A Functional Assessment of Fetal Liver and Monocyte-Derived Macrophages in the Lung Alveolar Environment.

It is becoming clear that every organ is seeded by a population of fetal liver-derived macrophages that are replaced at different rates by monocyte-derived macrophages. Using the Ms4a3tdTomato reporter mouse that reports on monocyte-derived alveolar macrophages (Mo-AMs) and our ability to examine AM function using our multichannel intravital microscopy, we examined the fetal-liver derived alveolar macrophage (FL-AM) and Mo-AM populations within the same mouse under various environmental conditions. The experiments unveiled that AMs migrated from alveolus to alveolus and phagocytosed bacteria identically regardless of ontogenic origin. Using 50 PFU of influenza A virus (IAV) determined using the Madin-Darby canine kidney (MDCK) cell line, we noted that both populations were susceptible to IAV-induced immunoparalysis, which also led to impaired phagocytosis of secondary bacterial infections. Both FL-AMs and Mo-AMs were trained by ß-glucan to resist IAV-induced paralysis. Over time (40 wk), Mo-AMs began to outperform FL-AMs, although both populations were still sensitive to IAV. Our data also show that clodronate depletion of AMs leads to replenishment, but by FL-AMs, and these macrophages do show some functional impairment for a limited time. Overall, the system is designed such that new macrophages rapidly assume the function of tissue-resident macrophages when both populations are examined in an identical environment. These data do differ from artificial depletion methods that compare Mo-AMs and FL-AMs.

Eimeria erythrorhynchosi n. sp. (Apicomplexa: Eimeriidae) from the American white pelican Pelecanus erythrorhynchos Gmelin, 1789 (Pelecaniformes: Pelecanidae) in Toluca, Mexico.

A new coccidian species, Eimeria erythrorhynchosi n. sp. (Apicomplexa: Eimeriidae) collected from the American white pelican Pelecanus erythrorhynchos Gmelin 1789, is reported from Toluca city, Mexico. Sporulated oocysts of the new species are ovoidal, 17.5-19.6 × 14.1-14.8 (18.5 × 14.5) µm, with a length/width (L/W) ratio of 1.0-1.5 (1.25); micropyle present, robust and protruding, W: 4.5-5.5, and polar body (1 or 2), L × W: 2.5 (2-3), associated with the micropyle; oocyst residuum absent. Sporocysts are ovoidal, 10.1-11.2 × 6.4-7.1 (10.7 × 6.8) µm, with a length/width (L/W) ratio of 1.0-1.6 (1.3); Stieda and sub-Stieda bodies are both present, but para-Stieda body is absent; sporocyst residuum of diffuse granules. Sporozoites are vermiform, 9.6 × 2.4 µm. The new species is the seventh species of Eimeria recorded in Pelecaniformes and the third in Pelecanidae.

Utilização da algometria e termografia infravermelha como instrumentos de avaliação da dor: uma revisão sistemática / Use of algometry and infrared thermography as tools for pain evaluation: a systematic review

Infrared thermography is a technique used for complementary diagnosis of pain, through the presentation of thermal images with an infrared sensor that assesses body surface temperature. Pressure algometry is an objective method that seeks to quantify pain at specific points. Both techniques have been employed for diagnostic purposes. Objective: To review the literature on publications that addressed the use of thermography and algometry in combination as an assessment tool in studies of evaluation of pain. Method: This was a systematic review conducted on Pubmed, Bireme and Scielo databases, using the following descriptors: "thermography" AND "pain threshold", and "thermography" AND "pain tolerance", without limitation of publication date, in English and Portuguese, in September 2020. Eligibility criteria for the studies were: use of thermography in combination with algometry in aimed at the outcome of temperature variation in chronic painful processes in humans. Results: The search resulted in thirty-two studies, and after abstract analysis, twenty-two were excluded for not meeting inclusion criteria. The remaining ten were read in full and made up the present review. Conclusion: Although few studies have employed both techniques in the same diagnostic assessment method, the use of algometry and thermography in combination may provide objective measures of subjective symptoms, which can bring a great contribution to the diagnostic accuracy and clinical monitoring of patients affected by painful processes.

A termografia infravermelha é uma técnica utilizada para diagnóstico complementar da dor, através da apresentação de imagens térmicas com uma câmera infravermelha que mensura a temperatura da superfície do corpo. A algometria de pressão é um método objetivo que busca quantificar a dor em pontos determinados. Ambas as técnicas vem sido empregadas para finalidades diagnósticas. Objetivo: Revisar a literatura acerca das publicações que abordaram a utilização da termografia e algometria em conjunto como instrumentos de avaliação da dor. Método: Trata-se de uma revisão sistemática nas bases de dados Pubmed, Bireme e Scielo utilizando os seguintes descritores: "thermography" AND "pain threshold", e "termografia" AND "tolerância à dor", sem limitação por data de publicação, em inglês e português, no mês de setembro de 2022. Os critérios de elegibilidade para os estudos foram: utilização da termografia em conjunto com a algometria na busca do desfecho variação da temperatura em processos dolorosos crônicos em seres humanos. Resultados: A busca resultou em trinta e dois estudos, e após a análise dos resumos, vinte e dois foram excluídos por não preencherem os critérios de inclusão, restando dez que foram lidos na íntegra e que compuseram a presente revisão. Conclusão: Apesar da algometria e termografia se apresentarem como técnicas pragmaticamente válidas no estudo da dor, esta revisão mostrou que poucos estudos incluíram em seu desenho a combinação destas técnicas como instrumentos de avaliação.

FK506 impairs neutrophil migration that results in increased polymicrobial sepsis susceptibility.

OBJECTIVE: This study aimed to investigate the effects of FK506 on experimental sepsis immunopathology. It investigated the effect of FK506 on leukocyte recruitment to the site of infection, systemic cytokine production, and organ injury in mice with sepsis. METHODS: Using a murine cecal ligation and puncture (CLP) peritonitis model, the experiments were performed with wild-type (WT) mice and mice deficient in the gene Nfat1 (Nfat1-/-) in the C57BL/6 background. Animals were treated with 2.0 mg/kg of FK506, subcutaneously, 1 h before the sepsis model, twice a day (12 h/12 h). The number of bacteria colony forming units (CFU) was manually counted. The number of neutrophils in the lungs was estimated by the myeloperoxidase (MPO) assay. The expression of CXCR2 in neutrophils was determined using flow cytometry analysis. The expression of inflammatory cytokines in macrophage was determined using ELISA. The direct effect of FK506 on CXCR2 internalization was evaluated using HEK-293T cells after CXCL2 stimulation by the BRET method. RESULTS: FK506 treatment potentiated the failure of neutrophil migration into the peritoneal cavity, resulting in bacteremia and an exacerbated systemic inflammatory response, which led to higher organ damage and mortality rates. Failed neutrophil migration was associated with elevated CXCL2 chemokine plasma levels and lower expression of the CXCR2 receptor on circulating neutrophils compared with non-treated CLP-induced septic mice. FK506 did not directly affect CXCL2-induced CXCR2 internalization by transfected HEK-293 cells or mice neutrophils, despite increasing CXCL2 release by LPS-treated macrophages. Finally, the CLP-induced response of Nfat1-/- mice was similar to those observed in the Nfat1+/+ genotype, suggesting that the FK506 effect is not dependent on the NFAT1 pathway. CONCLUSION: Our data indicate that the increased susceptibility to infection of FK506-treated mice is associated with failed neutrophil migration due to the reduced membrane availability of CXCR2 receptors in response to exacerbated levels of circulating CXCL2.

The mid-secretory endometrial transcriptomic landscape in endometriosis: a meta-analysis.

STUDY QUESTION: Do women with endometriosis have a different endometrial gene expression profile at the time of embryo implantation than women without endometriosis? SUMMARY ANSWER: The endometrial gene expression profile of women with endometriosis differs from that of women without endometriosis at the mid-secretory phase, although the differences are small. WHAT IS KNOWN ALREADY: About 50% of women with endometriosis suffer infertility. Several molecular studies have suggested impaired endometrial receptivity in women with endometriosis, while others have detected no dysregulation of endometrial receptivity. Nevertheless, the previous endometrial transcriptome studies comparing women with and without endometriosis have been performed in small sample size with limited statistical power. We set out to systematically search and compile data of endometrial gene expression signatures at the receptive phase in women with endometriosis versus control women. Based on the obtained data, we conducted a meta-analysis of differentially expressed genes in order to raise the power of the analysis for identifying the molecular profiles of receptive phase endometria in endometriosis. STUDY DESIGN SIZE DURATION: A systematic literature search was conducted up to February 2022 following PRISMA criteria and included PubMed, Cochrane and Web of Science databases. For the systematic search, the term 'endometriosis' was paired with the terms 'transcriptomics', 'transcriptome', 'gene expression', 'RNA-seq', 'sequencing' and 'array', by using the Boolean operator 'AND' to connect them. Articles written in English were screened and interrogated for data extraction. PARTICIPANTS/MATERIALS SETTING METHODS: A meta-analysis was performed on the selected studies to extract the differentially expressed genes described at the mid-secretory phase in women with endometriosis versus women without endometriosis in natural cycles, using the robust rank aggregation method. In total, transcriptome data of 125 women (78 patients and 47 controls) were meta-analysed, with a special focus on endometrial receptivity-specific genes based on commercial endometrial receptivity tests. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 8 studies were eligible for the quantitative meta-analysis, gathering transcriptome data from the mid-secretory phase endometria of 125 women. A total of 7779 differentially expressed transcripts between the study groups were retrieved (3496 up-regulated and 4283 down-regulated) and were meta-analysed. After stringent multiple correction, there was no differential expression of any single molecule in the endometrium of women with endometriosis versus controls, while enrichment analysis detected that the pathways of chemotaxis and locomotion are dysregulated in endometriosis. Further analysis of endometrial receptivity-specific genes highlighted dysregulation of C4BPA, MAOA and PAEP and enrichment of immune and defence pathways in women with endometriosis. LIMITATIONS REASONS FOR CAUTION: Most of the studies included into the meta-analysis were relatively small and had different study designs, which might have contributed to a bias. WIDER IMPLICATIONS OF THE FINDINGS: The current meta-analysis supports the hypothesis that endometrial receptivity is altered in women with endometriosis, although the changes are small. The molecules and pathways identified could serve as future biomarkers and therapeutical targets in detecting and treating endometriosis-associated infertility. STUDY FUNDING/COMPETING INTERESTS: The authors declare no competing interests. This work was supported by the Spanish Ministry of Education, Culture and Sport [grant FPU15/01193] and the Margarita Salas program for the Requalification of the Spanish University system [grant UJAR01MS]; Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; Programa Operativo FEDER Andalucía (B-CTS-500-UGR18; A-CTS-614-UGR20); the Junta de Andalucía [BIO-302; and PAIDI P20_00158]; the University of Jaén [PAIUJA-EI_CTS02_2017]; the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR; the Estonian Research Council (grant PRG1076); Horizon 2020 innovation (ERIN, grant no. EU952516) of the European Commission and Enterprise Estonia (grant EU48695). TRIAL REGISTRATION NUMBER: The systematic review was registered at PROSPERO (identifier: CRD42020122054).

Promoção da alimentação saudável via rede social entre universitários / Promotion of healthy eating using social network among university students

Este estudo verificou os efeitos de uma ação educativa via rede social no consumo alimentar, conhecimento em alimentação e nutrição e nos fatores que facilitam e dificultam a adoção de uma alimentação saudável entre universitários de um Centro Universitário de São Paulo. Trata-se de estudo de intervenção, com aplicação de questionário antes e depois da ação educativa. Participaram 141 universitários entre 18 e 56 anos e classe socioeconômica B (46,81%). 39,72% estavam com excesso de peso, 76,60% foram classificados em "Atenção" referente ao consumo alimentar e mais de 50% tinham moderado conhecimento em nutrição. O principal dificultador para se ter uma alimentação saudável foi o custo elevado dos alimentos. Conclui-se que os efeitos da ação educativa foram positivos na redução do Índice de Massa Corporal, aumento na pontuação do consumo alimentar e do conhecimento em nutrição. Houve aumento de comportamento adequado para oito questões do consumo alimentar.

This study verified the effects of an educational action using social network on food consumption, knowledge of food and nutrition and factors that facilitate and hinder the adoption of healthy eating, among university students at a University Center in São Paulo. It is an intervention study, with the application of a questionnaire before and after the educational action. 141 university students between 18 and 56 years old and socioeconomic class B (46,81%) participated. 39.72% were overweight, 76.60% were classified as "Attention" regarding food consumption and more than 50% had moderate knowledge of nutrition. The main obstacle to healthy eating was the high cost of food. It is concluded that the effects of the educational action were positive in reducing the Body Mass Index, increasing the score of food consumption and knowledge in nutrition. There was an increase in appropriate behavior for eight issues of food consumption.

Neurological symptoms associated with SARS-CoV-2 infection in a tertiary hospital in Bogota, Colombia.

Introduction: SARS-CoV-2 infection is an emerging disease that represents a threat to life globally, with more than 179 million confirmed cases and 3 million deaths. In Colombia, where almost 5 million infections and approximately 127 thousand deaths have been reported, it presents a wide variety of neurological manifestations that range from mild to severe symptoms. Objective: This study describes the characteristics of neurological manifestations in patients with COVID-19 in the period March-September 2020 at a tertiary hospital in Bogota. Methods: We performed a cross-sectional descriptive study. We selected patients by non-probability sampling, including all patients attended by the neurology service at our hospital. We included all patients with infection confirmed by RT-PCR test and neurological disease confirmed by tomography, study of cerebrospinal fluid, and clinical manifestations reported in the medical history. We excluded epileptic patients who presented seizures as the only clinical manifestation. Results: In a total of 58 patients, the mean age was 58 years, with 60.3% of patients being men; 65.5% were alert at admission. The main neurological symptom was brain ischaemia, in 36.2%, followed by seizures, in 25.9%. Arterial hypertension was observed in 58.6%. We observed no alterations in the cerebrospinal fluid; the mean hospital stay was 35 days, and 41.4% of patients died. Conclusions: SARS-CoV-2 infection not only affects the respiratory system, but can also cause a range of neurological manifestations ranging from mild symptoms such as headache, dysgeusia, and anosmia to severe complications such as seizures, brain ischaemia/haemorrhage, encephalopathy, or death.

Introducción: La infección por SARS-CoV2 es una enfermedad emergente que representa un peligro para la vida a nivel mundial, con más de 179 millones de casos confirmados y 3 millones de muertes. En Colombia, se han reportado casi 5 millones de personas contagiadas y alrededor de 127 mil fallecidos, presenta una amplia variedad de manifestaciones neurológicas que van desde leves a severas. Objetivo: Describir las características de las manifestaciones neurológicas en pacientes con infección por coronavirus SARS-CoV2 (Covid19) en el periodo marzo ­ septiembre de 2020 en un Hospital de 3er nivel en Bogotá. Metodología: Se trata de un estudio descriptivo tipo corte transversal. Se realizó un muestreo no probabilístico en el que se incluyeron todos los casos atendidos por el servicio de neurología de la institución seleccionada, se incluyeron todos los pacientes con infección confirmada por prueba de RT-PCR y aquellos con enfermedad neurológica documentada por tomografía, estudio de líquido cefalorraquídeo o manifestaciones clínicas registradas en la historia clínica. Fueron excluidos los pacientes epilépticos quienes presenten convulsiones como única manifestación clínica. Resultados: En un total de 58 pacientes, se encontró media de edad de 58 años, con un 60,3% correspondiente al sexo masculino, 65,5% estuvieron alerta, la principal manifestación neurológica fue la isquemia cerebral en un 36,2%, seguida de convulsiones con un 25,9%. La hipertensión arterial estuvo en el 58,6%. No hubo alteraciones en el LCR, el promedio de estancia hospitalaria fue de 35 días y el 41,4% fallecieron. Conclusiones: La infección por SARS-CoV2 condiciona no solo una afección al sistema respiratorio, sino que presenta un amplio espectro de manifestaciones neurológicas que van desde las más leves como cefalea, disgeusia y anosmia, hasta las más graves como convulsiones, isquemia/sangrado cerebral, encefalopatía o muerte.

ICAMs are dispensable for influenza clearance and anti-viral humoral and cellular immunity.

αLß2 (LFA-1) mediated interactions with ICAM-1 and ICAM-2 predominate leukocyte-vascular interactions, but their functions in extravascular cell-cell communications is still debated. The roles of these two ligands in leukocyte trafficking, lymphocyte differentiation, and immunity to influenza infections were dissected in the present study. Surprisingly, double ICAM-1 and ICAM-2 knock out mice (herein ICAM-1/2-/- mice) infected with a lab adapted H1N1 influenza A virus fully recovered from infection, elicited potent humoral immunity, and generated normal long lasting anti-viral CD8+ T cell memory. Furthermore, lung capillary ICAMs were dispensable for both NK and neutrophil entry to virus infected lungs. Mediastinal lymph nodes (MedLNs) of ICAM-1/2-/- mice poorly recruited naïve T cells and B lymphocytes but elicited normal humoral immunity critical for viral clearance and effective CD8+ differentiation into IFN-γ producing T cells. Furthermore, whereas reduced numbers of virus specific effector CD8+ T cells accumulated inside infected ICAM-1/2-/- lungs, normal virus-specific TRM CD8+ cells were generated inside these lungs and fully protected ICAM-1/2-/- mice from secondary heterosubtypic infections. B lymphocyte entry to the MedLNs and differentiation into extrafollicular plasmablasts, producing high affinity anti-influenza IgG2a antibodies, were also ICAM-1 and ICAM-2 independent. A potent antiviral humoral response was associated with accumulation of hyper-stimulated cDC2s in ICAM null MedLNs and higher numbers of virus-specific T follicular helper (Tfh) cells generated following lung infection. Mice selectively depleted of cDC ICAM-1 expression supported, however, normal CTL and Tfh differentiation following influenza infection, ruling out essential co-stimulatory functions of DC ICAM-1 in CD8+ and CD4+ T cell differentiation. Collectively our findings suggest that lung ICAMs are dispensable for innate leukocyte trafficking to influenza infected lungs, for the generation of peri-epithelial TRM CD8+ cells, and long term anti-viral cellular immunity. In lung draining LNs, although ICAMs promote lymphocyte homing, these key integrin ligands are not required for influenza-specific humoral immunity or generation of IFN-γ effector CD8+ T cells. In conclusion, our findings suggest unexpected compensatory mechanisms that orchestrate protective anti-influenza immunity in the absence of vascular and extravascular ICAMs.

Impulsive Neural Control to Schedule Antivirals and Immunomodulators for COVID-19.

New SARS-CoV-2 variants escaping the effect of vaccines are an eminent threat. The use of antivirals to inhibit the viral replication cycle or immunomodulators to regulate host immune responses can help to tackle the viral infection at the host level. To evaluate the potential use of these therapies, we propose the application of an inverse optimal neural controller to a mathematical model that represents SARS-CoV-2 dynamics in the host. Antiviral effects and immune responses are considered as the control actions. The variability between infected hosts can be large, thus, the host infection dynamics are identified based on a Recurrent High-Order Neural Network (RHONN) trained with the Extended Kalman Filter (EKF). The performance of the control strategies is tested by employing a Monte Carlo analysis. Simulation results present different scenarios where potential antivirals and immunomodulators could reduce the viral load.

Adaptive processing for noise attenuation in laser speckle contrast imaging.

BACKGROUND AND OBJECTIVE: Blood vessel visualization is an essential task to treat and evaluate diseases such as port-wine stain. Laser Speckle Contrast Imaging (LSCI) have applications in the analysis of the microvasculature. However, it is often limited to superficial depths because the tissue among skin and microvasculature introduces noise in the image. To analyze microvasculature, traditional LSCI methods compute a Contrast Image (CI) by using a shifting window of fixed size and shape, which is inadequate in images with structures different types of morphologies in it, as happens in LSCI. This work aims to reduce the noise in the CIs to improve the visualization of blood vessels at high depths (> 300 µ m). METHODS: The proposed method processes the CIs with analysis windows that change their size and shape for each pixel to compute the contrast representation with pixels more representatives to the region. RESULTS: We performed experiments varying the depth of the blood vessels, the number of frames required to compute the representation, and the blood flow in the blood vessel. We looked for an improvement in the Contrast to Noise Ratio (CNR) in the periphery of the blood vessels using an analysis of variance. Finding that the adaptive processing of the contrast images allows a significant noise attenuation, translated into a better visualization of blood vessels. An average CNR of 2.62 ± 1 and 5.26 ± 1.7 was reached for in-vitro and in-vivo tests respectively, which is higher in comparison with traditional LSCI approaches. CONCLUSIONS: The results, backed by the measured CNR, obtained a noise reduction in the CIs, this means a better temporal and spatial resolution. The proposed awK method can obtain an image with better quality than the state-of-the-art methods using fewer frames.

Immediate effect of quick massage on muscle tension and pressure pain threshold / Efeito imediato da quick massage sobre a tensão muscular e o limiar de tolerância de dor à pressão

ABSTRACT BACKGROUND AND OBJECTIVES: Massage is described as an effective complementary therapy for relieving muscle tension and pain. The aim of this study was to verify the benefits of quick massage on muscle tension and pressure pain tolerance threshold (PPT). METHODS: A randomized clinical study in which 40 professors participated and were randomly divided into control (CG) and experimental (EG) groups. They were assessed for the level of muscle tension in the shoulder and neck regions using the visual analogue scale (VAS). PPT was assessed through algometry at the upper trapezius and sternocleidomastoid muscles and at the following anatomical areas: base of the occipital, scapular spine, thoracic (T6-T7) and lumbar (L4-L5) regions. The EG received a single session of quick massage for 20 minutes on the shoulders, neck and spine. RESULTS: Regarding pain, a significant difference was observed only at the base of the occipital, the EG presented greater tolerance to pressure pain both before and after the intervention when compared to the CG. Regarding muscle tension, after the intervention, there was a reduction in the perception in the EG compared to the CG group. CONCLUSION: Quick massage was efficient to decrease the perception of muscle tension assessed by VAS, however, PPT did not increase after the intervention.

RESUMO JUSTIFICATIVA E OBJETIVOS: A massagem é descrita como terapia complementar efetiva no alívio de dor e tensão muscular. O objetivo deste estudo foi verificar os benefícios da Quick Massage sobre a tensão muscular e o limiar de tolerância de dor à pressão (LTDP). MÉTODOS: Estudo clínico randomizado que incluiu 40 docentes divididos aleatoriamente em grupo controle (GC) e grupo experimental (GE). Eles foram avaliados quanto ao nível de tensão muscular na região dos ombros e pescoço por meio da escala analógica visual (EAV). O LTDP foi avaliado por algometria sobre os músculos trapézio superior e esternocleidomastóideo e nos seguintes pontos anatômicos: base do occipital, espinha da escápula, região torácica (T6-T7) e região lombar (L4-L5). O GE recebeu uma única sessão de Quick Massage por 20 minutos na região dos ombros, pescoço e coluna vertebral. RESULTADOS: Em relação à dor, somente na base do occipital foi verificada diferença significante, o GE apresentou maior tolerância de dor à pressão tanto antes quanto após a intervenção em relação ao GC. Em relação à tensão muscular, após a intervenção, houve redução da percepção no GE em relação ao grupo GC. CONCLUSÃO: A Quick Massage foi eficiente para diminuir a percepção da tensão muscular, contudo, o limiar de tolerância de dor à pressão não aumentou após a intervenção.

Prevalence of chronic pain and associated factors in a small town in southern Brazil / Prevalência de dor crônica e fatores associados em uma pequena cidade do sul do Brasil

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic pain represents a relevant public health problem due to its high global prevalence, high costs of medical care, complexity of the treatment and loss of productive capacity. In Brazil, there are few population-based studies regarding chronic pain and associated factors, thus, the aim of this study was to evaluate the prevalence and factors associated with chronic pain among residents of urban and rural regions of the city of Irani-SC. METHODS: Cross-sectional population study, with random sampling, stratified by sex and age, in which 409 residents participated. Data was collected by individual interview, sociodemographic and clinical questionnaires, and application of a lifestyle profile instrument. RESULTS: The prevalence of chronic pain was 56% of the population. The most frequent associated factors were: female sex, being married, living in urban area, older age, more years of work, a higher number of children, fewer vacation periods in the last year, low schooling, higher body mass index, low coffee consumption and a higher number of comorbidities when compared to the group without chronic pain (p<0.05). There was no significant difference between groups regarding lifestyle. CONCLUSION: Prevalence of chronic pain was high when compared to that found by other studies. Chronic pain was more prevalent in women, married, white, and urban residents. Possible predictors of this condition were age, years of work, number of children, vacation days in the last 12 months, number of cups of coffee consumed per day, body mass index and number of comorbidities.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor crônica representa relevante problema de saúde pública pela alta prevalência, custo de cuidados médicos, complexidade de tratamento e perda da capacidade produtiva. No Brasil, há poucos estudos populacionais sobre dor crônica e fatores associados, assim, o objetivo deste estudo foi avaliar a prevalência e fatores associados à dor crônica entre os residentes das regiões urbana e rural da cidade de Irani-SC. MÉTODOS: Estudo transversal populacional, com amostragem aleatória, estratificada por sexo e idade, do qual participaram 409 pessoas. Os dados foram coletados por entrevista individual, questionários sociodemográfico e clínico e aplicação de instrumento de perfil de estilo de vida. RESULTADOS: A prevalência de dor crônica foi de 56%. Os fatores associados mais frequentes foram: sexo feminino, ser casado, morar em área urbana, idade mais avançada, mais anos trabalhados, maior número de filhos, menos períodos de férias no último ano, baixa escolaridade, consumo de menos xícaras de café por dia, maior índice de massa corporal e maior número de comorbidades quando comparados ao grupo sem dor crônica (p<0,05). Não houve diferença significante entre os grupos em relação ao estilo de vida. CONCLUSÃO: A prevalência de dor crônica foi alta quando comparada à encontrada por estudos correlatos. Foi mais prevalente em mulheres, indivíduos casados, brancos e residentes em área urbana. Possíveis preditores desta condição foram idade, anos trabalhados, número de filhos, dias de férias no último ano, número de xícaras de café consumidos por dia, índice de massa corporal e número de comorbidades.

A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies

Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome of respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, a key outstanding question is whether COVID-19 drives a unique program of neutrophil activation or effector functions that contributes to the severe pathogenesis of this pandemic illness, and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS compared to non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps (NETs). Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.

CCR2-deficient mice are protected to sepsis by the disruption of the inflammatory monocytes emigration from the bone marrow.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Inflammatory monocytes are recruited to both the infection site and vital organs during sepsis; however, the mechanisms that orchestrate their migration, as well as the participation of these cells in systemic inflammation and vital organ damage, are still not fully elucidated. In this context, we described that CCR2-deficient mice had diminished migration of inflammatory monocytes from bone marrow to the circulation and subsequently to the site of infection and vital organs during cecal ligation and puncture (CLP)-induced polymicrobial sepsis. The reduction in the migration of inflammatory monocytes to the infection site was accompanied by a significant increase in the number of neutrophils in the same compartment, which seemed to counterbalance the absence of inflammatory monocytes in controlling microbial growth. Indeed, wild-type (WT) and CCR2-deficient mice under CLP presented similar control of infection. However, the CCR2-deficient mice were more resistant to sepsis, which was associated with a decrease in inflammatory mediators and organ damage biomarkers. Furthermore, the systemic adoptive transfer of CCR2-WT or CCR2-deficient inflammatory monocytes into CCR2-deficient mice equally increased the susceptibility to sepsis, demonstrating the deleterious role of these cells in the periphery even when CCR2 is absent. Thus, despite the host-protective role of inflammatory monocytes in controlling infection, our results demonstrated that the mechanism by which CCR2 deficiency shows protection to CLP-induced sepsis is due to a decrease of inflammatory monocytes emigration from bone marrow to the circulation and vital organs, resulting in the reduction of organ damage and systemic cytokine production.

Model predictive control for optimal social distancing in a type SIR-switched model.

Social distancing strategies have been adopted by governments to manage the COVID-19 pandemic, since the first outbreak began. However, further epidemic waves keep out the return of economic and social activities to their standard levels of intensity. Social distancing interventions based on control theory are needed to consider a formal dynamic characterization of the implemented SIR-type model to avoid unrealistic objectives and prevent further outbreaks. The objective of this work is twofold: to fully understand some dynamical aspects of SIR-type models under control actions (associated with second waves) and, based on it, to propose a switching non-linear model predictive control that optimize the non-pharmaceutical measures strategy. Opposite to other strategies, the objective here is not just to minimize the number of infected individuals at any time, but to minimize the final size of the epidemic while minimizing the time of social restrictions and avoiding the infected prevalence peak to overpass a maximum established by the healthcare system capacity. Simulations illustrate the benefits of the aforementioned proposal.

Pain, disability and catastrophizing in individuals with knee osteoarthritis / Dor, incapacidade e catastrofização em indivíduos com osteoartrite do joelho

ABSTRACT BACKGROUND AND OBJECTIVES: Knee osteoarthritis is among the leading sources of chronic disability and may lead to depression, anxiety and pain catastrophizing, enhancing perceived pain. This study aimed at investigating the influence of pain catastrophizing on attitudes and perception of pain, and in the functionality of individuals with knee osteoarthritis. METHODS: This observational study involved 18 patients, who were assessed for weight and height, and completed the Pain-related Catastrophizing Thoughts Scale (PCTS), Survey of Pain Attitudes (SPA), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analog scale (VAS). Symptoms and disability were assessed by the Lequesne Index, functional mobility was evaluated by the Timed Up and Go (TUG) test. Pressure pain tolerance thresholds (PPT) were assessed by a digital algometer. RESULTS: Mean body mass index of the sample was classified as obese (32,2±4,3). When split by the median of PCTS, differences were observed in most domains of SPA. Patients with more catastrophic thoughts took longer to perform TUG and presented more pain, joint stiffness and worse functionality (WOMAC). Despite the tendency to report more pain (VAS) in patients above the median score of PCTS, no differences were observed between groups with higher or lower catastrophizing regarding PPT. Positive and significant associations between the Rumination factor of PCTS and WOMAC outcomes were observed, as well as between the Hopelessness factor and TUG, Lequesne and WOMAC. CONCLUSION: The higher the presence of catastrophic thoughts, the worse the attitudes towards pain and the physical functionality of knee osteoarthritis patients.

RESUMO JUSTIFICATIVA E OBJETIVOS: A osteoartrite do joelho está entre as principais causas de incapacidade crônica e pode levar à depressão, ansiedade e catastrofização, intensificando a percepção da dor. Este estudo teve como objetivo investigar a influência da catastrofização da dor nas atitudes e na percepção da dor e a funcionalidade de indivíduos com osteoartrite do joelho. MÉTODOS: Dezoito pacientes foram avaliados quanto ao peso e à estatura, e completaram a Escala de Pensamentos Catastróficos Sobre a Dor (EPCD), Inventário de Atitudes frente à Dor (IAD), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) e escala analógica visual (EAV). Os sintomas e a incapacidade foram avaliados pelo Índice de Lequesne, a mobilidade funcional foi avaliada pelo teste Timed Up and Go (TUG). Os limiares de tolerância à dor à pressão (LTDP) foram avaliados por um algômetro digital. RESULTADOS: A média do índice de massa corporal da amostra foi classificado como obesa (32,2±4,3). Quando divididas pela mediana do EPCD, foram observadas diferenças na maioria dos domínios do IAD. Pacientes com pensamentos mais catastróficos demoraram mais para realizar o TUG e apresentaram mais dor, rigidez articular e pior funcionalidade (WOMAC). Apesar da tendência de relatar mais dor (EAV) em pacientes acima do escore mediano do EPCD, não foram observadas diferenças entre os grupos com maior ou menor catastrofização em relação aos LTDP. Foram observadas associações positivas e significantes entre o fator ruminação da EPCD e o WOMAC, bem como entre o fator Desesperança e TUG, Lequesne e WOMAC. CONCLUSÃO: Quanto maior a presença de pensamentos catastróficos, piores as atitudes em relação à dor e funcionalidade física dos pacientes com osteoartrite do joelho.

Cutaneous temperature and pressure pain threshold in individuals with knee osteoarthritis.

INTRODUCTION: Osteoarthritis is a common disease in which skin temperature may be included among the pathophysiological factors. Thermography allows the mapping of cutaneous temperature and may be employed in the investigation of osteoarthritis. OBJECTIVES: To evaluate cutaneous temperature of the lower limbs, as well as to verify its association with pressure pain thresholds in individuals with knee osteoarthritis. MATERIAL AND METHODS: This case series study was conducted with individuals of both genders aged 48-77 years with unilateral knee osteoarthritis. Volunteers underwent thermographic evaluation by an infrared sensor (FLIR T650SC). The anterior region of the thigh and leg and the knee area were evaluated. Pressure pain thresholds (PPT) were evaluated by algometry (Pain Diagnostics, Great Neck, USA) at the vastus medialis, vastus lateralis, rectus femoris, and patellar tendon. Data analysis was conducted with the statistical package SPSS v.24 for Windows. Comparisons between affected and unaffected sides were made by paired Student's t-test or the Mann-Whitney U test, and associations between variables were assessed by Pearson or Spearman's correlation coefficient. In all cases, the significance level was set at p ≤ 0.05. RESULTS: Eleven volunteers (63.1 ±9.5 years) participated in this study. When comparing cutaneous temperature, only the region of the knee showed a significant difference between sides (p = 0.02). There were no differences between affected and unaffected knees regarding pain tolerance (PPT) at all sites evaluated. There were also no significant associations between the study variables. CONCLUSIONS: Individuals with knee osteoarthritis presented a higher temperature of the affected knee, but this was not associated with pressure pain thresholds.