Psychophysical Characteristics of Patients with Depression and Anxious-Depressive Disorders

Psychophysical investigations were carried out on patients with depressive and anxious-depressive disorders, including ECG, EEG, speech signal recordings, and testing of visuomotor reactions. Patients showed deterioration in measures of variational cardiometry relative to healthy subjects regardless of the presence or absence of anxiety syndrome. EEG dynamics during cognitive tests and the variability of the correlation dimension of the speech signal changed specifically in patients with anxiety syndrome. Increases in the standard deviation of the correlation dimension of the speech signal may provide an indicator of the presence of a depressive disorder, changes in the speech signal depending on the type of depressive disorder.

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Complete intracorporeal defect closure using unidirectional barbed suture in laparoscopic incisional hernia repair: Preliminary experience with short‐term follow‐up

Abstract

Introduction

Surgical techniques to close defects in laparoscopic incisional hernia repair vary across the literature. We herein demonstrate our original and standardized surgical technique for laparoscopic incisional hernia repair with complete intracorporeal defect closure using barbed suture.

Materials and Surgical Technique

Complete intracorporeal defect closures were indicated for defects less than or equal to 6 cm in transverse diameter. We performed a defect closure with a running suture using barbed suture in a caudal to cranial direction, with tissue bites and inter‐suture spacing of 1 cm each. The hernial sac was incorporated into the suturing to reduce possible dead space. After the procedure, intraperitoneal onlay mesh was placed. Seven patients underwent this procedure. The median total operative time was 188 min, and the median time specifically for defect closure was 25 min. There was no seroma, mesh bulge, persisting pain, or hernia recurrence at follow‐up.

Discussion

Our proposed technique is simple and can be safely performed with good short‐term outcomes.

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Genetic diversity and population structure analysis in Perilla crop and their weedy types from northern and southern areas of China based on simple sequence repeat (SSRs)

Abstract

Introduction

Identification of genetic variation is an essential ability for the long-term success of breeding programs and maximizes the use of germplasm resources. In East Asia, China has a long history of the cultivation of Perilla crop, but there has been little research on the genetic diversity and genetic relationships among accessions of Perilla crop and their weedy types.

Objectives

To better understand the genetic variations of the cultivated and weedy types of Perilla crop in China, the 91 accessions were evaluated for genetic diversity by 21 simple sequence repeat (SSR) markers.

Methods

SSR amplifications were conducted in a total volume of 20 µL, consisting of 20 ng genomic DNA, 1X PCR buffer, 0.5 µM forward and reverse primers, 0.2 mM dNTPs, and 1 U Taq polymerase. Power Marker version 3.25 was applied to obtain the information on the number of alleles, allele frequency, major allele frequency, gene diversity (GD), and polymorphic information content (PIC). The similarity matrix was used to construct an unweighted pair group method with arithmetic mean dendrogram by the application of SAHN-Clustering from NTSYS-pc.V.2.1.

Results

A total of 147 alleles were identified with an average of 7 alleles per locus. The average values of PIC and GD were 0.577 and 0.537, respectively. The genetic diversity level of accessions from Northern China was lower than accessions from Southern China. The genetic diversity level and PIC values for accessions of var. crispa were the highest. For accessions of cultivated var. frutescens, genetic diversity in Southern China was higher than that in Northern China.

Conclusion

Most cultivated Perilla accessions were clearly separated from weedy Perilla accessions, but there was no clear geographic structure between cultivated Perilla crop and weedy types based on their regional distribution. This study demonstrated the utility of SSR analysis for performing genetic and population analysis of cultivated and weedy types of Perilla accessions in China.

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The Transcriptional Regulator Hbx1 Affects the Expression of Thousands of Genes in the Aflatoxin-Producing Fungus Aspergillus flavus

In filamentous fungi, homeobox proteins are conserved transcriptional regulators described to control conidiogenesis and fruiting body formation. Eight homeobox (hbx) genes are found in the genome of the aflatoxin-producing ascomycete, Aspergillus flavus. While loss-of-function of seven of the eight genes had little to no effect on fungal growth and development, disruption of hbx1, resulted in aconidial colonies and lack of sclerotial production. Furthermore, the hbx1 mutant was unable to produce aflatoxins B and B₂, cyclopiazonic acid and aflatrem. In the present study, hbx1 transcriptome analysis revealed that hbx1 has a broad effect on A. flavus gene expression, and the effect of hbx1 increases overtime, impacting more than five thousand protein-coding genes. Among the affected genes, those in the category of secondary metabolism (SM), followed by that of cellular transport, were the most affected. Specifically, regarding the effect of hbx1 on SM, we found that genes in 44 SM gene clusters where upregulated while 49 were downregulated in the absence of hbx1, including genes in the SM clusters responsible for the synthesis of asparasone, piperazine and aflavarin, all known to be associated with sclerotia. In addition, our study revealed that hbx1 affects the expression of other transcription factor genes involved in development, including the conidiation central regulatory pathway and flb genes.

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The protective microRNA-199a-5p-mediated unfolded protein response in hypoxic cardiomyocytes is regulated by STAT3 pathway

Abstract

The protective effects of downregulated miR-199a-5p on ischemic and hypoxic cardiomyocytes were well recognized, but the underlying mechanism of inhibited miR-199a-5p is not yet clear. The present study explored the relationship between enhanced signal transducer and activator of transcription 3 (STAT3) signaling and lowered production of miR-199a-5p in hypoxic cardiomyocytes. This study firstly found the correlation between elevated interleukin (IL)-6 and IL-11, as well as subsequent STAT3 signaling activation and the downregulation of miR-199a-5p in hypoxic myocardial samples from children with congenital heart disease. Then, using model of hypoxic mice and the intervention of phosphorylated STAT3 (pSTAT3), it was observed that pSTAT3 affected the expression of miR-199a-5p and modulated the expression of its target genes, including endoplasmic reticulum stress (ERS)-related activating transcription factor 6 (ATF6) and 78 kDa glucose-regulated protein (GRP78). Further observation revealed that the pSTAT3 signal in cardiac tissue could affect the expression of pri-miR-199a-2, a precursor of miR-199a-5p. And the chromatin immunoprecipitation (ChIP) assay also confirmed that pSTAT3 could bind to the promoter region of miR-199a-2 gene, which is more significant under hypoxic conditions. In conclusion, the activation of STAT3 signaling in cardiomyocytes during chronic hypoxia leads to downregulation of miR-199a-5p, which promotes the expression of many downstream target genes. This is an important pathway in the adaptive protection mechanism of myocardium during hypoxia.

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Sacral Chordoma: A Clinical Review Of 101 Cases With 30-Year Experience In A Single Institution

Local recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse.

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Multifocal Visual Evoked Potentials and Contrast Sensitivity Correlate with Ganglion Cell-Inner Plexiform Layer Thickness in Multiple Sclerosis

Neurodegeneration is an important component of the pathological process in multiple sclerosis (MS), a chronic disease of the central nervous system (CNS). The anterior visual pathway, a small compartment within the CNS, is a prominent site of demyelination and neurodegenerative damage and serves as a good model in MS (Pisa et al., 2017, Toosy et al., 2017). It is well known that within the first 3 to 6 months following acute optic neuritis (ON), significant axonal and neuronal loss occurs (Costello et al., 2008, Syc et al., 2012), resulting in permanent visual dysfunction.

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Research Analysis: More than 1-in-20 EMT deaths are due to suicide

A study in Arizona over a seven-year period confirms a higher rate of death by suicide among EMTs vs. the general public

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A case–control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients

Abstract

Background

We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case–control study using a large-scale medical database in Japan.

Methods

We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month.

Results

The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia.

Conclusions

This case–control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.

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Surface microstructures are associated with mutational intratumoral heterogeneity in colorectal tumors

Abstract

Background

Recent studies revealed that colorectal tumors are composed of genetically diverse subclones. We aimed to clarify whether the surface microstructures of colorectal tumors are associated with genetic intratumoral heterogeneity (ITH).

Methods

The surface microstructures (pit patterns) of colorectal tumors were observed using magnifying endoscopy, and biopsy specimens were obtained from respective areas when tumors exhibited multiple pit patterns. A total of 711 specimens from 477 colorectal tumors were analyzed for BRAF, KRAS and TP53 mutations using pyrosequencing and direct sequencing. A panel of cancer-related genes was analyzed through targeted sequencing in 7 tumors.

Results

Colorectal tumors with multiple pit patterns exhibited more advanced pit patterns and higher frequencies of KRAS and/or TP53 mutations than tumors with a single pit pattern. In tumors with multiple pit patterns, mutations were observed as public (common to all areas) or private (specific to certain areas), and private KRAS and/or TP53 mutations were often variable and unrelated to the pit pattern grade. Notably, invasive CRCs frequently exhibited public TP53 mutations, even in adenomatous areas, which is indicative of their early malignant potential. Targeted sequencing revealed additional public and private mutations in tumors with multiple pit patterns, indicating their single clonal origin.

Conclusions

Our results suggest intratumoral pit pattern variation does not simply reflect the process of colorectal tumor evolution, but instead represents genetically diverse subclones, and this diversity may be associated with malignant potential.

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Study: Hands-only CPR training kiosks just as effective as classrooms

The American Heart Association found that a five-minute CPR lesson at a kiosk teaches people the lifesaving skill as well as a 30-minute class

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Gene‐targeted deletion in mice of the Ets−1 transcription factor, a candidate gene in the Jacobsen syndrome kidney “critical region,” causes abnormal kidney development

Ets‐1 is a member of the Ets family of transcription factors and has critical roles in multiple biological functions. Structural kidney defects occur at an increased frequency in Jacobsen syndrome (OMIM #147791), a rare chromosomal disorder caused by deletions in distal 11q, implicating at least one causal gene in distal 11q. In this study, we define an 8.1 Mb "critical region" for kidney defects in Jacobsen syndrome, which spans ~50 genes. We demonstrate that gene‐targeted deletion of Ets‐1 in mice results in some of the most common congenital kidney defects occurring in Jacobsen syndrome, including: duplicated kidney, hypoplastic kidney, and dilated renal pelvis and calyces. Taken together, our results implicate Ets‐1 in normal mammalian kidney development and, potentially, in the pathogenesis of some of the most common types of human structural kidney defects.

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EMS body armor: What providers need to know

EMS personnel must be familiar with the types of body armor and its practical on-duty use during patient assessment and care

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EMS body armor: What providers need to know

EMS personnel must be familiar with the types of body armor and its practical on-duty use during patient assessment and care

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Extremely short duration interval exercise improves 24-h glycaemia in men with type 2 diabetes

Abstract

Purpose

Reduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient exercise intervention that improves aerobic capacity and blood pressure in men with type 2 diabetes. However, the acute effects of REHIT on 24-h glycaemia have not been examined.

Methods

11 men with type 2 diabetes (mean ± SD: age, 52 ± 6 years; BMI, 29.7 ± 3.1 kg/m²; HbA_1c, 7.0 ± 0.8%) participated in a randomised, four-trial crossover study, with continual interstitial glucose measurements captured during a 24-h dietary-standardised period following either (1) no exercise (CON); (2) 30 min of continuous exercise (MICT); (3) 10 × 1 min at ~ 90 HR_max (HIIT; time commitment, ~ 25 min); and (4) 2 × 20 s 'all-out' sprints (REHIT; time commitment, 10 min).

Results

Compared to CON, mean 24-h glucose was lower following REHIT (mean ± 95%CI: − 0.58 ± 0.41 mmol/L, p = 0.008, d = 0.55) and tended to be lower with MICT (− 0.37 ± 0.41 mmol/L, p = 0.08, d = 0.35), but was not significantly altered following HIIT (− 0.37 ± 0.59 mmol/L, p = 0.31, d = 0.35). This seemed to be largely driven by a lower glycaemic response (area under the curve) to dinner following both REHIT and MICT (− 11%, p < 0.05 and d > 0.9 for both) but not HIIT (− 4%, p = 0.22, d = 0.38). Time in hyperglycaemia appeared to be reduced with all three exercise conditions compared with CON (REHIT: − 112 ± 63 min, p = 0.002, d = 0.50; MICT: -115 ± 127 min, p = 0.08, d = 0.50; HIIT − 125 ± 122 min, p = 0.04, d = 0.54), whilst indices of glycaemic variability were not significantly altered.

Conclusion

REHIT may offer a genuinely time-efficient exercise option for improving 24-h glycaemia in men with type 2 diabetes and warrants further study.

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Correction to: Physiological resolution of periodic breath holding during heavy-intensity Fartlek exercise

The original version of this article unfortunately contained a mistake.

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Ad libitum drinking adequately supports hydration during 2 h of running in different ambient temperatures

Abstract

Purpose

To examine if ad libitum drinking will adequately support hydration during exertional heat stress.

Methods

Ten endurance-trained runners ran for 2 h at 60% of maximum oxygen uptake under different conditions. Participants drank water ad libitum during separate trials at mean ambient temperatures of 22 °C, 30 °C and 35 °C. Participants also completed three trials at a mean ambient temperature of 35 °C while drinking water ad libitum in all trials, and with consumption of programmed glucose or whey protein hydrolysate solutions to maintain euhydration in two of these trials. Heart rate, oxygen uptake, rectal temperature, perceived effort, and thermal sensation were monitored, and nude body mass, hemoglobin, hematocrit, and plasma osmolality were measured before and after exercise. Water and mass balance equations were used to calculate hydration-related variables.

Results

Participants adjusted their ad libitum water intake so that the same decrease in body mass (1.1–1.2 kg) and same decrease in body water (0.8–0.9 kg) were observed across the range of ambient temperatures which yielded significant differences (p < .001) in sweat loss. Overall, water intake and total water gain replaced 57% and 66% of the water loss, respectively. The loss in body mass and body water associated with ad libitum drinking resulted in no alteration in physiological and psychophysiological variables compared with the condition when hydration was nearly fully maintained (0.3 L body water deficit) relative to pre-exercise status from programmed drinking.

Conclusions

Ad libitum drinking is an appropriate strategy for supporting hydration during running for 2 h duration under hot conditions.

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Effects of barefoot and footwear conditions on learning of a dynamic balance task: a randomized controlled study

Abstract

Purpose

Although barefoot balancing has shown to be more challenging compared to shod balancing, it is still unclear whether this may also influence the balance learning effects. The purpose of this study was to explore the impact of barefoot and shod exercising on learning of a dynamic balance task.

Methods

Sixty healthy and physically active adults (mean age 25.3 ± 3.4 years) were randomly allocated into one of three groups (barefoot, shod and controls). The barefoot and shod intervention groups exercised once weekly over 7 weeks on a stability platform with an unstable surface. Each training session included 15 trials over 30 s. Before and after the intervention period, all participants completed two balance tests (stability platform and Balance Error Scoring System = BESS) under barefoot and shod conditions. Group effects in stability gains (pre to post-test differences) were analysed using ANOVA. Development of balance learning curves during the intervention period was analysed using a mixed effects model.

Results

Balance times improved in both intervention groups (p < 0.001, 95% CI barefoot 5.82–9.22 s, shod 7.51–10.92 s) compared to controls. The barefoot intervention group showed a significantly less sloped balance learning curve compared to the shod intervention group (p = 0.033). No changes over time or differences between groups were found for the BESS test.

Conclusions

Improvements in the dynamic balance task did not differ between individuals exercising barefoot or with footwear although the progression was slower in the barefoot group. The lack of changes in the BESS supports the task-specificity of balance learning effects.

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Effects of ischemic preconditioning on economy, V O 2 kinetics and cycling performance in endurance athletes

Abstract

The aim of this study was to determine the effect of ischemic preconditioning (IPC) on several measures of aerobic function and 4-km cycling time-trial performance. An acute cross-over design was adopted involving eight well-trained cyclists (age 27.0 ± 7.0 years) who completed incremental and square-wave exercise tests for determination of peak O₂ uptake (VO_2peak), ventilatory threshold (VT) and moderate- and heavy-intensity domain VO₂ kinetics, as well as 4-km time trials. All were preceded by IPC, or sham–IPC, involving repeated bouts of thigh blood flow occlusion, interspersed with reperfusion. There was no significant difference between IPC and sham–IPC with respect to VO_2peak (4.4 ± 0.6 L min⁻¹ vs 4.4 ± 0.5 L min⁻¹, effect size − 0.01 ± 0.09), VT (3.4 ± 0.6 L min⁻¹ vs 3.5 ± 0.5 L min⁻¹, effect size 0.07 ± 0.28), cycling economy (4.9 ± 4.9%, ES 0.24 ± − 0.24, P > 0.05) or any moderate-domain VO₂ kinetic parameter. During heavy-intensity exercise, a reduced end-exercise VO₂, slow component amplitude and overall gain was observed following IPC compared to sham–IPC. Though not statistically significant, there was a possibly beneficial effect of IPC on 4-km time-trial mean power output (2.2 ± 2.0%; effect size: 0.18 ± 0.15, P > 0.05). The observed reduction in VO₂ slow component and tendency for improved economy and 4-km time-trial performance, albeit small, suggests that acute IPC shows some potential as a performance-enhancing priming strategy for well-trained cyclists prior to high-intensity exercise.

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Reply to Garcia-Tabar et al.: Quality control of open-circuit respirometry: real-time, laboratory-based systems. Let us spread “good practice”

Abstract

Purpose

This article is in response to the Letter of Garcia-Tabar et al. [Eur J Appl Physiol (in press), 2018] relating to the issue of post-test sensor calibration 'verification'. This issue is poorly addressed in contemporary patient-related position statements on cardiopulmonary exercise testing (CPET).

Methods

Post-test sensor calibration verification approaches were compared.

Result

The potential impact on data quality of changing sensor calibration during the course of an exercise test was described.

Conclusion

It is recommended that post-test sensor calibration verification be incorporated into existing CPET 'best practice'.

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The systemic myokine response of decorin, interleukin-6 (IL-6) and interleukin-15 (IL-15) to an acute bout of blood flow restricted exercise

Abstract

Purpose

Blood flow restricted resistance exercise (BFR-RE) is an emerging hypertrophy training modality. A complete profile of its mechanisms of action has yet to be elucidated. Cytokines are universal intercellular messengers. Recent research has implicated certain cytokines (termed "myokines") in skeletal muscle hypertrophy pathways; however, little research has been conducted on the systemic myokine response to BFR-RE as potential hypertrophic biomarkers. Therefore, this project was conducted to determine any differences in the systemic myokine response between BFR-RE and control conditions.

Methods

The appearance of systemic myokines interleukin-6 (IL-6), interleukin-15 (IL-15), and decorin were measured following acute bouts of low-load resistance exercise, BFR-RE, and high-load resistance exercise in physically active young males to determine if BFR-RE modifies the exercise-induced systemic myokine response.

Results

No measurable levels of IL-6 were observed during the project. No significant effects were observed for IL-15. A significant time (11.91% increase pre to post exercise; p < 0.05) but no condition or condition by time effect was observed for decorin.

Conclusion

These findings suggest that BFR-RE does not modify the systemic myokine appearance of IL-6, IL-15, or decorin when compared to control conditions.

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Quality control of open-circuit respirometry: real-time, laboratory-based systems. Let’s spread “good practice”

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Impact of maximal physical exertion on interference control and electrocortical activity in well-trained persons

Abstract

Purpose

The aim of this study was to examine the impact of a maximal physical load on cognitive control in twelve well-trained males focusing on the time course of changes in a 15 min post-exercise interval.

Methods

Prior to and three times after an incremental cycle ergometer task until exhaustion, behavioural performance and neurophysiological correlates using N2 and P3 event-related potentials (ERPs) were assessed during the execution of a modified flanker task. These data were compared to a control condition following the same protocol, however, without physical load between pre-test and post-tests.

Results

Regardless of compatibility (congruent, incongruent), behavioural findings revealed a significant interaction of Condition × Time with shorter reaction times in the post-exercise blocks as compared to the control condition. Neuroelectric measures demonstrated exercise induced effects of a reduced central N2 amplitude and shorter parietal P3 latency in the time course of post-exercise flanker blocks as compared to rest.

Conclusions

It is concluded that a state of maximal physical exhaustion facilitates information processing speed in a cognitive control task in well-trained persons. This effect persists even after a recovery period of 15 min. The current findings contribute to a deeper understanding of the neuronal mechanisms of interference control following maximal physical load, suggesting a reduced conflict monitoring as indicated by a reduced N2 amplitude and an increased stimulus classification speed as reflected by P3 latency. The flanker task, however, might have been too simple to elicit monitoring conflicts on the behavioural level.

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Neuromuscular responses of recreationally active women during a sustained, submaximal isometric leg extension muscle action at a constant perception of effort

Abstract

Purpose

The purpose of the present study was to examine the fatigue-related patterns of responses for electromyography (EMG), mechanomyography (MMG), and force during a sustained, submaximal isometric leg extension muscle action anchored at RPE = 5.

Methods

Ten women (23.1 ± 2.3 year) performed two, maximal voluntary isometric contractions (MVIC) prior to and following an isometric muscle action that was sustained at RPE = 5 (OMNI-RES) for a maximal time-limit of 5 min or until RPE = 5 could not be maintained (actual time-limit). EMG amplitude (AMP), EMG mean power frequency (MPF), MMG AMP, MMG MPF, and force values were determined every 5% of the actual or maximal time-limit. Regression analyses were used to examine the neuromuscular parameters and force vs. time relationships.

Results

The pretest MVIC (46.9 ± 8.9 kg) was significantly (p = 0.003; d = 1.8) greater than posttest (36.4 ± 5.3 kg) MVIC. The actual time-limit was 180 ± 90.9 s (range 84.8–300 s). The percent decline in force production during the sustained isometric muscle action was 34.7 ± 17.1%, and there was a significant negative, quadratic force vs. time relationship (p < 0.001; R = − 0.983). There was a significant positive, quadratic MMG AMP vs. time relationship (p < 0.001; R = 0.852), but no significant (p > 0.05) relationships for EMG AMP, EMG MPF, or MMG MPF vs. time.

Conclusions

The current findings indicated that it was necessary to reduce force to maintain RPE = 5. The neuromuscular and force responses supported the RPE clamp model and suggested that force was initially regulated by anticipatory feedforward mechanisms and then altered by afferent feedback.

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Standards and guidelines for canine clinical genetic testing laboratories

Abstract

This publication represents a proposed approach to quality standards and guidelines for canine clinical genetic testing laboratories. Currently, there are no guidelines for laboratories performing clinical testing on dogs. Thus, there is no consensus set of protocols that set the minimal standards of quality among these laboratories, potentially causing variable results between laboratories, inconsistencies in reporting, and the inability to share information that could impact testing among organizations. A minimal standard for quality in testing is needed as breeders use the information from genetic testing to make breeding choices and irreversible decisions regarding spay, neuter or euthanasia. Incorrect results can have significant impact on the health of the dogs being tested and on their subsequent progeny. Because of the potentially serious consequences of an incorrect result or incorrect interpretation, results should be reviewed by and reported by individuals who meet a minimum standard of qualifications. Quality guidelines for canine genetic testing laboratories should include not only the analytical phase, but also the preanalytical and postanalytical phases, as this document attempts to address.

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Survey Study on the Practice Patterns of the Evaluation and Management of Incidental Pancreatic Cysts

Abstract

Background and Aims

Various gastrointestinal societies have released guidelines on the evaluation of asymptomatic pancreatic cysts (PCs). These guidelines differ on several aspects, which create a conundrum for clinicians. The aim of this study was to evaluate preferences and practice patterns in the management of incidental PCs in light of these societal recommendations.

Methods

An electronic survey distributed to members of the American Society for Gastrointestinal Endoscopy (ASGE). Main outcomes included practice setting (academic vs. community), preferences for evaluation, management, and surveillance strategies for PCs.

Results

A total of 172 subjects completed the study (52% academic-based endoscopists). Eighty-six (50%) and 138 (80%) of the participants responded that they would recommend EUS surveillance of incidental PCs measuring less than 2 cm and 3 cm, respectively. Nearly half of the endosonographers (42.5% community and 44% academic; p = 1.0) would routinely perform FNA on PCs without any high-risk features. More academic-based endoscopists (57% academic vs. 32% community; p = 0.001) would continue incidental PC surveillance indefinitely.

Conclusions

There is significant variability in the approach of incidental PCs among clinicians, with practice patterns often diverging from the various GI societal guideline recommendations. Most survey respondents would routinely recommend EUS-FNA and indefinite surveillance for incidental PCs without high-risk features. The indiscriminate use of EUS-FNA and indefinite surveillance of all incidental PCs is not cost-effective, exposes the patient to unnecessary testing, and can further perpetuate diagnostic uncertainty. Well-designed studies are needed to improve our diagnostic and risk stratification accuracy in order to formulate a consensus on the management of these incidental PCs.

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Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

Abstract

Objectives

(a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF.

Methods

This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn's Disease < 3 for Crohn's disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough.

Results

A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 μg/mL), and for adalimumab 0.60 (best cutoff value 7.2 μg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing.

Conclusions

There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

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Concise Commentary: Caution, Not Cauterization—Management of Post-ESD Colorectal Hemorrhage

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An overview of rice genetics research in China

Publication date: Available online 12 November 2018

Source: Journal of Genetics and Genomics

Author(s): James A. Birchler

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Functional Neuroimaging of Speech-Related Brain Structures in Health and in Poststroke Aphasia

The introduction of noninvasive functional neuroimaging methods such as functional MRI (fMRI) into scientific and clinical studies has increased our knowledge of the organization of cognitive processes in health and during reorganization in poststroke aphasia. We present here the results of an fMRI study of the functional organization of the cerebral cortex in healthy adult humans during the processing of various types of speech information, and the main types of reorganization of the brain's speech structures in aphasia at different poststroke time points. The concepts of effective and ineffective cerebral neuroplasticity during poststroke aphasia are considered. There is a need for further complex studies, including neuropsychological investigations and some mutually complementary methods for functional neuroimaging to develop methods for the phased treatment and neurorehabilitation of patients with poststroke aphasia.

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GABAB receptors modulate Ca2+ but not G protein‐gated inwardly rectifying K+ channels in cerebrospinal‐fluid contacting neurones of mouse brainstem

Key points

Medullo‐spinal CSF contacting neurones (CSF‐cNs) located around the central canal are conserved in all vertebrates and suggested to be a novel sensory system intrinsic to the CNS. CSF‐cNs receive GABAergic inhibitory synaptic inputs involving ionotropic GABA_A receptors but the contribution of metabotropic GABA_B receptors (GABA_B‐Rs) was not studied yet. Here, we indicate that CSF‐cNs express functional GABA_B‐Rs that inhibit postsynaptic calcium channels but fail to activate inhibitory potassium channel of the kir3‐type. We further show that GABA_B‐Rs localize presynaptically on GABAergic and glutamatergic synaptic inputs contacting CSF‐cNs where they inhibit the release of GABA and glutamate. Our data are the first to address the function of GABA_B‐Rs in CSF‐cNs and show that on the presynaptic side they exert a classical synaptic modulation whereas at the postsynaptic level they have an atypical action by modulating calcium signalling without inducing potassium‐dependent inhibition.

Abstract

Medullo‐spinal neurones that contact the cerebrospinal fluid (CSF‐cNs) are a population of evolutionary conserved cells located around the central canal. CSF‐cNs activity was shown to be regulated by inhibitory synaptic inputs involving ionotropic GABA_A receptors, but the contribution of the G‐protein coupled GABA_B receptors was not studied yet. Here, we used a combination of immunofluorescence, electrophysiology and calcium imaging to investigate the expression and function of GABA_B‐Rs in CSF‐cNs of the mouse brainstem. We found that CSF‐cNs express GABA_B‐Rs, but their selective activation failed to induce G protein‐coupled inwardly‐rectifying potassium (GIRK) currents. Instead, CSF‐cNs express primarily N‐type voltage‐gated calcium (Ca_V 2.2) channels and GABA_B‐Rs recruit Gβγ subunits to inhibit Ca_v channels activity induced by membrane voltage steps or under physiological conditions by action potentials. Moreover, electrical stimulation evoked in CSF‐cNs GABAergic inhibitory (IPSCs) but also glutamatergic excitatory (EPSCs) synaptic currents, showing that mammalian CSF‐cNs are also under excitatory control by glutamatergic synaptic inputs. We further demonstrate that baclofen reversibly reduced the amplitudes of both IPSCs and EPSCs evoked in CSF‐cNs through a presynaptic mechanism of regulation. In summary, these results are the first to demonstrate the existence of functional postsynaptic GABA_B‐Rs in medullar CSF‐cNs as well as presynaptic GABA_B auto‐ and heteroreceptors regulating the release of GABA and glutamate. Remarkably, postsynaptic GABA_B‐Rs associate with Ca_V but not GIRK channels indicating that GABA_B‐Rs function as a calcium signalling modulator without GIRK‐dependent inhibition in CSF‐cNs.

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Spinal plasticity with motor imagery practice

KEY POINT SUMMARY

While the effect of Motor Imagery (MI) – the mental simulation of an action – on motor cortical areas has now reached a consensus, less is known about its impact on spinal structures. The current study, using H‐reflex conditioning paradigms, examined the effect of a 20‐min MI practice on several spinal mechanisms of the plantar flexors muscles. We observed modulations of spinal presynaptic circuitry while imagining, even more pronounced following an acute session of MI practice. We suggested that the small cortical output generated during MI may reach specific spinal circuits and that repeating MI may increase the sensitivity of the spinal cord to its effects. The short‐term plasticity induced by MI practice may include spinal network modulation in addition to cortical reorganization.

Abstract

Kinesthetic Motor imagery (MI) is the mental simulation of a movement with its sensory consequences but without its concomitant execution. While the effect of MI practice on cortical areas is well known, its influence on spinal circuitry remains unclear. Here, we assessed plastic changes in spinal structures following an acute MI practice. Thirteen young healthy participants accomplished two experimental sessions: a 20‐min MI training consisting of four blocks of twenty‐five imagined maximal isometric plantar flexions, and a 20‐min rest (control session). The level of spinal presynaptic inhibition was assessed by conditioning the triceps surae spinal H‐reflex with two methods: i) the stimulation of the common peroneal nerve that induced D1 presynaptic inhibition (H_PSI response), and ii) the stimulation of the femoral nerve that induced heteronymous Ia facilitation (H_FAC response). We then compared the effects of MI on unconditioned (H_TEST) and conditioned (H_PSI and H_FAC) responses before, immediately after and 10 minutes after the 20‐min session. After resting for 20 minutes, no changes have been observed on the recorded parameters. After MI practice, the amplitude of rest H_TEST was unchanged, while H_PSI and H_FAC significantly increased, showing a reduction of presynaptic inhibition with no impact on afferent‐motoneuronal synapse. The current results revealed the acute effect of MI practice on baseline spinal presynaptic inhibition, increasing the sensitivity of the spinal circuitry to MI. These findings would help understanding the mechanisms of neural plasticity following chronic practice.

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Blood‐brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

Key points

The blood‐brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant K_i. This paper provides evidence that K_i as measured by DCE‐MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE‐MRI for in vivo studies of human BBB permeability in health and disease.

Abstract

Background

Blood‐brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant K_i. To validate this method we compared measured K_i with biological expectations, namely (1) higher K_i in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically‐established GM/WM vascular density ratio, (3) higher K_i in visibly‐enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher K_i in MS NAWM versus healthy individual NAWM.

Methods

We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 Tesla. K_i and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Results: K_i was higher in control GM versus WM (p = 0.001). CBV was higher in GM versus WM (p = 0.005, mean ratio 1.9). K_i was higher in visibly‐enhancing MS lesions versus MS NAWM (p = 0.002), and in MS NAWM versus controls (p = 0.014). Bland‐Altman analysis showed no significant difference between ROI and segmentation methods (p = 0.638) and an intra‐class correlation coefficient showed moderate single measure consistency (0.610).

Conclusions

K_i behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of K_i measured by DCE‐MRI as a marker of overall BBB leakage.

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Age-Related ECoG Dynamics of and Convulsive Activity of Wistar Rats in a Cortical Model of Focal Epilepsy

The age-related dynamics of the ECoG and convulsive epileptiform activity induced by intracortical microinjections of 4-aminopyridine were studied in three groups of Wistar rats at ages corresponding to childhood (P20-30), adolescence (P30–45), and adulthood (P90–P120). With aging, ECoG spectral power was found to increase during waking and "sleep spindles" and to decrease during slow-wave sleep. Rats of adolescent age also showed statistically significant differences in measures of convulsive activity – mean frequency of peak-wave complexes – and the latent period of occurrence of epileptiform activity was greater than in childhood and adulthood. In addition, the total duration of epileptiform activity in rats of adolescent age was significantly lower than that in adult rats and rats at age P20–P30. The nervous system during the adolescent period may have specific protective mechanisms decreasing the intensity of convulsive activity (the ability to generate and propagate spike-wave activity), increasing resistance to epileptogen.

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The Role of the Autonomic Nervous System in the Mechanism Triggering the Adaptive Phenomenon of Remote Preconditioning

Data on the role of the autonomic nervous system in the mechanism of transmission of cardioprotective signals associated with remote ischemic preconditioning (RIPre) are contradictory. Most investigators refer to the important role of the autonomic nervous system in transmitting the defensive signal from the ischemic organ to the heart. Thus, blockade of autonomic ganglia or impairments to the integrity of the conducting nerves have been found to prevent the development of the infarct-limiting effect of RIPre. At the same time, the authors of other studies have not seen a role for the autonomic nervous system in the mechanism of the cardioprotective effect of RIPre, assigning the major role to humoral factors. Some studies have demonstrated a contribution to the cardioprotective effect of RIPre via both humoral factors and the autonomic nervous system. Analysis of these data showed that there is still no clear answer to the question of why in some cases the autonomic nervous system plays an important role in remote preconditioning while in others it does not.

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Effects of Oxytocin and Thyroliberin on Anxiety in Male White Mice in Social Stress

The effects of intranasal administration of oxytocin and thyroliberin solutions on changes in behavior in rats after moderate social stress were studied. Investigations were carried out on male Wistar rats (n = 100). Animals of experimental group 1 received intranasal oxytocin at a dose of 0.25 IU in 20 μl bilaterally and those of experimental group 2 received thyroliberin at a dose of 10 10 mmol in 10 μl, while control animals received the same volume of physiological saline. Animals were exposed to moderate social stress for 1 h starting 15 min after substance administration. Animals were tested in an elevated plus maze (EPM) after a further 3 h. These experiments showed that administration of oxytocin led to a decrease in the level of anxiety in social stress as compared with controls. Administration of thyroliberin had no effect on stress-induced changes in behavioral parameters.

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Activity Patterns in Neurons in the Retrosplenial Area of the Cortex in Operant Food-Procuring Behavior in Rats of Different Ages

Neuron spike activity was recorded in the retrosplenial area of the cortex during execution of acquired cyclic operant food-procuring behavior (COFPB) in adult (8–12 months) and elderly (20–27 months) Long-Evans rats. As compared with adult rats, elderly animals showed a significant decrease in the proportion of neurons specialized for COFPB. The normalized discharge frequency of all neurons in elderly animals during execution of basic food-procuring acts was significantly greater than that in adults. Elderly rats showed significantly fewer pairs of acts with significant differences in discharge frequency than adults, indicating that neuron activity on execution of COFPB was more uniform. These data indicate that in old age, learning involves less "extension" of existing experience due to formation of new neuronal specializations than in earlier stages of an individual's life and that the internal system structure of the newly formed behavior is more "homogeneous."

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Analysis of Sensory Information by Neurons in the Sensorimotor and Visual Cortex in Rabbits with a Rhythmic Protective Dominant

A series of experiments was performed to analyze the linked activity of neurons recorded simultaneously in the sensorimotor and visual areas of the cortex in rabbits with a defensive dominant in the CNS. The dominant focus was formed in the CNS using threshold electrical stimulation of the left paw at a frequency of 0.5 Hz. The analysis showed that trained animals responded to the tone by twitching the paw only when functional connections formed closed circuits, with a variety of different configurations, providing for circulation of rhythmic information, in the intervals between tests. In addition, these studies showed that this information was retained for weeks.

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Behavioral Symptoms of Anxiety and Depression and Brain Monoamine Contents in Rats after Chronic Intranasal Administration of Interferon-α

The effects of chronic (17 days) intranasal administration of low (50 IU/kg) and intermediate (8000 IU/kg) doses of human interferon-α (IA) on behavioral indicators of anxiety and depression and the monoaminergic system of the brain were studied in rats. Control rats received the same volume of intranasal physiological saline. IA was found to have any ambiguous effects on anxiety levels. Thus, anxiety in the open field test increased after administration of both doses of IA and decreased in the light-dark test and elevated plus maze test after small doses of IA. In the forced swimming test, administration of both doses of IA was followed by an increase in the duration of immobility (a behavioral symptom of depression). Administration of the intermediate (but not the small) dose of IA was followed by increases in the contents of dopamine and its metabolites in the olfactory bulb and decreases in the nucleus accumbens; the noradrenaline content decreased in the prefrontal cortex. It is suggested that these neurochemical changes in the brain may underlie the behavioral symptoms of depression induced by intranasal administration of intermediate doses of IA. Depression-like behavioral symptoms occurring after administration of small doses of IA were evidently not linked with changes in brain monoaminergic systems but could be due to other mechanisms.

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Effects of Derivatives of 3-Hydroxypyridine and Succinic Acid on Stereotypical Behavior and Catalepsy in Mice

The effects of derivatives of 3-hydroxypyridine and succinic acid (emoxypine, Reamberin, and Mexidol) on the state of cerebral dopaminergic processes were studied using catalepsy and stereotypical "verticalization" (climbing) behavior as criteria in experiments on mice. Single doses of emoxypine, Reamberin, and Mexidol at doses equivalent to the therapeutic range for humans were found to potentiate apomorphine-induced stereotypical behavior and to decrease the cataleptogenic effect of haloperidol. All studied derivatives of 3-hydroxypyridine and succinic acid increased spontaneous catalepsy. Emoxypine and Reamberin stimulated spontaneous stereotypical behavior in mice. The intrinsic cataleptogenic activity of the agents studied here correlated negatively with their influences on spontaneous stereotypical behavior. The nature of changes in stereotypical behavior and catalepsy in response to the test compounds provided evidence of an apparent similarity between their effects on dopaminergic processes and the phenotype of the pharmacological action of partial agonists of dopamine receptors.

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Electrographic Correlates of Predictions of the Time Course of Events

Correlates of predictive activity associated with observation of patterns in sequences of events were studied. Predictive cues consisted of fixed sequences of three stimuli preceding the appearance of a target (control) stimulus, to which the subject had to respond by pressing a computer mouse button as quickly as possible. Reaction times were analyzed for control stimuli, along with the characteristics (amplitude, duration) of contingent negative variation (CNV) in EEG fragments preceding the predictive cue stimuli and the control stimulus. Increases in CNV amplitude were demonstrated in the series of predictive stimuli preceding the appearance of the target stimulus, and this correlated positively with target stimulus reaction times.

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Molecular Mechanisms of the Effects of Metformin on the Functional Activity of Brain Neurons

Metformin (MF) is the most widely used drug for the treatment of type 2 diabetes mellitus and metabolic syndrome (MS). In the peripheral tissues, MF inhibits mitochondrial respiratory chain complex I and increases the activity of AMP-activated protein kinase (AMPK), leading to suppression of gluconeogenesis in the liver, increased insulin sensitivity, increased glucose utilization, and normalization of lipid metabolism. Recent years have seen the appearance of experimental and clinical evidence showing that the CNS is also a major target of MF, such that the action of MF on the functional state of neurons can be mediated both via AMPK-dependent and via AMPK-independent signal cascades. In contrast to the periphery, MF does not activate but suppresses AMPK activity in hypothalamic neurons, this influencing the ratio of anorexigenic (melanocortin peptides) and orexigenic (neuropeptide Y) factors and altering feeding behavior. A significant contribution to this effect is made by MF-induced activation of the leptin-dependent STAT3 signal cascade. As the leptin and melanocortin systems targeted by MF interact closely with the insulin and monoamine systems, MF, acting through them, affects the entire integrative signal system of the brain, on which the functioning of the nervous, endocrine, cardiovascular, and other body systems depend. This review analyzes and systematizes data on the molecular mechanisms and targets of the action of MF in brain neurons, and the effects of this drug, which are mediated or may be mediated by the interactions of MF with the CNS.

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