Cannabis sativa L. oil extract affects neuroinflammation, clinical score, and cannabinoid receptor-1 gene expression in C57bl/6 experimental autoimmune encephalomyelitis

Introduction: Multiple sclerosis (MS) is a degenerative central nervous system disease derived by immune mechanisms, which ultimately results in clinical debilities. Numerous nutraceuticals have been cited to be effective in treatment of central nervous system complications. Objectives: This study investigated the effect of Cannabis sativa L. seed oil on experimental autoimmune encephalomyelitis (EAE). Materials and Methods: Female C57bl/6 mice were assigned randomly into three groups (8 in each). Group-A received no myelin oligodendrocyte glycoprotein (MOG), group B was immunized by MOG and treated with oil, while in group C animals were immunized and treated with normal saline. Clinical scores were recorded every other day throughout the study and after four weeks, all mice were sacrificed and spinal cords were incised for molecular and histopathological evaluations. Results: Significant differences were observed in mean clinical scores between control and experiment groups (P&lt;0.001). Cannabinoid receptor-1 gene expression increased significantly in treatment group (P&lt;0.001). Histopathologic evaluations also showed a significant decrease in overall infiltrated and vacuolated area and immune cells infiltration into the central nervous system in the treatment group (P&lt;0.01). Conclusion: Cannabis sativa L. oil extract administration alleviated inflammation and paralysis in animal model. Therefore, its oil extract might be useful in soothing inflammatory and auto-immune diseases. However, additional research might be required.</jats:p

What factors affect patients' recall of general practitioners' advice?

<p>Abstract</p> <p>Background</p> <p>In order for patients to adhere to advice, provided by family doctors, they must be able to recall it afterwards. However, several studies have shown that most patients do not fully understand or memorize it. The aim of this study was to determine the influence of demographic characteristics, education, amount of given advice and the time between consultations on recalled advice.</p> <p>Methods</p> <p>A prospective survey, lasting 30 months, was conducted in an urban family practice in Slovenia. Logistic regression analysis was used to identify the risk factors for poorer recall.</p> <p>Results</p> <p>250 patients (87.7% response rate) received at least one and up to four pieces of advice (2.4 ± 0.8). A follow-up consultation took place at 47.4 ± 35.2 days. The determinants of better recall were high school (OR 0.4, 95% CI 0.15-0.99, p = 0.049) and college education (OR 0.3, 95% CI 0.10-1.00, p = 0.050), while worse recall was determined by number of given instructions three or four (OR 26.1, 95% CI 3.15-215.24, p = 0.002; OR 56.8, 95% CI 5.91-546.12, p < 0.001, respectively) and re-test interval: 15-30 days (OR 3.3, 95% CI 1.06-10.13, p = 0.040), 31-60 days (OR 3.2, 95% CI 1.28-8.07, p = 0.013) and more than 60 days (OR 2.5, 95% CI 1.05-6.02, p = 0.038).</p> <p>Conclusions</p> <p>Education was an important determinant factor and warrants further study. Patients should be given no more than one or two instructions in a consultation. When more is needed, the follow-up should be within the next 14 days, and would be of a greater benefit to higher educated patients.</p

Novelty Response of Wild African Apes to Camera Traps

Temperament and personality research in humans and nonhuman animals measures behavioral variation in individual, population, or species-specific traits with implications for survival and fitness, such as social status, foraging and mating success [1–5]. Curiosity and risk-taking tendencies have been studied extensively across taxa by measuring boldness and exploration responses to experimental novelty exposure [3,4,6–15]. Here, we conduct a natural field experiment using wildlife monitoring technology to test variation in the reaction of wild great apes (43 groups of naïve chimpanzees, bonobos and western gorillas, across 14 field sites in Africa) to a novel object, the camera-trap. Bonobo and gorilla groups demonstrated a stronger looking impulse towards the camera-trap device compared to chimpanzees, suggesting higher visual attention and curiosity. Bonobos were also more likely to show alarm and other fearful behaviors, although such neophobic (and conversely, neophilic) responses were generally rare. Among all three species, individuals looked at cameras longer when they were young, were associating with fewer individuals, and did not live near a long-term research site. Overall, these findings partially validate results from great ape novelty paradigms in captivity [7,8]. We further suggest that species-typical leadership styles [16] and social and environmental effects, including familiarity with humans, best explain novelty responses of wild great apes. In sum, this study illustrates the feasibility of large-scale field experiments and the importance of both intrinsic and extrinsic factors in shaping animal curiosity

Geographic distribution of the V1016G knockdown resistance mutation in aedes albopictus. A warning bell for Europe

Background: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality &lt; 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise.Methods: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries.Results: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations.Conclusions: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review

BACKGROUND: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality < 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise. METHODS: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries. RESULTS: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations. CONCLUSIONS: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities

Population dynamics and genetic connectivity in recent chimpanzee history

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation: results from phase II/III of the GLORIA-AF registry

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1-3) and 1 (IQR 0-2), respectively (p &lt; 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of &amp; GE; 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21-2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641-0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration:. Unique identifiers: NCT01468701, NCT01671007 and NCT0193737

Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17

Background Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2 center dot 5th and 97 center dot 5th percentiles of those 250 draws. Findings While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62 center dot 6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3&nbsp;years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0&nbsp;years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013