Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 218
Filtrar
1.
Support Care Cancer ; 28(11): 5291-5298, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32112353

RESUMO

Allogeneic hematopoietic cell transplantation (alloHCT) is a life-saving technology that can cure otherwise incurable diseases, but imposes significant physiologic stress upon recipients. This stress leads to short-term toxicity and mid- to long-term physical function impairment in some recipients. Exercise interventions have demonstrated preliminary efficacy in preserving physical function in HCT recipients, but the role of these interventions prior to HCT (prehabilitative) is less known. We tested a 5- to 12-week, prehabilitative higher intensity home-based aerobic exercise intervention in a randomized study of alloHCT candidates. Of 113 patients screened, 34 were randomized to control or intervention groups, 16 underwent pre- and post-intervention peak oxygen consumption (VO2peak) testing, and 12 underwent pre- and post-intervention 6-min walk distance (6MWD) testing. No significant differences in VO2peak or 6MWD were seen pre- to post-intervention between intervention and control groups, but final numbers of evaluable participants in each group were too small to draw inferences regarding the efficacy of the intervention. We conclude that the design of our prehabilitative intervention was not feasible in this pilot randomized study, and make recommendations regarding the design of future exercise intervention studies in alloHCT.


Assuntos
Terapia por Exercício/métodos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Serviços de Assistência Domiciliar , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Exercício Físico/fisiologia , Terapia por Exercício/organização & administração , Estudos de Viabilidade , Feminino , Serviços de Assistência Domiciliar/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina , Projetos Piloto , Padrões de Prática Médica , Transplante Homólogo , Resultado do Tratamento
2.
Int J Legal Med ; 134(2): 473-485, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989244

RESUMO

Biological traces found at crime scenes are analysed not only to genetically identify the donor(s) but also to determine the composition of the stain. For some cases, it is essential to associate a body fluid with a donor. Especially in mixed body fluid stains, but also in body fluid stains that appear to be single-source, this may be of importance. Linking a DNA profile (sub-source level) with evidence from a presumptive test or mRNA analysis (source level) is not straightforward. Our results support that associating donors and body fluids by means of comparing mixture ratios in RNA and DNA is not recommended. We introduce a set of 35 coding region SNPs (cSNPs) in body fluid-specific mRNA transcripts that represent a direct link between the body fluids and their donors. The discrimination power of the cSNPs was estimated based on allele frequencies calculated from a population sample (n = 188), and we investigated the practical application of the cSNPs in different scenarios. The results demonstrate that more cSNPs are needed to improve the discrimination power. However, the findings are promising as we were able to associate donors with body fluids in mixtures of different body fluids as well as in stains where both donors have contributed the same body fluid, e.g. a blood-blood mixture. In addition, the cSNP assay can be used for body fluid identification. The results of this proof-of-concept study support the use of cSNPs to assign body fluids to the respective donors.


Assuntos
Líquidos Corporais/química , Genética Forense/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Feminino , Humanos , Masculino , Estudo de Prova de Conceito , Análise de Sequência de DNA , Análise de Sequência de RNA
3.
Forensic Sci Int Genet ; 45: 102208, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31869731

RESUMO

In a previous EUROFORGEN/EDNAP collaborative exercise, we tested two assays for targeted mRNA massively parallel sequencing for the identification of body fluids/tissues, optimized for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms, respectively. The task of the second EUROFORGEN/EDNAP collaborative exercise was to analyze dried body fluid stains with two different multiplexes, the former Illumina 33plex mRNA panel for body fluid/tissue identification and a 35plex cSNP panel for assignment of body fluids/tissues to donors that was introduced in a proof-of-concept study recently. The coding region SNPs (cSNPs) are located within the body fluid specific mRNA transcripts and represent a direct link between the body fluid and the donor. We predicted the origin of the stains using a partial least squares discriminant analysis (PLS-DA) model, where most of the single source samples were correctly predicted. The mixed body fluid stains showed poorer results, however, at least one component was predicted correctly in most stains. The cSNP data demonstrated that coding region SNPs can give valuable information on linking body fluids/tissues with donors in mixed body fluid stains. However, due to the unfavorable performance of some cSNPs, the interpretation remains challenging. As a consequence, additional markers are needed to increase the discrimination power in each body fluid/tissue category.


Assuntos
Genética Forense/métodos , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/genética , Sangue , Muco do Colo Uterino , Feminino , Marcadores Genéticos , Humanos , Masculino , Menstruação , Polimorfismo de Nucleotídeo Único , Saliva , Sêmen , Pele/química
4.
Scand J Med Sci Sports ; 28(8): 1925-1933, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29668082

RESUMO

Exercise training reduces the side effects of cancer treatments; however, the stress hormone response to acute exercise during prostate cancer (PCa) treatment is unclear. The study purpose was to examine the effects of acute exercise on circulating cortisol, epinephrine (Epi), and norepinephrine (NE) concentrations during PCa treatment with and without androgen deprivation therapy (ADT). Men with PCa (n = 11), with PCa on ADT (n = 11), and with non-cancer controls (n = 8) had blood samples for stress hormones collected before and immediately (0 hour), 2 hours, and 24 hours after 45 minutes of intermittent cycling at 60% of peak wattage. NE increased by 385% (P < .001) at 0 hour and remained elevated at 2 hours (P < .05) with no group differences. Overall, cortisol significantly increased at 0 hour (36%, P < .012) and then significantly decreased below baseline at 2 hours (-24%, P < .001) before returning to resting levels at 24 hours. Cortisol levels during ADT were 32% lower than PCa (P = .006) with no differences vs controls. Epi increased immediately after exercise more in controls (817%, P < .001) than with ADT (700%) and PCa (333%) patients, and both cancer groups' absolute levels were attenuated relative to controls (ADT: -54%, PCa: -52%, P = .004). Compared with age-matched controls, PCa and ADT patients exhibited similar stress hormone responses with acute exercise for NE and cortisol but an attenuated EPI response that suggests altered adrenal function. Future studies should examine the physical stress of multiple exercise bouts to verify these findings and to explore the functional hormonal effects, such as immune and metabolic responses, during cancer treatment.


Assuntos
Epinefrina/sangue , Exercício Físico/fisiologia , Hidrocortisona/sangue , Norepinefrina/sangue , Neoplasias da Próstata/sangue , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Neoplasias da Próstata/tratamento farmacológico
5.
Forensic Sci Int Genet ; 34: 206-221, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29549744

RESUMO

The recovery of a DNA profile from the perpetrator or victim in criminal investigations can provide valuable 'source level' information for investigators. However, a DNA profile does not reveal the circumstances by which biological material was transferred. Some contextual information can be obtained by a determination of the tissue or fluid source of origin of the biological material as it is potentially indicative of some behavioral activity on behalf of the individual that resulted in its transfer from the body. Here, we sought to improve upon established RNA based methods for body fluid identification by developing a targeted multiplexed next generation mRNA sequencing assay comprising a panel of approximately equal sized gene amplicons. The multiplexed biomarker panel includes several highly specific gene targets with the necessary specificity to definitively identify most forensically relevant biological fluids and tissues (blood, semen, saliva, vaginal secretions, menstrual blood and skin). In developing the biomarker panel we evaluated 66 gene targets, with a progressive iteration of testing target combinations that exhibited optimal sensitivity and specificity using a training set of forensically relevant body fluid samples. The current assay comprises 33 targets: 6 blood, 6 semen, 6 saliva, 4 vaginal secretions, 5 menstrual blood and 6 skin markers. We demonstrate the sensitivity and specificity of the assay and the ability to identify body fluids in single source and admixed stains. A 16 sample blind test was carried out by one lab with samples provided by the other participating lab. The blinded lab correctly identified the body fluids present in 15 of the samples with the major component identified in the 16th. Various classification methods are being investigated to permit inference of the body fluid/tissue in dried physiological stains. These include the percentage of reads in a sample that are due to each of the 6 tissues/body fluids tested and inter-sample differential gene expression revealed by agglomerative hierarchical clustering.


Assuntos
Genética Forense/métodos , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise Química do Sangue , Muco do Colo Uterino/química , Feminino , Expressão Gênica , Humanos , Masculino , Menstruação , RNA Mensageiro/genética , Saliva/química , Sêmen/química , Sensibilidade e Especificidade , Pele/química
7.
Forensic Sci Int Genet ; 34: 105-115, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29453107

RESUMO

In a previous study we presented an assay for targeted mRNA sequencing for the identification of human body fluids, optimised for the Illumina MiSeq/FGx MPS platform. This assay, together with an additional in-house designed assay for the Ion Torrent PGM/S5 platform, was the basis for a collaborative exercise within 17 EUROFORGEN and EDNAP laboratories, in order to test the efficacy of targeted mRNA sequencing to identify body fluids. The task was to analyse the supplied dried body fluid stains and, optionally, participants' own bona fide or mock casework samples of human origin, according to specified protocols. The provided primer pools for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms included 33 and 29 body fluid specific targets, respectively, to identify blood, saliva, semen, vaginal secretion, menstrual blood and skin. The results demonstrated moderate to high count values in the body fluid or tissue of interest with little to no counts in non-target body fluids. There was some inter-laboratory variability in read counts, but overall the results of the laboratories were comparable in that highly expressed markers showed high read counts and less expressed markers showed lower counts. We performed a partial least squares (PLS) analysis on the data, where blood, menstrual blood, saliva and semen markers and samples clustered well. The results of this collaborative mRNA massively parallel sequencing (MPS) exercise support targeted mRNA sequencing as a reliable body fluid identification method that could be added to the repertoire of forensic MPS panels.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/metabolismo , Análise Química do Sangue , Muco do Colo Uterino/química , Feminino , Marcadores Genéticos , Humanos , Laboratórios , Análise dos Mínimos Quadrados , Masculino , Menstruação , Saliva/química , Sêmen/química , Pele/química
8.
Ultrasound Obstet Gynecol ; 47(6): 705-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26970114

RESUMO

OBJECTIVES: First, to examine in twin pregnancies the performance of first-trimester screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA testing of maternal blood and, second, to compare twin and singleton pregnancies regarding the distribution of fetal fraction of cfDNA and rate of failure to obtain a result. METHODS: This was a prospective study in 438 twin and 10 698 singleton pregnancies undergoing screening for fetal trisomies by cfDNA testing at 10 + 0 to 13 + 6 weeks' gestation. Chromosome-selective sequencing of cfDNA was used and, in twin pregnancies, an algorithm was applied that relies on the lower fetal fraction contributed by the two fetuses. Multivariate regression analysis was used to determine significant predictors of fetal fraction and a failed result. RESULTS: In twin pregnancies, the median fetal fraction was lower (8.0% (interquartile range (IQR), 6.0-10.4%) vs 11.0% (IQR, 8.3-14.4%); P < 0.0001) and failure rate after first sampling was higher (9.4% vs 2.9%; P < 0.0001) compared to in singletons. Multivariate logistic regression analysis demonstrated that the risk of test failure increased with increasing maternal age and body mass index and decreased with fetal crown-rump length. The risk was increased in women of South Asian racial origin and in pregnancies conceived by in-vitro fertilization (IVF). The main contributor to the higher rate of failure in twins was conception by IVF which was observed in 9.5% of singletons and 56.2% of twins. In the 417 twin pregnancies with a cfDNA result after first or second sampling, the detection rate was 100% (8/8) for trisomy 21 and 60% (3/5) for trisomies 18 or 13, at a false-positive rate (FPR) of 0.25% (1/404). In the 10 530 singleton pregnancies with a cfDNA result after first or second sampling, the detection rate was 98.7% (156/158) for trisomy 21 and 80.3% (49/61) for trisomies 18 or 13, at a FPR of 0.22% (23/10 311). CONCLUSIONS: In twin pregnancies undergoing first-trimester screening for trisomies by cfDNA testing, the fetal fraction is lower and failure rate higher compared to in singletons. The number of trisomic twin pregnancies examined was too small for an accurate assessment of performance of screening, but it may be similar to that in singleton pregnancies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
DNA/sangue , Gravidez de Gêmeos/sangue , Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico , Adulto , Sistema Livre de Células , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 21 , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sequência de DNA/métodos
9.
Space Sci Rev ; 204(1-4): 49-82, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29755144

RESUMO

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.

10.
Forensic Sci Int Genet ; 16: 139-147, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25600397

RESUMO

The European DNA profiling group (EDNAP) organized a sixth collaborative exercise on RNA/DNA co-analysis for body fluid/tissue identification and STR profiling. The task was to identify skin samples/contact traces using specific RNA biomarkers and test three housekeeping genes for their suitability as reference genes. Eight stains, a skin RNA dilution series and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 22 participating laboratories using RNA extraction or RNA/DNA co-extraction methods. Two sets of previously described skin-specific markers were used: skin1 pentaplex (LCE1C, LCE1D, LCE2D, IL1F7 and CCL27) and skin2 triplex (LOR, KRT9 and CDSN) in conjunction with a housekeeping gene, HKG, triplex (B2M, UBC and UCE). The laboratories used different chemistries and instrumentation. All laboratories were able to successfully isolate and detect mRNA in contact traces (e.g., human skin, palm-, hand- and fingerprints, clothing, car interiors, computer accessories and electronic devices). The simultaneous extraction of RNA and DNA provides an opportunity for positive identification of the tissue source of origin by mRNA profiling as well as a simultaneous identification of the body fluid donor by STR profiling. The skin markers LCE1C and LOR and the housekeeping gene marker B2M were detected in the majority of contact traces. Detection of the other markers was inconsistent, possibly due to the low amounts and/or poor quality of the genetic material present in shed skin cells. The results of this and the previous collaborative RNA exercises support RNA profiling as a reliable body fluid/tissue identification method that can easily be combined with current STR typing technology.


Assuntos
DNA/análise , Genética Forense , RNA/análise , Pele/química , Humanos
11.
Acta Psychiatr Scand ; 131(1): 51-60, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24954156

RESUMO

OBJECTIVE: This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL). METHOD: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out-patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow-up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring 'within-normal' QOL (within 10% of Q-LES-Q community norms) and those with 'severely impaired' QOL (>2 SD below Q-LES-Q community norms) were analyzed. RESULTS: Before treatment, no more than 3% of MDD patients experienced 'within-normal' QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving 'within-normal' QOL did not exceed 30%, with >50% of patients experiencing 'severely impaired' QOL. Although remitted patients had greater improvements compared with non-remitters, 32-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing 'within-normal' QOL show a statistically significant decrease in non-remitters. CONCLUSION: Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.


Assuntos
Transtorno Depressivo Maior/terapia , Qualidade de Vida/psicologia , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Terapia Combinada/métodos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
12.
Scand J Med Sci Sports ; 24(3): e148-55, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24118591

RESUMO

Peroxisome proliferator-activated receptor delta (PPARδ; encoded by the PPARD gene) plays a role in energy metabolism and mitochondrial function. We have investigated the distribution of PPARD rs2267668, rs2016520 and rs1053049 polymorphisms, individually and in haplotype, in a cohort of 660 elite athletes which was subdivided into four different groups based on the different metabolic demands of their respective sports and 704 healthy controls. PPARD rs2016529 and rs1053049 were individually associated with overall elite athletic performance (P = 0.00002; and P = 0.0002) and also with athletes grouped as strength endurance (P = 0.00008; and P = 0.0003). Furthermore, PPARD A/C/C haplotype (rs2267668/rs2016520/rs1053049) was significantly underrepresented in all athletes and each subgroup of athletes when compared with controls (P < 0.000001), suggesting that harboring this specific haplotype is unfavorable for becoming an elite athlete. These results help to identify which genetic profiles may contribute to elite athletic performance, specifically the role of variants within the PPARD gene, and may be useful in talent identification or optimizing the response to training.


Assuntos
Desempenho Atlético/fisiologia , Haplótipos , PPAR delta/genética , Resistência Física/genética , Adulto , Metabolismo Energético/genética , Feminino , Humanos , Masculino , Força Muscular/genética , Polimorfismo Genético , Adulto Jovem
13.
Forensic Sci Int Genet ; 8(1): 203-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24315610

RESUMO

The European DNA Profiling Group (EDNAP) organized a fourth and fifth collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling. The task was to identify dried menstrual blood and vaginal secretion stains using specific RNA biomarkers, and additionally test 3 housekeeping genes for their suitability as reference genes. Six menstrual blood and six vaginal secretion stains, two dilution series (1/4-1/64 pieces of a menstrual blood/vaginal swab) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 24 participating laboratories, using RNA extraction or RNA/DNA co-extraction methods. Two novel menstrual blood mRNA multiplexes were used: MMP triplex (MMP7, MMP10, MMP11) and MB triplex (MSX1, LEFTY2, SFRP4) in conjunction with a housekeeping gene triplex (B2M, UBC, UCE). Two novel mRNA multiplexes and a HBD1 singleplex were used for the identification of vaginal secretion: Vag triplex (MYOZ1, CYP2B7P1 and MUC4) and a Lactobacillus-specific Lacto triplex (Ljen, Lcris, Lgas). The laboratories used different chemistries and instrumentation and all were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA allowed for positive identification of the tissue/fluid source of origin by mRNA profiling as well as a simultaneous identification of the body fluid donor by STR profiling, also from old and compromised casework samples. The results of this and the previous collaborative RNA exercises support RNA profiling as a reliable body fluid identification method that can easily be combined with current STR typing technology.


Assuntos
Sangue , DNA/genética , Menstruação , RNA/genética , Vagina/metabolismo , Líquidos Corporais/metabolismo , Feminino , Humanos
14.
Placenta ; 34(6): 503-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23602336

RESUMO

INTRODUCTION: The fetus is dependent on the placenta for its supply of long chain polyunsaturated fatty acids (LCPUFA), which are essential in fetal growth and development. Previous work suggests that high maternal body mass index (BMI) inhibits fetal LCPUFA delivery and males have greater fatty acid requirements than females during development. We hypothesized that male placental fatty acid uptake would be more sensitive to maternal BMI compared to females. METHODS: Term placental samples were collected from healthy women receiving Cesarean section (n = 38). Placental fatty acid transporter and binding protein gene expression and uptake of oleic acid (OA), arachidonic acid, (AA) and docosahexanoic acid (DHA) were measured. Two-way ANOVA was used to assess the effects of fetal sex and maternal overweight/obesity (BMI >26 kg/m2). RESULTS: Placental fatty acid uptake of OA was 43% lower in male offspring and 73% higher in female offspring of obese compared to normal BMI women (P < 0.05). The interaction between fetal sex and maternal BMI had a significant effect on both OA (P = 0.002) and AA uptake (P = 0.01). DHA uptake was not affected by fetal sex or maternal obesity. Placental fatty acid transporter CD36 and binding protein FABP5 gene expression levels were lower in male offspring of obese mothers but were not affected by BMI among females. CONCLUSION: Maternal obesity and fetal sex significantly affect the placental uptake of oleate and arachidonate. Placental fatty acid uptake in both male and female fetuses is sensitive to maternal BMI, but males may have inadequate acquisition of the unsaturated fatty acid OA, when exposed to maternal obesity.


Assuntos
Feto/metabolismo , Obesidade/metabolismo , Ácido Oleico/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Ácido Araquidônico/metabolismo , Índice de Massa Corporal , Antígenos CD36/genética , Cesárea , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Expressão Gênica , Humanos , Masculino , Obesidade/complicações , Gravidez , Fatores Sexuais
15.
Forensic Sci Int Genet ; 7(2): 230-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23165093

RESUMO

A third collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 µl saliva, 5-0.01 µl semen) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 20 participating laboratories using an RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2, PSA, SEMG1 and TGM4). The laboratories used different chemistries and instrumentation and a majority (16/20) were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from individual stains not only permitted a confirmation of the presence of saliva/semen (i.e. tissue/fluid source of origin), but allowed an STR profile of the stain donor to be obtained as well. The method proved to be reproducible and sensitive, with as little as 0.05 µl saliva or semen, using different analysis strategies. Additionally, we demonstrated the ability to positively identify the presence of saliva and semen, as well as obtain high quality DNA profiles, from old and compromised casework samples. The results of this collaborative exercise involving an RNA/DNA co-extraction strategy support the potential use of an mRNA based system for the identification of saliva and semen in forensic casework that is compatible with current DNA analysis methodologies.


Assuntos
DNA/análise , RNA/análise , Saliva/química , Sêmen/química , DNA/genética , Eletroforese Capilar , Humanos , Reação em Cadeia da Polimerase , RNA/genética
16.
J Thromb Haemost ; 10(5): 848-56, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22409238

RESUMO

BACKGROUND: Factor VII-activating protease (FSAP) is a recently discovered plasma protease with a role in the regulation of hemostasis and vascular remodeling processes. Higher levels and activity of FSAP have been reported in patients with deep vein thrombosis, but there are no data on plasma FSAP in ischemic stroke (IS). OBJECTIVE: To investigate whether FSAP antigen levels and activity are associated with IS and/or etiologic subtypes of IS. PATIENTS AND METHODS: To assess the potential association between FSAP and IS, plasma FSAP antigen levels and activity were measured in 600 consecutive IS patients and 600 population-based controls from the case-control study the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Blood sampling was performed in the acute phase and 3 months after the index stroke. FSAP was also investigated at the genetic level by genotyping of 33 single-nucleotide polymorphisms. RESULTS: Increased FSAP antigen level and activity, at both time-points, were independently associated with IS. Subtype analysis revealed similar associations for both FSAP measures, at both time-points, in all main IS subtypes. FSAP genotypes showed association with both FSAP plasma measurements, but not with IS. CONCLUSIONS: Increased plasma FSAP antigen levels and activity were associated with IS and all main etiologic subtypes, suggesting a possible role for FSAP in the pathophysiology of IS, irrespective of the underlying etiology.


Assuntos
Isquemia Encefálica/enzimologia , Serina Endopeptidases/sangue , Acidente Vascular Cerebral/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Serina Endopeptidases/genética , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Suécia/epidemiologia , Regulação para Cima
17.
Forensic Sci Int Genet ; 6(5): 548-58, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22326111

RESUMO

In forensic casework analysis it is often necessary to attempt to obtain DNA profiles from microscopic amounts of biological material left behind by perpetrators of crime. The ability to obtain profiles from trace biological evidence is routinely demonstrated with so-called 'touch DNA' evidence, which is generally perceived to be the result of DNA obtained from shed skin cells transferred from donor to an object or person during physical contact. Although a genetic profile from trace biological evidence is routinely obtained, the tissue source of the profile is rarely known. This merely perpetuates the 'mystery' of the nature of 'touch DNA' evidence allowing the significance or meaningfulness of genetic profiles obtained from these samples to be challenged. Numerous reports state that the tissue source of origin of 'touch DNA' evidence cannot be determined due to the small amount of biological material present, while others conclude that the DNA profiles are obtained from shed skin cells (as opposed to, say, buccal epithelial cells present in saliva traces) without any scientific basis for this assertion. Proper identification of the biological material present might be crucial to the investigation and prosecution of a criminal offense and a misrepresentation of the nature of the evidence can have undue influence on the perception of the circumstance of the crime. Thus far, research has failed to provide forensic scientists with feasible, definitive methods to identify the tissue origin of 'touch DNA'. In the present work, we sought to identify novel highly specific and sensitive messenger RNA (mRNA) biomarkers for the identification of skin. Gene candidates were identified using both literature searches and whole transcriptome deep sequencing (RNA-Seq). Utilizing this dual approach, we identified and evaluated over 100 gene candidates. Five mRNA markers were identified that demonstrated a high degree of specificity for skin. Using these markers, we have been able to successfully detect and identify skin using as little as 5-25 pg of input total RNA from skin and, significantly, in swabs of human skin and various touched objects. One of the markers, LCE1C, is particularly highly sensitive and was detected in the majority of skin samples tested including touched objects. We have been successful in incorporating the five skin biomarkers into two multiplex systems. Although further work is needed to optimize the assay for routine casework, the initial studies demonstrate that a molecular-based characterization of the biological material recovered from touch samples is possible.


Assuntos
Biomarcadores/metabolismo , DNA/genética , Genética Forense , RNA Mensageiro/genética , Pele/metabolismo , Sequência de Bases , Primers do DNA , Humanos , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
18.
Forensic Sci Int Genet ; 6(1): 70-80, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21459062

RESUMO

A second collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Six human blood stains, two blood dilution series (5-0.001 µl blood) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by the participating laboratories using a RNA/DNA co-extraction or solely RNA extraction method. Two novel mRNA multiplexes were used for the identification of blood: a highly sensitive duplex (HBA, HBB) and a moderately sensitive pentaplex (ALAS2, CD3G, ANK1, SPTB and PBGD). The laboratories used different chemistries and instrumentation. All of the 18 participating laboratories were able to successfully isolate and detect mRNA in dried blood stains. Thirteen laboratories simultaneously extracted RNA and DNA from individual stains and were able to utilize mRNA profiling to confirm the presence of blood and to obtain autosomal STR profiles from the blood stain donors. The positive identification of blood and good quality DNA profiles were also obtained from old and compromised casework samples. The method proved to be reproducible and sensitive using different analysis strategies. The results of this collaborative exercise involving a RNA/DNA co-extraction strategy support the potential use of an mRNA based system for the identification of blood in forensic casework that is compatible with current DNA analysis methodology.


Assuntos
DNA/sangue , RNA/sangue , Comportamento Cooperativo , Humanos , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase
19.
J Phys Condens Matter ; 23(38): 386001, 2011 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-21891853

RESUMO

We report changes in the magnetic properties of hole-doped SCGO, SrCr8Ga4O19, induced by replacing non-magnetic Ga3+ with both non-magnetic (Mg2+ and Zn2+) and magnetic (Cu2+) cations. The resulting solid solutions, SrCr(8)Ga(4-x)M(x)O(19) (M = Zn, Mg, Cu) have been studied by x-ray diffraction and magnetic susceptibility measurements. For all cases, at least 10% of Ga can be replaced by divalent cations resulting in oxidation of ≥5% of the Cr3+ d3 to Cr4+ (d2). The hole doping results in an increase in ferromagnetic interactions and reduces the magnetic frustration. In the SrCr(8)Ga(4-x)Cu(x)O(19) series an enhancement of the spin-glass-like transition is observed, T(f)∼ 6 K, which we ascribe to the magnetic nature of the Cu2+ (d9) dopant.

20.
Clin Radiol ; 66(6): 566-74, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21371698

RESUMO

The availability of whole brain computed tomography (CT) perfusion has expanded the opportunities for analysing the haemodynamic parameters associated with varied neurological conditions. Examples demonstrating the clinical utility of whole-brain CT perfusion imaging in selected acute and chronic ischaemic arterial neurovascular conditions are presented. Whole-brain CT perfusion enables the detection and focused haemodynamic analyses of acute and chronic arterial conditions in the central nervous system without the limitation of partial anatomical coverage of the brain.


Assuntos
Angiografia Cerebral/métodos , Transtornos Cerebrovasculares/diagnóstico por imagem , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Protocolos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...