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Effective shelter has been demonstrated to reduce neonatal lamb mortality rates during periods of inclement weather. Periods of high wind speed and rainfall have been shown to influence shelter usage; however, it is not yet known how ewe factors such as breed, age and body condition score influence shelter-seeking behaviour. This study, conducted on a working upland farm in the UK, examined impact of artificial shelter on the biological and climatic factors that influence peri-parturient ewe behaviour. Pregnant ewes (n = 147) were randomly allocated between two adjacent fields which were selected for their similarity in size, topography, pasture management, orientation to the prevailing wind and available natural shelter. In one field, three additional artificial shelters were installed to increase the available shelter for ewes, this field was designated the Test field; no additional artificial shelter was provided in the second field which was used as the Control field. Individual ewes were observed every 2 h between 0800 and 1600 for 14 continuous days to monitor their location relative to shelter. Ewe breed (Aberfield and Highlander), age (2-8 years) and body condition score were considered as explanatory variables to explain flock and individual variance in shelter-seeking behaviour and the prevalence of issues which required the intervention of the shepherd, termed 'shepherding problems'. Any ewe observed with dystocia, a dead or poor vigour lamb or who exhibited mismothering behaviour was recorded as a shepherding problem. The prevalence of these shepherding problems which necessitate human intervention represents arguably the most critical limiting factor for the successful management of commercial sheep flocks in outdoor lambing systems. Overall, ewes in the Test field with access to additional artificial shelter experienced fewer shepherding problems than those in the Control field (P < 0.05). A significant breed effect was also observed, with Highlander ewes more likely to seek shelter than Aberfield ewes (P < 0.001), and experiencing significantly fewer shepherding interventions (P < 0.05). These findings demonstrate the substantial and significant benefits to animal welfare and productivity that can be achieved through the provision of shelter in commercial, upland, outdoor lambing systems in the UK.
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Cruzamento , Carneiro Doméstico , Animais , Feminino , Gravidez , Ovinos , Comportamento EspacialRESUMO
In late 2014, the first epigenome-wide association studies of DNA modifications in Alzheimer's disease brain samples were published. Over the last 5 years, further studies have been reported in the field and have highlighted consistent and robust alterations in DNA modifications in AD cortex. However, there are some caveats associated with the majority of studies undertaken to date; for example, they are predominantly restricted to profiling a limited number of loci, are principally focused on DNA methylation, are performed on bulk tissue at the end stage of disease and are restricted to nominating associations rather than demonstrating causal relationships. Consequently, the downstream interpretation of these studies is limited. Owing to recent advances in state-of-the-art cell profiling techniques, long-read genomic technologies and genetic engineering methodologies, identifying cell-type-specific causal epigenetic changes is becoming feasible. This review seeks to provide an overview of the last 5 years of epigenomic studies of DNA modifications in Alzheimer's disease brain samples and propose new avenues for future research.
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Doença de Alzheimer/genética , Encéfalo/metabolismo , DNA/metabolismo , Epigenoma/genética , Encéfalo/patologia , DNA/genética , Metilação de DNA/fisiologia , Epigênese Genética/genética , HumanosRESUMO
Adolescence is a sensitive period for the development of adaptive social behaviors and social anxiety, possibly due to aspects of brain development. However, research is needed to examine interactions among age, social anxiety, and social dynamics previously shown to influence neural responding. The current functional magnetic resonance imaging (fMRI) study examines brain function in 8-18 year-olds with varying levels of social anxiety. Interactions are examined among age, social anxiety, and two key task factors: valence and predictability of social interactions. Results demonstrate age, social anxiety severity, and each of the two key task-based factors interact to predict neural response in the caudate, middle and superior temporal gyri. In particular, among adolescents less-than 13 years of age, higher social anxiety predicted greater responding to unpredictable negative evaluations. However, in this same age group, the opposite pattern emerged during receipt of unpredictable positive evaluations, with less neural response in more anxious youth. Adolescents aged 13 and older overall showed less robust effects. We discuss these findings in terms of age- and anxiety-related differences in socioemotional processing.
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Relações Interpessoais , Comportamento Social , Adolescente , Fatores Etários , Criança , Feminino , Humanos , MasculinoRESUMO
Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.
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Transplante de Células-Tronco Hematopoéticas/métodos , Tumor de Wilms/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Tumor de Wilms/mortalidade , Adulto JovemRESUMO
Although single-center and cross-sectional studies have suggested a modest impact of liver donation on donor psychological well-being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0-3%), alcohol abuse (2-5%), and anxiety syndromes (2-3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well-being at various time points. We identified significant predictors for donors' perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data-driven follow-up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.
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Transtorno Depressivo Maior/psicologia , Transplante de Fígado/psicologia , Doadores Vivos/psicologia , Qualidade de Vida , Adulto , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.
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Transplante de Fígado , Doadores Vivos/psicologia , Fatores Socioeconômicos , Obtenção de Tecidos e Órgãos/economia , Adulto , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Apoio Social , Inquéritos e QuestionáriosRESUMO
Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12-45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.
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Hormônio Liberador de Gonadotropina/agonistas , Transplante de Células-Tronco Hematopoéticas/métodos , Leuprolida/uso terapêutico , Ovário/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Criança , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Agonistas Mieloablativos , Testes de Função Ovariana , Ovário/fisiologia , Projetos Piloto , Adulto JovemRESUMO
The purpose of this study was to explore long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). We analyzed 471 DDLTs and 565 LDLTs from 1998 to 2010 that were followed up to 10 years for 36 categories of complications. Probabilities of complications and their resolutions were estimated using the Kaplan-Meier method, and predictors were tested in Cox proportional hazards models. Median follow-up for DDLT and LDLT was 4.19 and 4.80 years, respectively. DDLT recipients were more likely to have hepatocellular carcinoma and higher disease severity, including Model for End-Stage Liver Disease score. Complications occurring with higher probability in LDLT included biliary-related complications and hepatic artery thrombosis. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and pulmonary edema were significantly more probable. Development of chronic kidney disease stage 4 or 5 was less likely in LDLT recipients (hazard ratio [HR] 0.41, p = 0.02). DDLT and LDLT had similar risk of grade 4 complications (HR 0.89, p = 0.60), adjusted for other risk factors. Once a complication occurred, the time to resolution did not differ between LDLT and DDLT. Future efforts should be directed toward reducing the occurrence of complications after liver transplantation.
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Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Complicações Pós-Operatórias , Adulto , Cadáver , Feminino , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , TransplantadosRESUMO
The two aspects of a scanning tunneling microscopy tip, the macroscopic profile and the nanoscale apex, can be tailored by controlling the tension during electrochemical etching and the solution-electrode contact area via acetone vapor. The apex diameter is shown to be proportional to the square root of the tension, and is demonstrated over apex diameters of 150-500 nm. The apex was found to be created in four distinct shapes where a secondary etching can reshape the tip into a single geometry. Improvement in tip height and stability of the profile are demonstrated versus a non-acetone fabrication control.
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OBJECTIVE: The relationship between obesity and suicidal ideation and behavior (suicidality) is not well understood, and conventional suicide risk factors do not adequately explain the associations observed. Thus, the current study aimed to further examine the relationship between body mass index (BMI; kg m(-2)) and suicidal ideation as well as potential mechanisms of this relationship. METHODS: Two hundred seventy-one adults (n=151 undergraduates; n=120 obesity treatment participants) completed self-report questionnaires assessing relevant variables, including suicidal ideation, perceived burdensomeness, thwarted belongingness and current height/weight used to calculate BMI. RESULTS: There was a significant, quadratic relationship between BMI and suicidal ideation (b=0.001, t=2.21, P=0.03, partial r=0.14) and between BMI and perceived burdensomeness (b=0.003, t=2.50, P=0.013, partial r=0.16), such that as BMI increased, these positive associations became more pronounced. Additionally, perceived burdensomeness partially mediated the relationship between BMI and suicidal ideation. CONCLUSIONS: Individuals with a higher BMI demonstrated increased suicidal ideation as well as greater feelings of perceived burdensomeness. These results provide novel information regarding potential mechanisms explaining the obesity-suicidal ideation association.
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Obesidade/psicologia , Ideação Suicida , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Fatores de Risco , Autoimagem , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION AND HYPOTHESIS: The objective of the study was to identify reasons why women declined participation in a pilot randomised controlled trial (RCT) comparing tension-free vaginal tape (TVT) under general anaesthetic (GA) with single incision sling (SIS) under local anaesthetic (LA). These data would inform the design of a larger trial to improve patient recruitment. METHODS: This was a qualitative interview study on women eligible to have a TVT for stress urinary incontinence in a tertiary referral hospital in the UK. Women were counselled in a standardised manner. They were informed that the short-term success rates were similar for both operations. Women who declined to take part in the RCT were interviewed using a topic guide. Themes and sub-themes on non-participation were identified by two independent observers using a constant comparison method. RESULTS: Twenty-three non-participants of the RCT were interviewed. Common themes for non-participation were a preference for TVT and request for GA. Sub-themes showed that the TVT was preferred due to its perceived better efficacy as well as a minimal benefit from a SIS and also an unwillingness to take unknown risks. GA was favoured due to fear of local awareness, past negative experiences and embarrassment. Additional tests and follow-up visits were not cited as a reason for non-participation. CONCLUSIONS: The study found that non-participants are not research averse in general but they had strong preferences about specific aspects of treatment. Risk propensity and personality may also influence this behaviour. The study also demonstrates how a qualitative pilot study may improve trial design.
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Participação do Paciente/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Anestesia Geral , Anestesia Local , Feminino , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Medição de Risco , Centros de Atenção Terciária , Reino UnidoRESUMO
Bulkamid is a periurethral bulking agent used to treat stress urinary incontinence (SUI). Manufacturers describe it as nontoxic, nonbiodegradable and biocompatible. Periurethral abscesses are one of the known complications of bulking agents. We present the first reported case of periurethral abscess following Bulkamid injection. The woman had previously had a transobturator tape (TOT) and total vaginal mesh repair. At 6 weeks after injection of the bulking agent, she reported 100 % cure of her SUI. Transperineal ultrasound was used to diagnose and monitor an abscess that developed anterior and lateral to the urethra and separate from the TOT. Magnetic resonance imaging was helpful in delineating the extent of the abscess into the retropubic space but was not able to identify the urethra or the TOT. Surgical drainage of the abscess was performed vaginally, resulting in successful resolution of pain but recurrence of incontinence.
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Abscesso/induzido quimicamente , Resinas Acrílicas/efeitos adversos , Resinas Acrílicas/uso terapêutico , Hidrogéis/efeitos adversos , Hidrogéis/uso terapêutico , Doenças Uretrais/induzido quimicamente , Incontinência Urinária por Estresse/tratamento farmacológico , Abscesso/patologia , Abscesso/cirurgia , Resinas Acrílicas/administração & dosagem , Idoso , Drenagem/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Hidrogéis/administração & dosagem , Injeções , Imageamento por Ressonância Magnética , Recidiva , Resultado do Tratamento , Doenças Uretrais/patologia , Doenças Uretrais/cirurgia , Incontinência Urinária por Estresse/epidemiologiaRESUMO
We use a combination of low temperature, high field magnetic circular dichroism, absorption, and emission spectroscopy with relativistic time-dependent density functional calculations to reveal a subtle interplay between the effects of chemical substitution and spin-orbit coupling (SOC) in a family of iridium(III) complexes. Fluorination at the ortho and para positions of the phenyl group of fac-tris(1-methyl-5-phenyl-3-n-propyl-[1,2,4]triazolyl)iridium(III) cause changes that are independent of whether the other position is fluorinated or protonated. This is demonstrated by a simple linear relationship found for a range of measured and calculated properties of these complexes. Further, we show that the phosphorescent radiative rate, k(r), is determined by the degree to which SOC is able to hybridize T(1) to S(3) and that k(r) is proportional to the inverse fourth power of the energy gap between these excitations. We show that fluorination in the para position leads to a much larger increase of the energy gap than fluorination at the ortho position. Theory is used to trace this back to the fact that fluorination at the para position increases the difference in electron density between the phenyl and triazolyl groups, which distorts the complex further from octahedral symmetry, and increases the energy separation between the highest occupied molecular orbital (HOMO) and the HOMO-1. This provides a new design criterion for phosphorescent iridium(III) complexes for organic optoelectronic applications. In contrast, the nonradiative rate is greatly enhanced by fluorination at the ortho position. This may be connected to a significant redistribution of spectral weight. We also show that the lowest energy excitation, 1A, has almost no oscillator strength; therefore, the second lowest excitation, 2E, is the dominant emissive state at room temperature. Nevertheless the mirror image rule between absorption and emission is obeyed, as 2E is responsible for both absorption and emission at all but very low (<10 K) temperatures.
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Associating quantitative genetic traits with quantitative behaviors is a relatively unexplored region of sensory neurobiology. The visual system is an ideal place to test models associating these levels of sensory perception. In this study, we reared cichlid fish from Lake Malawi in different ambient light environments. We then tested the visual sensitivities of these fish using the optomotor response (OMR) behavioral paradigm and measured the relative expression of cone opsin genes. We found that the light environment experienced by fish during development can alter gene expression, particularly as it applies to the long wavelength-sensitive (LWS) opsin gene. Also, fish from different rearing conditions exhibited different behavioral sensitivities. We combined these data with predictions of opsin pigment absorption by the different OMR stimuli to determine which cone types are most likely to influence the OMR behavior. While we hypothesized that this behavior would be controlled by a random-wiring model reflecting the expression of both medium wavelength-sensitive (MWS) and LWS opsins, our models suggest that only the LWS pigment is required to predict behavior. Furthermore, analyses show that LWS expression variation accounts for ~20% of the observed behavioral variance. This work confirms that sensory gene expression influences behavior in a predictable fashion. It also suggests that the neural wiring of basal visual pathways in cichlid fish may differ from that observed in mammals and zebrafish, but is similar to that described in goldfish. This finding has important implications for the evolution of the magnocellular neural pathway in teleosts.
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Ciclídeos/genética , Opsinas dos Cones/genética , Atividade Motora/genética , Percepção Visual/genética , Animais , Comportamento Animal/fisiologia , Ciclídeos/metabolismo , Opsinas dos Cones/metabolismo , Meio Ambiente , Expressão Gênica , Estimulação Luminosa , Locos de Características Quantitativas , Limiar Sensorial/fisiologiaRESUMO
Gaining a complete and comprehensive understanding of lung cancer nodule histological compositions and how these tissues are represented in radiological data is important not only for expanding the current knowledge base of cancer growth and development but also has potential implications for classification standards, radiological diagnosis methods and for the evaluation of treatment response. In this study we generate large scale histological segmentations of the cancerous and non-cancerous tissues within resected lung nodules. We have implemented a processing pipeline which allows for the direct correlation between histological data and spatially corresponding computed tomography data. Utilizing these correlated datasets we evaluated the statistical separation between Hounsfield Unit (HU) histogram values for each tissue type. The findings of this study revealed that lung cancer nodules contain a complex intermixing of cellular tissue types and that trends exist in the relationship between these tissue types. It was found that the mean Hounsfield Unit values for isolated lung cancer nodules imaged with computed tomography, had statistically significantly different values for non-solid bronchoalveolar carcinoma, solid cancerous tumor, blood, and inactive fibrotic stromal tissue.
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Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/patologia , Nódulo Pulmonar Solitário/diagnóstico , Tomografia Computadorizada por Raios X , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Adenocarcinoma/cirurgia , Bioestatística , Tecido Conjuntivo/diagnóstico por imagem , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Diagnóstico por Computador , Diagnóstico Diferencial , Fibrose , Ensaios de Triagem em Larga Escala , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/fisiopatologia , Nódulo Pulmonar Solitário/cirurgia , Estatística como Assunto , Carga TumoralRESUMO
Little is known about serum vitamin D levels following hematopoietic cell transplantation (HCT). Patients are instructed to avoid sun exposure because of an increased risk of skin cancers. Altered gastrointestinal absorptive capacity as a result of GVHD, bile acid or pancreatic enzyme insufficiency or bacterial overgrowth may lead to difficulty in absorbing the fat-soluble vitamin D. This study was undertaken to determine the prevalence of serum 25-hydroxyvitamin D (25(OH)D) deficiency, and factors associated with 25(OH)D deficiency, among children and adults who were at least 1 year following HCT. A total of 95 participants (54 males and 41 females) completed a questionnaire on usual diet and lifestyle, and provided a blood sample for 25(OH)D determinations between November 2008 and July 2009. The majority of participants had serum 25(OH)D levels ≥75 nmol/L (n=62, 65%), 23 had insufficient levels (50-75 nmol/L) and 10 participants were deficient (<50 nmol/L). The majority of participants reported regular use of vitamin D supplements (n=58, 61%). Prednisone use was significantly inversely associated with serum 25(OH)D concentrations. Total vitamin D intake was the strongest single predictor of 25(OH)D concentrations. These findings suggest that 400-600 IU vitamin D per day appears to be required to achieve optimal serum 25(OH)D concentrations following HCT.
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Transplante de Medula Óssea/efeitos adversos , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/efeitos adversos , Luz Solar , Sobreviventes , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
Pulmonary cytolytic thrombi (PCT) is an uncommon complication after hematopoietic cell transplantation. Although the pathogenesis is unknown, patients typically respond to systemic corticosteroid treatment. Considering corticosteroids may impair GVL reactions, we reviewed the records of 324 pediatric patients who received a transplant for leukemia and compared the outcomes of those with PCT (n=14) to those without PCT (n=310). PCT patients had a significantly more acute GVHD (aGVHD) and chronic GVHD (cGVHD). Though 3-year non-relapse mortality and OS were similar, there was significantly less relapse in patients with PCT compared to those without PCT (0 vs 28%, P=0.02), regardless of the presence or absence of aGVHD. In multivariate analysis, grade II-IV aGVHD (P=0.02), cGVHD (P=0.01) and development of PCT (P<0.01) were independently associated with less relapse. These data suggest that patients with PCT are at greater risk for GVHD, but at lower risk of leukemia relapse.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/patologia , Leucemia/cirurgia , Embolia Pulmonar/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Leucemia/sangue , Masculino , Análise Multivariada , Embolia Pulmonar/patologia , Recidiva , Resultado do TratamentoRESUMO
Large registry studies have shown superior disease-free survival (DFS) with matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT) over chemotherapy alone for patients with B-precursor acute lymphoblastic leukemia (ALL) and a late BM relapse. As most of these patients will not have an MSD, the decision to pursue an unrelated allo-HCT in second remission (CR2) or await a future relapse and perform HCT in third remission (CR3) continues to be debated. Between 1990 and 2006, 41 children with relapsed B-precursor ALL received a myeloablative allo-HCT at the University of Minnesota. Graft sources consisted of matched related donor (n=11), matched unrelated donor (n=9), and unrelated umbilical cord blood (n=21). Before allo-HCT, 15 patients had an early relapse (<36 months from diagnosis) and 26 had an initial late relapse (î¶36 months from diagnosis). In all, 30 patients (73%) were in CR2 and 11 were in CR3 (27%) at time of allo-HCT. Five year OS/DFS were similar for patients with an early or late marrow relapse, but there was inferior DFS among late-relapse patients transplanted in CR3 compared with CR2 (30% vs 75%, P=0.04). These results suggest that allo-HCT should be pursued in children after a first marrow relapse, rather than waiting for subsequent recurrence.
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Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
Deworming horses with anthelmintics that have activity against encysted small strongyle larvae (L(3) and L(4)) is a common practice in parasite control programs. The two drugs currently available for this use are moxidectin (MOX) administered in a single dose of 0.4 mg/kg and fenbendazole (FBZ) given at the larvicidal dose (10mg/kg for 5 days). Here, we report the efficacy of MOX and the larvicidal dose of FBZ for reducing counts of strongyle-type eggs per gram of feces in naturally infected horses. Fecal egg counts (FECs) of 15 yearlings were observed following deworming. On day 0, 6 of the 15 yearlings were administered a larvicidal dose of FBZ; 14 days later, all 15 yearlings received MOX at a single dose of 0.4 mg/kg. Feces were collected on day 0 for pre-treatment egg counts. Feces were collected at weekly intervals thereafter during FEC observation periods. FECs of FBZ-treated horses were compared at day 0 and 14 days post-treatment. The difference in means pre- and post-treatment with FBZ was not statistically significant (p=0.65). On days 0 and 42 of the MOX treatment observation period the mean FEC of the yearlings that had not received the FBZ treatment did not differ significantly from that of the FBZ-treated yearlings. MOX was effective in reducing fecal egg counts to 0 EPG for 21 days. At day 35 all but 2 of the yearlings had some eggs present (range=4-361 EPG) and at day 42 all but 1 yearling had eggs present (range=3-432 EPG). At day 42 the group mean FEC reduction had fallen from 100% to 67%. Results of this study do not support the use of the larvicidal dose of FBZ for small strongyle control. Larger field studies will be needed to investigate whether egg reappearance periods are shortening for MOX-treated horses.
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Anti-Helmínticos/farmacologia , Fenbendazol/farmacologia , Infecções Equinas por Strongyloidea/parasitologia , Strongylus/crescimento & desenvolvimento , Animais , Fezes/parasitologia , Feminino , Cavalos , Macrolídeos/farmacologia , Masculino , Contagem de Ovos de Parasitas/veterinária , Infecções Equinas por Strongyloidea/prevenção & controle , Fatores de TempoRESUMO
Lung cancer nodules, particularly adenocarcinoma, contain a complex intermixing of cellular tissue types: incorporating cancer cells, fibroblastic stromal tissue, and inactive fibrosis. Quantitative proportions and distributions of the various tissue types may be insightful for understanding lung cancer growth, classification, and prognostic factors. However, current methods of histological assessment are qualitative and provide limited opportunity to systematically evaluate the relevance of lung nodule cellular heterogeneity. In this study we present both a manual and an automatic method for segmentation of tissue types in histological sections of resected human lung cancer nodules. A specialized staining approach incorporating immunohistochemistry with a modified Masson's Trichrome counterstain was employed to maximize color contrast in the tissue samples for automated segmentation. The developed, clustering-based, fully automated segmentation approach segments complete lung nodule cross-sectional histology slides in less than 1 min, compared to manual segmentation which requires multiple hours to complete. We found the accuracy of the automated approach to be comparable to that of the manual segmentation with the added advantages of improved time efficiency, removal of susceptibility to human error, and 100% repeatability.