Why do herpes simplex encephalitis and semantic dementia show a different pattern of semantic impairment in spite of their main common involvement within the anterior temporal lobes?

Why do herpes simplex encephalitis and semantic dementia show a different pattern of semantic impairment in spite of their main common involvement within the anterior temporal lobes?

Rev Neurosci. 2018 Mar 24;:

Authors: Gainotti G

Abstract
A very challenging problem in the domain of the cognitive neurosciences is to explain why herpes simplex encephalitis and semantic dementia show, respectively, a category-specific semantic disorder for biological entities and an across-categories semantic disruption, despite highly overlapping areas of anterior temporal lobe damage. The aim of the present review consisted in trying to make a separate survey of anatomo-clinical investigations (single-case studies and group studies) and of activation studies, in order to analyse the factors that could explain these different patterns of semantic disruption. Factors taken into account in this review were laterality of lesions, disease aetiology, kind of brain pathology and locus of damage within the temporal lobes. Locus of damage within the temporal lobes and kind of brain pathology seemed to play the most important role, because in patients with herpes simplex encephalitis and category-specific semantic disorder for biological entities the lesions prevailed in the anteromedial temporal lobes. Furthermore, the neuropathology concerned both the anterior temporal cortices and the white matter pathways connecting these areas with the posterior visual areas, whereas in semantic dementia the inferior longitudinal fasciculus involvement was restricted to the rostral temporal lobe and did not extend into the cortically uninvolved occipital lobe.

PMID: 29573378 [PubMed - as supplied by publisher]

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Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia.

Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia.

Eur Arch Psychiatry Clin Neurosci. 2018 Mar 23;:

Authors: Kolomeets NS, Uranova NA

Abstract
Neuroimaging and post-mortem studies have implicated altered myelin integrity and oligodendrocyte abnormalities in the dysfunction of neuronal network in schizophrenia, including the prefrontal cortex, Brodmann area (BA) 10. Pyramidal neurons in layer 5 of BA10 are the important link of reciprocal frontal cortical-basal ganglia-thalamic circuits altered in schizophrenia. Previously, we found ultrastructural dystrophic and degenerative alterations of oligodendrocytes in layer 5 of BA10 in schizophrenia. The aim of the study was to estimate the numerical density (Nv) of oligodendrocytes in layer 5 of BA10 in schizophrenia as compared to normal controls. 17 chronic schizophrenia subjects and 22 healthy matched controls were studied in Nissl-stained sections using optical disector method. Group differences were analyzed using ANCOVA followed by post hoc Duncan's test. The Nv of oligodendrocytes was significantly lower (- 32%, p < 0.001) in the schizophrenia group as compared to the control group. Young controls (age < 50 years old) showed significantly higher Nv of oligodendrocytes as compared to elderly controls (age > 50 years old). Young and elderly schizophrenia subgroups did not differ significantly. Both control subgroups have significantly higher Nv of oligodendrocytes as compared to the schizophrenia subgroups. Decreased Nv of oligodendrocytes found in layer 5 of BA10 may be the result of dystrophic and destructive alterations and/or disrupted development of oligodendrocytes in schizophrenia.

PMID: 29572659 [PubMed - as supplied by publisher]

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Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

Eur Radiol. 2018 Mar 23;:

Authors: Thust SC, Hassanein S, Bisdas S, Rees JH, Hyare H, Maynard JA, Brandner S, Tur C, Jäger HR, Yousry TA, Mancini L

Abstract
OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis.
METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods.
RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98).
CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study.
KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

PMID: 29572636 [PubMed - as supplied by publisher]

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Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information.

Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information.

Mod Pathol. 2018 Mar 23;:

Authors: Koelsche C, Hartmann W, Schrimpf D, Stichel D, Jabar S, Ranft A, Reuss DE, Sahm F, Jones DTW, Bewerunge-Hudler M, Trautmann M, Klingebiel T, Vokuhl C, Gessler M, Wardelmann E, Petersen I, Baumhoer D, Flucke U, Antonescu C, Esteller M, Fröhling S, Kool M, Pfister SM, Mechtersheimer G, Dirksen U, von Deimling A

Abstract
Undifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection of entity-specific mutations. While this approach identifies the majority of Ewing sarcomas, a subset of lesions remains unclassified and, therefore, has been termed "Ewing-like sarcomas" or small blue round cell tumors not otherwise specified. We developed an approach for further characterization of small blue round cell tumors not otherwise specified using an array-based DNA-methylation profiling approach. Data were analyzed by unsupervised clustering and t-distributed stochastic neighbor embedding analysis and compared with a reference methylation data set of 460 well-characterized prototypical sarcomas encompassing 18 subtypes. Verification was performed by additional FISH analyses, RNA sequencing from formalin-fixed paraffin-embedded material or immunohistochemical marker analyses. In a cohort of more than 1,000 tumors assumed to represent Ewing sarcomas, 30 failed to exhibit the typical EWS translocation. These tumors were subjected to methylation profiling and could be assigned to Ewing sarcoma in 14 (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and to malignant rhabdoid tumor in 2 cases each. One single case each was allotted to mesenchymal chondrosarcoma and adamantinoma. 12/14 tumors classified as Ewing sarcoma could be verified by demonstrating either a canonical EWS translocation evading initial testing, by identifying rare breakpoints or fusion partners. The methylation-based assignment of the remaining small blue round cell tumors not otherwise specified also could be verified by entity-specific molecular alterations in 13/16 cases. In conclusion, array-based DNA-methylation analysis of undifferentiated tumors with small blue round cell histology is a powerful tool for precisely classifying this diagnostically challenging tumor group.

PMID: 29572501 [PubMed - as supplied by publisher]

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Regulation of Adipose Tissue Metabolism by the Endocannabinoid System

Publication date: Available online 24 March 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Robin van Eenige, Mario van der Stelt, Patrick C.N. Rensen, Sander Kooijman
White adipose tissue (WAT) stores excess energy as triglycerides, and brown adipose tissue (BAT) is specialized in dissipating energy as heat. The endocannabinoid system (ECS) is involved in a broad range of physiological processes and is increasingly recognized as a key player in adipose tissue metabolism. High ECS tonus in the fed state is associated with a disadvantageous metabolic phenotype, and this has led to a search for pharmacological strategies to inhibit the ECS. In this review we present recent developments that cast light on the regulation of adipose tissue metabolism by the ECS, and we discuss novel treatment options including the modulation of endocannabinoid synthesis and breakdown enzymes.



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Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.

Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.

Int J Lab Hematol. 2018 Mar 24;:

Authors: Arora RD, Dass J, Maydeo S, Arya V, Radhakrishnan N, Sachdeva A, Kotwal J, Bhargava M

Abstract
INTRODUCTION: Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia with heterogeneous clinico-laboratory manifestations. We evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT) for the diagnosis of hereditary spherocytosis (HS).
METHODS: One hundred two suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA) were included, and performance of the above 4 tests was evaluated. For EMA and FOFT, 5 normal controls were assessed together with the patients and cutoffs were calculated using receiver-operator-characteristics curve (ROC) analysis.
RESULTS: The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%, respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow cytometric tests performed better. Sensitivity and specificity of EMA was 86.2% and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of 100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the severity of the disease while %EMA decrease and %RRC did not correlate with severity of the disease.
CONCLUSION: Flow-cytometric osmotic fragility test is the best possible single test followed by EMA for diagnosis of HS. A combination of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to replace conventional OFTs in future.

PMID: 29573337 [PubMed - as supplied by publisher]

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Describing symptoms using the Symptom Screening in Pediatrics Tool in hospitalized children with cancer and hematopoietic stem cell transplant recipients.

Describing symptoms using the Symptom Screening in Pediatrics Tool in hospitalized children with cancer and hematopoietic stem cell transplant recipients.

Cancer Med. 2018 Mar 23;:

Authors: Johnston DL, Hyslop S, Tomlinson D, Baggott C, Gibson P, Orsey A, Dix D, Price V, Vanan M, Portwine C, Kuczynski S, Spiegler B, Tomlinson GA, Dupuis LL, Sung L

Abstract
Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms.

PMID: 29573197 [PubMed - as supplied by publisher]

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