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Brain injury in sickle cell disease (SCD) comprises a wide spectrum of neurological damage. Neurocognitive deficits have been described even without established neurological lesions. DTI is a rapid, noninvasive, and non-contrast method that enables detection of normal-appearing white matter lesions not detected by conventional magnetic resonance imaging (MRI). The aim of the study was to evaluate if stem cell transplantation can revert white matter lesions in patients with SCD. Twenty-eight SCD patients were evaluated with MRI and DTI before and after allogeneic hematopoietic stem cell transplantation (HSCT), compared with 26 healthy controls (HC). DTI metrics included fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity maps, global efficiency, path length, and clustering coefficients. Compared to HC, SCD patients had a lower FA (p = 0.0086) before HSCT. After HSCT, FA increased and was not different from healthy controls (p = 0.1769). Mean MD, RD, and AD decreased after HSCT (p = 0.0049; p = 0.0029; p = 0.0408, respectively). We confirm previous data of white matter lesions in SCD and present evidence that HSCT promotes recovery of brain injury with potential improvement of brain structural connectivity.

Almost 115 years ago, Alois Alzheimer described Alzheimer’s disease (AD) for the first time. Since then, many hypotheses have been proposed. However, AD remains a severe health public problem. The current medical approaches for AD are limited to symptomatic interventions and the complexity of this disease has led to a failure rate of approximately 99.6%in AD clinical trials. In fact, no new drug has been approved for AD treatment since 2003. These failures indicate that we are failing in mimicking this disease in experimental models. Although most studies have focused on the amyloid cascade hypothesis of AD, the literature has made clear that AD is rather a multifactorial disorder. Therefore, the persistence in a single theory has resulted in lost opportunities. In this review, we aim to present the striking points of the long scientific path followed since the description of the first AD case and the main AD hypotheses discussed over the last decades. We also propose insulin resistance as a common link between many other hypotheses.

Kazuhiro Shimizu,1 Mao Takahashi,1 Shuji Sato,1 Atsuhito Saiki,1 Daiji Nagayama,1 Masashi Harada,2 Chikao Miyazaki,2 Akira Takahara,3 Kohji Shirai1 1Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba, Japan; 2Department of Neurosurgery, Toho University Omori Medical Center, Omori, Tokyo, Japan; 3Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, JapanCorrespondence: Kohji ShiraiDepartment of Internal Medicine, Toho University Sakura Medical Center, 561-4 Shimoshizu, Sakura City, Chiba, 285-8741, JapanTel +81-43-462-8811Fax +81-43-462-8820Email kshirai@kb3.so-net.ne.jpAbstract: Cardiovascular diseases have been recognized as the main cause of death all over the world. Recently, the established cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. Considering the vasculature of the atheroma where vasa vasorum penetrates the smooth muscle cell layer and supplies blood to the intimal atheromatous lesion, a rapid rise of CAVI means “choked” atheroma. Thus, we proposed a “smooth muscle cell contraction” hypothesis of plaque rupture.Keywords: arterial stiffness, atherosclerosis, smooth muscle cell contraction, CAVI

Cerebral ischemic stroke is caused by a blockage in a artery that supplies blood to the brain. The blockage reduces the blood flow and oxygen to the brain leading to the damage or death of brain cells. Aim of our study is to identify and analyze the risk factors of cerebral ischemic stroke in young and elderly patients. The known Non modifiable risk factors are Age, Gender, Race,, Family history of stroke, Low birth weight. Modifiable and well documented risk facrors are Hypertension, Sickle cell disease, Atrial fibrillation symptomatic carotid stenosis, Diabetes, Post menopausal hormone therapy, Dyslipidemia. Life style factors-associated with stroke risk Cigarette smoking, Obesity, Over Alcohol consumption, Physical inactivity. Potentially modifiable but less documented risk factors are usage of Oral contraceptives, Migraine,, Drug and alcohol abuse,, Homocysteine condition, Sleep disordered breathing. A Prospective observational study on risk factors of cerebral ischemic stroke in young and elderly patients was performed from September 2018-February 2019 i.e for 6 months duration in In-patient department of General Medicine in Gandhi Hospital.140 CVA cases were collected, documented, analyzed and results are obtained as follows. Young subjects HTN (60.9%), Alcohol consumption (78%), Smoking (48%), History of stroke (36%), Diabetes mellitus (24%), Obesity (14.6%), Cardio-Vascular diseases (4.8%). Elderly subjects HTN (82.8%), Smoking (79%), Alcohol consumption (72.7), History of stroke (33.3%), Diabetes mellitus (27.2), Obesity (8.8%), Cardio-Vascular diseases (8%). Reporting of Stroke cases in young adults in India was uncommon in few years ago. But our studies now indicate that the incidence of young stroke is on the rise. It has been observed that for the past 4-5 years the occurrence of stroke is seen at age less than 45years.And lifestyle modifications can reduce the rate of risk.

Introduction: Doppler ultrasound velocimetry of uteroplacental umbilical and fetal vessels has become established method of antenatal monitoring. Cerebroplacental ratio has been studied to predict neonatal outcomes. Aim of the work: Our aim was to assess role of cerebro-placental ratio in prediction of perinatal outcome in high-risk pregnancies with intrauterine growth restriction. Patients and Methods: In this study was held in Ain Shams university maternity hospital which included 60 high risk pregnant women divided in to two groups: Group I: study group: 30 high risk pregnant women with IUGR, Group II- control group: 30 high risk pregnant women without IUGR. Results: The current study showed that among patients with IUGR and low CPR, 17 (56.7%) had CS for fetal distress, 12 (40.0%) had neonate with low APGAR, 13 (43.3%) had neonatal meconium aspiration, 6 (20.0%) had neonatal Hypoxic ischemic Encephalopathy, 15 (50.0%) had neonate need NICU admission, 3 (10.0%) had neonatal death, 1 (3.3%) had neonatal still birth. The current study showed that among patients without IUGR and low CPR, 8 (26.7%) had CS for fetal distress, 5 (16.7%) had neonate with low APGAR, 4 (13.3%) had neonatal meconium aspiration, 1 (3.3%) had neonatal Hypoxic ischemic Encephalopathy, 5 (16.7%) had neonate need NICU admission, 1 (3.3%) had neonatal death, 0 (0.0%) had neonatal still birth. Conclusion: Cerebro -placental ratio has high predictive value of perinatal outcome in high risk pregnancy with intrauterine growth restriction.

Concerning all etiological factors for the increasing factors of Chronic Cerebral Ischemia (CCI) fits into the concept of the creation of a stable pathological system in the central nervous system (CNS). Aim. The evaluation of the increasing factors for the formation of a pathological system of the brain, peculiarities of cerebro-cardial interactions with the help of parameters of quantitative electroencephalography and heart rate variability in patients with CNS of different genesis. Materials and methods. At aged from 40 to 68 were comprehensively examined 88 people in dynamics in the period from 2016 to 2019. The registration of brain biopotentials was recorded using Tredex Expert computer-based electroencephalograph. For the analysis of EEG, the amplitude-time representation of an unsteady signal and its result of continuous wavelet transform were used. In the dynamics of therapy, an analysis of quantitative EEG (qEEG), heart rate variability (HRV) (Utas UM 200) was proceed. Results and discussion. Using the method of quantitative EEG with a wavelet conversion of a stationary EEG signal [9], the formation and destruction of stable pathological systems of the brain in patients with stroke, transient cerebral ischemia (TCI), MCI grade 2 were studied. In patients with MCI grade 2, in contrast to the “healthy brain”, the role of the “central contour” of regulation of heart rate variability shifts from the vegetative centers of the medulla oblongata to the region of diencephalic formations; in the thalamus area; into the hypothalamic zone. In patients with stroke, the role of the "central contour" is shifted to the region of limbic-hippocampal formations, the diencephalic zone, the area of the thalamus and ascending thalamocortical pathways. In patients with TCI, the role of the “central contour” shifts to the cortical region (signs of cortical irritation), diencephalic zone, thalamus and descending corticothalamic pathways. Conclusions. The positive effect of therapy when acting on the formed pathological system should be considered the appearance of an EEG on the wavelet graph in parallel with the dominant frequency of the subdominant frequency in the alpha range, the movement of the “central contour” of regulation of heart rate variability in the region of the vegetative centers of the medulla oblongata.

Background and aims We explored the association between the total small vessel disease score obtained from baseline magnetic resonance imaging and subsequent cerebro-cardiovascular events in neurologically healthy Japanese adults. Methods The presence of small vessel disease features, including lacunae, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on magnetic resonance imaging, was summed to obtain a “total small vessel disease score” (range, 0–4). After excluding participants with previous stroke or ischemic heart disease, intracranial artery stenosis (≥50%), or cerebral aneurysm (≥4 mm), a total of 1349 participants (mean age, 57.7 years; range, 22.8–85.0 years; 46.9% male) were classified into three groups by total small vessel disease score: 0 ( n = 984), 1 ( n = 269), and ≥2 ( n = 96). Cerebro-cardiovascular events (i.e., any stroke, transient ischemic attack, ischemic heart disease, acute heart failure, and aortic dissection) were defined as the primary end point. The hazard ratio (HR) of events during follow-up was calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, diabetes mellitus, and smoking. Cumulative event-free rates were estimated using the Kaplan–Meier method. Results During follow-up (mean, 6.7 years), 35 cerebro-cardiovascular (16 cerebrovascular) events were identified. Higher small vessel disease score was associated with increased risk of cerebro-cardiovascular events (HR per unit increase, 2.17; 95% confidence interval, 1.36–3.46; P = 0.001). Events were more frequent among participants with higher score ( P Conclusions This study offered additional evidence for the clinical relevance of total small vessel disease score, suggesting the score as a promising tool to predict the risk of subsequent vascular events even in healthy populations.

Background: The assessment of fetal hemodynamic status via Doppler flow is increasingly regarded as likely to aid in the detection of pregnancies at risk of developing adverse fetal outcomes. Doppler flow provides useful information beyond the ultrasound-based assessment of fetal growth alone. Objective: This study aimed to evaluate the role of cerebro-placental ratio (CPR) in prediction of perinatal outcome in preeclamptic patients with intrauterine growth restriction (IUGR). Patients and methods: This case-control study was conducted at Obstetrics and Gynecology Department, Zagazig University, on 50 pregnant women divided in to two groups: Group I (study group) that included 25 high risk pregnant women with IUGR. Group II (control group) included 25 high risk pregnant women without IUGR. The study was conducted during the period from December 2020 till July 2021. Results: The current study showed that CPR had 90.9% sensitivity, 78.6% specificity and 84 % diagnostic accuracy to predict newborns with low Apgar score, with statistically significant positive correlation. CPR also had 100% sensitivity, 100% specificity and 100 % diagnostic accuracy to predict stillbirth, with highly statistically significant positive correlation. The CPR had 100% sensitivity, 83.3% specificity and 92 % diagnostic accuracy to predict newborns with NICU admission, with statistically significant positive correlation. Other complications as meconium aspiration and neonatal death had no statistically significant to be predicted by low CPR. Conclusion: This study concluded that the Cerebro-Placental Ratio had high predictive value of perinatal out come in preeclamptic patients.

Simple Summary Immune checkpoint inhibitor (ICI) therapy has changed the management of many cancers endowed with poor prognosis. However, cardiotoxicity, as well as the possible progression of atherosclerosis, have been described. 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated tool to quantify atherosclerotic inflammatory activity; therefore, we found it interesting to analyze the changes in maximum FDG standardized uptake values (SUVmax) and of target-to-background ratios (TBRs) in 117 arterial segments of 12 otherwise healthy, young lymphoma patients, underwent PET pre/post ICI treatment. As systemic immune activation surrogate markers, SUVmax of the bone marrow, spleen, and liver, as well high-sensitivity C-reactive protein (hsCRP) pre- and post-treatment, were additionally analyzed. ICI therapy induced arterial inflammatory activity, detected by increased TBR in all PET lesions. FDG uptake measured in other organs and hsCRP levels remained unchanged. Our findings show that cancer immunotherapy with ICI might be a critical moderator of atherosclerosis, with a possible subsequently increased risk of future cardiovascular events in oncological patients, even in young patients with low cardiovascular risk. Abstract Background: Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. Methods: We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUVmax) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. Results: ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, p < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, p < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. Conclusions: Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.

Highlights • Ketamine modulates cerebellar connectivity during response inhibition in depression. • Cerebellar–frontoparietal/sensory connectivity decreases in ketamine remitters. • Cerebellar-frontoparietal/salience connectivity predicts treatment outcome. • Cerebro-cerebellar loops serve as treatment biomarkers in major depression., Patients with major depressive disorder (MDD) exhibit impaired control of cognitive and emotional systems, including deficient response selection and inhibition. Though these deficits are typically attributed to abnormal communication between macro-scale cortical networks, altered communication with the cerebellum also plays an important role. Yet, how the circuitry between the cerebellum and large-scale functional networks impact treatment outcome in MDD is not understood. We thus examined how ketamine, which elicits rapid therapeutic effects in MDD, modulates cerebro-cerebellar circuitry during response-inhibition using a functional imaging NoGo/Go task in MDD patients (N = 46, mean age: 39.2, 38.1% female) receiving four ketamine infusions, and healthy controls (N = 32, mean age:35.2, 71.4% female). We fitted psychophysiological-interaction (PPI) models for a functionally-derived cerebellar-seed and extracted average PPI in three target functional networks, frontoparietal (FPN), sensory-motor (SMN) and salience (SN) networks. Time and remission status were then evaluated for each of the networks and their network-nodes. Follow-up tests examined whether PPI-connectivity differed between patient remitter/non-remitters and controls. Results showed significant decreases in PPI-connectivity after ketamine between the cerebellum and FPN (p

Background and Purpose Dyslipidemia is a significant risk factor for cerebro-cardiovascular diseases (CVD). Limited evidence is available on the prevention effect of statin in a nationwide large population. We aim to verify the primary and secondary prevention effects of statin on CVD among not only the general adult population but also elderly over 60 years.Methods This study is a big data cohort study using propensity score-matched data from the Korean National Health Screening Cohort. Differences in the cumulative incidence of major adverse cerebro-cardiovascular events and hazard ratio between the statin-user and the non-statin-user groups were investigated.Results A propensity score-matched pairs of statin-user and non-statin-user identified 64,182 population of 40–75 years old without CVD and 24,688 with accompanying diseases. In this group, statin showed both primary (HR 0.76, 95% CI 0.70–0.83, pConclusions Statin use in the elderly showed the primary prevention effect on CVD. Taking statin is desirable for both general population of dyslipidemia patients and elders over 60 years with CVD risk factors.

Keywords: cerebrovascular disease, clinico-neurological characteristics, quality of life. The results of examination of 100 patients with cerebrovascular disease are represented. Analysis of objective data indicating, thatcognitive, coordinative, and thinking impairments are leading in the compensated and subcompensated stages of cerebrovascular disease. These indicators make possible to take into consideration the individual characteristics of each patient for developing a comprehensive program of physical and medical rehabilitation.

Language processing depends on an integrated circuit involving the left supratentorial language areas and the right posterior lateral cerebellar hemisphere (lobule VI, lobule VII, Crus I, and Crus II). Reorganization of the language system after lesions of the cerebral language areas includes also cerebellar relocation. This is the first study assessing functional language reorganization after lesions concerning primarily the cerebellum, using a fMRI paradigm of phonological covert word production task in six children operated for right cerebellar astrocytoma and in 15 typically developing children. We found right cerebellar and left frontal activations in healthy controls and high variability of reorganizational patterns in patients with early right cerebellar lesion. Also lesions not located in the areas typically involved in language tasks (Crus I and Crus II) can cause reorganization between the two hemispheres or hemispheric language reinforcement of the original lateralization. We discuss the role of several variables in determining the reorganizational pattern such as the site, extension, and timing of surgery. No variables revealed as predictors, suggesting that co-occurring influence of other biological and/or pathological factors are not yet demonstrated. Lesions in the postero-lateral cerebellum seem related to less efficient language performances, as an indicator of the system's functioning.

The cerebroplacental ratio (CPR) has shown utility as a surrogate marker for fetal growth restriction and can be used to stratify the risk for adverse perinatal outcomes in affected pregnancies. However, recent studies suggest that its inverse, the umbilico-cerebral ratio (UCR), may be a better predictor of such outcomes. The aim of this study was to compare the prognostic accuracy of CPR to that of UCR Doppler in predicting short-term adverse perinatal outcomes in growth-restricted fetuses.We conducted a secondary analysis using data from a prospective study on women referred for fetal growth ultrasounds between 26 and 36 weeks of gestation and with an EFW10th percentile by Hadlock standard. The CPR and UCR were converted intoOver the study period, there were 197 women meeting inclusion criteria, of which 27 (13.7%) had a composite adverse neonatal outcome. The sensitivity using CPRThis study did not find any advantage in utilizing the UCR over the CPR.

International audience; Alcohol use disorder (AUD) is widely associated with cerebellar dysfunction and altered cerebro-cerebellar functional connectivity (FC) that lead to cognitive impairments. Evidence for this association comes from resting-state functional magnetic resonance imaging (rsfMRI) studies that assess time-averaged measures of FC across the duration of a typical scan. This approach, however, precludes the assessment of potentially FC dynamics happening at faster timescales. In this study, using rsfMRI data, we aim at exploring cerebro-cerebellar FC dynamics in AUD patients (N = 18) and age- and sex-matched controls (N = 18). In particular, we quantified group-level differences in the temporal variability of FC between the posterior cerebellum and large-scale cognitive systems, and we investigated the role of the cerebellum in large-scale brain dynamics in terms of the temporal flexibility and integration of its regions. We found that, relative to controls, the AUD group exhibited significantly greater FC variability between the cerebellum and both the frontoparietal executive control (F1,31 = 7.01, p(FDR) = 0.028) and ventral attention (F1,31 = 7.35, p(FDR) = 0.028) networks. Moreover, the AUD group exhibited significantly less flexibility (F1,31 = 8.61, p(FDR) = 0.028) and greater integration (F1,31 = 9.11, p(FDR) = 0.028) in the cerebellum. Finally, in an exploratory analysis, we found distributed changes in the dynamics of canonical large-scale networks in AUD. Overall, this study brings evidence of AUD-related alterations in dynamic FC within major cerebro-cerebellar networks. This pattern has implications for explaining the development and maintenance of this disorder and improving our understating of the cerebellum’s involvement in addiction.

Background: Observational scales are the most common methodology used to assess postural control and balance in people with stroke. The aim of this paper was to analyse the construct validity of the Postural Assessment Scale for Stroke Patients (PASS) scale in post-stroke patients in the acute, subacute, and chronic stroke phases. (2) Methods: Sixty-one post-stroke participants were enrolled. To analyze the construct validity of the PASS, the following scales were used: the Functional Ambulatory Category (FAC), the Wisconsin Gait Scale (WGS), the Barthel Index (BI) and the Functional Independence Measure (FIM). (3) Results: The construct validity of the PASS scale in patients with stroke at acute phase was moderate with the FAC (r = -0.791), WGS (r = -0.646) and FIM (r = -0.678) and excellent with the BI (r = 0.801). At subacute stage, the construct validity of the PASS scale was excellent with the FAC (r = 0.897), WGS (r = -0.847), FIM (r = -0.810) and BI (r = -0.888). At 6 and 12 months, the construct validity of the PASS with the FAC, WGS, FIM and BI was also excellent. (4) Conclusions: The PASS scale is a valid instrument to assess balance in post-stroke individuals especially, in the subacute and chronic phases (at 6 and 12 months). Sin financiación 3.992 Q2 JCR 2021 0.658 Q2 SJR 2021 No data IDR 2021 UEM

Fetuses with an estimated weight (EFW) below the 10th percentile are at risk for adverse perinatal outcome and clinical management remains a challenge. We examined EFW and cerebro-placental ratio (CPR) with regard to their predictive capability in the management and outcome of such cases. Fetuses were first diagnosed as small after 34 weeks of gestation with an actual EFW below the 10th percentile at our tertiary academic center. We determined the optimum cutoff value for CPR and EFW in predicting adverse neonatal outcome. Mean gestational age at diagnosis was 36 weeks. One hundred and two cases were included in our study. We determined a CPR of 1.4 and an EFW of 2152 g to be the best cutoff value for predicting adverse fetal outcome, with an area under the curve (AUC) of 0.65 (95% CI 0.54–0.76); p = 0.009, and 0.76 (95% CI 0.66–0.86); p < 0.0001, respectively. However, when comparing EFW with CPR, EFW seems to be slightly better in predicting adverse fetal outcome in our group. While the use of CPR alone for the management of small fetuses is not sufficient, it is an important additional tool that may be of value in the clinical setting.

Opportunistic fungal infections are life-threatening conditions with a high rate of morality, mostly occurring in immunocompromised hosts. We reported the case of mixed mold infection in a 69 year-old patient with latent diabetes mellitus. She was initially admitted for right orbital cellulitis. Cerebro-rhino-orbital mucormycosis and aspergillosis coinfection was diagnosed from mycological testing and histology after nasal biopsy sample. The patient received amphotericin B deoxycholate then voriconazole combined to surgical debridement with a favorable outcome.

179 p. El accidente cerebrovascular, o ictus, representa una de las principales causas de muerte en el mundo y además conlleva grandes consecuencias económicas y sociales. La carga global del ictus y la ausencia de un tratamiento eficaz hacen urgente la búsqueda de nuevas estrategias para el desarrollo de moléculas neuroprotectoras frente al ictus. En este estudio, se evalúan los efectos neuroprotectores del factor neurotrófico derivado del cerebro (“brainderived neurotrophic factor”, BDNF) en un modelo ex vivo de isquemia cerebral. El estrés oxidativo y la comunicación celular medida por las vesículas extracelulares (VE) son procesos alterados por la isquemia/reperfusión que juegan un papel fundamental en la evolución del daño isquémico, sin embargo, el papel del BDNF en estos dos procesos sigue siendo incierto. Por ello, este estudio ha tratado de aumentar el conocimiento sobre los mecanismos neuroprotectores del BDNF contra el ictus como posible molécula terapéutica. = Stroke, or cerebrovascular accident, represents one of the leading causes of death worldwide, with high associated economic and social costs. The global burden of stroke and the lack of an effective treatment leads to an urgent identification of new strategies to develop antistroke clinical molecules. In this study, we evaluated the neuroprotective effects of brainderived neurotrophic factor (BDNF) against ischemia. Oxidative stress and cellular communication mediated by extracellular vesicles (EVs) are altered by ischemia/reperfusion and are reported to be highly relevant in the progression of ischemic damage. However, the role of BDNF on these two processes is still uncertain and this study aimed to gain insight into the neuroprotective mechanisms of BDNF against stroke as a potential therapeutic molecule.

Background: The soluble fibrin monomer complex (SFMC) is a biomarker of fibrin formation, and has been shown to be abnormally elevated in various clinical situations of hypercoagulability. However, the association between SFMC and cardiovascular events in patients with heart failure (HF) remains uncertain. We aimed to examine the prognostic impact of SFMC concerning increased risk of major cardio- and cerebro-vascular events (MACCE) and all-cause mortality in patients with HF. Methods and Results: We conducted a prospective observational study. We analyzed data on 723 hospitalized patients with HF who discharged alive and measured SFMC at stable condition in prior to discharge. Patients were divided into tertiles based on levels of SFMC: 1 st (SFMC nd (1.8 ≤ SFMC rd (3.0 μg/ml ≤ SFMC, n = 240) tertiles. We compared baseline patients’ characteristics and their post-discharge MACCE and mortality. Prevalence of chronic kidney disease (CKD) and anemia was significantly higher in the 3 rd tertile than in the 1 st and 2 nd tertiles. In contrast, age, sex, CHADS 2 -Vasc score, left ventricular ejection fraction, and prevalence of hypertension, diabetes and atrial fibrillation did not differ among the tertiles. During the median follow-up period of 422 days, 61 patients experienced MACCE, and 82 patients died. In the Kaplan-Meier analysis ( Figure ), accumulated event rates of both MACCE and all-cause mortality progressively increased from the 1 st to the 3 rd tertiles (MACCE, 4.8%, 8.6% and 12.1%, log-rank P=0.014; all-cause mortality, 6.4%, 9.4% and 18.3%, log-rank Prd tertile was found to be an independent predictor of MACCE (HR 2.608, 95%CI 1.331-5.113, P=0.005) and all-cause mortality (HR 2.938, 95%CI 1.657-5.207, P Conclusion: SFMC is an independent predictor of adverse prognosis in patients with HF.

The extent of smoking history is causally linked to adverse cerebro‐ and cardiovascular health outcomes, while conversely, exercise decreases this risk and associated mortality. However, the acute cerebro‐ and cardiovascular responses to exercise in smokers are unknown, and may provide insight to understand chronic adaptation. This study examined the acute heart rate (HR) variability (R‐R intervals) and cerebral oxygenation responses to exercise in smokers compared to nonsmokers. Fifty‐four males classified as smokers (n = 27) or nonsmokers (n = 27) were allocated into either younger (YSM, YNS) or middle‐aged groups (MSM, MNS). Participants completed 40 min of stationary cycle ergometry at 50% of VO2peak. Cerebral oxygenation (near‐infrared spectroscopy) and autonomic function (HR variability) were collected before, during, and after exercise at 0, 30 min, 1, and 4 hr postexercise. The nonsmoker cohort (MNS and YNS) demonstrated higher values for the standard deviation (SD) of the R‐R interval (SDNN) and the root mean squared of the SD at 1 and 4 hr postexercise versus smokers (p, The findings suggest an effect of smoking history on cerebral oxygenation during and following an acute exercise bout of exercise with nonsmokers demonstrating higher oxygenated haemoglobin compared to that of both young and middle‐aged smokers.

Introduction:Infants with single ventricle following stage I palliation are at risk for poor nutrition and growth failure. We hypothesise a standardised enteral feeding protocol for these infants that will result in a more rapid attainment of nutritional goals without an increased incidence of gastrointestinal co-morbidities.Materials and methods:Single-centre cardiac ICU, prospective case series with historical comparisons. Feeding cohort consisted of consecutive patients with a single ventricle admitted to cardiac ICU over 18 months following stage I palliation (n = 33). Data were compared with a control cohort and admitted to the cardiac ICU over 18 months before feeding protocol implementation (n = 30). Feeding protocol patients were randomised: (1) protocol with cerebro-somatic near-infrared spectroscopy feeding advancement criteria (n = 17) or (2) protocol without cerebro-somatic near-infrared spectroscopy feeding advancement criteria (n = 16).Results:Median time to achieve goal enteral volume was significantly higher in the control compared to feeding cohort. There were no significant differences in enteral feeds being held for feeding intolerance or necrotising enterocolitis between cohorts. Feeding cohort had significant improvements in discharge nutritional status (weight, difference admit to discharge weight, weight-for-age z score, volume, and caloric enteral nutrition) and late mortality compared to the control cohort. No infants in the feeding group with cerebro-somatic near-infrared spectroscopy developed necrotising enterocolitis versus 4/16 (25%) in the feeding cohort without cerebro-somatic near-infrared spectroscopy (p = 0.04).Conclusions:A feeding protocol is a safe and effective means of initiating and advancing enteral nutrition in infants following stage I palliation and resulted in improved nutrition delivery, weight gain, and nourishment status at discharge without increased incidence of gastrointestinal co-morbidities.

We examine the effect of transcranial direct current stimulation (tDCS) of right superior temporal sulcus (rSTS) in memorization of approach/avoidance relationship-action sentences, for example, &ldquo, Alejandro accepted/rejected Marta in his group.&rdquo, Sixty-five university students participated in a tDCS study, in which a between-subjects design was adopted. Sixty-four participants were also given the behavioral approach system (BAS) and behavioral inhibition system (BIS) scales. Participants were subjected to 20 min of stimulation: anodal (N = 24), cathodal (N = 21), or sham (N = 20), subsequently, they were given a list of 40 sentences (half approach and half avoidance) and told to try to memorize them. Finally, they performed a changed/same memory task (half the sentences were the &ldquo, same&rdquo, and half were &ldquo, changed&rdquo, ). Previously, we had examined performance in the memory task without tDCS with another group of participants (N = 20). We found that anodal stimulation improved d&rsquo, index of discriminability (hits-false alarms) compared to sham and cathodal conditions for both approach and avoidance sentences. Moreover, the comparison between anodal and task-alone performance showed that stimulation improved d&rsquo, index of approach sentences more, as task-alone performance showed better discrimination for avoidance than for approach. Likewise, we explored a potential modulation of tDCS effect by (BAS) and (BIS) traits. We found that d&rsquo, index improvement in anodal stimulation condition only benefited low BAS and low BIS participants. Implications of these results are discussed in the context of rSTS function in encoding and memorizing verbally described intentional relationship-actions and the role of individual differences on modulating tDCS effect.

The Jake Mandell Tone Deaf Test (JMT) is an online measure designed to evaluate pitch discrimination in the normal population. The test has been available online since 2006, but no psychometric data have been published. The present research was designed to provide validity and reliability data for this test. Study 1 was conducted in university students, and the performance on the JMT was compared to the AMUSIA online screening tests. Correlations were high with the subtests of the AMUSIA online screening tests, but especially with the Tone discrimination test. Study 2 was conducted in children, and the JMT was compared to different tests of musical abilities. The JMT showed a good relationship with the Tone Discrimination and Rhythm Imitation subtest, but especially with the global score of musical abilities. In addition, the test showed good one-year test-retest reliability. Finally, external validation of the JMT was obtained by noting that musicians obtained higher scores than non-musicians. Discussion is focused on the possibility of using the JMTas a rapid screening measure of individual differences in pitch discrimination in the normal population. El test de Jake Mandell (JMT) es un test online diseñado para evaluar la discriminación tonal en la población normal. El test está disponible online desde 2006, pero no se han publicado datos psicométricos. La presente investigación fue diseñada para proporcionar datos de validez y fiabilidad para este test. El estudio 1 se realizó en estudiantes universitarios, y el rendimiento en el JMT se comparó con las pruebas de detección online denominadas AMUSIA. Las correlaciones fueron altas con los subtests de AMUSIA, pero especialmente con el de discriminación de tonos. El estudio 2 se realizó en niños, y el JMT se comparó con diferentes pruebas de habilidades musicales. El JMT mostró una buena relación con el subtest de discriminación de tono e imitación de ritmo, pero especialmente con la puntuación global de las habilidades musicales. Además, el test mostró una buena fiabilidad test-retest al cabo de un año. Finalmente, la validación externa del JMT se obtuvo al señalar que los músicos obtuvieron puntuaciones más altas que los no músicos. La discusión se centra en la posibilidad de utilizar el JMT como una medida de detección rápida de las diferencias individuales en la discriminación de tono en la población normal. O teste de surdez de tom de Jake Mandell (JMT) é uma medida on-line projetada para avaliar a discriminação de tom na população normal. O teste está disponível online desde 2006, mas nenhum dado psicométrico foi publicado. A presente pesquisa foi projetada para fornecer dados de validade e confiabilidade para este teste. O estudo 1 foi realizado em estudantes universitários, e o desempenho no JMT foi comparado aos testes de triagem on-line da AMUSIA. As correlações foram altas com os subtestes dos testes de triagem on-line da AMUSIA, mas principalmente com o teste de discriminação de tons. O estudo 2 foi realizado em crianças e o JMT foi comparado a diferentes testes de habilidades musicais. O JMT mostrou uma boa relação com o subteste Discriminação de Tom e Imitação de Ritmo, mas principalmente com o escore global de habilidades musicais. Além disso, o teste mostrou boa confiabilidade teste-reteste de um ano. Finalmente, a validação externa do JMT foi obtida observando que os músicos obtiveram pontuações mais altas que os não músicos. A discussão está focada na possibilidade de usar o JMT como uma medida de triagem rápida das diferenças individuais na discriminação de arremesso na população normal. &nbsp

Este artículo se encuentra disponible en la siguiente URL: https://journals.sagepub.com/doi/pdf/10.1177/0300985818817071 This is the pre-peer reviewed version of the following article: Ortega, J., Verdes, J. M., Morrell, E. L., Finnie, J. W., Manavis, J., & Uzal, F. A. (2019). Intramural vascular edema in the brain of goats with "Clostridium perfringens" Type D enterotoxemia. Veterinary Pathology, vol. 56, n. 3 (01 may.), pp. 452?459, which has been published in final form at https://doi.org/10.1177/0300985818817071 Este es el pre-print del siguiente artículo: Ortega, J., Verdes, J. M., Morrell, E. L., Finnie, J. W., Manavis, J., & Uzal, F. A. (2019). Intramural vascular edema in the brain of goats with "Clostridium perfringens" Type D enterotoxemia. Veterinary Pathology, vol. 56, n. 3 (01 may.), pp. 452?459, que se ha publicado de forma definitiva en https://doi.org/10.1177/0300985818817071 Enterotoxemia caused by Clostridium perfringens type D is an important disease of sheep and goats with a worldwide distribution. Cerebral microangiopathy is considered pathognomonic for ovine enterotoxemia and is seen in most cases of the disorder in this species. These lesions are, however, rare and poorly described in goats. In this paper, we describe the vasculocentric brain lesions observed in 44 cases of caprine spontaneous C. perfringens type D enterotoxemia. Only one goat had gross changes in the brain, which consisted of mild cerebellar coning. However, 8/44 (18%) of the cases showed microscopic brain lesions, characterized mainly by intramural vascular proteinaceous edema, a novel and diagnostically significant finding. The precise location of the edema was better observed with PAS and Gomori’s stains. The areas of the brain most frequently affected were cerebral cortex, corpus striatum (basal ganglia) and cerebellar peduncles and both arterioles and venules were involved. Most of the goats of this study showed lesions in the intestinal tract (enteritis, colitis and typhlitis), although pulmonary congestion and edema, hydrothorax, hydropericardium and ascites were also described. This is the largest study to date of neuropathological changes in naturally-occurring cases of caprine type D enterotoxemia, and it describes the main features of the cerebral microangiopathy in this species. Although the intramural edema found, for the first time, in these caprine cases is useful for the diagnosis of enterotoxemia when observed, its absence cannot exclude the disease because, in goats, it is only present in a small number of cases.

Background: Blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) shows association with subclinical cerebrovascular diseases (SCVDs). Although various studies reported this association, there are still controversy in the effect size of long period versus short period of these indexes to SCVDs. Aim: Identifying the effect size of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. Methods: Four office BP indexes were measured at two visits 4.5 years apart in general Japanese men aged 40-79 years. Participants without myocardial infarction or stroke history were analyzed (N=629). MRI obtained at 3 rd visit were investigated for prevalent of five SCVDs diagnosed as follows; lacunar infarction (LI)= any presence, periventricular hyperintensity (PVH)= Fazekas grade ≥2, deep subcortical white matter hyperintensity (DSWMH)= Fazekas grade ≥3, microbleeds= any presence, and intracranial arterial stenosis (ICAS)= ≥1% stenosis. Using multivariable logistic regression, we computed and compared odds ratio OR (95% CI) of each prevalent SCVD for 1 standard deviation higher of each of 4 BP indexes after adjusting for SCVDs’ conventional risk factors. Results: Participants’ mean age at Visit 1 was 63.9 years. Our results show all office BP indexes, except PP, similar association with MRI outcomes at both Visit 1 and Visit 2. SBP, DBP and MAP were associated with LI, PVH, DSWMH, microbleed and ICAS, while PP was associated with LI and ICAS only. Conclusion: In general Japanese men, BP indexes SBP, DBP and MAP measured at two distinct visits show similar association to all future MRI assessed SCVD, while PP shows association to LI and ICAS only.

Evidence suggests that physical exercise has effects on neuronal plasticity as well as overall brain health. This effect has been linked to exercise capacity in modulating the antioxidant status, when the oxidative stress is usually linked to the neuronal damage. Although high-intensity interval training (HIIT) is the training-trend worldwide, its effect on brain function is still unclear. Thus, we aimed to assess the neuroplasticity, mitochondrial, and redox status after one-week HIIT training. Male (C57Bl/6) mice were assigned to non-trained or HIIT groups. The HIIT protocol consisted of three days with short bouts at 130% of maximum speed (Vmax), intercalated with moderate-intensity continuous exercise sessions of 30 min at 60% Vmax. The mass spectrometry analyses showed that one-week of HIIT increased minichromosome maintenance complex component 2 (MCM2), brain derived neutrophic factor (BDNF), doublecortin (DCX) and voltage-dependent anion-selective channel protein 2 (VDAC), and decreased mitochondrial superoxide dismutase 2 (SOD 2) in the hippocampus. In addition, one-week of HIIT promoted no changes in H2O2 production and carbonylated protein concentration in the hippocampus as well as in superoxide anion production in the dentate gyrus. In conclusion, our one-week HIIT protocol increased neuroplasticity and mitochondrial content regardless of changes in redox status, adding new insights into the neuronal modulation induced by new training models.

External hydrocephalus (eHC) is commonly defined as a subtype of infant “hydrocephalus” consisting of macrocepahly associated with enlarged subarachnoid space and no or mild ventriculomegaly. This status is thought to be related to impaired CSF absorption because of arachnoid villi immaturity. However, other factors like the venous system might be involved in the development of the clinical picture. All patients diagnosed with eHC received prospectively contrast-enhanced 3D MR phlebography. Venous sis abnormalities were graded depending on the number of affected sinus segments and type. External CSF space volume was quantified planimetrically. Seventeen patients with the typical clinical feature of eHC were included. In 15, venous sinus abnormalities were found. There was a significant correlation between the volume of the widened cortical subarachnoid space (CSAS) and the number of venous sinus segments affected. Conversely, ventricular volume was not correlated. These results support the hypothesis that impaired venous outflow plays a major role in external hydrocephalus development. Raised venous pressure increases intracranial pressure accelerating head growth, resulting in an enlargement of the cortical subarachnoid space. Increased venous pressure increases the capillary bed pressure and brain turgor preventing ventricular space to enlarge forcing displacement of ventricular CSF to the subarachnoid space. As a result, ventriculomegaly is rarely found. The descriptive term “external hydrocephalus” implying a primary etiology within the CSF system is misleading and this work supports the notion that venous hypertension is the leading cause of the clinical picture.

This paper reports the effects of gestational hypertension in the pulsatility index (PI) of umbilical artery (UA) and middle cerebral artery (MCA), cerebro-placental ratio (CPR), and associated adverse perinatal outcomes, after 20 to 40 weeks’ gestation in singleton pregnancy. A total of 280 pregnant women, divided equally into control and gestational hypertension groups, were recruited prospectively. Alpinion Medical System ECUBE 7 ultrasound equipment was used to measure the UA-PI, MCA-PI, and CPR within the two groups. Data were analyzed to correlate the results with the presence of adverse perinatal outcomes. In gestational hypertension group, the UA-PI, MCA-PI, and CPR were associated with adverse perinatal outcomes after adjustment for gestational age. The increase in risk for lower birth weight, higher incidence of elective Cesarean section delivery, and preterm birth were statistically significant for UA-PI, MCA-PI, and CPR. Study of pulsatility indices of placental and fetal circulation in singleton pregnancy developed gestational hypertension can provide important information regarding fetal well-being, yielding an opportunity to improve fetal outcome. Keywords: Cerebro-placental ratio, Doppler ultrasound, Gestational hypertension, Pulsatility index

Posterior circulation aneurysms represent 10–15% of intracranial aneurysms. The diagnosis is usually secondary to subarachnoid hemorrhage due to its initial asymptomatic presentation and higher risk of rupture compared with aneurysms in the anterior circulation. The surgical treatment of posterior circulation aneurysms is complex and challenging for neurosurgeons because of the particular anatomy of the posterior circulation with its close relation to the brainstem and cranial nerves and also because of the depth and narrowness of the surgical approach. Aneurysms from different locations have specific anatomical relationships and surgical approaches for better visualization and dissection. Therefore, a detailed anatomy knowledge of the posterior circulation is mandatory for an individualized preoperative planning and good neurological and angiographic outcomes. We selected the main aneurysm sites on the posterior circulation, such as: posterior inferior cerebellar artery, basilar trunk, basilar bifurcation, posterior cerebral artery (PCA) and superior cerebellar artery for a detailed description of the relevant anatomy related to aneurysm, and the main surgical approaches for its surgical treatment. Furthermore, we performed a literature review with the most recent outcomes regarding to the surgical treatment of posterior circulation aneurysms.

Purpose To report the findings in five patients of Purtscher-like retinopathy that developed after cerebro- or cardiovascular surgeries. Observations Three women and two men with a mean age of 56.6 years were studied. They had had cerebro- or cardiovascular disease that was treated by major vascular surgery. Postoperatively, all of the patients developed multiple patches of retinal whitening in the area corresponding to the radial peripapillary capillaries in the posterior pole of the eye uni- or bilaterally. In two patients, the optic nerve head was involved which affected their vision severely. Hematological examinations showed hypercoagulable state after the surgeries. The retinal pathologies abated with time. Conclusions and importance These results indicate that major cardio- or cerebrovascular surgeries can cause Purtscher-like retinopathy. The hypercoagulable state and specific structures of the radial peripapillary capillaries may play a role in pathogenesis of this disease.

Senescence is a leading cause of mortality, disability, and non-communicable chronic diseases in older adults. Mounting evidence indicates that the presence of cardiovascular disease and risk factors elevates the incidence of both vascular cognitive impairment and Alzheimer's disease (AD). Age-related declines in cardiovascular function may impair cerebral blood flow (CBF) regulation, leading to the disruption of neuronal micro-environmental homeostasis. The brain is the most metabolically active organ with limited intracellular energy storage and critically depends on CBF to sustain neuronal metabolism. In patients with AD, cerebral hypoperfusion, increased CBF pulsatility, and impaired blood pressure control during orthostatic stress have been reported, indicating exaggerated, age-related decline in both cerebro- and cardiovascular function. Currently, AD lacks effective treatments; therefore, the development of preventive strategy is urgently needed. Regular aerobic exercise improves cardiovascular function, which in turn may lead to a better CBF regulation, thus reducing the dementia risk. In this review, we discuss the effects of aging on cardiovascular regulation of CBF and provide new insights into the vascular mechanisms of cognitive impairment and potential effects of aerobic exercise training on CBF regulation. This article is part of the Special Issue "Vascular Dementia".

El sulfato de magnesio ha sido el medicamento de elección en la profilaxis y tratamiento de la eclampsia. Sin embargo, la compresión de las manifestaciones neurológicas producidas por la preeclampsia englobadas dentro de la leucoencefalopatía posterior reversible ha puesto en evidencia que los mecanismos propuestos basados en estudios en animales son ciertos, revalorando más a este antiguo fármaco. Desde el estudio MAGPIE hasta nuestros días son muchas las interrogantes aun no resueltas con respecto al sulfato de magnesio en la preeclampsia, pero es indudable su valor como tratamiento de primera línea para las manifestaciones cerebrales en dicha complicación. Magnesium sulfate is the drug of choice in the prophylaxis and treatment of eclampsia. The recent understanding of the neurological manifestations within the reversible posterior leukoencephalopathy produced by preeclampsia has confirmed mechanisms that had been previously based on animal studies, thus adding value to this old drug. From the MAGPIE study to this day, many questions regarding the use of magnesium sulfate in preeclampsia remain ulsolved, but its value as a first-line treatment for brain manifestations in preeclampsia is undoubtedly high.