The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression.

Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons' firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons' activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons' activity may provide a valuable tool to improve melanoma patients' outcomes.

Serological Testing for COVID-19, Immunological Surveillance, and Exploration of Protective Antibodies.

Serological testing is a powerful tool in epidemiological studies for understanding viral circulation and assessing the effectiveness of virus control measures, as is the case of SARS-CoV-2, the pathogenic agent of COVID-19. Immunoassays can quantitatively reveal the concentration of antiviral antibodies. The assessment of antiviral antibody titers may provide information on virus exposure, and changes in IgG levels are also indicative of a reduction in viral circulation. In this work, we describe a serological study for the evaluation of antiviral IgG and IgM antibodies and their correlation with antiviral activity. The serological assay for IgG detection used two SARS-CoV-2 proteins as antigens, the nucleocapsid N protein and the 3CL protease. Cross-reactivity tests in animals have shown high selectivity for detection of antiviral antibodies, using both the N and 3CL antigens. Using samples of human serum from individuals previously diagnosed by PCR for COVID-19, we observed high sensitivity of the ELISA assay. Serological results with human samples also suggest that the combination of higher titers of antiviral IgG antibodies to different antigen targets may be associated with greater neutralization activity, which can be enhanced in the presence of antiviral IgM antibodies.

Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis.

Different body systems (epidermis, respiratory tract, cornea, oral cavity, and gastrointestinal tract) are in continuous direct contact with innocuous and/or potentially harmful external agents, exhibiting dynamic and highly selective interaction throughout the epithelia, which function as both a physical and chemical protective barrier. Resident immune cells in the epithelia are constantly challenged and must distinguish among antigens that must be either tolerated or those to which a response must be mounted for. When such a decision begins to take place in lymphoid foci and/or mucosa-associated lymphoid tissues, the epithelia network of immune surveillance actively dominates both oral and gastrointestinal compartments, which are thought to operate in the same immune continuum. However, anatomical variations clearly differentiate immune processes in both the mouth and gastrointestinal tract that demonstrate a wide array of independent immune responses. From single vs. multiple epithelia cell layers, widespread cell-to-cell junction types, microbial-associated recognition receptors, dendritic cell function as well as related signaling, the objective of this review is to specifically contrast the current knowledge of oral versus gut immune niches in the context of epithelia/lymphoid foci/MALT local immunity and systemic output. Related differences in 1) anatomy 2) cell-to-cell communication 3) antigen capture/processing/presentation 4) signaling in regulatory vs. proinflammatory responses and 5) systemic output consequences and its relations to disease pathogenesis are discussed.

Vigilância das pneumonias e meningites bacterianas em crianças menores de 5 anos. Guia prático. Segunda edição

O Manual de Vigilância de Pneumonia Bacteriana e Meningite em Menores de 5 anos: Guia Prático tornou-se referência de destaque para os profissionais de saúde da Região das Américas que lidam com atividades de vigilância epidemiológica. Abrange doenças, principais agentes etiológicos, vacinas disponíveis, procedimentos laboratoriais e de vigilância para captura e monitoramento de casos, bem como análise de dados para a produção de informações relevantes. Esta segunda edição introduz novos conceitos e procedimentos de atualização para refletir a introdução de testes de biologia molecular em diagnósticos laboratoriais e a disponibilidade de novas vacinas.

Yin-Yang-1 decreases Fas-induced apoptosis in acute lymphoblastic leukemia under hypoxic conditions: its implications in immune evasion / YY1 induce la disminución de la apoptosis a través de Fas en la leucemia linfoblástica aguda en condiciones hipóxicas: implicaciones en la evasión de la respuesta inmunitaria

Abstract Background: Acute lymphoblastic leukemia (ALL) is an aggressive malignant disease with high prevalence in pediatric patients. It has been shown that the downregulation of Fas expression is correlated with an inadequate response in ALL, although these mechanisms are still not well understood. Several reports demonstrated that hypoxia is involved in dysfunctional apoptosis. Yin-Yang-1 (YY1) transcription factor is involved in resistance to apoptosis, tumor progression, and it is increased in different types of cancer, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood, but it is known that YY1 negatively regulates Fas expression. The study aimed to evaluate the effect of YY1 on Fas expression under hypoxic conditions in ALL. Methods: Leukemia cell line RS4; 11 was cultured under normoxic and hypoxic conditions. YY1, Fas receptor, and hypoxia-inducible factor (HIF-1α) expression were analyzed. After treatment with a Fas agonist (DX2), apoptosis was analyzed through the detection of active caspase 3. Data were analyzed using Pearson’s correlation. Results: Leukemia cells co-expressed both HIF-1α and YY1 under hypoxia, which correlated with a downregulation of Fas expression. During hypoxia, the levels of apoptosis diminished after DX2 treatment. The analysis revealed that patients with high levels of HIF-1α also express high levels of YY1 and low levels of Fas. Conclusions: These results suggest that YY1 negatively regulates the expression of the Fas receptor, which could be involved in the escape of leukemic cells from the immune response contributing to the ALL pathogenesis.

Resumen Introducción: La leucemia linfoblástica aguda (LLA) es una enfermedad con alta prevalencia en la población pediátrica. El mecanismo por el cual el receptor de Fas participa en la regulación inmunitaria en los tumores es desconocido, pero se sabe que está subexpresado en LLA. El factor de transcripción Ying-Yang-1 (YY1) está involucrado en la resistencia a la apoptosis y la progresión tumoral; se encuentra aumentado en diferentes tumores, incluida la LLA. Aunque los mecanismos que regulan la expresión de YY1 en LLA son desconocidos, se sabe que YY1 regula la expresión del receptor de Fas. El objetivo de este trabajo fue evaluar el efecto de YY1 en la expresión de Fas en condiciones de hipoxia en la LLA. Métodos: Se cultivaron células RS4;11 en condiciones de hipoxia y se analizó la expresión de YY1, receptor de Fas y HIF-1α. La apoptosis fue inducida usando un agonista de Fas (DX2) y se analizó con la detección de caspasa 3 activa. Los datos se analizaron mediante correlación de Pearson. Resultados: Las células RS4;11 coexpresaron HIF-1αy YY1 en hipoxia, lo cual correlaciona con una baja expresión de Fas. La apoptosis se encontró disminuida durante condiciones de hipoxia, después del tratamiento con DX2. El análisis bioinformático mostró que los pacientes con altos niveles de HIF-1αpresentan YY1 elevado y bajos niveles del receptor de Fas. Conclusiones: Estos resultados sugieren que YY1 regula negativamente la expresión del receptor de Fas, lo cual podría estar involucrado en el escape de las células leucémicas a la respuesta inmunitaria, contribuyendo a la patogénesis de la LLA.

Yin-Yang-1 decreases Fas-induced apoptosis in acute lymphoblastic leukemia under hypoxic conditions: its implications in immune evasion.

Background: Acute lymphoblastic leukemia (ALL) is an aggressive malignant disease with high prevalence in pediatric patients. It has been shown that the downregulation of Fas expression is correlated with an inadequate response in ALL, although these mechanisms are still not well understood. Several reports demonstrated that hypoxia is involved in dysfunctional apoptosis. Yin-Yang-1 (YY1) transcription factor is involved in resistance to apoptosis, tumor progression, and it is increased in different types of cancer, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood, but it is known that YY1 negatively regulates Fas expression. The study aimed to evaluate the effect of YY1 on Fas expression under hypoxic conditions in ALL. Methods: Leukemia cell line RS4; 11 was cultured under normoxic and hypoxic conditions. YY1, Fas receptor, and hypoxia-inducible factor (HIF-1α) expression were analyzed. After treatment with a Fas agonist (DX2), apoptosis was analyzed through the detection of active caspase 3. Data were analyzed using Pearson's correlation. Results: Leukemia cells co-expressed both HIF-1α and YY1 under hypoxia, which correlated with a downregulation of Fas expression. During hypoxia, the levels of apoptosis diminished after DX2 treatment. The analysis revealed that patients with high levels of HIF-1α also express high levels of YY1 and low levels of Fas. Conclusions: These results suggest that YY1 negatively regulates the expression of the Fas receptor, which could be involved in the escape of leukemic cells from the immune response contributing to the ALL pathogenesis.

Introducción: La leucemia linfoblástica aguda (LLA) es una enfermedad con alta prevalencia en la población pediátrica. El mecanismo por el cual el receptor de Fas participa en la regulación inmunitaria en los tumores es desconocido, pero se sabe que está subexpresado en LLA. El factor de transcripción Ying-Yang-1 (YY1) está involucrado en la resistencia a la apoptosis y la progresión tumoral; se encuentra aumentado en diferentes tumores, incluida la LLA. Aunque los mecanismos que regulan la expresión de YY1 en LLA son desconocidos, se sabe que YY1 regula la expresión del receptor de Fas. El objetivo de este trabajo fue evaluar el efecto de YY1 en la expresión de Fas en condiciones de hipoxia en la LLA. Métodos: Se cultivaron células RS4;11 en condiciones de hipoxia y se analizó la expresión de YY1, receptor de Fas y HIF-1α. La apoptosis fue inducida usando un agonista de Fas (DX2) y se analizó con la detección de caspasa 3 activa. Los datos se analizaron mediante correlación de Pearson. Resultados: Las células RS4;11 coexpresaron HIF-1αy YY1 en hipoxia, lo cual correlaciona con una baja expresión de Fas. La apoptosis se encontró disminuida durante condiciones de hipoxia, después del tratamiento con DX2. El análisis bioinformático mostró que los pacientes con altos niveles de HIF-1αpresentan YY1 elevado y bajos niveles del receptor de Fas. Conclusiones: Estos resultados sugieren que YY1 regula negativamente la expresión del receptor de Fas, lo cual podría estar involucrado en el escape de las células leucémicas a la respuesta inmunitaria, contribuyendo a la patogénesis de la LLA.

Vigilancia de las neumonías y meningitis bacterianas en menores de 5 años. Guía práctica, segunda edición

El manual de Vigilancia de las neumonías y meningitis bacterianas en menores de 5 años: guía práctica se ha convertido en una referencia destacada para los profesionales de salud de la Región de las Américas que se ocupan de las actividades de vigilancia epidemiológica. En él se tratan las enfermedades, los principales agentes etiológicos, las vacunas disponibles, los procedimientos de laboratorio y de vigilancia para la captación y el seguimiento de los casos, así como el análisis de los datos para la producción de información pertinente. En esta segunda edición se presentan nuevos conceptos y se actualizan los procedimientos con el propósito de reflejar la introducción de pruebas de biología molecular en el diagnóstico por laboratorio y la disponibilidad de nuevas vacunas.

Is there a role played by HLA-E, if any, in HPV immune evasion?

Cervical cancer incidence worldwide exceeds half a million new cases per year. The human papillomavirus (HPV) being the major causative agent of CC uses a variety of strategies to evade immune surveillance, where the immune status varies amongst individuals. This immune evasion altered by HPV is reflected in persistent infections, causing the evolution of cervical neoplasia. The role of the immune system in viral recognition and elimination is of extreme relevance in the development of CC. The interactions of the HLA-E ligand in the target cell along with CD94/NKG2 receptors, which are expressed predominantly, but not exclusively, on NK cells' surface, are responsible for activating or inhibiting cytotoxic activity according to their function. The engagement between HLA-E and CD94/NKG2 molecules is one of the fundamental surveillance mechanisms in patients with CIN I, II and III, where HLA-E expression increases significantly, especially in HPV 16 and 18 infections. Higher HLA-E expression was observed in most histopathological types of CC, and at the same time was correlated to best survival of the patient. This review aims to summarize and discuss the immunological role of HLA-E in the context of HPV infection and immune system evasion, and the oncogenic process of cervical cancer.

Cervical Cancer Cells Express Markers Associated with Immunosurveillance.

Cervical cancer is the second most frequent cancer in women in Mexico, and its development depends on the presence of human papillomaviruses in the uterine cervix. These oncogenic viruses transform cells where the control over cell cycle disappears, and the capacity to induce apoptosis is absent. On the other hand, some mutations confer to the transformed cells the ability to evade recognition by the immune system. The expression of markers of the immune system such as CD95, MICA/B, CD39, CD73, NKp30, NKp46, CD44, CD24, NKG2A, and CTLA-4 was analysed by flow cytometry on cervical cancer cells INBL (HPV 18, stage IVB), HeLa (HPV 18), CaSki (HPV 16), and C33A (HPV-). Our results showed the presence of atypical markers on cervical cancer cells; some of them are molecules involved in tumour cell recognition such as MICA/B and CD95. Other markers associated with immune system escape, such as CD39, CD73, and CTLA-4, were also present. Furthermore, we found that some cervical cancer cells expressed typical markers of NK cells like NKp30, NKp46, NKG2A, and KIR3DL1. It is not clear whether these molecules confer any gain to the tumour cells or if they represent a disadvantage, but we hypothesise that these molecules that are present in cervical cancer cells allow them to mimic in front of the immune system.

From the "missing self" hypothesis to adaptive NK cells: Insights of NK cell-mediated effector functions in immune surveillance.

The original discovery of NK cells approximately 40 yr ago was based on their unique capability to kill tumor cells without prior sensitization or priming, a process named natural cytotoxicity. Since then, several studies have documented that NK cells can kill hematopoietic and nonhematopoietic cancer cells. NK cells also recognize and kill cells that have undergone viral infections. Besides natural cytotoxicity, NK cells are also major effectors of antibody-dependent cell cytotoxicity (ADCC). Therefore, NK cells are well "armed" to recognize and mount immune responses against "insults" that result from cell transformation and viral infections. Because of these attributes, an essential role of NK cells in tumor surveillance was noted. Indeed, several studies have shown a correlation between impaired NK cell cytotoxicity and a higher risk of developing cancer. This evidence led to the idea that cancer initiation and progress is intimately related to an abnormal or misdirected immune response. Whereas all these ideas remain current, it is also true that NK cells represent a heterogeneous population with different abilities to secrete cytokines and to mediate cytotoxic functions. In addition, recent data has shown that NK cells are prone to suffer epigenetic modifications resulting in the acquisition of previously unrecognized attributes such as memory and long-term survival. Such NK cells, referred as "adaptive" or "memory-like," also display effector functions that are not necessarily equal to those observed in conventional NK cells. Given the new evidence available, it is essential to discuss the conceptual reasoning and misconceptions regarding the role of NK cells in immune surveillance and immunotherapy.

CRTAM+ NK cells endowed with suppressor properties arise in leukemic bone marrow.

Due to their increasing rates of morbidity and mortality, childhood malignancies are considered a global health priority, with acute lymphoblastic leukemias (ALLs) showing the highest incidence worldwide. Control of malignant clone emergence and the subsequent normal-leukemic hematopoietic cell out-competition require antitumor monitoring mechanisms. Investigation of cancer surveillance innate cells may be critical to understand the mechanisms contributing in either disease progression or relapse, and to promote displacement of leukemic hematopoiesis by the normal counterpart. We report here that NK cell production is less and low hematopoietic progenitor numbers contribute to this defect. By investigating the expression of the activation molecule class I restricted T-cell associated molecule (CRTAM) along the hematopoietic lineage differentiation pathway, we have identified lymphoid precursor populations coexpressing CD34, CD56/CD3/CD19, and CRTAM as the earliest developmental stage where activation may take place in specialized niches that display the ligand nectin-like-2. Of note, bone marrow (BM) from patients with ALL revealed high contents of preactivated CD56high NK cells expressing CRTAM and endowed with an exhaustion-like phenotype and the functional capability of producing IL-10 and TGF-ß in vitro. Our findings suggest, for the first time, that the tumor microenvironment in ALL directly contribute to exhaustion of NK cell functions by the CRTAM/Necl-2 interaction, and that the potential regulatory role of exhausted-like NK cells may favor malignant progression at the expense of anti-tumor responses. Phenotypic and functional identity of this unique suppressor-like NK cell population within the leukemic BM would be of special interest for the pathobiology of ALL and development of targeting strategies.

Peripheral Inflammation Regulates CNS Immune Surveillance Through the Recruitment of Inflammatory Monocytes Upon Systemic α-Synuclein Administration.

Innate immune activation and chronic neuroinflammation are characteristic features of many neurodegenerative diseases including Parkinson's disease (PD) and may contribute to the pathophysiology of the disease. The discovery of misfolded alpha-synuclein (αSYN) protein aggregates, which amplify in a "prion-like" fashion, has led us to consider that pathogenic αSYN might be hijacking the activation and mobilization mechanism of the peripheral immune system to reach and disseminate within the CNS. Furthermore, our lab and other groups have recently shown that αSYN can adopt distinct fibril conformations or "strains" with varying levels of pathogenic impact. Therefore, the aim of this study was to assess the impact of peripheral inflammation on αSYN spreading in order to better understand the participation of the immune system in the progression of PD. The results presented here show that intraperitoneal LPS injection prior to systemic intravenous recombinant administration of two different αSYN pathogenic strains (fibrils or ribbons) in wild type mice, induces an increase in brain resident microglia and promotes the recruitment of leukocytes toward the brain and the spinal cord. Our findings show for the first time that αSYN can be internalized by LPS-primed inflammatory monocytes, which in turn favors the dissemination from the periphery toward the brain and spinal cord. Further, we found a differential recruitment of CD4+ and CD8+ T cells after LPS priming and subsequent administration of the αSYN ribbons strain. Together, these data argue for a role of the peripheral immune system in αSYN pathology.

New Insights Into the Role of Qa-2 and HLA-G Non-classical MHC-I Complexes in Malignancy.

It is well established that the immune system can identify and destroy neoplastic transformed cells in a process known as immunosurveillance. Most studies have focused on the classical major histocompatibility complex (MHC) class Ia molecules, which are known to play an important role on the presentation of tumor antigens to the immune system in order to activate a response against tumor cells. However, a larger family of non-classical MHC class Ib-related molecules has received less attention. In this mini-review, we discuss the role of class Ib murine Qa-2 and its proposed human HLA-G homolog on immunosurveillance during embryogenesis and cancer. Whereas, both HLA-G and Qa-2 are involved in immune tolerance in pregnancy, the current evidence suggests that they play opposite roles in cancer. HLA-G appears to promote tumor progression while Qa-2 acts as a tumor suppressor awaking the immune system to reject tumor cells, as suggested by studies on different cancer cell models, such as melanoma, lymphoma, lung carcinoma, and our own results in mammary carcinoma.

When and how NK cell-induced programmed cell death benefits immunological protection against intracellular pathogen infection.

NK cells are innate lymphoid cells that exert a key role in immune surveillance through the recognition and elimination of transformed cells and viral, bacterial, and protozoan pathogen-infected cells without prior sensitization. Elucidating when and how NK cell-induced intracellular microbial cell death functions in the resolution of infection and host inflammation has been an important topic of investigation. NK cell activation requires the engagement of specific activating, co-stimulatory, and inhibitory receptors which control positively and negatively their differentiation, memory, and exhaustion. NK cells secrete diverse cytokines, including IFN-γ, TNF-α/ß, CD95/FasL, and TRAIL, as well as cytoplasmic cytotoxic granules containing perforin, granulysin, and granzymes A and B. Paradoxically, NK cells also kill other immune cells like macrophages, dendritic cells, and hyper-activated T cells, thus turning off self-immune reactions. Here we first provide an overview of NK cell biology, and then we describe and discuss the life-death signals that connect the microbial pathogen sensors to the inflammasomes and finally to cell death signaling pathways. We focus on caspase-mediated cell death by apoptosis and pro-inflammatory and non-caspase-mediated cell death by necroptosis, as well as inflammasome- and caspase-mediated pyroptosis.

Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes.

High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes-individually or epistatically-were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies.

Eco-epidemiological analysis of rickettsial seropositivity in rural areas of Colombia: A multilevel approach.

Rickettsiosis is a re-emergent infectious disease without epidemiological surveillance in Colombia. This disease is generally undiagnosed and several deadly outbreaks have been reported in the country in the last decade. The aim of this study is to analyze the eco-epidemiological aspects of rickettsial seropositivity in rural areas of Colombia where outbreaks of the disease were previously reported. A cross-sectional study, which included 597 people living in 246 households from nine hamlets in two municipalities of Colombia, was conducted from November 2015 to January 2016. The survey was conducted to collect sociodemographic and household characteristics (exposure) data. Blood samples were collected to determine the rickettsial seropositivity in humans, horses and dogs (IFA, cut-off = 1/128). In addition, infections by rickettsiae were detected in ticks from humans and animals by real-time PCR targeting gltA and ompA genes. Data was analyzed by weighted multilevel clog-log regression model using three levels (person, household and hamlets) and rickettsial seropositivity in humans was the main outcome. Overall prevalence of rickettsial seropositivity in humans was 25.62% (95%CI 22.11-29.12). Age in years (PR = 1.01 95%CI 1.01-1.02) and male sex (PR = 1.65 95%CI 1.43-1.90) were risk markers for rickettsial seropositivity. Working outdoors (PR = 1.20 95%CI 1.02-1.41), deforestation and forest fragmentation for agriculture use (PR = 1.75 95%CI 1.51-2.02), opossum in peridomiciliary area (PR = 1.56 95%CI 1.37-1.79) and a high proportion of seropositive domestic animals in the home (PR20-40% vs <20% = 2.28 95%CI 1.59-3.23 and PR>40% vs <20% = 3.14 95%CI 2.43-4.04) were associated with rickettsial seropositivity in humans. This study showed the presence of Rickettsia antibodies in human populations and domestic animals. In addition, different species of rickettsiae were detected in ticks collected from humans and animals. Our results highlighted the role of domestic animals as sentinels of rickettsial infection to identify areas at risk of transmission, and the importance of preventive measures aimed at curtailing deforestation and the fragmentation of forests as a way of reducing the risk of transmission of emergent and re-emergent pathogens.

Influenza and other respiratory virus surveillance systems in the Americas, 2017

[Background]. Since the 2009 influenza pandemic, countries of the Americas have been strengthening their surveillance systems to improve detection of novel influenza subtypes and monitoring of seasonal influenza epidemics. These systems, when functioning optimally, allow public health decision makers to understand when, where, and who is being affected by influenza during seasonal epidemics and should detect the emergence of a novel influenza subtype in a timely manner. The first surveillance systems to be developed in most countries in the Region were laboratory-based surveillance systems, which would allow the detection of a novel influenza subtype if a clinical sample were collected and tested in the laboratory. Since this time, many other systems have been developed to complement and integrate with the laboratory surveillance platforms, which allow for monitoring of influenza, pneumonia, and clinical influenza proxy syndromes in the ambulatory and hospitalized settings (e.g. influenza-like illness [ILI] and severe acute respiratory infection [SARI]). There are systems which are both indicator-based as well as systems which rely upon event-based information (e.g., tracking of media reports).The result of these efforts is that now, there are a variety of systems that contribute to the understanding nationally, regionally, and globally, of influenza. This publication represents a compilation of the respiratory virus surveillance systems that exist in countries throughout the Americas Region and is an update to the 2014-publication, “Influenza and Other Respiratory Virus Surveillance Systems in the Americas, 2014”. he 2016-2017 inventory includes two sections: Regional Analyses and Country-by-country Analyses. The regional section includes regional data, maps showing capacities that exist in the region, and frequency of data reporting to FluID and FluNet...

Classificação de risco de transmissão de doenças imunopreveníveis a partir de indicadores de coberturas vacinais nos municípios brasileiros / Clasificación de riesgo de transmisión de enfermedades prevenibles a partir de indicadores de cobertura de vacunación en municipios / Classification of transmission risk of vaccine-preventable diseases based on vaccination indicators in Brazilian municipalities

OBJETIVO: descrever a classificação de risco de doenças imunopreveníveis nos municípios brasileiros. MÉTODOS: estudo epidemiológico descritivo com dados do Sistema de Informações do Programa Nacional de Imunizações (SI-PNI) para 2014; os indicadores de coberturas vacinais foram utilizados para classificar o risco de transmissão de doenças imunopreveníveis nos municípios. RESULTADOS: dos 5.570 municípios brasileiros, 12,0% foram classificados como de risco muito baixo, 29,6% de risco baixo, 2,2% de risco médio, 54,3% de risco alto e 1,8% de risco muito alto. CONCLUSÃO: a vigilância das coberturas vacinais permitiu identificar a maioria dos municípios em situação de alto risco e a minoria das crianças vivendo em municípios com cobertura adequada; a vigilância das coberturas utilizando indicadores pactuados no Sistema Único de Saúde (SUS) oferece nova ferramenta para identificação de áreas prioritárias, onde as ações poderão ter maiores chances de acerto pelos gestores e melhorar a qualidade e o sucesso do PNI.

OBJETIVO: describir la clasificación de riesgo de enfermedades prevenibles en municipios brasileños. MÉTODOS: estudio epidemiológico descriptivo con datos del Sistema de informaciones del programa nacional de inmunizaciones (PNI) de 2014; los indicadores de cobertura fueron utilizados para clasificar el riesgo de transmisión de enfermedades prevenibles en los municipios. RESULTADOS: de los 5.570 municipios brasileños, 12,0% fueron clasificados de muy bajo riesgo, 29,6% de bajo riesgo, 2,2% de riesgo medio, 54,3% de alto riesgo y 1,8% de riesgo muy alto. CONCLUSIÓN: la vigilancia de la cobertura de vacunación permitió identificar la mayoría de los municipios en situaciones de alto riesgo y la minoría de niños que viven en municipios con una cobertura adecuada; la vigilancia de la cobertura de vacunación según indicadores acordados en el sistema de salud pública ofrece una nueva herramienta para la identificación de áreas prioritarias en las que la acción pueda tener mayores posibilidades de éxito por los administradores de salud para mejorar la calidad y el éxito del programa de inmunización.

OBJECTIVE: to describe the transmission risk classification of vaccine-preventable diseases in Brazilian municipalities. METHODS: this was a descriptive epidemiologic study using 2014 data of the Brazilian National Immunization Program Information System; the vaccine coverage indicators were used to classify the transmission risk of vaccine-preventable diseases in the municipalities. RESULTS: of the 5,570 Brazilian municipalities, 12.0% were classified as very low risk, 29.6% as low risk, 2.2% as medium risk, 54.3% as high risk and 1.8% as very high risk. CONCLUSION: the vaccination coverage surveillance allowed to identify most of the municipalities in high risk situation and the minority of children living in municipalities with appropriate coverage; the vaccination coverage surveillance using indicators of the Brazilian National Health System (SUS) is a new tool for identifying priority areas where the actions can be more successful for health managers and improve the quality and the success of the immunizations program.

Anti-NeuGcGM3 reactivity: a possible role of natural antibodies and B-1 cells in tumor immunosurveillance.

While not naturally expressed in normal human tissues, N-glycolylated (NeuGc) gangliosides are overexpressed in several tumors and have immunosuppressive capacity, which contributes to cancer progression. Naturally occurring antibodies against NeuGcGM3 exist in healthy donors that specifically recognize and kill tumor cells expressing the antigen by complement-dependent and -independent mechanisms, the latter resembling an oncotic necrosis-type of cell death. Both the levels of anti-NeuGcGM3 antibodies in the sera of healthy donors and the percentage of donors with these natural antibodies decrease with age. Our work has shown that anti-NeuGcGM3 antibodies are not detected in the sera of non-small cell lung cancer (NSCLC) patients, compared to age- and sex-matched healthy donors, which have anti-NeuGcGM3. Interestingly, the level of serum total IgM, but not IgG, was significantly lower in cancer patients than in healthy donors. Screening of immortalized mouse splenic and peritoneal-derived hybridomas showed that peritoneal B-1 cells secrete anti-NeuGcGM3 with tumor cytotoxic capacity. Defects in the natural surveillance against tumor antigens could increase the risk of elderly donors developing cancer and affect the capacity of cancer patients to effectively fight against tumor cells.