Memory Rehabilitation Strategies in Nonsurgical Temporal Lobe Epilepsy: A Review

open8siPeople with temporal lobe epilepsy (TLE) who have not undergone epilepsy surgery often complain of memory deficits. Cognitive re- habilitation is employed as a remedial intervention in clinical settings, but research is limited and findings concerning efficacy and the criteria for choosing different approaches have been inconsistent. We aimed to appraise existing evidence on memory rehabilitation in nonsurgical individuals with temporal lobe epilepsy and to ascertain the effectiveness of specific strategies. A scoping review was preferred given the het- erogeneous nature of the interventions. A comprehensive literature search using MEDLINE, EMBASE, CINAHL, AMED, Scholars Portal/ PSYCHinfo, Proceedings First, and ProQuest Dissertations and Theses identified articles published in English before February 2016. The search retrieved 372 abstracts. Of 25 eligible studies, six were included in the final review. None included pediatric populations. Strategies included cognitive training, external memory aids, brain training, and noninvasive brain stimulation. Selection criteria tended to be general. Overall, there was insufficient evidence to make definitive conclusions regarding the efficacy of traditional memory rehabilitation strategies, brain training, and noninvasive brain stimulation. The review suggests that cognitive rehabilitation in nonsurgical TLE is underresearched and that there is a need for a systematic evaluation in this population.embargoed_20180216DEL FELICE, Alessandra; Alderighi, Marzia; Martinato, Matteo; Grisafi, Davide; Bosco, Anna; Thompson, Pamela J.; Sander, Josemir W.; Masiero, StefanoDEL FELICE, Alessandra; Alderighi, Marzia; Martinato, Matteo; Grisafi, Davide; Bosco, Anna; Thompson, Pamela J.; Sander, Josemir W.; Masiero, Stefan

South American medicinal plants for the symptomatic treatment of benign prostatic hyperplasia: A systematic review

Background & Aim: Benign prostatic hyperplasia (BPH) is one of the prevalent age-related medical conditionin men. In the last 20 years, alternative therapies, especially those based on herbs, are increasingly preferred. The most popularly consumed herb is Serenoa repens, a plant growing in the subtropical south-eastern United States which has shown very efficient results compared to pharmacological conventional treatments both in terms of cost and risks associated with them. Nevertheless, the same trial found no difference between S. repens and placebo according to the American Urological Association Symptom Score Index. As more and more consumers are turning increasingly towards natural therapies, it would be appropriate to promote the recognition of the value of other medicinal plants with potential applicability through comprehensive research. For this purpose, a descriptive comparison between several South-American plants little publicised in the pharmaceutical market is presented to slightly narrow the gap between the reliable evidence-based and popular information for consumers and the pharmaceutical industry. Experimental: With this approach, a review of the literature was conducted through an electronic consultation of two databases, Science Direct and Google Scholar™. Results: This narrative review highlights the wide range of natural medicines available for controlling the inflammatory symptoms of the lower urinary tract, which could be more explored from a pharmacological and chemical point of view. Recommended applications/industries: The future use of natural products requires further investment in pre-clinical research and in clinical trials that investigate stability and a profitable pharmacokinetic/pharmacodynamic ratio. Although they are well tolerated and used daily by South American populations, the industry's proper commercial focus on these natural remedies cannot be separated from appropriate phyto-vigilance actions promote

Hyperoxia-induced changes in morphometric parameters of postnatal neurogenic sites in rat

In literature many works address the effects of hypoxia exposure on postnatal neurogenesis but few data are available about hyperoxia effects, although high oxygen concentrations are frequently used for ventilation of premature newborns. Thus, the aim of the present study was to compare with controls the morphometrical parameters of the main neurogenic sites (subventricular zone and dentate gyrus) in newborn Sprague-Dawley rats exposed to 60% or 95% oxygen for the first 14 postnatal days. Six rats were studied for each of the three groups. The unbiased quantitative method of the optical disector was applied to analyze neuronal densities, nuclear volumes, and total neuron numbers of the subventricular zone and hippocampal dentate gyrus. Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling, TUNEL) and proliferation (Ki67) were also studied. The subventricular zone of newborn rats exposed to 95% hyperoxia showed statistically significant higher volume (mean value ± coefficient of variation: 0.40 ± 0.20 mm3) than subventricular zone of rats raised in normoxia (0.20 ± 0.11 mm3) or 60% hyperoxia (0.26 ± 0.18 mm3). Total neuron number was also significantly higher in 95% hyperoxia while neuronal densities did not reach statistically significant differences. TUNEL showed increased apoptotic indexes in hyperoxic rats. The percentage of proliferating KI67 positive cells was also higher in hyperoxia. The dentate gyrus granular layer of the normoxic rats showed higher volume (0.65 ± 0.11 mm3) than both the hyperoxic groups (60% hyperoxia: 0.39 ± 0.14 mm3; 95% hyperoxia: 0.36 ± 0.16 mm3). Total neuron numbers of hyperoxic dentate gyrus were also significantly reduced; neuronal densities were not modified. Hyperoxia-exposed rats also showed higher apoptotic and proliferating indexes in the dentate gyrus. Hyperoxia exposure in the first postnatal period may affect the main neurogenic areas (subventricular zone and dentate gyrus) increasing apoptosis but also inducing a certain reparative response consisting of increased proliferation. In particular, the increased volume of the subventricular zone may be ascribed to compensatory neurogenic response to the hyperoxic damage. Conversely, the decreased volume of the dentate gyrus granular layer could derive by a non sufficient neurogenic response to counterbalance the hyperoxic neuronal injury

L-citrulline is protective in hyperoxic lung damage and improves matrix remodelling and alveolarization

Moderate hyperoxia alters alveolar and vascular lung morphogenesis. Nitric oxide (NO) and matrix metalloproteinases (MMP) have a crucial role in the homeostasis of the matrix and bronchoalveolar structure and may be regulated abnormally by exposure to hyperoxia. Disruption of vascular endothelial growth factor (VEGF)-NO signaling impairs vascular growth and contributes to hyperoxia-induced vascular disease in bronchopulmonary dysplasia (BPD). We hypothesize that L-citrulline, by raising the serum levels of L-arginine and enhancing endogenous NO synthesis, might attenuate hyperoxia-induced lung injury in an experimental model of BPD. Neonatal rats (1 day old) were exposed to 60% oxygen or room air for 14 days and administered L-citrulline or a vehicle (sham). Lung morphometry were performed; Serum was tested for arginine level; Matrix metalloproteinases2 (MMP2) gene expression, VEGF gene and protein expression and endothelial NO synthase (eNOS) protein expression were compared. Mean linear intercept was higher in the hyperoxia and sham groups when compared with the room air (RA) and L-citr+hyperoxia treated group (p<0.02). Secondary crests number was higher in L-citrulline treated and RA when compared to hyperoxia and sham group (p<0.02). L-Arginine level rose in the L-citrulline-treated group (p<0.05). L-citrulline did not affect MMP2 gene expression, but it regulated the MMP2 active protein, which rose in bronchoalveolar lavage fluid (p<0.05), presumably due to a post-transductional effect. Compared with RA controls, hyperoxia significantly decreased VEGF and eNOS protein expression. At the same time, an increased lung VEGF gene and protein expression (p<0.05) were also seen in the rats treated with L-citrulline. We conclude that: (i) hyperoxia decreases growth and disrupts VEGF-NO signaling of lung; (ii) the main effects of L-citrulline are an increased serum level of arginine, as a promoter and a substrate of the nitric oxide synthase; and (ii) a better alveolar growth and matrix control than in hyperoxia-induced lung damage seems promising

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Possibile impiego delle cellule staminali del fluido amniotico per la riparazione del danno polmonare in un modello animale per broncodiplasia: valutazione in vitro e in vivo

Introduction. Since our knowledge on the replication and differentiating capability of the respiratory tract is still limited, the therapeutic potential of this system is quite unexplored. The respiratory disease in pediatric age concerns several pathologies among which broncopulmonary dysplasia (BPD) in neonate and premature newborns, asthma and cistyc fibrosys are the most studied because of their diffusion among children and their infaust prognosis.. In the last few years some studies have shown the possibility of deriving progenitors with various potential from the amniotic fluid. Amniocentesis is a widely accepted method for prenatal diagnosis; it is associated with low risk both for the mother and the fetus and overcomes the ethical problems commonly associated to other sources. Recently, it has been described that amniotic fluid stem (hAFS) cells, for their ability to differentiate to various lineages, could represent a good candidate for therapeutic applications. The recent characterization of hAFS and the consolidation of the techniques for intratracheal transplantation have shown new perspectives for gene and cell therapy applications. In particular, for these purposes hAFS cells should be genetically modified with a therapeutic gene and delivered systematically or injected directly into the tissue of interest. Materials and methods The in vitro phase has evaluated for the first time the possibility to infect hAFS with first generation E1-deleted adenoviral vectors, and the mantainence of the stemness and differentiating capability even after transduction with foreign gene sequences. In the in vivo phase of the project we verified the pulmonary homing and the eventual engraftment of hAFS cells, after intratracheal administration, in a 60% O2 rat model presenting a respiratory disease similar to the one observed in human patients affected by broncopulmonary dysplasia (BPD) and cystic fibrosis. The symptoms were reproduced by using OXYCYCLER, with two pressurized rooms in which animals are exposed at controlled percentages of O2 and CO2. In this trial, hAFS cells have been infected AdHCMVsp1LacZ, a first generation E1 deleted viral vector transducing LacZ, the β-gal specific gene used as marker. Results At first, we investigated the feasibility of transducing hAFS cells with adenoviral vectors and to determine whether transduced stem cells retain the ability to differentiate into different lineages. Herein, we showed that hAFS cells could be efficiently infected by first generation adenovirus vectors. In addition, we demonstrated that infection and expression of two different marker genes, LacZ and EGFP, have no effect on cells phenotype and differentiation potential. In particular, on undifferentiated status, hAFS cells continued to express both the transgenes and stemness cell markers OCT4 and SSEA4 (stage-specific embryonic antigen 4). When cultured under mesenchymal conditions, infected cells could still differentiate into osteocytes and adipocytes expressing lineage specific genes. Differently to what observed in embryonic stem cells, the amniotic fluid stem cells easily infect very efficiently. This could represent an excellent starting point for gene therapy studies in which a transient expression would be a necessary condition to the therapeutic approach. In the in vivo phase we transplanted hAFS cells with an intratracheal administration in a rat model generated exposing newborns at 60% O2 for two weeks, reproducing in this way the chronic damage that can be seen in human patients affected by BPD. The results show that the model for chronic lung damage has been properly implemented; specific staining for lacZ performed three weeks post-transplant confirmed for hAFS cells a bronchiolar homing. After four weeks transplantation LacZ positive cells have been detected inside alveolis. Finally, an important phenomenon of damage repair was observed in the treated animals as compared to untreated controls

Reconsidering clinical pharmacology frameworks as a necessary strategy for improving the health care of patients: a systematic review

Clinical pharmacology (CP) is a multidisciplinary scientific field involving all aspects of the relationship between drugs and humans, encompassing professionals with a wide variety of skills including medicine, pharmacology, pharmacy, and biomedical science. The term Bclinical pharmacologist^ is commonly used in the professional sense to refer to medical doctors or PhD-level natural scientists/pharmacists with proven experience in improving patient care by developing new medicines and promoting the safer and more effective use of drugs. Clinical pharmacologists today should have experience even in various phases of drug development in basic and clinical research, regulatory agencies, and/or the pharmaceutical industry

Early versus late cord clamping: effects on peripheral blood flow and cardiac function in term infants.

BACKGROUND: In the debate on the best cord clamping time in newborn infants, we hypothesized that late cord clamping enables an increased volemia due to blood transfer to the newborn from the placenta. AIM: To assess whether clamping time can affect limb perfusion and heart hemodynamics in a group of 22 healthy term newborn infants. STUDY DESIGN: A case-control study. SUBJECTS: Eleven early-clamped (at 30 s) vaginally-delivered newborn infants were compared with eleven late-clamped (at 4 min) newborns. OUTCOME MEASURES: The two groups were studied using near-infrared spectroscopy and M-mode echocardiography. RESULTS: Late cord clamping coincided with a higher hematocrit (median 62% versus 54%) and hemoglobin concentration (median 17.2 versus 15 g/dL), whilst there were no changes in bilirubin level. Echocardiography showed a larger end-diastolic left ventricle diameter (1.7 cm median value versus 1.5) coupled with unvaried shortening and ejection fraction values. There were no changes in calf blood flow, oxygen delivery, oxygen consumption or fractional oxygen extraction calculated from the NIRS measurements, or in foot perfusion index. CONCLUSIONS: Our results demonstrated that late cord clamping coincides with an increased placental transfusion, expressed by higher hematocrit and hemoglobin values, and larger left ventricle diameter at the end of the diastole, with no changes in peripheral perfusion or oxygen metabolism