RESUMEN
Purpose of Review: Chagas disease (CD) is a neglected tropical disease from the American continent that commonly causes cardiovascular disease. Some patients develop neurological manifestations. We discuss and summarize the pathogenesis, clinical characteristics, diagnosis, and treatment of the central nervous system manifestations of CD. Recent Findings: Cerebrospinal fluid quantitative polymerase chain reaction tests and next-generation sequencing in tissue samples have facilitated disease diagnosis and follow-up. Novel presentations, including retinitis, are now reported. A new MRI sign called "Bunch of açai berries appearance"-multiple hypointense nodular lesions-has been described recently. Treatment with benznidazole at higher doses and the role of therapeutic drug monitoring need to be further studied in this setting. Summary: A high suspicion index is paramount to diagnosing Chagas' central nervous system involvement. Standardized molecular diagnostics can aid in the initial workup. Future development of new therapeutic drugs is crucial because of the toxicity profile of the currently available medications.
RESUMEN
PURPOSE OF THE REVIEW: Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections' role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. RECENT FINDINGS: Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host's immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5 years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.
Asunto(s)
Cardiomiopatía Chagásica , Enfermedad de Chagas , Insuficiencia Cardíaca , Animales , Antiparasitarios/uso terapéutico , Cardiomiopatía Chagásica/etiología , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , ReinfecciónRESUMEN
We present the unusual case of a 60-year-old immunocompetent woman with chronic obstructive pulmonary disease who developed a necrotising pneumonia with isolation of Cunninghamella bertholletiae, Aspergillus niger, Staphylococcus pseudintermedius and adenovirus. The patient recovered with antimicrobial therapy and supportive care in the intensive care unit. The current literature on diagnosis and treatment of these pathogens is reviewed.
Asunto(s)
Mucormicosis , Neumonía Necrotizante , Adenoviridae , Aspergillus niger , Cunninghamella , Femenino , Humanos , Persona de Mediana Edad , StaphylococcusRESUMEN
BET proteins commonly activate cellular gene expression, yet inhibiting their recruitment paradoxically reactivates latent HIV-1 transcription. Here we identify the short isoform of BET family member BRD4 (BRD4S) as a corepressor of HIV-1 transcription. We found that BRD4S was enriched in chromatin fractions of latently infected T cells, and it was more rapidly displaced from chromatin upon BET inhibition than the long isoform. BET inhibition induced marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BRG1-associated factors (BAF), an SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription. BRD4S directly bound BRG1, a catalytic subunit of BAF, via its bromodomain and extraterminal (ET) domain, and this isoform was necessary for BRG1 recruitment to latent HIV-1 chromatin. Using chromatin immunoprecipitation sequencing (ChIP-seq) combined with assay for transposase-accessible chromatin coupled to high-throughput sequencing (ATAC-seq) data, we found that the latent HIV-1 promoter phenotypically resembles endogenous long terminal repeat (LTR) sequences, pointing to a select role of BRD4S-BRG1 complexes in genomic silencing of invasive retroelements.
Asunto(s)
Ensamble y Desensamble de Cromatina , Cromatina/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , ADN Viral/metabolismo , VIH-1/metabolismo , Proteínas Nucleares/metabolismo , Linfocitos T/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética , Latencia del Virus , Azepinas/farmacología , Proteínas de Ciclo Celular , Cromatina/genética , Ensamble y Desensamble de Cromatina/efectos de los fármacos , Inmunoprecipitación de Cromatina , Proteínas Cromosómicas no Histona/efectos de los fármacos , Proteínas Cromosómicas no Histona/genética , ADN Helicasas/genética , ADN Helicasas/metabolismo , ADN Viral/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Regulación Viral de la Expresión Génica , Células HEK293 , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno , Humanos , Células Jurkat , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Unión Proteica , Isoformas de Proteínas , Interferencia de ARN , Retroelementos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/virología , Factores de Tiempo , Factores de Transcripción/efectos de los fármacos , Factores de Transcripción/genética , Transcripción Genética/efectos de los fármacos , Transfección , Triazoles/farmacología , Latencia del Virus/efectos de los fármacosRESUMEN
Chronic rhinosinusitis (CRS) affects 12.5% of the U.S. POPULATION: CRS can be divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. Some individuals with CRSwNP do not respond to standard-of-care medical and surgical management. For these individuals, targeted biologic agents are emerging as an important therapeutic alternative. In this review, we described the most-relevant studies that addressed the use of anti-immunoglobulin E (omalizumab), anti-interleukin 5 (mepolizumab and reslizumab), and anti-interleukin 4/interleukin 13 (dupilumab) monoclonal antibodies for the treatment of CRSwNP. In addition, we discussed the importance of some of these clinical trials in identifying new CRS endotypes based on distinct inflammatory profiles.