Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1

In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly segregates with major depression, schizophrenia and related mental conditions. Thus, study of DISC1 may provide a clue to understand the biology of major mental illness. A neuropeptide precursor VGF has potent antidepressant effects and has been reportedly associated with bipolar disorder. Here we show that DISC1 knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in the cortices from sporadic cases with major mental disease. A positive correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia was also observed. We now propose that VGF participates in a common pathophysiology of major mental disease

Enhancement of PLA-PVA surface adhesion in bilayer assemblies by PLA aminolisation

Data Availability: The raw/processed data required to reproduce these findings cannot be shared at this time due to legal or ethical reasons.Poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) present complementary barrier properties, and their combination in multilayer assemblies (laminates) could provide materials with more effective barrier capacity for food packaging purposes. However, their low chemical affinity compromises adequate polymer adhesion. Surface free energy modification of thermo-processed PLA films through treatment with 1,6-hexanediamine was used to enhance adhesion with polar PVA aqueous solutions. Treatments of 1 and 3 min increased the polar component of the solid surface tension, while treatments above 10 min provoked a corrosive effect in the films structure. Extensibility analyses of PVA solutions loaded with carvacrol (15 wt.%) and different Tween 85 ratios on PLA-activated surfaces allowed the selection of the 1-min aminolysed surface for obtaining PLA-PVA bilayers, by casting PVA solutions on the PLA films. This study revealed that despite aminolisation enhancing the PLA surface affinity for aqueous PVA solutions, casting-obtained bilayers presented limited oxygen barrier effectiveness due to heterogeneous thickness of PVA layer in the laminates.The authors acknowledge the financial support provided by the Ministerio de Economia y Competitividad (MINECO) of Spain (project AGL2016-76699-R). The author A. Tampau thanks MINECO for the pre-doctoral research grant #BES-2014-068100.info:eu-repo/semantics/publishedVersio

The presence of extracellular matrix degrading metalloproteinases during fetal development of the intervertebral disc

Matrix metalloproteinases (MMPs) regulate connective tissue architecture and cell migration through extracellular matrix (ECM) degradation and are associated with both physiological and pathological processes. Although they are known to play a role in skeletal development, little is known about the role of MMPs in intervertebral disc (IVD) development. Sixteen fetal human lumbar spine segments, obtained at autopsy, were compared with five normal, non-fetal L4–L5 IVDs. Intensity and/or localization of immunohistochemical staining for MMP-1, -2, -3 and -14 were evaluated by three independent observers. MMP-2 production and activation was quantified by gelatin zymography. MMP-1 and -14 were abundantly present in the nucleus pulposus (NP) and notochordal (NC) cells of the fetal IVDs. In non-fetal IVDs, MMP-1 and -14 staining was significantly less intense (p = 0.001 and p < 0.001, respectively). MMP-3 was found in almost the entire IVD with no significant difference from non-fetal IVDs. MMP-2 staining in the NC and NP cells of the fetal IVD was moderate, but weak in the non-fetal IVD. Gelatin zymography showed a negative correlation of age with MMP-2 activity (p < 0.001). MMP-14 immunostaining correlated positively with MMP-2 activity (p = 0.001). For the first time, the presence of MMP-1, -2, -3 and -14 in the fetal human IVD is shown and the high levels of MMP-1, -2 and -14 suggest a role in the development of the IVD. In particular, the gradual decrease in MMP-2 activation during gestation pinpoints this enzyme as key player in fetal development, possibly through activation by MMP-1 and -14

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries

Anti-inflammatory Components from Functional Foods for Obesity

Obesity, defined as excessive fat accumulation that may impair health, has been described throughout human history, but it has now reached epidemic proportions with the WHO estimating that 39% of the world’s adults over 18 years of age were overweight or obese in 2016. Obesity is a chronic low-grade inflammatory state leading to organ damage with an increased risk of common diseases including cardiovascular and metabolic disease, non-alcoholic fatty liver disease, osteo-arthritis and some cancers. This inflammatory state may be influenced by adipose tissue hypoxia and changes in the gut microbiota. There has been an increasing focus on functional foods and nutraceuticals as treatment options for obesity as drug treatments are limited in efficacy. This chapter summarises the importance of anthocyanin-containing fruits and vegetables, coffee and its components, tropical fruit and food waste as sources of phytochemicals for obesity treatment. We emphasise that preclinical studies can form the basis for clinical trials to determine the effectiveness of these treatments in humans

Synthesis of cetyl ricinoleate catalyzed by immobilized Lipozyme® CalB lipase in a solvent-free system.

green process has been performed for the synthesis of the emollient ester cetyl ricinoleate with a new immobilized derivative of Candida antarctica lipase B, which has been prepared by physical adsorption of Lipozyme® CalB L on a macroporous anionic exchange resin (Lewatit® MonoPlus MP 64). An immobilized CalB lipase with protein content over 30 mg/g has been obtained and it has been successfully used as biocatalyst to produce cetyl ricinoleate from esterification of ricinoleic acid with cetyl alcohol. Influence of amount of biocatalyst and temperature was studied in the open-air reactor, and optimal values could be fixed in 2 mg and 70ºC respectively. Biocatalyst storage stability study was developed in this reactor and it was showed the high storage stability of the immobilized derivative, because it keeps 100% of its enzymatic activity after eight months. Studies of recovery and reuse of the immobilized derivative were performed in the vacuum reactor, and it was proved the posibility of using the same biocatalyst in three consecutive reaction cycles without apparent loss of activity. Finally, the characterization of the cetyl ricinoleate obtained in the vacuum reactor demonstrated that the product obtained after only 3 or 4 hours of reaction meets manufacturers’ specifications