Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke - a longitudinal MRI study using arterial spin labeling perfusion

BACKGROUND Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Prevalence, genetic diversity and antimicrobial susceptibility of Listeria monocytogenes isolated from open-air food markets in Greece

A total of 210 food samples originating from milk products, ready-to-eat salads, raw meat and raw meat products purchased in ten open-air market places in Thessaloniki, Greece, were analyzed for the presence of Listeria monocytogenes. Thirty (14.3%) contained L. monocytogenes with the highest prevalence in raw meat (27.5%), raw meat products (18%) and cheese (8%). The strains were susceptible to 16 antimicrobials as determined by microbroth dilution, except one strain which displayed resistance to tetracycline (MIC > 32 μg/ml). This strain carried the tetracycline resistance gene tet(M). Pulsed-field gel electrophoresis (PFGE) revealed a low genetic diversity among the isolates, irrespective of their origin. This suggests that dominant L. monocytogenes clones are widespread in different food product types in open-air food markets in Greece. The high prevalence of L. monocytogenes in these products indicates that appropriate hygienic measures and periodic bacteriological controls are also necessary in open-air food markets to reduce contamination with food-borne pathogens. Greek specialties made with raw meat and raw milk may contain L. monocytogenes and should not be consumed by persons at risk.

Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance

Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

BACKGROUND Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. METHODS 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. RESULTS Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048). CONCLUSIONS This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.

Real-time simulation of nonequilibrium transport of magnetization in large open quantum spin systems driven by dissipation

Using quantum Monte Carlo, we study the nonequilibrium transport of magnetization in large open strongly correlated quantum spin-12 systems driven by purely dissipative processes that conserve the uniform or staggered magnetization, disregarding unitary Hamiltonian dynamics. We prepare both a low-temperature Heisenberg ferromagnet and an antiferromagnet in two parts of the system that are initially isolated from each other. We then bring the two subsystems in contact and study their real-time dissipative dynamics for different geometries. The flow of the uniform or staggered magnetization from one part of the system to the other is described by a diffusion equation that can be derived analytically.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study is to investigate FAA and its correlation with resting – state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant for reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left – lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients) and in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right – lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls.

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. OBJECTIVE The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. METHODS Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. RESULTS Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. CONCLUSION Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations.

Determinants of stimulated salivary flow among haematopoietic stem cell transplantation recipients.

OBJECTIVES The aetiology of hyposalivation in haematopoietic stem cell transplantation (HSCT) recipients is not fully understood. This study examined the effects of treatment-related aetiological factors, particularly medications, on stimulated salivary flow in HSCT recipients. SUBJECTS AND METHODS Adult HSCT recipients (N = 118, 66 males, 27 autologous and 91 allogeneic transplants) were examined. Stimulated whole salivary flow rates (SWSFR) were measured before HSCT and at 6 and 12 months post-HSCT. Linear regression models were used to analyse the associations of medications and transplant-related factors with salivary flow rates, which were compared to salivary flow rates of generally healthy controls (N = 247). RESULTS The SWSFR of recipients were lower pre-HSCT (mean ± standard deviation, 0.88 ± 0.56 ml/min; P < 0.001), 6 months post-HSCT (0.84 ± 0.61; P < 0.001) and 12 months post-HSCT (1.08 ± 0.67; P = 0.005) than the SWSFR of controls (1.31 ± 0.65). In addition, hyposalivation (<0.7 ml/min) was more frequent among HSCT recipients pre-HSCT (P < 0.001), 6 months post-HSCT (P < 0.001) and 12 months post-HSCT (P = 0.01) than among controls. The SWSFR was observed to improve over time being significantly higher 12 months post-HSCT compared to pre-HSCT (P < 0.001). The observed decrease of salivary flow could not be explained by the examined transplant-related factors and medications. CONCLUSIONS Decreased stimulated salivary flow rates could not be explained by the examined factors alone; these findings indicate that hyposalivation in HSCT recipients exhibits a multifactorial aetiology. CLINICAL RELEVANCE All HSCT recipients should be considered to be at high risk of hyposalivation and consequent oral diseases, and they should be treated accordingly.

PP080. First trimester umbilical artery end-diastolic flow and pulsatility index: Comparison between preeclampsia and control.

INTRODUCTION The appearance of end-diastolic flow velocities (EDF) in the umbilical artery (UA), usually between 10 and 14 weeks of gestation, has been associated with the opening of the spiral arteries and consequently of the intervillous space. OBJECTIVES The aim of our study was to compare first trimester UA pulsatility index (PI) and EDF between women who developed preeclampsia (cases) and controls. METHODS Our database was searched for cases who had UA Doppler between 10-14 weeks. UA PI and EDF were compared between cases and two gestational age (GA) matched controls. RESULTS 15 cases with severe preeclampsia (PE) were matched to 30 controls. GA with negative EDF was lower than with positive EDF (12.1±0.79 vs. 12.8±0.34; p=0.001). UA PI in cases was higher than in controls, although not significant (cases: 2.18±0.6 vs. CONTROLS 1.92±0.48; p=0.12). However, comparing groups with negative EDF, the difference became significant (PI cases: 2.45±0.57 vs. PI controls: 1.94±0.56; p=0.038), while no difference was found comparing groups with positive EDF. CONCLUSION First trimester UA PI is significantly higher in women which will develop PE than in controls. Interestingly, the timing of screening for PE by UA Doppler seems to play an important issue.

Inherited structural controls on fault geometry, architecture and hydrothermal activity: an example from Grimsel Pass, Switzerland

Exhumed faults hosting hydrothermal systems provide direct insight into relationships between faulting and fluid flow, which in turn are valuable for making hydrogeological predictions in blind settings. The Grimsel Breccia Fault (Aar massif, Central Swiss Alps) is a late Neogene, exhumed dextral strike-slip fault with a maximum displacement of 25–45 m, and is associated with both fossil and active hydrothermal circulation. We mapped the fault system and modelled it in three dimensions, using the distinctive hydrothermal mineralisation as well as active thermal fluid discharge (the highest elevation documented in the Alps) to reveal the structural controls on fluid pathway extent and morphology. With progressive uplift and cooling, brittle deformation inherited the mylonitic shear zone network at Grimsel Pass; preconditioning fault geometry into segmented brittle reactivations of ductile shear zones and brittle inter-shear zone linkages. We describe ‘pipe’-like, vertically oriented fluid pathways: (1) within brittle fault linkage zones and (2) through alongstrike- restricted segments of formerly ductile shear zones reactivated by brittle deformation. In both cases, low-permeability mylonitic shear zones that escaped brittle reactivation provide important hydraulic seals. These observations show that fluid flow along brittle fault planes is not planar, but rather highly channelised into sub-vertical flow domains, with important implications for the exploration and exploitation of geothermal energy.