Sublingual sufentanil tablet system (SSTS) versus a single shot peri-nervous injection of ropivacaine for the management of postoperative pain after total knee arthroplasty: a single-center randomized trial.

INTRODUCTION: For several years, ropivacaine has been the standard-of-care for establishing postoperative femoral nerve block in total knee arthroplasty (TKA) setting and is still widely in use but new approaches such as the patient-controlled administration of sublingual sufentanil tablets system (SSTS) seem to offer good clinical results. Our aim is to compare the SSTS to single shot peri-nervous injection of ropivacaine (single shot) after TKA in terms of effectiveness in pain management and of time to recovery. MATERIALS AND METHODS: A total of 165 patients undergoing TKA were enrolled. Eighty-four patients were randomly allocated in the SSTS group and 81 patients in the single shot group. The primary objective of the study was to evaluate performance of Timed Up and Go test. Secondary objectives were to measure the length of stay, NRS pain scale, the adherence to the prescribed plan, the joint mobility, the frequency of rescue analgesic use, side effects and patients' satisfaction. RESULTS: Of all patients of the single shot group, 64 were withdrawn from the study as they unable to achieve pain control; only one patient was withdrawn from the SSTS group. Times for the "Timed Up and Go" test on the 3rd postoperative day were 8.4 ± 1.6 and 11.8 ± 3.6 in the SSTS group (n = 83) and single shot group (n = 17), respectively (p < .001). CONCLUSIONS: SSTS provides better pain management when compared to peri-nervous ropivacaine single shot injection after TKA.

Mapping research on LGBT+ persons' health: a bibliometric analysis.

AIMS: Lesbian, gay, bisexual, transgender and other people (LGBT+) individuals may have a greater risk of experiencing mental and physical health issues. In the past years, the predominant theme of research was HIV/AIDS and sexually transmitted infections (STIs). This study aimed to explore the most recent patterns in medical research concerning LGBT+ persons. METHODS: A bibliometric analysis using Biblioshiny was conducted. Based on previous studies, years of observation ranged between 2008 and 2021. Web of Science Core Collection was used. RESULTS: A total of 31,039 articles were selected. Top journals centered around HIV/AIDS and STIs (n = 6), followed by sexual behaviors/sexuality (n = 2) and LGBT+ health (n = 2). The US led in research output (n = 16,249). Papers were categorized into three main clusters (which showed different evolution across time): one addressing HIV/AIDS, STIs, and sexual behaviors, another focusing on mental health, discrimination, and stigma, and a third, smaller cluster examining transgender, intersex, and gender-diverse health. CONCLUSIONS: This article highlighted a growth in LGBT+ health research, uncovering research disparities among countries. While HIV/AIDS and STIs still dominated, a crucial theme concerning mental health, discrimination, and stigma has been rising. Declining interest in gender-diverse health, and disparities in research attention to different LGBT+ subgroups, underscored the need for more comprehensive and inclusive research to address complex health disparities.

Use of chloroprocaine in orthopedic day surgery: a brief report in a cohort of patients undergoing knee arthroscopy.

OBJECTIVE: Spinal anesthesia with local anesthetics is a viable alternative to general anesthesia in orthopedic surgery, and it is currently considered the standard of care for knee arthroscopy. The use of chloroprocaine may offer several potential advantages over other local anesthetics, including, above all, its rapid onset and short duration of action. The aim of the present retrospective study is to evaluate the post-surgical outcomes of patients who underwent knee arthroscopy using spinal anesthesia with chloroprocaine in an outpatient orthopedic setting. PATIENTS AND METHODS: Data from patients who underwent elective knee arthroscopy between January 2022 and December 2022 were collected for the present study. Spinal anesthesia with chloroprocaine 10 mg/mL was administered in the designated subarachnoid space (L3-L4 in the majority of patients). A dosage of 40 mg was used to obtain a satisfactory sensory and motor block. RESULTS: A total number of 302 patients met the inclusion criteria. No complications were reported during surgery in the present series of patients. None of the patients required bladder catheterization. In 84% of cases, the PADSS (Post-Anesthetic Discharge Scoring System) score at discharge was 10, whereas in 16% of cases, the PADSS score was 9. The mean time from anesthesia induction to first urination was 75±9.4 minutes, while the mean time from the anesthesia induction to the discharge from the hospital was 152±18.5 minutes. CONCLUSIONS: Spinal chloroprocaine for knee arthroscopy demonstrated a short motor block duration, resulting in a fast time to discharge. These limited data show that chloroprocaine may be safely and effectively applied in outpatient knee arthroscopy procedures. However, more studies, possibly with a randomized design, are required to confirm these findings.

A structured methodology for essential medicines lists and health emergency stockpiles: Experience with the Emergency Medicines Buffer Stock in the United Kingdom.

INTRODUCTION: Formularies of essential medicines, such as Essential Medicines Lists (EMLs) and health emergency stockpiles, are intended to be always available, including in emergency situations, acting as important tools for access to medicines. The Emergency Medicines Buffer Stock (EMBS) in the United Kingdom (UK) was a stockpile of critical medicines managed by the UK Department of Health and Social Care (DHSC). We propose a new methodology for selecting and including medicines in EMLs and health emergency stockpiles and empirically apply it for selecting medicines in the case of the UK EMBS. METHODS: We used Multi-Attribute Value Theory and Portfolio Decision Analysis to develop a three-phase methodological framework for medicines selection, involving: (i) the decision context definition and selection of evaluation criteria, (ii) the therapeutic area prioritisation, and (iii) the medicines value-for-money evaluation and product selection. The EMBS application took place in 2018-2019 and focused on therapeutic area prioritisation, involving primary data collection through expert interviews (n = 4), a workshop with DHSC decision-makers (n = 13), and an online survey with National Clinical Directors and relevant experts (n = 24). A Monte Carlo simulation supported therapeutic area prioritisation using the British National Formulary (BNF) classification. FINDINGS: Two criteria sets were selected for i) therapeutic area prioritisation, reflecting the value concerns of population need and shortage severity, and ii) medicines evaluation, reflecting magnitude of clinical benefit and supply vulnerability, among others. Primary evidence was collected for "national need" and "shortage severity", based on which a "population health loss" index was developed. A total of 51 therapeutic areas were ranked using their index value while assessing the robustness of the ranking. The top ranked therapeutic area was antisecretory drugs and mucosal protectants, closely followed by diabetes drugs. CONCLUSIONS: The methodological application generated a ranking of therapeutic areas based on expected "population health loss" index, while addressing evidence uncertainty. The methodology can be adapted for other EMLs and emergency stockpile contexts to inform medicines selection.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Atrial fibrillation: Epigenetic aspects and role of sodium-glucose cotransporter 2 inhibitors.

Atrial fibrillation (AF) is the most frequent arrhythmia and is associated with substantial morbidity and mortality. Pathophysiological aspects consist in the activation of pro-fibrotic signaling and Ca2+ handling abnormalities at atrial level. Structural and electrical remodeling creates a substrate for AF by triggering conduction abnormalities and cardiac arrhythmias. The care of AF patients focuses predominantly on anticoagulation, symptoms control and the management of risk factors and comorbidities. The goal of AF therapy points to restore sinus rhythm, re-establish atrioventricular synchrony and improve atrial contribution to the stroke volume. New layer of information to better comprehend AF pathophysiology, and identify targets for novel pharmacological interventions consists of the epigenetic phenomena including, among others, DNA methylation, histone modifications and noncoding RNAs. Moreover, the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in diabetic and non-diabetic patients at cardiovascular risk as well as emerging evidence on the ability of SGLT2i to modify epigenetic signature in cardiovascular diseases provide a solid background to investigate a possible role of this drug class in the onset and progression of AF. In this review, following a summary of pathophysiology and management, epigenetic mechanisms in AF and the potential of sodium-glucose SGLT2i in AF patients are discussed.

Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

Understanding the socioeconomic costs of dystrophic epidermolysis bullosa in Europe: a costing and health-related quality of life study.

BACKGROUND: Dystrophic epidermolysis bullosa (EB) is a family of rare genetic dermatological conditions. Recent evidence indicated that in addition to its detrimental implications on patient health-related quality of life (HRQoL), there are substantial socioeconomic cost implications, especially regarding direct non-medical costs. This study aims to understand the burden of dystrophic EB (DEB) in Europe, using a primary EB patient-level dataset. METHODS: A bottom-up, cross-sectional, study design was adopted for non-institutionalised patients diagnosed with EB who received outpatient care across EU5 countries: France, Germany, Italy, Spain, and the United Kingdom. A prevalence-based approach was used to estimate resource utilisation from a societal perspective, including direct (medical and non-medical) and indirect costs for patients and caregivers. Patient and caregiver outcomes were obtained using the EQ-5D questionnaire. RESULTS: A sample of 91 DEB patients was analysed. Overall, average EU5 annual cost per patient was estimated at €53,359, ranging from €18,783 (France) to €79,405 (Germany). Average EU5 annual direct medical costs were estimated at €8357 (15.7% of total), ranging from €5658 (France) to €12,576 (Germany); average direct non-medical costs were estimated at €41,353 (77.5% of total), ranging from €11,961 (France) to €57,000 (Germany); and average indirect costs were estimated at €3649 (6.8% of total), ranging from €1025 (Italy) to €9930 (United Kingdom). Costs varied across patients with different disability but also between children and adults. The mean EQ-5D index score for adult DEB patients ranged between 0.304 (United Kingdom) and 0.541 (Germany), with an EU5 average of 0.456, whereas the mean EQ-5D visual analogue scale score ranged between 47.5 (Germany) and 70.0 (France), with an EU5 average of 61.9. Limitations included potential patient selection bias, recall bias, and exclusion of bandaging and related costs. CONCLUSIONS: The study revealed a substantial socioeconomic burden for DEB in Europe, attributable mostly to high direct non-medical costs, with the majority of patients requiring support from caregivers at home. Compared to the average economic burden of the overall EB patient population, costs for DEB patients are higher across all components of direct medical, direct non-medical and indirect costs.

A rapid recovery protocol for hip and knee replacement surgery: a report of the outcomes in a referral center.

OBJECTIVE: The number of joint replacements is expected to dramatically increase, and the optimization of the available resources is fundamental to maintain high clinical standards while providing an efficient treatment to an increasing number of patients. The present study describes the outcomes of the application of a rapid recovery (RR) protocol in a referral center for hip and knee replacement surgery. PATIENTS AND METHODS: The medical records of every patient undergoing primary hip or knee replacement in 2019 were identified and all the relevant data were retrospectively extracted and compared to those of year 2016 (the last year before the onset of the rapid recovery protocol). The following outcomes were considered: 1) length of stay (LOS); 2) total number of TKR and THR; 3) pre- and post-operative subjective questionnaires; 4) NRS for pain at day 1 following surgery; 5) mean hemoglobin value at discharge; 6) number of blood transfusion performed; 7) complications following surgery. RESULTS: The mean LOS was significantly lower for patients managed through the rapid recovery protocol: 5.1 ± 1.4 days vs. 10.4 ± 2.3 days (p < 0.0001). The earlier discharge of patients promoted an overall increase in the total number of joint replacement procedures performed (2,806 in year 2019 vs. 2,236 in year 2016; p < 0.0001). Higher hemoglobin values at discharge were found in the RR group (10.6 ± 1.4 g/dl vs. 9.6 ± 1.2 g/dl, p = 0.049). No difference was observed in terms of clinical scores and overall complication rate. CONCLUSIONS: The application of a multimodal RR protocol for THR and TKR patients was able to reduce the length of stay and optimize the use of blood products, without increasing the risk of complications or jeopardizing the functional recovery.

Clinical efficacy of implementing a Patient Blood Management (PBM) Protocol in joint replacement surgery: a retrospective cohort study in a national referral center.

OBJECTIVE: The aging of population has dramatically broadened the total number of Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA) performed worldwide. To optimize the number of blood transfusions performed, a multimodal and multidisciplinary approach was introduced, called Patient Blood Management (PBM). The aim of the present retrospective study is to evaluate the feasibility and clinical outcomes of a PBM protocol applied in a national referral center for joint replacement surgery. PATIENTS AND METHODS: Clinical reports of 9,635 patients undergoing primary THA or TKA, from 2014 to 2019, were screened. The trends of hemoglobin value at admission and at day 4 after surgery were analyzed. Furthermore, the trend of blood bags' requests and blood transfusions was longitudinally evaluated to assess the efficacy of our PBM protocol and its potential impact in reducing the length of stay in the hospital. RESULTS: In 2014, mean hemoglobin (Hb) levels at postoperative day 4 were 10.3 g/dl and 10.2 g/dl for TKA (unilateral and bilateral, respectively), and in 2019 were 11.3 g/dl and 11.6 g/dl (unilateral and bilateral, respectively, p=0.001). Total requested red blood cell (RBC) transfusions by each surgery over time have decreased for THA (277 in 2014 vs. 120 in 2019, p=0.001).  A correlation matrix analysis between Hb level, body mass index (BMI), age, days spent in orthopedic (OR) ward and number of requested transfusions showed that RBC bags transfusions were related to the length of the hospital stay. CONCLUSIONS: A timely application of a PBM protocol in the perioperative period of TKA and THA was significantly associated to the reduction of blood transfusions and total length of hospital stay, with clear benefits for both the patients and the hospital.

Imagine that: cholinesterase inhibitor treatment of complex visual hallucinations of unknown aetiology.

Introduction: Our objective is to highlight the value of the neurophenomenological classification of complex visual hallucinations (VHs). This approach enabled the authors to successfully treat VHs of uncertain aetiology with cholinesterase inhibitors because the content of the hallucinations suggested dysfunction in cholinergic modulated networks.Methods: We utilise the single case report to describe the nature and content of chronic VHs experienced by a 49-year-old woman following a prolonged admission to ITU. Despite extensive investigation, no clear cause was identified for these hallucinations and the patient did not respond to rationalisation of medications or trials of antipsychotics. We therefore adopted the neurophenomenological approach to classifying and treating her VHs.Results: After several years of distressing visual hallucinations, a course of Rivastigmine was trialed despite no evidence suggestive of a Parkinsonian syndrome. Nevertheless, the patient reported a dose-effect response with significant reduction in the frequency and intensity of her hallucinations, almost to complete resolution.Conclusions: At present there is limited evidence about the medical management of visual hallucinations. This case report suggests that cholinesterase inhibitors may be of benefit, even in the absence of clear parkinsonsian features, if the form and content of the VHs suggest dysfunction in cholinergic modulated attentional networks.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Hypomimia in Parkinson's disease: an axial sign responsive to levodopa.

BACKGROUND AND PURPOSE: Hypomimia is a prominent clinical feature in people with Parkinson's disease (PD), but it remains under-investigated. We aimed to examine the clinical correlates of hypomimia in PD and to determine whether this is a levodopa-responsive sign. METHODS: We included 89 people with PD. Hypomimia was assessed from digital video recordings by movement disorder specialists. Clinical evaluation included use of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), and assessment of motor and non-motor symptoms using standardized clinical scales. The relationships between hypomimia and other clinical data were analysed using Mann-Whitney U-tests and regression analysis. RESULTS: Hypomimia occurred in up to 70% of patients with PD. Patients with hypomimia had worse UPDRS-III 'off-medication' scores, mainly driven by bradykinesia and rigidity subscores. Patients with hypomimia also had worse apathy than patients without hypomimia. Finally, we found that hypomimia was levodopa-responsive and its improvement mirrored the change by levodopa in axial motor symptoms. CONCLUSION: Our study provides novel information regarding the clinical correlates of hypomimia in people with PD. A better understanding of hypomimia may be relevant for improving treatment and quality of life in PD.

Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework.

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results. The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique. Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest "cost per unit of value" for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions. Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.

Protein-Polymer Dynamics as Affected by Polymer Coating and Interactions.

We investigate the relaxation dynamics of protein-polymer conjugates by neutron scattering spectroscopy to understand to which extent the coating of a protein by a polymer can replace water in promoting thermal structural fluctuations. For this purpose, we compare the dynamics of protein-polymer mixtures to that of conjugates with a variable number of polymers covalently attached to the protein. Results show that the flexibility of the protein is larger in protein-polymer mixtures than in native protein or in conjugates, even in the dry state. Upon hydration, both the native protein and the conjugate show equivalent dynamics, suggesting that the polymer grafted on the protein surface adsorbs all water molecules.

Microdosimetric Realistic Model of a Cell with Endoplasmic Reticulum.

When investigating the biophysical effects induced by the interaction between electromagnetic fields and biological cells, it is crucial to estimate the electromagnetic field intensity at the microscopic scale (microdosimetry). This information allows to find a connection between the external applied field and the observed biological event required to establish related biomedical applications. Here, authors present a microdosimetric study based on a 2D realistic model of a cell and its endoplasmic reticulum. The microdosimetric analysis of the cell and endoplasmic reticulum was quantified in terms of electric field and transmembrane potential induced by an externally applied high amplitude 10-ns pulsed electric field. In addition, electroporated local membrane sites and pore densities were also evaluated. This study opens the way to numerically assist experimental applications of nanosecond pulsed electric fields for controlled bio-manipulation of cells and subcellular organelles.

Genetic polymorphisms at candidate genes affecting fat content and fatty acid composition in Modicana cows: effects on milk production traits in different feeding systems.

Feeding greatly affects milk yield and composition. The research is highlighting the potential of genetic polymorphism at some loci to affect milk yield and quality traits. These loci can be up/down regulated depending on the production environment; therefore, we hypothesized that milk yield and composition could differ when cows with different genotype at SCD, DGAT1 and ABCG2 loci are reared in different feeding systems. The polymorphisms of SCD, DGAT1 and ABCG2 genes were investigated in Modicana breed. In all, three polymorphic sites, responsible for the genetic variation of quantitative trait loci and therefore defined quantitative trait nucleotides, were genotyped: the transition g.10329C>T in 5th exon determines a substitution p.A293V in the SCD, the dinucleotide mutation g.10433-10434AA>GC in 8th exon responsible for p.K232A substitution in the DGAT1 and the transition g.62569A>C in the 14th exon responsible for p.Y581S substitution in the ABCG2 gene. In the sample of 165 Modicana cows, SCD and DGAT1 genes resulted polymorphic; the alleles g.10329T and g.10433-10434GC were the most frequent in SCD and DGAT1 (0.73 and 0.91) respectively, whereas ABCG2 locus was monomorphic for allele A (p.581Y). Sequencing analysis was carried out on 14 samples with different genotypes to confirm the results of the PCR-RFLP protocols. Based on the genotypes at SCD locus, 47 Modicana cows were selected for the nutritional trial: 24 cows in a semi-intensive farm, with 2 h/day grazing on natural pasture, and 23 cows in an extensive farm, with 8 h/day grazing on natural pasture. Monthly, milk yield and composition were evaluated and individual milk samples were analyzed for fatty acids composition by gas chromatography. No differences in milk yield, fat, protein, lactose, casein and urea were associated to SCD genotype. Feeding systems affected milk yield and composition. No significant genotype×feeding system interaction was observed for milk yield and composition. Fatty acids composition was significantly affected only by the feeding system. Significant interactions were found between SCD genotype and feeding system for six fatty acids: 4:0, 6:0, 8:0, 10:0, 12:0 and t11 18:1. We concluded that the feeding system was the factor that mostly affected milk production and composition; moreover, our results do not confirm what reported in literature as regard the effect of the SCD polymorphism on milk fatty acid composition. The high amount of pasture seemed to have resized the SCD polymorphism effects because of the different fatty acids composition of the diet.

Vitamin E is the major contributor to the antioxidant capacity in lambs fed whole dried citrus pulp.

The aim of this study was to investigate the effect of dietary whole dried citrus pulp (DCP) on the antioxidant status of lamb tissues. In total, 17 lambs were divided into two groups and fed for 56 days: a barley-based concentrate diet (CON - eight animals), or a concentrate-based diet including 35% DCP to partially replace barley (CIT - nine animals). The CIT diet contained a double concentration of phenolic compounds than the CON diet (7.9 v. 4.0 g/kg dry matter (DM), respectively), but had no effect (P>0.05) on the overall antioxidant capacity of the hydrophilic fraction of blood plasma, liver and muscle. The CIT diet contained clearly more α-tocopherol than the CON diet (45.7 v. 10.3 mg/kg DM), which could explain the higher concentration of α-tocopherol in liver, plasma and muscle (P<0.05). The dietary treatment had no effect on the extent of lipid peroxidation, measured as thiobarbituric acid and reactive substances assay (TBARS values) in the faeces, small intestine, liver, plasma and muscle. Nevertheless, when muscle homogenates were incubated in the presence of Fe3+/ascorbate to induce lipid peroxidation, the muscle from lambs fed DCP displayed lower TBARS values (P<0.01), which negatively correlated with the concentration of α-tocopherol in muscle. These results showed that feeding whole DCP to ruminants increases the antioxidant status of muscle through an increase in the deposition of α-tocopherol.

New and old roles of the peripheral and brain renin-angiotensin-aldosterone system (RAAS): Focus on cardiovascular and neurological diseases.

It is commonly accepted that the renin-angiotensin-aldosterone system (RAAS) is a cardiovascular circulating hormonal system that plays also an important role in the modulation of several patterns in the brain. The pathway of the RAAS can be divided into two classes: the traditional pathway of RAAS, also named classic RAAS, and the non-classic RAAS. Both pathways play a role in both cardiovascular and neurological diseases through a peripheral or central control. In this regard, renewed interest is growing in the last years for the consideration that the brain RAAS could represent a new important therapeutic target to regulate not only the blood pressure via central nervous control, but also neurological diseases. However, the development of compounds able to cross the blood-brain barrier and to act on the brain RAAS is challenging, especially if the metabolic stability and the half-life are taken into consideration. To date, two drug classes (aminopeptidase type A inhibitors and angiotensin IV analogues) acting on the brain RAAS are in development in pre-clinical or clinical stages. In this article, we will present an overview of the biological functions played by peripheral and brain classic and non-classic pathways of the RAAS in several clinical conditions, focusing on the brain RAAS and on the new pharmacological targets of the RAAS.