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

Food mechanical properties and isotopic signatures in forest versus savannah dwelling eastern chimpanzees

Chimpanzees are traditionally described as ripe fruit specialists with large incisors but relatively small postcanine teeth, adhering to a somewhat narrow dietary niche. Field observations and isotopic analyses suggest that environmental conditions greatly affect habitat resource utilization by chimpanzee populations. Here we combine measures of dietary mechanics with stable isotope signatures from eastern chimpanzees living in tropical forest (Ngogo, Uganda) and savannah woodland (Issa Valley, Tanzania). We show that foods at Issa can present a considerable mechanical challenge, most saliently in the external tissues of savannah woodland plants compared to their tropical forest equivalents. This pattern is concurrent with different isotopic signatures between sites. These findings demonstrate that chimpanzee foods in some habitats are mechanically more demanding than previously thought, elucidating the broader evolutionary constraints acting on chimpanzee dental morphology. Similarly, these data can help clarify the dietary mechanical landscape of extinct hominins often overlooked by broad C3/C4 isotopic categories

Primate Archaeology Evolves

Since its inception, archaeology has traditionally focused exclusively on humans and our direct ancestors. However, recent years have seen archaeological techniques applied to material evidence left behind by non-human animals. Here, we review advances made by the most prominent field investigating past non-human tool use: primate archaeology. This field combines survey of wild primate activity areas with ethological observations, excavations and analyses that allow the reconstruction of past primate behaviour. Because the order Primates includes humans, new insights into the behavioural evolution of apes and monkeys also can be used to better interrogate the record of early tool use in our own, hominin, lineage. This work has recently doubled the set of primate lineages with an excavated archaeological record, adding Old World macaques and New World capuchin monkeys to chimpanzees and humans, and it has shown that tool selection and transport, and discrete site formation, are universal among wild stone-tool-using primates. It has also revealed that wild capuchins regularly break stone tools in a way that can make them difficult to distinguish from simple early hominin tools. Ultimately, this research opens up opportunities for the development of a broader animal archaeology, marking the end of archaeology’s anthropocentric era

Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors

Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7asinhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116. The effects were allele specific; a CDK7asmutation conferred both sensitivity to bulky adenine analogs and resistance to covalent inhibitors. Non-transformed colon epithelial cells were resistant to these combinations, as were cancer-derived cells with p53-inactivating mutations. Apoptosis was dependent on death receptor DR5, a p53 transcriptional target whose expression was refractory to Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to sensitize cancer cells to Cdk7 inhibition. Kalan et al. find that activation of the p53 tumor suppressor protein in human colon cancer-derived cells can induce transcriptional dependency on Cdk7, analogous to constitutive dependencies described in other tumors driven by oncogenic transcription factors. This work provides a proof of concept for combining p53-activating agents with Cdk7 inhibitors to elicit synthetic lethality. Keywords: Cdk7; p53; colon cancer; synthetic lethality; transcription; 5-fluorouracil; nutlin-3; apoptosis; chemical genetics; CDK inhibitorNational Institutes of Health (U.S.) (Grant HG002668

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

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

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

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