A multivariate neuromonitoring approach to neuroplasticity-based computerized cognitive training in recent onset psychosis

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.Subject terms: Predictive markers, Psychosis     

Últimos avances sobre los tumores pancreáticos

Pancreatic cancer (PC) continues to have a very poor prognosis. New epidemiological trials suggest that statins could play a protective role in smokers, while HbsAg-positive hepatitis B virus could be a risk factor. Endoscopic ultrasound (EUS) is the main diagnostic tool for PC, and new technologies associated with this technique have emerged, such as quantitative elastography, intravenous contrasts or, more recently, LASER confocal endomicroscopy. New markers in urine or pancreatic juice have appeared to distinguish between PC and chronic pancreatitis. The role of the “on site” cytopathologist to increase the diagnostic yield of EUS-guided pancreatic sampling is completely supported by new prospective trials and some multicenter studies have been reported that compare the standard cytologic needles with the new procore-histology needles. Regarding cystic pancreatic tumors, most studies have aimed to validate the 2012 Sendai international guidelines and to ascertain predictive factors of malignancy in cystic lesions, mainly intraductal papillary mucinous neoplasm (IPMN). The role of intracystic CEA levels in determining malignancy is challenged. From a therapeutic point of view, EUS-guided radiofrequency ablation of cystic and solid lesions has emerged as a feasible and safe procedure in specific circumstances.     

Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system

Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis. In Flt-1/eGFP-anillin mice, we found eGFP⁺ signals specifically in Ki67⁺/PECAM⁺ endothelial cells during vascular development. Quantification using this cell cycle reporter in embryos revealed a decline in endothelial cell proliferation between E9.5 to E12.5. By time-lapse microscopy, we determined the length of different cell cycle phases in embryonic endothelial cells in vivo and found a M phase duration of about 80 min with 2/3 covering karyokinesis and 1/3 cytokinesis. Thus, we have generated a versatile transgenic system for the accurate assessment of endothelial cell cycle dynamics in vitro and in vivo.     

An Ozone-Generating System and Chamber for Testing Injury to Cultured Cells

A system was constructed which alternately exposed cultured cells to specific concentrations of ozone in the gas phase and then to cell culture medium. It was designed to produce a constant mass transfer between the gas phase and the exposed cell phase. Monolayers of neonatal rat lung fibroblasts cultured in miniature glass dishes were used to test for ozone toxicity. The cells were alternately exposed to ozone (0.05, 0.15, 0.45, 1.35, and 4.05 ppm) for 30 sec and then to culture medium for 30 sec over a 1-hr period. Toxicity was measured as inhibition of cell growth 4 days after exposure to ozone. Growth was significantly inhibited at all concentrations with a 50% inhibitory concentration of 0.8 ppm. The system described was effective for quantifying ozone toxicity for cultured lung cells.     

Successful treatment of systemic juvenile xanthogranulomatosis with cytarabine and 2‐chlorodeoxyadenosine: case report and review of the literature

The non‐Langerhans cell histiocytosis (LCH) juvenile xanthogranulomatosis (JXG) is usually a benign disease limited to the skin. Only a few cases of systemic disease with at least two affected organs and lethal outcomes have been reported to date. Treatment is controversial and no standard protocol is available. We report the rare case of a 22‐month‐old boy presenting multiple erythematous brownish papules of the head, trunk and legs, which had developed starting from his 6th month of life. Additional symptoms were delayed psychomotor development, hydrocephalus and hepatosplenomegaly. Further diagnostics revealed a systemic JXG with involvement of the skin, central nervous system, liver and spleen. The patient did not respond to initial therapy with prednisone and vinblastine according to protocol III for LCH. However, further therapy with cytarabine and 2‐chlorodeoxyadenosine followed by a consolidation phase with 2‐chlorodeoxyadenosine alone was successful and the patient is in his 4th year of remission. We provide a comprehensive review of the reported cases of systemic JXG to date.     

Intraductal papillary mucinous tumor: diagnostic and therapeutic approach

Primary cystic pancreatic neoplasms are rare tumors, with an approximate prevalence of 10% of cystic pancreatic lesions. Most of these lesions correspond to mucinous cystic neoplasm, serous cystoadenoma and intraductal papillary mucinous tumor (IPMT). IPMT is characterized by diffuse dilatation of the main pancreatic duct and/or side branches with inner defects related to mucin or tumor, or mucin extrusion from a patent ampulla. IPMT has a low potential for malignancy, with a low growth rate, a low rate of metastatic spread and postsurgical recurrence. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this tumor.