Effects and cost of implementing a gender-sensitive reproductive health program in Bolivia

The Integral Health Coordination Program (Programa de Coordinación en Salud Integral or PROCOSI), a network of 24 Bolivian NGOs, and the Population Council’s Frontiers in Reproductive Health (FRONTIERS) program evaluated the effects of interventions on clinic clients and their partners, and estimated the costs of incorporating a gender perspective into service delivery. Results show that sexual and reproductive health service organizations can implement action plans to change organizational policies and service delivery practices and to improve their infrastructure and equipment to make them more convenient for clients. The results further show that the intervention made modest but important changes in partner dynamics. No evidence was found that the incorporation of a gender perspective had an effect on the demand for sexual and reproductive health services. In the context of the current study, if change in unmet need is posited as the measure of success, then the question for program managers is whether this expenditure is justified to achieve the resulting changes in unmet need

Efficiency in estimating age through the Index Coronal Pulp Cavity in an adult population

Objetivo: Determinar la eficiencia del método de estimación de la edad basada en el índice coronal dentario. Materiales y método: Se realizó el método de índice de la cavidad coronal pulpar en 432 piezas dentarias del cuarto cuadrante mandibular (primera premolar=129, segunda premolar=104, primera molar=113 y segunda molar=86), evaluadas en radiografías panorámicas digitales, pertenecientes a individuos adultos, de 20 y 40 años, que acudieron al Servicio de Imagenología de la Facultad de Odontología de la Universidad Nacional Mayor de San Marcos y se comparó con la edad cronológica de cada individuo. Resultados: Los resultados de las correlaciones fueron significativas, especialmente para los segundos molares en el sexo masculino (r = 0.814, r2 = 0.663). Conclusión: La aplicación del método de índice coronario dental es eficiente y la ecuación de regresión lineal encontrada muestra mayor aproximación en la estimación de la edad del individuo.Objetive: Determine the efficiency of the method of estimating age based on the coronal tooth index. Materials and method: The method of index Cavity Coronal Pulp was performed on 432 teeth of the fourth mandibular quadrant (first premolar = 129, second premolar = 104, first molar = 113 and second molar = 86) evaluated in digital panoramic radiographs belonging adult individuals, aged 20 and 40, who attended the Imaging Department of the Faculty of Dentistry, National University of San Marcos and compared with the chronological age of the individual. Results: The results of the correlations were significant, especially for the second molars in males (r = 0.814, r2 = 0.663). Conclusion: The application of the method of dental coronary index is efficient and linear regression equation found larger sample approach in estimating the age of the individual

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Metabolic rewiring underlies the effector functions of macrophages1-3, but the mechanisms involved remain incompletely defined. Here, using unbiased metabolomics and stable isotope-assisted tracing, we show that an inflammatory aspartate-argininosuccinate shunt is induced following lipopolysaccharide stimulation. The shunt, supported by increased argininosuccinate synthase (ASS1) expression, also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination. Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) further increases intracellular fumarate levels. Mitochondrial respiration is also suppressed and mitochondrial membrane potential increased. RNA sequencing and proteomics analyses demonstrate that there are strong inflammatory effects resulting from FH inhibition. Notably, acute FH inhibition suppresses interleukin-10 expression, which leads to increased tumour necrosis factor secretion, an effect recapitulated by fumarate esters. Moreover, FH inhibition, but not fumarate esters, increases interferon-β production through mechanisms that are driven by mitochondrial RNA (mtRNA) release and activation of the RNA sensors TLR7, RIG-I and MDA5. This effect is recapitulated endogenously when FH is suppressed following prolonged lipopolysaccharide stimulation. Furthermore, cells from patients with systemic lupus erythematosus also exhibit FH suppression, which indicates a potential pathogenic role for this process in human disease. We therefore identify a protective role for FH in maintaining appropriate macrophage cytokine and interferon responses

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Design and synthesis of a stable oxidized phospholipid mimic with specific binding recognition for macrophage scavenger receptors

Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with the phosphatidylcholine head group have been shown to exhibit binding affinity for these receptors. We report the preparation of a water soluble, stable peptide-phospholipid conjugate (9) that possesses the necessary physical properties to enable more detailed study of the role(s) of OxPL in metabolic disease

Design and Synthesis of a Stable Oxidized Phospholipid Mimic with Specific Binding Recognition for Macrophage Scavenger Receptors

Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide–phospholipid conjugates with the phosphatidylcholine headgroup have been shown to exhibit binding affinity for these receptors. We report the preparation of a water-soluble, stable peptide–phospholipid conjugate (<b>9</b>) that possesses the necessary physical properties to enable more detailed study of the role(s) of OxPL in metabolic disease

Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity

Oxidation reactions are vital parts of metabolism and signal transduction. However, they also produce reactive oxygen species, which damage lipids, proteins and DNA, generating “oxidation-specific” epitopes. In this review, we will discuss the hypothesis that such common oxidation-specific epitopes are a major target of innate immunity, recognized by a variety of “pattern recognition receptors” (PRRs). By analogy with microbial “pathogen associated molecular patterns” (PAMPs), we postulate that host-derived, oxidation-specific epitopes can be considered to represent “danger (or damage) associated molecular patterns” (DAMPs). We also argue that oxidation-specific epitopes present on apoptotic cells and their cellular debris provided the primary evolutionary pressure for the selection of such PRRs. Further, because many PAMPs on microbes share molecular identity and/or mimicry with oxidation-specific epitopes, such PAMPs provided a strong secondary selecting pressure for the same set of oxidation-specific PRRs as well. Because lipid peroxidation is ubiquitous and a major component of the inflammatory state associated with atherosclerosis, the understanding that oxidation-specific epitopes are DAMPs, and thus the target of multiple arcs of innate immunity, provides novel insights into the pathogenesis of atherosclerosis. As examples, we show that both cellular and soluble PRRs, such as CD36, toll-like receptor-4, natural antibodies, and CRP recognize common oxidation-specific DAMPs, such as oxidized phospholipids and oxidized cholesteryl esters, and mediate a variety of immune responses, from expression of proinflammatory genes to excessive intracellular lipoprotein accumulation to atheroprotective humoral immunity. These insights may lead to improved understanding of inflammation and atherogenesis and suggest new approaches to diagnosis and therapy