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The Western Australian mining industry is a global supplier of critical minerals, including lithium and rare earths. The lithology of these minerals is associated with elevated concentrations of naturally occurring radionuclides (NORs). An increase in the number of mines producing the minerals has witnessed a commensurate increase in the number of workers potentially exposed to the radiation from NORs. The regulatory framework in Western Australia underwent significant change in March 2022. Mining operations whose workers are likely to receive doses greater than one mSvy-1 are referenced as relevant mines and are required to submit an annual report of worker doses to the mining regulator. This research provides an overview of the new legislative framework and updates the information in Ralph and Cattani (2022) to include data derived from annual radiation doses reported by relevant mines in the period spanning 2020-21 to 2022-23. In 2022-23, 38 mining operations were identified as relevant mines, an increase of sixteen from 2020-21. The mean effective dose (ED) reported in the three-year period was 1.0 mSv, and the maximum ED was 4.9 mSv. The collective effective dose of the mine worker population reached an historical maximum of 2,339 man.mSv in 2022-23. Inhalation of long-lived alpha emitting radionuclides in dust remains the most significant contributor to worker doses. Inhalation of radon-22, radon-220 and their short-lived progeny, once considered as a negligible contributor to worker doses, is the second most significant exposure pathway. A declining trend in the number of samples collected per worker is highlighted as requiring remediation to provide confidence in the reported dose estimates. The transition to the new legislative framework for radiation protection in mines has been supported by the publication of guidance materials which have been widely endorsed by the industry. .
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BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).
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Biomarcadores , Proteína C-Reactiva , COVID-19 , Coinfección , SARS-CoV-2 , Componente Amiloide P Sérico , Humanos , COVID-19/sangre , COVID-19/diagnóstico , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Componente Amiloide P Sérico/metabolismo , Biomarcadores/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Infecciones Bacterianas/sangre , Infecciones Bacterianas/diagnóstico , Polipéptido alfa Relacionado con Calcitonina/sangre , Pronóstico , Micosis/sangre , Micosis/diagnóstico , Anciano de 80 o más AñosRESUMEN
Aging is the biggest risk factor for Parkinson's disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss and if so, how this intersects with PD-related neurodegeneration. Here, through examining a large collection of naturally varying Drosophila strains, we find a strong relationship between life span and age-related dopamine neuron loss. Naturally short-lived strains exhibit a loss of dopamine neurons but not generalized neurodegeneration, while long-lived strains retain dopamine neurons across age. Metabolomic profiling reveals lower glutathione levels in short-lived strains which is associated with elevated levels of reactive oxygen species (ROS), sensitivity to oxidative stress and vulnerability to silencing the familial PD gene parkin . Strikingly, boosting neuronal glutathione levels via glutamate-cysteine ligase (GCL) overexpression is sufficient to normalize ROS levels, extend life span and block dopamine neurons loss in short-lived backgrounds, demonstrating that glutathione deficiencies are central to neurodegenerative phenotypes associated with short longevity. These findings may be relevant to human PD pathogenesis, where glutathione depletion is frequently reported in idiopathic PD patient brain. Building on this evidence, we detect reduced levels of GCL catalytic and modulatory subunits in brain from PD patients harboring the LRRK2 G2019S mutation, implicating possible glutathione deficits in familial LRRK2-linked PD. Our study across Drosophila and human PD systems suggests that glutathione plays an important role in the influence of aging on PD neurodegeneration.
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BACKGROUND: Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion of pathogen through the hematologic route. Mixed osteomyelitis caused by bacteria and fungi is rare, and to date, there have been no reports of mixed osteomyelitis with Staphylococcus spp. and Microsporum canis. CASE PRESENTATION: This essay reports an atypical presentation of mixed osteomyelitis (Staphylococcus spp. and Microsporum canis) in a domestic cat. A 15-month-old female Persian cat was presented to a veterinary service; the main complaint was the appearance of a nodule in the mandibular ventral rostral region. A radiographic exam performed on the animal showed proliferative and osteolytic bone lesions. The patient was submitted to a biopsy for histopathological evaluation, along with bacterial and fungal cultures. Results showed mixed osteomyelitis by Staphylococcus spp. and Microsporum canis. Microbial Sensitivity Test was performed to choose a more suitable treatment. Two surgical procedures were executed to resect and curette the lesion, and treatments with anti-inflammatory, antibiotic, and antifungal drugs were established, showing a positive clinical evolution. After 8 months of treatment, the patient's owner moved to a different city, and the animal was seen by other veterinarians, who followed along with the same treatment. However, due to complications and a diminishing quality of life over 4 years of diagnosis, the patient was euthanized. CONCLUSION: Given the above, mixed osteomyelitis is difficult to treat and can cause losses of life quality resulting death, especially in infections where M. canis is the agent causing the disease. Bacterial osteomyelitis is more frequently reported. But the lack of investigation of microorganisms other than bacteria, such as fungal cases, may imply in underdiagnosed cases. Treatment of osteomyelitis can be difficult considering the difficulties in isolating the pathological agent, resistance to the drug used, prolonged treatment time, and cost.
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Enfermedades de los Gatos , Dermatomicosis , Microsporum , Osteomielitis , Gatos , Femenino , Animales , Dermatomicosis/veterinaria , Calidad de Vida , Antifúngicos/uso terapéutico , Osteomielitis/tratamiento farmacológico , Osteomielitis/veterinaria , Enfermedades de los Gatos/tratamiento farmacológicoRESUMEN
INTRODUCTION: The World Health Organization developed Emergency Triage Assessment and Treatment Plus (ETAT+) guidelines to facilitate pediatric care in resource-limited settings. ETAT+ triages patients as nonurgent, priority, or emergency cases, but there is limited research on the performance of ETAT+ regarding patient-oriented outcomes. This study assessed the diagnostic accuracy of ETAT+ in predicting the need for hospital admission in a pediatric emergency unit at Kenyatta National Hospital in Nairobi, Kenya. METHODS: This was a secondary analysis of a cross-sectional study of pediatric emergency unit patients enrolled over a 4-week period using fixed random sampling. Diagnostic accuracy of ETAT+ was evaluated using receiver operating curves (ROCs) and respective 95% confidence intervals (CIs) with associated sensitivity and specificity (reference category: nonurgent). The ROC analysis was performed for the overall population and stratified by age group. RESULTS: A total of 323 patients were studied. The most common reasons for presentation were upper respiratory tract disease (32.8%), gastrointestinal disease (15.5%), and lower respiratory tract disease (12.4%). Two hundred twelve participants were triaged as nonurgent (65.6%), 60 as priority (18.6%), and 51 as emergency (15.8%). In the overall study population, the area under the ROC curve was 0.97 (95% CI, 0.95-0.99). The ETAT+ sensitivity was 93.8% (95% CI, 87.0%-99.0%), and the specificity was 82.0% (95% CI, 77.0%-87.0%) for admission of priority group patients. The sensitivity and specificity for the emergency patients were 66.0% (95% CI, 55.0%-77.0%) and 98.0% (95% CI, 97.0%-100.0%), respectively. CONCLUSIONS: ETAT+ demonstrated diagnostic accuracy for predicting patient need for hospital admission. This finding supports the utility of ETAT+ to inform emergency care practice. Further research on ETAT+ performance in larger populations and additional patient-oriented outcomes would enhance its generalizability and application in resource-limited settings.
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Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains. Cluster of differentiation CD4+ resident memory T (TRM) cells are known to be crucial for this protection, but the diversity of lung CD4+ TRM cells has yet to be fully delineated. We aimed to identify unique subsets and their contributions to lung immunity. After recovery from pneumococcal infections, we identified a distinct subset of CD4+ T cells defined by the phenotype CD11ahiCD69+GL7+ in mouse lungs. Phenotypic analyses for markers of lymphocyte memory and residence demonstrated that GL7+ T cells are a subset of CD4+ TRM cells. Functional studies revealed that unlike GL7- TRM subsets that were mostly (RAR-related Orphan Receptor gamma T) RORγT+, GL7+ TRM cells exhibited higher levels of (T-box expressed in T cells) T-bet and Gata-3, corresponding with increased synthesis of interferon-γ, interleukin-13, and interleukin-5, inherent to both T helper 1 (TH1) and TH2 functions. Thus, we propose that these cells provide novel contributions during pneumococcal pneumonia, serving as important determinants of lung immunity.
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Pulmón , Streptococcus pneumoniae , Anciano , Animales , Niño , Humanos , Ratones , Linfocitos T CD4-Positivos , Memoria Inmunológica , Ligandos , Linfocitos TRESUMEN
Unlike single-gene mutations leading to Mendelian conditions, common human diseases are likely to be emergent phenomena arising from multilayer, multiscale, and highly interconnected interactions. Atrial and ventricular septal defects are the most common forms of cardiac congenital anomalies in humans. Atrial septal defects (ASD) show an open communication between the left and right atria postnatally, potentially resulting in serious hemodynamic consequences if untreated. A milder form of atrial septal defect, patent foramen ovale (PFO), exists in about one-quarter of the human population, strongly associated with ischaemic stroke and migraine. The anatomic liabilities and genetic and molecular basis of atrial septal defects remain unclear. Here, we advance our previous analysis of atrial septal variation through quantitative trait locus (QTL) mapping of an advanced intercross line (AIL) established between the inbred QSi5 and 129T2/SvEms mouse strains, that show extremes of septal phenotypes. Analysis resolved 37 unique septal QTL with high overlap between QTL for distinct septal traits and PFO as a binary trait. Whole genome sequencing of parental strains and filtering identified predicted functional variants, including in known human congenital heart disease genes. Transcriptome analysis of developing septa revealed downregulation of networks involving ribosome, nucleosome, mitochondrial, and extracellular matrix biosynthesis in the 129T2/SvEms strain, potentially reflecting an essential role for growth and cellular maturation in septal development. Analysis of variant architecture across different gene features, including enhancers and promoters, provided evidence for the involvement of non-coding as well as protein-coding variants. Our study provides the first high-resolution picture of genetic complexity and network liability underlying common congenital heart disease, with relevance to human ASD and PFO.
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Isquemia Encefálica , Foramen Oval Permeable , Cardiopatías Congénitas , Accidente Cerebrovascular , Humanos , Ratones , Animales , Foramen Oval Permeable/genética , Fenotipo , Perfilación de la Expresión GénicaRESUMEN
Controlled protein synthesis is required to regulate gene expression and is often carried out in a cell type-specific manner. Protein synthesis is commonly measured by labeling the nascent proteome with amino acid analogs or isotope-containing amino acids. These methods have been difficult to implement in vivo as they require lengthy amino acid replacement procedures. O-propargyl-puromycin (OPP) is a puromycin analog that incorporates into nascent polypeptide chains. Through its terminal alkyne, OPP can be conjugated to a fluorophore-azide for directly visualizing nascent protein synthesis, or to a biotin-azide for capture and identification of newly-synthesized proteins. To achieve cell type-specific OPP incorporation, we developed phenylacetyl-OPP (PhAc-OPP), a puromycin analog harboring an enzyme-labile blocking group that can be removed by penicillin G acylase (PGA). Here, we show that cell type-specific PGA expression in Drosophila can be used to achieve OPP labeling of newly-synthesized proteins in targeted cell populations within the brain. Following a brief 2 hr incubation of intact brains with PhAc-OPP, we observe robust imaging and affinity purification of OPP-labeled nascent proteins in PGA-targeted cell populations. We apply this method to show a pronounced age-related decline in neuronal protein synthesis in the fly brain, demonstrating the capability of PhAc-OPP to quantitatively capture in vivo protein synthesis states. This method, which we call POPPi (PGA-dependent OPP incorporation), should be applicable for rapidly visualizing protein synthesis and identifying nascent proteins synthesized under diverse physiological and pathological conditions with cellular specificity in vivo.
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Drosophila , Proteoma , Animales , Proteoma/metabolismo , Drosophila/metabolismo , Azidas/química , Aminoácidos/metabolismo , PuromicinaRESUMEN
Summary: Phaeochromocytoma, a rare neuroendocrine tumour of chromaffin cell origin, is characterised by catecholamine excess. Clinical presentation ranges from asymptomatic disease to life-threatening multiorgan dysfunction. Catecholamine-induced cardiomyopathy is a dreaded complication with high lethality. While there is lack of evidence-based guidelines for use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in the management of this condition, limited to case reports and small case series, V-A ECMO has been reported as 'bridge to recovery' therapy, providing circulatory support in the initial period of stabilisation prior to surgery. We report on two patients presenting with catecholamine-induced cardiomyopathy and circulatory collapse who were successfully treated with V-A ECMO for 5 and 6 days, respectively, providing initial haemodynamic support. After stabilisation and introduction of alpha-blockade, both cases had favourable outcomes, with successful laparoscopic adrenalectomies on days 62 and 83 of admission, respectively. Our case reports provide further support for the use of V-A ECMO in the treatment of such gravely ill patients. Learning points: Phaeochromocytoma should be considered in the diagnosis of patients presenting with acute cardiomyopathy. Management of catecholamine-induced cardiomyopathy is complex and requires multidisciplinary specialist input. Pre-operative management of phaeochromocytoma involves alpha-blockade; however, haemodynamic instability in the setting of cardiogenic shock can preclude alpha-blockade use. Veno-arterial extracorporeal membrane oxygenation is a life-saving intervention which may be considered in cases of acute catecholamine-induced cardiomyopathy and cardiogenic shock in order to provide the required haemodynamic support in the initial phase of treatment, enabling the administration of traditional pharmacological agents, including alpha-blockade.
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Antifungals are used widely in clinical and agricultural practice to control fungal growth, either treating or preventing infection. There are reports of increasing prevalence of resistance to antifungals in human pathogens and concern that their use in agriculture is driving clinical resistance in patients. While crop protection products are the most obvious source in agriculture, a further source may be biosolids from wastewater treatment. In the UK, these are applied to land to provide nutrients and improve soil structure for crops. In this study, biosolids from ten sites in England and one in Wales were analysed for clinical antifungals. Ketoconazole and miconazole were detected in all samples with a median concentration of 0.87 and 0.54 mg kg-1 dry weight (DW), respectively. Clotrimazole was detected at seven of eleven sites at a median level of 1.32 mg kg-1 DW and its absence at four others was considered treatment related. Two prescription-only and systemic medications, itraconazole and posaconazole, were frequently detected with median concentrations of 0.14 mg kg-1 DW and 0.09 mg kg-1 DW, respectively. The biosolid levels of itraconazole found in this study were two orders of magnitude higher than an indicative Predicted No Effect Concentration for resistance selection (PNEC-R) in soil. Neither fluconazole, griseofulvin, and voriconazole nor flucytosine and nystatin were found above the limit of detection of 0.01 or 0.1 mg kg-1 as received, respectively. The findings show that biosolids represent a viable pathway for antifungal agents to reach soil.
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Antifúngicos , Itraconazol , Humanos , Antifúngicos/análisis , Biosólidos , Gales , Suelo/química , Aguas del Alcantarillado/químicaRESUMEN
Excited delirium syndrome (ExDS) is a controversial and disputed diagnosis involving altered mentation, agitation, and, frequently, substance abuse. Recently, it has become a common pre-hospital diagnosis, serving as justification for use of force, restraint, and/or medication administration. To conduct a scoping review across three databases to describe the most frequently reported diagnostic criteria for ExDS, as well as to explore its use as a diagnosis for deaths of individuals in the custody of law enforcement. In 2021, three literature databases were searched: Ovid Medline, PsycInfo, and Scopus. Studies were included if they were peer-reviewed, English articles describing (1) ExDS symptoms, (2) substance intoxication with at least 2 ExDS symptoms present, or (3) centering on deaths occurring in the custody of law enforcement and attributed to ExDS. Key study data were extracted and the current literature was described qualitatively. Analysis took place between March and December 2021. A total of 97 studies were identified through initial abstract and secondary full-text review, with noted discrepancies in the definition of ExDS itself. After review, differences in ExDS diagnosis among organizations were explored, along with subsequent clinical impact, particularly in the pre-hospital setting. Resulting impact on patients, particularly those of minoritized ethnic and racial groups, was also noted. Prone aggressive restraint, in particular, is noted as an established risk factor for fatalities in ExDS cases. At this time, ExDS should not be utilized as a diagnosis; major medical organizations have an urgent responsibility to convene to formalize consensus-based diagnostic criteria or to propose alternate management guidelines for agitated and altered persons.
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Aging is the greatest risk factor for Parkinson's disease (PD), suggesting that mechanisms driving the aging process promote PD neurodegeneration. Several lines of evidence support a role for aging in PD. First, hallmarks of brain aging such as mitochondrial dysfunction and oxidative stress, loss of protein homeostasis, and neuroinflammation are centrally implicated in PD development. Second, mutations that cause monogenic PD are present from conception, yet typically only cause disease following a period of aging. Third, lifespan-extending genetic, dietary, or pharmacological interventions frequently attenuate PD-related neurodegeneration. These observations support a central role for aging in disease development and suggest that new discoveries in the biology of aging could be leveraged to elucidate novel mechanisms of PD pathophysiology. A recent rapid growth in our understanding of conserved molecular pathways that govern model organism lifespan and healthspan has highlighted a key role for metabolism and nutrient sensing pathways. Uncovering how metabolic pathways involving NAD+ consumption, insulin, and mTOR signaling link to the development of PD is underway and implicates metabolism in disease etiology. Here, we assess areas of convergence between nervous system aging and PD, evaluate the link between metabolism, aging, and PD and address the potential of metabolic interventions to slow or halt the onset of PD-related neurodegeneration drawing on evidence from cellular and animal models.
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Enfermedad de Parkinson , Animales , Enfermedad de Parkinson/metabolismo , Mitocondrias , Envejecimiento , Estrés Oxidativo/fisiología , Transducción de SeñalRESUMEN
BACKGROUND: We describe patient-visit volumes, patient acuity, and demographics in our 4 academic health system emergency departments (ED) before, during, and after implementation of a COVID-19 pandemic safer-at-home order. METHODS: Data were collected from the electronic health record, including patient-visit volumes, chief complaint, Emergency Severity Index (ESI), and patient demographics. Descriptive statistics were performed. RESULTS: There was a 37% decrease in combined ED patient-visit volume during the safer-at-home order period (42% at the academic medical center). ED patient-visit volumes increased after the safer-at-home order concluded. During the safer-at-home order period, there was an increase in the proportion of ESI-2 visits and admission rates from EDs across the system. CONCLUSIONS: Significant differences in ED patient-visit volumes and patient acuity were associated with a safer-at-home order in our academic health system. These differences are similar to experiences of other hospital systems across the country.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Servicio de Urgencia en Hospital , Centros Médicos Académicos , Registros Electrónicos de Salud , Estudios RetrospectivosAsunto(s)
Distinciones y Premios , Cirugía Bucal , Historia del Siglo XX , Humanos , Sociedades Odontológicas , Reino UnidoRESUMEN
Drugs that target histone deacetylase (HDAC) entered the pharmacopoeia in the 2000s. However, some enigmatic phenotypes suggest off-target engagement. Here, we developed a quantitative chemical proteomics assay using immobilized HDAC inhibitors and mass spectrometry that we deployed to establish the target landscape of 53 drugs. The assay covers 9 of the 11 human zinc-dependent HDACs, questions the reported selectivity of some widely-used molecules (notably for HDAC6) and delineates how the composition of HDAC complexes influences drug potency. Unexpectedly, metallo-ß-lactamase domain-containing protein 2 (MBLAC2) featured as a frequent off-target of hydroxamate drugs. This poorly characterized palmitoyl-CoA hydrolase is inhibited by 24 HDAC inhibitors at low nanomolar potency. MBLAC2 enzymatic inhibition and knockdown led to the accumulation of extracellular vesicles. Given the importance of extracellular vesicle biology in neurological diseases and cancer, this HDAC-independent drug effect may qualify MBLAC2 as a target for drug discovery.
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Histona Desacetilasas , Neoplasias , Descubrimiento de Drogas , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Humanos , Ácidos Hidroxámicos/químicaRESUMEN
Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and responses to infection. Mechanisms mediating alveolar macrophage phenotypes after pneumococcal pneumonia have not been delineated. IFN-γ and its receptor on alveolar macrophages were essential for certain, but not all, aspects of the remodeled alveolar macrophage phenotype. IFN-γ was produced by CD4+ T cells plus other cells, and CD4+ cell depletion did not prevent alveolar macrophage remodeling. In mice infected or recovering from pneumococcus, monocytes were recruited to the lungs, and the monocyte-derived macrophages developed characteristics of alveolar macrophages. CCR2 mediated the early monocyte recruitment but was not essential to the development of the remodeled alveolar macrophage phenotype. Lineage tracing demonstrated that recovery from pneumococcal pneumonias converted the pool of alveolar macrophages from being primarily of embryonic origin to being primarily of adult hematopoietic stem cell origin. Alveolar macrophages of either origin demonstrated similar remodeled phenotypes, suggesting that ontogeny did not dictate phenotype. Our data reveal that the remodeled alveolar macrophage phenotype in lungs recovered from pneumococcal pneumonia results from a combination of new recruitment plus training of both the original cells and the new recruits.
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Macrófagos Alveolares , Neumonía Neumocócica , Animales , Pulmón , Macrófagos , Ratones , MonocitosRESUMEN
Adult granulosa cell tumor (AGCT) is the most common sex cord-stromal tumor, accounting for about 1% of all ovarian tumors. It has a propensity for recurrences, especially late in the disease course. High-grade or sarcomatoid transformation has been rarely described in AGCT. We present a case of a 65 year old woman who presented with hemodynamic shock and bowel obstruction from a large pelvic mass. Histologic examination revealed predominantly high-grade epithelioid and spindled cells with high mitotic activity and necrosis. A minor component suggestive of AGCT was also identified. Molecular analysis confirmed the diagnosis of AGCT by revealing FOXL2 C134W mutations. Additionally, TP53 mutations were also detected which may contribute to the high-grade transformation. Our case is unique because the high-grade sarcomatous component constituted most of the tumor and the areas of "typical" AGCT were minor. Also, the clinical and operative findings did not suggest a specific site of origin leading to a broad differential diagnosis. High-grade transformation in AGCT is a rarely described phenomenon. The awareness of this presentation is helpful in reaching the correct diagnosis. Molecular analysis may be an extremely helpful adjunct in challenging cases.
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Tumor de Células de la Granulosa , Neoplasias Ováricas , Sarcoma , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Adulto , Anciano , Femenino , Tumor de Células de la Granulosa/diagnóstico , Tumor de Células de la Granulosa/genética , Tumor de Células de la Granulosa/patología , Humanos , Técnicas de Diagnóstico Molecular , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patologíaRESUMEN
Neutrophils are capable of extruding neutrophil extracellular traps (NETs), a network of granule proteins and chromatin material, upon activation. NETs provide defense against extracellular microbes, but histones in NETs can also induce cytotoxicity and activate inflammatory responses. The relevance of NETs to bacterial pneumonias is beginning to be defined. In the present study, we found that the extracellular concentration of citrullinated histone H3, a component of NETs, was elevated in bronchoalveolar lavage fluid recovered from mice with diverse bacterial pneumonias and correlated with neutrophil infiltration and cell death in the lungs as well as levels of H4. Because the histone H4 component of NETs is sufficient to stimulate inflammation, we tested its effects in the air spaces of the lungs. Recombinant histone H4 in the noninflamed lung produced only modest effects, but in the setting of neutrophilic inflammation, H4 substantially increased pulmonary neutrophils, NETs, necrosis, and edema. However, blockade of histone H4 with a monoclonal antibody during pneumonia did not significantly alter measures of lung damage. Taken together, these results implicate NETs and extracellular histone H4 in exacerbating the lung injury resulting from bacterial pneumonia.
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Trampas Extracelulares , Neumonía Bacteriana , Animales , Trampas Extracelulares/metabolismo , Histonas/metabolismo , Inflamación/metabolismo , Ratones , Neutrófilos , Neumonía Bacteriana/metabolismoRESUMEN
INTRODUCTION: The epidemiology and presence of pediatric medical emergencies and injury prevention practices in Kenya and resource-limited settings are not well understood. This is a barrier to planning and providing quality emergency care within the local health systems. We performed a prospective, cross-sectional study to describe the epidemiology of case encounters to the pediatric emergency unit (PEU) at Kenyatta National Hospital in Nairobi, Kenya; and to explore injury prevention measures used in the population. METHODS: Patients were enrolled prospectively using systematic sampling over four weeks in the Kenyatta National Hospital PEU. Demographic data, PEU visit data and lifestyle practices associated with pediatric injury prevention were collected directly from patients or guardians and through chart review. Data were analyzed with descriptive statistics with stratification based on pediatric age groups. RESULTS: Of the 332 patients included, the majority were female (56%) and 76% were under 5 years of age. The most common presenting complaints were cough (40%) fever (34%), and nausea/vomiting (19%). The most common PEU diagnoses were upper respiratory tract infections (27%), gastroenteritis (11%), and pneumonia (8%). The majority of patients (77%) were discharged from the PEU, while 22% were admitted. Regarding injury prevention practices, the majority (68%) of guardians reported their child never used seatbelts or car seats. Of 68 patients that rode bicycles/motorbikes, one reported helmet use. More than half of caregivers cook at potentially dangerous heights; 59% use ground/low level stoves. CONCLUSIONS: Chief complaints and diagnoses in the PEU population were congruent with communicable disease burdens seen globally. Measures for primary injury prevention were reported as rarely used in the sample studied. The epidemiology described by this study provides a framework for improving public health education and provider training in resource-limited settings.