Fatty liver is associated with an increased risk of diabetes and cardiovascular disease- Evidence from three different disease models: NAFLD, HCV and HIV

Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

Combination of Nonwoven Filters and Mesenchymal Stem Cells Reduced Glomerulosclerotic Lesions in Rat Chronic Kidney Disease Models

Background and Objectives: The increasing incidence of patients requiring hemodialysis has become a medical and economic problem globally;it is necessary to maintain renal glomerulus functionality to prevent the progression of chronic kidney disease. As a therapeutic tool for preventing the progression of chronic kidney disease, mesenchymal stem cells (MSCs) are a promising source of both growth factors and cells for regeneration. However, the escape of MSCs from injection sites, as well as the insufficient production of growth factors, is issues that remain unresolved. In the present study, a complex of cells and a nonwoven filter was localized in an injured kidney to provide growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). Methods and Results: Nonwoven biodegradable polylactic acid (PLA) filters were used to capture rat bone marrow stem cells (r-BMSCs). The capture rates of r-BMSCs on five PLA filter disks were over 85%. The production of HGF by r-BMSCs on PLA filters was markedly enhanced through interactions between the cells and the nonwoven filter. Conversely, the production of VEGF by r-BMSC on PLA filters was unchanged. Complexes of nonwoven filters and cells were implanted onto the surfaces of kidneys of 5/6-nephrectomized rats, which are characterized by progressive glomerulosclerosis. Within the r-BMSC/PLA complexes, deleterious changes in serum creatinine levels were not attenuated. However, PLA filters with r-BMSCs, which enhanced HGF production over 4 weeks of culture, significantly (P = 0.03) decreased urinary protein levels at 4 weeks after implantation compared to untreated nephrectomized rats. Further histopathological studies revealed that glomerulosclerotic lesions were significantly (P = 0.008) reduced by treatment with the r-BMSC/PLA complex. Conclusion: Devices made of PLA nonwoven filters and stem cells are potentially useful for the prevention and treatment of chronic kidney disease.

Mathematical Wave Functions and 3D Finite Element Modelling of the Electron and Positron

The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

Endoscopic tools for the diagnosis and evaluation of celiac disease

Celiac disease(CD)is an autoimmune disease of the small bowel induced by ingestion of wheat,rye and barley.Current guidelines indicate histological analysis on at least four duodenal biopsies as the only way to diagnose CD.These indications are based on the conception of the inability of standard endoscopy to make diagnosis of CD and/or to drive biopsy sampling.Over the last years,technology development of endoscopic devices has greatly ameliorated the accuracy of macroscopic evaluation of duodenal villous pattern,increasing the diagnostic power of endoscopy of CD.The aim of this paper is to review the new endoscopic tools and procedures proved to be useful in the diagnosis of CD,such as chromoendoscopy,Fujinon Intelligent Chromo Endoscopy,Narrow Band Imaging,Optical Coherence Tomography,Water-Immersion Technique,confocal laser endomicroscopy,high-resolution magnification endoscopy,capsule endoscopy and I-Scan technology.

World-Universe Model—Alternative to Big Bang Model

This manuscript provides a comparison of the Hypersphere World-Universe Model (WUM) with the prevailing Big Bang Model (BBM) of the Standard Cosmology. The performed analysis of BBM shows that the Four Pillars of the Standard Cosmology are model-dependent and not strong enough to support the model. The angular momentum problem is one of the most critical problems in BBM. Standard Cosmology cannot explain how Galaxies and Extra Solar systems obtained their substantial orbital and rotational angular momenta, and why the orbital momentum of Jupiter is considerably larger than the rotational momentum of the Sun. WUM is the only cosmological model in existence that is consistent with the Law of Conservation of Angular Momentum. To be consistent with this Fundamental Law, WUM discusses in detail the Beginning of the World. The Model introduces Dark Epoch (spanning from the Beginning of the World for 0.4 billion years) when only Dark Matter Particles (DMPs) existed, and Luminous Epoch (ever since for 13.8 billion years). Big Bang discussed in Standard Cosmology is, in our view, transition from Dark Epoch to Luminous Epoch due to Rotational Fission of Overspinning Dark Matter (DM) Supercluster’s Cores. WUM envisions Matter carried from the Universe into the World from the fourth spatial dimension by DMPs. Ordinary Matter is a byproduct of DM annihilation. WUM solves a number of physical problems in contemporary Cosmology and Astrophysics through DMPs and their interactions: Angular Momentum problem in birth and subsequent evolution of Galaxies and Extrasolar systems—how do they obtain it;Fermi Bubbles—two large structures in gamma-rays and X-rays above and below Galactic center;Diversity of Gravitationally-Rounded Objects in Solar system;some problems in Solar and Geophysics [1]. WUM reveals Inter-Connectivity of Primary Cosmological Parameters and calculates their values, which are in good agreement with the latest results of their measurements.

Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Discovery of a ULK1 activator that induces autophagy in vitro and in vivo Parkinson＇ s disease models

Aim It has been widely accepted that autophagy plays a key role in some human diseases such as Par- kinson＇ s disease （PD）. UNC-51-1ike kinasesl （ ULK1 ） has been widely reported to initiate autophagy via its com- plex ULKl-mAtg13-FIP200 at the first stage; however, targeting ULK1 as a therapeutic strategy in PD still remains in its infancy. This study aimed at developing a novel ULK1 activator as candidate drugs for PD therapy and valida- ting the possible mechanism and efficacy in vitro and in vivo. Methods Sequence alignment, phylogenetic analy- sis, homology modeling, molecular dockingand structure modificationwere applied forscreening of candidate com- pounds. Surface plasmon resonance （SPR） analysis and molecular dynamics （MD） simulations were carried outto prove the binding betweenULKland BL-UA07. Observations of cell morphology were executed through several methods including MDC staining and GFP-LC3 transfection. Flow cytometric analysis of MDC was used for quantifi- cation of autophagy ratio. Western blot and RNAi transfection were used to explore the detailed mechanisms of BL- UA07-induced autophagy. Furthermore, an in vivo PD mouse model was established for validating the PD treatment efficacy of BL-UA07. Results After a series of screening and structure modification, a novel compound BL-UA07 targeting ULK1 was obtained, which couldeffectivelybind with its target. Then, our results showed that BL-UA07 could induce autophagy via ULK1 complex and decrease damage induced by MPP ~ in SH-SY5Y cells. In addition, in vivomouse model was established to evaluate the protective effect of BL-UA07. The results demonstrated that BL- UA07 has a therapeutic effect on the in vivomouse model without apparent toxicity, which is dependent on the cyto- protective autophagy mediated by ULK1. Conclusion In this study, a novel specific ULK1 activator （BL-UA07） was computationally designed, chemically synthesized and biologically validatedthat could induce cytoprotective au- tophagy in neuroblastoma SH-SYSY cells and in vivo mouse models. Together, these results may uncover this small-molecule compound BL-UA07 as a novel ULK1 activator in autophagy and thus would provide a new clue for exploring more candidate drug targeting ULK1 for future PD therapy.

Semantic model and optimization of creative processes at mathematical knowledge formation

The aim of this work is mathematical education through the knowledge system and mathematical modeling. A net model of formation of mathematical knowledge as a deductive theory is suggested here. Within this model the formation of deductive theory is represented as the development of a certain informational space, the elements of which are structured in the form of the orientated semantic net. This net is properly metrized and characterized by a certain system of coverings. It allows injecting net optimization parameters, regulating qualitative aspects of knowledge system under consideration. To regulate the creative processes of the formation and realization of mathematical know- edge, stochastic model of formation deductive theory is suggested here in the form of branching Markovian process, which is realized in the corresponding informational space as a semantic net. According to this stochastic model we can get correct foundation of criterion of optimization creative processes that leads to “great main points” strategy (GMP-strategy) in the process of realization of the effective control in the research work in the sphere of mathematics and its applications.

Can mouse models mimic sporadic Alzheimer’s disease?

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the most common form of dementia worldwide.As age is the main risk factor,>97%of all AD cases are of sporadic origin,potentiated by various risk factors associated with life style and starting at an age>60 years.Only<3%of AD cases are of genetic origin caused by mutations in the amyloid precursor protein or Presenilins 1 or 2,and symptoms already start at an age<30 years.In order to study progression of AD,as well as therapeutic strategies,mouse models are state-of-the-art.So far many transgenic mouse models have been developed and used,with mutations in the APP or presenilin or combinations(3×Tg,5×Tg).However,such transgenic mouse models more likely mimic the genetic form of AD and no information can be given how sporadic forms develop.Several risk genes,such as Apolipoprotein E4 and TREM-2 enhance the risk of sporadic AD,but also many risk factors associated with life style(e.g.,diabetes,hypercholesterolemia,stress)may play a role.In this review we discuss the current situation regarding AD mouse models,and the problems to develop a sporadic mouse model of AD.

Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease

Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.

Achievements of Truss Models for Reinforced Concrete Structures

Achievements are presented for truss models of RC structures developed in previous years: 1. Two constitutive models, biaxial and triaxial, are based on regular trusses, with bars obeying nonlinear uniaxial σ-ε laws of material under simulation;both models have been compared with test results and show a dependence of Poisson ratio on curvature of σ-ε law. 2. A truss finite element has been used in the nonlinear static and dynamic analysis of plane RC frames;it has been compared with test results and describes, in a simple way, the formation of plastic hinges. 3. Thanks to the very simple geometry of a truss, the equilibrium equations can be easily written and the stiffness matrix can be easily updated, both with respect to the deformed truss, within each step of a static incremental loading or within each time step of a dynamic analysis, so that to take into account geometric nonlinearities. So the confinement of a RC column is interpreted as a structural stability effect of concrete. And a significant role of the transverse reinforcement is revealed, that of preventing, by its close spacing and sufficient amount, the buckling of inner longitudinal concrete struts, which would lead to a global instability of the RC column. 4. The proposed truss model is statically indeterminate, so it exhibits some features, which are not met by the “strut-and-tie” model.

Dark Matter Cosmology and Astrophysics

Hypersphere World-Universe Model (WUM) envisions Matter carried from Universe into World from fourth spatial dimension by Dark Matter Particles (DMPs). Luminous Matter is byproduct of Dark Matter (DM) annihilation. WUM introduces Dark Epoch (spanning from Beginning of World for 0.4 billion years) when only DMPs existed, and Luminous Epoch (ever since for 13.8 billion years). Big Bang discussed in standard cosmological model is, in our view, transition from Dark Epoch to Luminous Epoch due to Rotational Fission of Overspinning DM Supercluster’s Cores and annihilation of DMPs. WUM solves a number of physical problems in contemporary Cosmology and Astrophysics through DMPs and their interactions: Angular Momentum problem in birth and subsequent evolution of Galaxies and Extrasolar systems—how do they obtain it;Fermi Bubbles—two large structures in gamma-rays and X-rays above and below Galactic center;Mysterious Star KIC 8462852 with irregular dimmings;Coronal Heating problem in solar physics—temperature of Sun’s corona exceeding that of photosphere by millions of degrees;Cores of Sun and Earth rotating faster than their surfaces;Diversity of Gravitationally-Rounded Objects in Solar system and their Internal Heat;Lightning Initiation problem—electric fields observed inside thunderstorms are not sufficient to initiate sparks;Terrestrial Gamma-Ray Flashes—bursts of high energy X-rays and gamma rays emanating from Earth. Model makes predictions pertaining to Masses of DMPs, proposes New Types of their Interactions. WUM reveals Inter-Connectivity of Primary Cosmological Parameters and calculates their values, which are in good agreement with the latest results of their measurements.

Differences in pathological changes between two rat models of severe traumatic brain injury

The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relatively more stable,more reproducible,and shows obvious cerebral pathological changes at an earlier stage.Therefore,the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury,while the severe free weight drop model may be more apt for studies on diffuse axonal injury.All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University,China(approval No.IRB2012-028-02)in Febru ary 2012.

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

Microstructural damage pattern of vascular cognitive impairment: a comparison between moyamoya disease and cerebrovascular atherosclerotic disease

Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China(approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment

Inflammatory bowel diseases(IBD),Crohns disease and ulcerative colitis,are chronic conditions associated with high morbidity and healthcare costs.The natural history of IBD is variable and marked by alternating periods of flare and remission.Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing,a great proportion of IBD patients remain symptomatic despite effective control of inflammation.These symptoms may include but not limited to abdominal pain,dyspepsia,diarrhea,urgency,fecal incontinence,constipation or bloating.In this setting,commonly there is an overlap with gastrointestinal(GI)motility and absorptive disorders.Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment.Therefore,in this review we describe the prevalence,diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.