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OBJECTIVE: The purpose of this study is to develop an animal model of Chronic Intermittent Hypoxia (CIH) and investigate the role of the TRPC5 channel in cardiac damage in OSAHS rats. METHODS: Twelve male Sprague Dawley rats were randomly divided into the CIH group and the Normoxic Control (NC) group. Changes in structure, function, and pathology of heart tissue were observed through echocardiography, transmission electron microscopy, HE-staining, and TUNEL staining. RESULTS: The Interventricular Septum thickness at diastole (IVSd) and End-Diastolic Volume (EDV) of rats in the CIH group significantly increased, whereas the LV ejection fraction and LV fraction shortening significantly decreased. TEM showed that the myofilaments in the CIH group were loosely arranged, the sarcomere length varied, the cell matrix dissolved, the mitochondrial cristae were partly flocculent, the mitochondrial outer membrane dissolved and disappeared, and some mitochondria were swollen and vacuolated. The histopathological examination showed that the cardiomyocytes in the CIH group were swollen with granular degeneration, some of the myocardial fibers were broken and disorganized, and most of the nuclei were vacuolar and hypochromic. CONCLUSION: CIH promoted oxidative stress, the influx of Ca2+, and the activation of the CaN/NFATc signaling pathway, which led to pathological changes in the morphology and ultrastructure of cardiomyocytes, the increase of myocardial apoptosis, and the decrease of myocardial contractility. These changes may be associated with the upregulation of TRPC5.
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Modelos Animales de Enfermedad , Hipoxia , Canales Catiónicos TRPC , Animales , Masculino , Ratas , Apoptosis/fisiología , Enfermedad Crónica , Ecocardiografía , Hipoxia/fisiopatología , Hipoxia/metabolismo , Etiquetado Corte-Fin in Situ , Microscopía Electrónica de Transmisión , Miocardio/metabolismo , Miocardio/patología , Miocardio/ultraestructura , Miocitos Cardíacos/ultraestructura , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Canales Catiónicos TRPC/metabolismoRESUMEN
BACKGROUND: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA. METHODS: TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2. RESULTS: Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups. CONCLUSIONS: Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.
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In recent years, numerous studies have indicated that the combination of organic and inorganic fertilizers can effectively improve soil fertility and soil productivity. Distillers' grain (DG), the primary by-product of Chinese spirits production, has a high utilization value for producing organic fertilizer. We investigated the effects of distillers' grain organic fertilizer (DGOF) on soil chemical properties and microbial community composition, as well as the effects of chemical properties on the abundance of keystone species. The results indicated that the application of DGOF significantly increased tobacco yield by 14.8% and mainly affected the composition rather than the alpha diversity of the bacterial community. Ten amplicon sequence variants (ASVs) were identified as keystone species in the bacterial communities, and most of their relative abundance was influenced by the DGOF addition through affecting soil chemical properties. Our results elucidated the alterations in soil chemical properties and microbial community composition resulting from DGOF application, which is of great importance to better understand the relationship between DGOF and soil microorganisms in the flue-cured tobacco cultivation field.
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Microbiota , Suelo , Suelo/química , Fertilizantes/análisis , Bacterias/genética , Grano Comestible , Microbiología del SueloRESUMEN
Abstract Objective The purpose of this study is to develop an animal model of Chronic Intermittent Hypoxia (CIH) and investigate the role of the TRPC5 channel in cardiac damage in OSAHS rats. Methods Twelve male Sprague Dawley rats were randomly divided into the CIH group and the Normoxic Control (NC) group. Changes in structure, function, and pathology of heart tissue were observed through echocardiography, transmission electron microscopy, HE-staining, and TUNEL staining. Results The Interventricular Septum thickness at diastole (IVSd) and End-Diastolic Volume (EDV) of rats in the CIH group significantly increased, whereas the LV ejection fraction and LV fraction shortening significantly decreased. TEM showed that the myofilaments in the CIH group were loosely arranged, the sarcomere length varied, the cell matrix dissolved, the mitochondrial cristae were partly flocculent, the mitochondrial outer membrane dissolved and disappeared, and some mitochondria were swollen and vacuolated. The histopathological examination showed that the cardiomyocytes in the CIH group were swollen with granular degeneration, some of the myocardial fibers were broken and disorganized, and most of the nuclei were vacuolar and hypochromic. Conclusion CIH promoted oxidative stress, the influx of Ca2+, and the activation of the CaN/NFATc signaling pathway, which led to pathological changes in the morphology and ultrastructure of cardiomyocytes, the increase of myocardial apoptosis, and the decrease of myocardial contractility. These changes may be associated with the upregulation of TRPC5.
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BACKGROUND: Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. METHODS: MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT-PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. RESULTS: The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. CONCLUSION: In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.
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Accidente Cerebrovascular Isquémico , MicroARNs , Daño por Reperfusión , Ratas , Animales , MicroARNs/genética , Microglía , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/metabolismo , Neuroprotección , Daño por Reperfusión/genética , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , ApoptosisRESUMEN
OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.
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Cadmio , Mercurio , Masculino , Animales , Plomo , Marruecos/epidemiología , Estudios Transversales , Ecuador , ChinaRESUMEN
BACKGROUND: Little is known regarding the correlates of mental health, during the COVID-19 pandemic, in lower income countries. Using data from almost the entire population of graduating high school students in El Salvador, we examine the associations between depression and anxiety symptoms and potentially protective factors including peer and family relationships, health behaviours and artistic leisure activities. METHODS: Data comes from the AVANZO survey conducted in El Salvador with 42,314 graduating high school students aged 15-21 in November 2020. Participants completed the Revised Child Anxiety and Depression Scale and Socioemotional Skills Scale. Using a structural equation modelling framework, we tested the associations between these variables and whether these associations varied by sex. RESULTS: Participants who experienced more positive family relationships reported fewer symptoms of depression (ß = -0.304, p < .001) and anxiety (ß = -0.103, p < .001). Similar results were found between health behaviours and symptoms of depression (ß = -0.398, p < .001), and anxiety (ß = -0.312, p < .001). Peer relationships were non-significantly associated with depression and anxiety symptoms. Associations were similar for boys and girls. LIMITATIONS: Students undertook the mental health survey as part of an academic test, which might have increased mental stress. The Socioemotional Skills Scales is newly developed, and results are cross-sectional. CONCLUSIONS: Our findings provide insight into the experiences of an understudied population during the pandemic and identify positive family relationships and health behaviours as important correlates of mental health during this time.
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COVID-19 , Masculino , Femenino , Niño , Humanos , Adolescente , COVID-19/epidemiología , Pandemias , Depresión/psicología , Estudios Transversales , El Salvador/epidemiología , Ansiedad/psicología , Relaciones Familiares , Conductas Relacionadas con la SaludRESUMEN
INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.
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Hepatitis B Crónica , Humanos , Adulto , Tenofovir/efectos adversos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Estudios Retrospectivos , Alanina/uso terapéutico , Adenina/uso terapéutico , Riñón/fisiología , Antivirales/efectos adversos , Resultado del TratamientoRESUMEN
AIMS: We set out to investigate the potential sex differences in the association between diabetes and depressive symptoms by conducting an interaction analysis, and to investigate whether sex mediates the effect of diabetes on depressive symptoms. METHODS: We conducted analyses on cross-sectional data of adults aged 20 years or older in the Mexican National Health and Nutrition Survey 2018-2019 (ENSANUT 2018-2019). Diabetes was defined by self-reported medical diagnosis, and depressive symptoms were measured using the seven-item Centre for Epidemiologic Studies Depression scale. First, an unadjusted interaction analysis was conducted. Second, the inverse probability of treatment weighting was applied to account for imbalances and biases. Third, the four-way decomposition method was used to estimate the potential mediating effect of sex. RESULTS: In the study population (N=43 074), the prevalence of diabetes was 9.3% for men and 11.7% for women. Depressive symptoms were more prevalent in women (19.0%) than in men (9.5%). Women with diabetes had the greatest odds of having depressive symptoms, compared with men without diabetes (ORwomen-diabetes3.49 (95% CI: 3.16 to 3.86)). The interaction analysis indicated that diabetes and sex interact on both, multiplicative and additive scales (ratio of ORs (95% CI) 1.22 (1.02 to 1.45), and relative excess risk due to interaction (95% CI) 0.99 (0.63 to 1.36)). The four-way decomposition analysis showed that the interaction effect between diabetes and sex is larger than the mediation effect. CONCLUSIONS: We found a positive interaction between diabetes and sex in the odds of having depressive symptoms. Mental health and diabetes care services planning would benefit from adopting a sex-informed approach.
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Depresión , Diabetes Mellitus , Adulto , Humanos , Femenino , Masculino , Depresión/epidemiología , Depresión/psicología , Estudios Transversales , Caracteres Sexuales , Diabetes Mellitus/epidemiología , Encuestas NutricionalesRESUMEN
Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans.
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Inmunoterapia Adoptiva , Neoplasias , Antígenos de Neoplasias , Humanos , Recurrencia , Linfocitos T , Microambiente TumoralRESUMEN
In the Western Hemisphere, bat-associated rabies viruses (RABVs) have established independent transmission cycles in multiple mammal hosts, forming genetically distinct lineages. In New Mexico, USA, skunks, bats, and gray foxes are rabies reservoir hosts and represent a public health risk because of encounters with humans. During 2015 and 2019, two previously undescribed RABVs were detected in 2 gray foxes (Urocyon cinereoargenteus) in Lincoln County, New Mexico. Phylogenetic analysis of the nucleoprotein gene indicated that the isolates are a novel RABV variant. These 2 cases probably represent repeated spillover events from an unknown bat reservoir to gray foxes. Molecular analysis of rabies cases across New Mexico identified that other cross-species transmission events were the result of viral variants previously known to be enzootic to New Mexico. Despite a robust rabies public health surveillance system in the United States, advances in testing and surveillance techniques continue to identify previously unrecognized zoonotic pathogens.
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Quirópteros , Zorros , Virus de la Rabia , Rabia , Animales , Quirópteros/virología , Zorros/virología , México/epidemiología , New Mexico/epidemiología , Filogenia , Rabia/epidemiología , Rabia/veterinaria , Estados Unidos/epidemiologíaRESUMEN
Harmful algal blooms (HABs) are detrimental to aquatic ecosystems; thus, economical and practical HAB control methods are needed. We analyzed a microbial community closely related to the alga Karenia mikimotoi, which has HABs that can be toxic to aquatic environments. We studied the relationship between algicidal bacteria and the microbial community of K. mikimotoi culture using culture-dependent and culture-independent methods. Bacterial strains Marinobacter sp. (O-7) and Pseudomonas sp. (D-2) were isolated from a K. mikimotoi seawater culture containing a mixed microbial community and determined to have algicidal activity. Both strains produced alga-lysing substances that were toxic to K. mikimotoi. The algicidal extracellular substances produced by D-2 were stable at temperatures ranging from - 80 to 120 °C but sensitive to strong acidic/alkaline conditions. The substances produced by O-7 were inactivated at high temperatures and strong alkaline conditions. Extracellular substances produced by O-7 and D-2 caused K. mikimotoi and Prorocentrum donghaiense cell lysis, but no changes or inhibitory effects occurred in two other chlorophyta groups. O-7 and D-2 exhibited significantly greater algicidal activity during the logarithmic growth phase of K. mikimotoi growth compared to the stationary phase. Culture-independent analysis of the microbial community in association with K. mikimotoi was made using Illumina MiSeq sequencing. Phylogenetic analysis showed that Proteobacteria was the dominant bacterial population in the phycosphere of K. mikimotoi, containing Marinobacter sp. and Pseudomonas sp.. The Marinobacter was abundant and accounted for 5.3% of the total. Our results indicate that certain bacterial species from K. mikimotoi culture might be effective for removal of HABs.
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Dinoflagelados , Ecosistema , Bacterias/genética , Floraciones de Algas Nocivas , FilogeniaRESUMEN
Leprosy remains endemic in some regions and is a global health concern. However, the possible causes and risk factors of the disease remain unclear. Data in Wenshan, China were collected from the Wenshan Institute of Dermatology (1986-2015); data in Nepal were obtained from the Leprosy Control Division, Department of Health Services, Nepal (2011 to 2015); and data from Indonesia, India, and Brazil were collected from WHO records. We assessed the epidemiological trends of leprosy in Wenshan and compared the features of possible causes and risk factors with those of other countries. We then performed a descriptive and statistical analysis to make our study more purposeful and definitive. A total of 3,376 cases were detected in Wenshan from 1986 to 2015. The overall prevalence rate (PR) of leprosy presented a decreasing trend with a peak (4.9/10,000 population) in 1986. The detection of new leprosy cases was higher in males than in females. Visible deformity increased every year since 2005 with a disability of 34.8% in 2015 among new cases. In Nepal, 2,461 leprosy patients received multi-drug therapy (MDT) in 2015 which corresponded to the PR of 0.89/10,000 population. Geographic latitude and socio-economic situations appeared to be the main causes of leprosy, and the healthcare condition was an important factor associated with leprosy incidence. The introduction of MDT effectively reduced leprosy prevalence worldwide. Wenshan (China), Nepal, and other countries share similarities in various aspects with respect to socio-cultural features, geographical distribution, environmental factors, and economic situation, which may contribute to leprosy being endemic in these areas.
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Epidemias , Lepra , Brasil , China/epidemiología , Femenino , Humanos , India , Indonesia , Lepra/tratamiento farmacológico , Masculino , Nepal/epidemiologíaRESUMEN
OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.
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Antibióticos Antineoplásicos/uso terapéutico , Neoplasias Cardíacas/tratamiento farmacológico , Rabdomioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Esclerosis Tuberosa/complicaciones , Factores de Edad , Preescolar , Estudios de Cohortes , Femenino , Neoplasias Cardíacas/etiología , Humanos , Lactante , Masculino , Rabdomioma/etiología , Factores SexualesRESUMEN
Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.
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Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/terapia , Hígado Artificial , Intoxicación por Setas/complicaciones , Intercambio Plasmático , Bilirrubina/sangre , Coagulación Sanguínea , Niño , Preescolar , Femenino , Humanos , Fallo Hepático Agudo/sangre , Masculino , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In rabies diagnosis, it is essential to count on a rapid test to give a quick response. The combined sensitivity and robustness of the TaqMan RT-PCR assays (qRT-PCR) have made these methods a valuable alternative for rabies virus (RABV) detection. We conducted a study to compare the applicability of two widely used qRT-PCR assays targeting the nucleoprotein gene (LysGT1 assay) and leader sequences (LN34 qRT-PCR assay) of RABV genomes, in all variants circulating in Argentina. A total of 44 samples obtained from bats, dogs, cattle, and horses, that were previously tested for rabies by FAT and conventional RT-PCR, were used in the study. All variants were successfully detected by the pan-lyssavirus LN34 qRT-PCR assay. The LysGT1 assay failed to detect three bat-related variants. We further sequenced the region targeted by LysGT1 and demonstrated that the presence of three or more mismatches with respect to the primers and probe sequences precludes viral detection. We conclude that the LysGT1 assay is prone to yield variant-dependent false-negative test results, and in consequence, the LN34 assay would ensure more effective detection of RABV in Argentina.
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Variación Genética , Virus de la Rabia/genética , Rabia/diagnóstico , Rabia/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Secuencia de Aminoácidos , Animales , Argentina/epidemiología , Bovinos , Quirópteros , Geografía Médica , Caballos , Humanos , Nucleoproteínas/genética , Filogenia , Filogeografía , ARN Viral , Rabia/epidemiología , Virus de la Rabia/clasificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.
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Enfermedades de los Perros/virología , Virus de la Rabia/genética , Rabia/veterinaria , Rabia/virología , Análisis de Secuencia de ADN/instrumentación , Animales , Equipo para Diagnóstico , Perros , Enfermedades Endémicas/prevención & control , Enfermedades Endémicas/veterinaria , Guatemala , Humanos , India , Kenia , Nanoporos , Filogenia , Salud Pública , Virus de la Rabia/clasificación , Análisis de Secuencia de ADN/métodos , VietnamRESUMEN
WRKY transcription factors play important roles in plant growth and developmental processes and various stress responses, and are also associated with jasmonic acid (JA) signaling in the regulation of secondary metabolite biosynthesis in plants. The regulatory networks mediated by WRKY proteins in the latex production of Hevea brasiliensis (the Pará rubber tree) are poorly understood. In this study, one novel WRKY gene (designated HbWRKY83) was identified from the latex of H. brasiliensis, and its functions were characterized via gene expression analysis in both the latex and HbWRKY83-overexpressing transgenic Arabidopsis. HbWRKY83 gene contains an open reading frame (ORF) of 921 bp encoding a 306-amino-acid protein which is clustered with group IIc WRKY TF. HbWRKY83 is a nuclear-localized protein with transcriptional activity. Real-time quantitative PCR analysis demonstrated that the transcription level of HbWRKY83 was up-regulated by exogenous methyl jasmonate, Ethrel (ethylene releaser) stimulation, and bark tapping (mechanical wounding). Compared with the wild-type plants, overexpression of HbWRKY83 improved the tolerance of transgenic Arabidopsis lines to drought and salt stresses by enhancing the expression levels of ethylene-insensitive3 transcription factors (EIN3s) and several stress-responsive genes, including Cu/Zn superoxide dismutases CSD1 (Cu/Zn-SOD1) and CSD2 (Cu/Zn-SOD2), related to reactive oxygen species scavenging. Additionally, these genes were also significantly up-regulated by bark tapping. In combination, these results suggest that HbWRKY83 might act as a positive regulator of rubber production by activating the expression of JA-, ethylene-, and wound-responsive genes in the laticiferous cells of rubber trees.
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Hevea , Látex/biosíntesis , Proteínas de Plantas/genética , Factores de Transcripción/genética , Regulación de la Expresión Génica de las Plantas , Hevea/genética , Hevea/metabolismo , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.
Asunto(s)
Hormonas y Agentes Reguladores de Calcio/farmacología , Diabetes Mellitus Experimental/fisiopatología , Hormona Paratiroidea/farmacología , Extracción Dental/métodos , Alveolo Dental/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Glucemia/análisis , Calcio/sangre , Hidrogeles , Masculino , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Herida Quirúrgica/tratamiento farmacológico , Factores de Tiempo , Alveolo Dental/diagnóstico por imagen , Resultado del Tratamiento , Microtomografía por Rayos XRESUMEN
In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.