RESUMEN
Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed.
Asunto(s)
Fiebre Hemorrágica con Síndrome Renal , Animales , Fiebre Hemorrágica con Síndrome Renal/diagnóstico , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Fiebre Hemorrágica con Síndrome Renal/prevención & control , China , India , Japón , Tailandia , Zoonosis/diagnóstico , Zoonosis/epidemiología , Zoonosis/prevención & control , MamíferosRESUMEN
BACKGROUND AND AIMS: Within the next decade, NAFLD is predicted to become the most prevalent cause of childhood liver failure in developed countries. Predisposition to juvenile NAFLD can be programmed during early life in response to maternal metabolic syndrome (MetS), but the underlying mechanisms are poorly understood. We hypothesized that imprinted genes, defined by expression from a single parental allele, play a key role in maternal MetS-induced NAFLD, due to their susceptibility to environmental stressors and their functions in liver homeostasis. We aimed to test this hypothesis and determine the critical periods of susceptibility to maternal MetS. APPROACH AND RESULTS: We established a mouse model to compare the effects of MetS during prenatal and postnatal development on NAFLD. Postnatal but not prenatal MetS exposure is associated with histological, biochemical, and molecular signatures of hepatic steatosis and fibrosis in juvenile mice. Using RNA sequencing, we show that the Imprinted Gene Network (IGN), including its regulator Zac1, is up-regulated and overrepresented among differentially expressed genes, consistent with a role in maternal MetS-induced NAFLD. In support of this, activation of the IGN in cultured hepatoma cells by overexpressing Zac1 is sufficient to induce signatures of profibrogenic transformation. Using chromatin immunoprecipitation, we demonstrate that Zac1 binds the TGF-ß1 and COL6A2 promoters, forming a direct pathway between imprinted genes and well-characterized pathophysiological mechanisms of NAFLD. Finally, we show that hepatocyte-specific overexpression of Zac1 is sufficient to drive fibrosis in vivo. CONCLUSIONS: Our findings identify a pathway linking maternal MetS exposure during postnatal development to the programming of juvenile NAFLD, and provide support for the hypothesis that imprinted genes play a central role in metabolic disease programming.
Asunto(s)
Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Factores de Transcripción , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Modelos Animales de Enfermedad , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiología , Genes Supresores de Tumor/fisiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , Ratones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1RESUMEN
Cadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models and humans suggests maternal Cd exposure negatively impacts neurodevelopment; however, the underlying molecular mechanisms are unclear. To address this, we utilized multiple -omics approaches in a mouse model of maternal Cd exposure to identify pathways altered in the developing brain. Offspring maternally exposed to Cd presented with enlarged brains proportional to body weights at birth and altered behavior at adulthood. RNA-seq in newborn brains identified exposure-associated increases in Hox gene and myelin marker expression and suggested perturbed retinoic acid (RA) signaling. Proteomic analysis showed altered levels of proteins involved in cellular energy pathways, hypoxic response, and RA signaling. Consistent with transcriptomic and proteomic analyses, we identified increased levels of retinoids in maternally-exposed newborn brains. Metabolomic analyses identified metabolites with significantly altered abundance, supportive of changes to cellular energy pathways and hypoxia. Finally, maternal Cd exposure reduced mitochondrial DNA levels in newborn brains. The identification of multiple pathways perturbed in the developing brain provides a basis for future studies determining the mechanistic links between maternal Cd exposure and altered neurodevelopment and behavior.
Asunto(s)
Cadmio/toxicidad , Trastornos del Neurodesarrollo/inducido químicamente , Trastornos del Neurodesarrollo/genética , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/genética , Transcriptoma/genética , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/genética , Femenino , Desarrollo Fetal/efectos de los fármacos , Desarrollo Fetal/genética , Humanos , Exposición Materna , Metabolómica/métodos , Ratones , Ratones Endogámicos C57BL , Placenta/efectos de los fármacos , Embarazo , Proteómica/métodosRESUMEN
OBJECTIVE: Hazardous materials (HAZMAT) incidents, including the deliberate release of toxic chemicals, can cause a significant drain on resources as well as heightened anxiety in the community. Recent high-profile incidents, including the 2018 illegal waste storage fire in Victoria, Australia, have highlighted the complexity but also the value of multidisciplinary approaches to HAZMAT events. This brief report examines issues from a public health perspective and reflects on the experience of such events in South Australia. METHODS: The type, location and time of HAZMAT incidents for the period 2001 to 2018 (inclusive) in South Australia were compiled and classified from a database of the state Technical Advice Coordinator. RESULTS: The profile of HAZMAT events was diverse, including fires, spills, unknown chemicals, sabotage and suicides. Incidents frequently occurred around transportation corridors and storage facilities. Public health agency involvement was most evident for known or suspected biological agents (toxins) and chemical toxicants with persistent exposures. Conclusion and implications for public health: Public health agencies are likely to have a greater future role in HAZMAT management as the complexity of incidents increases (e.g. mass casualty events and events involving vulnerable subpopulations). There is a need for a national HAZMAT surveillance database to coordinate agency responses on a national level. A unified approach to risk communication for vulnerable communities is also critical.
Asunto(s)
Desastres , Sustancias Peligrosas/efectos adversos , Salud Pública , Australia , Urgencias Médicas , Humanos , Incidentes con Víctimas en MasaRESUMEN
PURPOSE: Meibum is considered to be a key component of tears that serve to protect the eye, and conformational changes in meibum have not been studied extensively within the population of patients who had hematopoietic stem cell transplantation (HSCT). The aim of this study was to determine possible lipid conformational changes in the meibum of patients who had HSCT. METHODS: Participants who had HSCT were randomly sampled for this prospective comparative study. Control participants did not have dry eye or had not undergone allogeneic or autologous stem cell transplantation. Fourier-transform infrared spectroscopy was used to measure meibum phase transition. RESULTS: Meibum was collected from both eyes of 36 donors without dry eye (Mc) and from 22 patients who had undergone HSCT (MHSCT). There were no significant differences between the phase transition parameters based on gender or race. The following were the significant differences (P < 0.0001) between the parameters for Mc compared with MHSCT : lipid order (% trans) at 33.4°C increased from 40 (1) to 54 (2), cooperativity decreased from 7.9 (0.4) to 5.4 (0.3), the phase transition temperature (C) increased from 30.3 (0.4) to 34.2 (0.9), and the magnitude of the phase transition (cm) increased from 4.0 (0.1) to 4.7 (0.5) (standard error of the mean). CONCLUSIONS: Conformational and thermodynamic differences were observed between Mc and MHSCT. The changes observed in the lipid conformation of meibum from patients receiving HSCTs suggest that meibum composition changes after stem cell transplantation, and clinicians should consider treating the meibomian glands to improve the ocular surface.