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Introduction: While the economic and clinical burden of chronic diseases are well documented, their environmental impact remains poorly understood. We developed a framework to estimate the environmental impact of a disease care pathway using chronic kidney disease (CKD) as an example., Methods: A life cycle assessment framework was developed for the CKD care pathway and validated by experts. Life cycle stages were characterised for resource utilisation based on a literature review and ecoinvent database inputs, in ten countries. The ReCiPe impact assessment method was used to calculate impacts across multiple environmental dimensions., Results: At CKD stage 5, kidney replacement therapies (KRT) have highest impact; emissions ranged between 3.5 and 43.9 kg carbon dioxide equivalents (CO 2 e) per session depending on dialysis modality, and 336-2022 kg CO 2 e for kidney transplant surgery, depending on donor type. Hospitalisations have a substantial environmental impact: a 1-day intensive care stay had highest impact (66.4-143.6 kg CO 2 e), followed by a 1-day hospital stay (28.8-63.9 kg CO 2 e) and an 8-h emergency room visit (14.4-27.5  kg CO 2 e). Patient transport to and from healthcare sites was a key driver of environmental impact for all life cycle stages, representing up to 99.5% of total CO 2 e emissions., Conclusion: Full care pathways should be analysed alongside specific healthcare processes. Application of this framework enables quantification of the environmental benefits of preventative medicine and effective management of chronic diseases. For CKD, early diagnosis, and proactive management to reduce the need for KRT and hospitalisations could improve patient outcomes and reduce environmental burden., Competing Interests: Declarations. Conflict of Interest: Katherine A. Barraclough, Aleix Cases, Roberto Pecoits-Filho, Celine Germond-Duret, Carmine Zoccali, and Matthew J. Eckelman received consulting fees for taking part in Scientific Steering Committee meetings regarding CKD environmental impact research. Aleix Cases has received research grants from CSL Vifor; consultancy fees from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Novo Nordisk, Otsuka, CSL Vifor, and lecture fees from Astellas, Astra Zeneca, Amgen, Bayer, Medscape, Novo Nordisk, Sanofi (Mexico), CSL Vifor. Roberto Pecoits-Filho has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Akebia, AstraZeneca, Bayer, Boehringer, and Fresenius Medical Care. Juan Jose Garcia Sanchez, Salvatore Barone, Nigel Budgen, Claudia Cabrera, and Viknesh Selvarajah are employees and shareholders of AstraZeneca. Nina Embleton, Antony Wright, Luke Hubbert, and Lindsay Nicholson received consulting fees from AstraZeneca. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Aim: This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults., Method: A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways., Results: The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein., Conclusion: This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Background: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis., Methods: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use., Results: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord., Conclusions: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

Background: Dropout in higher education is a socio-educational phenomenon that has the scope to limit the benefits of education as well as to widen social disparities. For this reason, governments have implemented various public policies for its prevention and mitigation. However, in rural populations, such policies have proven to be ineffective. The aim of this paper is to simulate public policy scenarios for the treatment of school dropout in rural higher education in Colombia from a Dynamic Performance Management approach. Methodology: To achieve the aim, a parameterised simulation model was designed with data from Colombian state entities in rural higher education. Five simulations were carried out. The analysis of the results was carried out using descriptive statistics and comparison of means using the Wilcoxon Sign Rank statistic. Results: The adoption of such an approach based on simulations suggests that policies to expand the coverage of educational credits and financial support, as well as the addition of a family income subsidy, allow for a reduction in the number of dropouts. Conclusions: A dynamic, data-driven approach can be effective in preventing and mitigating dropout in these areas. It also highlights the importance of identifying the key factors contributing to dropout. The results also suggest that government policies can have a significant impact on school retention in rural areas., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Guzman Rincón A et al.)

The objective of this work was the valorisation of sour cherry (Prunus cerasus L.) pomace as a source of biologically active compounds. To formulate microcapsules, polyphenolic compounds were extracted and encapsulated with maltodextrin as wall material, by freeze-drying. An in vitro digestion study was carried out on obtained encapsulates but also on sour cherry pomace extract and sour cherry pomace freeze-dried powder. The results indicated that encapsulation, as well as freeze-drying, provided a good protective effect on bioactive compounds during digestion. Furthermore, the potential antiproliferative and cytotoxic activities of encapsulates and sour cherry pomace extract were evaluated using breast adenocarcinoma MCF7 cell lines, colon adenocarcinoma HT-29 cell lines, and noncancer cell line. Encapsulates and sour cherry pomace extract showed variable anti-proliferative activity towards all cell lines. Obtained results showed that encapsulation of sour cherry pomace could be useful for improving the stability of polyphenolic compounds in the gastrointestinal tract. The results highlight the bioactive potential of sour cherry pomace as a nutraceutical resource and the protective effects of microencapsulation on the digestion of bioactive compounds., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Several phthalate acid esters (PAEs), often called phthalate esters or phthalates, are substances classified as harmful due to their carcinogenic and mutagenic properties, and moreover, as dangerous for humans because they interfere with the endocrine system. In general, phthalic esters are used as plasticizers for different polymers and more other consumer products. In the present study, we describe a simple method to quantify PAEs in coffee brew using a liquid-liquid extraction without purification processes through analysing the obtained organic phase by GCMS in the single ion monitoring mode. The totals of single PAEs, in coffee brew samples analysed by us, are in the range of 159-5305 μg L -1 . Considering that, on average, a person drinks three cups (total 90 mL) of the aforementioned drink per day, this will lead to the uptake of a total 14 to 477 μg of phthalates., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

The stimulator of interferon genes (STING) protein is a cornerstone of the human immune response. Its activation by cGAMP in the presence of cytosolic DNA stimulates the production of type I interferons and inflammatory cytokines. In the human population, several STING variants exist and exhibit dramatic differences in their activity, impacting the efficiency of the host defense against infections. Understanding the molecular mechanisms of these variants opens perspectives for personalized medicine treatments against diseases such as viral infections, cancers, or autoinflammatory diseases. Through microsecond-scale molecular modeling simulations, contact analyses, and machine learning techniques, we reveal the dynamic behavior of four STING variants (wild type, G230A, R293Q, and G230A/R293Q) and rationalize the variability of efficiency observed experimentally. Our results show that the decrease in STING activity is linked to a stiffening of key structural elements of the binding cavity together with changes in the interaction patterns within the protein.

Background:  We describe, step by step, a modified, less invasive, diamond-shaped mini-craniotomy that optimizes dural opening and can be performed in elderly patients affected by acute subdural or intracerebral hematomas, in therapy with antiplatelets or anticoagulants., Methods:  We retrospectively analyzed the clinical records of 67 patients (mean age of 78.5 years) treated in our institution, during a period of 10 years, with this novel diamond-shaped craniotomy. Seventeen patients were treated for intracerebral hemorrhage and 50 patients for acute subdural hematomas. All the patients were in therapy with antiplatelets or anticoagulants., Results:  Approach-related complications were not detected. Ten of 67 patients (14.9%) presented temporal muscle atrophy; there was no scar deformity, paresthesia, hyperalgesia, or ramus frontalis palsy around the scalp incision. Thirty-day mortality was 22%. The mean follow-up was 1.3 years. One-month postoperative brain computed tomography scans showed a satisfactory hematoma evacuation in 57 of 67 patients (85%)., Conclusions:  The diamond-shaped mini-craniotomy for acute subdural and intracerebral hematomas is safe and effective, and it should be considered as an alternative to traditional approaches, particularly in elderly patients., Competing Interests: None declared., (Thieme. All rights reserved.)

This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 ± 1.8 kPa. Mean stress of the basal, middle, and apical segments were 7.7 ± 1.8 kPa, 9.1 ± 3.8 kPa, and 6.4 ± 0.4 kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS., Competing Interests: AS were employed by the company CATIA, Dassault Systèmes. JY were employed by company Simulia, Dassault Systèmes Simulia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wisneski, Wang, Cutugno, Pasta, Stroh, Yao, Nguyen, Mahadevan and Guccione.)

Competing Interests: None declared.

Coronavirus 2019 pandemic lockdown in Italy lasted for 2 months, 1 week and 2 days. During this long period, one of the longest in Europe, the restrictions produced effects on people's psychological well-being, with consequences that also continued after lockdown. The purpose of the study is to investigate these effects and how they changed in the general population over a period of time. We are also interested in exploring people's post-lockdown anxiety and concerns. We conducted an online survey using snowball sampling techniques. The longitudinal study consisted of four administrations covering a period of 10 weeks between April (baseline) and June (last follow-up). Levels of anxiety and depression were assessed by GAD-7 and PHQ-9, coping strategies were assessed by Brief Resilient Coping Scale (BRCS) and social support was assessed by MSPSS. Post-lockdown anxiety was explored by developing a set of ad-hoc questions . PCA was used to determine the principal categories of post-lockdown anxiety/concern resulting from the ad-hoc questions. Longitudinal data, given their nested structure, were analyzed through mixed modeling. Of the 411 responders at baseline, 169 had at least 3 out of 4 data points; the analysis was therefore conducted on this sample. Levels of depression and anxiety were found to be significantly higher in the study sample in comparison with normative samples for each of the fourtime points; levels of coping showed that scores from the study sample were significantly lower than normative data at all-time points. Levels of perceived social support were significantly lower than normative data at the baseline and the first follow-up. The results of the study suggest that the lockdown experience had enduring consequences on the mental health of individuals. Prevention and support interventions to limit the psychological distress caused by COVID-19 should be taken into consideration in countries experiencing a second wave of the pandemic., (©Copyright: the Author(s).)

The severity of aortic stenosis (AS) has traditionally been graded by measuring hemodynamic parameters of transvalvular pressure gradient, ejection jet velocity, or estimating valve orifice area. Recent research has highlighted limitations of these criteria at effectively grading AS in presence of left ventricle (LV) dysfunction. We hypothesized that simulations coupling the aorta and LV could provide meaningful insight into myocardial biomechanical derangements that accompany AS. A realistic finite element model of the human heart with a coupled lumped-parameter circulatory system was used to simulate AS. Finite element analysis was performed with Abaqus FEA. An anisotropic hyperelastic model was assigned to LV passive properties, and a time-varying elastance function governed the LV active response. Global LV myofiber peak systolic stress (mean ± standard deviation) was 9.31 ± 10.33 kPa at baseline, 13.13 ± 10.29 kPa for moderate AS, and 16.18 ± 10.59 kPa for severe AS. Mean LV myofiber peak systolic strains were -22.40 ± 8.73%, -22.24 ± 8.91%, and -21.97 ± 9.18%, respectively. Stress was significantly elevated compared to baseline for moderate ( p < 0.01) and severe AS ( p < 0.001), and when compared to each other ( p < 0.01). Ventricular regions that experienced the greatest systolic stress were (severe AS vs. baseline) basal inferior (39.87 vs. 30.02 kPa; p < 0.01), mid-anteroseptal (32.29 vs. 24.79 kPa; p < 0.001), and apex (27.99 vs. 23.52 kPa; p < 0.001). This data serves as a reference for future studies that will incorporate patient-specific ventricular geometries and material parameters, aiming to correlate LV biomechanics to AS severity., (Copyright © 2020 Wisneski, Wang, Deuse, Hill, Pasta, Sack, Yao and Guccione.)

Background: Telomerase, a reverse transcriptase, maintains telomere and chromosomes integrity of dividing cells, while it is inactivated in most somatic cells. In tumor cells, telomerase is highly activated, and works in order to maintain the length of telomeres causing immortality, hence it could be considered as a potential marker to tumorigenesis.A series of 1,3,4-oxadiazole derivatives showed significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition., Methods: This series of 24 N-benzylidene-2-((5-(pyridine-4-yl)-1,3,4-oxadiazol-2yl)thio)acetohydrazide derivatives as telomerase inhibitors has been considered to carry out QSAR studies. The endpoint to build QSAR models is determined by the IC50 values for telomerase inhibition, i.e., the concentration (μM) of inhibitor that produces 50% inhibition. These values were converted to pIC50 (- log IC50) values. We used the most common and transparent method, where models are described by clearly expressed mathematical equations: Multiple Linear Regression (MLR) by Ordinary Least Squares (OLS)., Results: Validated models with high correlation coefficients were developed. The Multiple Linear Regression (MLR) models, by Ordinary Least Squares (OLS), showed good robustness and predictive capability, according to the Multi-Criteria Decision Making (MCDM = 0.8352), a technique that simultaneously enhances the performances of a certain number of criteria. The descriptors selected for the models, such as electrotopological state (E-state) descriptors, and extended topochemical atom (ETA) descriptors, showed the relevant chemical information contributing to the activity of these compounds., Conclusion: The results obtained in this study make sure about the identification of potential hits as prospective telomerase inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cyclin dependent kinase 7 (CDK7) plays a double role as it activates several other cyclin dependent kinases and participates to the initiation of transcription. This kinase is overexpressed in various types of tumors. Relatively few selective CDK7 inhibitors have been up to now disclosed. Most of these inhibitors belong to two chemical families: pyrazolopyrimidines and pyrazolotriazines on one side and pyrimidines on another side. They also differ by their molecular mechanism of action. Some are acting as competitive inhibitors and some others are covalent inhibitors. With these tools, the understanding of the potential therapeutic interest of CDK7 inhibitors in cancer is rapidly growing. They display antiproliferative activity against various types of tumors and leukemia and synergies have been identified. Two inhibitors are undergoing clinical testing. The most potent compounds inhibit a large number of cell-lines with IC 50  < 200 nM., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Mitochondrial heteroplasmy is the result from biparental transmission of mitochondrial DNA (mtDNA) to the offspring. In such rare cases, maternal and paternal mtDNA is present in the same individual. Though recent studies suggested that mtDNA heteroplasmy might be more common than previously anticipated, that phenomenon is still poorly documented and was mostly detected in case studies on hybrid populations. The Italian sparrow, Passer italiae is a homoploid hybrid form that occurs all across the Italian Peninsula mostly under strict absence of either of its parent species, the house sparrow ( P. domesticus ) and the Spanish sparrow ( P. hispaniolensis ). In this study, we document a new case of mitochondrial heteroplasmy from two island populations of P. italiae (Ustica and Lipari). Our analysis was based on the mitochondrial NADH dehydrogenase subunit 2 (ND2) that allows for a clear distinction between mitochondrial lineages of the two parental species. We amplified and sequenced the mitochondrial ND2 gene with specifically designed primer combinations for each of the two parental species. In two of our study populations, a single individual carried two different ND2 haplotypes from each of the two parental lineages. These findings contribute to current knowledge on the still poorly documented phenomenon of paternal leakage in vertebrates., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Several parasitoids attacking the same host may lead to competition. Adult parasitoids' abilities to find, parasitize and defend hosts determine resource's retention potential. In soybean, two egg parasitoid species, Telenomus podisi and Trissolcus urichi (Hymenoptera: Platygastridae), compete on the egg masses of Piezodorus guildinii (Hemiptera: Pentatomidae) one of the major pest of this crop. We evaluated parasitoid's abilities to exploit hosts' footprints; and parasitoid's behavior when competing for the same host. Both arena residence time and retention time were similar for T. podisi and T. urichi on male or female host footprints. In its turn, T. urichi reentered the area contaminated with P. guildinii more times and staid longer in it than T. podisi. Furthermore, when competing for the same egg mass, each parasitoid species won (was in possession of the host by the end of the experiment) half of the replicates, and the number of times each wasp species contacted host in the first place was similar, without affecting replicate outcome (who ultimately won). Both species started agonistic and non-agonistic encounters. This study provides information about the potential interspecific competition between these parasitoids, which contributes to evaluate the compatibility of multiple natural enemies' biological control programs for stink bugs.

Introduction: In humans, a major component of natural killer (NK) and T cell target recognition depends on the surveillance of human leukocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs)., Aims: To implement the knowledge about the immunological genetic background of acute ischemic stroke susceptibility in relation to the frequency of the KIR genes and HLA alleles., Methods: Subjects with acute ischemic stroke and subjects without stroke were genotyped for the presence of KIR genes and of the three major KIR ligand groups, HLA-C1, HLA-C2, and HLA-Bw4, both HLA-B and HLA-A loci., Results: Between November 2013 and February 2016, consecutive patients with acute ischemic stroke were recruited. As healthy controls, we enrolled subjects without acute ischemic stroke. Subjects with acute ischemic stroke in comparison with controls showed a higher frequency of 2DL3, 2DL5B, 2DS2, and 2DS4 KIR genes and a lower frequency of HLA-B-Bw4 I alleles. Subjects without acute ischemic stroke showed a higher frequency of interaction between KIR 2DS2 and HLAC2. We also observed a higher frequency of 2DL3 and 2 DL4 KIR genes in subjects with atherosclerotic (LAAS) subtype. Multiple logistic regression analysis showed a protective effect towards stroke of HLA-B-Bw4 I and interaction between KIR 2DL2 and HLAC1 and 2DS2-HLAC2 and a detrimental effect of 2DL2-HLA-C1&#95;A interactions., Conclusion: Our findings of a higher frequency of activating KIR genes seem to be consistent with findings previously reported patients with coronary syndrome. This higher frequency of "proinflammatory" genes in subjects with ischemic stroke could also explain the immunoinflammatory activation of the acute phase of stroke.

Background: Dyslipidaemias is a recognized risk factor for atherosclerosis, however, new evidence brought to light by trials investigating therapies to enhance HDLcholesterol have suggested an increased atherosclerotic risk when HDL-C is high., Results: Several studies highlight the central role in atherosclerotic disease of dysfunctional lipoproteins; oxidised LDL-cholesterol is an important feature, according to "oxidation hypothesis", of atherosclerotic lesion, however, there is today a growing interest for dysfunctional HDL-cholesterol. The target of our paper is to review the functions of modified and dysfunctional lipoproteins in atherogenesis., Conclusion: Taking into account the central role recognized to dysfunctional lipoproteins, measurements of functional features of lipoproteins, instead of conventional routine serum evaluation of lipoproteins, could offer a valid contribution in experimental studies as in clinical practice to stratify atherosclerotic risk., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid., Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters, either the latency or the duration of drug-induced statistically significant responses was calculated, as well as the response magnitude., Results: VPA-Phen significantly reduced both burst frequency and duration. Comparative analyses show that VPA-Phen and VPA-Tryp exert almost equivalent actions on both latency and magnitude of the observed inhibitory effects. The main observed difference between the two tested molecules concerned the duration of inhibitory effects, since VPA-Phen-dependent actions on both burst rate and duration were significantly shorter than the VPA-Tryp-induced ones. In addition, in some slices the above reported inhibitory responses were preceded by a "paradoxical" transient increase, more present at lower drug concentrations., Conclusions: Both VPA-Phen and VPA-Tryp exert significant inhibitory effects on hippocampal burst activity parameters. Although of comparable magnitude, VPA-Phen-dependent effects have a shorter duration than VPATryp- induced ones. Nevertheless, the present results confirm that the conjugation between VPA and aminoacids represents a valid tool to improve the efficacy of antiepileptic drugs and, as well as for VPA-Tryp, propose VPAPhen as a novel VPA derivative with enhanced pharmacological features., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background and Objective: Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives., Methods: The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory response, focusing our attention on human studies., Results: Our report highlights the effect of specific molecules obtained from EVOO on the modulation of specific cytokines and anti-oxidants suggesting the importance of the daily consumption of both EVOO and table olives in the context of a Mediterranean dietary pattern. In addition, the different action on immune-inflammatory biomarkers, are depending on the olive tree cultivar., Conclusion: Thanks to their bioactive compounds, EVOO and table olive can be considered as nutraceutical and functional foods. The beneficial effects analysed in this review will help to understand the potential application of specific olive components as therapeutic adjuvant, supplements or drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)