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Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in â¼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas.
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Nitrogen (N) is needed for plant growth and development and is the major limiting nutrient due to its higher demand in agricultural production globally. The use of N fertilizers has increased considerably in recent years to achieve higher cereal yields. High N inputs coupled with declining N use efficiency (NUE) result in the degradation of the environment. Plants have developed multidimensional strategies in response to changes in N availability in soil. These strategies include N stress-induced responses such as changes in gene expression patterns. Several N stress-induced genes and other regulatory factors, such as microRNAs (miRNAs), have been identified in different plant species, opening a new avenue of research in plant biology. This review presents a general overview of miRNA-mediated regulation of N response and NUE. Further, the in-silico target predictions and the predicted miRNA-gene network for nutrient metabolism/homeostasis in wheat provide novel insights. The information on N-regulated miRNAs and the differentially expressed target transcripts are necessary resources for genetic improvement of NUE by genome editing.
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The important roles of plant microRNAs (miRNAs) in adaptation to nitrogen (N) deficiency in different crop species especially cereals (rice, wheat, maize) have been under discussion since last decade with little focus on potential wild relatives and landraces. Indian dwarf wheat (Triticum sphaerococcum Percival) is an important landrace native to the Indian subcontinent. Several unique features, especially high protein content and resistance to drought and yellow rust, make it a very potent landrace for breeding. Our aim in this study is to identify the contrasting Indian dwarf wheat genotypes based on nitrogen use efficiency (NUE) and nitrogen deficiency tolerance (NDT) traits and the associated miRNAs differentially expressed under N deficiency in selected genotypes. Eleven Indian dwarf wheat genotypes and a high NUE bread wheat genotype (for comparison) were evaluated for NUE under control and N deficit field conditions. Based on NUE, selected genotypes were further evaluated under hydroponics and miRNome was compared by miRNAseq under control and N deficit conditions. Among the identified, differentially expressed miRNAs in control and N starved seedlings, the target gene functions were associated with N metabolism, root development, secondary metabolism and cell-cycle associated pathways. The key findings on miRNA expression, changes in root architecture, root auxin abundance and changes in N metabolism reveal new information on the N deficiency response of Indian dwarf wheat and targets for genetic improvement of NUE.
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MicroARNs , Triticum , Triticum/metabolismo , Nitrógeno/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fitomejoramiento , GenotipoRESUMEN
Neuroretinitis is a condition typically characterized by unilateral optic neuropathy and is most commonly a sequelae of cat scratch disease (CSD) due to infection with Bartonella henselae. Ophthalmologic examination will reveal a swollen optic nerve and may eventually reveal a canonical macular star; optical coherence tomography (OCT) will reveal flattening of the fovea, a thickened neurosensory retina, and subretinal fluid accumulation. Although CSD rarely presents with isolated neuorretinitis, it should be considered in patients presenting with unilateral visual changes. The differential diagnosis for neuroretinitis includes optic neuritis, inflammatory optic neuropathies (sarcoid, para-infectious, autoimmune), compressive, toxic, and more. We describe a pediatric patient presenting with visual changes that were initially concerning for optic neuritis and the diagnostic workup that ultimately led to a diagnosis of CSD neuroretinitis.
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Bartonella henselae , Enfermedad por Rasguño de Gato , Coriorretinitis , Neuritis Óptica , Retinitis , Humanos , Enfermedad por Rasguño de Gato/complicaciones , Enfermedad por Rasguño de Gato/diagnóstico , Retinitis/diagnóstico , Retinitis/complicaciones , Neuritis Óptica/diagnóstico , Neuritis Óptica/etiologíaRESUMEN
Aristolochic acids (AAs) are a group of naturally occurring compounds present in many plant species of the Aristolochiaceae family. Exposure to AA is a significant risk factor for severe nephropathy, and urological and hepatobiliary cancers (among others) that are often recurrent and characterized by the prominent mutational fingerprint of AA. However, herbal medicinal products that contain AA continue to be manufactured and marketed worldwide with inadequate regulation, and possible environmental exposure routes receive little attention. As the trade of food and dietary supplements becomes increasingly globalized, we propose that further inaction on curtailing AA exposure will have far-reaching negative effects on the disease trends of AA-associated cancers. Our Review aims to systematically present the historical and current evidence for the mutagenicity and carcinogenicity of AA, and the effect of removing sources of AA exposure on cancer incidence trends. We discuss the persisting challenges of assessing the scale of AA-related carcinogenicity, and the obstacles that must be overcome in curbing AA exposure and preventing associated cancers. Overall, this Review aims to strengthen the case for the implementation of prevention measures against AA's multifaceted, detrimental and potentially fully preventable effects on human cancer development.
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Ácidos Aristolóquicos , Neoplasias , Ácidos Aristolóquicos/toxicidad , Humanos , Mutagénesis , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Salud PúblicaRESUMEN
North-eastern states of India, including Assam, have a high prevalence of head and neck cancer cases. In these regions, Sadagura is a unique form of smokeless tobacco (SLT). There are fewer reports regarding the effects of simultaneous sadagura and arsenic co-exposure. Analysis of chemical compounds present in sadagura aqueous extract was done using gas chromatography-mass spectrometry. Estimation of arsenic contamination in groundwater and bioaccumulation in human tissues was performed by using atomic absorption spectroscopy. Buccal micronucleus cytome (BMCyt) assay and analysis of various peripheral blood parameters were performed among study volunteers. Chronic exposure (90 days) experiments were performed in mice test system in vivo to determine any possible protective potential of vitamin C (Vit-C) supplementation against sadagura and arsenic co-exposure. BMCyt assay results revealed a higher incidence of micronucleated cells (p < 0.001), and cell death biomarker among sadagura consumers residing in arsenic affected areas. Comet assay of mice femur bone marrow cells following chronic exposure of the test substances revealed a reduction in DNA damage due to Vit-C supplementation. Histological examination of the hepatic and renal tissues revealed marked improvement due to Vit-C supplementation in mice against sadagura and arsenic chronic co-exposure. Indiscriminate consumption, presence of various harmful compounds in sadagura along with arsenic co-exposure might be a vital link for the higher incidence of oral cancer in the region. Chronic Vit-C supplementation study results in mice show its effective remedial potential against combined sadagura and arsenic co-mediated genotoxicity and ultrastructural changes in major organs.
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Arsénico , Tabaco sin Humo , Animales , Arsénico/toxicidad , Daño del ADN , Suplementos Dietéticos , Cromatografía de Gases y Espectrometría de Masas , Inestabilidad Genómica , Ratones , Pruebas de Micronúcleos , Tabaco sin Humo/toxicidad , VitaminasRESUMEN
Smokeless tobacco (SLT) consumption is presumed to be one of the major causes of high incidence of oral cancer in India. The present study aimed to document various types of SLT products consumed and their potential impact on the genome instability on the population from Assam state in Northeast India. A cross-sectional study (n = 5000) showed that 60.56 % of the study population consumed at least one of the three forms (sadagura, zarda and khaini) of SLT of which 52.0 % were only sadagura users. Genotoxicity assessment using buccal cytome assay in 240 age and sex matched volunteers revealed that except for zarda, other forms of SLT induced significantly higher incidence micronuclei in the buccal epithelial cells compared to the control individuals. Similar effects were also observed in other cytome parameters related to cell proliferation, cytokinesis defects and cell death. Significantly higher incidence of micronucleus was observed among sadagura and khaini users in lymphocyte cytokinesis-blocked micronucleus assay. The addition of lime in sadagura increased the pH and anion levels which possibly result in higher absorption and may lead to the development of cellular anomalies.
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Mutágenos/toxicidad , Uso de Tabaco/efectos adversos , Tabaco sin Humo/toxicidad , Adolescente , Adulto , Anciano , Núcleo Celular/efectos de los fármacos , Estudios Transversales , Daño del ADN/efectos de los fármacos , Femenino , Humanos , India , Linfocitos/efectos de los fármacos , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos/métodos , Persona de Mediana Edad , Salud Pública , Adulto JovenRESUMEN
We present a 16-year-old girl with a history of well-controlled psoriasis, on immunosuppression, who sought evaluation in the emergency department for 4 months of fever, cough and unintentional weight loss. The patient had seen multiple providers who had diagnosed her with community-acquired pneumonia, but she was unimproved after oral antibiotic therapy. On presentation, she was noted to be febrile, tachycardic and chronically ill-appearing. Her chest X-ray showed diffuse opacities and a right upper lobe cavitary lesion concerning for tuberculosis. A subsequent chest CT revealed miliary pulmonary nodules in addition to the cavitary lesion. The patient underwent subsequent brain MRI, which revealed multifocal ring-enhancing nodules consistent with parenchymal involvement. The patient was diagnosed with miliary tuberculosis and improved on quadruple therapy. Though rates of tuberculosis are increasing, rates remain low in children, though special consideration should be given to children who are immunosuppressed.
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Psoriasis , Tuberculosis Miliar , Adolescente , Niño , Femenino , Humanos , Huésped Inmunocomprometido , Imagen por Resonancia Magnética , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Tuberculosis Miliar/diagnóstico , Tuberculosis Miliar/diagnóstico por imagenAsunto(s)
Educación Médica , Docentes Médicos , Tutoría , Historia del Siglo XX , Tutoría/historia , Estados UnidosRESUMEN
Tolosa-Hunt syndrome is characterized by a painful ophthalmoplegia secondary to a granulomatous inflammation in or adjacent to the cavernous sinus. Magnetic resonance imaging will show enhancement of the cavernous sinus and/or the orbital apex. Although this syndrome is extremely rare in children, it should be a diagnostic consideration in patients presenting with painful ophthalmoplegia with variable involvement of cranial nerves II to VI. The differential diagnosis for unilateral cavernous sinus lesion is broad, including vascular lesions (cavernous sinus thrombosis), inflammatory processes (sarcoidosis, autoimmune), neoplastic processes (schwannoma, lymphoma), as well as infectious etiologies. We describe a pediatric patient presenting with neurological symptoms from a unilateral cavernous sinus magnetic resonance imaging abnormality and the thorough diagnostic approach to arrive at the diagnosis of Tolosa-Hunt syndrome.
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Seno Cavernoso/patología , Diplopía/etiología , Cefalea/etiología , Síndrome de Tolosa-Hunt/diagnóstico , Adolescente , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Humanos , Aumento de la Imagen , Imagen por Resonancia Magnética , Síndrome de Tolosa-Hunt/tratamiento farmacológicoRESUMEN
Child maltreatment remains a significant problem in the USA. There is a dearth of literature examining the association of socioeconomic status (SES) and incidence of child maltreatment among hospitalized children across the entire USA. Our aim was to study the association between SES and incidence and mortality from child maltreatment among hospitalized children in the USA. We used 2013-2014 data from the Nationwide Inpatient Sample, a discharge database representative of all hospitals in the USA. International Classification of Diseases-9 codes for general child maltreatment were used to identify patients discharged with a primary diagnosis of child maltreatment. Trends in the incidence and outcomes of child maltreatment were compared with SES based on quartiles (Qx) of median household income. In 2013-2014, there were a total of about 2.3 million pediatric discharges. Out of these, a total of 8985 had a primary diagnosis of child maltreatment. Approximately 40 per cent of the cases were from families with the lowest SES (Q1). In-hospital mortality was 2.4 per cent in Q1 (lowest SES) compared with 0.4 per cent in Q4 (highest SES). We conclude that children from lower SES households have a higher incidence of child maltreatment and have worse outcomes, including significantly higher in-hospital mortality among hospitalized children. This trend was generally consistent across all age groups and ethnicities. To our knowledge, this is the first report studying the association between SES and children with child maltreatment among hospitalized children across the entire USA.
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Maltrato a los Niños/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Clase Social , Niño , Etnicidad , Composición Familiar , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Renta , Masculino , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
One of the most concerning causes of abdominal pain affecting children is acute appendicitis. However, there are benign conditions that can closely mimic appendicitis in children. In this article, we present a case of a child admitted for possible acute appendicitis and determined to have a condition known as omental infarction. The patient was managed medically and made a full recovery without surgical intervention. The aim of this case report is to review omental infarction and present a way of differentiating this disease from appendicitis, utilizing imaging, with the goal of avoiding surgical intervention. We also discuss the presentation and imaging findings of and another closely related condition-epiploic appendagitis. It is important to differentiate appendicitis from these 2 conditions as they can be often managed medically without surgical intervention.
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Cryptococcus neoformans/aislamiento & purificación , Meningitis Criptocócica/diagnóstico , Adolescente , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Diagnóstico Diferencial , Flucitosina/uso terapéutico , Cefalea/etiología , Humanos , Masculino , Meningitis Criptocócica/tratamiento farmacológico , Debilidad Muscular/etiologíaRESUMEN
BACKGROUND: Recently, high concentrations of arsenic have been documented in ground waters of Southern Assam, India. Indiscriminate smokeless tobacco consumption is a common practice in this region. Correlation between nutritional status and arsenic and smokeless tobacco-induced health effects has not been taken up in humans or other test systems. METHODS: Mice were divided into groups based on protein (casein) content in the diet: High protein (40%), optimum protein (20%), and low protein (5%). Simultaneous chronic exposure (90 days) to arsenic and smokeless tobacco (sadagura) orally was given to evaluate the extent of the cytological and genotoxicological damage. Micronucleus assay and Comet assay of the femur bone marrow cells were conducted. Germ cell toxicity was evaluated by recording the sperm head abnormalities and total sperm count. Cell cycle analysis was performed in femur bone marrow cells using flow cytometer. Hepatic, renal, and intestinal tissues were analyzed for various oxidative stress evaluations. Histological examination of liver and kidney was performed. RESULTS: Notably, high protein diet groups had lower arsenic and sadagura induced genotoxicity, germ cell abnormalities and oxidative stress as compared to optimum protein and low protein diet counterparts. CONCLUSION: Our study indicates that sufficient levels of dietary protein appear to reduce the long-term arsenic and smokeless tobacco-induced toxicity in mice test system, as compared to lower or deficient amount of protein in the diet. This observation has implications and invites further studies especially epidemiological studies in the human population exposed to arsenic in South East Asian countries. Environ. Mol. Mutagen. 59:386-400, 2018. © 2018 Wiley Periodicals, Inc.
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Arsénico/toxicidad , Mutágenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Tabaco sin Humo/toxicidad , Animales , Daño del ADN/efectos de los fármacos , Dieta , Humanos , India/epidemiología , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Estado Nutricional/efectos de los fármacos , Estado Nutricional/genética , Espermatozoides , Uso de Tabaco/efectos adversosRESUMEN
Bullous skin lesions are uncommon in children. While it is well known that Mycoplasma infections are associated with papular skin manifestations, bullous skin lesions are not commonly reported. Mycoplasma pneumoniae is a very common bacterial pathogen causing respiratory tract infection in children and adults. We report 2 children with serology-confirmed Mycoplasma infection who were hospitalized for blistering skin lesions. Both of our patients responded well to corticosteroids and one of them required intravenous immunoglobulin. The aim of this case report is to raise awareness that Mycoplasma pneumoniae infection can present with bullous skin lesions, and to briefly review the pathophysiology, diagnosis, and management of the skin manifestation of Mycoplasma infection.