The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis.

In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and subverts brain signals to ensure timely execution of epidermal daily physiology. Timely cell-cycle termination in the epidermal stem cell compartment depends upon incorporation of clock-driven signals originating from the brain. In contrast, the epidermal clock corrects or outcompetes potentially disruptive feeding-related signals to ensure the optimal timing of DNA replication. Together, we present an approach for cataloging the systemic dependencies of daily temporal organization in a tissue and identify an essential gate-keeping function of peripheral circadian clocks that guarantees tissue homeostasis.

A Portable Triboelectric Nanogenerator Based on Dehydrated Nopal Powder for Powering Electronic Devices.

Triboelectric nanogenerators (TENGs) based on organic materials can harvest green energy to convert it into electrical energy. These nanogenerators could be used for Internet-of-Things (IoT) devices, substituting solid-state chemical batteries that have toxic materials and limited-service time. Herein, we develop a portable triboelectric nanogenerator based on dehydrated nopal powder (NOP-TENG) as novel triboelectric material. In addition, this nanogenerator uses a polyimide film tape adhered to two copper-coated Bakelite plates. The NOP-TENG generates a power density of 2309.98 µW·m-2 with a load resistance of 76.89 MΩ by applying a hand force on its outer surface. Furthermore, the nanogenerator shows a power density of 556.72 µW·m-2 with a load resistance of 76.89 MΩ and under 4g acceleration at 15 Hz. The output voltage of the NOP-TENG depicts a stable output performance even after 27,000 operation cycles. This nanogenerator can light eighteen green commercial LEDs and power a digital calculator. The proposed NOP-TENG has a simple structure, easy manufacturing process, stable electric behavior, and cost-effective output performance. This portable nanogenerator may power electronic devices using different vibration energy sources.

Neuroprotective Epigenetic Changes Induced by Maternal Treatment with an Inhibitor of Soluble Epoxide Hydrolase Prevents Early Alzheimer's Disease Neurodegeneration.

Modulation of Alzheimer's disease (AD) risk begins early in life. During embryo development and postnatal maturation, the brain receives maternal physiological influences and establishes epigenetic patterns that build its level of resilience to late-life diseases. The soluble epoxide hydrolase inhibitor N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl] urea (TPPU), reported as ant-inflammatory and neuroprotective against AD pathology in the adult 5XFAD mouse model of AD, was administered to wild-type (WT) female mice mated to heterozygous 5XFAD males during gestation and lactation. Two-month-old 5XFAD male and female offspring of vehicle-treated dams showed memory loss as expected. Remarkably, maternal treatment with TPPU fully prevented memory loss in 5XFAD. TPPU-induced brain epigenetic changes in both WT and 5XFAD mice, modulating global DNA methylation (5-mC) and hydroxymethylation (5-hmC) and reducing the gene expression of some histone deacetylase enzymes (Hdac1 and Hdac2), might be on the basis of the long-term neuroprotection against cognitive impairment and neurodegeneration. In the neuropathological analysis, both WT and 5XFAD offspring of TPPU-treated dams showed lower levels of AD biomarkers of tau hyperphosphorylation and microglia activation (Trem2) than the offspring of vehicle-treated dams. Regarding sex differences, males and females were similarly protected by maternal TPPU, but females showed higher levels of AD risk markers of gliosis and neurodegeneration. Taken together, our results reveal that maternal treatment with TPPU impacts in preventing or delaying memory loss and AD pathology by inducing long-term modifications in the epigenetic machinery and its marks.

Effect of comprehensive smoke-free legislation on the tourism industry in countries of the Caribbean Community.

Objective: To assess whether the introduction of comprehensive smoke-free legislation affected tourism in four Caribbean Community (CARICOM) countries - Barbados, Guyana, Jamaica, and Trinidad and Tobago. Methods: We compared the evolution of three tourism variables - tourist arrivals, tourist expenditure, and average length of stay - in a country implementing smoke-free environments (treated country) with the evolution of these variables in the same country if smoke-free legislation had not been implemented. We used a synthetic control method to recreate this counterfactual scenario by constructing a synthetic country using a weighted average of several donor-pool CARICOM countries that did not introduce legislation on smoke-free environments during the period analyzed. We quantified the effect of the smoke-free environments on tourism as the difference between tourism variables in the treated and synthetic country. To assess whether the estimated effect of the smoke-free environments was the result of chance, we compared the effects of legislation in the treated country to placebo effects in the donor pool by assuming comprehensive smoke-free legislation was introduced in the same year as in the treated country. Results: Implementing smoke-free environments did not affect the arrival of tourists, tourism expenditure, or the average length of stay in the four countries. Conclusions: Our findings provide strong evidence that public policies banning smoking in public places do not affect hospitality and tourism businesses. Given the economic significance of this industry in the Caribbean, the local evidence provided by this study will help to effectively counteract interference by the tobacco industry and advance towards a smoke-free Caribbean.

Effect of comprehensive smoke-free legislation on the tourism industry in countries of the Caribbean Community

[ABSTRACT]. Objective. To assess whether the introduction of comprehensive smoke-free legislation affected tourism in four Caribbean Community (CARICOM) countries – Barbados, Guyana, Jamaica, and Trinidad and Tobago. Methods. We compared the evolution of three tourism variables – tourist arrivals, tourist expenditure, and aver- age length of stay – in a country implementing smoke-free environments (treated country) with the evolution of these variables in the same country if smoke-free legislation had not been implemented. We used a synthetic control method to recreate this counterfactual scenario by constructing a synthetic country using a weighted average of several donor-pool CARICOM countries that did not introduce legislation on smoke-free environ- ments during the period analyzed. We quantified the effect of the smoke-free environments on tourism as the difference between tourism variables in the treated and synthetic country. To assess whether the estimated effect of the smoke-free environments was the result of chance, we compared the effects of legislation in the treated country to placebo effects in the donor pool by assuming comprehensive smoke-free legislation was introduced in the same year as in the treated country. Results. Implementing smoke-free environments did not affect the arrival of tourists, tourism expenditure, or the average length of stay in the four countries. Conclusions. Our findings provide strong evidence that public policies banning smoking in public places do not affect hospitality and tourism businesses. Given the economic significance of this industry in the Carib- bean, the local evidence provided by this study will help to effectively counteract interference by the tobacco industry and advance towards a smoke-free Caribbean.

[RESUMEN]. Objetivo. Evaluar si la introducción de una legislación integral sobre ambientes libres de humo tuvo algún efecto sobre el turismo en cuatro países de la Comunidad del Caribe (CARICOM): Barbados, Guyana, Jamaica y Trinidad y Tobago. Métodos. Comparamos la evolución de tres variables turísticas (llegada de turistas, gasto de los turistas y duración promedio de la estancia) en un país que ha establecido entornos libres de humo de tabaco (país tratado) con la evolución de estas variables en el mismo país si no se hubiera adoptado una legislación sobre ambientes libres de humo. Se empleó un método de control sintético para recrear este escenario contrafáctico mediante la construcción de un país sintético utilizando un promedio ponderado de varios países del grupo de donantes de CARICOM que no habían introducido una legislación relativa a entornos libres de humo durante el período analizado. Se cuantificó el efecto de los entornos libres de humo de tabaco sobre el tur- ismo como la diferencia entre las variables turísticas en el país tratado y el sintético. Para evaluar si el efecto estimado de los entornos libres de humo fue estadísticamente significativo, se compararon los efectos de la legislación en el país tratado con los efectos placebo en el grupo de donantes mediante la suposición de que se hubiese introducido una legislación integral sobre ambientes libre de humo en el mismo año que en el país tratado. Resultados. La implementación de entornos sin humo de tabaco no tuvo ningún efecto en la llegada de tur- istas, el gasto de los turistas o la duración promedio de la estancia en los cuatro países. Conclusiones. Nuestros hallazgos ofrecen una prueba sólida de que las políticas públicas que prohíben fumar en lugares públicos no afectan a las empresas de hospitalidad y turismo. Dada la importancia económica de esta industria en el Caribe, la evidencia local proporcionada por este estudio ayudará a contrarrestar eficaz- mente la interferencia de la industria tabacalera y avanzar hacia una Comunidad del Caribe libre de humo de tabaco.

[RESUMO]. Objetivo. Avaliar se a promulgação de uma lei antifumo abrangente afetou o turismo em quatro países da Comunidade do Caribe (CARICOM), a saber: Barbados, Guiana, Jamaica e Trinidad e Tobago. Métodos. Comparamos a evolução de três variáveis relacionadas ao turismo (desembarque de turistas, des- pesas de turistas e duração média da estadia) em um país que havia implementado ambientes livres de fumo (país tratado) com a evolução dessas variáveis no mesmo país se a lei antifumo não tivesse sido implemen- tada. Usamos um método de controle sintético para recriar esse contrafactual, construindo um país sintético usando uma média ponderada de vários países doadores da CARICOM que não promulgaram leis sobre ambientes livres de fumaça durante o período analisado. Quantificamos o efeito dos ambientes livres de fumo no turismo como a diferença entre as variáveis de turismo no país tratado e no país sintético. Para avaliar se o efeito estimado dos ambientes livres de fumo foi resultado do acaso, comparamos os efeitos da legislação do país tratado com os efeitos placebo no grupo de doadores, supondo que uma lei antifumo abrangente havia sido promulgada no mesmo ano que no país tratado. Resultados. A implementação de ambientes livres de fumo não afetou o desembarque de turistas, as despe- sas de turistas ou a duração média da estadia nos quatro países. Conclusões. Nossas constatações fornecem evidências robustas de que as políticas públicas que proíbem o fumo em locais públicos não afetam o setor de hospitalidade e turismo. Considerando a importância econômica desta indústria para o Caribe, as evidências locais fornecidas por este estudo ajudarão a com- bater efetivamente a interferência da indústria do tabaco e a avançar rumo a um Caribe livre do fumo.

Mesoporous silica particles are phagocytosed by microglia and induce a mild inflammatory response in vitro.

Aim: Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses to MSPs of astrocytes and microglia, the two main cellular players in neuroinflammation. Materials & methods: Primary murine cortical mixed glial cultures were treated with rhodamine B-labeled MSPs. Results: MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. MSPs also do not affect mRNA levels of key proinflammatory genes; however, in combination with lipopolysaccharide, they significantly increase extracellular IL-1ß levels. Conclusion: These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells.

Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses of two types of brain cells, astrocytes and microglia, to MSPs. Mouse astrocytes and microglia were kept alive in cultures and were treated with MSPs that were labeled with a red fluorescent agent to facilitate visualization under the microscope. MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. When given alone, MSPs do not affect mRNA levels of key proinflammatory genes. However, MSPs given in combination with lipopolysaccharide, a strong proinflammatory agent, significantly increase extracellular levels of IL-1ß, one of the proinflammatory mediators studied. These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells.

Effect of comprehensive smoke-free legislation on the tourism industry in countries of the Caribbean Community / Efecto de una legislación integral sobre ambientes libres de humo en la industria del turismo en los países de la Comunidad del Caribe / Efeito de uma lei antifumo abrangente sobre a indústria do turismo em países da Comunidade do Caribe

ABSTRACT Objective. To assess whether the introduction of comprehensive smoke-free legislation affected tourism in four Caribbean Community (CARICOM) countries - Barbados, Guyana, Jamaica, and Trinidad and Tobago. Methods. We compared the evolution of three tourism variables - tourist arrivals, tourist expenditure, and average length of stay - in a country implementing smoke-free environments (treated country) with the evolution of these variables in the same country if smoke-free legislation had not been implemented. We used a synthetic control method to recreate this counterfactual scenario by constructing a synthetic country using a weighted average of several donor-pool CARICOM countries that did not introduce legislation on smoke-free environments during the period analyzed. We quantified the effect of the smoke-free environments on tourism as the difference between tourism variables in the treated and synthetic country. To assess whether the estimated effect of the smoke-free environments was the result of chance, we compared the effects of legislation in the treated country to placebo effects in the donor pool by assuming comprehensive smoke-free legislation was introduced in the same year as in the treated country. Results. Implementing smoke-free environments did not affect the arrival of tourists, tourism expenditure, or the average length of stay in the four countries. Conclusions. Our findings provide strong evidence that public policies banning smoking in public places do not affect hospitality and tourism businesses. Given the economic significance of this industry in the Caribbean, the local evidence provided by this study will help to effectively counteract interference by the tobacco industry and advance towards a smoke-free Caribbean.

RESUMEN Objetivo. Evaluar si la introducción de una legislación integral sobre ambientes libres de humo tuvo algún efecto sobre el turismo en cuatro países de la Comunidad del Caribe (CARICOM): Barbados, Guyana, Jamaica y Trinidad y Tobago. Métodos. Comparamos la evolución de tres variables turísticas (llegada de turistas, gasto de los turistas y duración promedio de la estancia) en un país que ha establecido entornos libres de humo de tabaco (país tratado) con la evolución de estas variables en el mismo país si no se hubiera adoptado una legislación sobre ambientes libres de humo. Se empleó un método de control sintético para recrear este escenario contrafáctico mediante la construcción de un país sintético utilizando un promedio ponderado de varios países del grupo de donantes de CARICOM que no habían introducido una legislación relativa a entornos libres de humo durante el período analizado. Se cuantificó el efecto de los entornos libres de humo de tabaco sobre el turismo como la diferencia entre las variables turísticas en el país tratado y el sintético. Para evaluar si el efecto estimado de los entornos libres de humo fue estadísticamente significativo, se compararon los efectos de la legislación en el país tratado con los efectos placebo en el grupo de donantes mediante la suposición de que se hubiese introducido una legislación integral sobre ambientes libre de humo en el mismo año que en el país tratado. Resultados. La implementación de entornos sin humo de tabaco no tuvo ningún efecto en la llegada de turistas, el gasto de los turistas o la duración promedio de la estancia en los cuatro países. Conclusiones. Nuestros hallazgos ofrecen una prueba sólida de que las políticas públicas que prohíben fumar en lugares públicos no afectan a las empresas de hospitalidad y turismo. Dada la importancia económica de esta industria en el Caribe, la evidencia local proporcionada por este estudio ayudará a contrarrestar eficazmente la interferencia de la industria tabacalera y avanzar hacia una Comunidad del Caribe libre de humo de tabaco.

RESUMO Objetivo. Avaliar se a promulgação de uma lei antifumo abrangente afetou o turismo em quatro países da Comunidade do Caribe (CARICOM), a saber: Barbados, Guiana, Jamaica e Trinidad e Tobago. Métodos. Comparamos a evolução de três variáveis relacionadas ao turismo (desembarque de turistas, despesas de turistas e duração média da estadia) em um país que havia implementado ambientes livres de fumo (país tratado) com a evolução dessas variáveis no mesmo país se a lei antifumo não tivesse sido implementada. Usamos um método de controle sintético para recriar esse contrafactual, construindo um país sintético usando uma média ponderada de vários países doadores da CARICOM que não promulgaram leis sobre ambientes livres de fumaça durante o período analisado. Quantificamos o efeito dos ambientes livres de fumo no turismo como a diferença entre as variáveis de turismo no país tratado e no país sintético. Para avaliar se o efeito estimado dos ambientes livres de fumo foi resultado do acaso, comparamos os efeitos da legislação do país tratado com os efeitos placebo no grupo de doadores, supondo que uma lei antifumo abrangente havia sido promulgada no mesmo ano que no país tratado. Resultados. A implementação de ambientes livres de fumo não afetou o desembarque de turistas, as despesas de turistas ou a duração média da estadia nos quatro países. Conclusões. Nossas constatações fornecem evidências robustas de que as políticas públicas que proíbem o fumo em locais públicos não afetam o setor de hospitalidade e turismo. Considerando a importância econômica desta indústria para o Caribe, as evidências locais fornecidas por este estudo ajudarão a combater efetivamente a interferência da indústria do tabaco e a avançar rumo a um Caribe livre do fumo.

Antibody Protection against Long-Term Memory Loss Induced by Monomeric C-Reactive Protein in a Mouse Model of Dementia.

Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer's disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk.

Monomeric C-Reactive Protein Localized in the Cerebral Tissue of Damaged Vascular Brain Regions Is Associated With Neuro-Inflammation and Neurodegeneration-An Immunohistochemical Study.

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and ß-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1ß) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury.

Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation.

BACKGROUND: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel to or appear at other locations within the brain that might account for later chronic neuroinflammatory or neurodegenerative effects. METHODS: Immunohistochemistry was performed on Formalin-fixed, paraffin-embedded archived brain tissue blocks obtained at autopsy from stroke patients and age-matched controls. We modelled mCRP migration into the brain after haemorrhagic stroke by infusing mCRP (3.5 µg) into the hippocampus of mice and localized mCRP with histological and immunohistochemistry methods. RESULTS: On human tissue in the early stages of haemorrhage, there was no staining of mCRP. However, with increasing post-stroke survival time, mCRP immunostaining was associated with some parenchymal brain cells, some stroke-affected neurons in the surrounding areas and the lumen of large blood vessels as well as brain capillaries. Further from the peri-haematoma region, however, mCRP was detected in the lumen of micro-vessels expressing aquaporin 4 (AQP4). In the hypothalamus, we detected clusters of neurons loaded with mCRP along with scattered lipofuscin-like deposits. In the peri-haematoma region of patients, mCRP was abundantly seen adjacent to AQP4 immunoreactivity. When we stereotactically injected mCRP into the hippocampus of mice, we also observed strong expression in distant neurones of the hypothalamus as well as cortical capillaries. CONCLUSIONS: mCRP is abundantly expressed in the brain after haemorrhagic stroke, directly impacting the pathophysiological development of the haematoma. In addition, it may have indirect effects, where the microcirculatory system appears to be able to carry it throughout the cortex as far as the hypothalamus, allowing for long-distance effects and damage through its capacity to induce inflammation and degenerate neuronal perivascular compartments.

Microglial Hyperreactivity Evolved to Immunosuppression in the Hippocampus of a Mouse Model of Accelerated Aging and Alzheimer's Disease Traits.

Neuroinflammation is a risk factor for Alzheimer's disease (AD). We sought to study the glial derangement in AD using diverse experimental models and human brain tissue. Besides classical pro-inflammatory cytokines, we analyzed chitinase 3 like 1 (CHI3L1 or YKL40) and triggering receptor expressed on myeloid cells 2 (TREM2) that are increasingly being associated with astrogliosis and microgliosis in AD, respectively. The SAMP8 mouse model of accelerated aging and AD traits showed elevated pro-inflammatory cytokines and activated microglia phenotype. Furthermore, 6-month-old SAMP8 showed an exacerbated inflammatory response to peripheral lipopolysaccharide in the hippocampus and null responsiveness at the advanced age (for this strain) of 12 months. Gene expression of TREM2 was increased in the hippocampus of transgenic 5XFAD mice and in the cingulate cortex of autosomal dominant AD patients, and to a lesser extent in aged SAMP8 mice and sporadic early-onset AD patients. However, gene expression of CHI3L1 was increased in mice but not in human AD brain samples. The results support the relevance of microglia activation in the pathways leading to neurodegeneration and suggest diverse neuroinflammatory responses according to the AD process. Therefore, the SAMP8 mouse model with marked alterations in the dynamics of microglia activation and senescence may provide a complementary approach to transgenic mouse models for the study of the neuroinflammatory mechanisms underlying AD risk and progression.

HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders.

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated in vivo. In C. elegans, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies.

Premature Mortality from Cardiovascular Disease in the Americas - Will the Goal of a Decline of "25% by 2025" be Met?

BACKGROUND: Cardiovascular diseases (CVD) are the underlying cause 1.6 million deaths per year in the Americas, accounting for 30% of total mortality and 38% of by non-communicable deaths diseases (NCDs). A 25% reduction in premature mortality due four main NCDs was targeted by the 2011 High-level Meeting of the General Assembly on the Prevention and Control of NCDs. While overall CVD mortality fell in the Americas during the past decade, trends in premature CVD mortality during the same period have not been described, particularly in the countries of Latin America and the Caribbean. METHODS: This is a population-based trend-series study based on a total of 6,133,666 deaths to describe the trends and characteristics of premature mortality due to CVD and to estimates of the average annual percentage of change during the period 2000-2010 in the Americas. FINDINGS: Premature mortality due to CVD in the Americas fell by 21% in the period 2000-2010 with a -2.5% average annual rate of change in the last 5 year-a statistically significant reduction of mortality-. Mortality from ischemic diseases, declined by 25% - 24% among men and 26% among women. Cerebrovascular diseases declined by 27% -26% among men and 28% among women. Guyana, Trinidad and Tobago, the Dominican Republic, Bahamas, and Brazil had CVD premature mortality rates over 200 per 100,000 population, while the average for the Region was 132.7. US and Canada will meet the 25% reduction target before 2025. Mexico, Costa Rica, Venezuela, Dominican Republic, Panama, Guyana, and El Salvador did not significantly reduce premature mortality among men and Guyana, the Dominican Republic, and Panama did not achieve the required annual reduction in women. CONCLUSIONS: Trends in premature mortality due to CVD observed in last decade in the Americas would indicate that if these trends continue, the Region as a whole and a majority of its countries will be able to reach the goal of a 25% relative reduction in premature mortality even before 2025.

Predicting the Development of Tuberculosis with the Tuberculin Skin Test and QuantiFERON Testing.

RATIONALE: The identification of patients with latent tuberculosis infection, who are at higher risk to develop active disease, is an important component of disease control. OBJECTIVES: We aim to compare the usefulness of the QuantiFERON-TB Gold in-tube assay and the tuberculin skin test to predict the development of active tuberculosis during follow-up, using positive and negative predictive values, positive likelihood ratios, and stratified level of risk. METHODS: The study included contacts of tuberculosis cases diagnosed between 2007 and 2009. All contacts included were from the first circle of exposure. Tuberculin skin test and QuantiFERON test were performed and a chest radiograph was obtained during the contact's study. MEASUREMENTS AND MAIN RESULTS: A total of 1,335 contacts were followed up for 4 years: a smear-positive index case was identified for 937 contacts, of whom 15 developed active tuberculosis and had initially presented with positive tuberculin skin test/QuantiFERON results, a normal chest radiograph, and no symptoms. The positive predictive value was 4% for QuantiFERON and 2% for the tuberculin skin test (when ≥5 mm). The probability of developing active disease was 2.36 times higher with a positive QuantiFERON, and 1.3 times higher with a positive tuberculin skin test. The positive predictive value was 17%, and the positive likelihood ratio was 7.53 for untreated contacts with a positive QuantiFERON. Stratifying according to initial QuantiFERON results showed a 6.36 times higher risk of developing active tuberculosis for patients with a QuantiFERON result greater than or equal to 10 IU/ml. Among bacillus Calmette-Guérin-vaccinated patients, a tuberculin skin test induration greater than or equal to 15 mm correlated better with a positive QuantiFERON. CONCLUSIONS: QuantiFERON results were more accurate than tuberculin skin test results in predicting tuberculosis. Although all contacts with QuantiFERON-positive results are at risk of developing tuberculosis, those with a tuberculin skin test induration greater than or equal to 15 mm and QuantiFERON greater than or equal to 10 IU/ml are at highest risk. This has important implications in the clinical management of tuberculosis contacts.

Cervical and female breast cancers in the Americas: current situation and opportunities for action.

OBJECTIVE: To understand better the current regional situation and public health response to cervical cancer and female breast cancer in the Americas. METHODS: Data on cervical cancer and female breast cancers in 33 countries, for the period from 2000 to the last year with available data, were extracted from the Pan American Health Organization (PAHO) Regional Mortality Database and analysed. Changes in mortality rates over the study period - in all countries except those with small populations and large fluctuations in time-series mortality data - were calculated using Poisson regression models. Information from the PAHO Country Capacity Survey on noncommunicable diseases was also analysed. FINDINGS: The Bahamas, Trinidad and Tobago and Uruguay showed relatively high rates of death from breast cancer, whereas the three highest rates of death from cervical cancer were observed in El Salvador, Nicaragua and Paraguay. Several countries - particularly Paraguay and Venezuela - have high rates of death from both types of cancer. Although mortality from cervical cancer has generally been decreasing in the Americas, decreases in mortality from breast cancer have only been observed in a few countries in the Region of the Americas. All but one of the 25 countries in the Americas included in the PAHO Country Capacity Survey reported having public health services for the screening and treatment of breast and cervical cancers. CONCLUSION: Most countries in the Americas have the public health capacity needed to screen for - and treat - breast and cervical cancers and, therefore, the potential to reduce the burden posed by these cancers.

Genital human papillomaviruses among women of reproductive age in Jamaica.

OBJECTIVE: To characterize the prevalence and distribution of genital human papillomavirus (HPV) types among women in Jamaica, and to explore risk factors associated with HPV infection. METHODS: This was a cross-sectional study that took place in April-July 2010 with 852 sexually-active women, 16-49 years of age, who had attended a selected public or private primary health clinic in one of Jamaica's four health authority regions. Sociodemographic data was collected from each participant by trained study staff. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the Research Use Only Linear Array (LA) genotyping assay (Roche Diagnostics Corp., Indianapolis, Indiana, United States). Overall and type-specific prevalence of HPV infection was calculated for 37 HPV types included in the LA genotyping assay. RESULTS: HPV DNA was detected in 460 of the 852 women (54.0%). Oncogenic HPV was detected in 297 women (34.9%) and HPV types 16/18 were found in 86 women (10.1%). The most frequently occurring HPV types were: 16 (6.2%); 35 (6.0%); 62 and 83 (5.5%); 61 and 58 (5.4%); 84 (4.7%); 18 (4.3%); and, 66 and 81 (4.2%). HPV prevalence was highest among women who were single, young (16-19 years), and had had more than three sexual partners in their lifetime. CONCLUSIONS: These results, coupled with high rates of cervical cancer, support introducing HPV vaccines while maintaining and strengthening cervical cancer screening services. Policy decision-making that reflects these results is instrumental to establishing a comprehensive cervical cancer program in Jamaica.

Genital human papillomaviruses among women of reproductive age in Jamaica / Virus de los papilomas humanos genitales en mujeres en edad reproductiva de Jamaica

OBJECTIVE: To characterize the prevalence and distribution of genital human papillomavirus (HPV) types among women in Jamaica, and to explore risk factors associated with HPV infection. METHODS: This was a cross-sectional study that took place in April-July 2010 with 852 sexually-active women, 16-49 years of age, who had attended a selected public or private primary health clinic in one of Jamaica's four health authority regions. Sociodemographic data was collected from each participant by trained study staff. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the Research Use Only Linear Array (LA) genotyping assay (Roche Diagnostics Corp., Indianapolis, Indiana, United States). Overall and type-specific prevalence of HPV infection was calculated for 37 HPV types included in the LA genotyping assay. RESULTS: HPV DNA was detected in 460 of the 852 women (54.0%). Oncogenic HPV was detected in 297 women (34.9%) and HPV types 16/18 were found in 86 women (10.1%). The most frequently occurring HPV types were: 16 (6.2%); 35 (6.0%); 62 and 83 (5.5%); 61 and 58 (5.4%); 84 (4.7%); 18 (4.3%); and, 66 and 81 (4.2%). HPV prevalence was highest among women who were single, young (16-19 years), and had had more than three sexual partners in their lifetime. CONCLUSIONS: These results, coupled with high rates of cervical cancer, support introducing HPV vaccines while maintaining and strengthening cervical cancer screening services. Policy decisionmaking that reflects these results is instrumental to establishing a comprehensive cervical cancer program in Jamaica.

OBJETIVO: Determinar la prevalencia y la distribución de los tipos de virus de los papilomas humanos (VPH) genitales en las mujeres de Jamaica y explorar los factores de riesgo asociados con la infección por VPH. MÉTODOS: Este estudio transversal se llevó a cabo de abril a julio del 2010. Participaron 852 mujeres sexualmente activas, de 16 a 49 años de edad, que acudieron a uno de los consultorios públicos o privados de atención primaria seleccionados en cada una de las cuatro autoridades sanitarias regionales de Jamaica. Personal capacitado del estudio recopiló datos sociodemográficos de cada participante. Todas las participantes fueron sometidas a un examen ginecológico que comprendía una prueba clínica de Papanicolaou y la obtención de una muestra del cuello uterino a efectos de detectar y tipificarlos VPH mediante la prueba de genotipado Linear Array (LA) (Roche Diagnostics Corp., Indianápolis, Indiana, Estados Unidos), de uso exclusivo en investigación. Se calcularon las prevalencias global y específica de tipo de la infección por VPH para los 37 tipos de VPH incluidos en la prueba de genotipado LA. RESULTADOS: Se detectó ADN de VPH en 460 de las 852 mujeres (54,0%). Se detectaron VPH oncógenos en 297 mujeres (34,9%), y VPH de los tipos 16 y 18 en 86 mujeres (10,1%). Los tipos de VPH detectados con mayor frecuencia fueron 16 (6,2%), 35 (6,0%), 62 y 83 (5,5%), 61 y 58 (5,4%), 84 (4,7%), 18 (4,3%), y 66 y 81 (4,2%). La prevalencia de VPH fue más elevada en mujeres solteras, jóvenes (de 16 a 19 años) y que habían tenido más de tres compañeros sexuales en sus vidas. CONCLUSIONES: Estos resultados, junto a las elevadas tasas de cáncer cervicouterino, fundamentan la introducción de las vacunas contra el VPH al tiempo que se mantienen y refuerzan los servicios de tamizaje del cáncer cervicouterino. Las decisiones políticas que se adopten como consecuencia de estos resultados serán determinantes para establecer un programa integral contra el cáncer cervicouterino en Jamaica.

Complications in immediate breast reconstruction after mastectomy.

OBJECTIVES: Immediate post-mastectomy breast reconstruction (IBR) is a procedure that has proven advantages, but it also entails risks. The aim of this study was to identify risk factors for reconstruction failure. METHODS: A review was made of all the IBR carried out at a general hospital from 2002 to 2009. Retrospective information was obtained about postoperative complications and the characteristics of patients and treatments applied. The minimum follow-up period was 9 months. Cox's regression analysis was performed on the variables related to the reconstruction failure requiring the removal of the prosthesis, with an explanatory model in which all the study variables were introduced and a predictive model that contained only the variables known before the intervention. RESULTS: A total of 115 IRB interventions carried out on 112 women with breast cancer were analyzed. The mean follow-up period was 25.5 months. In sixty cases (52.2 percent), there were no complications; in sixteen cases (13.9 percent) minor complications appeared, and in 39 (33.9 percent) the complications were moderate. In twenty-six cases (22.6 percent), a reconstruction failure occurred. Cox's regression model revealed that the reconstruction failures were related to the patient's age (Hazard Ratio 1.08), to neoadjuvant chemotherapy (HR 6.24) and to postoperative tamoxifen (HR 3.10). The predictive model included the age of the patient (HR 1.05) and the use of neoadjuvant chemotherapy (HR 5.11). CONCLUSIONS: A significant proportion of the patients receiving IBR developed reconstruction failure. Multivariate analysis identified three variables related to this complication, two of which were known before the intervention.