Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea

BackgroundIntermittent hypoxia and obesity which are two pathological conditions commonly found in patients with obstructive sleep apnea (OSA), potentially enhance cancer progression.ObjectiveTo investigate whether obesity and/or intermittent hypoxia (IH) mimicking OSA affect tumor growth.MethodsA subcutaneous melanoma was induced in 40 mice [22 obese (40–45 g) and 18 lean (20–25 g)] by injecting 10⁶ B16F10 cells in the flank. Nineteen mice (10 obese/9 lean) were subjected to IH (6 h/day for 17 days). A group of 21 mice (12 obese/9 lean) were kept under normoxia. At day 17, tumors were excised, weighed and processed to quantify necrosis and endothelial expression of vascular endothelial growth factor (VEGF) and CD-31. VEGF in plasma was also assessed.ResultsIn lean animals, IH enhanced tumor growth from 0.81 ± 0.17 to 1.95 ± 0.32 g. In obese animals, a similar increase in tumor growth (1.94 ± 0.18 g) was observed under normoxia, while adding IH had no further effect (1.69 ± 0.23 g). IH only promoted an increase in tumoral necrosis in lean animals. However, obesity under normoxic conditions increased necrosis, VEGF and CD-31 expression in tumoral tissue. Plasma VEGF strongly correlated with tumor weight (ρ = 0.76, p < 0.001) in the whole sample; it increased in lean IH-treated animals from 66.40 ± 3.47 to 108.37 ± 9.48 pg/mL, p < 0.001), while the high baseline value in obese mice (106.90 ± 4.32 pg/mL) was unaffected by IH.ConclusionsObesity and IH increased tumor growth, but did not appear to exert any synergistic effects. Circulating VEGF appeared as a crucial mediator of tumor growth in both situations.     

Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans

PurposeThere is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.Methods36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54 ± 27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45 ± 19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3⁺CD4⁺-, CD3⁺CD8⁺- and CD4⁺CD25⁺-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs.ResultsValproate intake resulted in a significant decrease of the total white blood count (6.96 ± 1.23/nl vs. 6.13 ± 1.57/nl, p = 0.026) and of absolute count and percentage of neutrophils (4.60 ± 1.05/nl vs. 3.69 ± 1.30/nl, p = 0.01; 65.4 ± 7.9% vs. 59.5 ± 11.5%, p = 0.01, respectively). The percentage of CD3⁺CD4⁺-lymphocytes dropped significantly (50.4 ± 10.9% vs. 45.3 ± 12.3%, p = 0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4⁺CD25⁺-lymphocytes (26.1 ± 8.0% vs. 21.5 ± 9.2%, p = 0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.ConclusionValproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.     

Epstein–Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis

Epstein–Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3 ?/? mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4 + and CD8 + T cells isolated from infected EBI3 ?/? mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection.     

Neural drive during continuous positive airway pressure (CPAP) and pressure relief CPAP

BackgroundPressure release continuous positive airway pressure (CPAP) is an evolution of CPAP that has been reported to improve patient comfort. We hypothesised the pressure release would lead to unloading of the inspiratory muscles and therefore conducted a prospective double-blind cross-over physiological study of autotitrating CPAP (APAP) against autotitrating pressure relief CPAP (PR-APAP).MethodsEleven patients with severe obstructive sleep apnoea (OSA; mean AHI 74.5 ± 14.4/h) were studied. We assessed neural drive by recording the oesophageal pressure, gastric pressure, transdiaphragmatic pressure and the diaphragm EMG during overnight polysomnography.ResultsBoth APAP and PR-APAP significantly reduced neural respiratory drive. Transdiaphragmatic pressure swings during apnoea (30.2 ± 11.5 cm H₂O) before treatment decreased to 9.1 ± 5.3 cm H₂O for PR-APAP and 8.5 ± 3.7 cm H₂O for APAP. The transdiaphragmatic pressure and the diaphragm EMG did not differ significantly between APAP and PR-APAP. The gastric pressure swing at expiration phase disappeared during both APAP and PR-APAP when sleep respiratory events were eliminated.ConclusionsPR-APAP is not superior to APAP in terms of reducing neural respiratory drive. It is unnecessary to replace conventional APAP with PR-APAP for patients who have been successfully treated with traditional APAP.     

Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes

PurposeTo further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8⁺ T lymphocytes in humans.MethodsIn 15 healthy subjects (9 female (60%), 35.7 ± 12.1 years), apoptosis and cytotoxic function of CD8⁺ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5 mg/L and 50 mg/L) and VPA (10 mg/L and 100 mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1 h or 24 h. Cytotoxic function was assessed following 2 h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8⁺ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR).ResultsHigh concentration of LEV decreased perforin release of CD8⁺ T lymphocytes (LEV 50 mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5–35.9%) vs. 16.6% (IQR 12–24.9%), p = 0.002). LEV had no influence on apoptosis and proliferation (p > 0.05). VPA (100 mg/L) slowed apoptosis of CD8⁺ T lymphocytes after 24 h (VPA 100 mg/L vs. control: 7.3% (IQR 5.4–9.5%) vs. 11.3% (IQR 8.2–15.1%), p < 0.001), but had no effects on perforin release (p > 0.05). SV2A protein was detected in CD8⁺ T lymphocytes.ConclusionLEV decreased degranulation of CD8⁺ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect.     

Visual evoked potentials in infants of diabetic mothers: Relations to clinical and metabolic status during pregnancy and delivery

ObjectiveTo evaluate Visual Evoked Potentials (VEPs) and psychomotor development of infants of diabetic mothers (IDMs) in relation to clinical and metabolic data during pregnancy and delivery.MethodsVEPs and psychomotor development (Brunet–Lézine) were analysed in 40 two-month-old IDMs (21 males, 19 females), 24 from mothers with type-1 diabetes, 13 gestational diabetes, and 3 type-2 diabetes. Normative VEP data were obtained from 63 age matched controls.ResultsVEP latencies were significantly longer in IDMs than in controls (O1 wave IV = 197.9 ± 35.5 vs 155.3 ± 30.3; P < 0.001; O2 wave IV = 200.2 ± 33.8 vs 155.6 ± 29.0; P < 0.001). The mean developmental quotient was normal. In IDMs with type-1 diabetes delayed VEPs were related to increased weight during pregnancy (r 0.516; P 0.009), 1st trimester fasting blood glucose (r 0.458; P 0.037), insulin requirement during the 2nd (r 0.441; P 0.035) and 3rd trimester (r 0.422; P 0.039); in IDMs with gestational diabetes, VEP latency showed negative relation to Apgar scores (r −0.748; P 0.008).ConclusionsIDMs have delayed VEPs, which may possibly be related to poor metabolic control in pre-gestational diabetes, and to delivery complications in gestational diabetes.SignificanceIDMs show subtle neurophysiologic changes detectable by VEPs.     

The effect of lamotrigine on learning in mice using the passive avoidance model

IntroductionLamotrigine (LTG) is an antiepileptic drug that inhibits the release of glutamate by blocking sodium channels. The present study was conducted to evaluate the effect of LTG in different stages of memory using a passive avoidance learning task in mice.MethodsMale albino mice in the weight range 20–25 g were used. They were divided into four groups (control group and three groups receiving various doses of LTG). LTG was given in three doses of 10, 25, and 50 mg/kg as intraperitoneal (IP) injections. The doses of LTG were used in three injection groups: before acquisition, after consolidation, and before retrieval at 24 h. The retention latency times in each group were recorded using a step-through passive avoidance task 24 h and one week after consolidation.ResultsRetention latency in the group receiving a high dose of LTG (25 mg/kg) after one week was significantly increased in comparison to the group receiving a low dose of LTG (10 mg/kg) (267 ± 49.96 vs. 198.87 ± 57.22, P = 0.015). With injection of LTG after consolidation, the retention latency times were increased in all doses after a one-week retrieval compared to the control (P = 0.023). Kaplan–Mayer surveillance analysis also showed significant differences in the latencies of the LTG-receiving group after 24 h and one week's retrieval (P = 0.041). Administration of LTG before retrieval at 24 h showed a significant difference in retention latency time, which was increased for two doses of LTG (10 and 50 mg/kg) after one week (203.5 ± 63.67 vs. 270.25 ± 19.78, P = 0.024).ConclusionLTG at higher doses may facilitate the learning process in mice and appears to improve memory function at different stages.     

Olfactory dysfunction in pure autonomic failure: Implications for the pathogenesis of Lewy body diseases

BackgroundPure autonomic failure (PAF) and Parkinson disease (PD) both are Lewy body diseases, and both entail substantia nigra dopaminergic, locus ceruleus noradrenergic, and cardiac sympathetic denervation. Multiple system atrophy (MSA) is a non-Lewy body disease in which alpha-synuclein accumulates in glial cells, with central catecholamine deficiency but preserved cardiac sympathetic innervation in most patients. PD is associated with more severe and consistent olfactory dysfunction than in MSA; whether PAF entails olfactory dysfunction has been unknown. In this study we assessed olfactory function in PAF in comparison with the two other synucleinopathies and whether olfactory dysfunction correlates with neuroimaging evidence of cardiac noradrenergic or nigrostriatal dopaminergic denervation.MethodThe University of Pennsylvania Smell Identification Test (UPSIT) was administered to 8 patients with PAF, 23 with PD, and 20 with MSA. 6-[¹⁸F]Fluorodopamine positron emission tomographic (PET) scanning was used to indicate cardiac noradrenergic innervation and the putamen:occipital cortex (PUT:OCC) and substantia nigra (SN):OCC ratios of 6-[¹⁸F]fluorodopa-derived radioactivity to indicate nigrostriatal dopaminergic innervation.ResultsThe PAF group had a low mean UPSIT score (22 ± 3), similar to that in PD (20 ± 2) and lower than in MSA (31 ± 2, p = 0.004). Individual UPSIT scores correlated positively with cardiac 6-[¹⁸F]fluorodopamine-derived radioactivity (r = 0.63 in the septum, p < 0.0001; r = 0.64 in the free wall, p < 0.0001) but not with PUT:OCC or SN:OCC ratios of 6-[¹⁸F]fluorodopa-derived radioactivity.DiscussionIn synucleinopathies, olfactory dysfunction is related to Lewy body pathology and cardiac sympathetic denervation, independently of parkinsonism or striatal dopamine deficiency.     

Unilateral strength training increases voluntary activation of the opposite untrained limb

ObjectiveWe investigated whether an increase in neural drive from the motor cortex contributes to the cross-limb transfer of strength that can occur after unilateral strength training.MethodsTwitch interpolation was performed with transcranial magnetic stimulation to assess changes in strength and cortical voluntary activation in the untrained left wrist, before and after 4 weeks of unilateral strength-training involving maximal voluntary isometric wrist extension contractions (MVCs) for the right wrist (n = 10, control group = 10).ResultsWrist extension MVC force increased in both the trained (31.5 ± 18%, mean ± SD, p < 0.001) and untrained wrist (8.2 ± 9.7%, p = 0.02), whereas wrist abduction MVC did not change significantly. The amplitude of the superimposed twitches evoked during extension MVCs decreased by 35% (±20%, p < 0.01), which contributed to a significant increase in voluntary activation (2.9 ± 3.5%, p < 0.01). Electromyographic responses to cortical and peripheral stimulation were unchanged by training. There were no significant changes for the control group which did not train.ConclusionUnilateral strength training increased the capacity of the motor cortex to drive the homogolous untrained muscles.SignificanceThe data show for the first time that an increase in cortical drive contributes to the contralateral strength training effect.     

Role of serum levels of neurotensin in children with autism spectrum disorder

AimNeuroinflammation may play a role in the pathogenesis of autism in some patients. The aim of this study was to measure serum levels of neurotensin (NTS) in relation to the degree of the severity of autism.MethodsSerum NTS was measured in autistic children (n = 38; mean age 7.02 ± 2.03 years) and healthy, unrelated sex matched controls (n = 39); mean age 7.25 ± 1.64 years). The severity of autism symptoms was assessed using Childhood Autism Rating Scale (CARS) scores.ResultsThe serum level of NTS was significantly (P < 0.001) lower in autistic children (mean ± S.D. = 54.71 ± 12.4 pg/ml) than control group (mean ± S.D. = 77.58 ± 10.29 pg/ml). Children with severe autism had significantly lower serum NTS levels than patients with mild to moderate autism (P < 0.002). There was significant negative correlation between serum levels of NTS and CARS SCORES (r² = 0.79, P = 0.001).ConclusionsSerum NTS levels were elevated in some autistic children and they were significantly correlated with the severity of autism. However, this is an initial report that warrants further research to determine the pathogenic role of NTS and its possible link to neuroinflammation in autism.     

Arginine vasopressin relates with spatial learning and memory in a mouse model of spinocerebellar ataxia type 3

Spinocerebellar ataxia is an inherited neurodegenerative disorder that the most prevalent type is type 3 (SCA3). Arginine vasopressin (AVP) is released within the lateral septum for controlling the learning and memory. This communication studied the effect of AVP on the spatial learning and memory of SCA3 mice. The spatial learning and memory were analyzed by Morris water maze test (MWM), and AVP concentration was measured by radioimmunoassay. The results showed that (Alves et al., 2010) the swimming velocity, distance traveled and latency to the platform of MWM in SCA3 mice were reduced slower than those in WT mice over 4 training days (p < 0.05, 0.01 or 0.001); (Antunes and Zimmerman, 1978) SCA3 mice showed a lower performance of spatial learning and memory of MWM during the fifth day (test day) compared to WT mice; (Bao et al., 2014) SCA3 mice had a decrease of AVP concentration in cerebral cortex (6.3 ± 0.6 pg/mg vs. 11.4 ± 1.0 pg/mg, p < 0.01), hypothalamus (6.1 ± 1.3 ng/mg vs. 10.3 ± 2.1 ng/mg, p < 0.05), hippocampus (3.2 ± 0.5 pg/mg vs. 5.2 ± 1.0 pg/mg, p < 0.01) and cerebellum (4.7 ± 0.9 pg/mg vs. 8.3 ± 1.1 pg/mg, p < 0.01), not in spinal cord, pituitary and serum; and (Barberies and Tribollet, 1996) intraventricular AVP could significantly quicken swimming velocity, cut down distance traveled and reduce latency to the platform of MWM in a dose-dependent manner, but intraventricular AVP receptor antagonist weakened the spatial learning and memory of MWM in SCA3 mice during the fifth day. The data suggested that AVP in the brain, not spinal cord and peripheral system of SCA3 mice related with the change of the spatial learning and memory of MWM.     

Targeted disruption of the orphan receptor Gpr151 does not alter pain-related behaviour despite a strong induction in dorsal root ganglion expression in a model of neuropathic pain

BackgroundGpr151 is an orphan GPCR whose function is unknown. The restricted pattern of neuronal expression in the habenula, dorsal horn of the spinal cord and dorsal root ganglion plus homology with the galanin family of receptors imply a role in nociception.ResultsReal-time quantitative RT-PCR demonstrated a 49.9 ± 2.9 fold highly significant (P < 0.001) increase in Gpr151 mRNA expression in the dorsal root ganglion 7 days after the spared nerve injury model of neuropathic pain. Measures of acute, inflammatory and neuropathic pain behaviours were not significantly different using separate groups of Gpr151 loss-of-function mutant mice and wild-type controls. Galanin at concentrations between 100 nM and 10 μM did not induce calcium signalling responses in ND7/23 cells transfected with Gpr151.ConclusionsOur results indicate that despite the very large upregulation in the DRG after a nerve injury model of neuropathic pain, the Gpr151 orphan receptor does not appear to be involved in the modulation of pain-related behaviours. Further, galanin is unlikely to be an endogenous ligand for Gpr151.     

The effect of cigarette smoking on vitamin D level and depression in male patients with acute ischemic stroke

ObjectiveThe association between low vitamin D levels and depression has been well documented in nonstroke subjects. Accumulating evidence shows that low vitamin D levels may be also associated with depression post stroke. Cigarette smoking was associated with lower vitamin D levels. The purposes of this study were to compare vitamin D levels in smokers to nonsmokers and examine the association between vitamin D levels and depression symptoms in patients with acute ischemic stroke.Materials and methodsSerum levels of 25-hydroxyvitamin D [25(OH)D] were measured in 194 males within 24 h after admission: 116 smokers and 78 nonsmokers. Depression symptoms were assessed with the 17-item Hamilton Depression Scale (HAMD-17). Patients with the HAMD-17 score >7 were identified to have depression symptoms.ResultsThe chi-square test showed that the frequency of depression in the smoker group was 23.3% (27/116), which was significantly higher than that in the nonsmoker group (11.5% = 9/78), with an odds ratios (OR) of 2.33 (95% CI: 1.03–5.27; χ² = 4.25, df = 1, p = 0.039, φ = 0.15). Vitamin D levels were significantly lower in smokers than in nonsmokers (52.4 ± 20.8 vs 61.7 ± 19.2; F = 9.88, p = 0.002), with an effect size of 0.05 (η_p²). Patients with depression symptoms showed lower vitamin D levels than those with no depression symptoms (49.2 ± 19.6 vs 57.7 ± 20.6; F = 5.03, p = 0.03), with an effect size of 0.03 (η_p²).ConclusionHigher rates of depression in smokers with acute ischemic stroke may be associated with lower vitamin D levels induced by smoking.     

Effects of insulin-like growth factor-1 (IGF-1) receptor signaling on rates of apoptosis in retina of dopamine beta hydroxylase (Dbh−/−) knockout mice

We have investigated whether insulin-like growth factor-1 (IGF-1) receptor signaling alters rates of apoptosis in dopamine beta-hydroxylase (Dbh^?/?) knockout mice. Retinal lysates from Dbh^?/? and their heterozygote littermates (Dbh^+/?) were used to examine the role of norepinephrine in the regulation of IGF-1 receptor signaling and apoptosis in the retina. Western blot analysis was done for protein levels of total and phosphorylated IGF-1 receptor, insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and Akt. A caspase 3 ELISA and dopamine ELISA were done on retinal lysates. To verify which regions of the retina were undergoing apoptosis, TUNEL labeling was performed. No changes in dopamine were noted between the KO and heterozygote mice. IGF-1 receptor phosphorylation was significantly decreased in Dbh^?/? mice as compared to their heterozygote littermates (P < 0.05 vs. heterozygous mice). IRS-1 protein phosphorylation was significantly decreased in KO mice (P < 0.05 vs. heterozygous mice), while no significant changes were noted in IRS-2 protein phosphorylation. Akt protein phosphorylation was also reduced in the KO mice, likely leading to increased cleaved caspase 3 levels. The increase in apoptosis in the Dbh^?/? mice occurred predominantly in the inner retina. Our results suggest that IGF-1 receptor signaling is reduced in the retina of mice with dysfunctional adrenergic receptor signaling. The data also indicate that IGF-1 receptor signaling occurs primarily through IRS-1, rather than IRS-2. The reduction in Akt phosphorylation, likely through reduced IGF-1 receptor signaling, could explain the increase in cleaved caspase 3, leading to apoptosis. These results suggest that alterations in adrenergic receptor signaling modulate IGF-1 receptor signaling, which can regulate apoptosis in the retina.     

Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

ObjectiveHigher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr).MethodsPlasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4⁺ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin.ResultsBefore ART, phe/tyr was mean ± S.D.: 0.99 ± 0.57 μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4⁺ counts (rs = ?0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 ± 0.16 (=?27%; U = 5.21, p = 0.01) which was due to an average decline of ?14% of phe concentrations from 73.1 ± 34.0 μmol/L at baseline to 62.9 ± 17.8 μmol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13%, U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART.ConclusionsIncreased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.     

Using a motor imagery questionnaire to estimate the performance of a Brain–Computer Interface based on object oriented motor imagery

ObjectivesThe primary objective was to test whether motor imagery (MI) questionnaires can be used to detect BCI ‘illiterate’. The second objective was to test how different MI paradigms, with and without the physical presence of the goal of an action, influence a BCI classifier.MethodsKinaesthetic (KI) and visual (VI) motor imagery questionnaires were administered to 30 healthy volunteers. Their EEG was recorded during a cue-based, simple imagery (SI) and goal oriented imagery (GOI).ResultsThe strongest correlation (Pearson r² = 0.53, p = 1.6e-5) was found between KI and SI, followed by a moderate correlation between KI and GOI (r² = 0.33, p = 0.001) and a weak correlation between VI and SI (r² = 0.21, p = 0.022) and VI and GOI (r² = 0.17, p = 0.05). Classification accuracy was similar for SI (71.1 ± 7.8%) and GOI (70.5 ± 5.9%) though corresponding classification features differed in 70% participants. Compared to SI, GOI improved the classification accuracy in ‘poor’ imagers while reducing the classification accuracy in ‘very good’ imagers.ConclusionThe KI score could potentially be a useful tool to predict the performance of a MI based BCI. The physical presence of the object of an action facilitates motor imagination in ‘poor’ able-bodied imagers.SignificanceAlthough this study shows results on able-bodied people, its general conclusions should be transferable to BCI based on MI for assisted rehabilitation of the upper extremities in patients.     

Tempéraments affectifs prébipolaires dans les dépressions récurrentes : vers un dépistage de « fausse unipolarité »

IntroductionThe current categorical split of mood disorders into bipolar disorders and depressive disorders has recently been questioned after the widening of the bipolar spectrum. Recent studies have suggested that clinicians may under-diagnose bipolarity in a substantial proportion of depressed patients, and have proposed the existence of a “pseudo-unipolar” depression. On the other hand, many studies were made to identify factors correlated to bipolarity in depressive disorders. They have shown that the main clinical factors correlated to bipolarity are: pharmacological hypomania, puerperal depression, early age of onset, psychotic features, hypersomnia and psychomotor inhibition. In this context, it should be interesting to study temperaments as predictive factors of bipolarity in depression and to explore their correlation with those clinical predictors.ObjectivesThe aims of this study were to assess affective temperaments in patients with recurrent depressive disorders, and to explore the correlations between these temperaments and clinical features of depressive disorders.MethodsThe study was a cross-sectional one bearing on 91 recurrent depressive patients (40 men and 51 women, mean age: 46.8 ± 10.1 years), who were interviewed using the DSM-IV Structured Clinical Interview during the partial or total recovery period. Data was collected using available medical records. The evaluation of affective temperaments consisted in filling in the Akiskal and Mallya semi-structured questionnaire.ResultsThe depressive temperament obtained the higher mean score (12.3 ± 4.74), followed by the hyperthymic temperament (7.8 ± 4.5), the cyclothymic temperament (5.9 ± 5.8) and the irritable temperament (4.9 ± 3.3). A significant association was found between the onset of the first depressive episode during the postpartum period and the cyclothymic temperament score (7.4 ± 6.9 versus 3.3 ± 3.6, p = 0.04). The psychotic features in the last depressive episode were significantly associated with the hyperthymic (p = 0,001), the cyclothymic (p < 10^?3) and the irritable temperament scores (p < 10^?3). A significant link was found between suicide attempts during the last depressive episode and the cyclothymic temperament on the one hand (p < 10^?3) and the irritable temperament on the other hand (p = 0.01).ConclusionsThe recurrent depressive disorders with hyperthymic, cyclothymic and the irritable temperaments seem to have clinical features similar to those of bipolar disorders. These results point to the importance of evaluating these temperaments in depressed patients, considering the risk of polarity change and of misdiagnoses of unipolar depression.     

Pulmonary capillary wedge pressure and pulmonary arterial pressure in heart failure patients with sleep-disordered breathing

BackgroundThere is a high prevalence of central sleep apnea (CSA) in patients with chronic heart failure (CHF). The present study investigates the hypotheses that CSA in CHF patients reflects heart failure severity as measured by cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP).MethodsIn 105 patients with stable CHF (NYHA ? II, LV-EF ? 40%) cardiorespiratory polygraphy and simultaneous right and left heart catheterization was performed.ResultsCSA was present in 58% and obstructive sleep apnea (OSA) in 23% of patients. In CSA patients, PAP and PCWP were significantly higher when compared to patients without SDB. In CSA patients, but not in OSA patients, PCWP showed a significant correlation with apnea–hypopnea index (AHI; r = 0.41, p = 0.005), apnea index (AI; r = 0.44, p = 0.003) and central AI (cAI; r = 0.358, p = 0.015). Cardiac index was more impaired in CSA (1.93 ± 0.5 l/min/m²) than in OSA patients (2.55 ± 1.0 l/min/m²) or those without SDB (2.22 ± 0.4 l/min/m²). A negative correlation of CI and cAI (r = ?0.344, p = 0.008), AI (r = ?0.31, p = 0.02) and AHI (r = ?0.21, p < 0.05) was documented exclusively in CSA patients.ConclusionThe present study supports the hypotheses that the occurrence and severity of CSA in CHF patients reflects heart failure severity.     

Microglial MyD88 signaling regulates acute neuronal toxicity of LPS-stimulated microglia in vitro

Although the role of microglial activation in neural injury remains controversial, there is increasing evidence for a detrimental effect in the immature brain, which may occur in response to release of neurotoxic substances including pro-inflammatory cytokines. However, the signaling mechanisms involved in microglial-induced neuronal cell death are unclear. Microglia isolated from the brains of wild-type (WT) or MyD88 knockout (KO) mice were exposed to PBS or the TLR4-ligand LPS (100 ng/mL) for 2, 6, 14, or 24 h, and the microglia-conditioned medium (MCM) collected. Detection of multiple inflammatory molecules in MCM was performed using a mouse 22-plex cytokine microbead array kit. Primary neuronal cultures were supplemented with the 14 or 24 h MCM, and the degree of neuronal apoptosis examined after exposure for 24 h. Results showed a rapid and sustained elevation in multiple inflammatory mediators in the MCM of WT microglia exposed to LPS, which was largely inhibited in MyD88 KO microglia. There was a significant increase in apoptotic death measured at 24 h in cultured neurons exposed to CM from either 14 or 24 h LPS-stimulated WT microglia (p < .05 vs. WT control). By contrast, there was no increase in apoptotic death in cultured neurons exposed to CM from 14 or 24 h LPS-stimulated MyD88 KO microglia (p = .15 vs. MyD88 KO control). These data suggest that MyD88-dependent activation of microglia by LPS causes release of factors directly toxic to neurons.     

Effect of pain on the modulation in discharge rate of sternocleidomastoid motor units with force direction

ObjectiveTo compare the behavior of sternocleidomastoid motor units of patients with chronic neck pain and healthy controls.MethodsNine women (age, 40.4 ± 3.5 yr) with chronic neck pain and nine age- and gender-matched healthy controls participated. Surface and intramuscular EMG were recorded from the sternocleidomastoid muscle bilaterally as subjects performed isometric contractions of 10-s duration in the horizontal plane at a force of 15 N in eight directions (0–360°; 45° intervals) and isometric contractions at 15 and 30 N force with continuous change in force direction in the range 0–360°. Motor unit behavior was monitored during the 10-s contractions and the subsequent resting periods.ResultsThe mean motor unit discharge rate depended on the direction of force in the control subjects (P < 0.05) but not in the patients. Moreover, in three of the nine patients, but in none of the controls, single motor unit activity continued for 8.1 ± 6.1 s upon completion of the contraction. The surface EMG amplitude during the circular contraction at 15 N was greater for the patients (43.5 ± 54.2 μV) compared to controls (16.9 ± 14.9 μV; P < 0.05).ConclusionsThe modulation in discharge rate of individual motor units with force direction is reduced in the sternocleidomastoid muscle in patients with neck pain, with some patients showing prolonged motor unit activity when they were instructed to rest.SignificanceThese observations suggest that chronic neck pain affects the change in neural drive to muscles with force direction.