Epistemonikos: a comprehensive database of systematic reviews for health decision-making.

BACKGROUND: Systematic reviews allow health decisions to be informed by the best available research evidence. However, their number is proliferating quickly, and many skills are required to identify all the relevant reviews for a specific question. METHODS AND FINDINGS: We screen 10 bibliographic databases on a daily or weekly basis, to identify systematic reviews relevant for health decision-making. Using a machine-based approach developed for this project we select reviews, which are then validated by a network of more than 1000 collaborators. After screening over 1,400,000 records we have identified more than 300,000 systematic reviews, which are now stored in a single place and accessible through an easy-to-use search engine. This makes Epistemonikos the largest database of its kind. CONCLUSIONS: Using a systematic approach, recruiting a broad network of collaborators and implementing automated methods, we developed a one-stop shop for systematic reviews relevant for health decision making.

What are the barriers, facilitators and interventions targeting help-seeking behaviours for common mental health problems in adolescents? A systematic review.

BACKGROUND: Increasing rates of mental health problems among adolescents are of concern. Teens who are most in need of mental health attention are reluctant to seek help. A better understanding of the help-seeking in this population is needed to overcome this gap. METHODS: Five databases were searched to identify the principal barriers, facilitators and interventions targeting help-seeking for common mental health problems in adolescents aged 10-19 years. The search was performed in June 2018 and updated in April 2019. Two independent screening processes were made using the eligibility criteria. Quality assessment of each study was performed, and findings summarised using a narrative synthesis. RESULTS: Ninety studies meet the inclusion criteria for this review for barrier and facilitators (n = 54) and interventions (n = 36). Stigma and negative beliefs towards mental health services and professionals were the most cited barriers. Facilitators included previous positive experience with health services and mental health literacy. Most interventions were based on psychoeducation, which focused on general mental health knowledge, suicide and self-harm, stigma and depression. Other types of interventions included the use of multimedia and online tools, peer training and outreach initiatives. Overall, the quality of studies was low to medium and there was no general agreement regarding help-seeking definition and measurements. CONCLUSION: Most of the interventions took place in an educational setting however, it is important to consider adolescents outside the educational system. Encouraging help-seeking should come with the increased availability of mental health support for all adolescents in need, but this is still a major challenge for Child and Adolescent Mental Health Services. There is also a need to develop shared definitions, theoretical frameworks and higher methodological standards in research regarding help-seeking behaviours in adolescents. This will allow more consistency and generalisability of findings, improving the development of help-seeking interventions and ensuring timely access to mental health treatments.

Evaluation of potential antigenotoxic, cytotoxic and proapoptotic effects of the olive oil by-product "alperujo", hydroxytyrosol, tyrosol and verbascoside.

Olive oil is an integral ingredient of the "Mediterranean diet". The olive oil industry generates large quantities of a by-product called "alperujo" (AL) during the two-phase centrifugation system developed in the early nineties. AL could be a potent exploitable source of natural phenolic antioxidants. Our results showed that AL and its distinctive phenols hydroxytyrosol, tyrosol and verbascoside were not genotoxic in the Somatic Mutation and Recombination Test (SMART) of Drosophila melanogaster and exerted antigenotoxic activity against DNA oxidative damage generated by hydrogen peroxide (H2O2). Alperujo and hydroxytyrosol also exhibited notable antiproliferative and caspase 3-dependent proapoptotic effects toward the human tumoral cell line HL60. AL can provide a cheap and efficient source of chemopreventive phenolic compounds with strong antioxidant properties, becoming a promising and potent therapeutic drug in the future.

Preliminary study of ventilation with 4 ml/kg tidal volume in acute respiratory distress syndrome: feasibility and effects on cyclic recruitment - derecruitment and hyperinflation.

INTRODUCTION: Cyclic recruitment-derecruitment and overdistension contribute to ventilator-induced lung injury. Tidal volume (Vt) may influence both, cyclic recruitment-derecruitment and overdistension. The goal of this study was to determine if decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation, and if it is possible to avoid severe hypercapnia. METHODS: Patients with pulmonary acute respiratory distress syndrome (ARDS) were included in a crossover study with two Vt levels: 6 and 4 ml/kg. The protocol had two parts: one bedside and other at the CT room. To avoid severe hypercapnia in the 4 ml/kg arm, we replaced the heat and moisture exchange filter by a heated humidifier, and respiratory rate was increased to keep minute ventilation constant. Data on lung mechanics and gas exchange were taken at baseline and after 30 minutes at each Vt (bedside). Thereafter, a dynamic CT (4 images/sec for 8 sec) was taken at each Vt at a fixed transverse region between the middle and lower third of the lungs. Afterward, CT images were analyzed and cyclic recruitment-derecruitment was determined as non-aerated tissue variation between inspiration and expiration, and hyperinflation as maximal hyperinflated tissue at end-inspiration, expressed as % of lung tissue weight. RESULTS: We analyzed 10 patients. Decreasing Vt from 6 to 4 ml/kg consistently decreased cyclic recruitment-derecruitment from 3.6 (2.5 to 5.7) % to 2.9 (0.9 to 4.7) % (P <0.01) and end-inspiratory hyperinflation from 0.7 (0.3 to 2.2) to 0.6 (0.2 to 1.7) % (P = 0.01). No patient developed severe respiratory acidosis or severe hypercapnia when decreasing Vt to 4 ml/kg (pH 7.29 (7.21 to 7.46); PaCO2 48 (26 to 51) mmHg). CONCLUSIONS: Decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation. Severe respiratory acidosis may be effectively prevented by decreasing instrumental dead space and by increasing respiratory rate.

Food restriction, ghrelin, its antagonist and obestatin control expression of ghrelin and its receptor in chicken hypothalamus and ovary.

The purpose of the present study was to identify the role of age, nutritional state and some metabolic hormones in control of avian hypothalamic and ovarian ghrelin/ghrelin receptor system. We examined the effect of food restriction, administration of ghrelin 1-18, ghrelin antagonistic analogue (D-Lys-3)-GHRP-6, obestatin and combinations of them on the expression of ghrelin and ghrelin receptor (GHS-R1a) in hypothalamus and ovary of old (23months of age) and young (7months of age) chickens. Expression of mRNAs for ghrelin and GHS-R1a in both hypothalamus and largest ovarian follicle was measured by RT-PCR. It was observed that food restriction could promote the expression of ghrelin and GHS-R1a in hypothalamus and ovary of the old chickens, but in the young chickens it reduced expression of ghrelin and did not affect expression of GHS-R1a in the ovary. Administration of ghrelin 1-18 did not affect hypothalamic or ovarian ghrelin mRNA, but significantly increased the expression of GHS-R1a in hypothalamus, but not in ovary. (D-Lys-3)-GHRP-6, significantly stimulated accumulation of ghrelin, but not GHS-R1a mRNA in hypothalamus or ghrelin or GHS-R1a in the ovary. Ghrelin 1-18 and (D-Lys-3)-GHRP-6, when given together, were able either to prevent or to induce effect of these hormones. Obestatin administration increased expression of ghrelin gene in the hypothalamus, but not expression of hypothalamic GHS-R1a, ovarian ghrelin and GHS-R1a. Furthermore, obestatin was able to modify effect of both ghrelin and fasting on hypothalamic and ovarian mRNA for ghrelin GHS-R1a. Our results (1) confirm the existence of ghrelin and its functional receptors GHS-R1a in the chicken hypothalamus and ovary (2) confirm the age-dependent control of ovarian ghrelin by feeding, (3) demonstrate, that nutritional status can influence the expression of both ghrelin and GHS-R1a in hypothalamus and in the ovary (3) demonstrates for the first time, that ghrelin can promote generation of its functional receptor in the hypothalamus, but not in the ovary, (4) show that ghrelin1-18 and (D-Lys-3)-GHRP-6 could not only be antagonists in the action on chicken hypothalamus and ovaries, but also independent regulators and even agonists, and (5) provide first evidence for action of obestatin on hypothalamic ghrelin and on the response of hypothalamic and ovarian ghrelin/GHS-R1a system to food restriction. These data indicate the involvement of both hypothalamic and ovarian ghrelin/GHS-R1 systems in mediating the effects of nutritional status, ghrelin and obestatin on reproductive processes.

Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid.

Medicinal plants represent an important resource in new drug research. Antioxidant properties of plants can help to scavenge reactive oxygen species. The objective of this work was to evaluate the genotoxic, antigenotoxic, tumoricidal, and apoptotic effect of some major phenols (apigenin, bisabolol, and protocatechuic acid) from two medicinal plants, Matricaria chamomilla and Uncaria tomentosa. The wing spot test of Drosophila melanogaster was used to evaluate the genotoxicity and antigenotoxicity of the three phenols. The human model of HL-60 leukemia cells was used for the assessment of the cytotoxic effect, growth, and cellular viability. The apoptotic effect was evaluated using a DNA fragmentation assay based on the formation of internucleosomal units. Protocatechuic acid (0.25 and 1 mM), apigenin (0.46 and 1.85 mM), and bisabolol (0.56 and 2.24 mM) did not exhibit any genotoxic effect. The three phenols showed an antigenotoxic effect against the hydrogen peroxide effect and also exhibited tumoricidal activity. Apigenin (2.24-35.96 mM) showed a lower 50% inhibitory concentration (0.75 and 3.87 mM for the trypan blue test and WST-8 colorimetric assay, respectively) than bisabolol and protocatechuic acid. These phenolics also induced apoptosis in HL-60 leukemia cells. This study suggests that the antioxidant activity of Chamomilla and Uncaria could be partially responsible of their beneficial activity.

Quantitative measurement of Plasmodium-infected erythrocytes in murine models of malaria by flow cytometry using bidimensional assessment of SYTO-16 fluorescence.

Flow cytometry is a powerful tool for measuring parasitemias in murine malaria models used to test new antimalarials. Measurement of the emission of the nonpermeable nucleic acid dye YOYO-1 (at 530 and 585 nm after excitation at 488 nm) allowed the unambiguous detection of low parasitemias (> or =0.01%) but required prolonged fixation and permeabilization of the sample. Thus, we tested whether this issue could be overcome by use of the cell-permeant dye SYTO-16 with this same bidimensional method. Blood samples from CD1 mice infected with Plasmodium yoelii, Plasmodium vinckei, or Plasmodium chabaudi or from NOD(scidbeta2m-/-) engrafted with human erythrocytes and infected with P. falciparum were stained with SYTO-16 in the presence or absence of TER-119 mAb (for engrafted mice) in 96-well plate format and acquired in Trucount tubes. Bidimensional analysis with SYTO-16 was quantitatively equivalent to YOYO-1. Moreover, by combining SYTO-16 with the use of TER-119-PE antimouse erythrocyte mAb and Trucount tubes, the measurement of the concentration of P. falciparum-infected erythrocytes over a range of five orders of magnitude was achieved. Bidimensional analysis using SYTO-16 can be used to accurately measure the concentration of Plasmodium spp.-infected erythrocytes in mice without complex sample preparation.

Modulation of genotoxicity and cytotoxicity by radish grown in metal-contaminated soils.

Members of the Brassicaceae family are known for their anticarcinogenic and genetic material protective effects. However, many of the species of this family accumulate high amounts of metals, which is an undesirable feature. Radish (Raphanus sativus L.) has shown to accumulate metals in roots to a higher extent than others members of Brassicaceae. The main objectives of this work are (i) to study the distribution of the accumulated As, Pb and Cd in radish plants and (ii) to establish the genotoxic, antigenotoxic and cytotoxic activities of the root and shoot of this vegetable. Results indicate that (i) the shoots of radish accumulate higher concentrations of metal(oid)s than roots; (ii) the shoots were genotoxic at the different concentrations studied, with the root showing such genotoxic effect only at the highest concentration assayed; (iii) the antigenotoxic potential of radish is reduced in plants with high metal content and (iv) the tumouricide activities of the radish plants were negatively correlated to their metal(oid) contents. An interaction between metal(oid)s and the isotyocianates (hydrolysis products of the glucosinolates) contained in the radish is suggested as the main modulator agents of the genotoxic activity of the plants grown in contaminated soils with metal(oid)s.

[Epidemiologic and situational panorama of hepatitis C in Mexico]. / Panorama epidemiológico y situacional de la hepatitis C en México.

OBJECTIVE: To determine the epidemiological situation of Chronic Hepatitis C (CHC) in our country. BACKGROUND DATA: Chronic Hepatitis C affects 170 million people worldwide, and about 0.7% of Mexican population. There is no enough epidemiological information about CHC in our country, and it is very probable that some cases are not even detected. METHODS: An investigation poll was performed. Age, gender, birthday, weight, race, residence and birth place, routes of transmission, ALT levels, histological, serological and molecular diagnosis, evidence of complications and previous treatments were recorded. A data recollection sheet was dispatched to different country provinces; they had 6 months to answer it, in order to recollect all information. RESULTS: 831 patients were analized (58.6% female and 41.4% male) with the following distribution in our country provinces: Aguascalientes 15, Chihuahua 12, Distrito Federal 495, Durango 10, Jalisco 89, Guanajuato 78, Yucatán 8, Querétaro 11, Sonora 40, Tabasco 15, Baja California 5, Veracruz 13, Tamaulipas 2 and 38 patients of Nuevo León. The highest incidence of CHC was found at fifth and sixth decade of life (28.5% y 26.7% respectively. The weight distribution was 36.2% < 65kg, 34.6% 65-75 kg and 29.2% > 75 kg. 86.5% had chronic hepatitis and 13.2% cirrhosis. The risk factors for HCV infection analysis showed that the main route of transmission was via contaminated blood (64.2%); when we excluded the patients that were exposed before 1995, the incidence was lowered to 4.5%. The higher incidence was showed between 1970 and 1990 (68%). The intravenous drug users were predominantly male and on those patients in the provinces near the north border line of our country. The predominant genotype was gen- 1 no matter the province (72.2%), in the intravenous drug users genotype 3 was found in 25%. The viral load was similar in all the provinces. 75% of the patients had have treatment and 22.5% had have two cycles, 50% of cirrhotic patients had have treatment whereas only 28% of the patients with late complications had have it. The most common treatment was pegylated alpha-2a interferon plus ribavirine. CONCLUSIONS: 1. The main route of transmission was blood transfusion. There is a marked decrease in the incidence of post-transfusional hepatitis since the introduction of anti-VHC antibody screening of blood donors (4.5%). 2. The time between the infection and diagnosis was 23 years for chronic hepatitis and 26 years for cirrhosis. 3. Intravenous drugs use was an important route of transmission in the north of our country. 4. The predominant genotype was gen-1. 5. Almost all the patients with chronic hepatitis received treatment, the most common used was pegylated interferon alpha-2a and ribavirin. 6.50% of the patients with CHC have late complications.

Genotoxicity and anti-genotoxicity of some traditional medicinal herbs.

Six herbal infusions used worldwide (Matricaria chamomilla, Tilia cordata, Mentha piperita, Mentha pulegium, Uncaria tomentosa and Valeriana officinalis) were assayed for anti-genotoxicity using the Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster. All these infusions are traditionally used for various medical purposes, including anti-inflammatory processes. Hydrogen peroxide was used as an oxidative genotoxicant to test the anti-genotoxic potency of the medicinal infusions. None of these infusions showed a significant genotoxicity, quite the reverse they were able to behave as desmutagens, detoxifying the mutagen hydrogen peroxide. The phenolic content of such herbal infusions is argued to be the possible scavenger of reactive oxygen radicals produced by the hydrogen peroxide.