Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma.

Cannabis has been used for decades as a palliative therapy in the treatment of cancer. This is because of its beneficial effects on the pain and nausea that patients can experience as a result of chemo/radiotherapy. Tetrahydrocannabinol and cannabidiol are the main compounds present in Cannabis sativa, and both exert their actions through a receptor-mediated mechanism and through a non-receptor-mediated mechanism, which modulates the formation of reactive oxygen species. These oxidative stress conditions might trigger lipidic changes, which would compromise cell membrane stability and viability. In this sense, numerous pieces of evidence describe a potential antitumor effect of cannabinoid compounds in different types of cancer, although controversial results limit their implementation. In order to further investigate the possible mechanism involved in the antitumoral effects of cannabinoids, three extracts isolated from Cannabis sativa strains with high cannabidiol content were analyzed. Cell mortality, cytochrome c oxidase activity and the lipid composition of SH-SY5Y cells were determined in the absence and presence of specific cannabinoid ligands, with and without antioxidant pre-treatment. The cell mortality induced by the extracts in this study appeared to be related to the inhibition of the cytochrome c oxidase activity and to the THC concentration. This effect on cell viability was similar to that observed with the cannabinoid agonist WIN55,212-2. The effect was partially blocked by the selective CB1 antagonist AM281, and the antioxidant α-tocopherol. Moreover, certain membrane lipids were affected by the extracts, which demonstrated the importance of oxidative stress in the potential antitumoral effects of cannabinoids.

Enantiospecific Response in Cross-Polarization Solid-State Nuclear Magnetic Resonance of Optically Active Metal Organic Frameworks.

We report herein on a NMR-based enantiospecific response for a family of optically active metal-organic frameworks. Cross-polarization of the 1H-13C couple was performed, and the intensities of the 13C nuclei NMR signals were measured to be different for the two enantiomers. In a direct-pulse experiment, which prevents cross-polarization, the intensity difference of the 13C NMR signals of the two nanostructured enantiomers vanished. This result is due to changes of the nuclear spin relaxation times due to the electron spin spatial asymmetry induced by chemical bond polarization involving a chiral center. These experiments put forward on firm ground that the chiral-induced spin selectivity effect, which induces chemical bond polarization in the J-coupling, is the mechanism responsible for the enantiospecific response. The implications of this finding for the theory of this molecular electron spin polarization effect and the development of quantum biosensing and quantum storage devices are discussed.

Self-Adaptation of Pseudomonas fluorescens Biofilms to Hydrodynamic Stress.

In some conditions, bacteria self-organize into biofilms, supracellular structures made of a self-produced embedding matrix, mainly composed of polysaccharides, DNA, proteins, and lipids. It is known that bacteria change their colony/matrix ratio in the presence of external stimuli such as hydrodynamic stress. However, little is still known about the molecular mechanisms driving this self-adaptation. In this work, we monitor structural features of Pseudomonas fluorescens biofilms grown with and without hydrodynamic stress. Our measurements show that the hydrodynamic stress concomitantly increases the cell density population and the matrix production. At short growth timescales, the matrix mediates a weak cell-cell attractive interaction due to the depletion forces originated by the polymer constituents. Using a population dynamics model, we conclude that hydrodynamic stress causes a faster diffusion of nutrients and a higher incorporation of planktonic bacteria to the already formed microcolonies. This results in the formation of more mechanically stable biofilms due to an increase of the number of crosslinks, as shown by computer simulations. The mechanical stability also relies on a change in the chemical compositions of the matrix, which becomes enriched in carbohydrates, known to display adhering properties. Overall, we demonstrate that bacteria are capable of self-adapting to hostile hydrodynamic stress by tailoring the biofilm chemical composition, thus affecting both the mesoscale structure of the matrix and its viscoelastic properties that ultimately regulate the bacteria-polymer interactions.

Arbovirosis emergentes y reemergentes transmitidas por Aedes en la Región de las Américas: implicaciones en materia de políticas de salud / Emerging and reemerging Aedes-transmitted arbovirus infections in the Region of the Americas: implications for health policy

[RESUMEN]. El aumento en la incidencia y distribución geográfica de las arbovirosis constituye uno de los principales problemas de salud pública en la Región de las Américas. La incidencia del dengue ha experimentado una tendencia creciente en los últimos decenios en la Región, donde se ha pasado de una endemicidad baja a hiperendemicidad. También, la incidencia de la fiebre amarilla se ha intensificado en este período, y ha pasado de una actividad restringida a zonas selváticas a presentar brotes urbanos. El chikunguña comenzó a propagarse de forma pandémica en el 2005 a un ritmo sin precedentes y llegó al continente americano en el 2013. Al año siguiente, la infección por el virus del Zika irrumpió también en la Región con un brote explosivo acompañado de gravísimas anomalías congénitas y trastornos neurológicos, hasta convertirse en una de las mayores crisis de salud en los últimos años. La inadecuada vigilancia de las arbovirosis en la Región y la carencia de pruebas serológicas para diferenciar entre los distintos virus plantean retos considerables. Sigue habiendo pocas evidencias científicas en respaldo de las intervenciones de control de vectores. El manejo clínico sigue siendo la piedra angular del control de estas enfermedades. En la actualidad, solo están autorizadas en la Región de las Américas las vacunas contra la fiebre amarilla y contra el dengue, si bien hay varias vacunas experimentales en fase de investigación en ensayos clínicos. El Grupo Mundial de Expertos en Arbovirus ofrece en este artículo un panorama de los progresos, los retos y las recomendaciones sobre prevención y control de las arbovirosis en los países de la Región de las Américas.

[ABSTRACT]. The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Currently, only yellow fever and dengue vaccines are licensed in the Americas, with several candidate vaccines in clinical trials. The Global Arbovirus Group of Experts provides in this article an overview of progress, challenges, and recommendations on arboviral prevention and control for countries of the Americas.

Emerging and Reemerging Aedes-Transmitted Arbovirus Infections in the Region of the Americas: Implications for Health Policy.

The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Currently, only yellow fever and dengue vaccines are licensed in the Americas, with several candidate vaccines in clinical trials. The Global Arbovirus Group of Experts provides in this article an overview of progress, challenges, and recommendations on arboviral prevention and control for countries of the Americas.

Hunter-gatherer mobility and technological landscapes in southernmost South America: a statistical learning approach.

The present work aims to quantitatively explore and understand the relationship between mobility types (nautical versus pedestrian), specific technological traits and shared technological knowledge in pedestrian hunter-gatherer and nautical hunter-fisher-gatherer societies from the southernmost portion of South America. To that end, advanced statistical learning techniques are used: state-of-the-art classification algorithms and variable importance analyses. Results show a strong relationship between technological knowledge, traits and mobility types. Occupations can be accurately classified into nautical and pedestrian due to the existence of a non-trivial pattern between mobility and a relatively small fraction of variables from some specific technological categories. Cases where the best-fitted classification algorithm fails to generalize are found significantly interesting. These instances can unveil lack of information, not enough entries in the training set, singular features or ambiguity, the latter case being a possible indicator of the interaction between nautical and pedestrian societies.

The past, present, and future of immunization in the Americas

The Pan American Journal of Public Health recognizes with appreciation the contributions of the members of the Editorial Committee, and authors of the Overview article. Their contributions and dedication to this issue on immunization in the Region of the Americas were extraordinary and helped make the manuscripts more interesting, more accurate, and more useful to our readers and all others who work to improve the health of the peoples of the Americas. The Journal would like to give special thanks to the General Coordination of the National Immunization Program, Department of Transmissible Disease Surveillance, Health Surveillance Secretariat, Ministry of Health, Brazil, whose financial and programmatic contributions were essential to the publication of this special issue.

Vaccine strategies: Optimising outcomes.

Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the factors that encourage success, which often include strong support from government and healthcare organisations, as well as tailored, culturally-appropriate local approaches to optimise outcomes.

Vaccination of special populations: Protecting the vulnerable.

One of the strategic objectives of the 2011-2020 Global Vaccine Action Plan is for the benefits of immunisation to be equitably extended to all people. This approach encompasses special groups at increased risk of vaccine-preventable diseases, such as preterm infants and pregnant women, as well as those with chronic and immune-compromising medical conditions or at increased risk of disease due to immunosenescence. Despite demonstrations of effectiveness and safety, vaccine uptake in these special groups is frequently lower than expected, even in developed countries with vaccination strategies in place. For example, uptake of the influenza vaccine in pregnancy rarely exceeds 50% in developed countries and, although data are scarce, it appears that only half of preterm infants are up-to-date with routine paediatric vaccinations. Many people with chronic medical conditions or who are immunocompromised due to disease or aging are also under-vaccinated. In the US, coverage among people aged 65years or older was 67% for the influenza vaccine in the 2014-2015 season and 55-60% for tetanus and pneumococcal vaccines in 2013, while the coverage rate for herpes zoster vaccination among those aged 60years or older was only 24%. In most other countries, rates are far lower. Reasons for under-vaccination of special groups include fear of adverse outcomes or illness caused by the vaccine, the inconvenience (and in some settings, cost) of vaccination and lack of awareness of the need for vaccination or national recommendations. There is also evidence that healthcare providers' attitudes towards vaccination are among the most important influences on the decision to vaccinate. It is clear that physicians' adherence to recommendations needs to be improved, particularly where patients receive care from multiple subspecialists and receive little or no care from primary care providers.

Slow Progress In Finalizing Measles And Rubella Elimination In The European Region.

All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe.

Demonstration of Lignin-to-Peroxidase Direct Electron Transfer: A TRANSIENT-STATE KINETICS, DIRECTED MUTAGENESIS, EPR, AND NMR STUDY.

Versatile peroxidase (VP) is a high redox-potential peroxidase of biotechnological interest that is able to oxidize phenolic and non-phenolic aromatics, Mn(2+), and different dyes. The ability of VP from Pleurotus eryngii to oxidize water-soluble lignins (softwood and hardwood lignosulfonates) is demonstrated here by a combination of directed mutagenesis and spectroscopic techniques, among others. In addition, direct electron transfer between the peroxidase and the lignin macromolecule was kinetically characterized using stopped-flow spectrophotometry. VP variants were used to show that this reaction strongly depends on the presence of a solvent-exposed tryptophan residue (Trp-164). Moreover, the tryptophanyl radical detected by EPR spectroscopy of H2O2-activated VP (being absent from the W164S variant) was identified as catalytically active because it was reduced during lignosulfonate oxidation, resulting in the appearance of a lignin radical. The decrease of lignin fluorescence (excitation at 355 nm/emission at 400 nm) during VP treatment under steady-state conditions was accompanied by a decrease of the lignin (aromatic nuclei and side chains) signals in one-dimensional and two-dimensional NMR spectra, confirming the ligninolytic capabilities of the enzyme. Simultaneously, size-exclusion chromatography showed an increase of the molecular mass of the modified residual lignin, especially for the (low molecular mass) hardwood lignosulfonate, revealing that the oxidation products tend to recondense during the VP treatment. Finally, mutagenesis of selected residues neighboring Trp-164 resulted in improved apparent second-order rate constants for lignosulfonate reactions, revealing that changes in its protein environment (modifying the net negative charge and/or substrate accessibility/binding) can modulate the reactivity of the catalytic tryptophan.

Effect of resource spatial correlation and hunter-fisher-gatherer mobility on social cooperation in Tierra del Fuego.

This article presents an agent-based model designed to explore the development of cooperation in hunter-fisher-gatherer societies that face a dilemma of sharing an unpredictable resource that is randomly distributed in space. The model is a stylised abstraction of the Yamana society, which inhabited the channels and islands of the southernmost part of Tierra del Fuego (Argentina-Chile). According to ethnographic sources, the Yamana developed cooperative behaviour supported by an indirect reciprocity mechanism: whenever someone found an extraordinary confluence of resources, such as a beached whale, they would use smoke signals to announce their find, bringing people together to share food and exchange different types of social capital. The model provides insight on how the spatial concentration of beachings and agents' movements in the space can influence cooperation. We conclude that the emergence of informal and dynamic communities that operate as a vigilance network preserves cooperation and makes defection very costly.

Vitamin A supplementation modifies the association between mucosal innate and adaptive immune responses and resolution of enteric pathogen infections.

BACKGROUND: The efficacy of vitamin A supplementation on diarrheal disease morbidity may reflect the divergent effects that supplementation has on pathogen-specific immune responses and pathogen-specific outcomes. OBJECTIVE: We examined how vitamin A supplementation modified associations between gut-cytokine immune responses and the resolution of different diarrheal pathogen infections. DESIGN: Stools collected from 127 Mexican children who were 5-15 mo old and enrolled in a randomized, placebo-controlled vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of interleukin (IL)-6, IL-8, IL-4, IL-5, IL-10, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by using an enzyme-linked immunosorbent assay. Hazard models that incorporated categorized cytokine variables (ie, nondetectable, less than the median of detectable concentrations, and at least the median of detectable concentrations) were fit to the length of pathogen infections stratified by treatment group. RESULTS: Vitamin A-supplemented children with fecal MCP-1 or IL-8 concentrations less than the median of detectable concentrations and IL-10 concentrations of at least median concentrations had longer durations of EPEC infection than did children in the placebo group. In supplemented children, detectable fecal TNF-α or IL-6 concentrations were associated with shorter ETEC infection durations, whereas MCP-1 concentrations of at least the median were associated with longer infection durations. Children in this group who had IL-4, IL-5, or IFN-γ concentrations of at least median detectable concentrations had shorter durations of G. lamblia infection. CONCLUSION: The effect of supplementation on associations between fecal cytokine concentrations and pathogen infection resolution depends on the role of inflammatory immune responses in resolving specific pathogen infections.

Effect of the DTwP Haemophilus influenzae b conjugate vaccination in Mexico (1999-2007).

The introduction of type b Haemophilus influenzae (Hi b) conjugate vaccines for children as part of immunization schedules has led to a sharp drop in the incidence of Hi b disease. In 1999, the Haemophilus influenzae b DTwP-HB/Hi b vaccine was introduced into the primary immunization program in Mexico. There have been no studies evaluating the vaccine after the widespread immunization in our country. The immune response to Hi b vaccines in different countries varies both quantitatively and qualitatively. Replacement of Hi b strains is expected between pre- and post-vaccination eras. Documentation on these three aspects will be useful for decisions regarding the use of the vaccine. In this review, we show and discuss the potential benefits of vaccination with DTwP-HB/Hi b in Mexico in terms of our collected data obtained during the last 8 years on population genotype variations and on concentration and avidity of IgG antibodies. As the epidemiological follow-up data are missing, the evaluation of the results of these three types of studies, as a whole, allows clarification of the scenario of the protection after vaccination in Mexico, in absence of the drop in cases reports. These results reinforce the findings of postvaccination studies done elsewhere.

Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections.

The identification of immune response mechanisms that contribute to the control of diarrheal disease in developing countries remains an important priority. We addressed the role of fecal chemokines and cytokines in the resolution of diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from 127 Mexican children 5 to 15 months of age enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma) were determined. Hazard models incorporating cytokine variables were fit to durations of asymptomatic and symptomatic pathogen infections, controlling for treatment group. Increased levels of TNF-alpha and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-gamma levels were associated with decreased and increased durations, respectively, of both EPEC and ETEC infections. Increased IL-10 levels were associated with increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of both asymptomatic and symptomatic ETEC infections. Increased levels of MCP-1, IFN-gamma, IL-4, and IL-5 were associated with increased G. lamblia infection duration, while increased IL-8 levels were associated with decreased durations. Differences in proinflammatory and Treg cytokine levels are associated with differences in the resolution of inflammatory and noninflammatory pathogen infections.

Increase in body mass index and waist circumference is associated with high blood pressure in children and adolescents in Mexico city.

BACKGROUND AND AIMS: Currently, obesity has become a worldwide health problem affecting even children and yet little is known about its role as a determinant of high blood pressure in this age group. The aim of this epidemiological study was to determine the relationship between the increment of body mass index (BMI) and waist circumference (WC) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in children and teenagers. METHODS: The study was performed in Mexico City schools. Overweight was established if BMI ranged from >or=85(th) to <95(th) percentiles and obesity if BMI was >or=95(th) percentile. WC was classified in two categories, one ranging between the 75(th) and 89.9(th) percentiles and >90(th) percentile. Blood pressure was measured four times during one visit by the auscultatory method. High blood pressure was defined if the levels were >or=90(th) percentile according to the guidelines of the 2004 North American Task Force. RESULTS: Ages of the study population ranged from 5-8 (n = 474), 9-12 (n = 643) and 13-17 (n = 912) years, respectively. The levels of blood pressure and prevalence of high blood pressure were higher in overweight and obese children and adolescents. In both genders, the prevalence of SBP and DBP increased directly correlated with increments in age, BMI and WC, although prevalence and odd ratios of high blood pressure were higher in individuals with increased WC in comparison to BMI. CONCLUSIONS: Increases in WC and BMI are parameters directly associated with high blood pressure in children and adolescents.