Σάββατο 5 Μαΐου 2018

Effects of Indigenous Enterococci on the Intestinal Microbiota and the Behavior of Rats on Correction of Experimental Dysbiosis

Autoprobiotic (indigenous) strains of Enterococcus faecium used in the correction of experimental intestinal dysbiosis, in contrast to probiotic E. faecium strain L-3, had a marked bifidogenic effect, preserved the populations of Escherichia, and inhibited the growth of Proteus, but had a relatively low antagonistic activity in relation to Klebsiella. Administration of autoprobiotics (A) and probiotic (P) led to faster disappearance of the symptoms of dyspepsia as compared with the control group of rats (C1) in which dysbiosis was not corrected. Animals from subgroup A1 were given A, whose genomes contained a large number of pathogenicity genes, including cytolysins and hyaluronidase. Investigations using the open field test identified various behavioral reactions to correction of dysbiosis. Animals of subgroup A1 showed suppression of movement and orientational-investigative activity. In the second group of rats (subgroup A2), movement and orientational-investigative activity was comparable with that in control group C2 (without induction of dysbiosis), as after use of P. These characteristics of the effects of autoprobiotic enterococci on the intestinal microbiota and the body support the existence of an intestinal microbiome–brain axis.



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Behavioral Characteristics of Mice with Knockout of the IRR Alkali Sensor Gene

The tyrosine kinase receptor IRR (insulin receptor-related receptor) can be activated on alkalinization of the cell medium. IRR is detected in organs in contact with fluids with extreme pH values, as well as in certain central nervous system cells, where its role is unclear. We report here our analysis of the behavioral characteristics of mice with knockout of the IRR gene in a series of ethological tests. The control group included animals with the IRR gene from the same litters as knockout mice. In the social interest test, knockout animals showed a reduction in the number of social contacts. The forced swimming test revealed no statistically significant differences in the duration of immobility, though there were more animals showing longer periods of immobility among knockout mice. In the resident-intruder test, wild-type mice showed typical aggression levels, while seven of 16 knockout animals remained inert and, conversely, were attacked by the "stranger." These data provide evidence that deletion of the IRR gene leads to impairment of the aggressive-defensive behavior typical of the parental strain.



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Organization of the Connections of the Rostromedial Tegmental Nucleus with Structures of the Morphofunctional Basal Ganglia System in the Dog Brain

The spatial organization of the projections of the rostromedial tegmental nucleus (RMTg) to functionally diverse segments of the structures of the basal ganglia in dogs (n = 25) were studied by retrograde axonal transport of horseradish peroxidase. Connections between the limbic segments of the RMTg and the limbic segments of the zona incerta and the pallidum constituted evidence pointing to the segregated conduction of limbic information. In addition, these studies showed that the projections of the limbic medial and motor lateral segments of the RMTg overlap, within the pedunculopontine and entopeduncular nuclei, with fibers arriving in these nuclei from neurons in functionally diverse nuclei. The presence of labeled sparsely branched, long-axon "reticular" RMTg neurons projecting to the structures of interest is also evidence that this nucleus has an integrative function. Thus, the morphological substrate for information processing in the morphofunctional system of the basal ganglia underlying the mechanisms of their functioning was analyzed.



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Reorganization of the Association between Intelligence and the Characteristics of Attention and Memory on Aging

The association between intelligence and measures of the functions of the systems underlying attention and the recognition of verbal and image stimuli presented for memorization, as well as the lateral characteristics of speech memory were studied in members of an elderly age group (64.5 ± 6.3 years, n = 83; 43 women) and a young age group (22.0 ± 4.5 years, n = 133; 83 women). The rate of selection of information in conditions of conflict served as a predictor of the level of intelligence, independently of age. In elderly subjects, a higher level of intelligence corresponded to shorter executive control times, while no significant link between intelligence and functional measures of the attention system was seen in young people. Analysis of the properties of memory showed that reproduction of words addressed to the left hemisphere made a positive contribution to intelligence; in young people verbal memory for words addressed to the right hemisphere also made a contribution, while in elderly people there was a contribution from the efficiency of recognizing remembered verbal and image stimuli. Gender-linked features were seen in the age-related reorganization of the contribution of attention and memory to intelligence, with more marked changes in men.



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Relationship between Burnout Syndrome and Personality Characteristics in Emergency Ambulance Crew

Objectives. Being an ambulance doctor is a profession characterized by high psychological and emotional loads. The aim of the present work was to determine the probability of developing professional burnout in ambulance doctors and to identify the relationship between its occurrence and the doctors' personality characteristics. Materials and methods. The MBI-GS questionnaire and the Freiburg personality inventory (FPI) were used in 97 ambulance doctors – 57 women and 40 men. Mean age was 37.0 ± 12.21 years. Relationships between variables were identified by correlation and regression analysis. Results. and conclusions The risk of developing professional burnout was detected in nine respondents (11.5%). Individual symptoms of burnout were seen in 28 doctors (35.9%). The risk of emotional burnout was not diagnosed in the ≥45 age group. These results led to the conclusion that ambulance staff in general are characterized by stable personality features but nonetheless we emphasize the need to detect the symptoms of professional burnout to prevent it and develop programs for measures increasing personal stress resistance among workers.



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Impairments to Body Image in Meningioma of the Parietal-Occipital Area

Objectives. To study impairments to body image in patients with typical meningioma of the parietal-occipital area before and after surgical treatment. Materials and methods. A total of 23 patients with diagnosis of "typical meningioma of the parietal-occipital area" were studied. A set of neuropsychological tests was used, along with the "Image-I" dissociation method and the "Silhouette" method. Results and conclusions. Derangements to body image were found in patients with meningioma of the parietal-occipital area, these being apparent as disorders of left-right orientation and impairment to the positioning of body parts in space and relative to each other, along with mismatch between objective weight and height values and subjective views of the individuals' own bodies. After surgery, orientation in the body improved significantly, with clear differentiation of the positions of body parts relative to each other, an appropriate relationship between the positions of the two hands, and error-free right-left orientation. Own-body perceptions became more appropriate in relation to the number of body parts and their sizes, though people's views on their own body types generally remained inappropriate.



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Gene Polymorphisms Associated with Sleep and Cognitive Functions and Their Associations with Accident Proneness in Shift-Working Bus Drivers

The aim of the present work was to investigate a series of single-nucleotide gene polymorphisms and their associations with accident proneness in bus drivers. The study involved 299 shift-working professional drivers for whom accident statistics were available. Polymorphisms in genes associated with the sleep-waking rhythm and cognitive and emotional functions were investigated, i.e., CLOCK (rs12649507), RORA (rs1159814), NPAS2 (rs4851377), NPSR1 (rs324981), PER3 (rs2640909), DRD3 (rs6280), SLC6A3 (rs6347), and DBH (rs1611125). The study identifi ed signifi cant associations between accident parameters and polymorphisms in the CLOCK, NPSR1, and SLC6A3 genes. We suggest that these are due to differences in chronotype and resistance to impairments to the sleep regime for the CLOCK gene and in cognitive and emotional control for the NPSR1 and SLC6A3 genes.



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Use of the Placebo Effect in the Psychotherapy of Narcology Patients: Therapeutic and Ethical Aspects

This review assesses the therapeutic potential of placebo and nocebo effects in the treatment of narcological disorders. The background of this issue is discussed and the neurobiological and psychological mechanisms of the placebo effect are addressed. Use of the placebo effect in psychotherapy is discussed. Particular attention is paid to the therapeutic and ethical aspects of the practical application of the placebo effect, including as part of treatment methods such as placebo therapy, object-oriented psychotherapy, motivational and cognitive behavioral psychotherapy, Antabuse treatment, and psychopharmacotherapy with opioid receptor antagonists. The authors conclude that placebo effects can be used in the treatment of narcological disorders with the aim of increasing efficacy, subject to compliance with the main principles of medical ethics.



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Effects of the Atypical Antipsychotic Quetiapine on the Immune Response in Aggressive Mice in a Model of Social Stress

Chronic (10 days)administration of the atypical antipsychotic quetiapine (3.75 mg/kg) induced significant suppression of the IgM immune response in mice with aggressive behavior formed as a result of prolonged (14 days in CBA mice, 20 days in C57BL/6J mice) confrontations and in animals with unaltered psychoemotional status. The immunosuppressive action of quetiapine was independent of the genotype of the mice and the route (i.p. or p.o.) and scheme (single or repeated) of administration. Possible serotonin (5-HT) and dopamine (DA) receptor mechanisms of the immunomodulatory effects of quetiapine are discussed.



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Effects of Cytoflavin on Recovery of Cognitive Functions in Elderly Alcoholics

Objectives. To assess and study the effects of Cytoflavin, which is used in the complex therapy of elderly patients with alcoholism, on the dynamics of cognitive functions. Materials and methods. A prospective, randomized, parallel, cohort study was performed in 74 patients aged over 60 years with alcoholism. Results and conclusions. A statistically significant (p < 0.05) improvement in the dynamics of clinical-neurological status of the patients was obtained on the background of optimized and combined treatment including Cytoflavin, apparent as faster and more marked improvements in neuropsychological test measures than in the reference group (not treated with Cytoflavin).



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Experience in Continuous Neurobiocontrol Using fMRI Signals from the Primary Motor Cortex Using a 1.5-T MR Tomograph

Biocontrol based on fMRI signals from the motor area of the cortex is a potential approach to restoring motor functions in poststroke states and Parkinson's disease. The region of interest in most studies is in the secondary motor areas and the strength of the magnetic field is 3 T. We report here our studies on biocontrol using the fMRI signal from an area of the primary motor cortex associated with the operation of the right hand obtained using a 1.5-T tomograph and settings optimal for obtaining optimal images at this magnetic field strength. Subjects were 16 healthy subjects who took part in 30-min fMRI recording including 1) individual localization of the region of interest (rhythmic fist clenching test) and attempts to control its activity using 2) imaginary movements and 3) any cognitive strategy of the participant's choice. Attempts to carry out self-control in both cases led to activation of the precentral, anterior cingulate, superior frontal, and inferior parietal gyri and Brodmann zone 6. fMRI signal maps for these tasks did not show any statistically significant differences and the activation zones showed little if any overlap with the region of interest, evidencing lack of success of sessions. The limitations of the experiments are discussed, as are factors with adverse influences on the effectiveness of biocontrol.



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Studies of the Association between the Kynurenine-3-Monooxygenase Gene and Depression

Objective. To study the association between the kynurenine-3-monooxygenase (KMO) gene and depression. Materials and methods. Polymorphic loci rs2275163 (C/T) and rs1053230 (A/G) of the KMO gene were studied in patients with depression (study group) and mentally healthy subjects of comparable gender and age (control group). Results and conclusions. The rs2275163 polymorphism was not associated with depression. An association between the rs1053230 polymorphism and depression was found. The frequency of the GG genotype, linked with lower KMO activity and increased kynurenic acid levels in patients with endogenous psychoses, was greater in the study group than the control group (p = 0.001, OR 2.8 (95% CI 1.73–4.24). thus, the GG genotype can be regarded as a risk allele for developing depression.



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Changes in the Ultrastructure of Synapses in the Anterior Cortical Nucleus of the Amygdaloid Body of the Brain in Female Rats in Relation to Sex Hormone Levels

We present here an analysis of the ultrastructural characteristics of synapses in the anterior cortical nucleus of the amygdaloid body of the brain in female WAG/Rij rats (n = 9) with different levels of female sex hormones. The results of this study demonstrated that ovariectomy led to structural changes in synapses and decreases in the total number of synapses as compared with the control group, while hormone replacement therapy led to recovery of synapse structure and number. In terms of the level of dense projections, the control and post-ovariectomy groups were dominated by asymmetrical synapses (52%); in terms of the type of curvature of the plane of the synaptic contact, synapses with positively curved contacts dominated. Replacement therapy was followed by a minor decrease in the number of asymmetrical synapses (47%), most having negatively curved contacts. Complex synaptic contacts of the divergent and convergent types were seen, which is evidence that contacts were in an active functional state. The number of perforated synapses increased significantly from 14.3 to 50%, which may be evidence of estrogen activation of synapses.



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Biomechanical Analysis of Posture and Movement Coordination in Standing Humans during Bending of the Trunk in the Sagittal Plane

Achievement of the behavioral aim of most motor acts requires coordination of posture and movement. We report here our studies of this coordination using body bending in the sagittal plane in standing humans as an example. These movements are particularly complex to study, as both components of the motor act (the main component, with the aim of producing a behavioral result, i.e., bending per se, and the "accessory" postural component, i.e., with the aim of maintaining balance during the movement) include movements of large body parts, which hinders the separation of these two components. These were discriminated on the basis of current views of the features of postural components as compared with those of the main target component. The main and postural components were shown to correspond to movements along the eigenvectors of the dynamic equation. These movements were unique, as they simultaneously demonstrated both "kinematic" and "dynamic" synergies, so they were termed "natural synergies." The coordination of natural synergies in conditions of standing on wide and narrow supports was studied. The experimentally observed coordination was found to be close to the optimum coordination providing minimal movements of the center of pressure. This guarantees maintenance of the position of the center of pressure within the support area, as required to maintain balance.



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The Adaptogenic and Neuroprotective Properties of Lithium Ascorbate

Objectives. To study the neuroprotective properties of lithium ascorbate (LA) in in vivo and in vitro stress models. Materials and methods. Neurocytological and behavioral studies were run in models of stress in nerve cell cultures and experimental animals. Results. LA was shown to have a marked neuroprotective effect in conditions of glutamate-induced cytotoxicity in vitro and an adaptogenic effect on induction of stress in vivo. Conclusions. The results obtained here demonstrated that LA has high neuroprotective potential in stress induced in vivo and in vitro.



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Effects of Instructions on the Early Stages of the Visual Perception of Verbal Stimuli in Health and Schizophrenia

We report here studies of the early stages in the selection of meaningful and meaningless verbal information in one implicit and two explicit tasks on the latency and amplitude of the P100 component of event-related potentials in healthy subjects (n = 99) and patients with schizophrenia in the first psychotic episode (n = 102). Schizophrenia patients displayed greater impairment to the passive perception of meaningful verbal information. Giving instructions made no difference to the properties of the P100 wave from those in healthy subjects. A decrease in the amplitude of the P100 component on perception of words in passive observation conditions seen in patients may be linked with the severity of hallucinations. The relationships of the P100 wave showed that provision of instructions, as compared with passive perception, decreased the time taken for primary analysis of stimuli in healthy subjects regardless of category and relevance, while this occurred only on reading pseudowords in schizophrenia patients. The results obtained here provide evidence of impairments to the automatic attraction of attention to the semantically significant content of verbal stimuli. The studies reported here demonstrated a link between the properties of the P100 wave and behavioral parameters.



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Impulsivity in Adolescents with Attention Deficit Hyperactivity Disorder

Objectives. To study impulsivity in adolescents with attention deficit hyperactivity disorder (ADHD) and to evaluate the efficacy of Noofen (500 mg/day for 45 days) in the treatment of this pathology. Materials and methods. The results of clinical, psychological, and psychophysiological studies of 60 adolescents aged 12–15 years with ADHD are presented. The clinical pictures of illness and data from psychophysiological studies in ADHD with a predominance of hyperactivity (ADHD-H) and the combined type of illness (ADHD-C) were compared. Results and conclusions. Significantly higher levels of impulsivity and anxiety were found in children with ADHD-H. Treatment with Noofen was shown to have high clinical efficacy: status improved in 63.3% of patients.



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Characteristics of the Formation of Memories Relating to Fear in Mice with Depression- and Schizophrenia-Like Phenotypes: Effects of Gender and Age

We report here a comparative analysis of the acquisition of a conditioned passive avoidance reaction in mice of the mutant strains DISC1-Q31L and DISC1-L100P and mice of the control strain C57Bl/6NCr1 and detection of the effects of gender and age on learning. DISC1-L100P mice showed impairments to associative learning to avoid the dangerous dark sector of the apparatus regardless of gender and age. In DISC1-Q31L mice, the fear memory trace formed only in young males. A deficit of aversive learning was demonstrated in old mice of all the strains tested, with identically lower levels of learning ability in female DISC1-Q31L and C57Bl/6NCr1 mice than males. These characteristics of learning avoidance provide an additional argument for regarding DISC1-L100P mice as a genetic model of a schizophrenia-like state and DISC1-Q31L mice as a model of a depression-like state.



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Corticosterone-Induced Changes in Inhibitory Neurotransmission in Hippocampal Field CA1 Synapses Depending on the Activity of Inhibitory Synapses Expressing Cannabinoid Receptors

Objectives. To study the effects of corticosterone (100 nM) on spontaneous inhibitory postsynaptic currents(sIPSC) in pyramidal neurons in hippocampal field CA1 and to identify the role of inhibitory synapses expressing cannabinoid receptors in the changes induced by corticosterone. Materials and methods. Experiments were performed on living slices of rat ventral hippocampus using a patch clamp method in the whole cell configuration. Results and conclusions. Addition of corticosterone led to a significant increase in the frequency of sIPSC in the first 10 min, after which the magnitude of this parameter returned to baseline. In addition, the use of corticosterone led to a significant decrease in sIPSC amplitude 40 min after the start of exposure. Activation of cannabinoid CB1 receptors had weak effects on the properties of sIPSC, though addition of corticosterone did not induce the rapid rise in sIPSC frequency occurring at 10 min in controls or the drop in sIPSC amplitude (at 40 min in controls). These data indicate that both the rapid and slow effects of corticosterone developing in the ventral hippocampus are associated with the activity of CB1-expressing inhibitory synapses.



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Effects of Neuropeptide Y on the Functional State of the Afferent Inputs from the Arcuate Nucleus to the Suprachiasmatic Nucleus in Rats in Vitro

Experiments on sagittal sections of rat hypothalamus using electrophysiological methods for constructing and analyzing peristimulus time histograms (PSTH) addressed the modulatory influence of 10 nM neuropeptide Y on the functional state of the afferent inputs to neurons in the suprachiasmatic nucleus from the hypothalamic arcuate nucleus. Statistically significant responses to stimulation of the arcuate nucleus were recorded in 24 of the 54 suprachiasmatic nucleus neurons tested. Eight neurons produced responses consisting of short-latency arousal, while responses in six consisted of short-latency inhibition and 23 neurons showed complex biphasic and triphasic responses with different combinations of arousal and inhibition. Neuropeptide Y induced qualitative changes in responses (with disappearance of the initial or appearance of new responses) in seven of the neurons initially responding to stimuli and one neuron initially not responding to stimulation of the arcuate nucleus. In addition, a number of responses to peptide consisted of changes in the latent periods and durations of responses. These results point to the ability of neuropeptide Y to modulate the functional state of the afferent inputs to the circadian oscillator of the suprachiasmatic nucleus from the hypothalamic arcuate nucleus, which plays an important role in controlling appetite and metabolism.



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Flight Nurse - Guardian Flight

**COMPANY DESCRIPTION** Guardian Flight/Gallup Med Flight has been providing air medical transport to Gallup and the surrounding areas for more than 30 years. We are committed to clinical excellence, long term relationships and a culture of safety that promotes the highest quality of care. Strategically located to respond to the Four Corners Area, we execute thousands of calls per year with the most ...

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Flight Nurse - Guardian Flight

**COMPANY DESCRIPTION** Guardian Flight/Eagle Air Med has served Northern Arizona, Northern New Mexico, Southern Colorado and Southern Utah with more aircraft, more fully dedicated crews and for a longer period of time than any other air medical program in the area. Eagle has developed an extensive history of success in a geographical, cultural and politically sensitive market. We pride ourselves in ...

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Flight Nurse - Guardian Flight

**COMPANY DESCRIPTION** Guardian Flight/AeroCare has served Northern Arizona, Northern New Mexico, Southern Colorado and Southern Utah with more aircraft, more fully dedicated crews and for a longer period of time than any other air medical program in the area. Guardian has developed an extensive history of success in a geographical, cultural and politically sensitive market. We pride ourselves in being ...

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Critical Care Paramedic or Respiratory Therapist - UnityPoint Health - Grinnell Regional Medical Center

Critical Care Paramedic - The Critical Care Paramedic provides patient care as defined by the Iowa Department of Public Health scope of practice for Paramedics and/or Critical Care Paramedics and as authorized by the Medical Director.  Participates in Patient and family teaching and provides leadership by working cooperatively with other health care team members.  Collaborates with physicians and other ...

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Flight Paramedic - Guardian Flight

**COMPANY DESCRIPTION** Guardian Flight/AeroCare has been providing quality air medical services nationally and internationally for 20 years and has been devoted to providing the desert Southwest prompt, responsive and safe fixed-wing medical transport since February 2003. **JOB DESCRIPTION** AeroCare is seeking a highly motivated Flight Paramedic for our fixed-wing/rotor-wing operations in Gallup ...

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Paramedic - 24 hour shift (Urbana) - OSF HealthCare

W**Work Location:** OSF Heart of Mary Medical Center, Urbana, IL **Work Schedule:** 0700-0700 **Hours per Week:** 40 **Benefits Status:** Full-Time **Salary: **will discuss at time of interview The EMT-Paramedic drives ambulance in response to emergency situations such as fires, automobile or other accidents, cardiac arrests, traumatic injuries, etc. Assesses patient's condition and performs basic and ...

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Paramedic - Charleston County EMS, SC - Charleston County EMS

Voted one of the top tourist destinations in the world, Charleston County EMS serves over 1,100 square miles of historic and scenic areas including City of Charleston, Kiawah Island, and highly regarded beach communities on the Atlantic coastline. Charleston County is an EMS system that relies on Innovation, Trust, Compassion, Respect and Dedication to provide exceptional customer service to our community ...

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Selective Certification Paramedic - New Castle County EMS

An employee in this class performs highly responsible work involving the delivery of out-of-hospital basic and advanced life support services by responding to scenes of medical and traumatic emergencies, evaluating patients, and providing safe transportation to an appropriate medical facility with continuous care. Additional duties include the daily inspection, cleaning, and maintenance of the assigned ...

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Supervisor - Ready Responders

**About the Role** As a Ready Responders Supervisor you will directly manage and provide ongoing support to our team of Responders. Supervisors hold a high bar for patient care, quality assurance, and compliance standards and they do whatever it takes to make sure each Responder not only meets that bar, but constantly improves and grows as a healthcare provider.  Although Supervisors will be based in ...

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Medic, EMT/Paramedic (part-time, flexible hours) - Ready Responders

**About the role** When you join our team as a medic, you will join a group of dedicated healthcare providers who are committed to delivering positive, lasting healthcare solutions to members of their communities. As a member of our medical operations team you will respond to acute and non-acute medical needs of residents in the New Orleans community, and initiate video conferencing encounters with ...

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Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy through Suppression of Src Signaling Pathway

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Development and Validation of RAPID: A Patient-Specific Monte Carlo Three-Dimensional Internal Dosimetry Platform

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial–Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Oral administration of lipid oil-in-water emulsions performed with synthetic or protein-type emulsifiers differentially affects post-prandial triacylglycerolemia in rats

Abstract

In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 μm diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (β-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry.



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Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles

Abstract

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.



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The relationship between adiposopathy and glucose-insulin homeostasis is not affected by moderate-intensity aerobic training in healthy women with obesity

Abstract

The contribution of adiposopathy to glucose-insulin homeostasis remains unclear. This longitudinal study examined the potential relationship between the adiponectin/leptin ratio (A/L, a marker of adiposopathy) and insulin resistance (IR: homeostasis model assessment (HOMA)), insulin sensitivity (IS: Matsuda), and insulin response to an oral glucose tolerance test before and after a 16-week walking program, in 29 physically inactive pre- and postmenopausal women with obesity (BMI, 29–35 kg/m2; age, 47–54 years). Anthropometry, body composition, VO2max, and fasting lipid-lipoprotein and inflammatory profiles were assessed. A/L was unchanged after training (p = 0.15), despite decreased leptin levels (p < 0.05). While the Matsuda index tended to increase (p = 0.07), HOMA decreased (p < 0.05) and fasting insulin was reduced (p < 0.01) but insulin area under the curve (AUC) remained unchanged (p = 0.18) after training. Body fatness and VO2max were improved (p < 0.05) while triacylglycerols increased and HDL-CHOL levels decreased after training (p < 0.05). At baseline, A/L was positively associated with VO2max, HDL-CHOL levels, and Matsuda (0.37 < ρ < 0.56; p < 0.05) but negatively with body fatness, HOMA, insulin AUC, IL-6, and hs-CRP levels (− 0.41 < ρ < − 0.66; p < 0.05). After training, associations with fitness, HOMA, and inflammation were lost. Multiple regression analysis revealed A/L as an independent predictor of IR and IS, before training (partial R2 = 0.10 and 0.22), although A/L did not predict the insulin AUC pre- or post-intervention. A significant correlation was found between training-induced changes to A/L and IS (r = 0.38; p < 0.05) but not with IR or insulin AUC. Although changes in the A/L ratio could not explain improvements to glucose-insulin homeostasis indices following training, a relationship with insulin sensitivity was revealed in healthy women with obesity.



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CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation

Abstract

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-α (TNF-α) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways.



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miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and Sertad2

Abstract

Differentiation of adipocytes and their aggregation to adipose tissue are critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play important roles in adipogenesis and lipid metabolism. miR-128-3p may contribute to adipose tissue development according to the previous studies. However, the role of miR-128-3p in the process of preadipocyte differentiation and lipid metabolism is not yet understood. The purpose of this research was to investigate the biological function and molecular mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR-128-3p was downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-128-3p obstructed the expressions of adipogenic marker genes as well as the lipid droplets accumulation and triglyceride content, suggesting the importance of miR-128-3p for adipogenesis. Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3-L1 preadipocytes. Further evidences showed that, as a negative regulator of adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated receptor γ (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte differentiation, and miR-128-3p could also bind with SERTA domain containing 2 (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition, inhibition of Sertad2 with siRNA displayed the same effects as overexpression of miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte differentiation and promotion of lipolysis. Taken together, this study offers profound insight into the mechanism of miRNA-mediated adipogenesis and lipid metabolism.



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Evidence for the link between defective autophagy and inflammation in peripheral blood mononuclear cells of type 2 diabetic patients

Abstract

Autophagy was shown to modulate inflammation in immune cells. This study was designed to evaluate the association between autophagy and inflammation in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and non-diabetic (ND) subjects. The autophagy markers were measured by real-time PCR and western blot. The gene expression of pro- and anti-inflammatory cytokines was assessed by real-time PCR. Reduced transcription of BECN1 and LAMP2 and unchanged expression of MAP1LC3B and ATG5 were observed in PBMCs of T2D patients. Decreased LC3B-II and increased p62/SQSTM1 levels were found in PBMCs of diabetic patients. The p-mTOR level was higher in PBMCs of diabetic patients. An increase in both IL-1β and TNF-α gene expression, along with a decrease in the expression of IL-10, was observed in PBMCs of T2D patients. TNF-α mRNA expression was inversely correlated with the mRNA expression of BECN1 and LAMP2. TNF-α and IL-1β expression were negatively correlated with the protein levels of LC3B-II. TNF-α and IL-1β expression had also a positive correlation with protein level of p62. IL-10 mRNA expression was positively correlated with the mRNA expression of BECN1 and LAMP2 and protein levels of LC3B-II and negatively correlated with protein level of p62. In addition, p-mTOR level was positively correlated with IL-1β and TNF-α mRNA expression. The results revealed a reduced autophagy in PBMCs of T2D patients that is liked with an enhanced inflammation. The suppression of autophagy in PBMCs of diabetic patients may be associated with the activation of the mTOR signaling.



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Effect of high chronic intake of sucrose on liver metabolism in aging rats. Modulation by rutin and micronutrients

Abstract

High-sugar intake and senescence share common deleterious effects, in particular in liver, but combination of these two factors was little studied. Our aims were to examine the effect of a high-sucrose diet in liver of old rats and also the potential benefices of a polyphenol/micronutrient supplementation. Four groups of 22-month-old male rats fed during 5 months with a diet containing either 13 or 62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc were compared. We measured liver macronutrient composition, glycation/oxidative stress, enzyme activities (lipogenesis, β-oxidation, fructokinase), gene expression (enzymes and transcription factors), in vivo protein synthesis rates and plasma parameters. Sucrose induced an increase in plasma and liver lipid content, and a stimulation of liver protein synthesis rates. Gene expression was little changed by sucrose, with lower levels for LXR-α and LXR-β. Polyphenol/micronutrient supplementation tended to limit liver triglyceride infiltration through variations in fatty acid synthase, acyl coA oxidase, and possibly ATP-citrate lyase activities. In conclusion, despite differences in enzymatic regulations, and blunted responses of gene expression, high-sucrose diet was still able to induce a marked increase in liver lipid content in old animals. However, it probably attenuated the positive impact of polyphenol/micronutrients.



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Editorial Board



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Genetic polymorphism of sterol transporters in children with future gallstones

Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease.

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Preliminary study of magnetically controlled capsule gastroscopy for diagnosing superficial gastric neoplasia

Magnetically controlled capsule gastroscopy (MCCG) is a newly developed non-invasive method designed for gastric examination. Although favourable diagnostic accuracy has been reported, there is little if any data about its ability to diagnose gastric cancer.

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FXR deletion in hepatocytes does not affect the severity of alcoholic liver disease in mice

Emerging evidence has shown that FXR activation ameliorates the development of alcoholic liver diseases (ALD) while whole-body deficiency of FXR in mice leads to more severe ALD. However, it's unknown whether the enhanced susceptibility to ALD development in FXR−/− mice is due to deficiency of hepatic FXR or increased toxicity secondary to increased bile acid (BA) levels. Hepatocyte-specific FXR knockout mice (FXRhep−/−) present similar BA levels compared to wild-type mice, and are therefore a useful model to study a direct role of hepatic FXR in ALD development.

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☆EUS–guided reconstruction of the biliary system in a patient post right hemihepatectomy



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Reticulocyte Hemoglobin content (MCHr) in the assessment of iron deficient erythropoiesis in inflammatory bowel disease

In conditions associated with inflammation, biochemical parameters alone could be inadequate for assessing iron status. We investigated the potential utility of mean reticulocyte hemoglobin content (MCHr) in the assessment of the erythropoiesis status in inflammatory bowel disease (IBD).

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How to get the most out of costly Barrett’s oesophagus surveillance

Current endoscopic surveillance protocols for Barrett's oesophagus have several limitations, mainly the poor cost-effectiveness and high miss rate. However, there is sufficient evidence that patients enrolled in a surveillance program have better survival chances of oesophageal cancer due to earlier tumor stages at diagnosis compared to patients with de novo diagnosed oesophagus cancer. Risk stratifications aim to identify patients at highest risk of developing adenocarcinoma of the oesophagus; most of them base on the length of the Barrett's segment and the presence of dysplasia.

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Diminished neural network dynamics in amnestic mild cognitive impairment

Publication date: Available online 5 May 2018
Source:International Journal of Psychophysiology
Author(s): Einat K. Brenner, Frank G. Hillary, Emily C. Grossner, Rachel A. Bernier, Nicholas Gilbert, K. Sathian, Benjamin M. Hampstead
Mild cognitive impairment (MCI) is widely regarded as an intermediate stage between typical aging and dementia, with nearly 50% of patients with amnestic MCI (aMCI) converting to Alzheimer's dementia (AD) within 30 months of follow-up (Fischer et al., 2007). The growing literature using resting-state functional magnetic resonance imaging reveals both increased and decreased connectivity in individuals with MCI and connectivity loss between the anterior and posterior components of the default mode network (DMN) throughout the course of the disease progression (Hillary et al., 2015; Sheline & Raichle, 2013; Tijms et al., 2013). In this paper, we use dynamic connectivity modeling and graph theory to identify unique brain "states," or temporal patterns of connectivity across distributed networks, that distinguish individuals with aMCI from healthy older adults (HOAs). We enrolled 44 individuals diagnosed with aMCI and 33 HOAs of comparable age and education. Our results indicated that individuals with aMCI spent significantly more time in one state in particular, whereas neural network analysis in the HOA sample revealed approximately equivalent representation across four distinct states. Among individuals with aMCI, spending a higher proportion of time in the dominant state relative to a state where participants exhibited high cost (a measure combining connectivity and distance), predicted better language performance and perseveration. This is the first report to examine neural network dynamics in individuals with aMCI.



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The role of salinity in the trophic transfer of 137Cs in euryhaline fish

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Publication date: September 2018
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): Simon Pouil, François Oberhänsli, Peter W. Swarzenski, Paco Bustamante, Marc Metian
In order to better understand the influence of changing salinity conditions on the trophic transfer of 137Cs in marine fish that live in dynamic coastal environments, its depuration kinetics was investigated in controlled aquaria. The juvenile turbot Scophthalmus maximus was acclimated to three distinct salinity conditions (10, 25 and 38) and then single-fed with compounded pellets that were radiolabelled with 137Cs. At the end of a 21-d depuration period, assimilation efficiencies (i.e. AEs = proportion of 137Cs ingested that is actually assimilated by turbots) were determined from observational data acquired over the three weeks. Our results showed that AEs of 137Cs in the turbots acclimated to the highest salinity condition were significantly lower than for the other conditions (p < 0.05). Osmoregulation likely explains the decreasing AE observed at the highest salinity condition. Indeed, observations indicate that fish depurate ingested 137Cs at a higher rate when they increase ion excretion, needed to counterbalance the elevated salinity. Such data confirm that ambient salinity plays an important role in trophic transfer of 137Cs in some fish species. Implications for such findings extend to seafood safety and climate change impact studies, where the salinity of coastal waters may shift in future years in response to changing weather patterns.



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A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy

Gastrointestinal Endoscopy

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Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms

Neurogastroenterology & Motility

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Capsule endoscopy vs colonoscopy vs histopathology in colorectal cancer screening: Matched analyses of polyp size, morphology, and location estimates

International Journal of Colorectal Disease

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Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain

Abstract

Background

The Douleur Neuropathique 4 questionnaire (DN4) is a simple and objective tool developed by the French Neuropathic Pain Group to screen for neuropathic pain.

Methods

This prospective observational study was undertaken in three hospitals to assess the validity of a Japanese translation of the DN4. We first translated the DN4 into Japanese using a forward–backward method. Pain specialists then examined patients independently and diagnosed them with neuropathic or non-neuropathic pain, according to the International Association for the Study of Pain definitions. The Japanese version of the DN4 questionnaire was then given to each patient.

Results

Of 187 patients that met our inclusion criteria, 100 and 87 were diagnosed with neuropathic and non-neuropathic pain, respectively. The test–retest intra-class correlation coefficient (95% confidence interval) was 0.827 (0.769–0.870). Among patients with identical diagnoses of neuropathic or non-neuropathic pain, receiver-operating characteristic curve analysis revealed an area under the curve of 0.89. A cut-off point of equal or greater than 4 resulted in a sensitivity of 71% and specificity of 92%.

Conclusion

The Japanese version of the DN4 was found to be a helpful tool for discriminating between neuropathic and non-neuropathic pain.



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Association of electromyographic activation patterns with pain and functional disability in people with chronic neck pain

Abstract

Purpose

This study examined the activation patterns of the cervical and thoracic muscles in people with and without chronic neck pain during functional activities and their associations with pain intensity and functional disability.

Methods

Thirty-four adults with chronic neck pain and 34 asymptomatic adults were recruited. They were requested to perform active cervical movements and an upper limb lifting task. Electromyographic activation patterns (EMG) of bilateral upper trapezius, cervical erector spinae, sternocleidomastoid, and thoracic erector spinae were recorded during these tasks. Correlation and multiple regression analysis were used to examine the associations between EMG variables and severity of pain and functional disability.

Results

When performing the cervical movements, the neck pain group displayed lower EMG activity levels, especially in the cervical and thoracic extensors. In addition, significantly prolonged activation was observed in seven of the ten muscles during the upper limb lifting task. The changes in EMG amplitude and activation duration were found to be significantly correlated with severity of pain (R2 = 0.716) and functional disability (R2 = 0.623).

Conclusions

Significant differences in the activation patterns of multiple cervical and thoracic muscles were found in individuals with neck pain compared with those without neck pain. These were significantly associated with their degree of pain and functional limitation. The findings of this study highlight the importance of assessing and optimising the neuromuscular activation of these muscles in the rehabilitation of those suffering from chronic neck pain.



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Model-based analysis of fatigued human knee extensors

Abstract

This study investigated the effect of isometrically induced fatigue on Hill-type muscle model parameters and related task-dependent effects. Parameter identification methods were used to extract fatigue-related parameter trends from isometric and ballistic dynamic maximum voluntary knee extensions. Nine subjects, who completed ten fatiguing sets, each consisting of nine 3 s isometric maximum voluntary contractions with 3 s rest plus two ballistic contractions with different loads, were analyzed. Only at the isometric task, the identified optimized model parameter values of muscle activation rate and maximum force generating capacity of the contractile element decreased from \(20.8 \pm 8.4\) to \(11.2 \pm 4.1\) Hz and from \(18{,}137 \pm 150\) to \(10{,}666 \pm 2139\) N, respectively. For all tasks, the maximum efficiency of the contractile element, mathematically related to the curvature of the force–velocity relation, increased from \(0.35 \pm 0.04\) to \(0.42 \pm 0.05\) . The model parameter maximum contraction velocity decreased from \(0.93 \pm 0.1\) to \(0.9 \pm 0.1\) m/s and the stiffness of the serial elastic element from \(1936 \pm 227\) to \(1432 \pm 245\) N/mm. Thus, models of fatigue should consider fatigue dependencies in active as well as in passive elements, and muscle activation dynamics should account for the task dependency of fatigue.



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Phlegmonous gastritis associated with advanced esophageal cancer

Abstract

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient's condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.



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