Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.

Overview of the participation of community health workers in primary health care in 6 Latin American countries and a proposal for their integration into the health system: a qualitative study.

BACKGROUND: According to some health programmes, implementing primary health care through community health workers (CHWs) facilitates the connection between community and health services in Latin America. However, these are isolated processes that face different obstacles and would benefit from an overview of the corresponding health policies and programmes. OBJECTIVE: To provide an overview of CHW participation in 6 Latin American countries. METHODS: This exploratory qualitative study was based on 3 sources of information: a literature review, a review of public health policy documents, and interviews with experts who have led CHW programmes in 6 Latin American countries. RESULTS: The role of CHWs in Latin America and some advances in public health policies in the region were evidenced. However, limitations arising from variable implementation of the WHO guidelines on health programmes with CHWs were also apparent. CONCLUSIONS: CHWs contribute to the primary healthcare processes in the 6 Latin American countries studied in versatile and comprehensive ways. However, they constitute an underutilized human resource because they must provide various services that are not always relevant in different work contexts. Therefore, we propose a classification of the CHW profile, using the level of access to healthcare services of the population they serve as the main differentiator. This way, CHWs will not have to provide a wide range of services but only those most relevant to the specific needs of each community.

Substance P/calcitonin gene-related peptide and their receptors expression in human periodontal ligament after root canal preparation with five different systems.

AIM: The purpose of this study was to quantify the effect of five different root canal preparation instruments on Substance P (SP), Calcitonin gene-related peptide (CGRP) and their receptors expression in healthy human periodontal ligament. METHODOLOGY: STROBE guidelines were used to design a study using 60 periodontal ligament samples obtained from healthy lower premolars where extraction was indicated for orthodontic reasons. Prior to extraction 40 of these premolars were equally divided into four groups and root canals were prepared using different systems: Mtwo, Reciproc Blue, HyFlex EDM and Plex-V. Ten premolars were prepared with hand files and served as a positive control group. The remaining 10 premolars where extracted without treatment and served as a negative control group. All periodontal ligament samples were processed to measure the expression of SP, CGRP and their receptors by radioimmunoassay. Kruskal-Wallis and Duncan tests were performed to determine statistically significant differences between the groups for each variable. RESULTS: Greater expression of all the peptides measured were found in the hand-file preparation group, followed by the Reciproc Blue, Mtwo, HyFlex EDM and Plex-V groups. The lower SP, CGRP and their receptors values were for the intact teeth control group. Kruskal-Wallis test showed statistically significant differences amongst groups (p < .001). Dunn post-hoc tests showed statistically significant differences in SP, CGRP and their receptors expression between the intact teeth and the hand-file and Reciproc Blue groups. Hand-file group showed significant differences with the other groups, except with Reciproc Blue, where no differences were observed in any of the peptides measured. Finally, no differences were observed between Plex-V and HyFlex in any of the peptides measured. CONCLUSIONS: Root canal preparation with hand files and Reciproc Blue generates the highest expression of SP, CGRP, NK1 and CGRP1R in human periodontal ligament, whilst Plex-V and HyFlex maintain the basal expression of neuropeptides and their receptors. Mtwo showed intermediate results between Reciproc Blue and HyFlex.

Cytosine base editing inhibits hepatitis B virus replication and reduces HBsAg expression in vitro and in vivo.

Chronic hepatitis B virus (HBV) infection remains a global health problem due to the lack of treatments that prevent viral rebound from HBV covalently closed circular (ccc)DNA. In addition, HBV DNA integrates in the human genome, serving as a source of hepatitis B surface antigen (HBsAg) expression, which impairs anti-HBV immune responses. Cytosine base editors (CBEs) enable precise conversion of a cytosine into a thymine within DNA. In this study, CBEs were used to introduce stop codons in HBV genes, HBs and Precore. Transfection with mRNA encoding a CBE and a combination of two guide RNAs led to robust cccDNA editing and sustained reduction of the viral markers in HBV-infected HepG2-NTCP cells and primary human hepatocytes. Furthermore, base editing efficiently reduced HBsAg expression from HBV sequences integrated within the genome of the PLC/PRF/5 and HepG2.2.15 cell lines. Finally, in the HBV minicircle mouse model, using lipid nanoparticulate delivery, we demonstrated antiviral efficacy of the base editing approach with a >3log10 reduction in serum HBV DNA and >2log10 reduction in HBsAg, and 4/5 mice showing HBsAg loss. Combined, these data indicate that base editing can introduce mutations in both cccDNA and integrated HBV DNA, abrogating HBV replication and silencing viral protein expression.

Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients.

Currently, tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb) that primarily affects the lungs. The severity of active pulmonary TB (APTB) is an important determinant of transmission, morbidity, mortality, disease experience, and treatment outcomes. Several publications have shown a high prevalence of disabling complications in individuals who have had severe APTB. Furthermore, certain strains of Mtb were associated with more severe disease outcomes. The use of biomarkers to predict severe APTB patients who are candidates for host-directed therapies, due to the high risk of developing post-tuberculous lung disease (PTLD), has not yet been implemented in the management of TB patients. We followed 108 individuals with APTB for 6 months using clinical tools, flow cytometry, and whole-genome sequencing (WGS). The median age of the study population was 26.5 years, and the frequency of women was 53.7%. In this study, we aimed to identify biomarkers that could help us to recognize individuals with APTB and improve our understanding of the immunopathology in these individuals. In this study, we conducted a follow-up on the treatment progress of 121 cases of APTB. The follow-up process commenced at the time of diagnosis (T0), continued with a control visit at 2 months (T2), and culminated in an exit appointment at 6 months following the completion of medical treatment (T6). People classified with severe APTB showed significantly higher levels of IL-6 (14.7 pg/mL; p < 0.05) compared to those with mild APTB (7.7 pg/mL) at T0. The AUCs for the ROC curves and the Matthews correlation coefficient values (MCC) demonstrate correlations ranging from moderate to very strong. We conducted WGS on 88 clinical isolates of Mtb, and our analysis revealed a total of 325 genes with insertions and deletions (Indels) within their coding regions when compared to the Mtb H37Rv reference genome. The pattern of association was found between serum levels of CHIT1 and the presence of Indels in Mtb isolates from patients with severe APTB. A key finding in our study was the high levels of CHIT1 in severe APTB patients. We identified a biomarker profile (IL-6, IFN-γ, IL-33, and CHIT1) that allows us to identify individuals with severe APTB, as well as the identification of a panel of polymorphisms (125) in clinical isolates of Mtb from individuals with severe APTB. Integrating these findings into a predictive model of severity would show promise for the management of APTB patients in the future, to guide host-directed therapy and reduce the prevalence of PTLD.

Moderating effects of impulsivity and morning cortisol on the genotype-phenotype relationship of attention deficit hyperactivity disorder in young adults.

Dysregulation of the morning cortisol response in young adults with attention deficit hyperactivity disorder (ADHD) has been shown to underlie several of the alterations present in their lives. Thus, the interaction of this mechanism with genetic and behavioural characteristics could explain a large proportion of the aetiology of ADHD in this population. For these reasons, the present study explores the associations of 30 single nucleotide polymorphisms (SNPs) previously identified as significant (after correction for multiple comparisons) in the aetiology of ADHD with an assessment of morning cortisol and impulsivity traits in a group of 120 adults aged 18-24 years. Participants were recruited through private centres of neuropsychology and psychiatry, as well as through events in local universities. Morning cortisol within 30 min of awakening and motor impulsivity traits were shown to moderate the effect of SNP rs10129500 on the severity of the symptoms of ADHD measured by the Adult Self-Report Scale. This variant associated with cortisol-binding globulin would explain the low concentrations of this hormone found in young adults with high symptoms of ADHD, which is accentuated when there are high levels of impulsivity. The proposed model allows for transferring the theoretical relationships between the dimensions that explain the aetiology of ADHD to an applied exploratory model with good performance.

Recoil Measurements in Drosophila Embryos: from Mounting to Image Analysis.

Tension and force propagation play a central role in tissue morphogenesis, as they enable sub- and supra-cellular shape changes required for the generation of new structures. Force is often generated by the cytoskeleton, which forms complex meshworks that reach cell-cell or cell-extracellular matrix junctions to induce cellular rearrangements. These mechanical properties can be measured through laser microdissection, which concentrates energy in the tissue of interest, disrupting its cytoskeleton. If the tissue is undergoing tension, this cut will induce a recoil in the surrounding regions of the cut. This protocol describes how one can perform laser microdissection experiments and subsequently measure the recoil speed of the sample of interest. While we explain how to carry out these experiments in Drosophila embryos, the recoil calibration and downstream analyses can be applied to other types of preparations. Key features Allows measuring tension in live Drosophila embryos with a relatively simple approach. Describes a quick way to mount a high number of embryos. Includes a segmentation-free recoil quantification that reduces bias and speeds up analysis. Graphical overview.

Large genomic deletions delineate Mycobacterium tuberculosis L4 sublineages in South American countries.

Mycobacterium tuberculosis (Mtb) is still one of the primary pathogens of humans causing tuberculosis (TB) disease. Mtb embraces nine well-defined phylogenetic lineages with biological and geographical disparities. The lineage L4 is the most globally widespread of all lineages and was introduced to America with European colonization. Taking advantage of many genome projects available in public repositories, we undertake an evolutionary and comparative genomic analysis of 522 L4 Latin American Mtb genomes. Initially, we performed careful quality control of public read datasets and applied several thresholds to filter out low-quality data. Using a genome de novo assembly strategy and phylogenomic methods, we spotted novel south American clades that have not been revealed yet. Additionally, we describe genomic deletion profiles of these strains from an evolutionary perspective and report Mycobacterium tuberculosis L4 sublineages signature-like gene deletions, some of the novel. One is a specific deletion of 6.5 kbp that is only present in sublineage 4.1.2.1. This deletion affects a complex group of 10 genes with putative products annotated, among others, as a lipoprotein, transmembrane protein, and toxin/antitoxin system proteins. The second novel deletion spans for 4.9 kbp and specific of a particular clade of the 4.8 sublineage and affects 7 genes. The last novel deletion affects 4 genes, extends for 4.8 kbp., and is specific to some strains within the 4.1.2.1 sublineage that are present in Colombia, Peru and Brasil.

Epirubicin, cisplatin plus ifosfamide versus standard chemotherapeutic regimens for advanced/unresectable primary thoracic sarcomas.

PURPOSE: Thoracic sarcomas are rare malignancies, with limited data for unresectable/advanced scenarios. Our goal is to provide insights of a three-drug chemotherapy regimen improving patient survival compared to standard regimens. METHODS: Retrospective cohort analysis of patients diagnosed with unresectable/advanced primary thoracic sarcoma divided between primary pulmonary sarcomas (PPS) and chest wall sarcomas (CWS) comparing chemotherapeutical regimens efficacy. Not true soft tissue sarcomas (STS) for PPS were excluded from the analysis. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier with hazard ratio (HR) obtained via Mantel-Haenszel or log rank. RESULTS: 157 total cases were included, from which 50 cases were PPS and 107 cases CWS. For PPS, 4 cases were excluded from the analysis as they were not true STS. The most common histology was undifferentiated sarcomas, 63% of cases were treated with E/C/I and 37% with another regimen. The E/C/I regimen demonstrated a benefit for both OS (p = 0.020) and PFS (p = 0.010) when compared to any other regimen as well as when compared to non-platinum regimens (p = 0.016 and p = 0.001). Regarding CWS, the most common histology was synovial and undifferentiated sarcomas, 55.1% were treated with E/C/I and 44.9% treated with another regimen. The E/C/I regimen did not demonstrate a benefit for OS or PFS compared to any other regimen, neither when compared to other non-platinum regimens. However, a benefit was observed in favor of E/C/I when compared to other platinum regimens in both OS (p = 0.049) and PFS (0.015). Both analyses for PPS and CWS demonstrated a benefit in favor of cisplatin therapies compared to carboplatin in both OS and PFS. CONCLUSION: This study demonstrates that platinum therapy alone does not work, and that cisplatin must be the agent of choice and it's used in combination could increase treatment response. The E/C/I regimen demonstrated a in PPS but not for CWS, this is due do their rarity of PPS and that no standard treatment is established yet. The regimen proposed here could represent a possible new standard of treatment for PPS as long as it is validated in a prospective study.

The effect of orthodontic forces on calcitonin gene-related peptide (CGRP) expression in the human periodontal ligament and its relationship with the human dental pulp.

Background: The purpose of this study was to quantify the effect of moderate and severe orthodontic forces on Calcitonin gene-related peptide (CGRP) expression in the healthy human periodontal ligament (PDL) and its possible relationship with the human dental pulp. Material and Methods: Ninety human periodontal ligament samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, teeth were divided in 3 groups of 30 samples each: I) Untreated teeth control group; II) Moderate force group: A 56 g force was applied to the premolars for 24 hours; and III) Severe force group: A 224 g force was applied to the premolars for 7 days. All periodontal ligament samples were processed and CGRP was measured by radioimmunoassay. Results: Greater CGRP expression was found in the severe force group, followed by the moderate force group. The lower CGRP values were for the untreated teeth. Kruskal-Wallis test showed statistically significant differences between groups (p<0.001). LSD post hoc tests showed statistically significant differences in CGRP expression between the untreated teeth and the severe forces group (p<0.001). Differences between the moderate and severe force groups were statistically significant (p<0.001). There was no statistically significant differences between the untreated teeth and the moderate forces group (p<0.261). Conclusions: CGRP expression in human periodontal ligament increases when teeth are submitted to severe orthodontic forces. This elevated expression of CGRP, which is proportional to the applied force, may affect the way the dental pulp responds to different stimuli from the orthodontic forces. Key words:Calcitonin gene-related peptide, orthodontic force, human periodontal ligament, neurogenic inflammation.

Estudio del desempeño analítico del dispositivo portátil microINR en pacientes anticoagulados con acenocumarol / Analytical performance of the microINR portable device in acenocoumarol anticoagulated patients

Resumen La razón internacional normalizada (RIN) se utiliza para controlar a los pacientes anticoagulados con antagonistas de la vitamina K. El objetivo de este estudio fue evaluar el desempeño del nuevo dispositivo portátil microINR, que utiliza tromboplastina recombinante, en pacientes anticoagulados con acenocumarol. Grupo 1: los pacientes proporcionaron muestras de sangre venosa y capilar para realizar pruebas paralelas que permitieron comparar microINR con cinco combinaciones diferentes de reactivo/sistema de detección: tromboplastina de cerebro de conejo con detección nefelométrica, foto-óptica y por viscosidad y tromboplastina humana recombinante con detección nefelométrica y fotoóptica. Todas las tromboplastinas tenían un índice de sensibilidad internacional (ISI) específico de equipo informado por el fabricante menor de 1,10. Grupo 2: los resultados de microINR se compararon con CoaguChek como dispositivo preestablecido. La precisión se evaluó utilizando materiales de control líquidos. El coeficiente de variación del material de control en microINR fue de 6,2%. El análisis de regresión de Passing-Bablok y Bland-Altman mostró un coeficiente de correlación superior a 0,92 y un pequeño sesgo cercano a cero para todas las comparaciones de microINR con cada método tradicional realizado con sangre venosa. Ambos dispositivos portátiles tuvieron un muy buen coeficiente de correlación (r=0,98) y un pequeño sesgo de 0,02. Los resultados muestran un acuerdo clínico del 100% con un grado de concordancia Kappa mayor de 0,63 para todos los métodos tradicionales y de 0,82 para la comparación con Coagu- Chek. De acuerdo a los resultados obtenidos, el microINR es adecuado para el control de pacientes anticoagulados con acenocumarol.

Abstract The international normalised ratio (INR) is used to monitor vitamin K antagonist anticoagulated patients. The aim of this study was to evaluate the performance of the microINR portable device in acenocoumarol anticoagulated patients. Group 1: patients provided capillary and venous blood samples for parallel testing comparing microINR with five different pairs of reagent/clot detection systems: brain rabbit thromboplastin with nephelometric, photooptic and viscocity clot detection and recombinant human thromboplastin with nephelometric and photooptical detection. All thromboplastins have an instrument-specific International Sensitivity Index (ISI) lower than 1.10 reported by the manufacturer. Group 2: microINR results were compared with CoaguChek as an established device. Precision was assessed using liquid control materials. The control material coefficient of variation obtained in microINR device was 6.2%. The Passing-Bablok and Bland-Altman regression analysis showed a correlation coefficient greater than 0.92 and a small bias close to zero for all comparisons of microINR with each traditional coagulation method performed on venous blood samples. Both portable devices had a good correlation (r=0.98) and a very low bias of 0.02. The results show clinical agreement of 100% with a Kappa greater than 0.63 for different traditional INR and greater than 0.83 for CoaguChek. The performance microINR is suitable for the anticoagulation control of patients taking acenocumarol.

Resumo A razão normalizada internacional (INR) é utilizada para monitorar pacientes anticoagulados com antagonistas da vitamina K. O objetivo deste estudo foi avaliar o desempenho do dispositivo portátil microINR, um novo dispositivo que utiliza tromboplastina recombinante, em pacientes anticoagulados com acenocumarol. Grupo 1: os pacientes forneceram amostras de sangue venoso e capilar para testes paralelos que permitiram a comparação do microINR com cinco combinações diferentes de reagente/ sistema de detecção: tromboplastina de cérebro de coelho com detecção nefelométrica, foto-óptica e de viscosidade. Tromboplastina humana recombinante com detecção nefelométrica e foto-óptica. Todas as tromboplastinas tinham o Índice de Sensibilida de Internacional (ISI) específico do kit relatado pelo fabricante inferior a 1,10. Grupo 2: os resultados do microINR foram comparados com o CoaguChek como dispositivo padrão. A precisão foi avaliada usando materiais de controle líquidos. O coeficiente de variação do material de controle em microINR foi de 6,2%. A análise de regressão de Passing-Bablok e Bland-Altman mostrou um coeficiente de correlação maior que 0,92 e um pequeno viés próximo a zero para todas as variáveis. sangue. Ambos os wearables tiveram um coeficiente de correlação muito bom (r=0,98) e um pequeno viés de 0,02. Os resultados mostram 100% de concordância clínica com grau de concordância Kappa maior que 0,63 para todos os métodos tradicionais e 0,82 para a comparação com CoaguChek. De acordo com os resultados obtidos, o microINR é adequado para o controle de pacientes anticoagulados com acenocumarol.

Survival prognostic factors in unresectable/advanced primary thoracic sarcomas.

Background: Primary thoracic sarcomas (PTS) including primary pulmonary and chest wall sarcomas (CWS), are aggressive lung malignancies with limited information specially in an advanced/unresectable setting. Unfortunately, prognostic factors for these malignancies are not well identified. Methods: Retrospective cohort analysis of patients diagnosed with unresectable/advanced soft tissue PTS from a third level reference institute. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier method. Results: A total of 157 patients were identified, 55.4% female, mean age 51.8 years (range, 18-90 years), 19.1% tobacco exposure and 10.8% asbestos exposure. The most common performance status was Eastern Cooperative Oncology Group (ECOG) 1 (38.9%), most common clinical presentation cough (58.4%) and thoracic pain (55.4%). Undifferentiated sarcoma (37.6%) followed by synovial sarcoma (34.4%) were the most common histologies. Most patients received five chemotherapeutic cycles (37.6%), 57.3% of patients obtained a partial response and 61.1% an overall response rate (ORR). Median PFS was 9 months [95% confidence interval (CI): 8.717-9.283 months]. The multivariable analysis identified ECOG ≥2, a poorer response to chemotherapy (less number of chemotherapy cycles) and an increase Response Evaluation Criteria in Solid Tumors (RECIST) to be associated with a shorter progression-free period. Median OS was 11 months (95% CI: 10.402-11.958 months) with an ECOG ≥2 and a poorer response to chemotherapy (less number of chemotherapy cycles) associated with a shorter survival. Conclusions: Age, gender, comorbidities, tobacco and asbestos exposure, clinical presentation and histopathological diagnosis are not useful prognostic factors in unresectable/advanced PTS, however, an adequate initial ECOG, RECIST and a better response to chemotherapy should be used as prognostic factors in the management of these tumors.

Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL.

Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using gene editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target editing outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G to T•A point mutations in T cells, with between 90% and 99% efficiency to silence gene expression without creating DSBs, greatly reducing or eliminating undesired editing outcomes following multiplexed editing as compared with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using CBE, we developed 7CAR8, a CD7-directed allogeneic CART created using 4 simultaneous base edits. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation, or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells, with high potential for clinical translation for relapsed and refractory T-ALL.

Esquistossomose e o Coração - Em Nome das Doenças Tropicais Negligenciadas e Outras Doenças Infecciosas que Afetam o Coração (Projeto NET-Heart) / Schistosomiasis & Heart - On Behalf of the Neglected Tropical Diseases and other Infectious Diseases affecting the Heart (the NET-Heart Project)

Resumo Fundamento A esquistossomose é uma doença tropical negligenciada que pode levar a complicações cardiovasculares. No entanto, o envolvimento cardiovascular na esquistossomose ainda precisa ser totalmente elucidado, devido ao número limitado de casos e ausência de evidência confiável, uma vez que a doença ocorre tipicamente em locais sem infraestrutura adequada para uma coleta de dados robusta. Objetivo Esta revisão sistemática teve como objetivo avaliar as implicações cardiovasculares da esquistossomose, incluindo no diagnóstico e tratamento, e propor um algoritmo para rastrear as manifestações cardiovasculares. Métodos Foi realizada uma revisão sistemática nos bancos de dados MEDLINE/PubMed e LILACS, com busca por artigos sobre o comprometimento cardiovascular na esquistossomose. Resultados Trinta e três artigos foram considerados para esta revisão: seis artigos de revisão, uma revisão sistemática, um ensaio clínico, 14 estudos observacionais, sete relatos de casos, e quatro séries de casos. O comprometimento cardiovascular inclui um amplo espectro de condições clínicas, tais como isquemia do miocárdio, disfunção ventricular, miocardite, hipertensão arterial pulmonar, e pericardite. Conclusões As complicações cardíacas da esquistossomose podem causar incapacidade em longo prazo e morte. O monitoramento clínico, exame físico, eletrocardiograma precoce, e ecocardiograma devem ser considerados como medidas chave para detectar o envolvimento cardiovascular. Dada a ausência de um tratamento eficaz das complicações, são necessários saneamento e educação nas áreas endêmicas para a eliminação desse problema de saúde mundial.

Abstract Background Schistosomiasis is a Neglected Tropical Disease which may lead to cardiovascular (CV) complications. However, the CV involvement in schistosomiasis has yet to be fully elucidated due to the limited number of cases and lack of reliable evidence, as schistosomiasis typically occurs in locations without adequate infrastructure for robust data collection. Objective This systematic review aims to assess cardiovascular implications of schistosomiasis, including in the diagnosis and treatment, and propose an algorithm for screening of CV manifestations. Methods A systematic review was performed in the MEDLINE/PubMed and LILACS databases of articles on the CV involvement in schistosomiasis. Results Thirty-three records were considered for this review: six review articles, one systematic review, one clinical trial, 14 observational studies, seven case reports, and four cases series. CV involvement includes a wide spectrum of clinical conditions, such as myocardial ischemia, ventricular dysfunction, myocarditis, pulmonary arterial hypertension, and pericarditis. Conclusions Cardiac complications of schistosomiasis may cause long-term disability and death. Clinical monitoring, physical examination, early electrocardiogram, and echocardiogram should be considered as key measures to detect CV involvement. Due to the lack of effective treatment of complications, sanitation and education in endemic areas are necessary for the elimination of this global health problem.

Schistosomiasis & Heart - On Behalf of the Neglected Tropical Diseases and other Infectious Diseases affecting the Heart (the NET-Heart Project). / Esquistossomose e o Coração - Em Nome das Doenças Tropicais Negligenciadas e Outras Doenças Infecciosas que Afetam o Coração (Projeto NET-Heart).

BACKGROUND: Schistosomiasis is a Neglected Tropical Disease which may lead to cardiovascular (CV) complications. However, the CV involvement in schistosomiasis has yet to be fully elucidated due to the limited number of cases and lack of reliable evidence, as schistosomiasis typically occurs in locations without adequate infrastructure for robust data collection. OBJECTIVE: This systematic review aims to assess cardiovascular implications of schistosomiasis, including in the diagnosis and treatment, and propose an algorithm for screening of CV manifestations. METHODS: A systematic review was performed in the MEDLINE/PubMed and LILACS databases of articles on the CV involvement in schistosomiasis. RESULTS: Thirty-three records were considered for this review: six review articles, one systematic review, one clinical trial, 14 observational studies, seven case reports, and four cases series. CV involvement includes a wide spectrum of clinical conditions, such as myocardial ischemia, ventricular dysfunction, myocarditis, pulmonary arterial hypertension, and pericarditis. CONCLUSIONS: Cardiac complications of schistosomiasis may cause long-term disability and death. Clinical monitoring, physical examination, early electrocardiogram, and echocardiogram should be considered as key measures to detect CV involvement. Due to the lack of effective treatment of complications, sanitation and education in endemic areas are necessary for the elimination of this global health problem.

FUNDAMENTO: A esquistossomose é uma doença tropical negligenciada que pode levar a complicações cardiovasculares. No entanto, o envolvimento cardiovascular na esquistossomose ainda precisa ser totalmente elucidado, devido ao número limitado de casos e ausência de evidência confiável, uma vez que a doença ocorre tipicamente em locais sem infraestrutura adequada para uma coleta de dados robusta. OBJETIVO: Esta revisão sistemática teve como objetivo avaliar as implicações cardiovasculares da esquistossomose, incluindo no diagnóstico e tratamento, e propor um algoritmo para rastrear as manifestações cardiovasculares. MÉTODOS: Foi realizada uma revisão sistemática nos bancos de dados MEDLINE/PubMed e LILACS, com busca por artigos sobre o comprometimento cardiovascular na esquistossomose. RESULTADOS: Trinta e três artigos foram considerados para esta revisão: seis artigos de revisão, uma revisão sistemática, um ensaio clínico, 14 estudos observacionais, sete relatos de casos, e quatro séries de casos. O comprometimento cardiovascular inclui um amplo espectro de condições clínicas, tais como isquemia do miocárdio, disfunção ventricular, miocardite, hipertensão arterial pulmonar, e pericardite. CONCLUSÕES: As complicações cardíacas da esquistossomose podem causar incapacidade em longo prazo e morte. O monitoramento clínico, exame físico, eletrocardiograma precoce, e ecocardiograma devem ser considerados como medidas chave para detectar o envolvimento cardiovascular. Dada a ausência de um tratamento eficaz das complicações, são necessários saneamento e educação nas áreas endêmicas para a eliminação desse problema de saúde mundial.

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host-Pathogen Response to Infection.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), leading to pulmonary and extrapulmonary TB, whereby Mtb is disseminated to many other organs and tissues. Dissemination occurs early during the disease, and bacteria can be found first in the lymph nodes adjacent to the lungs and then later in the extrapulmonary organs, including the spleen. The early global gene expression response of human tissue macrophages and intracellular clinical isolates of Mtb has been poorly studied. Using dual RNA-seq, we have explored the mRNA profiles of two closely related clinical strains of the Latin American and Mediterranean (LAM) family of Mtb in infected human splenic macrophages (hSMs). This work shows that these pathogens mediate a distinct host response despite their genetic similarity. Using a genome-scale host-pathogen metabolic reconstruction to analyze the data further, we highlight that the infecting Mtb strain also determines the metabolic response of both the host and pathogen. Thus, macrophage ontogeny and the genetic-derived program of Mtb direct the host-pathogen interaction.