Social isolation, physical inactivity and inadequate diet among European middle-aged and older adults.

BACKGROUND: Social isolation is a growing public health concern for older adults, as it has been associated with poor health and premature mortality. On the other hand, physical inactivity and an inadequate diet are important health risk behaviours associated with physical and mental health problems. Considering that there is no research examining the possible relationship between social isolation and the above mentioned health risk behaviours of European middle-aged and older adults, this cross-sectional study aims to contribute to filling this gap. METHODS: We used data from the SHARE project (Survey of Health, Ageing and Retirement in Europe), wave 6 (2015), release 7.0.0 (N = 67,173 individuals from 17 European countries plus Israel). Statistical tests for a two-group comparison were carried out to assess the differences between highly socially isolated individuals and low/intermediate socially isolated ones. Logistic regressions by country were performed to examine whether social isolation is associated with physical inactivity and an inadequate diet in the population aged 50 + . RESULTS: Our results point out that, for the majority of the countries analysed, highly socially isolated individuals are more likely than low/intermediate isolated ones to be physically inactive and to consume less fruit or vegetables on a daily basis. In 9 European countries (Austria, Germany, Sweden, Denmark, Greece, Belgium, Poland, Luxembourg and Estonia) highly socially isolated individuals are more likely to be physically inactive. On the other hand, in 14 European countries (Austria, Germany, Sweden, Italy, France, Denmark, Greece, Switzerland, Belgium, Czech Republic, Luxembourg, Slovenia, Estonia and Croatia), high social isolation increases the likelihood of having an inadequate diet. CONCLUSION: Highly socially isolated European middle-aged and older adults are more prone to be physically inactive and to have an inadequate diet in terms of daily consumption of fruit and vegetables. The reduced social integration, social support and companionship of the highly socially isolated individuals may explain this association. Our results reinforce the importance of social and health policies targeting highly socially isolated European individuals aged 50 + .

Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development.

The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite's hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host-parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies.

Use of plant materials for the bioremediation of soil from an industrial site.

Bioremediation is one of the existing techniques applied for treating oil-contaminated soil, which can be improved by the incorporation of low-cost nutritional materials. This study aimed to assess the addition of two low-cost plant residues, sugarcane bagasse (SCB) and leaf litter (LL) of the forest leguminous Mimosa caesalpiniifolia plant (sabiá), either separately or combined, to a contaminated soil from a petroleum refinery area, analyzed after 90 days of treatment. Individually, both amounts of SCB (20 and 40 g kg-1) favored the growth of total heterotrophic bacteria and total fungi, while LL at 20 g kg-1 better stimulated the hydrocarbon-degrading microorganism's activity in the soil. However, no TPH removal was observed under any of these conditions. Higher microbial growth was detected by the application of both plant residues in multicontaminated soil. The maximum TPH removal of 30% was achieved in amended soil with 20 g kg-1 SCB and 20 kg-1 LL. All the experimental conditions revealed changes in the microbial community structure, related to the handling of the soil, with abundance of Alphaproteobacteria. This study demonstrates the effectiveness of the plant residues SCB and LL as low-cost nutritional materials for biodegradation of hydrocarbon in real oil contaminated soil by indigenous populations.

Chemical attenuation of Plasmodium in the liver modulates severe malaria disease progression.

Cerebral malaria is one of the most severe complications of malaria disease, attributed to a complicated series of immune reactions in the host. The syndrome is marked by inflammatory immune responses, margination of leukocytes, and parasitized erythrocytes in cerebral vessels leading to breakdown of the blood-brain barrier. We show that chemical attenuation of the parasite at the very early, clinically silent liver stage suppresses parasite development, delays the time until parasites establish blood-stage infection, and provokes an altered host immune response, modifying immunopathogenesis and protecting from cerebral disease. The early response is proinflammatory and cell mediated, with increased T cell activation in the liver and spleen, and greater numbers of effector T cells, cytokine-secreting T cells, and proliferating, proinflammatory cytokine-producing T cells. Dendritic cell numbers, T cell activation, and infiltration of CD8(+) T cells to the brain are decreased later in infection, possibly mediated by the anti-inflammatory cytokine IL-10. Strikingly, protection can be transferred to naive animals by adoptive transfer of lymphocytes from the spleen at very early times of infection. Our data suggest that a subpopulation belonging to CD8(+) T cells as early as day 2 postinfection is responsible for protection. These data indicate that liver stage-directed early immune responses can moderate the overall downstream host immune response and modulate severe malaria outcome.

Abnormally differentiated CD4+ or CD8+ T cells with phenotypic and genetic features of double negative T cells in human Fas deficiency.

Accumulation of CD3(+) T-cell receptor (TCR)αß(+)CD4(-)CD8(-) double-negative T cells (DNT) is a hallmark of autoimmune lymphoproliferative syndrome (ALPS). DNT origin and differentiation pathways remain controversial. Here we show that human ALPS DNT have features of terminally differentiated effector memory T cells reexpressing CD45RA(+) (TEMRA), but are CD27(+)CD28(+)KLRG1(-) and do not express the transcription factor T-bet. This unique phenotype was also detected among CD4(+) or CD8(+) ALPS TEMRA cells. T-cell receptor ß deep sequencing revealed a significant fraction of shared CDR3 sequences between ALPS DNT and both CD4(+) and CD8(+)TEMRA cells. Moreover, in ALPS patients with a germ line FAS mutation and somatic loss of heterozygosity, in whom biallelic mutant cells can be tracked by absent Fas expression, Fas-negative T cells accumulated not only among DNT, but also among CD4(+) and CD8(+)TEMRA cells. These data indicate that in human Fas deficiency DNT cannot only derive from CD8(+), but also from CD4(+) T cells. Furthermore, defective Fas signaling leads to aberrant transcriptional programs and differentiation of subsets of CD4(+) and CD8(+) T cells. Accumulation of these cells before their double-negative state appears to be an important early event in the pathogenesis of lymphoproliferation in ALPS patients.

The influence of nickel on the bioremediation of multi-component contaminated tropical soil: microcosm and batch bioreactor studies.

Large petrochemical discharges are responsible for organic and inorganic pollutants in the environment. The purpose of this study was to evaluate the influence of nickel, one of the most abundant inorganic element in crude oil and the main component of hydrogen catalysts for oil refining, on the microbial community structure in artificially petroleum-contaminated microcosms and in solid phase bioreactor studies. In the presence of metals, the oil biodegradation in microcosms was significantly delayed during the first 7 days of operation. Also, increasing amounts of moisture generated a positive influence on the biodegradation processes. The oil concentration, exhibiting the most negative influence at the end of the treatment period. Molecular fingerprinting analyses (denaturing gradient gel electrophoresis--DGGE) indicated that the inclusion of nickel into the contaminated soil promoted direct changes to the microbial community structure. By the end of the experiments, the results of the total petroleum hydrocarbons removal in the bioreactor and the microcosm were similar, but reductions in the treatment times were observed with the bioreactor experiments. An analysis of the microbial community structure by DGGE using various markers showed distinct behaviors between two treatments containing high nickel concentrations. The main conclusion of this study was that Nickel promotes a significant delay in oil biodegradation, despite having only a minor effect over the microbial community.

Is Formal Social Participation Associated with Cognitive Function in Middle-Aged and Older Adults? A Systematic Review with Meta-Analysis of Longitudinal Studies.

This systematic review with meta-analysis aimed to explore the association between formal social participation and cognitive function in middle-aged and older adults using data from longitudinal studies. A comprehensive search was conducted in Scopus, PubMed, and Web of Science for longitudinal studies that assessed the association between formal social participation and cognitive function in middle-aged and older adults published between January 2010 to 19 August 2022. Risk of bias was judged using the RoBANS tool. Meta-analysis using a random-effects model was computed with odds ratio (OR) and 95% confidence interval (CI) for cognitive decline probability. Sensitivity analyses were made to explore any changes to the pooled statistical heterogeneity and pooled effect size. Certainty of evidence was judged using the GRADE framework. We included 15 studies comprising 136,397 participants from 5 countries. Meta-analyses showed that formal social participation was associated with reduced cognitive decline (OR = 0.78, 95% CI 0.75-0.82, p < 0.001), with very low certainty of evidence. Formal social participation appears to enhance cognition in middle-aged and older adults, but further high-quality research is needed given the very low certainty of evidence.

Association between formal social participation and cognitive function in middle-aged and older adults: a longitudinal study using SHARE data.

Formal social participation significantly impacts health and well-being, potentially mitigating cognitive decline, although not consistently across all studies. Existing research often focuses solely on baseline participation levels, and age-related differences have primarily been explored among the Asian population. Therefore, this longitudinal study aims to assess the association between formal social participation and cognition across different age groups in individuals aged 50+ living in Europe and Israel, while capturing the dynamic nature of formal social participation. We use data from three waves (four, six, and eight) of the Survey of Health, Ageing, and Retirement in Europe (SHARE), comprising 85,601 respondents. Linear mixed-effects models were applied. The results show that participation in formal social activities mitigates cognitive decline in middle-aged and older adults, especially among those aged 70 to 79 and 80+. These findings support the need for social policies promoting formal social activities, for lasting cognitive health benefits.

Real-world evaluation of vascular complications and comorbidities in Portuguese patients with type 2 diabetes: Results from the cMORE study.

INTRODUCTION AND OBJECTIVES: Type 2 diabetes poses a significant health challenge in Portugal, increasing the susceptibility to complications/comorbidities such as hypertension, obesity, and cardiovascular (CV) disease. This study aimed to evaluate the prevalence of type 2 diabetes-related vascular complications/comorbidities and their pharmacological management in Portugal. METHODS: cMORE was a non-interventional, cross-sectional, multicenter study conducted in 32 Portuguese primary healthcare units between October 2020 and 2022. Secondary data, including sociodemographic, anthropometric, clinical information, cardiometabolic comorbidities, HbA1c levels, lipid parameters and medication, were collected from electronic medical records. RESULTS: Seven hundred and eighty adult patients with type 2 diabetes were included, predominantly male (55.5%), with an average age of 67.7 years and a mean disease duration of 10.5 years. Family history of type 2 diabetes (43.1%) and CV disease (32.1%) was prevalent. Mean HbA1c was 7.0%, progressively increasing with disease duration (p<0.001). Microvascular and macrovascular complications occurred in 38.1% and 19.6% of patients, respectively. The most prevalent comorbidities included overweight/obesity (85.5%), dyslipidemia (85.4%), and hypertension (82.6%). Multimorbidity burden was significant (99.3%) and positively correlated with older age, larger waist circumference, and overweight/obesity. Longer type 2 diabetes duration was associated with higher odds of diabetic retinopathy and CV disease/procedures, while dyslipidemia and hypertension were linked with older age, regardless of disease duration. Most patients received oral antidiabetic medications (94.6%), primarily biguanides (92.4%), followed by DPP-4 (39.1%) and SGLT2 inhibitors (34.2%). CONCLUSIONS: The cMORE study reveals a substantial burden of vascular complications/comorbidities among Portuguese patients with type 2 diabetes. Despite the high multimorbidity rates, effective type 2 diabetes management is observed, emphasizing the country's commitment to personalized care.

Colostrum Antibodies and Cytokines in Puerperal Women with Diabetes Before and During the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: Breastfeeding maintains the maternal-fetal immune link after birth, favors the transmission of immunological competence, and is considered an important contributing factor to the development of the babies' immune system. OBJECTIVE: This study aimed to obtain data related to the effects of gestational diabetes on immunoglobulin A (IgA) and cytokines levels in the colostrum, before and during the pandemic of the new coronavirus, in order to study the possible outcomes regarding the immunological characteristics of human milk. METHODS: This systematic review was registered in PROSPERO CRD42020212397, and the question elaborated using the PICO strategy was: does maternal hyperglycemia associated or not with Covid-19 influence the immunological composition of colostrum? Electronic searching and reference lists of published reports were used to identify studies that reported the influence of gestational diabetes on colostrum and milk composition. RESULTS: Seven studies were selected from the 51 found, six of them were cross-sectional and one was a case report. Six studies included Brazilian groups and only one was conducted in USA. The mothers with gestational diabetes presented a reduced level of IgA and other immunoreactive proteins in colostrum. Those alterations could be related to changes in macronutrient metabolism and cellular oxidative metabolism. CONCLUSION: It was possible to conclude that diabetes changes the immunological composition of breast milk; however, data on the impact of the association between gestational diabetes and Covid-19 infection on the composition of antibodies and cytokines present in human milk are still scarce and inconclusive.

Genomic history of coastal societies from eastern South America.

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr BP) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr BP from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr BP, corroborating evidence of cultural change.

Neisseria meningitidis Opc invasin binds to the sulphated tyrosines of activated vitronectin to attach to and invade human brain endothelial cells.

The host vasculature is believed to constitute the principal route of dissemination of Neisseria meningitidis (Nm) throughout the body, resulting in septicaemia and meningitis in susceptible humans. In vitro, the Nm outer membrane protein Opc can enhance cellular entry and exit, utilising serum factors to anchor to endothelial integrins; but the mechanisms of binding to serum factors are poorly characterised. This study demonstrates that Nm Opc expressed in acapsulate as well as capsulate bacteria can increase human brain endothelial cell line (HBMEC) adhesion and entry by first binding to serum vitronectin and, to a lesser extent, fibronectin. This study also demonstrates that Opc binds preferentially to the activated form of human vitronectin, but not to native vitronectin unless the latter is treated to relax its closed conformation. The direct binding of vitronectin occurs at its Connecting Region (CR) requiring sulphated tyrosines Y(56) and Y(59). Accordingly, Opc/vitronectin interaction could be inhibited with a conformation-dependent monoclonal antibody 8E6 that targets the sulphotyrosines, and with synthetic sulphated (but not phosphorylated or unmodified) peptides spanning the vitronectin residues 43-68. Most importantly, the 26-mer sulphated peptide bearing the cell-binding domain (45)RGD(47) was sufficient for efficient meningococcal invasion of HBMECs. To our knowledge, this is the first study describing the binding of a bacterial adhesin to sulphated tyrosines of the host receptor. Our data also show that a single region of Opc is likely to interact with the sulphated regions of both vitronectin and of heparin. As such, in the absence of heparin, Opc-expressing Nm interact directly at the CR but when precoated with heparin, they bind via heparin to the heparin-binding domain of the activated vitronectin, although with a lower affinity than at the CR. Such redundancy suggests the importance of Opc/vitronectin interaction in meningococcal pathogenesis and may enable the bacterium to harness the benefits of the physiological processes in which the host effector molecule participates.

Gold nanoparticle-based fluorescence immunoassay for malaria antigen detection.

The development of rapid detection assays for malaria diagnostics is an area of intensive research, as the traditional microscopic analysis of blood smears is cumbersome and requires skilled personnel. Here, we describe a simple and sensitive immunoassay that successfully detects malaria antigens in infected blood cultures. This homogeneous assay is based on the fluorescence quenching of cyanine 3B (Cy3B)-labeled recombinant Plasmodium falciparum heat shock protein 70 (PfHsp70) upon binding to gold nanoparticles (AuNPs) functionalized with an anti-Hsp70 monoclonal antibody. Upon competition with the free antigen, the Cy3B-labeled recombinant PfHsp70 is released to solution resulting in an increase of fluorescence intensity. Two types of AuNP-antibody conjugates were used as probes, one obtained by electrostatic adsorption of the antibody on AuNPs surface and the other by covalent bonding using protein cross-linking agents. In comparison with cross-linked antibodies, electrostatic adsorption of the antibodies to the AuNPs surfaces generated conjugates with increased activity and linearity of response, within a range of antigen concentration from 8.2 to 23.8 µg.mL(-1). The estimated LOD for the assay is 2.4 µg.mL(-1) and the LOQ is 7.3 µg.mL(-1). The fluorescence immunoassay was successfully applied to the detection of antigen in malaria-infected human blood cultures at a 3% parasitemia level, and is assumed to detect parasite densities as low as 1,000 parasites.µL(-1).

Precautionary behaviours of individuals with multimorbidity during the COVID-19 pandemic.

Studies show that older individuals with multimorbidity are more susceptible to develop a more severe case of COVID-19 when infected by the virus. These individuals are more likely to be admitted to Intensive Care Units and to die from COVID-19-related conditions than younger individuals or those without multimorbidity. This research aimed to assess whether there are differences in terms of precautionary behaviours between individuals aged 50 + with multimorbidity and their counterparts without multimorbidity residing in 25 European countries plus Israel. We used data from the SHARE-COVID19 questionnaire on the socio-demographic and economic characteristics, multimorbidity, and precautionary behaviours of individuals. SHARE wave 8 and 7 databases were also used to fully identify individuals with multimorbidity. Our results showed that individuals with multimorbidity were more likely to exhibit precautionary behaviours than their counterparts without multimorbidity when gender, age, education, financial distress and countries were included as controls. Additionally, we found that women, more educated individuals and those experiencing more financial distress adopt more protective behaviours than their counterparts. Our results also indicate that the prevalence of precautionary behaviours is higher in Spain and Italy and lower in Denmark, Finland and Sweden. To guarantee the adoption of preventive actions against COVID-19, public health messaging and actions must continue to be disseminated among middle and older aged persons with multimorbidity, and more awareness campaigns should be targeted at men and less educated individuals but also at persons experiencing less financial distress, particularly in countries where people engaged in fewer precautionary behaviours.

Application of extracellular polymers on soil communities exposed to oil and nickel contamination.

The petrochemical industry is responsible for many accidental releases of pollutants in soil such as hydrocarbons and toxic metals. This co-contamination is responsible for a delay in the degradation of the organic pollution. Many successful technologies to remove these metals apply extracellular polymeric substances (EPS). In this study, we tested the application of an EPS from a Paenibacillus sp. to aid the bioremediation of soils contaminated with crude oil and nickel. We conducted a microcosm experiment to soils containing combinations of oil, nickel, and EPS. The final concentration of oil was evaluated with an infrared spectrometer. Also, we sequenced the metagenomes of the samples in an ion torrent sequencer. The application of EPS did not aid the removal of hydrocarbons with or without the presence of nickel. However, it led to a smaller decrease in the diversity indexes. EPS decreased the abundance of Actinobacteria and increased that of Proteobacteria. The EPS also decreased the connectivity among Actinobacteria in the network analysis. The results indicated that the addition of EPS had a higher effect on the community structure than nickel. Altogether, our results indicate that this approach did not aid the bioremediation of hydrocarbons likely due to its effect in the community structure that affected hydrocarbonoclastic microorganisms.

Neisseria meningitidis Opc invasin binds to the cytoskeletal protein alpha-actinin.

Neisseria meningitidis Opc protein is an effective invasin for human endothelial cells. We have investigated novel human endothelial receptors targeted by Opc and observed that Opc-expressing bacteria interacted with a 100 kDa protein in whole-cell lysates of human endothelial and epithelial cells. The identity of the protein was established as alpha-actinin by mass spectrometry. Opc expression was essential for the recognition of alpha-actinin whether provided in a purified form or in cell extracts. The interaction of the two proteins did not involve intermediate molecules. As there was no demonstrable expression of alpha-actinin on the surfaces of any of the eight cell lines studied, the likelihood of the interactions after meningococcal internalization was examined. Confocal imaging demonstrated considerable colocalization of N. meningitidis with alpha-actinin especially after a prolonged period of internalization. This may imply that bacteria and alpha-actinin initially occur in separate compartments and co-compartmentalization occurs progressively over the 8 h infection period used. In conclusion, these studies have identified a novel and an intracellular target for the N. meningitidis Opc invasin. Since alpha-actinin is a modulator of a variety of signalling pathways and of cytoskeletal functions, its targeting by Opc may enable bacteria to survive/translocate across endothelial barriers.

Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection.

Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination.

Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice.

The role of nitric oxide (NO) in granulomas of Paracoccidioides brasiliensis-infected inducible NO synthase-deficient C57BL/6 mice (iNOS KO) and their wild-type counterparts and its association with osteopontin (OPN) and matrix metalloproteinases (MMPs) was studied. At 15 days after infection (DAI), iNOS KO mice showed compact and necrotic granulomas with OPN+ macrophages and multinucleated giant cells, whereas wild-type mice developed loose granulomas with many fungi and OPN+ cells distributed throughout the tissue. In addition, high OPN levels and fungal load were observed in iNOS KO mice. Both experimental groups had MMP-9 activity. At 120 DAI, iNOS KO had smaller granulomas with OPN+ cells, lower OPN levels, lower fungal load and decreased MMP-9 activity compared with wild-type mice. These findings suggest that NO has an important role in granuloma modulation, by controlling OPN and MMP production, as well as by inducing loose granulomas formation and fungal dissemination, resulting, at later phases, in progression of paracoccidioidomycosis.

Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection.

The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN+ cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.