SARS-CoV-2, which caused the coronavirus pandemic in 2019 (COVID-19), is a beta-coronavirus, and its infection in host cells can activate innate and adaptive immune responses through the activation of several pro-inflammatory cytokines. Thus, in this study we established the relationship between the severity and immunopathology of COVID-19 through the main inflammatory cytokines. Results show that tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins (IL), such as IL-6, are stimulated by the activation of T cell subsets, which results in immune-mediated cellular destruction. Several cytokines reduce the immune response and predispose to a pro-inflammatory and auto-reactive state, including IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, and associated inflammatory markers (LDH, GM-CSF and VEGF). These higher cytokine levels end up favoring tissue damage in multiple systems, including lungs, heart, gastrointestinal, brain, kidneys and other organs. Increasingly, a greater impact of the markers IL-6, ferritin, pro-calcitonin, lactic dehydrogenase, D-dimer and hypoalbuminemia was observed in patients with severe infection of the disease. In general, the data analyzed confirmed that COVID-19 severity is not caused simply by the viral infection, but rather by immune response and aberrant inflammation. In this way, this study allows a contribution to clinical practice, and it shows that it is essential to carry out in-depth studies about the immunopathology of COVID-19, in order to determine the severity markers involved in the pathogenesis of the viral infection.

O SARS-CoV-2, causador da doença coronavírus 2019 (COVID-19), é um beta-coronavírus, e sua infecção nas células do hospedeiro pode ativar respostas imunes inata e adaptativa, por meio da secreção de várias citocinas pró-inflamatórias. Assim, estabelecemos neste estudo a correlação da gravidade e imunopatologia da COVID-19 com as principais citocinas inflamatórias. Resultados mostram que o fator de necrose tumoral alfa (TNF-α), interferon-gama (IFN-γ) e interleucinas (IL), como a IL-6, são estimulados pela ativação de subconjuntos de células T, o que resulta em destruição celular imunomediada. Sendo que, diversas citocinas deprimem a resposta imune sadia, e predispõem a um estado pró-inflamatório e auto-reativo, dentre elas, IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, e os marcadores inflamatórios associados (LDH, GM-CSF e VEGF). Isso acaba por favorecer danos teciduais em múltiplos sistemas, como no pulmonar, cardíaco, gastrointestinal, cerebral, renal, dentre outros. Acrescenta-se que foi observado um impacto maior dos marcadores IL-6, ferritina, pró-calcitonina, desidrogenase láctica, D-dímero e hipoalbuminemia em pacientes com infecção grave da doença. De forma geral, pela análise de dados, verificou-se que a gravidade da doença COVID-19 parece ser modulada não apenas pela infecção viral, mas também por respostas imunes e inflamatórias aberrantes no hospedeiro. Dessa forma, este estudo permite contribuir para o auxílio da prática clínica, sendo imprescindível a realização de estudos aprofundados acerca da imunopatologia da COVID-19, a fim de que se determine os marcadores de gravidade envolvidos na patogênese da infecção viral.

Abstract Background Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. Objective To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. Methods Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. Results The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). Study limitations The mechanism of the IFNGR1 gene has not been further investigated in this study. Conclusions The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms. (TM factors antiinterferonγ anti interferon γ HIV (HIV infection DNA (DNA s blood WES, WES , (WES) IFNGR NM_001363526.1 NM0013635261 NM 001363526 1 (NM_001363526.1 c.4C&gtT c4CgtT cCgtT c.4C&gt T c 4C gt C p.L2F pL2F pLF p L2F L F (p.L2F NM_001363526.1. . study symptoms (WES NM_001363526. NM001363526 00136352 (NM_001363526. gtT CgtT c4Cgt cCgt pL LF NM_001363526 NM00136352 0013635 (NM_001363526 Cgt NM_00136352 NM0013635 001363 (NM_00136352 NM_0013635 NM001363 00136 (NM_0013635 NM_001363 NM00136 0013 (NM_001363 NM_00136 NM0013 001 (NM_00136 NM_0013 NM001 00 (NM_0013 NM_001 NM00 0 (NM_001 NM_00 NM0 (NM_00 NM_0 (NM_0 NM_ (NM_ (NM

ABSTRACT Objective: To perform a systematic review of randomized controlled trials, evaluating the effect of probiotics, prebiotics or symbiotics supplementation on glycemic and inflammatory control in children with Type 1 Diabetes Mellitus (T1DM). Data source: The Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO) databases were searched. Randomized clinical trials of pediatric patients with DM1 using probiotics, prebiotics or symbiotics were included, regardless of year or language of publication. Studies that did not evaluate glycated hemoglobin (HbA1c) were excluded. Metabolic results (HbA1c, total insulin dose and C-peptide) and inflammatory control [interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)] during probiotic supplementation or similar, related to modification of the intestinal microbiota, were analyzed. PROSPERO ID: CRD42022384485. Data synthesis: Five studies were selected for a systematic review. Regarding metabolic markers, only one of the articles that analyzed HbA1c showed a significant decrease (p=0.03) in the intervention group. One study identified a reduction in the total dose of insulin and increased C-peptide levels. Regarding the evaluation of inflammatory parameters (IL-10, TNF-α, INF-γ), there were no statistical relevant modifications. Conclusions: Current data from the literature were not conclusive in identifying an improvement in glycemic control and did not observe changes in inflammatory parameters with the use of probiotics, prebiotics or symbiotics in pediatric patients with T1DM. Objective probiotics T1DM TDM . T DM (T1DM) source MEDLINE/PubMed, MEDLINEPubMed MEDLINE/PubMed , MEDLINE PubMed (MEDLINE/PubMed) Trials LatinoAmericana Latino Americana LILACS (LILACS SciELO (SciELO searched included publication HbAc HbA c (HbA1c excluded HbA1c, Cpeptide C peptide interleukin10 interleukin 10 [interleukin-1 IL10, IL10 IL (IL-10) factoralpha factor alpha TNFα TNF α (TNF-α interferongamma interferon gamma IFNγ IFN γ (IFN-γ) similar microbiota ID CRD42022384485 CRD synthesis markers p=0.03 p003 p 0 03 (p=0.03 group levels 10, (IL-10 TNFα, α, TNF-α INFγ, INFγ INF INF-γ) modifications Conclusions (T1DM (MEDLINE/PubMed interleukin1 [interleukin- IL1 (IFN-γ CRD4202238448 p=0.0 p00 (p=0.0 (IL-1 INF-γ [interleukin CRD420223844 p=0. p0 (p=0. (IL- CRD42022384 p=0 (p=0 (IL CRD4202238 p= (p= CRD420223 (p CRD42022 CRD4202 CRD420 CRD42 CRD4

RESUMO Objetivo: Realizar uma revisão sistemática de ensaios clínicos randomizados controlados avaliando o efeito da suplementação de probióticos, prebióticos ou simbióticos no controle glicêmico e inflamatório em crianças com diabetes mellitus tipo 1 (DM1). Fontes de dados: As bases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SciELO) foram pesquisadas. Foram incluídos ensaios clínicos randomizados de pacientes pediátricos com DM1 em uso de probióticos, prebióticos ou simbióticos, independentemente de ano ou idioma de publicação. Foram excluídos os trabalhos que não avaliaram hemoglobina glicada (HbA1c). Os resultados metabólicos (HbA1c, dose de insulina total e peptídeo C) e o controle inflamatório [interleucina-10 — IL-10), fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ)] durante a suplementação de probióticos ou similares, relacionados à modificação da microbiota intestinal, foram analisados. ID PROSPERO: CRD42022384485. Síntese dos dados: Cinco estudos foram selecionados para revisão sistemática. Com relação aos marcadores metabólicos, apenas um dos artigos que analisaram a HbA1c apresentou diminuição significativa (p=0,03) no grupo intervenção. Um estudo identificou redução da dose total de insulina e aumento dos níveis de peptídeo C. Quanto à avaliação dos parâmetros inflamatórios (IL-10, TNF-α, INF-γ), não houve modificações de relevância estatística. Conclusões: Os dados atuais da literatura não foram conclusivos em identificar melhora no controle glicêmico e não observaram mudanças nos parâmetros inflamatórios com o uso de probióticos, prebióticos ou simbióticos em pacientes pediátricos com DM1. Objetivo DM . (DM1) MEDLINE/PubMed, MEDLINEPubMed MEDLINE/PubMed , MEDLINE PubMed (MEDLINE/PubMed) Trials LatinoAmericana Latino Americana LILACS (LILACS SciELO (SciELO pesquisadas publicação HbA1c. HbAc HbA c (HbA1c) HbA1c, (HbA1c C interleucina10 interleucina 10 [interleucina-1 IL10, IL10 IL IL-10) tumoralalfa tumoral alfa TNFα TNF α (TNF-α interferongama interferon gama IFNγ IFN γ (IFN-γ) similares intestinal analisados PROSPERO CRD42022384485 CRD p=0,03 p003 p 0 03 (p=0,03 intervenção 10, (IL-10 TNFα, α, TNF-α INFγ, INFγ INF INF-γ) estatística Conclusões (DM1 (MEDLINE/PubMed interleucina1 [interleucina- IL1 IL-10 (IFN-γ CRD4202238448 p=0,0 p00 (p=0,0 (IL-1 INF-γ (DM [interleucina IL-1 CRD420223844 p=0, p0 (p=0, (IL- IL- CRD42022384 p=0 (p=0 (IL CRD4202238 p= (p= CRD420223 (p CRD42022 CRD4202 CRD420 CRD42 CRD4

The current study was designed to evaluate the reliability of the interferon-gamma release assay (IGRA) as a screening test compared to intensive post-mortem inspection using agreement analyses. This study also aimed to determine the prevalence and risk factors of bovine tuberculosis (bTB) among bovines presented for slaughter in the largest abattoir in Lahore, Pakistan. After anti-mortem inspection, a total of 102 animals were randomly selected for sample and data collection. Selected animals were slaughtered and a thorough post-mortem examination was done for all carcasses to find TB-like lesions. Blood samples were processed by IGRA. Prevalence estimates were generated and Cohen's Kappa test was done for agreement analyses to compare the reliability of the two tests for bTB diagnosis. A substantial agreement (κ = 0.79) was estimated between the IGRA and intensive post-mortem inspection. The apparent prevalence was computed as 5.88% (95% CI; 2.59-11.97) and the true prevalence was estimated as 3.92% (95% CI; 1.35-9.47). A parallel testing strategy with IGRA and intensive post-mortem inspection is a useful approach for screening bTB.

Resumen Objetivos: En prisiones, existe una alta prevalencia de reclusos que tienen una prueba de tuberculina (PT) positiva mayor de 10 mm y, en ocasiones, se realizan tratamientos para infección tuberculosa latente (ITL) innecesarios. El programa de pre- vención y control de la tuberculosis (TB) en el medio penitenciario no ha generalizado el uso de uso de QuantiFERON®-TB (QFT) en las cárceles. Nos propusimos describir la implementación y la utilidad del QFT en una población de internos con PT positiva y, de forma secundaria, detectar falsos positivos y evitar tratamientos innecesarios. Secundariamente se han analizado las distintas variables sociodemográficas de la población reclusa. Material y método: Entre diciembre de 2020 y diciembre de 2021, de una población promedio de 300 internos de la cárcel de Burgos, se analizaron todas las pruebas de PT positivas. A todos estos casos positivos, se les midió el valor del QFT. Se analiza- ron diferentes variables sociodemográficas, y finalmente se evaluó la cantidad de internos con PT positiva, pero con resultado de QFT negativo. Resultados: Un total de 41 internos fueron incluidos en el estudio, con una edad media de 44 años. La proporción de internos nacidos en España fue del 56%, el resto habían nacido en otros países. El 48,8% de todas las PT positivas, fueron QFT negativo. De los 21 internos con QFT+, 12 (57%) estaban vacunados con bacilo de Calmette y Guérin (BCG). Discusión: Se ha observado que el QFT es un método seguro para el diagnóstico de la ITL en prisiones, y que su utilización contribuiría a una selección más específica de los internos que realmente necesitan un tratamiento para ITL.

Abstract Objectives: A high prevalence of prison inmates have a positive tuberculin skin test (TST) and sometimes unnecessary treatment for latent tuberculosis infection (LTBI) is prescribed. The prison tuberculosis prevention and control program has not generalized the use of QuantiFERON (QFT) in prisons. We set out to describe the implementation and usefulness of QFT in a population of inmates with positive TST, and to detect false positives and avoid unnecessary treatments. We also analysed the sociodemographic variables of the inmate population. Material and methods: All the positive TST tests between December 2020 and December 2021 from an average population of 300 inmates in Burgos prison were analysed. The QFT value was measured in all the positive cases. Sociodemographic variables were analysed and finally the number of inmates with positive TST, but with a negative QFT result and therefore not requiring LTBI treatment, was evaluated. Results: A total of 41 inmates were included in the study, with a mean age of 44 years. The proportion between Spanish inmates and foreigners was similar. Of all the positive TST, 48.8% were QFT negative. Discussion: It was observed that QFT is a safe method for the diagnosis of LTBI in prisons and that its use would contribute to a more specific selection of inmates who actually need chemoprophylactic treatment for LTBI.

Resumen Introducción: El objetivo de este estudio fue describir las características clínicas y demográficas de niños con enfermedad tuberculosa confirmada e identificar los factores asociados. Métodos: Se realizó un estudio observacional retrolectivo en el Hospital Civil de Guadalajara Dr. Juan I. Menchaca. Se incluyeron menores de 18 años hospitalizados y ambulatorios que se notificaron al Sistema Nacional de Vigilancia Epidemiológica (SINAVE) por sospecha de tuberculosis y que contaron con pruebas moleculares o microbiológicas para micobacterias. El estudio de los factores asociados se realizó mediante análisis multivariado con regresión logística. Resultados: Se incluyeron en el estudio 109 menores de 18 años con sospecha de tuberculosis. El 50.5% (55/109) fueron de sexo masculino y la mediana de edad fue de 11 años. Se confirmó enfermedad tuberculosa en el 55% (n = 60) de los casos: el 15% (9/60) presentaron infección pulmonar y el resto extrapulmonar. Las pruebas diagnósticas utilizadas fueron el estudio histopatológico (n = 26), tinciones de expectoración o aspirado gástrico (n = 17), reacción en cadena de la polimerasa (n = 12) y cultivos (n= 5). 33.9% de los pacientes presentaron prueba de derivado proteico purificado (PPD) o ensayo de liberación de interferón gamma (IGRA) positiva. Se observó que la desnutrición (razón de momios (RM) 15.9, intervalo de confianza (IC) 95% 2.3 - 109) y el consumo de productos no pasteurizados (RM 7.45, IC 95% 1.02 - 54.3) se asociaron con enfermedad tuberculosa en niños. Conclusiones: La desnutrición y el consumo de lácteos no pasteurizados se asocian con la enfermedad tuberculosa.

Abstract Background: This study aimed to describe the clinical and demographic characteristics of children with confirmed tuberculosis disease and identify associated factors. Methods: We conducted a retrospective and observational study at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca. Inpatient and outpatient children under 18 years of age who were reported to the National Epidemiological Surveillance System (SINAVE, for its Spanish acronym) for suspected tuberculosis and who had molecular or microbiological tests for mycobacteria were included in the study. Multivariate analysis with logistic regression was used to analyze associated factors. Results: One hundred and nine patients under 18 years of age with suspected tuberculosis were included in the study. About 50.5% (55/109) were male, and the median age was 11 years. Tuberculosis was confirmed in 55% (n = 60): 15% (9/60) had a pulmonary infection, and the rest (51/60) had an extrapulmonary infection. The diagnostic tests used were histopathological study (n = 26), expectoration or gastric aspirate stains (n = 17), polymerase chain reaction (n = 12), and cultures (n = 5). Positive purified protein derivative (PPD) or interferon-gamma release assay (IGRA) tests were found in 33.9%. Malnutrition (odds ratio [OR] 15.9, 95% confidence interval [CI]: 2.3-109), and consumption of unpasteurized products (OR 7.45, 95% CI: 1.02-54.3) were associated with tuberculosis disease in children. Conclusions: Malnutrition and consumption of unpasteurized dairy products are associated with tuberculosis.

Abstract Concentration of interferon-gamma and interleukin-10 in maternal serum and in maternal and fetal porcine placental extracts from different gestation periods was determined. Crossbred pigs’ placental samples of 17, 30, 60, 70, and 114 days gestation and non-pregnant uteri were used. Interferon-gamma concentration was increased at the placental interface at 17 days, in maternal and fetal placenta, and decreased significantly in the remaining gestation periods. Interferon-gamma showed a peak in serum at 60 days. Regarding interleukin-10, placental tissue concentrations were unaltered, there were no significant differences with non-gestating uteri samples. In serum interleukin-10 increased at 17, 60, and 114 days gestation. At 17 days there are uterus structural and molecular changes that allow the embryos implantation and placenta development. The presence of interferon-gamma found at this moment in the interface would favor that placental growth. Moreover, its significant increase in serum at 60 days, would generate a proinflammatory cytokine pattern that facility the placental remodeling characteristic of this moment of porcine gestation. On the other hand, a significant interleukin-10 increase in serum at 17, 60 and 114 days could indicate its immunoregulatory role at a systemic level during pig gestation. interferongamma interferon gamma interleukin10 interleukin 10 interleukin-1 determined pigs 30 70 11 nonpregnant non pregnant used Interferongamma Interferon 1 6 interleukin10, 10, unaltered nongestating gestating development growth Moreover hand interleukin1 interleukin- 3 7

Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD. CD, , (CD) Social psychological processes stroke refuted neuroinflammation however Overall T stress Interferongamma Interferon gamma IFNγbearing bearing forms IFNγstimulated stimulated oxide taken requirements recognised (CD

ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients. threat Asia America (DENV fever Cytokines interferons outcomes SNPs (SNPs interferongamma interferon gamma IFNG (IFNG) AG A G rs2069716 rs (rs2069716 rs2069727. rs2069727 . (rs2069727) 27 3 11 DWoWS, DWoWS , (DWoWS) 15 DWWS (DWWS SD. SD (SD) extracted TaqMan probes. probes probes) OR models AAAA AA A256G/A325G, A256GA325G AGAG A256G/A325G (A256G/A325G) AAAG DWWSSD 0.51 051 0 51 95 0.241.10, 024110 0.24 1.10, 24 1 10 0.24-1.10 0.085, 0085 0.085 085 0.085) sex DENV3infected DENVinfected DENV3 (IFNG rs206971 (rs206971 rs206972 (rs2069727 2 (DWoWS (SD GA (A256G/A325G 0.5 05 5 9 241 0.241.10 02411 024 0.2 110 1.10 0.24-1.1 008 0.08 08 rs20697 (rs20697 (rs206972 0. 0.241.1 0241 02 1.1 0.24-1. 00 0.0 rs2069 (rs2069 0.241. 1. 0.24-1 rs206 (rs206 0.241 0.24- rs20 (rs20 rs2 (rs2 (rs

ABSTRACT Detecting latent tuberculosis infection (LTBI) is important, especially in high-risk populations including healthcare workers (HCWs). QuantiFERON-TB Gold Plus (QFT-Plus) is a new version of the interferon-gamma release assays (IGRAs) to replace the QuantiFERON-TB Gold In-tube (QFT-GIT). However, data on the use of QFT-Plus for LTBI detection in high TB-burden countries are limited. This study was conducted in a TB-endemic setting in Thailand. HCWs were enrolled in the study and underwent both tests during the annual health screening. The testing results were compared and the concordance was determined. Of 102 HCWs, 11 (10.78%) were positive according to both tests, and 15 (14.71%) were positive according to QFT-Plus. The overall agreement between assays was 96.08%, with Cohen’s kappa coefficient (k) at 0.82. All four discordant results occurred with QFT-GIT negative and QFT-Plus positive. The comparison between QFT-GIT and QFT-Plus based on each antigen tube (TB1 or TB2) exhibited similar concordance with 99.02% and 95.10% agreement, respectively. The intra-comparison between TB1 and TB2 of QFT-Plus also showed good concordance at 96.08%. Among this group of HCWs, the LTBI prevalence of any positive results in both tests was low. Overall, the study showed good agreement between QFT-Plus and QFT-GIT (k = 0.82) with a minimal difference, suggesting similar assay performance to that mainly carried out in TB-low incidence countries. The results support the use of QFT-Plus for detecting LTBI in a format similar to QFT-GIT. (LTBI important highrisk risk HCWs. . (HCWs) QuantiFERONTB QuantiFERON TB QFTPlus QFT (QFT-Plus interferongamma interferon gamma IGRAs (IGRAs Intube In QFTGIT. QFTGIT GIT (QFT-GIT) However TBburden burden limited TBendemic endemic Thailand screening determined 10 1 10.78% 1078 78 (10.78% 14.71% 1471 14 71 (14.71% QFTPlus. Plus. 9608 96 08 96.08% Cohens Cohen s k 082 0 82 0.82 (TB 9902 99 02 99.02 9510 95 95.10 respectively intracomparison intra low Overall difference TBlow GIT. (HCWs (QFT-GIT 10.78 107 7 (10.78 14.71 147 (14.71 960 9 96.08 8 0.8 990 99.0 951 95.1 10.7 (10.7 14.7 (14.7 96.0 0. 99. 95. 10. (10. 14. (14. 96. (10 (14 (1 (

Regular exercise reduces the risk of malignancy and decreases the recurrence of cancer. However, the mechanisms behind this protection remain to be elucidated. Natural killer (NK) cells are lymphocytes of the innate immune system, which play essential roles in immune defense and effectively prevent cancer metastasis. Physical exercise can increase the activity of NK cells. Interleukin-15 (IL-15) is the best-studied cytokine activator of NK cells, and it was shown to have many positive functional effects on NK cells to improve antitumor responses. The aim of this study was to clarify the possible important mechanisms behind endurance exercise-induced changes in NK cell function, which may be highly correlated with IL-15. An animal model was used to study IL-15 expression level, tumor volume, cancer cell apoptosis, and NK cell infiltration after treadmill exercise. Although IL-15 was highly expressed in skeletal muscle, treadmill exercise further elevated IL-15 levels in plasma and muscle (P<0.05). In addition, tumor weight and volume of tumor-bearing mice were decreased (P<0.05), and liver tumor cell apoptosis was increased after 12 weeks of treadmill exercise (P<0.05). NK cell infiltration was upregulated in tumors from treadmill exercise mice, and the level of interferon-gamma (IFN-γ) and IL-15 were higher than in sedentary mice (P<0.05). The study indicated that regular endurance training can reduce cancer risk, which was related to increased IL-15 expression, activation of the immune killing effect of NK cells, and promotion of tumor cell apoptosis, which can ultimately control tumor growth. However elucidated (NK system metastasis Interleukin15 Interleukin 15 Interleukin-1 IL15 IL (IL-15 beststudied best studied responses exerciseinduced induced function IL15. 15. IL-1 P<0.05. P005 P P<0.05 . 0 05 (P<0.05) addition tumorbearing bearing P<0.05, , 1 interferongamma interferon gamma IFNγ IFN γ (IFN-γ growth Interleukin1 Interleukin- IL1 (IL-1 IL- P00 P<0.0 (P<0.05 (IL- P0 P<0. (P<0.0 (IL P<0 (P<0. P< (P<0 (P< (P

Abstract Interferons constitute a family of proteins involved in antiviral, immunomodulatory, and antiinflammatory activities. In the last years, the study of interferons in the cancer context has increased, and one of the most important findings is that interferons are part of the tumor microenvironment. The interferon-gamma (IFN-γ) is one of the members of the interferons family and has protumoral and antitumoral functions depending on the type of cancer and tumoral microenvironment. In this review, we discussed the elements of the canonical transduction pathway of IFN-γ and their implications for the study of malign neoplasms. Studies suggest that the elements of the pathway activated by IFN-γ could be useful as biomarkers and/or therapy targets against cancer.

Resumen Los interferones son una familia de proteínas involucradas en actividades antivirales, inmunomoduladoras y antiinflamatorias. En los últimos años, su estudio se ha incrementado en el contexto del cáncer, y uno de los hallazgos más importantes es que son parte del microambiente de los tumores. El interferón-gamma (IFN-γ) es uno de los miembros de la familia de los interferones y tiene funciones protumorales o antitumorales dependiendo del tipo de cáncer y del microambiente tumoral. En esta revisión se discuten los elementos de la vía de transducción de señales canónica del IFN-γ y sus implicaciones en el desarrollo de las neoplasias malignas. Los estudios sugieren que los elementos de la vía activada por el IFN-γ podrían ser útiles como biomarcadores y/o como blanco de terapias para el cáncer.

ABSTRACT Introduction: chronic stress affects the immune balance by altering the serum levels of interleukin-6 (IL-6) and gamma interferon (INF-γ), this alteration affects the nervous system and human behavior. Appropriate chewing would lessen these effects. The aim of this study was to determine the effect of chewing and chronic stress over serum levels of IL-6 and INF-γ. Methods: experiment in which 64 Balb/C mice of 8 weeks of age were used, they were divided into 4 treatments: Group NE: Normal chewing + stress, Group N: normal chewing without stress, Group DE: Chewing poor + stress, Group D: poor chewing without stress. IL-6 and IFN-γ were measured by ELISA after 4 and 8 weeks of treatment. Results: both IL-6 and IFN-γ were higher in the DE group (p < 0,05) at the end of fourth week of treatment. When evaluating the animals at the end of the eighth week of treatment, it was observed that in the NE group, the IL-6 was increased with respect to the rest (p < 0,0001) and the DE group showed more IFN-γ (p < 0,0001). Conclusion: stress and poor chewing increase serum IL-6 and IFN-γ. In contrast, appropriate chewing decreases the effects of stress on the increase of such cytokines at the end of the fourth week of treatment in animals.

RESUMEN: Introducción: el estrés crónico afecta el equilibrio inmunológico alterando los niveles séricos de interleuquina-6 (IL-6) e interferón gama (INF-γ), dicha alteración afecta al sistema nervioso y al comportamiento humano. La masticación adecuada disminuiría dichos efectos. El objetivo del estudio fue determinar el efecto del estrés crónico y de la masticación sobre los niveles séricos de IL-6 e INF-γ. Métodos: experimento donde se emplearon 64 ratones Balb/c de 8 semanas de edad. Se dividieron en 4 tratamientos: Grupo NE: Masticación normal + estrés, Grupo N: masticación normal sin estrés, Grupo DE: Masticación deficiente + estrés, Grupo D: masticación deficiente sin estrés. Mediante test de ELISA se midió IL-6 e IFN-γ alfinal de la 4ta y de la 8va semana de tratamiento. Resultados: tanto la IL-6 como el IFN-γ fueron mayores en el grupo DE (p<0,05) al final de la 4ta semana. Al evaluarlos al término de la 8va semana se observó que en el grupo NE se incrementó la IL-6 respecto al resto de grupos (p<0,0001), y en el grupo DE fue donde se encontró mayor cantidad de IFN-γ (p<0,0001). Conclusión: el estrés crónico y la masticación deficiente incrementan los niveles séricos de IL-6 e IFN-γ. En cambio, la adecuada masticación disminuye el nivel de tales citoquinas al final de la cuarta semana de tratamiento.

Abstract Tuberculosis is rare in pediatric age but remains an issue in populations with risk factors. A new pediatric diagnosis frequently reflects a recent infection in the community. Herein is reported the case of an adolescent with prolonged but well-tolerated dyspnea, anorexia, fever, and night sweats, whose radiograph showed a massive pleural effusion. Pleural fluid analysis was compatible with pleural TB, and pleural biopsy confirmed the diagnosis. Pleural fluid polymerase chain reaction was later positive for Mycobacterium tuberculosis, and interferon-gamma release assay was also positive.

Resumo A tuberculose é uma doença rara em idade pediátrica, mas continua a ser um problema em populações de risco. Um diagnóstico de novo numa criança frequentemente traduz uma infeção recente na comunidade. É descrito o caso de um adolescente com dispneia, anorexia, febre e sudorese noturna prolongadas, mas bem toleradas, cuja radiografia evidenciou um derrame pleural de grandes dimensões. A análise do líquido pleural foi compatível com o diagnóstico de tuberculose pleural e a biópsia pleural permitiu confirmar o diagnóstico. A reação em cadeia da polimerase no líquido pleural foi posteriormente positiva para Mycobacterium tuberculosis e o teste de libertação de interferão gama foi igualmente positivo.

ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.

RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.