Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).     

The Good News About Preventing Adolescent Depression

Prevention Science -     

Investigational hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) for the treatment of anemia associated with chronic kidney disease

Introduction: In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive.

Areas covered: We searched PubMed for original articles, reviews, and editorials having as a topic anemia, CKD, hypoxia inducible factor, hepcidin, iron, and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). HIF-PHI are a new class of small molecules activating HIF-alfa isoforms (the main mediators of the effects of hypoxia on the body). This causes the secretion of endogenous erythropoietin and increased iron availability. Differing from ESA, HIF-PHI are administered orally. Preliminary data from phase-II clinical studies have shown their efficacy and safety in the short term.

Expert Opinion: HIF-PHI are a new promising class of drugs. The results of large, phase-III clinical studies are awaited to prove their efficacy and safety on cardiovascular events and cancer development in the long term. Their capability of penetrating the ESA market in the future will be influenced also by their selling price. The oral administration of HIF-PHI will be weighed to the ‘intra-lines’ infusion of ESA in hemodialysis or to the infrequent subcutaneous injections of long-acting ESA.     

Roxadustat in the treatment of anaemia in chronic kidney disease

Introduction: Anaemia is one of the hallmarks of advanced chronic kidney disease (CKD); it correlates with a lower quality of life and increased cardiovascular risk. Currently its management is based on iron and erythropoiesis-stimulating agents (ESAs) therapy. Given safety issues on ESA therapy and excessive iron use, anaemia management is still suboptimal.

Areas covered: The inhibitors of the prolyl-hydroxylases domain (PHD) are oral drugs which activate the hypoxia-inducible factors (HIF) and stimulate the production of endogenous erythropoietin. Roxadustat (FG-4592) is a second-generation PHD inhibitor; it is undergoing now phase-III clinical development.

Expert opinion: Phase-II clinical trials have shown that roxadustat is effective and save in the short term in either non-dialysis or dialysis CKD patients. Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies.     

Strong YB-1 Expression Predicts Liver Recurrence Following Resection for Colorectal Metastases

Introduction

The Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein involved in the proliferation and aggressiveness of cancer cells. The aim of this study was to determine whether strong YB-1 expression in neoplastic cells of colorectal liver metastases (CRLM) may have an impact on liver disease-free survival following liver resection.

Materials and Methods

Immunohistochemistry was performed to evaluate YB-1 in 66 patients who underwent liver resection for CRLM. YB-1 expression was classified as weak (low-staining intensity) and strong (high-staining intensity).

Results

YB-1 expression was observed in the cytoplasm of all CRLM. YB-1 expression was weak in 17 patients (25.8 %) and strong in 49 patients (74.2 %). Liver recurrence rate was significantly higher in the strong than in the weak expression group: 55.1 vs. 23.5 % (p?=?0.023). Multivariable logistic regression analysis showed that YB-1 strong expression was the only independent risk factor for liver recurrence. The 5-year specific liver disease-free survival rate was 76.0 % in the weak expression group and 41.5 % in the strong expression group (p?=?0.034). These results were not influenced by clinical prognostic factors of tumor recurrence.

Conclusions

This is the first study showing that the degree of YB-1 expression in tissue specimens of CRLM predicts liver recurrence following liver resection.     

Phage-Displayed Peptides for Targeting Tyrosine Kinase Membrane Receptors in Cancer Therapy

Receptor tyrosine kinases (RTKs) regulate critical physiological processes, such as cell growth, survival, motility, and metabolism. Abnormal activation of RTKs and relative downstream signaling is implicated in cancer pathogenesis. Phage display allows the rapid selection of peptide ligands of membrane receptors. These peptides can target in vitro and in vivo tumor cells and represent a novel therapeutic approach for cancer therapy. Further, they are more convenient compared to antibodies, being less expensive and non-immunogenic. In this review, we describe the state-of-the-art of phage display for development of peptide ligands of tyrosine kinase membrane receptors and discuss their potential applications for tumor-targeted therapy.     

Epic Allies: A Gamified Mobile App to Improve Engagement in HIV Care and Antiretroviral Adherence among Young Men Who have Sex with Men

AIDS and Behavior - HIV incidence among young men who have sex with men (YMSM) is disproportionally high. Youth living with HIV demonstrate low rates of sustained virologic suppression (VS). Epic...     

Red blood cell transfusions and potentially related morbidities in neonates under 32 weeks’ gestation

BackgroundPreterm neonates are likely to require red blood cell (RBC) transfusion, and extremely low birth weight infants almost invariably receive multiple transfusions. Transfusion-reduction strategies can reduce transfusion rates, and might diminish certain adverse outcomes associated with transfusions.Materials and methodsIn a single centre, we retrospectively evaluated RBC transfusion rates among preterm infants ≤32 weeks’ gestational age (GA), over a 6-year period before and after adopting national transfusion-reduction strategies. We compared demographic data, adverse events, and outcomes between transfused vs not-transfused neonates. Univariate logistic regression was used to evaluate associations between dichotomous outcomes and number of transfusions, and day of first transfusion. Multivariate logistic regression evaluated the correlation between dichotomous outcomes and transfusion as an independent risk factor.ResultsDuring the 6 years studied, 181 infants born at ≤32 weeks’ GA were admitted to our Neonatal Intensive Care Unit of whom 80 (44%) received at least one RBC transfusion. The transfusion rate tended downwards after adopting transfusion-reduction strategies, reaching 31% in 2018. The reduction was largely due to a marked fall in transfusions of neonates born at 29–32 weeks’ GA (p<0.001). The number of transfusions received correlated with odds of having intraventricular haemorrhage (IVH) (OR=1.9; 95% CI: 1.3–2.7; p=0.0001) and the duration of oxygen supplementation (rho=0.51; 95% CI: 0.33–0.66; p≤0.0001). In multivariate logistic regression analysis, transfusion was an independent risk factor for IVH (adjusted OR=7.38; 95% CI: 2.24–24.30; p=0.0001).DiscussionThe application of national, standardised transfusion-reduction strategies was associated with a lower transfusion rate in neonates born at 29–32 weeks’ GA, but was less effective among neonates ≤28 weeks, in whom transfusions appeared to be an independent risk factor for severe IVH.     

Earliest Videofluoromanometric Pharyngeal Signs of Dysphagia in ALS Patients

The aim of this study was to find whether there are manometric pharyngeal changes that may have diagnostic and prognostic relevance in the amyotrophic lateral sclerosis (ALS) patient who does not show changes in contrast-medium oropharyngeal transit in a videofluoroscopic swallowing study. Ten ALS patients, with an ALS Severity Scale Score of at least 7, no need to change dietary habit, no aspiration and/or penetration, and no other changes in contrast-medium oropharyngeal transit, were collected from our institution’s database of videofluoromanometric swallowing studies. They were included in the study together with a group of 11 healthy volunteers. For each subject, 12 manometric items—7 for the pharyngeal phase and 5 for UES functionality—were evaluated. Statistically significant differences between the ALS patients and the healthy volunteers were found for pharyngeal contraction time of the upper region (median = 1,120, range = 880–1,420 vs. median = 970, range = 800–1,140), pharyngeal contraction time of the intermediate region (median = 1140, range = 960–1,360 vs. median = 770, range = 280–1,180), pharyngeal contraction time of the lower region (median = 1,320, range = 920–1,760 vs. median = 800, range = 620–1,780), and residual pressure after the relaxation of the UES (median = 2.2, range = ?20.2 to 27.8 vs. median = ?5.7, range = ?2.9 to 8.4). A videofluoromanometric swallowing study may show an increase in the pharyngeal contraction time and in residual pressure after relaxation of the UES in ALS patients without videofluoroscopic changes in contrast-medium oropharyngeal transit.     

Human brain networks: a graph theoretical analysis of cortical connectivity normative database from EEG data in healthy elderly subjects

GeroScience - Moving from the hypothesis that aging processes modulate brain connectivity networks, 170 healthy elderly volunteers were submitted to EEG recordings in order to define age-related...