Clinical profile of Oropouche Fever in Bahia, Brazil: unexpected fatal cases / Perfil clínico de la fiebre de Oropouche en Bahía, Brasil: casos fatales inesperados

Oropouche virus (OROV) is an arbovirus transmitted to humans by mosquitoes, with the Culicoides paraensis mosquito species as its primary vector, causing Oropouche fever. Records of an outbreak in Brazil have so far been restricted to Central-North region of the country. However, an increase in the occurrence of cases of this disease has been observed in the state of Bahia, where the rapid spread of the OROV virus is configured as an outbreak in the South and East macro-regions of great concern for public health. This is a case-based study of acute OROV infection that led to the death of two young women without comorbidities amid an outbreak of the disease. The patient's biological samples were subjected to routine real-time PCR assays for the diagnosis of Oropouche fever and other pathologies. In addition, serological tests and metagenomics were performed during the laboratory investigation. This study shows the need for an active and efficient surveillance system to control the spread of this virus, as well as the importance of carrying out prospective studies to better clarify the natural history of this disease.

El virus Oropouche (OROV) es un arbovirus transmitido al ser humano por mosquitos, siendo el mosquito de la especie Culicoides paraensis su vector principal, causante de la fiebre de Oropouche. Los registros de un brote en Brasil hasta ahora se han restringido a la región Centro-Norte del país. Sin embargo, se ha observado un aumento en la ocurrencia de casos de esta enfermedad en el estado de Bahía, donde la rápida propagación del virus OROV se configura como un brote en las macrorregiones Sur y Este de gran preocupación para la salud pública. Se trata de un estudio de caso de infección aguda por OROV que provocó la muerte de dos mujeres jóvenes sin comorbilidades en medio de un brote de la enfermedad. Las muestras biológicas de la paciente fueron sometidas a ensayos rutinarios de PCR en tiempo real para el diagnóstico de la fiebre de Oropouche y otras patologías. Además, se realizaron pruebas serológicas y metagenómicas durante la investigación de laboratorio. Este estudio muestra la necesidad de un sistema de vigilancia activo y eficiente para controlar la propagación de este virus, así como la importancia de realizar estudios prospectivos para esclarecer mejor la historia natural de esta enfermedad.

The impact of arthritogenic viruses in oral tissues.

Arthritis and periodontitis are inflammatory diseases that share several immunopathogenic features. The expansion in the study of virus-induced arthritis has shed light on how this condition could impact other parts of the human body, including the mouth. Viral arthritis is an inflammatory joint disease caused by several viruses, most notably the alphaviruses Chikungunya virus (CHIKV), Sindbis virus (SINV), Ross River virus (RRV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV). These viruses can induce an upsurge of matrix metalloproteinases and immune-inflammatory mediators such as Interleukin-6 (IL6), IL-1ß, tumor necrosis factor, chemokine ligand 2, and receptor activator of nuclear factor kappa-B ligand in the joint and serum of infected individuals. This can lead to the influx of inflammatory cells to the joints and associated muscles as well as osteoclast activation and differentiation, culminating in clinical signs of swelling, pain, and bone resorption. Moreover, several data indicate that these viral infections can affect other sites of the body, including the mouth. The human oral cavity is a rich and diverse microbial ecosystem, and viral infection can disrupt the balance of microbial species, causing local dysbiosis. Such events can result in oral mucosal damage and gingival bleeding, which are indicative of periodontitis. Additionally, infection by RRV, CHIKV, SINV, MAYV, or ONNV can trigger the formation of osteoclasts and upregulate pro-osteoclastogenic inflammatory mediators, interfering with osteoclast activation. As a result, these viruses may be linked to systemic conditions, including oral manifestations. Therefore, this review focuses on the involvement of alphavirus infections in joint and oral health, acting as potential agents associated with oral mucosal inflammation and alveolar bone loss. The findings of this review demonstrate how alphavirus infections could be linked to the comorbidity between arthritis and periodontitis and may provide a better understanding of potential therapeutic management for both conditions.

Kinetics of neutrophil extracellular traps and cytokines in oral mucositis and Candida infection.

OBJECTIVE: This study investigated the concentrations of neutrophil extracellular traps (NET) and salivary cytokines (IL-1ß, IL-6, IL-8/CXCL8, TNF, and TGF-ß1) in patients undergoing chemotherapy and their associations with oral mucositis (OM) and Candida infection. MATERIALS AND METHODS: This prospective longitudinal study performed at a Brazilian service included 60 adults diagnosed with hematolymphoid diseases. Saliva samples were collected on days D0, D3, D10, and D15. Cytokines were analyzed by ELISA and NET formation by identification of the myeloperoxidase-DNA complex. Oral Candida spp. was cultured. RESULTS: OM occurred in 43.3% of patients and oral candidiasis in 20%. However, 66% of individuals had positive cultures for C. albicans. Higher concentrations of IL-6, IL-8/CXCL8, and TNF and lower concentrations of TGF-ß1 were observed in patients with OM. C. albicans infection contributed to the increase in IL-8/CXCL8, TGF-ß1, and TNF. Individuals with OM or with oral candidiasis had significant reductions in NET formation. In contrast, individuals with C. albicans and with concomitant C. albicans and OM exhibited higher NET formation. CONCLUSION: The kinetics of cytokine levels and NET formation in chemotherapy-induced OM appears to be altered by Candida infection, even in the absence of clinical signs of oral candidiasis.

Avaliação da qualidade dos registros do processo de enfermagem por meio de auditoria retrospectiva / Quality assessment of nursing process records through retrospective audit / Evaluación de la calidad de los registros del proceso de enfermería a través de auditoría retrospectiva

Objetivo: analisar a qualidade dos registros do processo de enfermagem e compará-la segundo as unidades de internação. Método: estudo transversal, retrospectivo que analisou 258 prontuários, entre os meses de março e julho de 2022, de pacientes internados no ano de 2019, em um hospital de grande porte da região Centro-Oeste. Para mensurar a qualidade dos registros, utilizou-se o instrumento Quality of Diagnoses, Interventions and Outcomes, validado para o Brasil. Pesquisa aprovada pelo Comitê de Ética. Resultados: considerando as dimensões dos diagnósticos de enfermagem como processo e como produto, os escores médios gerais de 4,5(±2,6) e 7,1(±4,1), respectivamente. Quanto às dimensões intervenções e resultados de enfermagem, médias de 3,0(±2,1) e 4,7(±4,8). Observaram-se variações das médias de escores entre as unidades analisadas, com diferença significativa (p<0,001). Conclusão: os resultados demonstraram baixos escores de qualidade dos registros do processo de enfermagem, e a média de escores divergiu entre as unidades de internação analisadas(AU)

Objective: To analyze the quality of nursing process records and compare them according to hospitalization units. Method: a cross-sectional, retrospective study that analyzed 258 medical records, between the months of March and July 2022, of patients admitted in 2019, in a large hospital in the Midwest region. The Quality of Diagnoses, Interventions and Outcomes instrument, validated for Brazil, was used to measure the quality of the records. The study was approved by the Ethics Committee. Results: considering the dimensions of nursing diagnoses as a process and as a product, the overall mean scores were 4.5(±2.6) and 7.1(±4.1), respectively. As for the dimensions of nursing interventions and outcomes, the mean scores were 3.0(±2.1) and 4.7(±4.8). There were variations in the mean scores between the units analyzed, with a significant difference (p<0.001). Conclusion: The results showed low quality scores for nursing process records, and the mean scores differed between the inpatient units analyzed(AU)

Objetivo: analizar la calidad de los registros del proceso de enfermería y compararla según las unidades de hospitalización. Método: estudio transversal, retrospectivo, que analizó 258 historias clínicas, entre marzo y julio de 2022, de pacientes internados en 2019 en un gran hospital de la región Centro-Oeste. Para medir la calidad de los registros, se utilizó el instrumento Quality of Diagnoses, Interventions and Outcomes (Calidad de Diagnósticos, Intervenciones y Resultados), validado para Brasil. El Comité de Ética aprobó la investigación. Resultados: considerando las dimensiones de los diagnósticos de enfermería como proceso y como producto, las puntuaciones medias globales fueron 4,5(±2,6) y 7,1(±4,1), respectivamente. En cuanto a las dimensiones de las intervenciones de enfermería y los resultados, los promedios fueron de 3,0(±2,1) y 4,7(±4,8). Hubo variaciones en los promedios de las puntuaciones entre las unidades analizadas, con una diferencia significativa (p<0,001). Conclusión: Los resultados mostraron bajas puntuaciones de calidad en los registros de procesos de enfermería, y los promedios de las puntuaciones difirieron entre las unidades de hospitalización analizadas(AU)

The Th2 Response and Alternative Activation of Macrophages Triggered by Strongyloides venezuelensis Is Linked to Increased Morbidity and Mortality Due to Cryptococcosis in Mice.

Cryptococcosis is a systemic mycosis that causes pneumonia and meningoencephalitis. Strongyloidiasis is a chronic gastrointestinal infection caused by parasites of the genus Strongyloides. Cryptococcosis and strongyloidiasis affect the lungs and are more prevalent in the same world regions, i.e., Africa and tropical countries such as Brazil. It is undeniable that those coincidences may lead to the occurrence of coinfections. However, there are no studies focused on the interaction between Cryptococcus spp. and Strongyloides spp. In this work, we aimed to investigate the interaction between Strongyloides venezuelensis (Sv) and Cryptococcus gattii (Cg) in a murine coinfection model. Murine macrophage exposure to Sv antigens reduced their ability to engulf Cg and produce reactive oxygen species, increasing the ability of fungal growth intracellularly. We then infected mice with both pathogens. Sv infection skewed the host's response to fungal infection, increasing lethality in a murine coinfection model. In addition to increased NO levels and arginase activity, coinfected mice presented a classic Th2 anti-Sv response: eosinophilia, higher levels of alternate activated macrophages (M2), increased concentrations of CCL24 and IL-4, and lower levels of IL-1ß. This milieu favored fungal growth in the lungs with prominent translocation to the brain, increasing the host's tissue damage. In conclusion, our data shows that primary Sv infection promotes Th2 bias of the pulmonary response to Cg-infection and worsens its pathological outcomes.

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review.

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.

Staphylococcus aureus triggers a protective inflammatory response against secondary Cryptococcus gattii infection in a murine model.

Prior infections can provide protection or enhance susceptibility to a subsequent infection through microorganism's interaction or host immunomodulation. Staphylococcus aureus (SA) and Cryptococcus gattii (CG) cause lungs infection, but it is unclear how they interact in vivo. This study aimed to study the effects of the primary SA lung infection on secondary cryptococcosis caused by CG in a murine model. The mice's survival, fungal burden, behavior, immune cells, cytokines, and chemokines were quantified to evaluate murine cryptococcosis under the influence of a previous SA infection. Further, fungal-bacterial in vitro interaction was studied in a culture medium and a phagocytosis assay. The primary infection with SA protects animals from the subsequent CG infection by reducing lethality, improving behavior, and impairing the fungal proliferation within the host. This phenotype was associated with the proinflammatory antifungal host response elicited by the bacteria in the early stage of cryptococcosis. There was no direct inhibition of CG by SA, although the phagocytic activity of macrophages was reduced. Identifying mechanisms involved in this protection may lead to new approaches for preventing and treating cryptococcosis.

Tumour necrosis factor plays a deleterious role in the pathogenesis of chikungunya virus infection.

Arthralgia is a hallmark of chikungunya virus (CHIKV) infection and can be very debilitating and associated with a robust local inflammatory response. Many pathophysiological aspects associated with the disease remain to be elucidated. Here, we describe a novel model of CHIKV infection in immunocompetent mice and evaluate the role of tumour necrosis factor in the pathogenesis of the disease. C57BL/6 wild type (WT) or TNF receptor 1 deficient (TNFR1-/- ) mice were inoculated with 1 × 106 PFU of CHIKV in the paw. Alternatively, etanercept was used to inhibit TNF in infected WT mice. Hypernociception, inflammatory and virological analysis were performed. Inoculation of CHIKV into WT mice induced persistent hypernociception. There was significant viral replication in target organs and local production of inflammatory mediators in early time-points after infection. CHIKV infection was associated with specific humoral IgM and IgG responses. In TNFR1-/- mice, there was a decrease in the hypernociception threshold, which was associated with a milder local inflammatory response in the paw but delayed viral clearance. Local or systemic treatment with etanercept reduced CHIKV-induced hypernociception. This is the first study to describe hypernociception, a clinical correlation of arthralgia, in immunocompetent mice infected with CHIKV. It also demonstrates the dual role of TNF in contributing to viral clearance but driving tissue damage and hypernociception. Inhibition of TNF may have therapeutic benefits but its role in viral clearance suggests that viral levels must be monitored in CHIKV-infected patients and that TNF inhibitors should ideally be used in combination with anti-viral drugs.

Riverhood: political ecologies of socionature commoning and translocal struggles for water justice.

Mega-damming, pollution and depletion endanger rivers worldwide. Meanwhile, modernist imaginaries of ordering 'unruly waters and humans' have become cornerstones of hydraulic-bureaucratic and capitalist development. They separate hydro/social worlds, sideline river-commons cultures, and deepen socio-environmental injustices. But myriad new water justice movements (NWJMs) proliferate: rooted, disruptive, transdisciplinary, multi-scalar coalitions that deploy alternative river-society ontologies, bridge South-North divides, and translate river-enlivening practices from local to global and vice-versa. This paper's framework conceptualizes 'riverhood' to engage with NWJMs and river commoning initiatives. We suggest four interrelated ontologies, situating river socionatures as arenas of material, social and symbolic co-production: 'river-as-ecosociety', 'river-as-territory', 'river-as-subject', and 'river-as-movement'.

Dysbiotic oral microbiota contributes to alveolar bone loss associated with obesity in mice.

INTRODUCTION: Periodontal diseases (PD) are inflammatory conditions that affect the teeth supporting tissues. Increased body fat tissues may contribute to activation of the systemic inflammatory response, leading to comorbidities. Some studies have shown that individuals with obesity present higher incidence of PD than eutrophics. OBJECTIVE: To investigate the impact of obesity on periodontal tissues and oral microbiota in mice. METHODOLOGY: Two obesity mice models were performed, one using 12 weeks of the dietary protocol with a high-fat (HF) diet in C57BL/6 mice and the other using leptin receptor-deficient mice (db/db-/-), which became spontaneously obese. After euthanasia, a DNA-DNA hybridization technique was employed to evaluate the microbiota composition and topical application of chlorhexidine (CHX), an antiseptic, was used to investigate the impact of the oral microbiota on the alveolar bone regarding obesity. RESULTS: Increased adipose tissue may induce alveolar bone loss, neutrophil recruitment, and changes in the oral biofilm, similar to that observed in an experimental model of PD. Topical application of CHX impaired bone changes. CONCLUSION: Obesity may induce changes in the oral microbiota and neutrophil recruitment, which are associated with alveolar bone loss.

Notificação dos casos de tuberculose: um perfil comparativo entre indígenas e não indígenas / Tuberculosis case reporting: a comparative profile between indigenous and non-indigenous people / Notificación de casos de tuberculosis: un perfil comparativo entre indígenas y no indígenas

Considerando que o risco de adoecimento por tuberculose (TB) é maior em grupos mais vulneráveis, tais como a população indígena, este estudo teve como objetivo comparar o perfil dos casos notificados de TB na população indígena e não indígena em Rondônia, no período entre 2015 e 2020. Trata-se de um estudo epidemiológico descritivo, realizado de forma transversal e com abordagem quantitativa, a partir do levantamento das variáveis sociodemográficas e clínicas dos registros dos casos no Sistema de Informação de Agravos de Notificação (Sinan). Considerou-se como critério de inclusão idade igual ou superior a 18 anos, e como critérios de exclusão os registros de pessoas que residiam em outros estados e com raça/cor ignorada ou em branco. Os dados foram analisados por meio de estatística descritiva, teste qui-quadrado e teste exato de Fisher no software Statistic 13.4, da TIBCO, considerando nível de significância de 5%, após atender aos preceitos éticos. Verificou-se significância estatística em relação às variáveis sexo (p = 0,034), escolaridade (p = 0,000), zona de residência (p = 0,000), aids (p = 0,011), alcoolismo (p = 0,038), uso de drogas ilícitas (p = 0,008), tabagismo (p = 0,003), teste de sensibilidade (p = 0,047), HIV (p = 0,002), tratamento diretamente observado (p = 0,000), contatos examinados (p = 0,000) e situação de encerramento (p = 0,035). Diante dos achados, foi possível identificar a diferença no perfil entre indígenas e não indígenas com TB, cujas particularidades do processo saúde-doença exigem capacitação profissional, trabalho em equipe, ações intersetoriais e melhorias na comunicação, inclusive no registro dos dados, para a continuidade da assistência e o fortalecimento das linhas de cuidado.

Considering that the risk of tuberculosis (TB) infection is greater among more vulnerable groups, such as the Indigenous population, this study sought to compare the epidemiological profile of TB cases reported by the Indigenous population of Rondônia, between 2015 and 2020. A descriptive cross-sectional epidemiological study with a quantitative approach was conducted based on the survey of sociodemographic and clinical variables of cases registered at the Information System for Notifiable Diseases (SINAN). Inclusion criterion consisted of individuals aged 18 years or older, and the exclusion criteria were records of people who resided in other states and with unknown or blank race/ethnicity. Data were analyzed using descriptive statistics, chi-square test and Fisher's exact test using TIBCO's Statistic 13.4 software, considering a 5% significance level, after meeting the ethical precepts. The variables gender (p = 0.034), education (p = 0.000), area of residence (p = 0.000), AIDS (p = 0.011), alcoholism (p = 0.038), use of illicit drugs (p = 0.008), smoking (p = 0.003), sensitivity test (p = 0.047), HIV (p = 0.002), directly observed treatment (p = 0.000), contacts examined (p = 0.000), and termination status (p = 0.035) showed statistical significance. These findings indicate a difference in the profile between Indigenous and non-indigenous TB patients, whose particularities of the health-disease process require professional training, teamwork, intersectoral actions and improved communication, including data recording, for the continuity and strengthening of care approaches.

Considerando que el riesgo de enfermar de tuberculosis (TB) es mayor en grupos más vulnerables, como la población indígena, este estudio tuvo como objetivo comparar el perfil de los casos notificados de TB en la población indígena y no indígena de Rondônia (Brasil), en el período comprendido entre 2015 y 2020. Se trata de un estudio epidemiológico descriptivo, realizado de forma transversal y con abordaje cuantitativo, a partir de la encuesta de variables sociodemográficas y clínicas de los registros de casos en el Sistema de Información de Agravamientos de Notificación (Sinan). Se consideró como criterio de inclusión la edad igual o mayor a 18 años, y como exclusión, los registros de casos que residían en otros estados y de raza/color desconocido o en blanco. Los datos fueron analizados mediante estadística descriptiva, prueba de chi-cuadrado y prueba exacta de Fisher en el software Statistic 13.4 de TIBCO, considerando un nivel de significación del 5%, después de cumplir con los preceptos éticos. Se encontró significación estadística para las variables sexo (p = 0,034), escolaridad (p = 0,000), zona de residencia (p = 0,000), sida (p = 0,011), alcoholismo (p = 0,038), consumo de drogas ilícitas (p = 0,008), tabaquismo (p = 0,003), prueba de sensibilidad (p = 0,047), VIH (p = 0,002), tratamiento directamente observado (p = 0,000), contactos examinados (p = 0,000) y situación de terminación (p = 0,035). Los hallazgos encontrados permitieron identificar la diferencia en el perfil entre pueblos indígenas y no indígenas con TB, cuyas particularidades del proceso salud-enfermedad requieren capacitación profesional, trabajo en equipo, acciones intersectoriales, mejoras en la comunicación, incluido el registro de datos, para la continuidad de la atención y el fortalecimiento de las líneas de atención.

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. MATERIAL AND METHODS: Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). CONCLUSION: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

Fcγ RIIb protects from reperfusion injury by controlling antibody and type I IFN-mediated tissue injury and death.

Intestinal ischemia and reperfusion (I/R) is accompanied by an exacerbated inflammatory response characterized by deposition of IgG, release of inflammatory mediators, and intense neutrophil influx in the small intestine, resulting in severe tissue injury and death. We hypothesized that Fcγ RIIb activation by deposited IgG could inhibit tissue damage during I/R. Our results showed that I/R induction led to the deposition of IgG in intestinal tissue during the reperfusion phase. Death upon I/R occurred earlier and was more frequent in Fcγ RIIb-/- than WT mice. The higher lethality rate was associated with greater tissue injury and bacterial translocation to other organs. Fcγ RIIb-/- mice presented changes in the amount and repertoire of circulating IgG, leading to increased IgG deposition in intestinal tissue upon reperfusion in these mice. Depletion of intestinal microbiota prevented antibody deposition and tissue damage in Fcγ RIIb-/- mice submitted to I/R. We also observed increased production of ROS on neutrophils harvested from the intestines of Fcγ RIIb-/- mice submitted to I/R. In contrast, Fcγ RIII-/- mice presented reduced tissue damage and neutrophil influx after reperfusion injury, a phenotype reversed by Fcγ RIIb blockade. In addition, we observed reduced IFN-ß expression in the intestines of Fcγ RIII-/- mice after I/R, a phenotype that was also reverted by blocking Fcγ RIIb. IFNAR-/- mice submitted to I/R presented reduced lethality and TNF release. Altogether our results demonstrate that antibody deposition triggers Fcγ RIIb to control IFN-ß and IFNAR activation and subsequent TNF release, tailoring tissue damage, and death induced by reperfusion injury.

Pyrazinamide photodegradation on NiWO4-palygorskite nanocomposites under polychromatic irradiation.

In this work, antibiotic pyrazinamide (PZA) photodegradation on palygorskite (Pal), NiWO4 crystals, and NiWO4-Pal (2, 6, and 10%) nanocomposites was evaluated under polychromatic irradiation. In the characterization of the samples, XRD patterns displayed good crystallinity for NiWO4 crystals and nanocomposites. In addition, the diffractograms were used in the Rietveld refinement for phase indexing, revealing a wolframite-type monoclinic structure with the space group P2/c. The active vibrational modes related to the characteristic groups of the samples were identified using Raman and FTIR spectroscopy. Photoluminescence (PL) spectra revealed that NiWO4 and NiWO4-Pal (2%) nanocomposite have the highest electron-hole pair recombination rate, and the contribution of the green component in the NiWO4-Pal (2%) nanocomposite indicates a greater contribution of deep energy levels to the PL profile. DRS in the UV-visible region indicated that NiWO4 crystals have indirect band-gap energy (Egap) 2.64 eV; NiWO4-Pal (2, 6, and 10%) nanocomposites have 2.62, 2.58, and 2.59 eV, respectively; and Pal has 2.83 eV. The catalytic tests showed that the NiWO4-Pal (2%) nanocomposite samples, under polychromatic radiation, exhibit greater efficiency in photodegradation at 110 min, with yield of 98.5%. The ROS tests indicated that the studied reactive species play a similar role in PZA photodegradation.

Back pain prevalence and associated factors in Brazilian Unified Health System users / Prevalência de dor nas costas e fatores associados em usuários do Sistema Único de Saúde

ABSTRACT BACKGROUND AND OBJECTIVES: Back pain is one of the main causes of disability worldwide, resulting in higher rates of work absenteeism and years lived with disability. This study aimed to evaluate back pain prevalence and its associated factors in Primary Health Units (PHU) users. METHODS: A community-based cross-sectional study was conducted at PHU located in Pelotas, Brazil. Fifteen individuals of each PHU, aged 18 years or more, were interviewed (n=540). Back pain was defined as pain in one to three back areas (neck, dorsal and lumbar). Demographic, economic, behavioral, nutritional status (body mass index) and health characteristics were assessed as covariates. Poisson regression was used to estimate the prevalence ratio and 95% confidence intervals. RESULTS: Prevalence of back pain in PHU users was 20% (95%CI 16.8 - 23.6). Fair (PR 2.66 95%CI 1.00 - 7.09) and poor (PR 3.65 95%CI 1.31 - 10.16) self-perceived health, musculoskeletal disease (RP 2.71 95%CI 1.84 - 3.98) and current smoking (PR 1.71 95%CI 1.18 - 2.47) were associated with back pain. CONCLUSION: Back pain is a common problem in PHU users in Brazil. Patients with musculoskeletal disease, who are current smokers and have a poor self-perceived health, are more likely to experience back pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor nas costas é uma das principais causas de incapacidade em todo o mundo, resultando em maiores taxas de absenteísmo no trabalho e anos vividos com incapacidade. Este estudo teve como objetivo avaliar a prevalência de dor nas costas e seus fatores associados em usuários de Unidades Básicas de Saúde (UBS). MÉTODOS: Foi realizado um estudo transversal de base comunitária em UBS localizadas em Pelotas, Brasil. Foram entrevistados 15 indivíduos de cada UBS, com idade igual ou superior a 18 anos (n=540). A dor nas costas foi definida como dor em uma a três áreas das costas (pescoço, dorsal e lombar). Características demográficas, econômicas, comportamentais, nutricionais (índice de massa corporal) e de saúde foram avaliadas como covariáveis. A regressão de Poisson foi utilizada para estimar a razão de prevalência e os intervalos de confiança de 95%. RESULTADOS: A prevalência de dor nas costas em usuários de UBS foi de 20% (IC95% 16,8 - 23,6). Autopercepção de saúde regular (RP 2,66 IC95% 1,00 - 7,09) e ruim (RP 3,65 IC95% 1,31 - 10,16), doença musculoesquelética (RP 2,71 IC95% 1,84 - 3,98) e tabagismo atual (RP 1,71 IC95% 1,18 - 2,47) foram associados à dor nas costas. CONCLUSÃO: A dor nas costas é um problema comum em usuários de UBS. Pacientes com doença musculoesquelética, fumantes atuais e com autopercepção de saúde ruim são mais propensos a sentir dor nas costas.

Pseudomonas aeruginosa Infection Modulates the Immune Response and Increases Mice Resistance to Cryptococcus gattii.

Cryptococcosis is an invasive mycosis caused by Cryptococcus spp. that affects the lungs and the central nervous system (CNS). Due to the severity of the disease, it may occur concomitantly with other pathogens, as a coinfection. Pseudomonas aeruginosa (Pa), an opportunistic pathogen, can also cause pneumonia. In this work, we studied the interaction of C. gattii (Cg) and Pa, both in vitro and in vivo. Pa reduced growth of Cg by the secretion of inhibitory molecules in vitro. Macrophages previously stimulated with Pa presented increased fungicidal activity. In vivo, previous Pa infection reduced morbidity and delayed the lethality due to cryptococcosis. This phenotype was correlated with the decreased fungal burden in the lungs and brain, showing a delay of Cg translocation to the CNS. Also, there was increased production of IL-1ß, CXCL-1, and IL-10, together with the influx of iNOS-positive macrophages and neutrophils to the lungs. Altogether, Pa turned the lung into a hostile environment to the growth of a secondary pathogen, making it difficult for the fungus to translocate to the CNS. Further, iNOS inhibition reverted the Pa protective phenotype, suggesting its important role in the coinfection. Altogether, the primary Pa infection leads to balanced pro-inflammatory and anti-inflammatory responses during Cg infection. This response provided better control of cryptococcosis and was decisive for the mild evolution of the disease and prolonged survival of coinfected mice in a mechanism dependent on iNOS.

Anti-Zika Virus Activity of Plant Extracts Containing Polyphenols and Triterpenes on Vero CCL-81 and Human Neuroblastoma SH-SY5Y Cells.

Zika virus (ZIKV) infection is a global threat associated to neurological disorders in adults and microcephaly in children born to infected mothers. No vaccine or drug is available against ZIKV. We herein report the anti-ZIKV activity of 36 plant extracts containing polyphenols and/or triterpenes. ZIKV-infected Vero CCL-81 cells were treated with samples at non-cytotoxic concentrations, determined by MTT and LDH assays. One third of the extracts elicited concentration-dependent anti-ZIKV effect, with viral loads reduction from 0.4 to 3.8 log units. The 12 active extracts were tested on ZIKV-infected SH-SY5Y cells and significant reductions of viral loads (in log units) were induced by Maytenus ilicifolia (4.5 log), Terminalia phaeocarpa (3.7 log), Maytenus rigida (1.7 log) and Echinodorus grandiflorus (1.7 log) extracts. Median cytotoxic concentration (CC50 ) of these extracts in Vero cells were higher than in SH-SY5Y lineage. M. ilicifolia (IC50 =16.8±10.3 µg/mL, SI=3.4) and T. phaeocarpa (IC50 =22.0±6.8 µg/mL, SI=4.8) were the most active extracts. UPLC-ESI-MS/MS analysis of M. ilicifolia extract led to the identification of 7 triterpenes, of which lupeol and a mixture of friedelin/friedelinol showed no activity against ZIKV. The composition of T. phaeocarpa extract comprises phenolic acids, ellagitannins and flavonoids, as recently reported by us. In conclusion, the anti-ZIKV activity of 12 plant extracts is here described for the first time and polyphenols and triterpenes were identified as the probable bioactive constituents of T. phaeocarpa and M. ilicifolia, respectively.

Mitochondrial DNA as a Possible Ligand for TLR9 in Irinotecan-induced Small Intestinal Mucositis.

Cancer chemotherapy and radiotherapy may result in mucositis characterized by stem cell damage and inflammation in the gastrointestinal tract. The molecular mechanisms underlying this pathology remain unknown. Based on the assumption that mitochondrial CPG-DNA (mtDNA) released and sensed by TLR9 could underlie mucositis pathology, we analyzed the mtDNA levels in sera as well as inflammatory and disease parameters in the small intestine from wild-type (WT) and TLR9-deficient mice (TLR9-/-) in an experimental model of intestinal mucositis induced by irinotecan. Additionally, we verified the ability of WT and TLR9-/- macrophages to respond to CpG-DNA in vitro. WT mice injected with irinotecan presented a progressive increase in mtDNA in the serum along with increased hematocrit, shortening of small intestine length, reduction of intestinal villus:crypt ratio and increased influx of neutrophils, which were followed by higher expression of Nlrp3 and Casp1 mRNA and increased IL-1ß levels in the ileum when compared to vehicle-injected mice. TLR9-deficient mice were protected in all these parameters when compared to WT mice. Furthermore, TLR9 was required for the production of IL-1ß and NO after macrophage stimulation with CpG-DNA. Overall, our findings show that the amount of circulating free CpG-DNA is increased upon chemotherapy and that TLR9 activation is important for NLRP3 inflammasome transcription and further IL-1ß release, playing a central role in the development of irinotecan-induced intestinal mucositis. We suggest that TLR9 antagonism may be a new therapeutic strategy for limiting irinotecan-induced intestinal inflammation.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice.

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1ß levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.