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Millions of people suffer from different types of skin diseases worldwide. In the last decade, the development of nanocarriers has been the focus of the pharmaceutical and cosmetic industries to enhance the performance of their products, and to meet consumers' demands. Several delivery systems have been developed to improve the efficiency and minimize possible side effects. In this study, retinyl palmitate and Dead Sea water loaded nanoemulsions were developed as carriers to treat skin conditions such as photoaging, psoriasis, or atopic dermatitis. Toxicity profiles were carried out by means of viability, cell membrane asymmetry study, evaluation of oxidative stress induction (reactive oxygen species), and inflammation via cytokines production with a human keratinocyte cell line (HaCaT) and a mouse embryo fibroblasts cell line (BALB/3T3). Results showed that loaded nanoemulsions were found to be non-cytotoxic under the conditions of the study. Furthermore, no oxidative stress induction was observed. Likewise, an efficacy test of these loaded nanoemulsions was also tested on human skin organ cultures, before and after ultraviolet B light treatment. Viability and caspase-3 production assessment, in response to the exposure of skin explants to the loaded nanoemulsions, indicated non-toxic effects on human skin in culture, both with and without ultraviolet B irradiation. Further the ability of loaded nanoemulsions to protect the skin against ultraviolet B damage was assessed on skin explants reducing significantly the apoptotic activation after ultraviolet B irradiation. Our promising results indicate that the developed loaded nanoemulsions may represent a topical drug delivery system to be used as an alternative treatment for recurrent skin diseases.

{Background and aims In sub-Saharan Africa, infectious diseases are still the leading causes of mortality; however, this may soon be surpassed by non-communicable illnesses, namely hypertension, diabetes and cardiovascular disease. This study determined the prevalence and patterns of metabolic syndrome and cardio-risk factors in men and women in rural Uganda.Methods A household-based, cross-sectional survey was carried out following the WHO STEP-wise approach to surveillance. It included demographic and lifestyle questionnaires, anthropometric measurements and biochemical analyses. Of the 200 randomly recruited participants, 183 successfully completed two steps of the study and 161 provided blood samples.Results Data were collected from 183 adults, aged 18–69 years; 62% were female. Based on the National Cholesterol Education Program-Adult Treatment Panel-III criteria, the prevalence of metabolic syndrome was 19.1% (95% CI 14.0 to 22.5). Elevated fasting plasma glucose was observed in 14.2% (95% CI 9.1 to 19.3) of participants, hypertriglyceridaemia in 16.9% (95% CI 12.1 to 23.1); hypertension in 36.1% (95% CI 29.0 to 43.0) and 52.5% (95% CI 45.2 to 59.6) had low HDL (high-density lipoprotein) cholesterol. Abdominal obesity was found in 24.6% (95% CI 18.8 to 31.4) of participants. Sex disparities were significant for several risk factors. Females had significantly higher prevalence of abdominal obesity (38.6% vs 1.5% in males

BACKGROUND: Self-medication can lead to serious consequences but its overall prevalence in students is not known. AIMS: The aim of this study was to determine the prevalence of self-medication in students through a systematic review and meta-analysis of studies on the prevalence of self-medication in students across the world. METHODS: PubMed/MEDLINE, EMBASE, ISI/Web of Science and Google Scholar were searched up to October 2017. Studies reporting the prevalence of self-treatment in university students were selected. Data recorded included year of publication, country where the study was conducted, sample size, prevalence of self-medication, sex and mean age of students, and faculty of students (medical or non-medical). A random-effect model was used to determine effect size with a 95% confidence interval (CI). Heterogeneity across studies was assessed with the I(2) test. A sensitivity analysis assessed stability of the findings. RESULTS: A total of 89 studies were included in the analysis, which comprised 60 938 students. The overall prevalence of self-medication in university students was 70.1% (95% CI: 64.3-75.4%). Female students self-medicated more often than male students: odds ratio = 1.45 (95% CI%: 1.17-1.79). The prevalence of self-medication in medical students (97.2%) was higher than in non-medical students (44.7%). The I(2) test indicated high, statistically significant heterogeneity. The sensitivity analysis showed that the results were stable. CONCLUSION: The prevalence of self-medication among students worldwide is high. Programmes on the risks of self-medication and increasing control and monitoring of the sale of drugs are recommended. Facilitating students' access to doctors and health centres could reduce self-medication in students.

, cleaved caspase-3, PARP and Bax, and decreased the expression of Cyclin D1 and Bcl-2. LY294002 or Akt-siRNA inhibited the PI3K/Akt/FoxO3a pathway and promoted the Pristimerin-induced apoptosis, while Pristimerin effects were partially abolished in FoxO3a knockdown UM-1 cell cultures. Taken together, present results showed that Pristimerin induced apoptotic cell death through inhibition of PI3K/Akt/FoxO3a pathway in UM-1 cells. These findings indicate that Pristimerin may be considered as a potential chemotherapeutic agent for patients with UM.

Uveal melanoma (UM) is a highly invasive intraocular malignancy with high mortality. Presently, there is no FDA-approved standard for the treatment of metastatic UM. Pristimerin is a natural quinine methide triterpenoid compound with anti-angiogenic, anti-cancer and anti-inflammatory activities. However, Pristimerin potential cytotoxic effect on UM was poorly investigated. In the present study, we found the migration and invasion of UM-1 cells were inhibited by Pristimerin which also caused a rapid increase of ROS, decreased mitochondrial membrane potential, induced the accumulation of cells in G0/G1 phase, ending with apoptotic cell death. Pristimerin inhibited Akt and FoxO3a phosphorylation and induced nuclear accumulation of FoxO3a in UM-1 cells, increased the expression of pro-apoptotic proteins Bim、p27(Kip1) , cleaved caspase-3, PARP and Bax, and decreased the expression of Cyclin D1 and Bcl-2. LY294002 or Akt-siRNA inhibited the PI3K/Akt/FoxO3a pathway and promoted the Pristimerin-induced apoptosis, while Pristimerin effects were partially abolished in FoxO3a knockdown UM-1 cell cultures. Taken together, present results showed that Pristimerin induced apoptotic cell death through inhibition of PI3K/Akt/FoxO3a pathway in UM-1 cells. These findings indicate that Pristimerin may be considered as a potential chemotherapeutic agent for patients with UM.

We have previously shown that grazing in East-Mediterranean brushlands is associated with improved milk quality. However, grazing exposes animals to predation, heat stress, and parasites, and imposes labor constraint. In order to verify the hypothesis that feeding the tannin-rich browse species lentisk (Pistacia lentiscus L.) to confined dairy goats could serve as proxy to grazing in improving milk composition, 30 Damascus goats were assigned to 3 treatments for 3 weeks: goats were grazing for 4 h daily in Mediterranean brushland (treatment P) or were fed indoors with vetch hay without (H), or with (HPIS) lentisk foliage. Milk yield and dry matter intake were not affected by treatment. HPIS milk was richer in protein and milk-fat content than H milk. H milk had highest urea concentration, smallest milk-fat globules and highest phospholipid content (milk-fat basis). Curd firmness was 39 and 50% higher in the HPIS group, compared with P and H, respectively. HPIS milk had 39 and 90% higher n-3 fatty acids concentration than P and H, respectively. This study suggests that access to P. lentiscus intensifies the effect of grazing in Mediterranean woodland on milk composition. Thus, we present a nutritional strategy that not only retains the exceptional nutritional values and productivity of pasture feeding, but also participates in a profitable and sustainable agriculture with an emphasis on intensive ruminant animal-production systems.

Recombinant expression of toxins enables us to produce adequate quantities of these proteins which can be used to perform experiments at molecular, cellular, and behavioral levels. Furthermore, toxins can be edited by using simple molecular biology methods when producing them recombinantly. Thus, in many cases establishing a protocol for the recombinant expression of a toxin of interest is crucial in exploring the structure and function of the toxin and its effectors. To date, Escherichia coli (E. coli) represents the most widely used heterologous expression system in which recombinant proteins are usually accumulated in the bacterium cytoplasm. However, as many animal toxins contain disulfide bonds they tend to be misfolded and aggregate when found in the reducing E. coli cytoplasm. In contrast, conditions in the bacterium periplasm allow disulfide bond formation and correct folding of such toxins. Here, we describe a protocol for the production and purification of bioactive recombinant disulfide-rich toxins via periplasmic expression.

Profiling immunoglobulin (Ig) receptor repertoires with specialized assays can be cost-ineffective and time-consuming. Here we report ImReP, a computational method for rapid and accurate profiling of the Ig repertoire, including the complementary-determining region 3 (CDR3), using regular RNA sequencing data such as those from 8,555 samples across 53 tissues types from 544 individuals in the Genotype-Tissue Expression (GTEx v6) project. Using ImReP and GTEx v6 data, we generate a collection of 3.6 million Ig sequences, termed the atlas of immunoglobulin repertoires (TAIR), across a broad range of tissue types that often do not have reported Ig repertoires information. Moreover, the flow of Ig clonotypes and inter-tissue repertoire similarities across immune-related tissues are also evaluated. In summary, TAIR is one of the largest collections of CDR3 sequences and tissue types, and should serve as an important resource for studying immunological diseases.

Profiling immunoglobulin (Ig) receptor repertoires with specialized assays can be cost-ineffective and time-consuming. Here we report ImReP, a computational method for rapid and accurate profiling of the Ig repertoire, including the complementary-determining region 3 (CDR3), using regular RNA sequencing data such as those from 8,555 samples across 53 tissues types from 544 individuals in the Genotype-Tissue Expression (GTEx v6) project. Using ImReP and GTEx v6 data, we generate a collection of 3.6 million Ig sequences, termed the atlas of immunoglobulin repertoires (TAIR), across a broad range of tissue types that often do not have reported Ig repertoires information. Moreover, the flow of Ig clonotypes and inter-tissue repertoire similarities across immune-related tissues are also evaluated. In summary, TAIR is one of the largest collections of CDR3 sequences and tissue types, and should serve as an important resource for studying immunological diseases.

Progesterone plays a pivotal role during mammogenesis and serves as an inhibitor of the secretory activation of mammary cells in the last days of gestation. However, its role during lactogenesis, in particular its involvement in lipid metabolism, and milk fat content and composition, is unknown. Here, we provide new evidence of progesterone's involvement in the regulation of milk fat globule (MFG) synthesis and secretion. Findings from bothin vivoandin vitrostudies indicated that the concentration and the direction (increase vs. decrease) of progesterone concentration to which the mammary epithelial cells (MECs) are exposed affect MFG size. This was found to be very-low-density lipoprotein (VLDL) dependent: in the presence of VLDL, the proportion of MEC with small lipid droplets (<1 mu m) increased 2.4-fold, and the proportion of large lipid droplets (>1 mu m) increased 4-fold; in the absence of VLDL, no differences were found. The findings add to our understanding of the mechanism underlying the regulation of MFG size and provide new evidence for progesterone's role in lipid metabolism in the mammary gland during lactogenesis. The fact that the size, synthesis, and composition of MFG are affected by the cyclic pattern of progesterone concentration in the circulation might have physiologically relevant consequences, in particular on milk as a nutritional source.

Since 1992, the Eilat Conferences have provided a forum for all stakeholders in the epilepsy community to appraise the latest data on new antiepileptic drugs and emergency seizure treatments, including, in recent years, updates on progress with the development of novel monitoring and therapeutic devices. Because of the COVID-19 pandemic, the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference on July 27-30, 2020 for the sessions on drugs and on August 3, 2020 for the sessions on devices, and was attended during the 5 days by >500 participants from 63 countries. This progress report summarizes key preclinical and initial (phase 1) clinical data on eight investigational treatments that are currently in early development, including 2-deoxy-D-glucose, GAO-3-02, JNJ-40411813, NBI-921352, NTX-001, sec-butylpropylacetamide, XEN1101, and XEN496. This report provides an overview of current scenarios in the area of treatment discovery and development. The information presented illustrates a variety of innovative strategies, including exploration of compounds with novel mechanisms of action, transplantation of interneurons into epileptogenic brain regions, and the targeting of rare, previously neglected syndromes.

The Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference from July 27 to July 30, 2020 for the sessions on drugs, and on August 3, 2020 for the sessions on devices. A total of 534 delegates from 63 countries attended lectures and interactive discussions, representing a broad range of disciplines from basic science, clinical research, and clinical care. This progress report provides summaries of recent findings on investigational compounds for which preclinical data as well as data from patient studies were presented. The report includes the following five compounds: anakinra, cenobamate, CVL-865, fenfluramine, and ganaxolone, all with novel modes of action compared to more established antiepileptic drugs. Some of these compounds demonstrated promising results in placebo-controlled phase 3 trials, and two have recently received approval from the US Food and Drug Administration (FDA). These include cenobamate, which was approved by the FDA on November 21, 2019 for the treatment of partial onset (focal) seizures in adults, and fenfluramine oral solution, which was approved by the FDA on June 25, 2020 for the treatment of seizures associated with Dravet syndrome in patients 2 years and older.

The Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference from July 27 to July 30, 2020 for the sessions on drugs, and on August 3, 2020 for the sessions on devices. A total of 534 delegates from 63 countries attended lectures and interactive discussions, representing a broad range of disciplines from basic science, clinical research, and clinical care. This progress report provides summaries of recent findings on investigational compounds for which preclinical data as well as data from patient studies were presented. The report includes the following five compounds: anakinra, cenobamate, CVL-865, fenfluramine, and ganaxolone, all with novel modes of action compared to more established antiepileptic drugs. Some of these compounds demonstrated promising results in placebo-controlled phase 3 trials, and two have recently received approval from the US Food and Drug Administration (FDA). These include cenobamate, which was approved by the FDA on November 21, 2019 for the treatment of partial onset (focal) seizures in adults, and fenfluramine oral solution, which was approved by the FDA on June 25, 2020 for the treatment of seizures associated with Dravet syndrome in patients 2 years and older.