Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

The first Non-LRV RNA virus in leishmania

In this work, we describe the first Leishmania-infecting leishbunyavirus—the first virus other than Leishmania RNA virus (LRV) found in trypanosomatid parasites. Its host is Leishmania martiniquensis, a human pathogen causing infections with a wide range of manifestations from asymptomatic to severe visceral disease. This virus (LmarLBV1) possesses many characteristic features of leishbunyaviruses, such as tripartite organization of its RNA genome, with ORFs encoding RNA-dependent RNA polymerase, surface glycoprotein, and nucleoprotein on L, M, and S segments, respectively. Our phylogenetic analyses suggest that LmarLBV1 originated from leishbunyaviruses of monoxenous trypanosomatids and, probably, is a result of genomic re-assortment. The LmarLBV1 facilitates parasites’ infectivity in vitro in primary murine macrophages model. The discovery of a virus in L. martiniquensis poses the question of whether it influences pathogenicity of this parasite in vivo, similarly to the LRV in other Leishmania species

Detección de Pneumocystis jirovecii mediante PCR anidada en pacientes VIH negativos con enfermedad pulmonar

Nested PCR can be used to determine the status of Pneumocystis jirovecii infection in other lung diseases. This study sought to detect a target DNA fragment (mitochondrial large subunit rRNA or mtL SUrRNA) of P. jirovecii in patients with lung disease who underwent bronchoscopy with collection of bronchoalveolar lavage (BAL). The results from toluidine blue staining were compared with those obtained using molecular methods that included an “in house” DNA extraction procedure, PCR and nested PCR. Fifty-five BAL samples from patients with atypical chest X-rays were screened for P. jirovecii. None of the samples was positive for P. jirovecii using toluidine blue staining. In contrast, P. jirovecii DNA was detected by nested PCR in BAL samples from 36 of 55 patients (65.5%). The lung diseases in the patients included cancer, pneumonia, tuberculosis, and chronic obstructive pulmonary disease (COPD). Other chronic problems in the patients included hypertension, diabetes, smoking, and alcoholism. Nested PCR showed high sensitivity for detecting P. jirovecii, especially when compared with toluidine blue staining. Using this method, P. jirovecii infection was detected in HIV-negative patients with lung disease.3428388El diagnóstico de laboratorio mediante la técnica de PCR anidada permite determinar estados de infección por Pneumocystis jirovecii en otras enfermedades pulmonares. El objetivo de este estudio fue detectar fragmentos de ADN mitocondrial (mtLSU rRNA) de P. jirovecii en muestras de lavado broncoalveolar (LBA) de pacientes con enfermedades pulmonares, sometidos a broncoscopia. Se compara la técnica de coloración con azul de toluidina para la microscopia, con los métodos moleculares PCR y PCR anidada; se realizó una extracción in house de ADN para las reacciones moleculares. La presencia de P. jirovecii fue estudiada en 55 muestras de LBA de pacientes que presentaron patrones radiográficos de tórax atípicos. Ninguna de las muestras fue positiva para P. jirovecii con la técnica de coloración con azul de toluidina. Por la técnica de PCR anidada se detectó el ADN de P. jirovecii en 36 de los 55 pacientes (65,5%). Las enfermedades pulmonares de los pacientes fueron cáncer, neumonía, tuberculosis y enfermedad pulmonar obstructiva crónica (EPOC). Las otras enfermedades crónicas presentadas por los pacientes fueron hipertensión, diabetes, alcoholismo y tabaquismo. La PCR anidada mostró ser altamente sensible en la detección de P. jirovecii en comparación con la coloración por azul de toluidina. Este método permite detectar infecciones por P. jirovecii en pacientes VIH negativos con enfermedades pulmonares

Detección De Pneumocystis Jirovecii Mediante Pcr Anidada En Pacientes Vih Negativos Con Enfermedad Pulmonar

Nested PCR can be used to determine the status of Pneumocystis jirovecii infection in other lung diseases. Aims This study sought to detect a target DNA fragment (mitochondrial large subunit rRNA or mtL SUrRNA) of P. jirovecii in patients with lung disease who underwent bronchoscopy with collection of bronchoalveolar lavage (BAL). Methods The results from toluidine blue staining were compared with those obtained using molecular methods that included an “in house” DNA extraction procedure, PCR and nested PCR. Results Fifty-five BAL samples from patients with atypical chest X-rays were screened for P. jirovecii. None of the samples was positive for P. jirovecii using toluidine blue staining. In contrast, P. jirovecii DNA was detected by nested PCR in BAL samples from 36 of 55 patients (65.5%). The lung diseases in the patients included cancer, pneumonia, tuberculosis, and chronic obstructive pulmonary disease (COPD). Other chronic problems in the patients included hypertension, diabetes, smoking, and alcoholism. Conclusions Nested PCR showed high sensitivity for detecting P. jirovecii, especially when compared with toluidine blue staining. Using this method, P. jirovecii infection was detected in HIV-negative patients with lung disease. © 2016 Asociación Española de Micología342838

Comparative genomics of Leishmania (Mundinia)

Background Trypanosomatids of the genus Leishmania are parasites of mammals or reptiles transmitted by bloodsucking dipterans. Many species of these flagellates cause important human diseases with clinical symptoms ranging from skin sores to life-threatening damage of visceral organs. The genus Leishmania contains four subgenera: Leishmania, Sauroleishmania, Viannia, and Mundinia. The last subgenus has been established recently and remains understudied, although Mundinia contains human-infecting species. In addition, it is interesting from the evolutionary viewpoint, representing the earliest branch within the genus and possibly with a different type of vector. Here we analyzed the genomes of L. (M.) martiniquensis, L. (M.) enriettii and L. (M.) macropodum to better understand the biology and evolution of these parasites. Results All three genomes analyzed were approximately of the same size (~ 30 Mb) and similar to that of L. (Sauroleishmania) tarentolae, but smaller than those of the members of subgenera Leishmania and Viannia, or the genus Endotrypanum (~ 32 Mb). This difference was explained by domination of gene losses over gains and contractions over expansions at the Mundinia node, although only a few of these genes could be identified. The analysis predicts significant changes in the Mundinia cell surface architecture, with the most important ones relating to losses of LPG-modifying side chain galactosyltransferases and arabinosyltransferases, as well as β-amastins. Among other important changes were gene family contractions for the oxygen-sensing adenylate cyclases and FYVE zinc finger-containing proteins. Conclusions We suggest that adaptation of Mundinia to different vectors and hosts has led to alternative host-parasite relationships and, thereby, made some proteins redundant. Thus, the evolution of genomes in the genus Leishmania and, in particular, in the subgenus Mundinia was mainly shaped by host (or vector) switches

Who’s afraid of a world state? A global sovereign and the statist-cosmopolitan debate

Wary of quick statist dismissal of their proposals, cosmopolitans have been careful not to associate themselves with a world state. I argue that this caution is mistaken: cosmopolitans should see the vision of a world state as strategically valuable in exposing weaknesses in statist accounts, particularly of the Rawlsian variety. This strategic value follows if the only cogent arguments against a world state belong to non-ideal theory which assumes non-compliance, rather than to ideal theory with its core assumption of full compliance. If our only convincing reasons to reject a world state are non-ideal, then any liberal theory revolving around separate states must itself be considered a non-ideal theory. As a non-ideal theory, a statist law of peoples cannot be presented as an end-state, but is rather a transitional stage. Yet once seen as a transitional theory, the statist “realistic utopia” can no longer dodge the cosmopolitan charge that it is neither sufficiently realistic nor sufficiently utopian