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The role of neutrophils in the development of atherosclerosis has long been an enigma, with few neutrophils detected within the plaque. Here, the authors show that microvesicles released from neutrophils increase vascular inflammation and enhance atherosclerotic plaque formation through delivery of miR-155.

Abstract Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1 in vitro has confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent. We used a mouse model of peritoneal neutrophilic inflammation to determine if Ang-1 could stimulate neutrophil migration in vivo. Tie2 expression was demonstrated on mouse neutrophils. In addition, recombinant human Ang-1 induced significant chemotaxis of isolated mouse neutrophils in a Tie2- and CD18-dependent manner. Subsequently, co-immunoprecipitation of Ang-1 and CD18 demonstrated their interaction. Intraperitoneal injection of an engineered angiopoietin-1, MAT.Ang-1, induced significant neutrophil migration into the peritoneum and a significant increase in the levels of CCL4 in peritoneal lavage fluid. Depletion of resident peritoneal macrophages prior to, or concomitant injections of an anti-CCL4 antibody with MAT.Ang-1 resulted in a significant reduction in neutrophil recruitment. These data indicate a pro-inflammatory role for Ang-1 with respect to neutrophil recruitment.

In response to pathophysiological stress, the cardiac tissue undergoes profound remodeling process that incorporates the elimination of dying resident cells, compensatory hypertrophy of functional cardiomyocytes, growth and remodeling of the vascular compartment and formation of a fibrotic scar. Accumulating evidences indicate that cardiac remodeling is, at least in part, controlled by a complex crosstalk between cardiomyocytes and macrophages. The strategic location of abundant macrophages to the proximity of cardiomyocytes suggest that they could regulate the fate of cardiomyocytes in the injured heart. As such, macrophages appear as critical support cells for cardiomyocytes and play central roles in cardiac hypertrophy, fibrosis and remodeling. Notably, the cardiac tissue expands heterogeneous population of cardiac macrophages through local proliferation of resident macrophage as well as recruitment and differentiation of blood-derived monocytes. It has also been suggested that cardiac-resident macrophages display distinct functional properties from that of monocyte-derived macrophages in cardiac tissue. Furthermore, macrophages are an overflowing source of biological entities with non-canonical roles on cardiac conduction or cardiomyocyte proliferation by regulating action potential diffusion or cardiac cell cycle reentry. Alternatively, stressed cardiomyocytes can trigger the release of a broad repertoire of instructive signals that can regulate macrophage number, skew their phenotype and therefore direct their beneficial or deleterious actions. In this review, we highlight recent discoveries describing how the intricate dialogue between cardiomyocytes and macrophages can shape the deleterious or healing signaling mechanisms in the injured cardiac tissue.

Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-γ-lyase (CSE) and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA). Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension).

Varicose veins are elongated and dilated saphenous veins. Despite the high prevalence of this disease, its pathogenesis remains unclear.In this study, we investigated the control of matrix metalloproteinases (MMPs) expression by prostaglandin (PG)E₂ during the vascular wall remodeling of human varicose veins.Varicose (small (SDv) and large diameter (LDv)) and healthy saphenous veins (SV) were obtained after surgery. Microsomal and cytosolic PGE-synthases (mPGES and cPGES) protein and mRNA responsible for PGE₂ metabolism were analyzed in all veins. cPGES protein was absent while its mRNA was weakly expressed. mPGES-2 expression was similar in the different saphenous veins. mPGES-1 mRNA and protein were detected in healthy veins and a significant decrease was found in LDv. Additionally, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), responsible for PGE₂ degradation, was over-expressed in varicose veins. These variations in mPGES-1 and 15-PGDH density account for the decreased PGE₂ level observed in varicose veins. Furthermore, a significant decrease in PGE₂ receptor (EP4) levels was also found in SDv and LDv. Active MMP-1 and total MMP-2 concentrations were significantly decreased in varicose veins while the tissue inhibitors of metalloproteinases (TIMP -1 and -2), were significantly increased, probably explaining the increased collagen content found in LDv. Finally, the MMP/TIMP ratio is restored by exogenous PGE₂ in varicose veins and reduced in presence of an EP4 receptor antagonist in healthy veins.In conclusion, PGE₂ could be responsible for the vascular wall thickening in human varicose veins. This mechanism could be protective, strengthening the vascular wall in order to counteract venous stasis.

La Región de las Américas ha experimentado históricamente desigualdades sociales enraizadas en el colonialismo, las cuales se reflejan y reproducen en el ámbito de la salud. La incursión de la pandemia de COVID-19 afectó a toda la Región, pero golpeó con mayor fuerza a los grupos socialmente más desaventajados, y agravó las inequidades en salud. Bajo la premisa que las pandemias no son fenómenos socialmente neutrales, en este informe especial se analizan los impactos desiguales de la pandemia desde distintas perspectivas –histórica, epidemiológica, política, social, económica, ambiental y poblacional. Se ofrecen aquí reflexiones críticas sobre las implicaciones negativas de las desigualdades para el bienestar, no solo de las poblaciones más afectadas, sino de la sociedad en su conjunto. Se concluye con recomendaciones estratégicas para progresar hacia la equidad en salud en el escenario pospandémico. Se destaca la importancia de avanzar en la madurez de los sistemas de información para el monitoreo de la equidad en salud, la resiliencia de los sistemas de salud, y la implementación de políticas y prácticas explícitas dirigidas a eliminar las inequidades en salud. Se espera que todo lo anterior allane el camino hacia la prosperidad y el desarrollo sostenible en la Región.

Abstract Background Despite the resources and personnel mobilized in Latin America and the Caribbean to reduce the maternal mortality ratio (MMR, maternal deaths per 100 000 live births) in women aged 10–54 years by 75% between 2000 and 2015, the region failed to meet the Millenium Development Goals (MDGs) due to persistent barriers to access quality reproductive, maternal, and neonatal health services. Methods Using 1990–2019 data from the Global Burden of Disease project, we carried out a two-stepwise analysis to (a) identify the differences in the MMR temporal patterns and (b) assess its relationship with selected indicators: government health expenditure (GHE), the GHE as percentage of gross domestic product (GDP), the availability of human resources for health (HRH), the coverage of effective interventions to reduce maternal mortality, and the level of economic development of each country. Findings In the descriptive analysis, we observed a heterogeneous overall reduction of MMR in the region between 1990 and 2019 and heterogeneous overall increases in the GHE, GHE/GDP, and HRH availability. The correlation analysis showed a close, negative, and dependent association of the economic development level between the MMR and GHE per capita, the percentage of GHE to GDP, the availability of HRH, and the coverage of SBA. We observed the lowest MMRs when GHE as a percentage of GDP was close to 3% or about US$400 GHE per capita, HRH availability of 6 doctors, nurses, and midwives per 1,000 inhabitants, and skilled birth attendance levels above 90%. Conclusions Within the framework of the Sustainable Development Goals (SDGs) agenda, health policies aimed at the effective reduction of maternal mortality should consider allocating more resources as a necessary but not sufficient condition to achieve the goals and should prioritize the implementation of new forms of care with a gender and rights approach, as well as strengthening actions focused on vulnerable groups.

Se presenta el posicionamiento del grupo de trabajo latinoamericano de la Fundación Internacional para los Cuidados Integrados (1) (IFIC, por su sigla en inglés). Este reúne a diversos actores y organizaciones de América Latina, con el objeto de apoyar acciones que faciliten la transformación de los sistemas de salud en la Región hacia sistemas integrados y centrados en las personas, no como individuos aislados, sino como sujetos de derecho, en los contextos sociales y ambientales complejos donde viven y se vinculan. El grupo de trabajo plantea nueve pilares de la atención integrada para ser utilizados como marco conceptual en la elaboración de políticas y de cambios en las prácticas: 1) visión y valores compartidos, 2) salud de las poblaciones, 3) las personas y las comunidades como socias, 4) comunidades resilientes, 5) capacidades del talento humano en salud, 6) gobernanza y liderazgo, 7) soluciones digitales, 8) sistemas de pago alineados, y 9) transparencia ante la ciudadanía. Desde estos pilares se proponen líneas de trabajo en los ámbitos del fortalecimiento de alianzas y redes, la abogacía, la investigación y generación de capacidades, que contribuyan a materializar sistemas de salud y sociales efectivamente integrados y centrados no solo en las personas, sino también en las comunidades en América Latina.

Cet article vise à mettre en évidence le parcours linguistique du Cameroun. Nous analyserons les langues nationales, ainsi que les langues of cielles parlées dans ce pays, a n de montrer son bilinguisme actuel. Este artículo pretende poner en evidencia el recorrido lingüístico de Camerún. Analizaremos los idiomas nacionales, así como los o ciales hablados en este país, con el n de mostrar su actual bilingüismo.

El riesgo de suicidio en prisión constituye uno de los temas a tener en cuenta en el diseño de políticas penitenciarias ya que las tasas de suicidios suelen ser superiores a las que se dan entre la población general. De acuerdo a la literatura, las conductas de suicidio parecen ser más frecuentes en internos jóvenes, en hombres, en aquellos que tienen problemas de toxicomanía y con historia de psicopatología previa, pero no con depresión. Además, las complicaciones en el proceso judicial o en las condiciones de encarcelamiento, aparecen relacionadas con conductas de autolesión, a las que el interno recurriría como forma de llamar la atención. Desde este marco se analizó mediante cuestionario aplicado a internos de cinco prisiones de Bogotá (n=400) la presencia de indicadores psicológicos de suicidio y de variables asociadas como psicopatología previa, estresores cotidianos en prisión, clima emocional, y antecedentes familiares y de consumo de drogas. Mediante análisis de regresión se encontró que el riesgo de suicidio se asociaba con una menor edad, una mayor dificultad para ajustarse a las normas del centro y con la existencia en el pasado de enfermedades físicas y de dificultades sexuales.

El riesgo de suicidio en prisión constituye uno de los temas a tener en cuenta en el diseño de políticas penitenciarias ya que las tasas de suicidios suelen ser superiores a las que se dan entre la población general. De acuerdo a la literatura, las conductas de suicidio parecen ser más frecuentes en internos jóvenes, en hombres, en aquellos que tienen problemas de toxicomanía y con historia de psicopatología previa, pero no con depresión. Además, las complicaciones en el proceso judicial o en las condiciones de encarcelamiento, aparecen relacionadas con conductas de autolesión, a las que el interno recurriría como forma de llamar la atención. Desde este marco se analizó mediante cuestionario aplicado a internos de cinco prisiones de Bogotá (n=400) la presencia de indicadores psicológicos de suicidio y de variables asociadas como psicopatología previa, estresores cotidianos en prisión, clima emocional, y antecedentes familiares y de consumo de drogas. Mediante análisis de regresión se encontró que el riesgo de suicidio se asociaba con una menor edad, una mayor dificultad para ajustarse a las normas del centro y con la existencia en el pasado de enfermedades físicas y de dificultades sexuales