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1.
J Pharm Biomed Anal ; 178: 112906, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31634756

RESUMO

In this study, the employment of a purpose-made capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C4D) as a simple and cost-effective approach for simultaneous determination of different carbapenem antibiotics is reported. The developed CE-C4D approach was for the first time applied for quality control of various pharmaceutical formulations in Vietnam, as well as for therapeutic monitoring of these antibiotics in plasma samples from patients under intensive care. Four of the most popular carbapenems in Vietnam, doripenem, meropenem, imipenem and ertapenem, were determined using an electrolyte composed of 10 mM Tris adjusted to pH 8.0 with acetic acid. The best detection limits achieved using the developed CE-C4D method were 0.36 mg/L and 0.45 mg/L for pharmaceutical and plasma samples, respectively. Good agreement between results from CE-C4D and the confirmation method (HPLC-PDA) was achieved, with a coefficient of determination (r2) for the two pairs of data of 0.9967.

2.
Nature ; 576(7786): 274-280, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31802000

RESUMO

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2-4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.

3.
Neuro Oncol ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883020

RESUMO

BACKGROUND: Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METHODS: Clinical, genetic and treatment data of 143 patients from 13 European countries were analyzed (2009 - 2017). Therapy consisted of surgery, anthracycline-based induction and either radiotherapy or high dose chemotherapy following a consensus among European experts. FISH, MLPA and sequencing were employed for assessment of somatic and germline mutations in SMARCB1. Molecular subgroups (ATRT-SHH, -TYR and -MYC) were determined using DNA-methylation arrays resulting in profiles of 84 tumors. RESULTS: Median age at diagnosis of 67 girls and 76 boys was 29.5 months. 5-year overall survival (OS) and event-free survival (EFS) were 34.7±4.5% and 30.5±4.2%. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRT (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC 17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission and omission of radiotherapy were negative prognostic factors in univariate analyses (p<0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 year + non-TYR; 5-year OS = 0%), intermediate risk (<1 year + ATRT-TYR or ≥1 year + non-TYR; 5-year OS = 32.5±8.7%) and standard risk (≥1 year + ATRT-TYR, 5-year OS = 71.5±12.2%). CONCLUSIONS: Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.

4.
JMIR Res Protoc ; 8(10): e14889, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31599730

RESUMO

BACKGROUND: Deaf American Sign Language (ASL) users often struggle with limited health literacy compared with their hearing peers. However, the mechanisms driving limited health literacy and how this may impact access to and understanding of health information for Deaf individuals have not been determined. Deaf individuals are more likely than hearing individuals to use the internet, yet they continue to report significant barriers to health information. This study presents an opportunity to identify key targets that impact information access for a largely marginalized population. OBJECTIVE: This study aims to elucidate the role of information marginalization on health literacy in Deaf ASL users and to better understand the mechanisms of health literacy in this population for the purpose of identifying viable targets for future health literacy interventions. METHODS: This is an exploratory mixed methods study to identify predictors and moderators of health literacy in the Deaf population. These predictors of health literacy will be used to inform the second step that qualitatively explains the findings, including how Deaf individuals access and understand Web-based health information. Multiple interviewer- and computer-based instruments underwent translation and adaptation, from English to ASL, to make them accessible for the Deaf participants in our study. A planned sample of 450 Deaf ASL users and 450 hearing native English speakers, aged 18 to 70 years, will be recruited from 3 partnering sites: Rochester, NY; Flint, MI; and Chicago, IL. These individuals will participate in a single data collection visit. A subset of participants (approximately 30) with key characteristics of interest will be invited for a second data collection visit to observe and inquire more about their ability to directly access, navigate, and comprehend Web-based health information. The study will help assess how the ways health literacy and information are visualized may differ between Deaf individuals and hearing individuals. The study will also survey participants' ownership and use of computer and mobile devices and their level of Web-based information use, including health information. RESULTS: Adaptation and translation of protocols and instruments have been completed and are now in use for the study. Recruitment is underway and will continue until late 2020. Results from this study will be used to provide a guide on how to structure Web-based health information in a way that maximizes accessibility and improves health literacy for Deaf individuals. CONCLUSIONS: The results from this mixed methods proposal will advance what is known about health literacy and health information accessibility for Deaf individuals. This innovative study will generate rich data on how to formulate health information and health literacy interventions more accurately to take advantage of visual learning skills. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14889.

5.
J Clin Oncol ; 37(34): 3192-3202, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553693

RESUMO

PURPOSE: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

6.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

7.
J Chromatogr A ; 1605: 360356, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31327480

RESUMO

A simple and inexpensive approach for determination of various antimicrobial drugs using a purpose-made compact capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C4D) is reported. The objective of the work is to propose an affordable and easily-implemented tool for quality control and detection of counterfeiting of antibiotic formulations in resource constrained developing countries. The design of the purpose-made CE-C4D system was improved according to the feedback from over 10 years of use of our previous instrument. CE-C4D methods were for the first time developed to analyze ß-lactam-based antibiotics commonly used in Vietnam, including single- ß-lactam antibiotics (i.e. Cephalexin, Cefotaxime Sodium, Cefixime and Sulbactam) as well as ß-lactams co-formulated with Sulbactam (i.e. Amoxicillin, Ampicillin, Cefoperazone and Sulbactam). Single ß-lactam antibiotics were analyzed using a background electrolyte (BGE) composed of Tris/Ace (10 mM, pH 7.8) whereas ß-lactam - Sulbactam combinations were simultaneously separated using a BGE containing Tris/Ace (10 mM, pH 7.5). The best achieved detection limits were 2.0 mg/L and 1.0 mg/L for these two groups, respectively. Good agreement between results obtained from CE-C4D and standard confirmation methods (LCMS) was achieved, with a coefficient of determination, r2, of 0.9991. The applicability of the developed CE-C4D method was demonstrated for quality control of 24 ß-lactam-based antimicrobial drugs available in Vietnam.


Assuntos
Antibacterianos/análise , Análise Custo-Benefício , Condutividade Elétrica , Eletroforese Capilar/economia , Eletroforese Capilar/métodos , beta-Lactamas/análise , Concentração de Íons de Hidrogênio , Limite de Detecção , Controle de Qualidade
8.
Anal Chim Acta ; 1062: 156-164, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30947992

RESUMO

This study reports on the conception of magneto-Capillary Electrophoresis (magneto-CE), an approach integrating immuno-capture on circulating bio-functionalized magnetic beads into a unique capillary for preconcentration and electrokinetic separation. This hybrid mode is an evolution of in-capillary magnetic bead-based operation from static cluster format to dynamic configuration where beads are allowed to controllably circulate inside a CE capillary for interaction improvement. To implement the magneto-CE operation, a purpose-made instrument was constructed, allowing visual observation of the movement of the magnetic beads. We applied a new methodological strategy for determination of the amyloid ß peptide (Aß 1-42), which is as an established biomarker for molecular diagnosis of Alzheimer's disease (AD). The methodology is based on magneto-immuno-capture of fluorescently labeled Aß 1-42 followed by a chemical elution with a basic solution prior to CE separation with laser induced fluorescent (LIF) detection. The superiority of this dynamic configuration of magneto-CE was demonstrated for this target analyte, with sample pretreatment and separation being performed in-capillary without any delay in between and without any waste of pretreated sample, which otherwise would not be the case with offline/batch-wise operation.


Assuntos
Peptídeos beta-Amiloides/isolamento & purificação , Eletroforese Capilar , Separação Imunomagnética , Campos Magnéticos , Fragmentos de Peptídeos/isolamento & purificação , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/química , Humanos , Fragmentos de Peptídeos/química
9.
Anal Chim Acta ; 1058: 18-28, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-30851850

RESUMO

The use of the computer language Forth for controlling experimental analytical instruments built in laboratories is described. Forth runs on a microcontroller and as it is an interpreted language the user can directly communicate with it by employing a terminal emulator program running on a personal computer. Thus the user can test attached hardware, such as pumps, valves, electronic pressure regulators, detectors and chemical sensors, directly from the keyboard. This overcomes the lack of interactivity, a significant shortcoming, of the computer languages C and C++, the default on such microcontroller platforms as the Arduinos, which have become very popular in recent years for laboratory applications. Common examples of purpose built experimental analytical laboratory instruments are sequential injection analysis systems, microfluidic devices, or automated sample extraction systems. Application examples from our laboratory are given, namely the regulation of mass-flow controllers for gases, the sequencing of an experimental capillary electrophoresis instrument and the acquisition of a signal from an alcohol sensor.

10.
Talanta ; 195: 366-371, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625556

RESUMO

A water quality analyzer based on the working principle of capillary electrophoresis (CE) was developed to determine ionic inorganic nitrogen compounds contained in wastewater samples. The instrument provides simultaneous quantification of anions and cations by superimposing hydrodynamic pumping with electrokinetic motion. It features a single separation capillary with contactless conductivity detection and a sequential injection manifold for fluid handling. Dynamic adaption of the system calibration was enabled by the use of a high precision pressure regulator to cover a wide measurement range showing low relative standard deviations (< 2 %) and high measurement accuracy comparable to conventional wastewater analyzers. The prototype is transportable, integrated in a 19 in. rack and connected to a membrane filter system developed for direct sample aspiration in the wastewater process. For operation on site, only a power supply and a network connection for remote control is necessary. Continuous operation was demonstrated over 24 h at the aeration tank of a pilot scale wastewater treatment plant at TU Wien and a good correlation with laboratory results was achieved. At this time, there is no device available, on the market, to analyze all nitrogen species in one assembly with limited hardware complexity and chemical demand. This entails a significant step forward towards automated water quality monitoring with respect to the implementation of new advanced wastewater treatment technologies.

11.
Biochim Biophys Acta Gene Regul Mech ; 1862(1): 58-70, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30416088

RESUMO

Emerging evidence from recent studies has unraveled the roles of long noncoding RNAs (lncRNAs) in the function of various tissues. However, little is known about the roles of lncRNAs in kidney development. In our present study, we aimed to identify functional lncRNAs in one of the three lineages of kidney progenitor cells, i.e., metanephric mesenchymal (MM) cells. We conducted comprehensive analyses of the chromatin signature and transcriptome by RNA-seq and ChIP-seq. We found seventeen lncRNAs that were expressed specifically in MM cells with an active chromatin signature, while remaining silenced in a bivalent chromatin state in non-MM cells. Out of these MM specific lncRNAs, we identified a lncRNA, Gm29418, in a distal enhancer region of Six2, a key regulatory gene of MM cells. We further identified three transcript variants of Gm29418 by Rapid Amplification of cDNA Ends (RACE), and confirmed that the transcription-start-sites (TSSs) of these variants were consistent with the result of Cap Analysis Gene Expression (CAGE). In support of the enhancer-like function of Gm29418 on Six2 expression, we found that knock-down of Gm29418 by two independent anti-sense locked nucleic acid (LNA) phosphorothioate gapmers suppressed Six2 mRNA expression levels in MM cells. We also found that over-expression of Gm29418 led to an increase in Six2 mRNA expression levels in a mouse MM cell line. In conclusion, we identified a lncRNA, Gm29418, in nephron progenitor cells that has an enhancer-like function on a key regulatory gene, Six2.


Assuntos
Rim/crescimento & desenvolvimento , Néfrons/citologia , RNA Longo não Codificante/fisiologia , Células-Tronco/metabolismo , Animais , Cromatina , Proteínas de Homeodomínio/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Transcriptoma
12.
Electrophoresis ; 40(1): 124-139, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010203

RESUMO

The publications concerning capacitively coupled contactless conductivity detection for the 2-year period from mid-2016 to mid-2018 are covered in this update to the earlier reviews of the series. Relatively few reports on fundamental investigations or new designs have appeared in the literature in this time interval, but the development of new applications with the detection method has continued strongly. Most often, contactless conductivity measurements have been employed for the detection of inorganic or small organic ions in conventional capillary electrophoresis, less often in microchip electrophoresis. A number of other uses, such as detection in chromatography or the gauging of bubbles in streams have also been reported.


Assuntos
Eletroforese Capilar , Biomarcadores/análise , Condutividade Elétrica , Eletroforese em Microchip , Análise de Alimentos , Humanos
13.
Electrophoresis ; 40(3): 410-413, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30152034

RESUMO

A fast automated system for rapid electrophoretic separations in short conventional capillaries employing contactless conductivity detection is presented. The instrument is based on pneumatic pressurization and does not require a conventional pump. The required pressures and flow rates for the different steps of the injection and flushing processes are produced with the help of two flow restrictors. The device is implemented on a microfluidic breadboard with dimensions of ca. 13 × 20 cm and employs miniature valves. Nine inorganic cations, namely NH4 + , K+ , Na+ , Ca2+ , Mg2+ , Mn2+ , Sr2+ , Li+ , and Ba2+ , could be separated in a capillary of 10 µm inner diameter and 6 cm effective length within 25 s. Following a reduction of the effective length to 4 cm, still five inorganic cations could be separated in a time span of 12 s. The repeatability of peak areas was better than 3.1 % and limits of detection between 3.5 and 5.5 µM were achieved.


Assuntos
Eletroforese Capilar , Técnicas Analíticas Microfluídicas/instrumentação , Cátions/análise , Cátions/química , Cátions/isolamento & purificação , Eletroforese Capilar/instrumentação , Eletroforese Capilar/métodos , Desenho de Equipamento , Pressão
14.
Magy Onkol ; 62(4): 230-236, 2018 Dec 12.
Artigo em Húngaro | MEDLINE | ID: mdl-30540865

RESUMO

The survival of children treated with Ewing sarcoma at Semmelweis University were investigated. Pediatric patients with Ewing sarcoma treated at Semmelweis University from 2001 through 2013 were analyzed in terms of overall survival and clinical factors (age, primary localization and extent of the tumor, time interval from primary complaints to diagnosis). For statistical analysis Kaplan-Meier estimated survival and log rank test were applied. Mean age and follow-up time of the 78 patients were 11.16 and 6.29 years, respectively. In 57% of patients time interval from primary symptoms to diagnosis was less than half year. In 53.8% of the patients the disease was metastatic at primary diagnosis (pulmonary only: 29.5%, any other: 24.3%). 5- and 10-year overall survival of patients were 68.1% and 60.4%, respectively. Among the analyzed factors, the presence of metastasis impaired 5-year overall survival significantly (88.5% for localized disease, 63.5% for pulmonary only and 40.9% for any other metastasis). The survival rate of pediatric patients with Ewing sarcoma treated at Semmelweis University is similar to the result in Western European countries.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Adolescente , Fatores Etários , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hospitais Universitários , Humanos , Hungria , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sarcoma de Ewing/patologia , Fatores Sexuais , Análise de Sobrevida
15.
Magy Onkol ; 62(4): 237-241, 2018 Dec 12.
Artigo em Húngaro | MEDLINE | ID: mdl-30540866

RESUMO

The atypical teratoid/rhabdoid tumour (ATRT) is a rare type of central nervous system tumour appearing usually under 2 years of age. The survival of patients is insufficient despite the combined treatment (neurosurgical removal, intensive chemo- and radiotherapy). ATRT recurs one year after completion of treatment in 60% of cases. Maintaining appropriate nutritional status during treatment is of great importance in this young age group. Nutritional treatment of patients with ATRT is especially difficult due to young age and possible neurological sequelae. A successful case of a three-month-old female infant is presented, with special emphasis on the importance of feeding therapy.


Assuntos
Terapia Nutricional/métodos , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/terapia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/terapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Hungria , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Doenças Raras , Tumor Rabdoide/patologia , Medição de Risco , Neoplasias da Base do Crânio/patologia , Fatores de Tempo
16.
J Psychiatr Res ; 105: 132-136, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30219562

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are prevalent and frequently comorbid. Approximately 42-48% of patients with PTSD also meet diagnostic criteria for MDD. Maintenance electroconvulsive therapy (mECT) has been found to be efficacious for the prevention of recurrence of MDD. This study investigated the efficacy of mECT in the treatment of MDD with and without comorbid syndromal PTSD. METHODS: This retrospective study includes 36 patients, 26 with MDD and 10 with comorbid MDD & PTSD receiving monthly mECT for a mean of 1.5 years. The mean age was 52 ±â€¯14 years and 25% were female. The change in PTSD and MDD symptoms in response to mECT was assessed using Clinical Global Impression - Severity Scale (CGI-S). Heart rate variability (HRV), 12-month hospitalization rate, suicide rate and all-cause mortality in response to mECT were assessed and compared between groups using repeated generalized linear regression (GLM) analysis. RESULTS: At mECT baseline, there were no statistically significant differences in CGI-S scores, HRV between patients with MDD alone and those with comorbid MDD and PTSD (P > 0.05). After 12-months of mECT, a significant increase in HRV (mean difference: 10.9 95%CI 4.8-20.3, p = 0.001) and decrease in CGI-S overall (mean difference: 3.5, 95% CI 3.3-3.6, p = 0.001)], PTSD (mean difference: 3.4, 95% CI 3.2-3.6, p = 0.001)], and MDD (mean difference: 3.8, 95% CI 3.5-3.9, p = 0.001)] symptoms in both groups were noted (p < 0.05). No psychiatric hospitalization or suicide occurred in any of the patients. CONCLUSIONS: Maintenance ECT is associated with improved HRV, reduction of both major depression and PTSD symptoms, and a favorable clinical outcome.


Assuntos
Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Idoso , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/epidemiologia
17.
Eur J Cancer Care (Engl) ; 27(6): e12912, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30204287

RESUMO

Children with medulloblastoma (MB) are predisposed for negative cognitive sequela, which has been widely identified in this population. The purpose of the present study was to explore cognitive deficits and psychopathological symptoms and analyse their relation among MB survivors. The Wechsler Intelligence Scale for Children and the Mini International Neuropsychiatric Interview (MINI-KID) was administered to 34 MB survivors to measure cognitive functioning and psychopathological symptoms. The MB survivors had lower global IQ (86.41 [79.70-93.13]) compared with the control population mean. We found impaired functioning in all IQ subscales in the MB survivors group, of which processing speed (84.15 [77.71-90.58]) was the most affected. Higher radiation dose and high-dose chemotherapy with stem cell rescue were significantly associated factors for lowered global IQ, while age at diagnosis, sex and time period from diagnosis were not significantly associated. Compulsive disorder, generalised anxiety, separation anxiety and posttraumatic stress disorder were significantly more prevalent in the MB survivor group than a group of 46 control participants. No correlation was found between the cognitive deficits and the psychopathological symptoms. Our results identify that MB survivors suffer from cognitive and psychopathological impairments, and these could exist independently from each other.


Assuntos
Antineoplásicos/administração & dosagem , Ansiedade de Separação/psicologia , Sobreviventes de Câncer/psicologia , Neoplasias Cerebelares/terapia , Disfunção Cognitiva/psicologia , Irradiação Craniana , Meduloblastoma/terapia , Transtorno Obsessivo-Compulsivo/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Fatores Etários , Transtornos de Ansiedade/psicologia , Estudos de Casos e Controles , Neoplasias Cerebelares/psicologia , Quimiorradioterapia , Criança , Feminino , Humanos , Masculino , Meduloblastoma/psicologia , Doses de Radiação , Transplante de Células-Tronco , Escalas de Wechsler
18.
CBE Life Sci Educ ; 17(3): es10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30142044

RESUMO

Scientists are shaped by their unique life experiences and bring these perspectives to their research. Diversity in life and cultural experiences among scientists, therefore, broadens research directions and, ultimately, scientific discoveries. Deaf individuals, for example, have successfully contributed their unique perspectives to scientific inquiry. However, deaf individuals still face challenges in university science education. Most deaf students in science, technology, engineering, and mathematics (STEM) disciplines interact with faculty who have little to no experience working with deaf individuals and who often have preconceptions or simply a lack of knowledge about deaf individuals. In addition to a lack of communication access, deaf students may also feel unwelcome in STEM, as do other underrepresented groups. In this essay, we review evidence from the literature and, where data are lacking, contribute the expert opinions of the authors, most of whom are deaf scientists themselves, to identify strategies to best support deaf students in university STEM education. We describe the journey of a hypothetical deaf student and methods for faculty to create a welcoming environment. We describe and provide recommendations for classroom seating and layout, accommodations, teaching strategies, and research mentoring. We also discuss the importance of including deaf scientists in research about deaf individuals.


Assuntos
Engenharia/educação , Matemática/educação , Pessoas com Deficiência Auditiva , Ciência/educação , Estudantes , Tecnologia/educação , Universidades , Docentes , Humanos , Aprendizagem , Tutoria , Mentores , Pesquisa , Ensino
19.
Biomicrofluidics ; 12(4): 044107, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30034570

RESUMO

Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or urine flow. Recent studies suggest that changes in FSS could contribute to the function and injury of these kidney cells. However, it is unclear whether FSS influences kidney development when urinary flow starts in the embryonic kidneys. In this study, we evaluated the influence of FSS on in vitro cultured ureteric bud (UB) cells by using a pumpless microfluidic device, which offers the convenience of conducting parallel cell culture experiments while also eliminating the need for cumbersome electronic driven equipment and intricate techniques. We first validated the function of the device by both mathematical model and experimental measurements. UB cells dissected from E15.5 mouse embryonic kidneys were cultured in the pumpless microfluidic device and subjected to FSS in the range of 0.4-0.6 dyn mm-2 for 48 h (dynamic). Control UB cells were similarly cultured in the device and maintained under a no-flow condition (static). We found from our present study that the exposure to FSS for up to 48 h led to an increase in mRNA expression levels of UB tip cell marker genes (Wnt11, Ret, Etv4) with a decrease in stalk cell marker genes (Wnt7b, Tacstd2). In further support of the enrichment of UB tip cell population in response to FSS, we also found that exposure to FSS led to a remarkable reduction in the binding of lectin Dolichos Biflorus Agglutinin. In conclusion, results of our present study show that exposure to FSS led to an enrichment in UB tip cell populations, which could contribute to the development and function of the embryonic kidney when urine flow starts at around embryonic age E15.5 in mouse. Since UB tip cells are known to be the proliferative progenitor cells that contribute to the branching morphogenesis of the collecting system in the kidney, our finding could imply an important link between the FSS from the initiation of urine flow and the development and function of the kidney.

20.
Alcohol Clin Exp Res ; 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29953169

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. METHODS: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood-brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. RESULTS: Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. CONCLUSIONS: These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.

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