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Background Neuroinflammation is a proposed mechanism by which Alzheimer’s disease (AD) pathology potentiates neuronal death and cognitive decline. Consumption of omega-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of AD in human observational studies and exerts protective effects on cognition and pathology in animal models. These fatty acids and molecules derived from them are known to have anti-inflammatory and pro-resolving properties, presenting a potential mechanism for these protective effects. Methods Here, we explore this mechanism using fat-1 transgenic mice and their wild type littermates weaned onto either a fish oil diet (high in n-3 PUFA) or a safflower oil diet (negligible n-3 PUFA). The fat-1 mouse carries a transgene that enables it to convert omega-6 to omega-3 PUFA. At 12 weeks of age, mice underwent intracerebroventricular (icv) infusion of amyloid-β 1-40. Brains were collected between 1 and 28 days post-icv, and hippocampal microglia, astrocytes, and degenerating neurons were quantified by immunohistochemistry with epifluorescence microscopy, while microglia morphology was assessed with confocal microscopy and skeleton analysis. Results Fat-1 mice fed with the safflower oil diet and wild type mice fed with the fish oil diet had higher brain DHA in comparison with the wild type mice fed with the safflower oil diet. Relative to the wild type mice fed with the safflower oil diet, fat-1 mice exhibited a lower peak in the number of labelled microglia, wild type mice fed with fish oil had fewer degenerating neurons, and both exhibited alterations in microglia morphology at 10 days post-surgery. There were no differences in astrocyte number at any time point and no differences in the time course of microglia or astrocyte activation following infusion of amyloid-β 1-40. Conclusions Increasing brain DHA, through either dietary or transgenic means, decreases some elements of the inflammatory response to amyloid-β in a mouse model of AD. This supports the hypothesis that omega-3 PUFA may be protective against AD by modulating the immune response to amyloid-β.

Current methods applied to study the origin and metabolism of brain fatty acids involve the administration of synthesized fatty acid tracers. The high cost of these tracers makes it infeasible to conduct chronic studies through this approach, limiting study durations to acute time points that may not reflect the chronic, steady-state, metabolism of fatty acids. Here, we provide the proof-of-concept of a cost-efficient alternative method: natural abundance compound specific isotope analysis by isotope ratio mass spectrometry. Through the application of this method, we differentiated between tissue docosahexaenoic acid (DHA) originating directly from diet or DHA biochemically synthesized in a complex transgenic model: the fat-1 mouse. We further determined pre-formed dietary DHA to be the main source of brain DHA in fat-1 mice fed a diet rich in n-6 and/or n-3 PUFA. Future studies could utilize this approach to answer complex question pertaining to brain fatty acids origin and metabolism.

O Brasil dispõe de reservas de rochas silicáticas potássicas de baixa solubilidade, sendo necessário o desenvolvimento de alternativas de beneficiamento capazes de aumentar sua solubilidade, para o suprimento da demanda desse nutriente na agricultura. Este estudo objetivou a obtenção de novas rotas tecnológicas para a produção de fontes alternativas de potássio, a partir do verdete. Prepararam-se misturas de verdete com calcário, para as quais foram realizados testes de calcinação e solubilização alcalina. O processo de calcinação seguido de resfriamento à temperatura ambiente proporcionou maior disponibilidade de potássio que os outros métodos empregados. Porém, o aumento na proporção de calcário, em relação ao verdete, ocasionou diminuição na solubilidade do potássio. O tratamento calcário:verdete, na proporção 0:100, calcinado por uma hora a 800ºC e tratado com NH4OH, e na proporção 25:75, submetida à calcinação, liberam, proporcionalmente, maior quantidade de potássio que as misturas não calcinadas. ABSTRACT: Brazil owns reserves of low solubility potassium silicate rocks, being necessary the development of alternative processing methods to increase their solubility, so they can be efficiently used in agriculture. This study aimed to get new technological routes to produce alternative potassium sources from verdete. Calcination and alkaline solubilization tests were performed for verdete and limestone mixtures. The calcination process followed by cooling at room temperature provided a higher potassium availability than other methods used. However, the increase of limestone content, concerning verdete, decreased the potassium solubility. The treatment limestone:verdete, in the proportion of 0:100, after calcination at 800 ºC during one hour and then treated with NH4OH, and in the proportion of 25:75, after calcination, release proportionally higher amounts of K than non-calcinated samples.

This paper investigates the causal effect of co-payment exemption on the number of specialist visits in the Italian National Health System. Exploiting a discontinuity in the multiple eligibility criteria, we apply multiple regression discontinuity in a quasi-experimental setting, considering both age and income requirements. Differently from the standard regression discontinuity, this twofold discontinuity allows to identify the effect of co-payment on a particularly needy sub-population of less wealthy people and how it changes according to the eligibility criteria. We find positive effects of co-payment exemption and the effects are stronger for less wealthy and older individuals. The result may be useful to the policy maker to tailor ad-hoc policies aimed at disadvantaged sub-populations.

The current therapeutic options for Inflammatory Bowel Diseases (IBD) are limited. Even using common anti-inflammatory, immunosuppressive or biological therapies, many patients become unresponsive to the treatments, immunosuppressed or unable to restrain secondary infections. Statins are cholesterol-lowering drugs with non-canonical anti-inflammatory properties, whose underlying mechanisms of action still remain poorly understood. Here, we described that in vitro atorvastatin (ATO) treatment was not toxic to splenocytes, constrained cell proliferation and modulated IL-6 and IL-10 production in a dose-dependent manner. Mice exposed to dextran sulfate sodium (DSS) for colitis induction and treated with ATO shifted their immune response from Th17 towards Th2, improved the clinical and histological aspects of intestinal inflammation and reduced the number of circulating leukocytes. Both experimental and in silico analyses revealed that PPAR-α expression is reduced in experimental colitis, which was reversed by ATO treatment. While IBD patients also downregulate PPAR-α expression, the responsiveness to biological therapy relied on the restoration of PPAR-α levels. Indeed, the in vitro and in vivo effects induced by ATO treatment were abrogated in Ppara -/- mice or leukocytes. In conclusion, the beneficial effects of ATO in colitis are dependent on PPAR-α, which could also be a potential predictive biomarker of therapy responsiveness in IBD.

This study compared the postoperative analgesic efficacy of intraperitoneal and incisional lidocaine versus ropivacaine in dogs undergoing major abdominal surgeries. Dogs randomly received intraperitoneal lidocaine irrigation (4 mg kg -1 , diluted to 5 ml kg -1 , L group), ropivacaine (4 mg kg -1 , diluted to 5 ml kg -1 , R group) or 0.9% saline (5 ml kg -1 , C group). Prior to skin closure, dogs received incisional lidocaine 2 mg kg -1 (group L), incisional ropivacaine 2 mg kg -1 (group R) or incisional saline 0.2 ml kg -1 (group C). Pain was assessed at different time points up to 24 hours after extubation, using the Short Form-Glasgow Composite Measure Pain Scale and VAS Scale. In group C, postoperative pain scores were significantly higher than in groups L and R from T0.5 to T6 (p < 0.05). In R group, postoperative pain scores were significantly lower than in groups L and C from T12 to T24 (p < 0.05). Rescue analgesia was administered to 5/11 dogs in L group, 1/10 dogs in R group and 8/10 dogs in C group. Groups L and R experienced a significantly lower postoperative pain during the first 6 hours after extubation, compared with group C. Ropivacaine provided lower postoperative pain scores than lidocaine and saline up to 24 hours after extubation. According to the obtained results, ropivacaine seemed to provide better and longer lasting postoperative analgesia compared with lidocaine. Therefore, intraperitoneal and incisional administration of ropivacaine in dogs undergoing major abdominal surgeries is recommended.

The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD (n = 9), OTM CBD (2 mg kg−1 every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C (n = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.

The population biology of the three sympatric species of caprellids (Caprella danilevskii, C. equilibra and C. scaura) associated with a Sargassum bed was studied in the northern coast of São Paulo state, Brazil. Samplings were carried out monthly from October 2010 to February 2012. In each month, 25 fronds of Sargassum were randomly collected through snorkelling. The caprellids were identified, counted, classified by sex and separated into size classes. Caprella danilevskii was the most abundant species, with 14939 specimens recorded. The body size of males was larger than that of females for C. danilevskii and C. equilibra, and the sex ratio was skewed toward males for all species. The size-frequency distribution was polymodal for C. danilevskii and C. scaura and bimodal for C. equilibra. Mature males of C. scaura and C. equilibra were recorded in all size classes. The last size classes (from 8.3–9.4 to 12.7–13.8 mm) were dominated by mature males. Mature and ovigerous females were more frequent in intermediate size classes. Significant temporal variations were recorded for the three species with higher densities in spring and summer that are related to higher algal biomass; but other environmental factors are certainly important for explaining caprellid density variation.

Redondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters. Saliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported. ReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients' sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents. ReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.