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The varus knee has been defined as a Hip-Knee-Ankle alignment of less than 180 degrees. Varus knee alignment increases the load on the medial knee and also the risk of osteoarthritis. High tibial osteotomy has been designed to modify the malalignment of varus knee. The aim of this study was to investigate the osteotomy effects on knee adduction moment (KAM) and contact forces using a musculoskeletal and subject-specific knee model. A patient with varus knee and no symptoms of any other disease or disability participated in this study. The geometry of the multibody knee model has been modified using MR images. The solutions of its finite element model have been used to determine the parameters of the multibody model. The motion data, ground reaction force and kinetic data have been applied to run the subject-specific musculoskeletal model during the stance phase of gait. After osteotomy, the adduction moment decreased, where the maximum values are comparable to other studies. The pattern of KAM did not witness any significant changes. The total and medial contact forces reduced considerably after surgery, but the lateral contact force did not significantly change. The changes in total and medial contact forces and lack of change in lateral contact force could be explained by modification of the gait pattern after surgery. [ABSTRACT FROM AUTHOR]

The liver is a major hematopoietic organ during embryonic and fetal development in humans. Its hematopoietic activity starts during the first weeks of gestation and continues until birth. During this period the liver is colonized by undifferentiated hematopoietic stem cells (HSCs) that gradually differentiate and once mature, enter the circulatory system through the hepatic sinusoids, this process is called hepatic hematopoiesis. The morphology of hepatic hematopoiesis, has been studied in humans through the years, and led to a characterization of all the cell types that make up these phenomena. Studies on murine models also helped to describe the extent of hepatic hematopoiesis at different gestational ages. Using this knowledge, we attempted to describe how hepatic hematopoiesis morphologically evolves as gestation progresses, in human embryos and fetuses. Thus, we observed a total of 32 tissue specimens obtained from the livers of embryos and fetuses at different gestational ages. Basing our observations on the four stages of liver hematopoiesis identified by Sasaki and Sonoda in mice, we also described four consecutive stages of liver hematopoiesis in humans, which resulted to be highly similar to those described in murine models. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effects of n-3 and n-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) in a murine model of herpetic chorioretinitis.Methods: BALB/c mice were fed on three high fat diets, which contained: Menhaden oil (rich in n-3 PUFAs); Safflower oil (rich in n-6 PUFAs); or Corn oil (rich in saturated fatty acids) as control group, 14 days previously and until 12 days following anterior chamber (AC) HSV-1 inoculation.Results: Mice fed on Menhaden oil present an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also significant increase of RNA HSV-1 expression compared with Safflower and Corn oil groups. Furthermore, mice fed on Menhaden oil showed a significant decrease secretion of TNF-α, IFN-γ, IL-2 and IL-10 in splenic cells and both retinas.Conclusion: Our results showed that mice fed on Menhaden oil (n-3 PUFAs) presented an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also a significant increase in RNA HSV-1 expression compared with animals fed on Safflower and Corn oils. This increase of HSV-1 could be associated with the higher development of chorioretinitis. [ABSTRACT FROM AUTHOR]

The Dysexecutive Questionnaire (DEX) is a tool for measuring everyday problems experienced with the dysexecutive syndrome. This study investigated the psychometric properties of a revised version of the measure (DEX-R), a comprehensive tool, grounded in current theoretical conceptualisations of frontal lobe function and dysexecutive problems. The aim was to improve measurement of dysexecutive problems following acquired brain injury (ABI). Responses to the DEX-R were collected from 136 men and women who had experienced an ABI (the majority of whom had experienced a stroke or subarachnoid haemorrhage) and where possible, one of their carers or family members (n = 71), who acted as an informant. Rasch analysis techniques were employed to explore the psychometric properties of four newly developed, theoretically distinct subscales based on Stuss model of frontal lobe function and to evaluate the comparative validity and reliability of self and informant ratings of these four subscales. The newly developed subscales were well targeted to the range of dysexecutive problems reported by the current sample and each displayed a good level of internal validity. Both self- and independent-ratings were found to be performing reliably as outcome measures for at least a group-level. This new version of the tool could help guide selection of interventions for different types of dysexecutive problems and provide accurate measurement in neurorehabilitation services. [ABSTRACT FROM PUBLISHER]

Conclusions: The co-existence of cupulolithiasis and canalolithiasis might be a possible mechanism for the spontaneous inversion of positional nystagmus. Objective: To investigate the mechanism of spontaneous inversion of nystagmus direction without a positional change in experimental models of co-existing cupulolithiasis and canalolithiasis. Methods: Co-existing canalolithiasis and cupulolithiasis models were prepared using the bullfrog posterior semicircular canal (PSC). Ten bullfrogs were used. The ampullary nerve discharges were recorded as compound action potentials (CAPs). First, an otoconial mass was placed on the cupula to produce cupulolithiasis. Subsequently, another otoconial mass was introduced into the canal lumen to produce canalolithiasis. Decremental time constants for cupulolithiasis and incremental time constants for canalolithiasis were determined. Results: At first the CAPs increased and continued for a long time when the cupulolithiasis was generated. Subsequently the CAPs were suppressed by creating canalolithiasis. Finally, the CAPs increased again after the motion of otoconia inside the canal lumen stopped. The decremental time constant for cupulolithiasis was significantly longer than the incremental time constant for canalolithiasis. [ABSTRACT FROM AUTHOR]

Robot-assisted bilateral arm therapy (RBAT) has shown promising results in stroke rehabilitation; however, connectivity mapping of the sensorimotor networks after RBAT remains unclear. We used fMRI before and after RBAT and a dose-matched control intervention (DMCI) to explore the connectivity changes in 6 subacute stroke patients. Sensorimotor functions improved in the RBAT and DMCI groups after treatment. Enhanced activation changes were observed in bilateral primary motor cortex (M1) and bilateral supplementary motor area (SMA) after RBAT. Dynamic causal model analysis revealed that interhemispheric connections were enhanced in RBAT patients. These preliminary findings suggest that intracortical and intercortical coupling might underlie poststroke RBAT. [ABSTRACT FROM PUBLISHER]

Background: Pro-inflammatory cytokines play an essential role in maintenance of normal brain function as well as in repair after traumatic brain injuries (TBI). However, massive and uncontrolled release of these cytokines, particularly interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, can also result in a great deal of additional brain damage. Levels of these cytokines may increase in the brain thousands of times more than do the corresponding levels in serum. Research design: Narrative literature review. Outcome and conclusions: Strategies to control the levels of these pro-inflammatory cytokines and to reduce the cytokine-induced brain damage are discussed. There is extensive evidence from experiments in animal models that suppression of cytokines is effective in ameliorating neurologic damage after TBI. However, the efficacy of this approach remains to be proven in patient trials. [ABSTRACT FROM PUBLISHER]

Objective: This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI).Methods: The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months.Results: PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p < 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms.Conclusions: Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance. [ABSTRACT FROM AUTHOR]

The relation between force and temporal variability in discrete impulse production has been viewed as independent (R. A. Schmidt, H. Zelaznik, B. Hawkins, J. S. Frank, & J. T. Quinn, 1979 ) or dependent on the rate of force (L. G. Carlton & K. M. Newell, 1993 ). Two experiments in an isometric single finger force task investigated the joint force-time entropy with (a) fixed time to peak force and different percentages of force level and (b) fixed percentage of force level and different times to peak force. The results showed that the peak force variability increased either with the increment of force level or through a shorter time to peak force that also reduced timing error variability. The peak force entropy and entropy of time to peak force increased on the respective dimension as the parameter conditions approached either maximum force or a minimum rate of force production. The findings show that force error and timing error are dependent but complementary when considered in the same framework with the joint force-time entropy at a minimum in the middle parameter range of discrete impulse. [ABSTRACT FROM AUTHOR]

Impacts of exogenous microorganisms and tea polyphenols on acid production and conversion duringin vitrocolonic fermentation of konjac glucomannan (KGM) were assessed in this study. Colonic fermentation of KGM by the fecal extract of healthy adults resulted in a propionate-rich profile, as acetic, propionic, butyric and lactic acids production were 16.1, 13.0, 3.3 and 20.2 mmol/L, respectively. Inoculation of one of ten exogenous microorganisms in the fermentative systems increased acetic, propionic and butyric acids production by 50−230%, 9−190% and 110−350%, respectively, and also accelerated lactic acid conversion by 14−40%. Tea polyphenols in the fermentative systems showed clear inhibition on both acid production and conversion; however, this inhibition could be partially or mostly antagonised by the inoculated exogenous microorganisms, resulting in improved acid production and conversion. In total,Lactobacillus brevisandSterptococcus thermophiluswere more able to increase acid production, and the propionate-rich profile was not changed in all cases. [ABSTRACT FROM PUBLISHER]

Objective: The goal of this study was to investigate the protective effect of recombinant human EPO(rhEPO) on cerebral microvascular endothelial cells and the mechanisms by which rhEPO interacts with TJs proteins, claudin-5, Occludin and ZO-1 during the early period following traumatic brain injury. Research design: Rats (n = 81) were randomly divided into sham-operated group, TBI group and rhEPO+TBI group. Traumatic brain injury was induced by the Marmarou method. Methods and procedures: Rats were killed at 3, 24, 72 and 168 hours after TBI. The integrity of the blood–brain barrier was investigated by using a spectrophotometer to assess extravasation of Evans blue dye. The expression of Claudin-5, Occludin and ZO-1 were determined by immunohistochemistry and real-time fluorescence quantitative PCR. Results: From 3 hours to 3 days, rats in the TBI group demonstrated a remarkable increase in Evans blue content in the brain, relative to rats in the sham-operated group (p < 0.05). The expression of Claudin-5 and Occludin was significantly lower than those in the sham-operated group (p < 0.05). In contrast, rats in the TBI+rhEPO group demonstrated a significant decrease in brain levels. Conclusion: It was found that administration of rhEPO protected cerebral microvascular endothelial cells and reduced permeability of BBB and the mechanisms may be due to increasing the expression of TJs proteins. [ABSTRACT FROM AUTHOR]

Objective: To construct reference limits for gestation of umbilical vein blood flow (UVBF) in normal singleton pregnancies between 14 and 40 weeks of gestation using quantile regression.Methods: We ultrasonographycally examined 852 fetuses from low-risk pregnancies between 16 and 40 weeks of gestation in a prospective cross-sectional study. UV diameter and time-averaged maximum velocity (TAMXV) were measured in UV intra-abdominal portion by real time and Doppler ultrasonography. A semi-automatic measurement software was used to obtain UV diameter values. UVBF was then calculated from UV diameter and TAMXV measurements and expressed both as absolute value and as value normalized for fetal abdominal circumference (UVBF/AC). Individual centile values of the variables investigated were established by quantile regression in the gestational interval considered. In 50 cases UVBF was measured twice by the same investigator or by a second investigator and the intra- and inter-observer agreement were calculated.Results: A significant increase in UV diameter, TAMXV, UVBF absolute value and UVBF/AC was evidenced in the gestational period considered. Growth charts were established based on these measurements. The intra- and inter-observer intraclass correlation coefficients resulted as 0.92 (0.87-0.96) and 0.89 (0.84-0.97), respectively, for UBVF.Conclusions: In this study we constructed UVBF charts using quantile regression in a large cohort of low-risk pregnancies. These charts offer the advantage of specific estimated regression parameters for each percentile, better defining the normal range of UVBF. This promises to be useful in the diagnosis and management of fetuses with abnormal fetal growth. [ABSTRACT FROM AUTHOR]

Despite their considerable importance to biomechanics, there are no existing methods available to directly measure apparent Poisson’s ratio and friction coefficient of oral mucosa. This study aimed to develop an inverse procedure to determine these two biomechanical parameters by utilizingin vivoexperiment of contact pressure between partial denture and beneath mucosa through nonlinear finite element (FE) analysis and surrogate response surface (RS) modelling technique. First, thein vivodenture–mucosa contact pressure was measured by a tactile electronic sensing sheet. Second, a 3D FE model was constructed based on the patient CT images. Third, a range of apparent Poisson’s ratios and the coefficients of friction from literature was considered as the design variables in a series of FE runs for constructing a RS surrogate model. Finally, the discrepancy between computedin silicoand measuredin vivoresults was minimized to identify the best matching Poisson’s ratio and coefficient of friction. The established non-invasive methodology was demonstrated effective to identify such biomechanical parameters of oral mucosa and can be potentially used for determining the biomaterial properties of other soft biological tissues. [ABSTRACT FROM PUBLISHER]

Conclusion: This study developed an easy way to induce otitis media in an animal model and find the relation between tensor veli platini muscle (TVP) and levetor veli platini muscle (LVP) in the opening and closing of the pharyngeal orifice of Eustachian tube. It was proved that otitis media is caused due to the dysfunction of Eustachian tube and the only muscle responsible for opening and closing of ETPO (Eustachian tube pharyngeal orifice) is TVP and LVP has no role in the opening and closing of the Eustachian tube pharyngeal orifice. Objective: To develop valid animal model for otitis media of effusion and to study the relation of paratubular muscles in the functioning of Eustachian tube. Methods: Two different methods were used to induce middle ear disease: (1) Excision of tensor veli platini and levetor veli platini muscles (TVP and LVP); and (2) Injection of botulinum toxin type A on TVP and LVP. Result: Otomiscroscopic, tympanograph, and pathological examination showed the presence of middle ear disease in those animals whose TVP was excised and paralyzed, but on those groups of animals whose LVP was excised and paralyzed, abnormalities were seen. [ABSTRACT FROM PUBLISHER]

Eaten foodstuffs are usually fortified with prebiotic ingredients, such as inulin and oligofructose (FOS). The main goal of this study was to evaluate the combined effects of inulin and FOS with either suboptimal pH or storage temperature on the viability of Lactobacillus reuteri DSM 20016. Data were modeled through Weibull equation for the evaluation of the microbiological shelf life and the survival time. Prebiotics enhanced the microbiological shelf life and enhanced the survival time of the target bacterium. The use of the factorial ANOVA highlighted that inulin and FOS exerted a different effect as a function of pH and temperature. Inulin prolonged survival time under acidic conditions, while the effect of glucose + FOS was significant at pH 8. Finally, temperature could act by increasing or decreasing the effect of prebiotics, as they could exert a protective effect at 30 °C but not at 44 °C. As the main output of this research, we could suggest that the effect of prebiotics on L. reuteri could be significantly affected by pH and temperature, thus pinpointing that the design of a symbiotic food should also rely on these factors. [ABSTRACT FROM AUTHOR]

Introduction: Soy isoflavones have been shown to be an alternative to hormone therapy at menopause, without causing side-effects such as breast cancer. However, the effects of early and late treatment with isoflavones on the mammary gland remain controversial.Objective: To investigate the effects of early and late treatment with soy isoflavones on the mammary gland of ovariectomized rats.Methods: Thirty 3-month-old rats were ovariectomized and divided equally into groups: Control, treated with vehicle solution; or with 150 mg/kg/body weight of isoflavones by gavage; or subcutaneously treated with 10 μg/kg/body weight with 17β-estradiol. Treatments started 3 days (early treatment) or 30 days (late treatment) after ovariectomy and lasted for 30 consecutive days. Thereafter, the animals were euthanized and the mammary glands were removed and processed for paraffin embedding. Sections were stained with hematoxylin and eosin for histomorphometry or subjected to immunohistochemical detection of Ki-67 and VEGF-A.Results: The ductal, lobular and total epithelial fractions were similar between controls and the early/late isoflavone groups, but they were significantly higher in the groups treated with estradiol. In both epithelial and stromal regions, the immunoreactivity of VEGF-A and the percentage of Ki-67-positive cells were significantly higher in the groups treated with estradiol, while they were similar in the early/late isoflavone groups and control groups.Conclusion: Our results indicate that early and late treatment with soy isoflavones at the dose of 150 mg/kg/body weight does not show proliferative and angiogenic effects on the mammary gland of ovariectomized rats. [ABSTRACT FROM AUTHOR]

Objectives: Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length.Design: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation.Results: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms).Conclusions: Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the leading causes of visual impairment worldwide. Classically, clinicians have evaluated patients through a full ophthalmological examination including gonioscopy, measurement of intraocular pressure (IOP), and assessment of the optic nerve. New imaging modalities have further enhanced our ability to evaluate glaucoma; however, our treatments have not evolved as much. Whether one uses medical treatment with topical ocular antihypertensives, laser trabeculoplasty, or filtering surgery, the mainstay of treatment is to lower IOP. However, as our understanding of the disease evolves, mechanisms other than elevated IOP have been implicated in glaucoma pathogenesis. Recent animal model studies have shown a possible role of the immune system in the pathophysiology of glaucoma. This article explores the current understanding of immune reactions in glaucoma, which could lead to a new paradigm of treatment for human disease. [ABSTRACT FROM AUTHOR]

Primary objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis. Research design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction. Methods and procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue. Main outcomes and results: LPS (1 μg ml-1) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment. Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs,ERCC4 R415Q(rs1800067),MSH3 R940Q(rs184967),MSH6 G39E(rs1042821),POLD1 R119H(rs1726801),XRCC1 R194W(rs1799782), andXPC A499V(rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95% confidence interval = 1.01–7.64) and 10.89 (95% confidence interval = 3.50–33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women. [ABSTRACT FROM AUTHOR]

Crude ethanol extracts (CEE) of purple rice was fractionated to obtain hexane soluble (HSF) and ethyl acetate soluble fractions (EASF). Total antioxidant capacity was higher in CEE than the HSF and EASF. However, HSF exhibited strong antiproliferation and apoptosis induction against colon cancer cell lines, both p53 wild-type (RKO) and mutant (SW620) strains. Then, the CEE was used to determine the effects on the progression of aberrant crypt foci (ACF), a preneoplastic lesion seen in colon carcinogenesis in rats. Male Wistar rats were subcutaneously injected of 40 mg/kg body weight dimethylhydrazin (DMH) once weekly for 2 wk. After 2 wk, rats were orally administered ethanol extract at 100 and 1000 mg/kg body weight, for 4 wk. Rats fed with only the high dose of CEE had significantly decreased numbers of ACF per rat (45.56%) and crypt multiplicity (AC/focus) (16.67%) compared to rats that received DMH alone. The result also demonstrated that CEE induced apoptosis in colonic epithelium cells of rat received colon carcinogen as detected the increasing of caspase-3 activity. This finding could be concluded that purple rice extracts inhibited aberrant colonic epithelial cell progression via apoptosis induction. [ABSTRACT FROM PUBLISHER]

The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P< 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression. [ABSTRACT FROM PUBLISHER]

Background: Worse functional outcomes after controlled cortical impact (CCI) in Bace1−/− mice have previously been demonstrated. This study investigated whether reconstitution of amyloid-beta (A β) after CCI in Bace1−/− animals would reverse the detrimental effect of Bace1 deletion. Methods: Bace1−/− and wild type Bace1+/+ (C57Bl/6) mice were subjected to CCI ( n = 14-23/group) or sham injury ( n = 6/group). After injury, mice underwent intracerebroventricular injections of A β40 ( n = 23 Bace1−/− and 17 Bace1+/+ per group) or vehicle ( n = 14 Bace1−/− and 22 Bace1+/+ per group). Functional outcomes were assessed with wire grip (motor) and Morris water maze (spatial memory). Soluble A β levels were assessed at 24 hours and 21 days after CCI. Lesion volume was assessed 21 days after injury. Results: At 24 hours after injury, A β-treated Bace1−/− mice had A β40 levels similar to vehicle-treated Bace1+/+ mice, but by 21 days after injury there were no differences between A β-treated versus vehicle-treated Bace1−/− mice. Reconstitution with A β40 improved motor but not spatial memory or histopathological outcome in injured Bace1−/− mice. In contrast, treatment with A β40 worsened motor performance in Bace1+/+ mice. Conclusions: The data suggest A β40 may have some beneficial effects after CCI in young adult mice and that therapies targeting BACE should be approached cautiously. [ABSTRACT FROM AUTHOR]

Reactivation of tumor suppressor genes (TSGs) involved in carcinogenesis by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Recently, curcumin has been demonstrated to inhibit a bacterial DNA methyltransferase (M. Sss I) activity, induce global DNA hypomethylation in leukemia cells, and reactivate several hypermethylation silenced genes in lung and prostate cancer cells. Herein, we demonstrated that curcumin can enhance the mRNA and protein levels of ras-association domain family protein 1A (RASSF1A), 1 hypermethylation-silenced TSG, and decrease its promoter methylation in breast cancer cells. Mechanistic study demonstrated that curcumin can decrease DNA methylation activity of nuclear extract and downregulate the mRNA and protein levels of DNMT1 in MCF-7 cells, which may be associated with curcumin-induced disruption of NF-κB/Sp1 complex bound to the promoter region of DNMT1. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for breast cancer through hypomethylation reactivation of RASSF1A. [ABSTRACT FROM PUBLISHER]

Primary objective: This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells. Research design: The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model. Methods and procedure: P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7--day--old SD rats by whole cell patch clamp recording. The expression and distribution of P2X receptors were observed through immunohistochemistry and western blot at HH 3--day and 7--day. Main outcomes and results: In acute HH conditions, the amplitudes of ATP evoked peak currents were decreased compared to control. The immunohistochemistry and western blot results reflected there was no change in P2X receptors expression after 3 days HH injury, while P2X receptors expression was up--regulated in response to 7 days HH injury. Conclusions: These findings supported the possibility that the function of P2X receptors was sensitive to HH damage and long--term function decrease should result in the expression increase of P2X receptors. [ABSTRACT FROM AUTHOR]

Conclusions: Phased-array stimulation is a promising technique, which uses electrical interaction to focus the stimulation in cochlear implants, at the expense of limited threshold shifts. It has potential advantages over, for example, tripolar stimulation. Objectives: Current spread imposes limitations in cochlear implants. Van Compernolle (1985) suggested using all electrode contacts simultaneously to reduce these effects. Van den Honert et al. (2007) validated this so-called phased array algorithm in patients with respect to the electrode potentials but the effect on neural excitation remained unclear. The present study used computational modeling to relate the effect of phased-array stimulation to the neural elements. Methods: A computational model of the implanted human cochlea was used to compare the neural excitation patterns induced by conventional monopolar stimulation and by phased-array stimulation. Neural thresholds and electrical dynamic ranges were visualized with excitation profiles, showing the auditory nerve's response to a range of stimulus levels. Results: Phased-array stimulation of a single region reduces the spread of excitation and increases the dynamic range. The phased array paradigm can be extended to stimulate multiple sites simultaneously, thereby eliminating the need for sequential stimulation, but with a more limited range of usable stimulus levels, especially with perimodiolar electrodes. [ABSTRACT FROM AUTHOR]

Primary objective: To analyse the efficacy of bone marrow-derived mononuclear cells (MNCs) in traversing the blood-brain barrier (BBB) in an experimental model of stroke. Methods and procedures: The middle cerebral artery occlusion (MCAo) mouse model was established and behavioural and histological analysis was performed, subsequently the carboxyfluorescein diacetate (CFDA)-labelled MNCs were transplanted through the tail vein immediately after 23 hours of reperfusion. The fluorescence microscopic analysis of the brain sections was analysed in both acute and sub-acute phases of transplantation. Results: The neurological deficit was confirmed by TTC staining and contra lateral turning behaviour. After 2 and 7 days of transplantation, the CFDA-labelled MNCs were observed in the infarcted regions along the line of cortex. Conclusion: The presence of the CFDA-labelled cells in the ischaemic injured brain lesions proved homing of the implanted MNCs in the infarcted regions of the brain. The successful homing of MNCs may pave way for future clinical trials using MNC in stroke. [ABSTRACT FROM AUTHOR]

Background: Neural stem cell treatment and neurogenesis stimulation have gained attention as potential treatments for vascular dementia (VD). Currently, research mainly focuses on neurogenesis occurring in the sub-ventricular zone and dentate gyrus, while the research of the piriform cortex (Pir) is limited. Few results showed that weak neurogenesis exists in the Pir of adult rats. Since neurogenesis occurs in the Pir and is closely related to cognitive function, this study addressed the question of whether neurogenesis occurs in the Pir of an animal with the VD. Primary objective and hypothesis: This study investigated the effects of hyperbaric oxygen therapy on brain blood supply and neurogenesis in the piriform cortex (Pir) of rats with VD. Main outcomes and results: Compared to non-VD control rats (NC), rats with VD showed reduced rCBF, increased rCBV and slower MTT in the Pir. However, following hyperbaric oxygen (HBO) treatment in VD rats, rCBF increased, rCBV decreased and MTT increased. To determine whether the restoration in brain blood supply was associated with increased neurogenesis, immunohistochemical detection of nestin and doublecortin (DCX) was used. In the Pir of both normal and VD rats, nestin positive cells were localized to layer II (superficial cellular layer) and layer III (deep cellular layer). Nestin expression was increased in Pir cells in VD rats and was even more intensely expressed after the HBO treatment. DCX positive cells were mostly located in layer II from amygdaline fissure to rhinal fissure. Conclusion: These results suggest that HBO therapy can improve the blood supply and promote the neurogenesis in the Pir of adult rats with the VD. [ABSTRACT FROM AUTHOR]

Objective: We wanted to assess the effect of glucose-insulin-potassium (GIK) and glutamine on the oxidative metabolism during and after prolonged warm continuous blood cardioplegia (WB).Design: WB was given to 21 pigs divided into three equally sized groups: WB (control), WB and GIK, or WB and glutamine. Oxidation rates of radiolabeled glucose (14C) and free fatty acid (FFA) (3H) were assessed before, during, and at 30 and 60 min after 3 h of cardiac arrest with WB.Results: During standstill the substrate oxidation dropped markedly (<60%), glucose oxidation was highest in the WB + GIK group (p < 0.05) and FFA oxidation highest in the WB + glutamine group (NS). During recovery the GIK group had an elevated glucose oxidation (47 and 40% vs WB at 30 and 60 min recovery, respectively -p < 0.05). Following 30 min recovery the addition of GIK suppressed FFA oxidation some 60%. Glutamine increased the oxidation of both glucose (30%) and FFA (150%) following 60 min recovery (p < 0.05). During the whole recovery phase the relative FFA oxidation was significantly lowered in the GIK group. There were no differences between the groups regarding arterial levels or uptake of substrates, except for a higher myocardial oxygen consumption (MVO2) during cardioplegia in the glutamine group. All the hearts performed similarly.Conclusion: Addition of GIK or glutamine to the well-perfused and oxygenated heart during WB led to a postcardioplegic increase in oxidative metabolism and MVO2. GIK resulted in a significant metabolic shift from FFA to glucose. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to discuss the influence of the pre-impact posture to the response of a finite element human body model (HBM) in frontal impacts.Methods: This study uses previously published cadaveric tests (PMHS), which measured six realistic pre-impact postures. Seven postured models were created from the THUMS occupant model (v4.0): one matching the standard UMTRI driving posture as it was the target posture in the experiments, and six matching the measured pre-impact postures. The same measurements as those obtained during the cadaveric tests were calculated from the simulations, and biofidelity metrics based on signals correlation (CORA) were established to compare the response of the seven models to the experiments.Results: The HBM responses showed good agreement with the PMHS responses for the reaction forces (CORA = 0.80 ± 0.05) and the kinematics of the lower part of the torso but only fair correlation was found with the head, the upper spine, rib strains (CORA= 0.50 ± 0.05) and chest deflections (CORA = 0.67 ± 0.08). All models sustained rib fractures, sternal fracture and clavicle fracture. The average number of rib fractures for all the models was 5.3 ± 1.0, lower than in the experiments (10.8 ± 9.0). Variation in pre-impact posture greatly altered the time histories of the reaction forces, deflections and the rib strains, mainly in terms of time delay, but no definite improvement in HBM response or injury prediction was observed. By modifying only the posture of the HBM, the variability in the impact response was found to be equivalent to that observed in the experiments. The postured HBM sustained from 4 to 8 rib fractures, confirming that the pre-impact posture influenced the injury outcome predicted by the simulation.Conclusions: This study tries to answer an important question: what is the effect of occupant posture on kinematics and kinetics. Significant differences in kinematics observed between HBM and PMHS suggesting more coupling between the pelvis and the spine for the models which makes the model response very sensitive to any variation in the spine posture. Consequently, the findings observed for the HBM cannot be extended to PMHS. Besides, pre-impact posture should be carefully quantified during experiments and the evaluation of HBM should take into account the variation in the predicted impact response due to the variation in the model posture. [ABSTRACT FROM AUTHOR]