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Rabies is a fatal zoonotic infection of the central nervous system of mammals and has been known to humans for millennia. The etiological agent, is a neurotropic RNA virus in the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus. There are currently accepted to be two cycles for rabies transmission: the urban cycle and the sylvatic cycle. The fact that both cycles originated from a common RABV or lyssavirus ancestor and the adaptive divergence that occurred since then as this ancestor virus adapted to a wide range of fitness landscapes represented by reservoir species in the orders Carnivora and Chiroptera led to the emergence of the diverse RABV lineages currently found in the sylvatic and urban cycles. Here we study full genome phylogenies and the time to the most recent common ancestor (TMRCA) of the RABVs in the sylvatic and urban cycles. Results show that there were differences between the nucleotide substitution rates per site per year for the same RABV genes maintained independently in the urban and sylvatic cycles. The results identify the most suitable gene for phylogenetic analysis, heterotachy among RABV genes and the TMRCA for the two cycles.
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Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.
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Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Leishmaniasis Cutánea/microbiología , Piel/microbiología , Adulto , Femenino , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/clasificación , Humanos , Masculino , Persona de Mediana Edad , Piel/parasitología , Adulto JovenRESUMEN
Spontaneous cerebrospinal fluid leak with meningoencephaloceles in sphenoid sinus lateral recess is challenging. Transnasal visualization of this area is difficult, especially when large pneumatization is present. External approaches to this region involve aggressive surgery and are often associated with significant morbidity. The aim of this study is to assess the real effectiveness of a modification of the endoscopic endonasal approach for their management. This is a prospective case series study and was conducted at Otolaryngology department, Ain Shams University Hospitals, Cairo, Egypt. Seven patients with spontaneous cerebrospinal fluid leak with meningoencephaloceles in the sphenoid sinus lateral recess were included. Diagnosis was confirmed by: analysis for beta-2 transferrin and imaging. They were managed with endoscopic endonasal retrograde trans-sphenoid approach described in this study with multilayered reconstruction of the defect. Mean age of our patients was 40.14 ± 8.35 years; mean BMI was 36.37 ± 2.59 kg/m2. Primary empty sella was present and osteodural defect was identified in superior wall of sphenoid sinus lateral recess with punched out and regular smooth edges. Mean intra-cranial pressure was (26.42 ± 3.87 mmH2O) and size of defect was less than 10 mm, mean 7.85 ± 1.34. Mean-operative time was 169.28 ± 21.87 min. The mean hospital stay was 7.42 ± 1.39 days. No cerebrospinal fluid leak recurrences were observed during follow-up period that ranged from 37 to 48 months. Endoscopic endonasal retrograde trans-sphenoid approach provides a wide, safe, and direct route to the management of sphenoid sinus lateral recess cerebrospinal fluid leak.
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Encefalocele/cirugía , Cirugía Endoscópica por Orificios Naturales/métodos , Enfermedades de los Senos Paranasales/cirugía , Seno Esfenoidal/cirugía , Adulto , Rinorrea de Líquido Cefalorraquídeo/diagnóstico , Manejo de la Enfermedad , Egipto , Encefalocele/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Seno Esfenoidal/diagnóstico por imagen , Senos TransversosRESUMEN
BACKGROUND: The Coronator Group currently encompasses six morphologically similar species (Culex camposi Dyar, Culex coronator Dyar and Knab, Culex covagarciai Forattini, Culex usquatus Dyar, Culex usquatissimus Dyar, and Culex ousqua Dyar). Culex coronator has been incriminated as a potential vector of West Nile Virus (WNV), Saint Louis Encephalitis Virus (SLEV), and Venezuelan Equine Encephalitis Virus (VEEV). The complete mitochondrial genome of Cx. coronator, Cx. usquatus, Cx.usquatissimus, and Cx. camposi was sequenced, annotated, and analyzed to provide genetic information about these species. RESULTS: The mitochondrial genomes of Cx. coronator, Cx. usquatus, Cx.usquatissimus, and Cx. camposi varied from 15,573 base pairs in Cx. usquatus to 15,576 in Cx. coronator. They contained 37 genes (13 protein-encoding genes, 2 rRNA genes, and 22 tRNA genes) and the AT-rich control region. Comparative analyses of the 37 genes demonstrated the mitochondrial genomes to be composed of variable and conserved genes. Despite the small size, the ATP8, ATP6 plus NADH5 protein-encoding genes were polymorphic, whereas tRNAs and rRNAs were conserved. The control region contained some poly-T stretch. The Bayesian phylogenetic tree corroborated that both the Coronator Group and the Culex pipens complex are monophyletic taxa. CONCLUSIONS: The mitochondrial genomes of Cx. coronator, Cx. usquatus, Cx. usquatissimus and Cx. camposi share the same gene composition and arrangement features that match to those reported for most Culicidae species. They are composed of the same 37 genes and the AT-rich control region, which contains poly-T stretches that may be involved in the functional role of the mitochondrial genome. Taken together, results of the dN/dS ratios, the sliding window analyses and the Bayesian phylogenetic analyses suggest that ATP6, ATP8 and NADH5 are promising genes to be employed in phylogenetic studies involving species of the Coronator Group, and probably other species groups of the subgenus Culex. Bayesian topology corroborated the morphological hypothesis of the Coronator Group as monophyletic lineage within the subgenus Culex.
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Culex/genética , Genoma de los Insectos , Genoma Mitocondrial , Animales , Composición de Base , Brasil , Codón , Biología Computacional , Culex/clasificación , Genes de Insecto , Genes Mitocondriales , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Insectos Vectores , Anotación de Secuencia Molecular , Sistemas de Lectura Abierta , FilogeniaRESUMEN
BACKGROUND: Here, we report application of high-throughput near full-length genome (NFLG) and partial human immunodeficiency virus Type 1 (HIV-1) proviral genome deep sequencing to characterize HIV in recently infected blood donors at four major blood centers in Brazil. STUDY DESIGN AND METHODS: From 2007 to 2011, a total of 341 HIV+ blood donors from four blood centers were recruited to participate in a case-control study to identify HIV risk factors and motivations to donate. Forty-seven (17 from São Paulo, eight from Minas Gerais, 11 from Pernambuco, and 11 from Rio de Janeiro) were classified as recently infected based on testing by less-sensitive enzyme immunoassays. Five overlapping amplicons spanning the HIV genome were polymerase chain reaction amplified from peripheral blood mononuclear cells. The amplicons were molecularly barcoded, pooled, and sequenced by a paired-end protocol (Illumina). RESULTS: Of the 47 recently infected donor samples studied, 39 (82.9%) NFLGs and six (12.7%) partial fragments were de novo assembled into contiguous sequences and successfully subtyped. Subtype B was the only nonrecombinant virus identified in this study and accounted for 62.2% (28/45) of samples. The remaining 37.8% (17/45) of samples showed various patterns of subtype discordance in different regions of HIV-1 genomes, indicating two to four circulating recombinant subtypes derived from Clades B, F, and C. Fourteen samples (31.1%) from this study harbored drug resistance mutations, indicating higher rate of drug resistance among Brazilian blood donors. CONCLUSION: Our findings revealed a high proportion of HIV-1 recombinants among recently infected blood donors in Brazil, which has implications for future blood screening, diagnosis, therapy, and vaccine development.
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Genoma Viral/genética , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Donantes de Sangre/estadística & datos numéricos , Brasil , Humanos , Técnicas para Inmunoenzimas , Datos de Secuencia MolecularRESUMEN
BACKGROUND: The interaction of HIV-1 and target cells involves sequential binding of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage therapy in patients with CCR5 using variants (R5) but not with variants capable of using CXCR4 (×4) phenotype. Thus, it is critically important to determine cellular tropism of a country's circulating HIV strains to guide a management decision to improve treatment outcome. In this study, we report the prevalence of R5 and ×4 HIV strains in 45 proviral DNA massively parallel sequencing "MPS" data from recently infected Brazilian blood donors. METHODS: The MPS data encompassing the tropism-related V3 loop region of the HIV-1 env gene was extracted from our recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina). HIV-1 tropism was inferred using Geno2pheno[coreceptor] algorithm (3.5 % false-positive rate). V3 net charge and 11/25 rules were also used for coreceptor prediction. RESULTS: Among the 45 samples for which tropism were determined, 39 were exclusively R5 variants, 5 ×4 variants, and one dual-tropic or mixed (D/M) populations of R5 and ×4 viruses, corresponding to 86.7, 11.1 and 2.2 %, respectively. Thus, the proportion of all blood donors that harbor CXCR4-using virus was 13.3 % including individuals with D/M-tropic viruses. CONCLUSIONS: The presence of CCR5-tropic variants in more than 85 % of our cohort of antiretroviral-naïve blood donors with recent HIV-1 infection indicates a potential benefit of CCR5 antagonists as a therapeutic option in Brazil. Therefore, determination of viral co-receptor tropism is an important diagnostic prerequisite.
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Donantes de Sangre , Infecciones por VIH/virología , VIH-1/genética , VIH-1/fisiología , Receptores del VIH/metabolismo , Tropismo Viral , Acoplamiento Viral , Brasil , VIH-1/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , HumanosRESUMEN
Leukoplakia is a descriptive clinical term designating a white patch or plaque of the mucosa and must be complemented by histology, which can range from simple totally benign keratosis with or without atypia up to invasive carcinoma. The aim of this study is to evaluate the accuracy of videostroboscopy in preoperative differentiation of early invasive glottic carcinoma from intraepithelial atypia and dysplasia. 46 patients with a total of 60 leukoplakia lesions on the vocal folds were included in the study. Videostroboscopy was used to divide them into two groups based on preservation of the mucosal wave and this was correlated with the final pathology after treatment. The sensitivity and specificity of videostroboscopy in predicting invasive nature of the lesions based on absence or reduction of the mucosal wave were 96.8 and 92.8 %, respectively, with an overall accuracy of 95 %. We suggest that routine application of videostroboscopy can be an important, simple, non-invasive tool, to achieve, in a single procedure, proper and accurate evaluation of glottic leukoplakia.
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Carcinoma , Glotis , Neoplasias Laríngeas , Estroboscopía/métodos , Adulto , Carcinoma/patología , Carcinoma/cirugía , Diagnóstico Diferencial , Femenino , Glotis/patología , Glotis/cirugía , Humanos , Hiperplasia/diagnóstico , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Leucoplasia/diagnóstico , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Selección de Paciente , Lesiones Precancerosas , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: This study aimed to evaluate the implementation stage of Malaysia's GeKo-Integrated Service Delivery (ISD) model for frailty management in primary care and explore its effectiveness in improving frailty scores. METHODS: The implementation stage of Malaysia's first three GeKo- ISD clinics was assessed using the WHO-ICOPE (Integrated Care of the Older Persons) scorecard. This involved evaluating documents related to the GeKo services and conducting in-depth interviews with key informants identified from those documents. The efficacy of GeKo-ISD was assessed by documenting the change in mean frailty scores between baseline and 3 months post intervention, measured by the Pictorial Fit Frail Scale Malay Version (PFFS-M), in patients who received GeKo-ISD care from October 2022 to April 2023. RESULTS: All three GeKo clinics achieved the sustaining implementation level, scoring a total of 50 out of 52. The paired t-test reported a significant reduction (p= 0.001) in the PFFS-M scores from baseline to 3 months after the GeKo-ISD intervention. The mean (SD) scores were 8.6 (4.6) at baseline and 7.0 (4.1) at 3 months post-intervention. CONCLUSION: GeKo-ISD is a comprehensive approach of integrated care for older people, leveraging existing public funded primary care infrastructure. It shows promise, was impacted by the pandemic but now, with support from the government, exists in 32 centers across one state in Malaysia.
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Prestación Integrada de Atención de Salud , Anciano Frágil , Fragilidad , Atención Primaria de Salud , Humanos , Malasia , Atención Primaria de Salud/organización & administración , Anciano , Prestación Integrada de Atención de Salud/organización & administración , Masculino , Femenino , Fragilidad/terapia , Fragilidad/diagnóstico , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Servicios de Salud para Ancianos/organización & administración , Pueblos del Sudeste AsiáticoRESUMEN
OBJECTIVES: To estimate the prevalence and determinants of obesity in childhood and adolescence and their association with blood pressure (BP) in Abu Dhabi, United Arab Emirates (UAE). DESIGN: A cross-sectional population-representative study. SUBJECTS: A total of 1541 students (grades 1-12; aged 6-19 years) were randomly selected from 246 schools (50% male). Anthropometric and demographic variables were measured, and CDC criteria were used to classify children's weights. RESULTS: A total of 1440 (93%) students provided complete results. Crude prevalences were: 7.6% underweight, 14.7% overweight and 18.9% obesity. Further analyses were restricted to UAE nationals (n=1035), of whom these figures were: 8.3% underweight (females 6.5%, males 10.1%; P=0.06), 14.2% overweight (females 16.7%, males 11.6%; P<0.01), 19.8% obesity (females 18.1%, males 21.4%; P=0.09). Obesity significantly (P<0.001) increased with age. The majority (61.3%) of students had body mass index (BMI) percentiles above the 50th CDC percentile. Stepwise linear regression of BMI percentile on age, sex, dairy consumption, exercise and family income showed a significant (P<0.01) positive association with age and lack of dairy consumption, but not exercise and income. BP significantly (P<0.01) increased with BMI percentile. CONCLUSIONS: The prevalence of childhood obesity is high across the age spectrum in the UAE. Older age, male sex, lack of dairy intake and higher parental BMI, are independent determinants of childhood obesity in this population. Higher BMI percentile is associated with a higher BP. Prevention strategies should focus on younger children, particularly children of obese parents. Longitudinal studies are needed to investigate trends and the impact of childhood obesity on the risk of non-communicable diseases.
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Índice de Masa Corporal , Ejercicio Físico , Conducta Alimentaria , Obesidad/epidemiología , Adolescente , Análisis de Varianza , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad/etiología , Obesidad/prevención & control , Padres , Prevalencia , Factores de Riesgo , Instituciones Académicas , Encuestas y Cuestionarios , Emiratos Árabes Unidos/epidemiología , Adulto JovenRESUMEN
The quantum Hall effect is observed in a two-dimensional electron gas formed in millimeter-scale hydrogenated graphene, with a mobility less than 10 cm2/V·s and corresponding Ioffe-Regel disorder parameter (k(F)λ)(-1) â« 1. In a zero magnetic field and low temperatures, the hydrogenated graphene is insulating with a two-point resistance of the order of 250h/e2. The application of a strong magnetic field generates a negative colossal magnetoresistance, with the two-point resistance saturating within 0.5% of h/2e2 at 45 T. Our observations are consistent with the opening of an impurity-induced gap in the density of states of graphene. The interplay between electron localization by defect scattering and magnetic confinement in two-dimensional atomic crystals is discussed.
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Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.
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Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva , Mutación Missense , Piperazinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Tirosina Quinasas/genética , Pirimidinas/administración & dosificación , Tiazoles/administración & dosificación , Adulto , Anciano , Sustitución de Aminoácidos , Benzamidas , Análisis Mutacional de ADN , Dasatinib , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , MasculinoRESUMEN
Patients with esophageal cancer may present with dysphagia and weight loss. Resectable lesions require consideration of neoadjuvant chemotherapy, which improves survival but have side effects, which compound already poor intake. Prevention of malnutrition has historically required interventions such as surgical jejunostomy or percutaneous endoscopic gastrostomy, which carry associated morbidity. With established roles in palliation, self-expanding removable metal stents (SERMS) may provide an alternative intervention in resectable disease. We sought to evaluate outcomes from our unit's introduction of SERMS in dysphagic patients prior to esophagectomy. All dysphagic patients presenting with esophageal cancer and considered for curative surgery between April 2006 and November 2008 were offered preoperative treatment of dysphagia with SERMS during neoadjuvant chemotherapy. Baseline and preoperative outcomes assessed included dysphagia score and nutritional markers. Sixteen patients underwent esophageal stenting during neoadjuvant therapy of whom 7/16 (44%) were female with mean age 63 (53-76). In 12/16 (75%), tumors were located in the lower one third of the esophagus. There was a significant fall in mean dysphagia score from 2.5 (range 1-4) to 1.1 (range 0-3) immediately preoperatively. There was no significant change in serum albumin, weight, or body mass index. Stent-related morbidity occurred in 4/16 (25%) patients and stomach migration occurred in 7/16 (43.8%). All were resolved endoscopically and there was no stent-related mortality. Of 10/16 (62.5%) patients ultimately progressing to esophagectomy, 30-day mortality was 6.3%. Anastomotic leak occurred in one patient (10%) and R1 resection rate was 20%. SERMS are a safe and effective intervention in dysphagic patients undergoing neoadjuvant chemotherapy for esophageal cancer. Complications are minor and readily treatable with endoscopy. Objective parameters suggest nutritional status is maintained and symptoms are improved. SERMS do not appear to compromise resection.
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Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Trastornos de Deglución/terapia , Neoplasias Esofágicas/terapia , Stents , Adenocarcinoma/complicaciones , Adenocarcinoma/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Índice de Masa Corporal , Peso Corporal , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Trastornos de Deglución/etiología , Epirrubicina/administración & dosificación , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/tratamiento farmacológico , Esofagectomía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Desnutrición/prevención & control , Persona de Mediana Edad , Terapia Neoadyuvante , Falla de Prótesis , Albúmina Sérica/metabolismo , Índice de Severidad de la Enfermedad , Stents/efectos adversosRESUMEN
BACKGROUND: In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1-infected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. METHODS: A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. RESULTS: Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p < 0.05), but not between subjects with a low or intermediate PvL (p > 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p < 0.03). No significant difference was found between the groups in relation to age, sex or viral subtypes (p > 0. 05). CONCLUSIONS: The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.
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Portador Sano/virología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Mutación Puntual , Provirus/fisiología , Secuencias Repetidas Terminales/genética , Adulto , Anciano , Anciano de 80 o más Años , Portador Sano/fisiopatología , Estudios Transversales , Femenino , Productos del Gen tax/genética , Productos del Gen tax/metabolismo , Genes pX , Infecciones por HTLV-I/fisiopatología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Provirus/genética , Elementos de Respuesta , Carga Viral , Replicación Viral , Adulto JovenRESUMEN
OBJECTIVES: To examine the rate of monitoring of metabolic syndrome and actual rates of metabolic syndrome in two patient cohorts [clozapine treatment and long-acting injectable (LAI) antipsychotic] who are reviewed on an equally regular basis (1-4 weekly) for administration of treatment. METHODS: Clinical and laboratory data are examined on 119 patients treated with clozapine and 116 patients treated with LAI antipsychotic medications to determine the rates of metabolic syndrome and evidence of monitoring for metabolic syndrome in the previous 6 months. Individuals with insufficient data from these cohorts were invited to attend for metabolic screening to determine actual rates of metabolic syndrome in these two cohorts of patients. RESULTS: All metabolic parameters were monitored to a significantly greater extent in the clozapine cohort (>90%), compared to those treated with LAI antipsychotic medications (<50%) (blood pressure, weight, lipid and glucose levels; p < 0.001). Metabolic syndrome was present in 38.9% of those treated with clozapine compared to 31.1% of patients treated with LAI antipsychotic medications (X2 = 0.54, p = 0.46). CONCLUSIONS: These findings suggest that a robust screening plan should be in place to monitor for metabolic syndrome in individuals treated with LAI antipsychotic medications. This screening should include measurement of body weight, waist circumference, fasting glucose, lipids and fasting insulin levels. Early recognition of abnormal metabolic parameters allows early intervention, therefore, improving long-term cardiovascular outcomes.
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Antipsicóticos , Clozapina , Síndrome Metabólico , Esquizofrenia , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Estudios Transversales , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Esquizofrenia/tratamiento farmacológicoRESUMEN
AIMS: Skin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer. MATERIALS AND METHODS: This phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms. RESULTS: In total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT. CONCLUSIONS: Our study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.
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Neoplasias de la Mama , Efectos Adversos a Largo Plazo , Radiodermatitis , Radioterapia de Intensidad Modulada , Piel , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Supervivencia sin Enfermedad , Femenino , Humanos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/etiología , Persona de Mediana Edad , Estadificación de Neoplasias , Radiodermatitis/diagnóstico , Radiodermatitis/etiología , Radiodermatitis/prevención & control , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Piel/patología , Piel/efectos de la radiaciónRESUMEN
BACKGROUND: The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment of chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who achieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib treatment. METHODS: The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols. RESULTS: Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained in a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR. CONCLUSIONS: Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of imatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for preserving other therapeutic options in imatinib-resistant patients.
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We report our experience treating four patients with acutely bleeding angiomyolipoma (AML) of sizes between 4 and 12 cm who were managed with endovascular embolisation with a mean follow-up of 10 months. In our case series, we demonstrate that endovascular embolisation in the acute setting for bleeding AMLs is a viable treatment option. AML should be in the differential diagnosis of acutely bleeding renal masses, even when there is no fat assessed by computed tomography (CT) imaging in the renal mass.
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Angiomiolipoma/terapia , Cateterismo/métodos , Embolización Terapéutica/métodos , Hemorragia/terapia , Neoplasias Renales/terapia , Enfermedad Aguda , Adulto , Angiografía , Angiomiolipoma/complicaciones , Angiomiolipoma/diagnóstico , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico , Masculino , Persona de Mediana Edad , Nefrectomía , Espacio Retroperitoneal , Tomografía Computarizada por Rayos XRESUMEN
The aim of the present study is to provide insight on the induced compressive perturbations together with the modifications of the environmental parameters in the course of Alfvén wave interaction with a solar magnetic null-point. The shock-capturing Godunov-type code PLUTO is used to solve the set of ideal magnetohydrodynamic equations. The nonlinear effects connected with an initial Alfvén pulse nearing a magnetic null point induces fast and slow magnetoacoustic waves with anti phase conduct. The induced current density and flows are independent of the local plasma-[Formula: see text] at the reconnection site. The induced inflows and outflows highly depend on the polarization. The inflows have a stronger effect compared to the outflows in both the x and y directions showing its peak in the x-direction. The dominant wave that couples to flows is the fast wave due to the in-phase harmony between perturbations of the compressive parameters and the fast wave. The induced current density possesses a steady orientation at the reconnection site which governs the diffusion or propagation of the waves. Induced perturbations by the nonlinear forces together with their back reaction on the Alfvén wave have a significant role in the current density excitation being responsible for the creation of inflows and outflows that are possible candidates for the creation of solar jets which has a significant contribution towards coronal seismology.
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Development of novel point of care diagnostic methods in order to help in implementing disease control program and identifying the causative agent of an outbreak is crucial. Classical diagnostic techniques, e.g., real-time polymerase chain reaction (PCR), rely on the presence of the nucleic acid sequence of the target in GenBank. In the case of an emerging new strain of a known or novel pathogen, false-negative results will be recorded by PCR. On the other hand, next-generation sequencing technologies allow rapid whole genome sequencing without previous knowledge of the target. One of these methods is the Oxford Nanopore sequencing technique, which utilizes a portable device named MinION and has a short run time. In this protocol, we describe the development of a novel nanopore sequencing protocol by combining random isothermal amplification technology and nanopore sequencing. The established protocol is rapid (<7 h) and sensitive as less than 4% of the sequenced RNA belonged to the target virus, Zika. Interestingly, we have established an offline BLAST search for the data analysis that facilitates the use of the whole protocol at remote settings without the need of an Internet connection.
Asunto(s)
Secuenciación de Nanoporos/métodos , Reacción en Cadena de la Polimerasa/métodos , Infección por el Virus Zika/diagnóstico , Virus Zika/genética , ADN Complementario/análisis , ADN Complementario/biosíntesis , ADN Complementario/aislamiento & purificación , Brotes de Enfermedades , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Unidades Móviles de Salud , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Pruebas en el Punto de Atención , ARN Viral/genética , ARN Viral/aislamiento & purificación , Juego de Reactivos para Diagnóstico , Análisis de Secuencia de ADN/métodos , Flujo de Trabajo , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/virologíaRESUMEN
Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to explore their potential use as a less-invasive diagnostic tool for endometriosis. Overall, 59 women were included, n = 35 with endometriosis and n = 24 controls. Rectal and vaginal samples were collected in two different periods of the menstrual cycle from all subjects. Gut and vaginal microbiomes from patients with different rASRM (revised American Society for Reproductive Medicine) endometriosis stages and controls were analyzed. Illumina sequencing libraries were constructed using a two-step 16S rRNA gene PCR amplicon approach. Correlations of 16S rRNA gene amplicon data with clinical metadata were conducted using a random forest-based machine-learning classification analysis. Distribution of vaginal CSTs (community state types) significantly differed between follicular and menstrual phases of the menstrual cycle (p = 0.021, Fisher's exact test). Vaginal and rectal microbiome profiles and their association to severity of endometriosis (according to rASRM stages) were evaluated. Classification models built with machine-learning methods on the microbiota composition during follicular and menstrual phases of the cycle were built, and it was possible to accurately predict rASRM stages 1-2 verses rASRM stages 3-4 endometriosis. The feature contributing the most to this prediction was an OTU (operational taxonomic unit) from the genus Anaerococcus. Gut and vaginal microbiomes of women with endometriosis have been investigated. Our findings suggest for the first time that vaginal microbiome may predict stage of disease when endometriosis is present.