Association between Glucocorticoid Receptor Methylation and Hippocampal Subfields in Major Depressive Disorder

Background

DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls.

Methods

We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed.

Results

In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2–3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas.

Conclusions

Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.     

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background

Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer''s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects.

Methodology/Principal Findings

aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%).

Conclusions/Significance

It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects.     

Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants

Objective

Late onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.

Study Design

We examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.

Results

Infants with LOS in Cincinnati, as compared to controls, had less abundant Actinobacteria in the first samples after birth (median 18 days before sepsis onset), and less abundant Pseudomonadales in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.

Conclusions

Translocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.     

Planning the International Competition Schedules for the Health of Elite Athletes: A 21-Year Retrospective Study Evaluating the Effectiveness and Economic Impact in an Olympic Sport

Background

The increased number of trips and competitions scheduled in the international agonistic calendars meets commercial demands while acting as a source of stress for the athletes. A model, developed in biathlons to monitor the so-called competition load, revealed an upward trend over time. The aim of this study was to evaluate, in a 21-year period, the effects of the International Biathlon Union’s rescheduling of the competitive calendars to control the competition load, as well as its stability over time and the economic impact of this intervention.

Methods

For each season competition, the load factors from the international agonistic calendar (number of venues/events, competition days/distance) were considered, and the athletes’ daily and maximal stress scores were calculated. The calendar rescheduling, which started in 2001, involved the length of competitions, number of resting days and frequency of travels. Data from the period pre (1994–2000) and post (2001–2007) the intervention, as well as follow-up (2008–2015), were compared and analyzed in relation to the federation’s budget.

Results

The competition load and athletes’ daily stress score progressively increased pre, plateaued post and remained stable in follow-up. Their annual variations within the final two periods were significantly lower than in the pre period, in spite of the higher average values. The maximal stress score decreased over time. The direct correlation between most of the competition load factors with the economic budget present in pre was lost in post and follow-up. Similarly, the athletes’ daily stress score had a stable trend in post and follow-up, while budget continued to increase.

Conclusions

The management of an athlete’s potential source of stress by an international federation stabilized the competition load over time, but it did not affect the budget. Furthermore, it uncoupled the relationship between the athlete’s effort and federation income.     

Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing

Background

Subjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL), a marker of biological age, is associated with increased risk of cardiovascular disease.

Objectives

To compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age.

Methods

We measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186) and at term (n = 284). Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease.

Results

Gestational age was positively associated with LTL (r = 0.11, p = 0.02). Subjects born preterm had shorter LTL (mean (SD) T/S ratio = 3.12 (0.44)) than subjects born at term (mean (SD) T/S ratio = 3.25 (0.46)), p = 0.003). The difference remained significant after adjustment for gender and size at birth (p = 0.001). There was no association of LTL with any one of the putative risk factors analyzed.

Conclusions

Young adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm.     

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

Background

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology.

Objectives

The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls.

Method

Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained.

Results

The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences.

Conclusion

We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.     

Effect of Saccharomyces boulardii and Mode of Delivery on the Early Development of the Gut Microbial Community in Preterm Infants

Background

Recent advances in culture-independent approaches have enabled insights into the diversity, complexity, and individual variability of gut microbial communities.

Objectives

To examine the effect of oral administration of Saccharomyces (S.) boulardii and mode of delivery on the intestinal microbial community in preterm infants.

Study Design

Stool samples were collected from preterm newborns randomly divided into two groups: a probiotic-receiving group (n = 18) or a placebo group (n = 21). Samples were collected before probiotic intake (day 0), and after 2 and 6 weeks of supplementation. The composition of colonizing bacteria was assessed by 16S ribosomal RNA (rRNA) gene sequencing of fecal samples using the Ion 16S Metagenomics Kit and the Ion Torrent Personal Genome Machine platform.

Results

A total of 11932257 reads were generated, and were clustered into 459, 187, and 176 operational taxonomic units at 0 days, 2 weeks, and 6 weeks, respectively. Of the 17 identified phyla, Firmicutes Actinobacteria, Proteobacteria, and Bacteroidetes were universal. The microbial community differed at day 0 compared with at 2 weeks and 6 weeks. There was a tendency for increased bacterial diversity at 2 weeks and 6 weeks compared with day 0, and infants with a gestational age of 31 weeks or higher presented increased bacterial diversity prior to S. boulardii administration. Firmicutes and Proteobacteria remained stable during the observation period, whereas Actinobacteria and Bacteroidetes increased in abundance, the latter particularly more sharply in vaginally delivered infants.

Conclusion

While the mode of delivery may influence the development of a microbial community, this study had not enough power to detect statistical differences between cohorts supplemented with probiotics, and in a consequence, to speculate on S. boulardii effect on gut microbiome composition in preterm newborns.     

Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method

Background

Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.

Aim

To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).

Materials and Methods

127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen’s d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.

Results

The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.

Conclusion

GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.     

Neonatal Mortality and Long-Term Outcome of Infants Born between 27 and 32 Weeks of Gestational Age in Breech Presentation: The EPIPAGE Cohort Study

Objective

To determine whether breech presentation is an independent risk factor for neonatal morbidity, mortality, or long-term neurologic morbidity in very preterm infants.

Design

Prospective population-based cohort.

Population

Singletons infants without congenital malformations born from 27 to 32 completed weeks of gestation enrolled in France in 1997 in the EPIPAGE cohort.

Methods

The neonatal and long-term follow-up outcomes of preterm infants were compared between those in breech presentation and those in vertex presentation. The relation of fetal presentation with neonatal mortality and neurodevelopmental outcomes was assessed using multiple logistic regression models.

Results

Among the 1518 infants alive at onset of labor included in this analysis (351 in breech presentation), 1392 were alive at discharge. Among those eligible to follow up and alive at 8 years, follow-up data were available for 1188 children. Neonatal mortality was significantly higher among breech than vertex infants (10.8% vs. 7.5%, P = 0.05). However the differences were not significant after controlling for potential confounders. Neonatal morbidity did not differ significantly according to fetal presentation. Severe cerebral palsy was less frequent in the group born in breech compared to vertex presentation but there was no difference after adjustment. There was no difference according to fetal presentation in cognitive deficiencies/learning disabilities or overall deficiencies.

Conclusion

Our data suggest that breech presentation is not an independent risk factor for neonatal mortality or long-term neurologic deficiencies among very preterm infants.     

Does AMH Reflect Follicle Number Similarly in Women with and without PCOS?

Context

Increased Anti-Mullerian Hormone in polycystic ovary syndrome, may be due to overactive follicles rather than reflect antral follicle count.

Objective

Does Anti-Mullerian Hormone reflect antral follicle count similarly in women with or without polycystic ovary syndrome or polycystic ovarian morphology?

Design

Cross-sectional, case-control.

Setting

Women who delivered preterm in 1999–2006. For each index woman, a woman with a term delivery was identified.

Patients

Participation rate was 69%. Between 2006–2008, 262 women were included, and diagnosed to have polycystic ovary syndrome, polycystic ovarian morphology or to be normal controls.

Intervention(s)

Blood tests, a clinical examination and vaginal ultrasound.

Main Outcome Measure(s)

Anti-Mullerian Hormone / antral follicle count -ratio, SHBG, androstenedione and insulin, to test potential influence on the Anti-Mullerian Hormone / antral follicle count -ratio.

Results

Mean Anti-Mullerian Hormone / antral follicle count ratio in women with polycystic ovary syndrome or polycystic ovarian morphology was similar to that of the controls (polycystic ovary syndrome: 1,2 p = 0,10 polycystic ovarian morphology: 1,2, p = 0,27 Controls 1,3). Anti-Mullerian Hormone showed a positive linear correlation to antral follicle count in all groups. Multivariate analysis did not change the results.

Conclusions

We confirmed the positive correlation between AMH and follicle count. Anti-Mullerian Hormone seems to be a reliable predictor of antral follicle count, independent of polycystic ovary syndrome diagnosis or ovarian morphology.     

Workplace Bullying and Mental Health: A Meta-Analysis on Cross-Sectional and Longitudinal Data

Background

A growing body of research has confirmed that workplace bullying is a source of distress and poor mental health. Here we summarize the cross-sectional and longitudinal literature on these associations.

Methods

Systematic review and meta-analyses on the relation between workplace bullying and mental health.

Results

The cross-sectional data (65 effect sizes, N = 115.783) showed positive associations between workplace bullying and symptoms of depression (r = .28, 95% CI = .23–.34), anxiety (r = .34, 95% CI = .29–.40) and stress-related psychological complaints (r = .37, 95% CI = .30–.44). Pooling the literature that investigated longitudinal relationships (26 effect sizes, N = 54.450) showed that workplace bullying was related to mental health complaints over time (r = 0.21, 95% CI = 0.13–0.21). Interestingly, baseline mental health problems were associated with subsequent exposure to workplace bullying (r = 0.18, 95% CI = 0.10–0.27; 11 effect sizes, N = 27.028).

Limitations

All data were self-reported, raising the possibility of reporting- and response set bias.

Conclusions

Workplace bullying is consistently, and in a bi-directional manner, associated with reduced mental health. This may call for intervention strategies against bullying at work.     

Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

Objective

It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design

Observational, epidemiological study design.

Setting

Population-based cohort, German Neonatal Network (GNN).

Population

6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth).

Methods

Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age.

Results

PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes.

Conclusions

The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.     

Aberrations Involving Chromosome 1 as a Possible Predictor of Odds Ratio for Colon Cancer - Results from the Krakow Case-Control Study

Background

There is still an open question how to predict colorectal cancer risk before any morphological changes appear in the colon.

Objective

The purpose was to investigate aberrations in chromosomes 1, 2 and 4 in peripheral blood lymphocytes analyzed by fluorescence in situ hybridization technique as a tool to assess the likelihood of colorectal cancer.

Methods

A hospital-based case-control study included 20 colon cancer patients and 18 hospital-based controls. Information about potential covariates was collected by interview. The frequency of stable and unstable chromosome aberrations in chromosome 1, 2 and 4 was assessed by fluorescence in situ hybridization technique.

Results

Colorectal cancer patients, as compared to controls, had a relatively higher frequency of chromosome 1 translocations (median: 3.5 versus 1.0 /1000 cells, p = 0.006), stable aberrations (3.8 versus 1.0 /1000 cells, p = 0.007) and total aberrations (p = 0.009). There were no differences observed for chromosomes 2 and 4. Our results showed an increase in the odds of having colon cancer by about 50–80% associated with an increase by 1/1000 cells in the number of chromosome 1 aberrations.

Conclusions

The results revealed that the frequency of chromosomal aberrations, especially translocations in chromosome 1, seems to be a promising method to show a colon cancer risk. Additionally, our study suggests the reasonableness of use of biomarkers such as chromosome 1 aberrations in peripheral blood lymphocytes in screening prevention programs for individuals at higher colon cancer risk to identify those who are at increased risk and require more frequent investigations, e.g. by sigmoidoscopy.     

Lung Volume,Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

Background

Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques.

Methodology/Principal Findings

We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t _PTEF/t _E) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity.

Conclusions

Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.     

Longitudinal Cerebral Perfusion Change in Transient Global Amnesia Related to Left Posterior Medial Network Disruption

Background

The pathophysiology of transient global amnesia (TGA) is not fully understood. Previous studies using single photon emission computed tomography (SPECT) have reported inconclusive results regarding cerebral perfusion. This study was conducted to identify the patterns of regional cerebral blood flow (rCBF) in TGA patients via longitudinal SPECT analysis. An association between the observed SPECT patterns and a pathophysiological mechanism was considered.

Methods

Based on the TGA registry database of Seoul National University Bundang Hospital, 22 TGA patients were retrospectively identified. The subjects underwent initial Tc-99m-ethyl cysteinate dimer (ECD) SPECT within 4 days of an amnestic event and underwent follow-up scans approximately 6 months later. The difference in ECD uptake between the two scans was measured via voxel-based whole brain analysis, and the quantified ECD uptake was tested using a paired t-test.

Results

The TGA patients had significantly decreased cerebral perfusion at the left precuneus (P<0.001, uncorrected) and at the left superior parietal and inferior temporal gyrus according to the voxel-based whole brain analysis (P<0.005, uncorrected). A difference in the quantified ECD uptake between the 2 scans was also found at the left precuneus among the 62 cortical volumes of interest (P = 0.018, Cohen’s d = -0.25).

Conclusion

We identified left hemispheric lateralized hypoperfusion that may be related to posterior medial network disruption. These findings may be a contributing factor to the pathophysiology of TGA.     

UCP1 and UCP3 Expression Is Associated with Lipid and Carbohydrate Oxidation and Body Composition

Background/Objective

Uncoupling proteins (UCPs) are located in the inner membrane of mitochondria. These proteins participate in thermogenesis and energy expenditure. This study aimed to evaluate how UCP1 and UCP3 expression influences substrate oxidation and elicits possible changes in body composition in patients submitted to bariatric surgery.

Subjects/Methods

This is a longitudinal study comprising 13 women with obesity grade III that underwent bariatric surgery and 10 healthy weight individuals (control group). Body composition was assessed by bioelectrical impedance. Carbohydrate and fat oxidation was determined by indirect calorimetry. Subcutaneous adipose tissue was collected for gene expression analysis. QPCR was used to evaluate UCP1 and UCP3 expression.

Results

Obese patients and the control group differed significantly in terms of lipid and carbohydrate oxidation. Six months after bariatric surgery, the differences disappeared. Lipid oxidation correlated with the percentage of fat mass in the postoperative period. Multiple linear regression analysis showed that the UCP1 and UCP3 genes contributed to lipid and carbohydrate oxidation. Additionally, UCP3 expression was associated with BMI, percentage of lean body mass, and percentage of mass in the postoperative period.

Conclusions

UCP1 and UCP3 expression is associated with lipid and carbohydrate oxidation in patients submitted to bariatric surgery. In addition, UCP3 participates in body composition modulation six months postoperatively.     

Impaired H-Reflex Gain during Postural Loaded Locomotion in Individuals Post-Stroke

Objective

Successful execution of upright locomotion requires coordinated interaction between controllers for locomotion and posture. Our earlier research supported this model in the non-impaired and found impaired interaction in the post-stroke nervous system during locomotion. In this study, we sought to examine the role of the Ia afferent spinal loop, via the H-reflex response, under postural influence during a locomotor task. We tested the hypothesis that the ability to increase stretch reflex gain in response to postural loads during locomotion would be reduced post-stroke.

Methods

Fifteen individuals with chronic post-stroke hemiparesis and 13 non-impaired controls pedaled on a motorized cycle ergometer with specialized backboard support system under (1) seated supported, and (2) non-seated postural-loaded conditions, generating matched pedal force outputs of two levels. H-reflexes were elicited at 90°crank angle.

Results

We observed increased H-reflex gain with postural influence in non-impaired individuals, but a lack of increase in individuals post-stroke. Furthermore, we observed decreased H-reflex gain at higher postural loads in the stroke-impaired group.

Conclusion

These findings suggest an impaired Ia afferent pathway potentially underlies the defects in the interaction between postural and locomotor control post-stroke and may explain reduced ability of paretic limb support during locomotor weight-bearing in individuals post-stroke.

Significance

These results support the judicious use of bodyweight support training when first helping individuals post-stroke to regain locomotor pattern generation and weight-bearing capability.     

Norwegian PUQE (Pregnancy-Unique Quantification of Emesis and Nausea) Identifies Patients with Hyperemesis Gravidarum and Poor Nutritional Intake: A Prospective Cohort Validation Study

Objective

The English questionnaire Pregnancy-Unique Quantification of Emesis and nausea (PUQE) identifies women with severe Hyperemesis Gravidarum. Our aim was to investigate whether scores from the translated Norwegian version; SUKK (SvangerskapsUtløst Kvalme Kvantifisering) was associated with severity of hyperemesis and nutritional intake.

Design

A prospective cohort validation study.

Setting

Hospital cohort of Hyperemesis Gravidarum (HG) patients from western Norway and healthy pregnant women from Bergen, Norway.

Sample

38 women hospitalized due to HG and 31 healthy pregnant controls attending routine antenatal check-up at health centers.

Methods

Data were collected May 2013-January 2014. The study participants answered the Norwegian PUQE-questionnaire (scores ranging from 3 to15) and registered prospectively 24-hours nutritional intake by a food list form.

Main outcome measures

Differences of PUQE-scores, QOL-score and nutritional intake between hyperemesis patients and controls.

Results

Hyperemesis patients had shorter gestational age compared to controls (median 9.7 weeks; 95% CI 8.6-10.6 versus 11.9; 95% CI 10.1-12.9, p=0.004), and larger weight-change from pre-pregnant weight (loss of median 3 kg; 95% CI 3-4 versus gain of 2 kg; 95% CI 0.5-2, p<0.001) otherwise groups were similar regarding pre-pregnant BMI, age, gravidity, and inclusion weight. Compared to controls, hyperemesis patients had significant higher PUQE-score (median 13; 95% CI 11-14 vs. 7; 95% CI 4-8), lower QOL (median score 3; 95% CI 2-4 vs. 6; 95% CI 4.5-8) and lower nutritional intake (energy intake median 990 kcal/24 hours; 95% CI 709-1233 vs. 1652; 95% CI 1558-1880 all p<0.001). PUQE-score was inversely correlated to nutritional intake (-0.5, p<0.001). At discharge PUQE-score had fallen to median 6 (95% CI 5-8) and QOL score risen to 7 (95% CI 6-8) in the HG group, (both p<0.001 compared to admission values).

Conclusion

PUQE-scoring has been validated as a robust indicator of severe hyperemesis gravidarum and insufficient nutritional intake in a Norwegian setting.     

Microstructural White Matter Changes,Not Hippocampal Atrophy,Detect Early Amnestic Mild Cognitive Impairment

Background

Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.

Methods

We studied 155 cognitively normal (CN) and 27 ‘late’ aMCI individuals with stable diagnosis over 2 years, and 39 ‘early’ aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts.

Results

Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes.

Conclusions

Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.