Farmland expansion and intensification do not foster local food self-sufficiency. Insights from the Mediterranean area.

Bridging the gap between the micro and the macro scale in modelling food security to inform context-specific regionalised policies remains a major scientific challenge. A better understanding of the relations between global and local drivers impacting local food self-sufficiency (LFSS) is essential. We applied to the whole Mediterranean environmental area (Southern and Northern) a modelling framework for structural estimates (PLS-PM) using qualitative and quantitative methods to combine local-level information from field surveys and participatory workshops with global-level data. Our findings show that farmland expansion and intensification spatially disconnected from urban consumption areas do not appear to foster LFSS. On the other hand, public policies appear key to enhancing LFSS in the Mediterranean area if appropriate to the particular regional context. We outline how this multi-level modelling methodology can contribute to a place-based approach by informing context-specific regionalised policies aimed at food security.

[Primary care management of sexually transmitted infections (I). Epidemiology. Secreting syndrome]. / Manejo en atención primaria de las infecciones de transmisión sexual (I). Epidemiología. Síndrome secretor.

These days sexually transmitted infections (STIs) are important public health problems not only due to their high prevalence, but also because they require early diagnosis and treatment to avoid complications. In recent years, there has been an exponential increase in cases of infections caused by Chlamydia trachomatis and gonococcus in the population under 25years of age. In addition, an increase in the incidence of syphilis and hepatitisC (HCV) has also been detected, especially in men who have sex with other men (MSM). Genital herpes continues to be the second most frequent STI in the world, behind condyloma acuminata, and the first cause of genital ulcer among Spain in the sexually active population. A decrease in reported HIV cases was observed during 2020, but almost half of these new cases had a late diagnosis (<350CD4cell/µL). Current guidelines recommend offering STI annual screening to populations at risk or more often depending on the risk. STIs can appear in the form of syndromes, such as secretory syndrome (urethritis, proctitis, and cervicitis) or ulcerated syndrome (ulcers). The STIs that can cause secretory syndrome are mainly caused by Neisseria gonorrhoeae and C.trachomatis, which co-infect up to 40% of cases, and also cause urethritis, cervicitis or proctitis depending on where they are located. Gonococcus has an incubation period of 2-7days and Chlamydia 2-6weeks, and they are diagnosed using PCR and/or culture (the last one only valid for gonococcus) of samples collected according to sexual activities. Empirical treatment to cover both germs will be accomplished with ceftriaxone, 1g single intramuscular dose plus doxycycline 100mg every 12h orally for 7days, or azithromycin 1g single dose orally (we will use azithromycin only if we suspect a poor compliance with treatment, difficulty in going to the control or in pregnancy). Likewise, whenever we diagnose an STI firstly, we must offer advice and health education in order to promote the adoption of safe sexual behaviours and the correct use of barrier methods. Secondly, we must also screen for other STIs (HIV, syphilis, hepatitisB, and hepatitisA andC depending on the risk), offer HBV and HAV vaccination if it is appropriate, and finally study and treat all sexual partners from the previous 3months.

Insights on novel type V deep eutectic solvents based on levulinic acid.

Type V natural deep eutectic solvents considering menthol, thymol, and levulinic acids are studied considering a combined experimental and theoretical approach to develop a multiscale characterization of these fluids with particular attention to intermolecular forces (hydrogen bonding) and their relationships with macroscopic behavior. Density, viscosity, refraction index, and thermal conductivity were measured as a function of temperature, providing a thermophysical characterization of the fluids. Quantum chemistry was applied to characterize hydrogen bonding in minimal molecular clusters, allowing us to quantify interaction strength, topology (according to atoms in a molecule theory), and electronic properties. Classical molecular dynamics simulations were also performed, allowing us to characterize bulk liquid phases at the nanoscopic level, analyzing the fluid's structuring, void distribution, and dynamics. The reported results allowed us to infer nano-macro relationships, which are required for the proper design of these green solvents and their application for different technologies.

Nanostructuring and macroscopic behavior of type V deep eutectic solvents based on monoterpenoids.

Type V natural deep eutectic solvents based on monoterpenoids (cineole, carvone, menthol, and thymol) are studied using a combined experimental and molecular modeling approach. The reported physicochemical properties showed low viscous fluids whose properties were characterized as a function of temperature. The theoretical study combining quantum chemistry and classical molecular dynamics simulations provided a nanoscopic characterization of the fluids, particularly for the hydrogen bonding network and its relationship with the macroscopic properties. The considered fluids constitute a suitable type of solvents considering their properties, cost, origin, and sustainability in different technological applications and sow the possibility of developing type V NADES from different types of molecules, especially in the terpenoid family of compounds.

Disability and quality of life in heart failure patients: a cross-sectional study.

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.

Neural crest Notch/Rbpj signaling regulates olfactory gliogenesis and neuronal migration.

The neural crest-derived ensheathing glial cells of the olfactory nerve (OECs) are unique in spanning both the peripheral and central nervous systems: they ensheathe bundles of axons projecting from olfactory receptor neurons in the nasal epithelium to their targets in the olfactory bulb. OECs are clinically relevant as a promising autologous cell transplantation therapy for promoting central nervous system repair. They are also important for fertility, being required for the migration of embryonic gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode along terminal nerve axons to the medial forebrain, which they enter caudal to the olfactory bulbs. Like Schwann cell precursors, OEC precursors associated with the developing olfactory nerve express the glial marker myelin protein zero and the key peripheral glial transcription factor Sox10. The transition from Schwann cell precursors to immature Schwann cells is accelerated by canonical Notch signaling via the Rbpj transcription factor. Here, we aimed to test the role of Notch/Rbpj signaling in developing OECs by blocking the pathway in both chicken and mouse. Our results suggest that Notch/Rbpj signaling prevents the cranial neural crest cells that colonize the olfactory nerve from differentiating as neurons, and at later stages contributes to the guidance of GnRH neurons.

STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population.SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal parts of injured nerves repair, Schwann cells gradually lose regeneration-supporting features and eventually die. Identification of signals that sustain repair cells is therefore an important goal. We have found that in mice the transcription factor STAT3 protects these cells from death and contributes to maintaining the molecular and morphological repair phenotype that promotes axonal regeneration. Defining the molecular mechanisms that maintain repair Schwann cells is an essential step toward developing therapeutic strategies that improve nerve regeneration and functional recovery.

After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration.SIGNIFICANCE STATEMENT After injury to peripheral nerves, the myelin and Remak Schwann cells distal to the injury site reorganize and modify their properties to form cells that support the survival of injured neurons, promote axon growth, remove myelin-associated growth inhibitors, and guide regenerating axons to their targets. We show that the generation of these repair-supportive Schwann cells involves an extensive cellular elongation and branching, often to form long, parallel processes. This generates a distinctive repair cell morphology that is favorable for the formation of the regeneration tracks that are essential for nerve repair. Remyelination, conversely, involves a striking cell shortening to form the typical short myelin cells of regenerated nerves. We also provide evidence for direct lineage relationships between: (1) repair cells and myelin and Remak cells of uninjured nerves and (2) remyelinating cells in regenerated nerves.

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial.

RATIONALE: Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes. OBJECTIVES: To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. METHODS: In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged. MEASUREMENTS AND MAIN RESULTS: HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1ß, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1ß were independently related to the 6-month change in HbA1c levels (r(2) = 0.510, P = 0.002). CONCLUSIONS: Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain by (i) administering quinolinic acid to conditional mutant animals lacking CB1 receptors selectively in GABAergic or glutamatergic neurons, and (ii) manipulating corticostriatal glutamatergic projections remotely with a designer receptor exclusively activated by designer drug pharmacogenetic approach. We next examined the alterations that occur in the R6/2 mouse, a well-established model of Huntington disease, upon (i) fully knocking out CB1 receptors, and (ii) deleting CB1 receptors selectively in corticostriatal glutamatergic or striatal GABAergic neurons. The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies.

Evidence for a Notch1-mediated transition during olfactory ensheathing cell development.

Olfactory ensheathing cells (OECs) are a unique glial population found in both the peripheral and central nervous system: they ensheath bundles of unmyelinated olfactory axons from their peripheral origin in the olfactory epithelium to their central synaptic targets in the glomerular layer of the olfactory bulb. Like all other peripheral glia (Schwann cells, satellite glia, enteric glia), OECs are derived from the embryonic neural crest. However, in contrast to Schwann cells, whose development has been extensively characterised, relatively little is known about their normal development in vivo. In the Schwann cell lineage, the transition from multipotent Schwann cell precursor to immature Schwann cell is promoted by canonical Notch signalling. Here, in situ hybridisation and immunohistochemistry data from chicken, mouse and human embryos are presented that suggest a canonical Notch-mediated transition also occurs during OEC development.

Distribution and growth of Vibrio parahaemolyticus in southern Chilean clams (Venus antiqua) and blue mussels (Mytilus chilensis).

We evaluated the distribution and growth of Vibrio parahaemolyticus in the inland sea of southern Chile, where the world's largest foodborne gastroenteritis outbreak by the pandemic strain O3:K6 occurred in 2005. Intertidal samples of Mytilus chilensis and Venus antiqua were collected around port towns between 41°28'S and 43°07'S, during April to May 2011 and January to March 2012. We used most probable number real-time polymerase chain reaction (MPN-PCR) for enumeration of the tlh, tdh, and trh genes in freshly harvested bivalves and after a controlled postharvest temperature abuse. Pathogenic markers (tdh+ or trh+) were not detected. Total V. parahaemolyticus (tlh+) in freshly harvested samples reached up to 0.38 and 3.66 log MPN/g in 2011 and 2012, respectively, with values close to or above 3 log MPN/g only near Puerto Montt (41°28'S, 72°55'W). Enrichments by temperature abuse (>2 log MPN/g) occurred mainly in the same zone, regardless of the year, suggesting that both natural or anthropogenic exposure to high temperatures were more critical. Lower salinity and higher sea surface temperature in Reloncaví Sound and Reloncaví Estuary were consistent with our observations and allowed confirmation of the existence of a high-risk zone near Puerto Montt. Based on the results, a strategy focused on risk management inside this defined hazard zone is recommended.

Endocannabinoid-hydrolysing enzymes in the post-mortem cerebellum of humans affected by hereditary autosomal dominant ataxias.

OBJECTIVES: Spinocerebellar ataxias (SCAs) are characterized by a loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. We recently found important changes in cannabinoid CB1 and CB2 receptors in the post-mortem cerebellum of patients affected by different SCAs. METHODS: We wanted to further explore this issue by analysing the two major endocannabinoid-hydrolysing enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL), in the post-mortem cerebellum of SCA patients and control subjects. RESULTS: Immunoreactivity for the FAAH and MAGL enzymes was found in the granular layer, in Purkinje cells, in neurons of the dentate nucleus and in areas of white matter in the cerebellum of patients at levels frequently notably higher than those in control subjects. Using double-labelling procedures, we found co-localization of FAAH and MAGL with calbindin, supporting the presence of these enzymes in Purkinje neurons. CONCLUSIONS: Degradative endocannabinoid enzymes are significantly increased in the cerebellum of SCA patients, which would presumably lead to reduced endocannabinoid levels. The identification of these enzymes in Purkinje neurons suggests a relationship with the pathogenesis of SCAs and suggests that the endocannabinoid system could provide potential therapeutic targets for the treatment of disease progression in SCAs.

Clinical and subclinical arteriosclerotic disease in octagenarians with hip fracture. A case-control study.

BACKGROUND AND OBJECTIVES: Evaluate clinical and subclinical arteriosclerotic disease in older patients with hip fracture compared with patients without fracture in order to increase knowledge about the relation between both diseases in older individuals. PATIENTS AND METHODS: Age- and sex-matched case-control study of octogenarians with and without recent hip fracture. Vascular risk factors, subclinical vascular diseases (assessed by carotid plaques, carotid intima media thickness and arterial stiffness) as well as cardiovascular diseases were analyzed. Univariate and multivariate logistic models were used to estimate odds ratios (OR) with their 95% confidence intervals (CI) to assess the association of the arteriosclerosis and hip fracture. RESULTS: We analyzed 95 patients per group with a median age of 82 [79-87] years of whom 77.9% were female. Patients in both groups have elevated rates of vascular disease (25%) without differences between them. Patients with hip fracture had higher subclinical arteriosclerotic alterations with higher percentage of carotid plaques (OR 3.25 [1.06-9.97]) compared with the control group. CONCLUSIONS: Older patients with hip fracture had significantly higher presence of subclinical alterations but not increase on rate of cardiovascular arteriosclerotic disease compared with those without hip fracture.

Nature of a Tetrabutylammonium Chloride-Levulinic Acid Deep Eutectic Solvent.

A deep eutectic solvent was formed by considering the mixtures of tetrabutylammonium chloride and levulinic acid, and it is studied via a combined theoretical and experimental approach. Physicochemical properties were measured as a function of temperature, providing a macroscopic characterization of the fluid. Quantum chemistry and classical molecular dynamics simulations were carried out for the nanoscopic characterization, providing attention to the nature, extension, and dynamics of the hydrogen bonding network, which is at the root of the properties of the fluid. The reported study allows multiscale characterization of this fluid as an archetypical example of a natural, low-cost, and sustainable fluid.

Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.

Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropathology and molecular pathology of the disease. Moreover, pharmacological administration of the cannabinoid Δ(9)-tetrahydrocannabinol to mice expressing human mutant huntingtin exon 1 exerted a therapeutic effect and ameliorated those parameters. Experiments conducted in striatal cells show that the mutant huntingtin-dependent downregulation of the receptors involves the control of the type 1 cannabinoid receptor gene promoter by repressor element 1 silencing transcription factor and sensitizes cells to excitotoxic damage. We also provide in vitro and in vivo evidence that supports type 1 cannabinoid receptor control of striatal brain-derived neurotrophic factor expression and the decrease in brain-derived neurotrophic factor levels concomitant with type 1 cannabinoid receptor loss, which may contribute significantly to striatal damage in Huntington's disease. Altogether, these results support the notion that downregulation of type 1 cannabinoid receptors is a key pathogenic event in Huntington's disease, and suggest that activation of these receptors in patients with Huntington's disease may attenuate disease progression.

Impact of COVID-19 lockdown in a biomedical research campus: A gender perspective analysis.

From March to September 2020, researchers working at a biomedical scientific campus in Spain faced two lockdowns and various mobility restrictions that affected their social and professional lifestyles. The working group "Women in Science," which acts as an independent observatory of scientific gender inequalities on campus launched an online survey to assess the impact of COVID-19 lockdowns on scientific activity, domestic and caregiving tasks, and psychological status. The survey revealed differences in scientific performance by gender: while male researchers participated in a larger number of scientific activities for career development, female researchers performed more invisible scientific tasks, including peer review or outreach activities. Mental impact was greater in researchers caring for children or dependents, and this was aggravated for women. Results spot a disproportionate impact of COVID-19 lockdowns on female scientific career development, and urges for equity measures to mitigate the consequences of an increase in the gender gap in biomedical sciences for current and future pandemics.

Validity and reliability of 1-h automated office blood pressure measurement for the diagnosis of hypertension.

AIMS: The objective of this study was to examine the validity of 1 h automated office blood pressure measurement for the diagnosis of hypertension. METHODS: We included patients requiring a hypertension diagnostic test. Participants underwent ambulatory blood pressure monitoring, 1 h automated office blood pressure measurement, office blood pressure measurement and home blood pressure monitoring. The prevalence of hypertension and subtypes were calculated. Mean values of ambulatory blood pressure monitoring were compared with 1 h automated office blood pressure measurement using the correlation coefficient and Bland-Altman graphs. The Kappa concordance index, sensitivity, specificity and diagnostic accuracy were calculated, and the area under the receiver operating characteristic curve was used to establish the diagnostic threshold of the 1-h measurement. RESULTS: Of 562 participants, 438 (87.6%) completed the four diagnostic methods. The 1-h method had a sensitivity of 76.6 [95% confidence interval (95% CI): 71.1-81.5], a specificity of 64.8% (95% CI: 57-72.1) and the best diagnostic accuracy (72.1%, 95% CI: 67.7-76.3) compared with the office and home measurements. Moderate-high correlations were observed between DBP (r = 0.73) and SBP (r = 0.58) readings. The 1-h method classified more patients as normotensive (24.4%) and fewer patients with white-coat hypertension (13.3%). A diagnostic threshold of at least 133/83 mmHg for the 1-h method could improve diagnostic accuracy by 2.3%. CONCLUSION: One-hour automated blood pressure measurement is a valid, reliable method for the diagnosis of hypertension in undiagnosed patients. The diagnostic accuracy permits detection of white-coat and masked hypertension. To diagnose hypertension, the 1-h method or conventional home blood pressure monitoring should be used rather than office measurements. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03147573.

Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study.

BACKGROUND: The phytocannabinoid cannabidiol (CBD) exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS). METHODS: Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. RESULTS: CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. CONCLUSIONS: These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.

The impact of antimalarial agents on traditional and non-traditional subclinical atherosclerosis biomarkers in systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVE: Cardiovascular (CV) morbidity is a well-established problem in systemic lupus erythematosus (SLE). Antimalarial (AM) therapy has been seen as a potential atheroprotective agent. The aim was to assess the impact of AM therapy on traditional and novel atherosclerosis (AT) biomarkers in patients with SLE. METHODS: A search of MEDLINE, EMbase, and Cochrane library for studies evaluating the impact of AM on AT biomarkers in SLE was conducted. Data extraction included serum, functional and structural traditional and novel biomarkers. A narrative synthesis of the findings and a meta-analysis with random effects was conducted estimating mean differences (MD), OR, HR and 95% CIs. RESULTS: The search strategy produced 148 articles, of which 64 were extracted for analysis. The MD in VLDL-cholesterol (-10.29, 95% CI -15.35, 5.24), triglycerides (-15.68, 95% CI -27.51, -3.86), and diastolic BP (-3.42, 95% CI -5.62, -1.23) differed significantly in patients on AM therapy compared with those without AM therapy. Patients on AM had a lower prevalence and incidence of diabetes mellitus than patients not on AM (HR: 0.39, 95% CI 0.17, 0.88). HCQ use was associated with lower blood pressure (BP) variability. Structural markers like carotid intima-media thickness (IMT), carotid plaque (CP) and coronary artery calcification (CAC) were not influenced by AM. For functional markers like endothelial and arterial stiffness the benefit was unclear. The GRADE approach showed a very low-to-low quality of evidence (QoE) per outcome. CONCLUSIONS: There is some evidence on the associations between AM therapy and some AT markers. However, the data on which this conclusion was based was of low to very low evidence.