Increased PrPC expression correlates with endoglin (CD105) positive microvessels in advanced carotid lesions

Normal cellular prion protein (PrP^C) has multiple functions but its role in the development of atherosclerosis has not been studied. Our pilot microarray data showed increased expression of PrP^C in tissue samples of complicated carotid lesions. Therefore in this study, we aimed to investigate its localisation within atherosclerotic arteries and its concentration in patient plasma. PrP^C expression was examined using an enzyme immunometric assay (EIA) in plasma from patients undergoing endarterectomy. Carotid specimens and control vascular transplants were studied for PrP^C and CD105 (endoglin, a marker of active vessels) expression by immunohistochemistry and real-time PCR. Patients with carotid disease had higher levels of plasma PrP^C than the control group [4.35 ng/ml (n = 22; 3.1–5.3) vs. 1.95 ng/ml (n = 21; 1.1–2.5), P < 0.001]. Furthermore, CD105-positive plaques had higher PrP^C expression which colocalized with CD105 in neovessels. There was a significant correlation between mRNA expression of PrP^C and CD105 in tested plaques (P < 0.001; r = 0.7) supporting our immunohistochemical findings. We conclude that PrP^C is expressed in carotid specimens and may be associated with neovessel growth or survival in these plaques. Our results suggest a role for PrP^C in modulating neovessel formation in complicated plaques.     

Neutrophil-lymphocyte ratio in Guillain-Barré syndrome: A prognostic biomarker of severe disease and mechanical ventilation in Bangladesh

In addition to cellular and humoral immunity, inflammatory markers play an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and are used to predict prognosis in many autoimmune diseases. The aim of this study was to identify whether the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and monocyte-lymphocyte ratio in the early stages of GBS have prognostic value for severe disease, mechanical ventilation (MV) and poor long-term outcome. A prospective cohort study of 140 adult patients with GBS and 140 healthy controls (HC) was performed in Bangladesh during 2019–2022. Clinicodemographic characteristics of the patients were recorded, and hematological parameters were measured using an automated hematology analyzer. Median patient age was 35 (44–23) years; 71% were male; 88% were severely affected (GBS Disability Score> 3); 32% required MV. Patients had higher NLR than HC (P< .0001). Among patients, elevated NLR was associated with severe GBS and MV (P= .001 and <.0001, respectively) and moderately positively correlated with poor outcomes at 4 weeks (r = 0.423). Multiple logistic regression revealed NLR was an independent risk factor for severe GBS (OR = 5.2, 95% CI = 1.6–17.4) and MV (OR = 1.5 1.1–2.1). No significant association was observed between elevated NLR and the long-term outcome of GBS. Receiver operating characteristic curves revealed NLR cut-off values of ≥ 2.432 and ≥ 4.4423 predicted severe disease (sensitivity = 71%, specificity = 75%, AUC = 0.750, 95% CI = 0.651–0.849, P = .001) and MV (sensitivity = 65.9%, specificity = 81.7%, AUC = 0.804, 95% CI=0.724–0.884; P< .001). The NLR in the early stage of GBS may represent an independent prognostic factor of severe GBS and the requirement for MV.     

Negative symptoms and concordant impairments in attention in schizophrenia: Associations with social functioning, hope, self-esteem and internalized stigma

Research has suggested that negative symptoms in schizophrenia may be closely linked to impairments in schizophrenia. Research on the strength and nature of this association has been equivocal, however. One possible explanation is that there are two distinct groups of persons with negative symptoms: those with and those without attentional impairments. To examine this question we performed a cluster analysis on 99 adults with schizophrenia or schizoaffective disorder on the basis of their level of negative symptoms and performance on a continuous performance task. Four groups were found: low negative/relatively better attention (n = 31), low negative/relatively poor attention (n = 20), high negative/ relatively poor attention (n = 28), and high negative/relatively better attention (n = 20). To determine whether these groups differed meaningfully from one another, we next compared their performance on other assessments of positive symptoms, social function, self-esteem and stigma. A MANOVA found significant differences (Wilks' lambda F = 3.2; p < .01) with the high negative/poor attention group having poorer self esteem and greater acceptance of stigma than the other three groups and the high negative/relatively better attention group having higher levels of positive symptoms than the other groups. Implications for research and treatment are discussed.     

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis

ObjectiveIt may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM.MethodsThis prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18–75).ResultsIn total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02).ConclusionPediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.     

Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Sex differences in the prognostic value of the lipid profile after the first ischemic stroke

Post-stroke levels of total cholesterol (TC) appear to be negatively associated with stroke mortality. Statin pretreatment might affect this association. Sex differences in the prognostic value of the lipid profile have not yet been studied. We have evaluated the impact of TC, high- and low-density lipoprotein (HDL and LDL, respectively), and triglyceride (TG) levels on the 3-month outcome after a first ischemic stroke (IS) according to sex and previous statin use. The study group consisted of a hospital-based cohort of consecutive patients with a diagnosis of first IS. Poor outcome was defined as a modified Rankin Scale (mRS) score ≥3 at 90 days. The odds ration (OR) for poor prognosis was analyzed for each sex using logistic regression models adjusted for vascular risk factors and statin pretreatment. A total of 591 patients were included in the analysis (318 men). The predictors of a 90-day poor outcome were age and initial NIH Stroke Scale (NIHSS) score in women, and age, initial NIHSS, smoking, atrial fibrillation, and thrombolytic treatment in men. In women, none of the lipids studied affected the 90-day prognosis. Men falling in the last quintile of TC [OR: 0.68 95% confidence interval (95% CI) 0.52–0.88; p = 0.004] and LDL (OR 0.74, 95% CI 0.56–0.98; p = 0.04) have better outcome than men in the first quintile. Adjusting for statin pretreatment did not change the results. The results indicated that an association between poststroke lipids and prognosis may vary by sex. In women, lipids were not associated with the outcome; in men, lower TC and LDL were associated with worse prognosis. These differences can not be explained by statin use and require further research.     

Structural gray and white matter changes in patients with HIV

In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson’s Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.     

MiR-29a-Mediated CD133 Expression Contributes to Cisplatin Resistance in CD133<Superscript>+</Superscript> Glioblastoma Stem Cells

CD133 positive (CD133⁺) cells are cancer stem cells in glioblastoma that are associated with poor prognosis and resistance to radiotherapy. However, the role of CD133 in chemoresistance is inconclusive, although recent studies suggest that increased CD133 expression may lead to increased cisplatin resistance under certain circumstances. In this study, we further explored the mechanism underlying CD133-mediated cisplatin resistance in glioblastoma stem cells. We sorted human glioblastoma T98G and U87MG cells into CD133⁺ and CD133^? pools and measured apoptosis and CD133 expression levels in response to cisplatin treatment. We predicted candidate microRNAs that might target CD133 and assessed their levels in cisplatin-treated CD133⁺ cells. Finally, we overexpressed miR-29a in CD133⁺ cells and tested its effects in cisplatin-mediated apoptosis and survival of CD133⁺ tumor bearing mice receiving cisplatin treatment. We found that CD133⁺ glioblastoma stem cells showed more resistance to cisplatin treatment. Cisplatin increased CD133 expression by suppressing miR-29a levels. MiR-29a overexpression improved sensitivity of cisplatin in CD133⁺ cells and significantly suppressed tumor growth in CD133⁺ tumor bearing mice in response to cisplatin treatment. Our data show that miR-29a ameliorates CD133-mediated chemoresistance in glioblastoma stem cells, suggesting it as a potential therapeutic target for treating glioblastoma.     

Embryonic stem cell-like subpopulations are present within Schwannoma

BackgroundThere is accumulating evidence of the presence of embryonic stem cell (ESC)-like cells in benign tumors.AimThis study aimed to identify ESC-like cells in Schwannoma using the induced-pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4 and c-MYC.MethodsImmunohistochemical (IHC) staining (n = 20) and RT-qPCR (n = 6) were performed on Schwannoma tissue samples (STS) to investigate protein and mRNA expression of these iPSC markers, respectively. Immunofluorescence (IF) staining was performed to investigate co-localization of the iPSC markers with CD34, α-SMA and CD133.ResultsIHC staining and RT-qPCR demonstrated protein and mRNA expression of all five iPSC markers, respectively. IF staining showed expression of SOX2, KLF4 and c-MYC on the tumor cells and the endothelium of the tumor microvessels which also expressed OCT4, while NANOG was exclusively expressed on the endothelium of the tumor microvessels. The OCT4+/CD34+ endothelium expressed CD133.ConclusionWe have identified a putative OCT4+/SOX2+/NANOG+/KLF4+/c-MYC+/CD133+ ESC-like subpopulation on the endothelium of tumor microvessels and an OCT4-/SOX2+/NANOG-/KLF4+/c-MYC+/CD133+ ESC-like subpopulation, within Schwannoma.     

Complication Burden Index—A tool for comprehensive evaluation of the effect of complications on functional outcome after status epilepticus

Systemic complications are common in status epilepticus. We have no tools to evaluate total burden of complications and its effect on the outcome of status epilepticus. For Complication Burden Index (CBI) a patient is assessed for 13 complication categories: respiratory, cardiovascular, nervous, renal, hepatic, coagulation, gastrointestinal and musculoskeletal systems, electrolyte/acid‐base balance, infection, hypo‐/hyperglycemia, skin/allergic reactions, and mental condition. Maximum CBI is 13. CBI was internally validated in a retrospective cohort of 70 consecutive adult patients with generalized convulsive status epilepticus (GCSE) treated in a tertiary hospital over a period of 2 years. Functional outcome at discharge was defined Poor for Glascow Outcome Scale (GOS) 1‐3 or worse‐than‐baseline condition and Good for GOS >3 or return to baseline condition. Relative risks (RRs) and receiver‐operating characteristic (ROC) ‐curves were calculated to obtain optimal cutoff. Functional outcome was poor in 40% and worse‐than‐baseline in 59%. In‐hospital mortality was 7%. Average CBI was 3.8 (range 0‐10, median 3). Cutoff value predicting poor functional outcome was a CBI >3 (GOS 1‐3 RR 1.84, P = .045, 95% confidence interval [CI 1.01‐3.33; ROC‐AUC [area under the curve] 0.687, P = .008, sensitivity 64%, specificity 61%; worse‐than‐baseline condition RR 1.52, P = .04, 95% CI 1.02‐2.26; ROC‐AUC 0.662, P = .022, sensitivity 56%, specificity 69%). CBI with cutoff >3 and as a continuous variable was associated with GOS1‐3 (P = .046, P = .002) and with worse‐than‐baseline condition (P = .041, P = .004). CBI is a novel tool for comprehensive assessment of status epilepticus complications predicting poor/worse‐than‐baseline functional outcome with cutoff >3.     

The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients

PurposeSonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress.MethodsA total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups.ResultsThe expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation.ConclusionOur observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.     

Effects of nidus microarchitecture on cerebral arteriovenous malformation hemodynamics

Intranidal vessel geometry and organization underlying flow within cerebral arteriovenous malformations (AVM) is poorly understood. We examine the relationship between intranidal vessel characteristics and AVM flow. Records of patients with AVM evaluated at our institution between 2007 and 2013 were retrospectively reviewed. Patients were included if surgical specimens were available and flows were obtained before treatment using quantitative magnetic resonance angiography. Intranidal vessels were identified and the diameter and cross-sectional area of each vessel were measured from digitized images of specimen slides. The relationship between vessel diameter, vessel cross-sectional area, AVM volume, and AVM flow was assessed. Twenty-nine patients were included. Mean total number of vessels per specimen was 133. Mean total AVM flow was 340 ± 276 mL/min. Mean vessel diameter ranged from 0.18–2.37 mm and mean vessel cross-sectional area ranged from 0.09–9.46 mm². Linear regression analysis showed that total flow is significantly associated with larger AVM volume (R² = 0.28, P = 0.007), but not with number of vessels per section of the specimen (P = 0.20) or mean vessel diameter (P = 0.92). Exponential regression analysis demonstrated that AVM flow is significantly correlated to the sum of the cross-sectional vessel areas within each specimen (R² = 0.16, P = 0.05). Total AVM flow is significantly related to sum of the cross-sectional areas of all vessels within each nidus, rather than to total number of vessels or mean nidal vessel diameter. This finding suggests that the sum of the cross-sectional areas of intranidal vessels likely determines the resistance to flow within a cerebral AVM.     

The association between preschool behavioural problems and internalizing difficulties at age 10–12 years

The aim was to study the association between preschool behavioural problems and emotional symptoms in 10- to 12-year-old children. The study was based on the Aarhus Birth cohort, Denmark, and included 1,336 children. Based on the parent-administered preschool behaviour questionnaire (PBQ), we identified three not mutually exclusive preschool behavioural categories: anxious–fearful (n = 146), hyperactive–distractible (n = 98), and hostile–aggressive (n = 170). Children without any known symptoms were considered well adjusted (n = 1,000). Borderline emotional (n = 105) and emotional difficulties (n = 136) were measured at age 10–12 years with the parent-administered strength and difficulties questionnaire (SDQ). Multinomial logistic regression analyses were used to adjust for potential confounding factors. We found that anxious–fearful behaviour and hostile–aggressive preschool behaviour were associated with twice the risk of school-age emotional difficulties. Comorbidity or confounding failed to explain these results. Hyperactive–distractible preschool behaviour was not associated with school-age emotional difficulties. Preschool anxious–fearful behaviour was associated with school-age emotional difficulties, suggesting internalizing symptom stability in some children from early childhood. Preschool hostile–aggressive behaviour was also associated with school-age emotional difficulties, which suggests transformation of one behavioural dimension into another through childhood, and the need to focus on both early internalizing difficulties and hostile–aggressive behaviour as risk factors for later internalizing difficulties.     

Primary intracranial papillary meningioma: Analysis of factors of prognosis and systematic review

ObjectivePapillary meningioma is rare and displays an aggressive clinical behavior with poor prognosis. Therefore, we performed an extensive literature review to evaluate the adverse factors and treatment strategy of survival.MethodWe performed Ovid, Medline, Embase, Pubmed, Web of Science and Cochrane database queries for articles published between 1938 and 2019 with the search term “WHO grade III meningioma” or “papillary meningioma” and “central nervous system”, “cerebral”, or “intracranial”.ResultsAfter a careful evaluation, a total of 19 studies were included. The entire cohort included the 67 patients, 34 (50.7%) were male and 33 (49.3%) were female with a mean age of 32.6 ± 2.1 years ranging from 4.5 months to 74 years. Gross total resection was achieved in 48 (71.6%) cases, and 29 (51.8%) patients received postoperative radiation. The mean follow-up period was 42.3 ± 4.4 months (range, 2–197 months). Thirty-six (53.7%) patients happened to recurrences, 11 (16.4%) patients happened to extracranial metastasis and 25 (37.3%) patients died. Univariate analysis revealed that the MIB > 5% trended toward a shorter time to recurrence (p = 0.084). Gross total resection was associated with favorable progression-free survival (p = 0.007) and overall survival (p = 0.001). Postoperative radiation was associated with favorable progression-free survival (p = 0.001).ConclusionsGross total resection and adjuvant radiation were recommended as the initial treatment option for patients with papillary meningioma.     

Mechanisms of in-hospital acute ischemic stroke and their relevance to prognosis: A retrospective analysis

ObjectivesIn-hospital stroke (IHS) is common and has a poor prognosis. Limited data were about the mechanisms of IHS, posing a challenge in taking measures to prevent stroke during hospitalization. This study aims to investigate the mechanisms of IHS and their relevance to prognosis.Materials and MethodsPatients with in-hospital acute ischemic stroke at Peking Union Medical College Hospital from June 2012 to April 2022 were consecutively enrolled. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of stroke and detailed mechanisms were evaluated by two experienced neurologists. Functional outcome at discharge was evaluated.ResultsA total of 204 IHS patients were included, with a median age of 64 (IQR 52-72) and 61.8% male. The most common mechanism was embolism (57.8%), followed by hypoperfusion (42.2%), hypercoagulation (36.3%), small vessel mechanism (19.1%), discontinuation of antithrombotic drugs (13.2%), and iatrogenic injury (9.8%). Iatrogenic injury (P = 0.001), hypoperfusion (P = 0.006), embolism (P = 0.03), and discontinuation of antithrombotic drugs (P = 0.004) were more common in perioperative stroke compared to non-perioperative stroke. Median NIHSS improvement (2 vs 1, P = 0.002) and median mRS improvement (1 vs 0.5, P = 0.02) at discharge were higher in perioperative patients. Advanced age and higher NIHSS at onset were significantly associated with a poorer prognosis, whereas embolism mechanism was associated with a better prognosis.ConclusionsThe etiologies and mechanisms of IHS are complex. Perioperative and non-perioperative IHS have different mechanisms and prognostic features. Determining the causes and mechanisms of IHS will help to identify the population at risk and prevent stroke appropriately during hospitalization.     

Immunohistochemical evaluation of the microvascular density through the expression of TGF‐β (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas

Angiogenesis has been proposed as essential for the growth of solid tumors. The determinants of this process, the growth factors and the vascular endothelial receptors have brought a potential in the tumor prognostic determination as well as perspectives of “targets” for antiangiogenic therapy. In oligodendrogliomas (OL), angiogenesis is little known and/or has generated conflicting results. In order to clarify angiogenesis in OL, we have evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and the microvascular density (MVD) through the expression of TGF‐β (CD105/endoglin) (MVD‐CD105) and CD34 (MVD‐CD34) receptors using the Chalkley point method in 30 OL. No significant immune reaction was found for the VEGF. There was expression in <10% of tumor cells and/or staining of weak intensity in 15 (50.0%), >10% of cells and moderate intensity staining in 1 (3.33%), and negative expression in 14 (46.67%). If present, the expression was restricted to tumor and endothelial cells. Our findings suggest that VEGF has little influence on OL angiogenesis. All specimens showed CD105 and CD34 expression in the intratumor vascular endothelium, suggesting involvement of CD105 in OL angiogenesis. The mean ± SD MVD‐CD105 and MVD‐CD34 were 10.83 ± 2.24 and 11.00 ± 2.76 in OL (P = 0.086; r = 0.319); 10.00 ± 2.00 and 10.40 ± 3.02 in OL grade II (n = 15) (P = 0.547; r = 0.105), and 11.67 ± 2.22 and 11.53 ± 2.45 in OL grade III (n = 15) (P = 0.817; r = 0.551), respectively. The absence of correlation between DMV‐CD105, DMV‐CD34 and tumor grades suggests that anti‐CD105 and anti‐CD34 antibodies have different vascular specificities. MVD‐CD105 was greater in OL grade III than in OL grade II (P = 0.0032), indicating an increase in the vascular neoformation, something which must be evaluated as a possible prognostic factor in OL. Both TGF‐β and CD105 bring perspectives as “targets” for antiangiogenic treatments in OL.     

The link between negative affect,vagal tone,and visceral sensitivity in quiescent Crohn's disease

Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12 ± 3 in patients vs 4 ± 1 in controls on the Center for Epidemiologic Studies‐Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 ± 84 ms² vs 1607 ± 1032 ms², p = 0.043; LF 455 ± 153 ms² vs 1629 ± 585 ms², p = 0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43 ± 3 mmHg vs 30 ± 2 mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS.     

High glycemic variability: An underestimated determinant of stroke functional outcome following large vessel occlusion

Background and purposeEarly glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion.MethodsA single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24 hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24 hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed.ResultsAmong the 93 patients evaluated, 26 had early high GV (≥ 20.9 mg/dl). High GV was associated with poor functional outcome (OR = 8.00; 95%CI [1.34–47.89]; P = 0.02) unlike admission glycemia and mean glycemia (OR = 2.92; 95%CI [0.51–16.60]; P = 0.23 and OR = 0.36; 95%CI [0.05-2.6]; p = 0.31, respectively). High GV was not associated with NIHSS at 24 hours or hemorrhagic transformation.ConclusionAcute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.     

Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome

Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS‐ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S‐100β protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S‐100β protein and GFAp in CSF from patients with RHS (n = 15) and RHS‐ZSH (n = 13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n = 52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House‐Brackmann score. NFL and GFAp concentrations were increased compared with controls (P = 0.008 and P = 0.04), while S‐100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS‐ZSH (NS and P = 0.028). The amount of viral DNA in CSF correlated with increased GFAp (P = 0.003) and NFL (P = 0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.     

The relevance of social anxiety for understanding social functioning and facial emotion recognition in individuals at clinical high-risk for psychosis

Aim

Individuals at clinical high risk (CHR) for psychosis often experience poor social functioning and impaired facial emotion recognition (FER); however, the impact of frequently comorbid symptoms upon these processes is underexplored. In particular, social anxiety is characteristic of this population and also related to poor social functioning and FER biases, such as misinterpreting neutral faces as negative or threatening; however, little is known about how social anxiety relates to these processes in CHR individuals. The present study examined the overlap of social anxiety, social functioning, and FER accuracy and bias.

Method

Participants (CHR N = 62, healthy controls N = 52) completed the self-report Social Interaction Anxiety Scale (SIAS), Penn Emotion Recognition-40 (ER-40) behavioural task, and interviewer-rated Global Functioning Scale-Social (GFS-S). The ER-40 was used to assess both FER accuracy (e.g., overall number of correct responses) and bias (e.g., mislabelling neutral faces as angry).

Results

Consistent with previous research, relative to controls, CHR participants had more social anxiety (d = −1.07), poorer social functioning (d = −1.62), and performed more poorly on the FER task (e.g., d = −.37). Within CHR participants, social anxiety was related to an anger detection bias (r = .28), above and beyond positive symptom severity, which in turn was related to FER accuracy (r = .26) and social functioning (r = −.28).

Conclusion

These findings suggest that ongoing work examining social processes within CHR individuals needs to account for social anxiety and that social anxiety may be a useful preventive intervention target.