known about foreclosure and health by examining annual measures of glycemic control in relation to local foreclosure activity. They provided evidence that between 2007 and 2010, glycemic control was not associated with rates of completed foreclosure among a continuously insured managed-care population of persons with type 2 diabetes living in 9 California counties. In this commentary, I consider 5 possible interpretations of the null results: 1) foreclosures do not affect health in general, 2) glycated hemoglobin is insensitive to local foreclosure activity, 3) the presence of real estate owned foreclosures (rather than the competed foreclosure rate) affects health, 4) an integrated health-care delivery system buffers patients from the effects of the foreclosure crisis, and 5) community conditions and responses to the foreclosure crisis buffer patients from the effects of the foreclosure crisis. I close by arguing that research on the contextual effects of foreclosure on health should continue despite the ongoing recovery of the housing market.</span>

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Beyond the Great Recession: Was the Foreclosure Crisis Harmful to the Health of Individuals With Diabetes?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The housing foreclosure crisis was harmful to the financial well-being of many households. In the present study, we investigated the health effects of the housing foreclosure crisis on glycemic control within a population of patients with diabetes. We hypothesized that an increase in the neighborhood foreclosure rate could worsen glycemic control by activating stressors such as higher neighborhood crime, lower housing prices, and erosion of neighborhood social cohesion. To test this, we linked public foreclosure records at the census-block level with clinical records from 2006 to 2009 of patients with diabetes. We specified individual fixed-effects models and controlled for individual time-invariant confounders and area-level time-varying confounders, including housing prices and unemployment rate, to estimate the effect of the foreclosure rate per census-block group on glycated hemoglobin. We found no statistically significant relationship between changes in the neighborhood foreclosure rate per block group in the prior year and changes in glycated hemoglobin. There is no evidence that increased foreclosure rates worsened glycemic control in this continuously insured population with diabetes. More research is needed to inform our knowledge of the role of insurance and health-care delivery systems in protecting the health of diabetic patients during times of economic stress.</span>

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Downing et al. Respond to “Foreclosures and Health in a Neighborhood Context”

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Diet-Induced Overweight and Obesity and Periodontitis Risk: An Application of the Parametric G-Formula in the 1982 Pelotas Birth Cohort

<span class="paragraphSection"><div class="boxTitle">Abstract</div>We aimed to estimate hypothetical effects of habits (smoking, alcohol consumption, and fat and carbohydrates consumption) combined with diet-induced overweight/obesity on the risk of periodontitis. The risk of any periodontitis, moderate/severe periodontitis, and the combination of bleeding on probing (BOP) and clinical attachment loss (CAL) was estimated using the parametric g-formula in adults aged 31 years from the 1982 Pelotas Birth Cohort in Brazil. Individuals in this cohort have been followed since birth. Hypothetical conditions were set independently for each risk factor and in combination for the entire population. A total of 539 participants had oral examinations in 2013. The cumulative 31-year risk under no intervention was 33.3% for any periodontitis, 14.3%, for moderate/severe periodontitis, and 14.7%, for BOP and CAL. According to our statistical approach, diet-induced overweight/obesity increased the risk of all outcomes: 11% (overweight) and 22% (obesity) higher risk of periodontitis; 12% (overweight) and 27% (obesity) higher risk of moderate/severe periodontitis; 21% (overweight) and 57% (obesity) higher risk of CAL and BOP. When overweight/obesity was combined with other unhealthy habits, the risk was even greater. Our findings suggest that the combination of diet-induced obesity with other risk factors may increase the risk of periodontitis. Further research in the field is required to corroborate our study.</span>

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Observed and Expected Mortality in Cohort Studies

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Epidemiologists often compare the observed number of deaths in a cohort with the expected number of deaths, obtained by multiplying person-time accrued in the cohort by mortality rates for a reference population (ideally, a reference that represents the mortality rate in the cohort in the absence of exposure). However, if exposure is hazardous (or salutary), this calculation will not consistently estimate the number of deaths expected in the absence of exposure because exposure will have affected the distribution of person-time observed in the study cohort. While problems with interpretation of this standard calculation of expected counts were discussed more than 2 decades ago, these discussions had little impact on epidemiologic practice. The logic of counterfactuals may help clarify this topic as we revisit these issues. In this paper, we describe a simple way to consistently estimate the expected number of deaths in such settings, and we illustrate the approach using data from a cohort study of mortality among underground miners.</span>

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Toward a Framework for Benefit-Risk Assessment in Diagnostic Imaging

Publication date: Available online 31 March 2017
Source:Academic Radiology
Author(s): Maria Agapova, Brian W. Bresnahan, Ken F. Linnau, Louis P. Garrison, Mitchell Higashi, Larry Kessler, Beth Devine
Rationale and ObjectivesDiagnostic imaging has many effects and there is no common definition of value in diagnostic radiology. As benefit-risk trade-offs are rarely made explicit, it is not clear which framework is used in clinical guideline development. We describe initial steps toward the creation of a benefit-risk framework for diagnostic radiology.Materials and MethodsWe performed a literature search and an online survey of physicians to identify and collect benefit-risk criteria (BRC) relevant to diagnostic imaging tests. We operationalized a process for selection of BRC with the use of four clinical use case scenarios that vary by diagnostic alternatives and clinical indication. Respondent BRC selections were compared across clinical scenarios and between radiologists and nonradiologists.ResultsThirty-six BRC were identified and organized into three domains: (1) those that account for differences attributable only to the test or device (n = 17); (2) those that account for clinical management and provider experiences (n = 12); and (3) those that capture patient experience (n = 7). Forty-eight survey participants selected 22 criteria from the initial list in the survey (9–11 per case). Engaging ordering physicians increased the number of criteria selected in each of the four clinical scenarios presented. We developed a process for standardizing selection of BRC in guideline development.ConclusionThese results suggest that a process relying on elements of comparative effectiveness and the use of standardized BRC may ensure consistent examination of differences among alternatives by way of making explicit implicit trade-offs that otherwise enter the decision-making space and detract from consistency and transparency. These findings also highlight the need for multidisciplinary teams that include input from ordering physicians.



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The Management of Esophagogastric Cancers Enters a New Era

Publication date: Available online 31 March 2017
Source:Hematology/Oncology Clinics of North America
Author(s): Manish A. Shah




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Specific Recruitment of Circulating Angiogenic Cells Using Biomaterials as Filters

Publication date: Available online 1 April 2017
Source:Acta Biomaterialia
Author(s): Matthew Parlato, James Molenda, William L. Murphy
Endogenous recruitment of circulating angiogenic cells (CACs) is an emerging strategy to induce angiogenesis within a defect site, and multiple recent strategies have deployed soluble protein releasing biomaterials for this purpose. However, the way in which the design of biomaterials affects CAC recruitment and invasion are poorly understood. Here we used an enhanced-throughput cell invasion assay to systematically examine the effects of biomaterial design on CAC recruitment. The screens co-optimized hydrogel presentation of a stromal-derived factor-1α (SDF-1α) gradient, hydrogel degradability, and hydrogel stiffness for maximal CAC invasion. We also examined the specificity of this invasion by assessing dermal fibroblast, mesenchymal stem cell, and lymphocyte invasion individually and in co-culture with CACs to identify hydrogels specific to CAC invasion. These screens suggested a subset of MMP-degradable hydrogels presenting a specific range of SDF-1α gradient slopes that induced specific invasion of CACs, and we posit that the design parameters of this subset of hydrogels may serve as instructive templates for the future design of biomaterials to specifically recruit CACs. We also posit that this design concept may be applied more broadly in that it may be possible to utilize these specific subsets of biomaterials as "filters" to control which types of cell populations invade into and populate the biomaterial.Statement of SignificanceThe recruitment of specific cell types for cell-based therapies in vivo is of great interest to the regenerative medicine community. Circulating angiogenic cells (CACs), CD133+ cells derived from the blood stream, are of particular interest for induction of angiogenesis in ischemic tissues, and recent studies utilizing soluble-factor releasing biomaterials to recruit these cells in vivo show great promise. However, these studies are largely "proof of concept" and are not systematic in nature. Thus, little is currently known about how biomaterial design affects the recruitment of CACs.In the present work, we use a high throughput cell invasion screening platform to systematically examine the effects of biomaterial design on circulating angiogenic cell (CAC) recruitment, and we successfully screened 263 conditions at 3 replicates each. Our results identify a particular subset of conditions that robustly recruit CACs. Additionally, we found that these conditions also specifically recruited CACs and excluded the other tested cells types of dermal fibroblasts, mesenchymal stem cells, and lymphocytes. This suggests an intriguing new role for biomaterials as "filters" to control the types of cells that invade and populate that biomaterial.

Graphical abstract

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Choose Your Cell Model Wisely: The In Vitro Nanoneurotoxicity of Differentially Coated Iron Oxide Nanoparticles for Neural Cell Labeling

Publication date: Available online 1 April 2017
Source:Acta Biomaterialia
Author(s): Freya Joris, Daniel Valdepérez, Beatriz Pelaz, Tianqiang Wang, Shareen H. Doak, Bella B. Manshian, Stefaan J. Soenen, Wolfgang J. Parak, Stefaan C. De Smedt, Koen Raemdonck
Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models.Statement of significanceInorganic nanoparticle (NP) optimization is chiefly performed in vitro. For the optimization of iron oxide (IO)NPs for neural stem cell labeling in the context of regenerative medicine human or rodent neural stem cells, immortalized or cancer cell lines are applied. However, the use of certain cell models can be questioned as they phenotypically differ from the target cell. The impact of the neural cell model on nanosafety remains relatively unexplored. Here we evaluated cell homeostasis upon exposure to PMA- and DMSA-coated IONPs. Of note, the DMSA-IONPs outperformed the PMA-IONPs in each cell type. However, distinct cell type-specific effects were witnessed indicating that nanosafety should be evaluated in a human cell model that represents the target cell as closely as possible.

Graphical abstract

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Optical imaging and anticancer chemotherapy through carbon dot created hollow mesoporous silica nanoparticles

Publication date: Available online 1 April 2017
Source:Acta Biomaterialia
Author(s): Min Sil Kang, Rajendra K. Singh, Tae-Hyun Kim, Joong-Hyun Kim, Kapil D. Patel, Hae-Won Kim
Multifunctional nanocarrier-based theranostics is currently considered to solve some key unmet challenges in cancer treatment. Here we report a nanocarrier platform, named carbon dot (CD) created mesoporous hollow organosilica (C-hMOS) nanoparticles, to deliver anticancer drug and to enable optical imaging. The hollow structure was formed by the removal of a nanorod core template, and at the same time, the fluorescent signal was endowed from the heat-treated organosilica network. Thanks to the hollow and mesoporous structure, the C-hMOS effectively loaded doxorubicin (DOX) for cancer chemotherapy. The DOX was released from C-hMOS highly sustainably (over 12 days) and pH-dependently (pH 5.0 > pH 7.4). The DOX-loading C-hMOS internalized cancer cells efficiently (> 90%), and induced cellular apoptosis including the expression of caspase-3. The treatment of C-hMOS to cancer cells enabled multi-color visualization in vitro, suggesting the possibility of cell tracing. Moreover, when injected intratumorally in mice, the C-hMOS exhibited strong optical signals in vivo along with a high optical stability (over a week). The injected C-hMOS were distributed only a fraction in liver but not in heart, lung, spleen or kidney and displayed good biocompatibility. The DOX-delivering C-hMOS significantly suppressed the in vivo tumor growth associated with apoptotic functions. Taken together, the developed C-hMOS nanoparticles can be a promising nanoplatform for drug delivery and in vivo imaging in cancer treatment.Significance of workMultifunctional nanoparticles that combine chemotherapeutic ability with imaging modality comprise promising platform for cancer theranostics. Here we developed a novel theranostic nanoparticle, i.e., carbon-dot created mesoporous hollow silica nanoparticle, to offer unique merit for this purpose. The in vitro and in vivo findings to support this include: i) carbon dots with 1-2 nm size in situ generated discretely and uniformly within silica network, ii) hollow and mesoporous structure effective for loading of DOX at high content, iii) release behavior of DOX in a sustainable and pH-dependent manner, iv) chemotherapeutic efficacy in killing cancer cells and suppressing tumor growth through DOX delivery, and v) carbon dot induced multi-color fluorescence imaging within cells and tumor tissues. These collective multifaceted properties may facilitate the novel carbon dot nanocarriers to be a potential candidate for delivering anticancer drug and non-invasive imaging in cancer treatment.

Graphical abstract

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3D screening device for the evaluation of cell response to different electrospun microtopographies

Publication date: Available online 1 April 2017
Source:Acta Biomaterialia
Author(s): G. Criscenti, A. Vasilevich, A. Longoni, C. De Maria, C.A. van Blitterswijk, R. Truckenmuller, G. Vozzi, J. De Boer, L. Moroni
Micro- and nano-topographies of scaffold surfaces play a pivotal role in tissue engineering applications, influencing cell behavior such as adhesion, orientation, alignment, morphology and proliferation. In this study, a novel microfabrication method based on the combination of soft-lithography and electrospinning for the production of micro-patterned electrospun scaffolds was proposed. Subsequently, a 3D screening device for electrospun meshes with different micro-topographies was designed, fabricated and biologically validated. Results indicated that the use of defined patterns could induce specific morphological variations in human mesenchymal stem cell cytoskeletal organization, which could be related to differential activity of signaling pathways.Statement of SignificanceWe introduce a novel and time saving method to fabricate 3D micropatterns with controlled micro-architectures on electrospun meshes using a custom made collector and a PDMS mold with the desired topography. A possible application of this fabrication technique is represented by a 3D screening system for patterned electrospun meshes that allows the screening of different scaffold/electrospun parameters on cell activity. In addition, what we have developed in this study could be modularly applied to existing platforms. Considering the different patterned geometries, the cell morphological data indicated a change in the cytoskeletal organization with a close correspondence to the patterns, as shown by phenoplot and boxplot analysis, and might hint at the differential activity of signaling. The 3D screening system proposed in this study could be used to evaluate topographies favoring cell alignment, proliferation and functional performance, and it has the potential to be upscaled for high-throughput.

Graphical abstract

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Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys

Abstract

Aims

Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure.

Materials and methods

Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks.

Results and discussion

Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp.

Conclusion

Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

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Reply to: Microwave Thermosphere™ Ablation in the multimodal management of colorectal cancer liver metastasis’

Publication date: Available online 1 April 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Petter Frühling




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Patterns of care and clinical outcomes in primary oesophageal gastrointestinal stromal tumours (GIST): a retrospective study of the French Sarcoma group (FSG)

Publication date: Available online 1 April 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Florence Duffaud, Pierre Meeus, Francois Bertucci, Jean-Baptiste Delhorme, Eberhard Stoeckle, Nicolas Isambert, Emmanuelle Bompas, Johan Gagniere, Olivier Bouché, Maud Toulmonde, Sebastien Salas, Jean-Yves Blay, Sylvie Bonvalot
BackgroundOesophageal GIST (ESOGIST) are very rare tumours requiring special consideration regarding diagnosis, surgical management, and perioperative treatment.MethodsA retrospective study was conducted across 9 centres in the French Sarcoma Group (FSG) to characterize all patients in the years 2000-2014.ResultsSeventeen patients (pts) with primary localized ESOGIST were identified, with median age 69 years (36-81) and 11 females. Eight tumours (T) occurred in the lower third of the oesophagus, five in the oesophageal gastric junction, two in the superior third, and two in the middle third. All pts underwent oesophagoscopy and/or endoscopic ultrasound (EUS) and CT scan. Fifteen had EUS guided biopsy. Nine pts received imatinib (IM) as initial treatment resulting in six PR, three SD. Tumours were resected in nine pts (53%) (7 upfront, 2 after IM); via enucleation in four (44%) [median size 4 cm], oesophagectomy in five (56%) [median size 10 cm]. Resections were R0 in three pts (33%), R1 in six (66%). Eight pts (47%) had no tumour resection, and one patient was never treated. Six pts received adjuvant IM. With a median follow-up of 24 months (7-101), 11 pts are alive (64.7%), five died (29.4%), one was lost to follow-up. Two pts of 4 pts relapsed following enucleation.ConclusionsESOGIST can be reliably identified pre-operatively by EUS-guided biopsy. Surgery for ESOGIST is either enucleation or oesophagectomy depending on tumour size, location, and patient's individual surgical risk. Preoperative IM therapy could improve resectability and should be considered if surgery is contraindicated or would lead to negative impact on the functional status of the patient.



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Scholar : International Journal of Molecular Medicine - Volume:39 Number:4

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TABLE OF CONTENTS April-2017 Volume 39 Issue 4

Senescence of mesenchymal stem cells (Review) Yi Li, Qiong Wu, Yujia Wang, Li Li, Hong Bu, Ji Bao View Abstract ❯

Fisetin regulates astrocyte migration and proliferation in vitro Nan Wang, Fang Yao, Ke Li, Lanlan Zhang, Guo Yin, Mingjun Du, Bingyi Wu View Abstract ❯

MicroRNA-182 prevents vascular smooth muscle cell dedifferentiation via FGF9/PDGFRβ signaling Nana Dong, Wei Wang, Jinwei Tian, Zulong Xie, Bo Lv, Jiannan Dai, Rui Jiang, Dan Huang, Shaohong Fang, Jiangtian Tian, Hulun Li, Bo Yu View Abstract ❯

ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint Seiji Yokota, Naoyuki Chosa, Seiko Kyakumoto, Hitomichi Kimura, Miho Ibi, Masaharu Kamo, Kazuro Satoh, Akira Ishisaki View Abstract ❯

Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity Simone Aparecida de Bessa Garcia, Ana Carolina Pavanelli, Natália Cruz e Melo, Maria Aparecida Nagai View Abstract ❯

Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: Implications for the treatment of neurodegenerative disorders Hui Wang, You Song Xu, Miao Lin Wang, Chao Cheng, Rui Bian, Hao Yuan, Yi Wang, Ting Guo, Lin Lin Zhu, Hang Zhou View Abstract ❯

Autophagy induction in the skeletal myogenic differentiation of human tonsil-derived mesenchymal stem cells Saeyoung Park, Yoonyoung Choi, Namhee Jung, Jieun Kim, Seiyoon Oh, Yeonsil Yu, Jung-Hyuck Ahn, Inho Jo, Byung-Ok Choi, Sung-Chul Jung View Abstract ❯

AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice Kazuhiro Nakano, Sen Takeshita, Noriko Kawasaki, Wataru Miyanaga, Yoriko Okamatsu, Mizuki Dohi, Tadakiyo Nakagawa View Abstract ❯

Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes Lin Wu, Mingyu Chen, Huijuan Mao, Ningning Wang, Bo Zhang, Xiufen Zhao, Jun Qian, Changying Xing View Abstract ❯

Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer Shuang Bai, Qiang Feng, Xin-Yan Pan, Hong Zou, Hao-Bin Chen, Peng Wang, Xin-Liang Zhou, Yan-Ling Hong, Shu-Ling Song, Ju-Lun Yang View Abstract ❯

Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2 Yue Tian, Xiuying Wu, Shanbin Guo, Ling Ma, Wei Huang, Xiaochun Zhao View Abstract ❯

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling Jinyan Liu, Feng Hu, Jintian Tang, Shijie Tang, Kun Xia, Song Wu, Chaoqi Yin, Shaohua Wang, Quanyong He, Huiqing Xie, Jianda Zhou View Abstract ❯

Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects Jae-Yong Kim, Seong-Min Kim, Suk-Jeong Kim, Eun-Young Lee, Jae-Ryong Kim, Kyung-Hyun Cho View Abstract ❯

MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma Yiliang Bi, Wei Shen, Min Min, Yan Liu View Abstract ❯

Tissue engineered vascularized periosteal flap enriched with MSC/EPCs for the treatment of large bone defects in rats Christoph Nau, Dirk Henrich, Caroline Seebach, Katrin Schröder, John H. Barker, Ingo Marzi, Johannes Frank View Abstract ❯

Comparison of the proliferation, migration and angiogenic properties of human amniotic epithelial and mesenchymal stem cells and their effects on endothelial cells Qianqian Wu, Tao Fang, Hongxin Lang, Min Chen, Ping Shi, Xining Pang, Guoxian Qi View Abstract ❯

Overexpression of TMPRSS4 promotes tumor proliferation and aggressiveness in breast cancer Xiao-Mei Li, Wen-Lou Liu, Xu Chen, Ya-Wen Wang, Duan-Bo Shi, Hui Zhang, Ran-Ran Ma, Hai-Ting Liu, Xiang-Yu Guo, Feng Hou, Ming Li, Peng Gao View Abstract ❯

Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice Liang-Liang Sun, Tian-Jin Liu, Limei Li, Wei Tang, Jun-Jie Zou, Xiang-Fang Chen, Jiao-Yang Zheng, Bei-Ge Jiang, Yong-Quan Shi View Abstract ❯

Kindlin-1 contributes to EGF-induced re-epithelialization in skin wound healing Congcong Shen, Linlin Sun, Ningwen Zhu, Fazhi Qi View Abstract ❯

Fenofibrate exerts protective effects against gentamicin-induced toxicity in cochlear hair cells by activating antioxidant enzymes Channy Park, Hye-Min Ji, Se-Jin Kim, Sung-Hee Kil, Joon No Lee, Seongae Kwak, Seong-Kyu Choe, Raekil Park View Abstract ❯

A long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, as a preventive drug for the development of hepatic steatosis in high-fructose diet-fed ob/ob mice Ken Nakamura, Shinya Fukunishi, Keisuke Yokohama, Hideko Ohama, Yusuke Tsuchimoto, Akira Asai, Yasuhiro Tsuda, Kazuhide Higuchi View Abstract ❯

Icaritin, a novel plant-derived osteoinductive agent, enhances the osteogenic differentiation of human bone marrow- and human adipose tissue-derived mesenchymal stem cells Tao Wu, Tao Shu, Le Kang, Jinhui Wu, Jianzhou Xing, Zhiqin Lu, Shuxiang Chen, Jun Lv View Abstract ❯

Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling Yandong Lu, Fangguo Li, Tao Xu, Jie Sun View Abstract ❯

Heat shock protein 90/Akt pathway participates in the cardioprotective effect of exogenous hydrogen sulfide against high glucose-induced injury to H9c2 cells Xiao Ke, Jingfu Chen, Longyun Peng, Wei Zhang, Yiying Yang, Xinxue Liao, Liqiu Mo, Ruixian Guo, Jianqiang Feng, Chengheng Hu, Ruqiong Nie View Abstract ❯

Possible protective role of the ABCA4 gene c.1268A>G missense variant in Stargardt disease and syndromic retinitis pigmentosa in a Sicilian family: Preliminary data Rosalia D'Angelo, Luigi Donato, Isabella Venza, Concetta Scimone, Pasquale Aragona, Antonina Sidoti View Abstract ❯

3'-Daidzein sulfonate sodium inhibits neuronal apoptosis induced by cerebral ischemia-reperfusion Ruizhen Liu, Xinming Zhong, Jing Zeng, Zhihua Huang, Xiao Li, Hai Xiao, Qin Chen, Dongliang Li View Abstract ❯

Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes Tao Hao, Hongtao Zhang, Sheyu Li, Haoming Tian View Abstract ❯

ICT1 knockdown inhibits breast cancer cell growth via induction of cell cycle arrest and apoptosis Chen Wang, Chenlu Liang, Weiliang Feng, Xianghou Xia, Feng Chen, Enqi Qiao, Xiping Zhang, Daobao Chen, Zhiqiang Ling, Hongjian Yang View Abstract ❯

Regulation of Runx2 by microRNA-9 and microRNA-10 modulates the osteogenic differentiation of mesenchymal stem cells Hong Luo, Hualin Gao, Fang Liu, Bing Qiu View Abstract ❯

Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway Kazuhiko Fujita, Haruhiko Tokuda, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Gen Kuroyanagi, Rie Matsushima‑Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka View Abstract ❯

5-7 October, 2017, Metropolitan Hotel, Athens, Greece 22nd World Congress on Advances in Oncology & 20th International Symposium on Molecular Medicine 3-4 October 2017, Pre-Congress Workshop: 'Next-Generation Sequencing – Library construction and quality control'

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