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Importance: Blood-based biomarkers may clarify underlying neuropathology and potentially assist in clinical management of adolescents with sport-related concussion (SRC). Objective: To investigate the association between SRC and plasma biomarkers in adolescents. Design, Setting, and Participants: Prospective cohort study in Canadian sport and clinic settings (Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study; September 2019 to November 2022). Participants were a convenience sample of 849 adolescent (ages 10-18 years) sport participants with blood samples. Data were analyzed from February to September 2023. Exposures: Blood collection and clinical testing preseason (uninjured) and post-SRC follow-ups (ie, ≤72 hours, 1 week, and biweekly until medical clearance to return to play [RTP]). Main Outcomes and Measures: Plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) were assayed. Group-level comparisons of biomarker levels were conducted between uninjured and post-SRC intervals (postinjury day [PID] 0-3, 4-10, 11-28, and >28) considering age and sex as modifiers. Secondary analyses explored associations between biomarker concentrations and clinical outcomes (Sport Concussion Assessment Tool, Fifth Edition [SCAT5] symptom scores and time to RTP). Results: This study included 1023 plasma specimens from 695 uninjured participants (467 male participants [67.2%]; median [IQR] age, 15.90 [15.13-16.84] years) and 154 participants with concussion (78 male participants [51.0%]; median [IQR] age, 16.12 [15.31-17.11] years). Acute (PID 0-3) differences relative to uninjured levels were found for GFAP (female participants: 17.8% increase; ß = 0.164; 95% CI, 0.064 to 0.263; P = .001; male participants: 17.1% increase; ß = 0.157; 95% CI, 0.086 to 0.229; P < .001), UCH-L1 (female participants: 43.4% increase; ß = 0.361; 95% CI, 0.125 to 0.596; P = .003), NfL (male participants: 19.0% increase; ß = 0.174; 95% CI, 0.087 to 0.261; P < .001), and t-tau (female participants: -22.9%; ß = -0.260; 95% CI, -0.391 to -0.130; P < .001; male participants: -18.4%; ß = -0.203; 95% CI, -0.300 to -0.106; P < .001). Differences were observed for all biomarkers at PID 4 to 10, 11 to 28, and greater than 28 compared with uninjured groups. GFAP, NfL, and t-tau were associated with SCAT5 symptom scores across several PID intervals. Higher GFAP after 28 days post-SRC was associated with earlier clearance to RTP (hazard ratio, 4.78; 95% CI, 1.59 to 14.31; P = .01). Male participants exhibited lower GFAP (-9.7%), but higher UCH-L1 (21.3%) compared with female participants. Age was associated with lower GFAP (-5.4% per year) and t-tau (-5.3% per year). Conclusions and Relevance: In this cohort study of 849 adolescents, plasma biomarkers differed between uninjured participants and those with concussions, supporting their continued use to understand concussion neuropathology. Age and sex are critical considerations as these biomarkers progress toward clinical validation.
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Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Proteínas tau , Humanos , Adolescente , Masculino , Feminino , Biomarcadores/sangue , Concussão Encefálica/sangue , Concussão Encefálica/complicações , Estudos Prospectivos , Traumatismos em Atletas/sangue , Traumatismos em Atletas/complicações , Criança , Proteínas tau/sangue , Proteínas de Neurofilamentos/sangue , Ubiquitina Tiolesterase/sangue , Proteína Glial Fibrilar Ácida/sangue , Canadá , Lesões Encefálicas Traumáticas/sangueRESUMO
INTRODUCTION: This study investigates the effect of apolipoprotein E (APOE) genotype on neurology plasma biomarkers in cognitively healthy Super-Seniors. METHODS: Three hundred seventy plasma specimens from Super-Senior participants ≥ 85 years old, who have never been diagnosed with dementia, cancer, diabetes, cardiovascular, or major pulmonary disease, were analyzed on the Quanterix Simoa HD-X analyzer using commercial Neurology 4-plex E and phosphorylated tau (p-tau)181 assays. RESULTS: Eighty (22%) participants were APOE ε4 carriers and 290 (73%) were non-carriers. No significant differences were found between APOE ε4 carriers and non-carriers regarding age, sex, or Mini-Mental State Examination scores. In APOE ε4 carriers, plasma amyloid beta 42/40 was lower and p-tau181 and glial fibrillary acidic protein were higher compared to non-APOE ε4 carriers. After adjusting for demographic variables, p-tau181 was the only biomarker to remain significantly associated with APOE ε4 carrier status. DISCUSSION: APOE ε4 genotype modifies plasma p-tau181 concentration in seniors resilient to age-related clinical disease, suggesting that some Super-Seniors may have Alzheimer's disease pathology without progressing to cognitive decline. HIGHLIGHTS: Healthy seniors enable identification of associations that may be masked by disease. Plasma phosphorylated tau (p-tau)181 concentrations associate with apolipoprotein E (APOE) ε4 carriership in healthy seniors. APOE should be accounted for when interpreting p-tau181, regardless of disease.
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Apolipoproteína E4 , Biomarcadores , Proteínas tau , Humanos , Feminino , Masculino , Proteínas tau/sangue , Apolipoproteína E4/genética , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Genótipo , Heterozigoto , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , FosforilaçãoRESUMO
Importance: Advancing research on fluid biomarkers associated with sport-related concussion (SRC) highlights the importance of detecting low concentrations using ultrasensitive platforms. However, common statistical practices may overlook replicate errors and specimen exclusion, emphasizing the need to explore robust modeling approaches that consider all available replicate data for comprehensive understanding of sample variation and statistical inferences. Objective: To evaluate the impact of replicate error and different biostatistical modeling approaches on SRC biomarker interpretation. Design, Setting, and Participants: This cross-sectional study within the Surveillance in High Schools to Reduce the Risk of Concussions and Their Consequences study used data from healthy youth athletes (ages 11-18 years) collected from 3 sites across Canada between September 2019 and November 2021. Data were analyzed from November 2022 to February 2023. Exposures: Demographic variables included age, sex, and self-reported history of previous concussion. Main Outcomes and Measures: Outcomes of interest were preinjury plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament-light (NFL), total tau (t-tau) and phosphorylated-tau-181 (p-tau-181) assayed in duplicate. Bland-Altman analysis determined the 95% limits of agreement (LOAs) for each biomarker. The impact of replicate error was explored using 3 biostatistical modeling approaches assessing the associations of age, sex, and previous concussion on biomarker concentrations: multilevel regression using all available replicate data, single-level regression using the means of replicate data, and single-level regression with replicate means, excluding specimens demonstrating more than 20% coefficient variation (CV). Results: The sample included 149 healthy youth athletes (78 [52%] male; mean [SD] age, 15.74 [1.41] years; 51 participants [34%] reporting ≥1 previous concussions). Wide 95% LOAs were observed for GFAP (-17.74 to 18.20 pg/mL), UCH-L1 (-13.80 to 14.77 pg/mL), and t-tau (65.27% to 150.03%). GFAP and UCH-L1 were significantly associated with sex in multilevel regression (GFAP: effect size, 15.65%; ß = -0.17; 95% CI, -0.30 to -0.04]; P = .02; UCH-L1: effect size, 17.24%; ß = -0.19; 95% CI, -0.36 to -0.02]; P = .03) and single-level regression using the means of replicate data (GFAP: effect size, 15.56%; ß = -0.17; 95% CI, -0.30 to -0.03]; P = .02; UCH-L1: effect size, 18.02%; ß = -0.20; 95% CI, -0.37 to -0.03]; P = .02); however, there was no association for UCH-L1 after excluding specimens demonstrating more than 20% CV. Excluding specimens demonstrating more than 20% CV resulted in decreased differences associated with sex in GFAP (effect size, 12.29%; ß = -0.14; 95% CI, -0.273 to -0.004]; P = .04) and increased sex differences in UCH-L1 (effect size, 23.59%; ß = -0.27; 95% CI, -0.55 to 0.01]; P = .06), with the widest 95% CIs (ie, least precision) found in UCH-L1. Conclusions and Relevance: In this cross-sectional study of healthy youth athletes, varying levels of agreement between SRC biomarker technical replicates suggested that means of measurements may not optimize precision for population values. Multilevel regression modeling demonstrated how incorporating all available biomarker data could capture replicate variation, avoiding challenges associated with means and percentage of CV exclusion thresholds to produce more representative estimates of association.
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Concussão Encefálica , Esportes , Adolescente , Humanos , Masculino , Feminino , Estudos Transversais , Ubiquitina Tiolesterase , Concussão Encefálica/diagnóstico , BiomarcadoresRESUMO
INTRODUCTION: In this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aß42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). METHODS: 900 plasma specimens from male and female participants aged 3-79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aß42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression. RESULTS: For discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aß42/40: 3-<55y = 0.053-0.098, 55-<80y = 0.040-0.090; p-tau-181: 3-<12y = 1.4-5.6 pg/ml, 12-<60y = 0.8-3.1 pg/ml, 60-<80y = 0.9-4.0 pg/ml; NfL: 3-<40y = 2.6-11.3 pg/ml, 40-<60y = 4.6-17.7 pg/ml, 60-<80y = 8.1-47.1 pg/ml; GFAP; 3-<10y = 47.0-226 pg/ml, 10-<60y = 21.2-91.9 pg/ml, 60-<80y = 40.7-228 pg/ml. Continuous RIs produced smooth centile curves across the age range, from which point estimates for each year of age were calculated. CONCLUSIONS: Discrete and continuous RIs for neurological plasma biomarkers will help refine normative cut-offs across the lifespan and improve the precision of interpretating biomarker levels. Continuous RIs are recommended for use in age groups, such as pediatrics and older adults, that experience rapid concentration changes by age.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Masculino , Criança , Feminino , Idoso , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Canadá , Proteínas tau , BiomarcadoresRESUMO
Background: Sexually transmitted infections (STIs) are one of the world's most severe health challenges. The existence of STIs such as human papillomavirus (HPV) might cause cervical cell changes leading to cervical cancer. Objective: This study aims to assess the association of STIs with cervical cytological abnormalities and genital warts among women in northeastern Iran. Materials and Methods: This cross-sectional study was carried out on 190 women referred to the central laboratory of Academic Center for Education, Culture, and Research, Mashhad, Iran from March to July 2022. The presence of genital infections caused by Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Herpes simplex viruses (1 and 2) were assessed using the real-time polymerase chain reaction method. HPV genital infection was detected based on the principles of reverse hybridization, and cellular changes in the cervix were examined by the liquid-based cytology technique. Results: The mean age of participants was 35.33 ± 8.9 yr. 34 different HPV genotypes were detected in all HPV-positive cases, and the most common genotype was low-risk HPV6. No significant association was found between STIs and cervical cytology abnormalities. The prevalence rates of sexually transmitted pathogens among HPV-positive and HPV-negative individuals were 10.9 and 1.6%, respectively. The frequency of genital warts was significantly higher in cases with multiple infections of high- and low-risk HPV genotypes. Conclusion: High percentages of the participants with non-HPV STIs and HPV infection had normal cervical cytology. It is advised to use STIs and HPV diagnostic tests along with cytology examinations for cervical cancer screening.
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Abstract Developing objective measures to diagnose sport-related concussion (SRC) is a top priority, particularly in the pediatric context, given the vulnerability of the developing brain. While advances in SRC blood biomarkers are being made in adult populations, less data are available for adolescents. Clinical validation of blood biomarkers post-SRC will first require investigation in a healthy uninjured state. Further, rapid pubertal changes during adolescence may implicate possible interactions with circulating sex hormones and the menstrual cycle for females. This cross-sectional study aimed to characterize pre-injury plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), ubiquitin C-terminal hydrolase-L1 (UCH-L1), total tau (T-tau), and phosphorylated tau-181 (P-tau-181), considering previous concussion, age, and sex in healthy adolescent sport participants. Possible associations with menstrual cycle phase and circulating sex hormone levels (i.e., progesterone, estradiol, testosterone) were also explored. Pre-injury blood samples were obtained from 149 healthy adolescents (48% female, ages 11-18) participating in a larger Surveillance in High Schools and Community Sports to Reduce Concussions and their Consequences (SHRed Concussions) multi-site longitudinal cohort study. Main outcomes were natural log (ln) transformed plasma GFAP, NF-L, UCH-L1, T-tau, and P-tau-181 concentrations, quantified on the Quanterix Simoa HD-X platform. Mixed-effects multi-variable linear regression was used to assess associations between biomarkers and self-reported previous concussion (yes/no), age (years), sex (male/female), objectively determined menstrual cycle phase (follicular/luteal), plasma progesterone, estradiol, and testosterone. Males had 19.8% lower UCH-L1 (ß = -0.221, 95% confidence interval [CI; -0.396, -0.046]), 18.9% lower GFAP (ß = -0.210, 95% CI [-0.352, -0.068]), and 21.8% higher P-tau-181 (ß = 0.197, 95% CI [0.048, 0.346]) compared with females, adjusting for age and previous concussion. GFAP decreased 9.5% with each 1-year increase in age, adjusting for previous concussion and sex (ß = -0.100, 95% CI [-0.152, -0.049]). No biomarkers were associated with a history of previous concussion. Exploratory investigations found no associations between biomarkers and menstrual cycle phase. Females displayed an age-adjusted negative association between T-tau and progesterone (ß = -0.010, 95% CI [-0.018, -0.002]), whereas males had a negative age-adjusted association between UCH-L1 and testosterone (ß = -0.020, 95% CI [-0.037, -0.002]). As such, age- and sex-specific reference intervals may be warranted for pediatric athlete populations prior to clinical validation of blood biomarkers for SRC. Additionally, hormonal associations highlight the need to consider puberty and development in adolescent studies. Overall, findings suggest these biomarkers are resilient to a history of previous concussion and menstrual cycle phase, supporting continued investigation in adolescent SRC.
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Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Adolescente , Feminino , Humanos , Masculino , Traumatismos em Atletas/sangue , Biomarcadores/sangue , Concussão Encefálica/sangue , Estudos Transversais , Estradiol/sangue , Proteína Glial Fibrilar Ácida , Estudos Longitudinais , Progesterona/sangue , Testosterona/sangue , Criança , Ciclo Menstrual/sangue , PuberdadeRESUMO
Background: Endometriosis is associated with abnormal immunologic responses and combined inflammatory and anti-inflammatory conditions. Objective: This study aims to investigate follicular fluid (FF) concentration of interleukin (IL)-3, IL-5, and IL-6 in women with and without endometriosis. Materials and Methods: In this cross-sectionalstudy 68 women who were referred to the in vitro fertilization center of Imam Reza hospital in Mashhad during 2018 were selected randomly. Leaves of cytokines in the FF samples were evaluated in the endometriosis and the control group (n = 34/each). The diagnostic accuracy of cytokines and clinical characteristics were evaluated. Results: IL-3 and IL-6 were significantly changed in the FF of the women with endometriosis compared with the control group (p = 0.04, and p < 0.01, respectively), and the mean concentration of IL-5 in the endometriosis group was lower than in the control group (p = 0.5), but this was not significant. There were significant differences in the menstrual cycle, dyspareunia, and dysmenorrhea between the groups (p < 0.01, p = 0.04, and p = 0.02, respectively). The diagnostic accuracy of IL-3 and IL-6 in the FF was low, with the area under the curve of 0.614 and 0.645, respectively. Conclusion: Although none of the cytokines had a predictive value for endometriosis, the decreased levels of IL-3 and increased levels of IL-6 in the FF samples of women with endometriosis, and risk factors, including irregular menstrual cycle, dyspareunia, and dysmenorrhea, could be associated with the pathogenesis of this painful disease.
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BACKGROUND: The leadership of an organization requires specific features to adapt to changes and to survive and grow in new environments, and emotional intelligence is one of the most important attributes that can help leaders and managers respond to these changes. OBJECTIVE: This study aimed to determine the relationship between emotional intelligence with administrators' performance at Mashhad University of Medical Sciences, Mashhad, Iran. METHODS: This cross-sectional study was conducted on 100 basic and middle managers of Mashhad University of Medical Sciences, Mashhad, Iran who were selected by census method in 2016. The instrument of data collecting was the "Inventory Shrinkage", and the "Organizational performance evaluation forms". The data were analyzed by SPSS version 16 using descriptive statistics and Spearman correlation. RESULTS: The results showed there was a significant negative correlation between emotional intelligence and organizational performance in administrators (r=-0.214, p=0.032). The findings also showed that among the components of emotional intelligence and administrators' performance, only components of empathy, was there a significant negative correlation (r=-0.199, p=0.047). Also, there was no statistically significant relationship between emotional intelligence and demographic variables such as work experience, age, marital status and education level (p>0.05). There was no significant relationship between organizational performance and demographic variables, either (p>0.05). But between the components of emotional intelligence, only for social skills and work place of administrators, a significant positive correlation was confirmed (r=0.203, p=0.043). CONCLUSIONS: The results of this study showed that there was a negative and significant correlation between the components of emotional intelligence and administrators' performance of Mashhad University of Medical Sciences administrators, only in the empathy component.
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Gastric cancer (GC) as the fourth most common cause of malignancies shows high rate of morbidity appropriating the second leading cause of cancer-related death worldwide. Developmental pluripotency associated-2 (DPPA2), cancer-testis antigen (CT100), is commonly expressed only in the human germ line and pluripotent embryonic cells but it is also present in a significant subset of malignant tumors. To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to elucidate DPPA2 protein expression in gastric cancer. Fifty five GC tumor and their related margin normal tissues were recruited to evaluate DPPA2 protein expression and its probable associations with different clinicopathological features of the patients. DPPA2 was overexpressed in GC cases compared with normal tissues (P < .005). While DPPA2 expression was detected in all GC samples, its high expression was found in 23 of 55 tumor tissues (41.8%). Interestingly, 50 of 55 normal samples (90.9%) were negative for DPPA2 protein expression and remained 5 samples showed very low expression of DPPA2. DPPA2 protein expression in GC was significantly correlated with lymph node metastasis (p = 0.012). The clinical relevance of DPPA2 in GC illustrated that high level expression of this protein was associated with lymph node metastasis supporting this hypothesis that alteration in DPPA2 was associated with aggressiveness of gastric cancer and may be an early event in progression of the disease. DPPA2 may be introduced as a new marker for invasive and metastatic GCs.
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Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Estômago/patologia , Adenocarcinoma/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Proteínas de Ciclo Celular , Feminino , Seguimentos , Mucosa Gástrica/metabolismo , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Fatores de TranscriçãoRESUMO
INTRODUCTION: Colorectal cancer (CRC) is one of the most important common causes of cancer-related death globally and reorganization of regulatory mechanisms controlling initiation, progression and metastasis of the CRC is critical to improve the prognosis, diagnosis and effective therapeutic treatment of the patients. One of the newly identified pluripotency genes which is expressed specifically in pluripotent stem cells is developmental pluripotency-associated 2 (DPPA2). It may play important roles in the maintenance of pluripotency of ESCs and is associated with abnormal cell growth and cancer formation. METHODS: Protein expression of DPPA2 was specifically analyzed in tumors and their margin normals of colorectal epithelium in 50 new cases CRC patients by immunohistochemical staining. RESULTS: DPPA2 protein was significantly overexpressed in 60% of samples (30 of 50, P<0.01). This level of protein expression was significantly correlated to the depth of tumor invasion (p=0.047) and the stage of tumor progression (p=0.028). DISCUSSION: Due to existence of transcriptional linkage between DPPA2/Nanog and OCT4 in mouse ESCs, our results suggest that a pluripotency transcriptional network consisting of SALL4/OCT4/DPPA2/Nanog, as similar as ESCs, is activated in CRC which not only play essential roles in maintenance of stemness state and self-renewal characteristics of tumor cells, but also in progression of CRC cells through advanced stages leading to increase depth of tumor cell invasion. CONCLUSION: DPPA2 protein expression is correlated with different indices of poor prognosis and may be introduced as a new therapeutic marker in adjuvant therapy of colorectal cancer.
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Neoplasias Colorretais/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Células-Tronco Pluripotentes/metabolismo , Idoso , Animais , Proteínas de Ciclo Celular , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Prognóstico , Fatores de TranscriçãoRESUMO
Differences in the lateralization of language processes between healthy subjects and patients with neurological complaints other than epilepsy have been less documented than those between healthy subjects and epilepsy patients. Moreover, the contribution of factors such as the location and type of lesion in determining interhemispheric shift of language function is poorly understood. Sixty-seven patients who underwent presurgical evaluations at the Medical Imaging Center of the Imam Khomeini University Hospital, Tehran, and the same number of healthy controls, were recruited. The laterality index (LI) of language activation, calculated from two separate functional magnetic resonance imaging tasks, was compared between the patients and the age-/gender-/handedness-matched controls. Chi square testing showed that the percentages of subjects with "typical" and "atypical" language dominance in the patient group were significantly different from the percentages recorded in the matched healthy controls for both tasks (p<0.005). Lesion type, lesion location, lesion hemisphere, presenting symptom and patient gender had no statistically significant effect on the hemispheric LI (p>0.05). In a logistic regression model including all potential determinants of atypical LI, age emerged as the only independent predictor (p<0.05, odds ratio=0.9). Abnormal language lateralization is found in patients with a variety of cerebral lesions and with a diversity of clinical manifestations. In our selected population, symptom duration, lesion hemisphere and anatomical site of the lesion were not found to impact significantly on the development of an abnormal LI while patient age can independently predict the presence of an atypical LI.
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Encefalopatias/patologia , Encefalopatias/psicologia , Lateralidade Funcional/fisiologia , Idioma , Adolescente , Adulto , Idoso , Envelhecimento/psicologia , Encefalopatias/fisiopatologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/psicologia , Criança , Interpretação Estatística de Dados , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Leitura , Medida da Produção da Fala , Adulto JovemRESUMO
OBJECTIVE: Exophytic gliomas of the medulla are rare childhood tumors that mostly are pilocytic astrocytomas. Here we report our experience in 11 -children with this rare tumor. METHODS: A retrospective study was performed using the records of children with exophytic gliomas of the medulla at Children's Hospital Medical Center in Tehran, Iran, from 2002 through 2013. The general, clinical, and radiological data and follow-up of all patients were reviewed. RESULTS: The patients mostly were male aged from 11 months to 7 years. Swallowing problems, failure to thrive and nausea and vomiting were the most common symptoms. The time span between the onset of symptoms and the diagnosis was 2-24 months. Gross total resection of tumor was possible in 8 patients. Most tumors were pilocytic astrocytomas. Patients were followed for 2 months to 11 years (mean = 3.6 years). There was no intraoperative mortality. Recurrence occurred in 1 child with fibrillary astrocytoma. CONCLUSION: Gross total resection of symptomatic dorsal exophytic medullary glioma is recommended. Most tumors are pilocytic astrocytomas. The attachment of these tumors to important brainstem structures usually inhibits total resection. Electrophysiological monitoring of sensorimotor pathways and cranial nerves can be helpful to preserve surrounding neural tissue during tumor resection and to minimize complications. Regular follow-up of patients with clinical examination and brain MRI is mandatory. Repeated surgery, radiation therapy and chemotherapy are suggested in cases with tumor recurrence or progression.
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Neoplasias do Tronco Encefálico , Glioma , Recidiva Local de Neoplasia , Astrocitoma/diagnóstico por imagem , Astrocitoma/fisiopatologia , Astrocitoma/terapia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/fisiopatologia , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Glioma/fisiopatologia , Glioma/terapia , Humanos , Lactente , Masculino , Radiografia , Resultado do TratamentoRESUMO
The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.
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Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenoma/genética , Boca/microbiologia , Doenças Periodontais/genética , Doenças Periodontais/microbiologia , Actinomyces/efeitos dos fármacos , Actinomyces/genética , Adulto , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Genes Bacterianos/genética , Variação Genética/efeitos dos fármacos , Variação Genética/genética , Saúde , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Metagenoma/efeitos dos fármacos , Metagenômica , Metais/farmacologia , Pessoa de Meia-Idade , Boca/efeitos dos fármacos , Periodontite/genética , Periodontite/microbiologia , RNA Ribossômico 16S/genética , Padrões de Referência , Fatores de Virulência/metabolismoRESUMO
BACKGROUND: A major goal of metagenomics is to characterize the microbial composition of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from metagenomic shotgun sequencing data by matching individual reads against a database of reference sequences. One major limitation of prior computational methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels. RESULTS: We propose that better classification results can be obtained by tuning the taxonomic classifier to each matching length, reference gene, and taxonomic level. We present a novel taxonomic classifier MetaPhyler (http://metaphyler.cbcb.umd.edu), which uses phylogenetic marker genes as a taxonomic reference. Results on simulated datasets demonstrate that MetaPhyler outperforms other tools commonly used in this context (CARMA, Megan and PhymmBL). We also present interesting results by analyzing a real metagenomic dataset. CONCLUSIONS: We have introduced a novel taxonomic classification method for analyzing the microbial diversity from whole-metagenome shotgun sequences. Compared with previous approaches, MetaPhyler is much more accurate in estimating the phylogenetic composition. In addition, we have shown that MetaPhyler can be used to guide the discovery of novel organisms from metagenomic samples.
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Bactérias/classificação , Marcadores Genéticos , Genoma Bacteriano , Metagenômica/métodos , Software , Algoritmos , Archaea/classificação , Archaea/genética , Bactérias/genética , Bases de Dados Genéticas , Genes de RNAr , Humanos , Filogenia , RNA Ribossômico 16S/genética , Alinhamento de Sequência , Fatores de TempoRESUMO
To determine the prevalence of pituitary hormone deficiencies after moderate traumatic brain injury (TBI). We conducted a prospective cohort and included 75 patients with moderate TBI with GCS between 9 and 13 who referred to emergency department of Shariati Hospital, Tehran/Iran, during 2004-2007. Pituitary hormones were assessed 3 and 6 months after injury. In 3(rd) month post-injury, 39 cases had not any pituitary dysfunction; however, deficiencies in one, two and three of the pituitary hormones were found in 26, 8 and 2 patients, respectively. Twenty one patients showed a deficiency in one of the pituitary hormones and only one case with deficiency of two after 6 months. The most prevalent changes occur in IGF-1 and LH/FSH after moderate TBI. However, the whole deficiencies decrease over the time.
Assuntos
Lesões Encefálicas/fisiopatologia , Hipófise/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Hormônios Hipofisários/metabolismo , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Molecular studies of microbial diversity have provided many insights into the bacterial communities inhabiting the human body and the environment. A common first step in such studies is a survey of conserved marker genes (primarily 16S rRNA) to characterize the taxonomic composition and diversity of these communities. To date, however, there exists significant variability in analysis methods employed in these studies. RESULTS: Here we provide a critical assessment of current analysis methodologies that cluster sequences into operational taxonomic units (OTUs) and demonstrate that small changes in algorithm parameters can lead to significantly varying results. Our analysis provides strong evidence that the species-level diversity estimates produced using common OTU methodologies are inflated due to overly stringent parameter choices. We further describe an example of how semi-supervised clustering can produce OTUs that are more robust to changes in algorithm parameters. CONCLUSIONS: Our results highlight the need for systematic and open evaluation of data analysis methodologies, especially as targeted 16S rRNA diversity studies are increasingly relying on high-throughput sequencing technologies. All data and results from our study are available through the JGI FAMeS website http://fames.jgi-psf.org/.
Assuntos
Marcadores Genéticos/genética , Variação Genética , Filogenia , Análise por Conglomerados , DNA Bacteriano/genética , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Alinhamento de SequênciaRESUMO
OBJECTIVE: Today, trauma is a major public health problem in some countries. Abdominal trauma is the source of significant mortality and morbidity with both blunt and penetrating injuries. We performed an epidemiological study of abdominal trauma (AT) in Tehran, Iran. We used all our sources to describe the epidemiology and outcome of patients with AT. METHODS: This study was done in Tehran. The study population included trauma patients admitted to the emergency department of six general hospitals in Tehran during one year. The data were collected through a questionnaire that was completed by a trained physician at the trauma center. The statistical analysis was performed using the SPSS software (version 11.5 for Windows). The statistical analysis was conducted using the chi-square and P < 0.05 was accepted as being statistically significant. RESULTS: Two hundred and twenty-eight (2.8%) out of 8,000 patients were referred to the above mentioned centers with abdominal trauma. One hundred and twenty-five (54.9%) of the patients were in their 2nd and 3rd decades of life and 189 (83%) of our patients were male. Road traffic accidents (RTA) were the leading cause of AT with 119 (52.2%) patients. Spleen was the commonly injured organ with 51 cases. Following the analysis of injury severity, 159 (69.7%) patients had mild injuries (ISS < 16) and 69 (30.3%) patients had severe injuries (ISS equal to 16). The overall mortality rate was 46 (20.2%). CONCLUSIONS: Blunt abdominal trauma is more common than penetrating abdominal trauma. Road traffic accidents and stab wound are the most common causes of blunt and penetrating trauma, respectively. Spleen is the most commonly injured organ in these patients. The mortality rate is higher in blunt trauma than penetrating one.
Assuntos
Traumatismos Abdominais/terapia , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hospitais , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Índices de Gravidade do Trauma , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/terapiaRESUMO
OBJECT: The goal of this paper was to investigate the long-term outcome and the possible prognostic factors that might have influenced the persistence of posttraumatic epilepsy after penetrating head injuries sustained during the Iraq-Iran war (1980-1988). METHODS: In this retrospective study, the authors evaluated 189 patients who sustained penetrating head injury and suffered posttraumatic epilepsy during the Iraq-Iran war (mean 18.6 +/- 4.7 years after injury). The probabilities of persistent seizures (seizure occurrence in the past 2 years) in different periods after injury were estimated using the Kaplan-Meier method. The possible prognostic factors (patients and injury characteristics, clinical findings, and seizure characteristics) were studied using log-rank and Cox regression analysis. RESULTS: The probability of persistent seizures was 86.4% after 16 years and 74.7% after 21 years. In patients with < 3 pieces of shrapnel or no sphincter disturbances during seizure attacks, the probability of being seizure free after these 16 and 21 years was significantly higher. CONCLUSIONS: Early seizures, prophylactic antiepileptics drugs, and surgical intervention did not significantly affect long-term outcome in regard to persistence of seizures.
Assuntos
Epilepsia Pós-Traumática/etiologia , Traumatismos Cranianos Penetrantes/complicações , Guerra do Iraque 2003-2011 , Veteranos , Ferimentos por Arma de Fogo/complicações , Adulto , Lesão Encefálica Crônica/diagnóstico , Lesão Encefálica Crônica/etiologia , Lesão Encefálica Crônica/terapia , Epilepsia Pós-Traumática/diagnóstico , Epilepsia Pós-Traumática/terapia , Feminino , Seguimentos , Traumatismos Cranianos Penetrantes/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Prognóstico , Remissão Espontânea , Ferimentos por Arma de Fogo/terapiaRESUMO
BACKGROUND: Many studies have investigated the variations in the anatomy of each segment of the cerebral arterial circle while a few have addressed the variations of the cerebral arterial circle as a whole. METHODS: Thirty brains of recently deceased Iranian infants and fetuses were dissected. The dissection process was filmed and digitized so as to be readily available for further studies. The variations of the circle as a whole and segmental variations were evaluated. RESULTS: Variants with uni- and bilateral hypoplasia of posterior communicating arteries (PcoAs) were the most common in our study, similar to previous works. No aplasia of the precommunicating part of the anterior cerebral artery (A1), the precommunicating part of the posterior cerebral artery (P1) and anterior communicating artery was seen. Hypoplasia of the right and left PcoA was observed in 8 and 5 cases, respectively. Aplasia of the right PcoA was found in 16.6% and of the left PcoA in 3.3%. CONCLUSION: In this study, we confirmed the previously described finding that the symmetrical, circular configuration of the circulus arteriosus cerebri is present in only about 42.1%. The main differences between the fetal and adult disposition are the diameter of the PcoA and the circular part of the posterior cerebral artery. According to previous studies, the fetal brain older than 4 months has anatomical characteristics very similar to the adult's circle; our finding was mostly similar to adult samples as most samples were from infants, not fetuses.