Abstract Auditory hallucinations (AH) are clinical hallmarks of schizophrenia, however little is known about molecular genetics of these symptoms. In this study, gene expression profiling of ...postmortem brain samples from prefrontal cortex of schizophrenic patients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved in this pathway was performed in a larger sample. PLXNB1, SEMA3A, SEMA4D and SEM6C were upregulated in SNA or SA patients compared to controls. PLXNA1 and SEMA3D showed down-regulation in their expression in the patient’s samples, but differences remained statistically significant between the SNA patients and controls. Differences between SNA and SA were found in PLXNB1 expression which is decreased in SA patients. This study strengthens the contribution of brain plasticity in pathophysiology of schizophrenia and shows that non-hallucinatory patients present more alterations in frontal regions than patients with hallucinations concerning neural plasticity.
During the Late Cretaceous, pleurodiran turtles were taxonomically diverse and, inhabited a variety of environments, within a practically worldwide distribution. Among this group, the most widespread ...at that time was Bothremydidae, which was represented in North America by four taxa: Algorachelus tibert, Chedighaii hutchisoni, Chedighaii barberi, and Bothremys cooki. Nevertheless, the presence of Bothremydidae in Mexico is so far very scarce, and the few reports were recognized at indeterminate generic level and have, not been analyzed in detail. In this paper we describe the first Bothremydini from Mexico, collected in a coal mine in Coahuila in the Late Cretaceous of the Olmos Formation (upper Campanian). The coal mines in this region are known for their paleoflora, but this turtle specimen is the first vertebrate to be notified. This specimen displays a unique combination of characters that allows its attribution to a new representative, Palauchelys montellanoi gen. et sp. nov., thus expanding knowledge about the diversity of this group in the American Cretaceous record.
•New Bothremydini material discovered in the Olmos Formation of Coahuila, Mexico is described.•The characteristics of this material allow the recognition of a new genus and species, Palauchelys montellanoi.•Palauchelys montellanoi is the first Bothremydini turtle described from the late Campanian of Mexico.•The new specimen adds to the diversity of Bothremydini in North America.
Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to ...peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r=0.491, p=0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD.
Objectives
The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, ...unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP).
Methods
In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI).
Results
A total of 244 patients were followed up for a median of 21.9 months range 1.2–34.7. Median duration of durvalumab was 45.5 weeks (11.4 months) 0–145. Median PFS was 16.7 months (95% CI 12.2–25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients.
Conclusions
These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
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