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1.
Artigo em Inglês | MEDLINE | ID: mdl-38967895

RESUMO

To evaluate a convolutional neural network's performance (nnU-Net) in the assessment of vascular contours, calcification and PET tracer activity using Ga-68 DOTATATE PET/CT. Patients who underwent Ga-68 DOTATATE PET/CT imaging over a 12-month period for neuroendocrine investigation were included. Manual cardiac and aortic segmentations were performed by an experienced observer. Scans were randomly allocated in ratio 64:16:20 for training, validation and testing of the nnU-Net model. PET tracer uptake and calcium scoring were compared between segmentation methods and different observers. 116 patients (53.5% female) with a median age of 64.5 years (range 23-79) were included. There were strong, positive correlations between all segmentations (mostly r > 0.98). There were no significant differences between manual and AI segmentation of SUVmean for global cardiac (mean ± SD 0.71 ± 0.22 vs. 0.71 ± 0.22; mean diff 0.001 ± 0.008, p > 0.05), ascending aorta (mean ± SD 0.44 ± 0.14 vs. 0.44 ± 0.14; mean diff 0.002 ± 0.01, p > 0.05), aortic arch (mean ± SD 0.44 ± 0.10 vs. 0.43 ± 0.10; mean diff 0.008 ± 0.16, p > 0.05) and descending aorta (mean ± SD < 0.001; 0.58 ± 0.12 vs. 0.57 ± 0.12; mean diff 0.01 ± 0.03, p > 0.05) contours. There was excellent agreement between the majority of manual and AI segmentation measures (r ≥ 0.80) and in all vascular contour calcium scores. Compared with the manual segmentation approach, the CNN required a significantly lower workflow time. AI segmentation of vascular contours using nnU-Net resulted in very similar measures of PET tracer uptake and vascular calcification when compared to an experienced observer and significantly reduced workflow time.

2.
Domest Anim Endocrinol ; 84-85: 106807, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37364520

RESUMO

Progesterone (P4) has a pivotal role on female puberty attainment in most farm animals. However, there are no studies evaluating the effect of P4 treatment previously to boar exposure for puberty induction in gilts. Therefore, serum P4 concentration, estrus expression and reproductive performance after boar stimuli were evaluated in gilts intramuscularly treated with long-acting P4 before boar exposure. In Experiment I, prepubertal gilts received either 1 mL of saline (control) or intramuscular (I.M.) P4 treatment (150 mg, 300 mg or 600 mg; n = 6 per treatment). Serum P4 concentration for P4-treated gilts was greater than for control gilts for at least 8 d for P4300 and P4600 groups (P < 0.05), but greater until after 16 d only for those treated with 600 mg (P < 0.05). In Experiments II (prepubertal) and III (peripubertal), gilts received either saline (control) or 300 mg P4 I.M. and those showing estrus signs were artificially inseminated (AI), whereas gilts without estrus expression were culled. In prepubertal gilts (Exp. II), estrus expression rate did not differ (P < 0.05) for control (79.1%; n = 110) and P4-treated gilts (81.5%; n = 108). In peripubertal gilts (Exp. III), although estrus expression did not differ between control (77.6%; n = 106) and P4-treated (69.6%; n = 102) gilts (P > 0.05), P4-treated gilts presented longer (23.1 ± 1.4 days) interval from treatment to estrus expression than control gilts (17.1 ± 1.3 days; P < 0.05). In Experiments II and III, the proportion of culled gilts with ovarian structures consistent with normal estrous cycles, farrowing rate, and litter size did not differ between treatments (P > 0.05). In conclusion, I.M. treatment with 300 or 600 mg of long-acting P4 was efficient in maintaining high P4 concentrations in prepubertal gilts for at least 8 days. However, P4 treatment over this time interval did not benefit the reproductive performance of prepubertal and peripubertal gilts.


Assuntos
Progesterona , Maturidade Sexual , Suínos , Feminino , Animais , Masculino , Sus scrofa , Estro , Ciclo Estral
3.
Climacteric ; 25(2): 147-154, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34668812

RESUMO

BACKGROUND: Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS: MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS: Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS: BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO: CRD42020141644.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Gravidez , Fatores de Risco
4.
Int J Behav Med ; 29(5): 597-609, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34932202

RESUMO

BACKGROUND: Based on promising effects seen in a pilot study evaluating a generic mindfulness-based program for migraine, we developed a migraine-specific adaptation of the Mindfulness-Based Cognitive Therapy (MBCT) program. The aim of this study was to evaluate this program for feasibility and effectiveness in a randomized controlled trial. METHOD: Fifty-four patients suffering from migraine were randomly allocated to either waitlist or the adapted MBCT. Outcomes were migraine-related parameters as well as variables of psychological functioning and coping. Assessment took place at baseline and post-intervention, for the intervention group also at follow-up (7 months). The effects of the intervention were analyzed by the use of ANCOVAs and linear mixed models. RESULTS: With respect to migraine parameters we did not find a significant group difference in the primary outcome (headache-related impairment), but the intervention resulted in a significant reduction of headache frequency (p = .04). In the analysis of secondary outcomes, MBCT showed superiority in four out of eight psychological parameters (perceived stress, anxiety, rumination, catastrophizing) with small to medium effect sizes. The intervention proved to be feasible and participants reported high degrees of contentment and achievement of personal goals. CONCLUSIONS: The migraine-specific MBCT program did not result in improvements with regard to headache-related impairment but showed a reduction in headache frequency as well as improved psychological functioning in secondary outcomes. TRIAL REGISTRATION: This trial was registered in the German Trial Registry "Deutsches Register Klinischer Studien" (ID: DRKS00007477), which is a WHO-listed primary trial register.


Assuntos
Terapia Cognitivo-Comportamental , Transtornos de Enxaqueca , Atenção Plena , Terapia Cognitivo-Comportamental/métodos , Cefaleia , Humanos , Transtornos de Enxaqueca/terapia , Atenção Plena/métodos , Projetos Piloto , Resultado do Tratamento
5.
Am J Otolaryngol ; 42(5): 103146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34171529

RESUMO

PURPOSE: 30-day hospital readmissions after head and neck cancer surgery continue to be a significant source of patient harm and healthcare expenditure. While there is substantial data in the literature assessing predictive factors for readmissions after head and neck cancer surgery, there are a paucity of studies which attempt to understand if such readmissions are preventable. The goal of this paper is to determine factors associated with 30-day hospital readmissions after head and neck cancer surgery and to understand if these readmissions were preventable. MATERIALS AND METHODS: Retrospective review from a single academic tertiary care center. Patients readmitted within 30 days after undergoing surgery for cancers of the head and neck between 2015 and 2018 were identified. RESULTS: Over a 3-year period, 26 patients undergoing resection with or without reconstruction of head and neck cancers were readmitted to the hospital within 30 days of discharge. There were 15 (58%) men and 11 (42%) women with a mean age of 68 years (SD 14 years). Twenty-one (81%) patients had squamous cell carcinoma and 13 (50%) had a primary site in the oral cavity. Thirteen (50%) had undergone free or regional flap reconstruction. The indication for readmission was related to the surgical wound in 19 (73%) and to medical complications in 7 (27%). Each case was categorized as "possibly preventable" versus "uncertain if preventable" based on whether a reasonable and feasible change in management may have prevented readmission. Six (23%) readmissions were deemed possibly preventable. Four were related to the surgical wound where initial free or regional flaps may have prevented complication. Two were medical complications that may have benefited from longer inpatient observation. CONCLUSIONS: For a subset of patients readmitted within 30 days of head and neck cancer surgery, a reasonable and feasible change in management may have prevented their hospital readmission. The significance of better understanding this patient population is underscored by the high mortality rate.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Readmissão do Paciente , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Previsões , Gastos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Readmissão do Paciente/economia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Infecção da Ferida Cirúrgica/prevenção & controle
6.
Environ Toxicol Chem ; 40(7): 1861-1872, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33661534

RESUMO

Nanomaterials (NMs) are thermodynamically unstable by nature, and exposure of soil organisms to NMs in the terrestrial environment cannot be assumed constant. Thus, steady-state conditions may not apply to NMs, and bioaccumulation modeling for uptake should follow a dynamic approach. The one-compartment model allows the uptake and elimination of a chemical to be determined, while also permitting changes in exposure and growth to be taken into account. The aim of the present study was to investigate the accumulation of Ag from different Ag NM types (20 nm Ag0 NMs, 50 nm Ag0 NMs, and 25 nm Ag2 S NMs) in the crop plant wheat (Triticum aestivum). Seeds were emerged in contaminated soils (3 or 10 mg Ag/kg dry soil, nominal) and plants grown for up to 42 d postemergence. Plant roots and shoots were collected after 1, 7, 14, 21, and 42 d postemergence; and total Ag was measured. Soil porewater Ag concentrations were also measured at each sampling time. Using the plant growth rates in the different treatments and the changing porewater concentrations as parameters, the one-compartment model was used to estimate the uptake and elimination of Ag from the plant tissues. The best fit of the model to the data included growth rate and porewater concentration decline, while showing elimination of Ag to be close to zero. Uptake was highest for Ag0 NMs, and size did not influence their uptake rates. Accumulation of Ag from Ag2 S NMs was lower, as reflected by the lower porewater concentrations. Environ Toxicol Chem 2021;40:1861-1872. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Assuntos
Nanoestruturas , Poluentes do Solo , Bioacumulação , Cinética , Plantas , Solo/química , Poluentes do Solo/análise
8.
Eur Arch Psychiatry Clin Neurosci ; 270(5): 533-539, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30542819

RESUMO

Resilience is defined as the psychological resistance which enables the processing of stress and adverse life events and thus constitutes a key factor for the genesis of psychiatric illness. However, little is known about the morphological correlates of resilience in the human brain. Hence, the aim of this study is to examine the neuroanatomical expression of resilience in healthy individuals. 151 healthy subjects were recruited and had to complete a resilience-specific questionnaire (RS-11). All of them underwent a high-resolution T1-weighted MRI in a 3T scanner. Fine-grained cortical thickness was analyzed using FreeSurfer. We found a significant positive correlation between the individual extent of resilience and cortical thickness in a right hemispherical cluster incorporating the lateral occipital cortex, the fusiform gyrus, the inferior parietal cortex as well as the middle and inferior temporal cortex, i.e., a reduced resilience is associated with a decreased cortical thickness in these areas. We lend novel evidence for a direct linkage between psychometric resilience and local cortical thickness. Our findings in a sample of healthy individuals show that a lower resilience is associated with a lower cortical thickness in anatomical areas are known to be involved in the processing of emotional visual input. These regions have been demonstrated to play a role in the pathogenesis of stress and trauma-associated disorders. It can thus be assumed that neuroanatomical variations in these cortical regions might modulate the susceptibility for the development of stress-related disorders.


Assuntos
Córtex Cerebral/anatomia & histologia , Resiliência Psicológica , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Cortex ; 117: 147-156, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30978565

RESUMO

There is growing evidence for structural brain alterations in obsessive-compulsive disorder (OCD). The overall picture is however rather heterogeneous. To detect meaningful associations between clinical symptom profiles and structural alterations, we applied a classification approach, the k-means cluster analysis on clinical data, i.e., the Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire. 73 OCD patients were assigned to three distinct symptom profiles. Using structural MRI and surface-based morphometric analysis (SBM), we compared cortical thickness between all OCD patients and 69 matched healthy subjects as well as among patients according to three symptom profiles. The total sample of OCD patients exhibited a thicker cortex in the pre-supplementary motor cortex (pre-SMA), dorsomedial prefrontal (DMPFC), anterior cingulate cortex and in the right anterior insula. Comparing patients of the three symptom clusters, a subgroup of OCD patients with a specific symptom profile was identified, which showed a thicker cortex in pre-SMA/DMPFC and in the contralateral primary motor cortex. In contrast to both other subgroups, patients in this group were mainly characterized by the predominance of a combination of checking and washing rituals. The other two OCD symptom subgroups showed comparable cortical thickness to healthy controls. Higher cortical thickness in regions of the motor circuitry seems to be related to motor activity-induced neuroplasticity in a specific group of OCD patients. Thicker anterior insular cortex in the total sample of patients points toward a more general pathophysiological process in OCD and potentially indicates abnormal interoceptive processing in OCD.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Comportamento Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Tamanho do Órgão/fisiologia , Adulto Jovem
10.
Chem Sci ; 10(9): 2687-2692, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30996985

RESUMO

Among many cellular functions, inositol pyrophosphates (PP-InsPs) are metabolic messengers involved in the regulation of glucose uptake, insulin sensitivity, and weight gain. However, their mechanisms of action are still poorly understood. So far, the influence of PP-InsPs on cellular metabolism has been studied by overexpression or knockout/inhibition of relevant metabolizing kinases (IP6Ks, PPIP5Ks). These approaches are, inter alia, limited by time-resolution and potential compensation mechanisms. Here, we describe the synthesis of cell-permeant caged PP-InsPs as tools to rapidly modulate intracellular levels of defined isomers of PP-InsPs in a genetically non-perturbed cellular environment. We show that caged prometabolites readily enter live cells where they are enzymatically converted into still inactive, metabolically stable, photocaged PP-InsPs. Upon light-triggered release of 5-PP-InsP5, the major cellular inositol pyrophosphate, oscillations of intracellular Ca2+ levels in MIN6 cells were transiently reduced to spontaneously recover again. In contrast, uncaging of 1-PP-InsP5, a minor cellular isomer, was without effect. These results provide evidence that PP-InsPs play an active role in regulating [Ca2+]i oscillations, a key element in triggering exocytosis and secretion in ß-cells.

11.
Oper Dent ; 44(1): 65-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29570025

RESUMO

In this laboratory study, a composite resin was stained to a visibly discernible level using both coffee and red wine over 14 days (change was considered clinically noticeable and significant when ΔEab*≥2.7). Color change was measured at one, three, seven, and 14 days of staining. Although the nature of color change was different for the two staining solutions, the overall degree of staining (ΔEab*) rendered by either coffee or wine at each time interval was not significantly different ( p≥0.05). Four whitening protocols were applied to stained composites. Treatment included applications of distilled water (control), Crest Pro-Health [HD] toothpaste, Crest Whitestrips, Opalescence PF bleach (15%), and application of a fine pumice polishing (Preppies). HD toothpaste and Whitestrips were applied daily for 21 days, Opalescence was applied daily for 10 days, and polishing was applied once. Each of the whitening products, applied in a manner simulating at-home or in-office treatment, was effective in producing color improvements (lightening) over controls ( p<0.05), but none of the four treatments produced lightening that was significantly different from the other treatments ( p≥0.05). A comparison of final composite color with that measured at baseline showed that Opalescence returned composite color to an acceptable level following exposure to both staining solutions (ΔEab*<2.7), Whitestrips returned color close to baseline for wine-stained composites, and HD paste and polishing permitted residual stain to remain (ΔEab*≥2.7).


Assuntos
Resinas Compostas/química , Clareadores Dentários/química , Clareamento Dental/métodos , Café , Polimento Dentário/métodos , Dentifrícios , Peróxido de Hidrogênio , Teste de Materiais , Silicatos , Propriedades de Superfície , Vinho
12.
Clin Transl Oncol ; 21(5): 630-635, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30361796

RESUMO

BACKGROUND AND AIM: Ototoxicity is a potential adverse effect of chemotherapy with platin drugs, such as cisplatin and carboplatin, in children. Hearing loss (HL) affecting frequencies below 4 kHz can compromise speech perception. The aim of this study was to investigate whether genetic variants previously implicated in ototoxicity are associated with HL overall and HL below 4 kHz in pediatric oncology patients treated with cisplatin or carboplatin. MATERIALS AND METHODS: Patients given cisplatin or carboplatin for a pediatric cancer at least 5 years prior to the start of the study were enrolled. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GJB2 c.35delG, GSTP1 c.313A>G, and MT-RNR1 m.1555A>G polymorphisms. RESULTS: HL was identified in 31/61 patients (50.8%), including 28/42 treated with cisplatin (66.6%) and 3/19 treated with carboplatin (15.8%). HL was associated with higher mean doses of cisplatin (p = .002) and carboplatin (p = .010). The c.313A>G variant of GSTP1 (heterozygous or homozygous) was detected in 31/61 patients (50.8%). An association between this variant allele and HL involving frequencies ≤ 4 kHz was identified (p = .020; 10-fold vs. non-carriers). No associations with HL were observed for GJB2 or MT-RNR1 gene variants. CONCLUSION: The GSTP1 c.313A>G variant may increase the risk of low-frequency HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Glutationa S-Transferase pi/genética , Perda Auditiva/genética , Neoplasias/tratamento farmacológico , Polimorfismo Genético , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Feminino , Seguimentos , Perda Auditiva/induzido quimicamente , Perda Auditiva/patologia , Humanos , Masculino , Neoplasias/patologia , Prognóstico , Estudos Prospectivos
14.
Eur Arch Psychiatry Clin Neurosci ; 267(6): 579-584, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28386766

RESUMO

The personality trait neuroticism has been identified as a vulnerability factor for common psychiatric diseases and defining potential neuroanatomical markers for early recognition and prevention strategies is mandatory. Because both personality traits and cortical folding patterns are early imprinted and timely stable there is reason to hypothesize an association between neuroticism and cortical folding. Thus, to identify a putative linkage, we tested whether the degree of neuroticism is associated with local cortical folding in a sample of 109 healthy individuals using a surface-based MRI approach. Based on previous findings we additionally tested for a potential association with cortical thickness. We found a highly significant negative correlation between the degree of neuroticism and local cortical folding of the left dorsolateral prefrontal cortex (DLPFC), i.e., high levels of neuroticism were associated with low cortical folding of the left DLPFC. No association was found with cortical thickness. The present study is the first to describe a linkage between the extent of local cortical folding and the individual degree of neuroticism in healthy subjects. Because neuroticism is a vulnerability factor for common psychiatric diseases such as depression our finding indicates that alterations of DLPFC might constitute a neurobiological marker elevating risk for psychiatric burden.


Assuntos
Imageamento por Ressonância Magnética/métodos , Personalidade/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Adulto , Feminino , Humanos , Masculino , Neuroticismo , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
15.
Psychiatry Res Neuroimaging ; 261: 91-95, 2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28171781

RESUMO

The neuronal underpinnings of cortical folding alterations in schizophrenia remain unclear. Theories on the physiological development of cortical folds stress the importance of white matter fibers for this process and disturbances of fiber tracts might be relevant for cortical folding alterations in schizophrenia. Nine-teen patients with schizophrenia and 19 healthy subjects underwent T1-weighted MRI and DTI. Cortical folding was computed using a surface based approach. DTI was analyzed using FSL and SPM 5. Radial diffusivity and cortical folding were correlated covering the entire cortex in schizophrenia. Significantly increased radial diffusivity of the superior longitudinal fasciculus (SLF) in the left superior temporal region was negatively correlated with cortical folding of the left dorsolateral prefrontal cortex (DLPFC) in patients, i.e. higher radial diffusivity, as an indicator for disturbed white matter fiber myelination, was associated with lower cortical folding of the left DLPFC. Patients with pronounced alterations of the SLF showed significantly reduced cortical folding in the left DLPFC. Our study provides novel evidence for a linkage between prefrontal cortical folding alterations and deficits in connecting white matter fiber tracts in schizophrenia and supports the notion that the integrity of white matter tracts is crucial for intact morphogenesis of the cortical folds.


Assuntos
Rede Nervosa/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Methods Enzymol ; 583: 173-195, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28063490

RESUMO

An optimal tool to unravel the role of a specific player within a cellular network or process requires its spatiotemporally resolved perturbation. Chemically induced dimerization (CID) by the rapamycin system has proven useful to induce protein dimerization or translocation with high spatiotemporal precision. Recently, we and others have added reversibility of the dimerization event as a novel feature to CID approaches. Among those, our reversible chemical dimerizer (rCD1) shows the fastest release kinetics observed, comparable to optogenetic methods. Induction and termination of enzyme activities, including phosphatidylinositol 3-kinase (PI3K) and 5-phosphatase (5Ptase), therefore allowed us to monitor the relaxation of the downstream effectors within living cells by imaging and traditional biochemical methods. Because switching off the rCD1-induced enzyme activity is sufficiently fast, it is possible to estimate kinetic parameters for enzyme activity and metabolism. Fast reversible CIDs are therefore unique tools for performing semiquantitative biochemistry in intact cells. In this chapter, we discuss advantages and constraints for the design of reversible CID applications. We provide detailed protocols for rCD1 synthesis, CID component expression in and delivery to mammalian cells and the determination of enzyme kinetics inside intact cells by a specially designed image acquisition and data analysis method.


Assuntos
Guanidinas/farmacologia , Fosfatidilinositol 3-Quinases/genética , Monoéster Fosfórico Hidrolases/genética , Multimerização Proteica/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Domínios de Homologia de src/genética , Animais , Sítios de Ligação , Ligação Competitiva , Inibidores de Calcineurina/farmacologia , Expressão Gênica , Guanidinas/síntese química , Células HeLa , Humanos , Cinética , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/metabolismo , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/metabolismo , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Sirolimo/farmacologia , Tacrolimo/farmacologia , Proteínas de Ligação a Tacrolimo/farmacologia
17.
Eur Arch Psychiatry Clin Neurosci ; 267(1): 41-49, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26678081

RESUMO

Anorexia nervosa (AN) is highly heritable, and the perspective on the etiology of AN has changed from a behavioral to a neurobiological and neurodevelopmental view. However, cortical folding as an important marker for deviations in brain development has yet rarely been explored in AN. Hence, in order to determine potential cortical folding alterations, we investigated fine-grained cortical folding in a cohort of 26 patients with AN, of whom 6 patients were recovered regarding their weight at the time point of MRI measurement. MRI-derived cortical folding was computed and compared between patients and healthy controls at about 150,000 points per hemisphere using a surface-based technique (FreeSurfer). Patients with AN exhibited highly significant increased cortical folding in a right dorsolateral prefrontal cortex region (DLPFC). Furthermore, a statistical trend in the same direction was found in the right visual cortex. We did not find a correlation of local cortical folding and current symptoms of the disease. In conclusion, our analyses provide first evidence that altered DLPFC cortical folding plays a role in the etiology of AN. The absence of correlations with clinical parameters implicates a relatively independence of cortical folding alterations from the current symptomatology and might thus be regarded as a trait characteristic of the disease potentially related to other neurobiological features of AN.


Assuntos
Anorexia Nervosa/patologia , Córtex Cerebral/patologia , Adolescente , Adulto , Anorexia Nervosa/diagnóstico por imagem , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Método de Monte Carlo , Escalas de Graduação Psiquiátrica , Adulto Jovem
18.
AJNR Am J Neuroradiol ; 37(12): 2201-2208, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27492073

RESUMO

BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit regions of diffusion restriction following the initiation of bevacizumab therapy. Studies suggest that these regions represent either diffusion-restricted necrosis or hypercellular tumor. This study explored postmortem brain specimens and a population analysis of overall survival to determine the identity and implications of such lesions. MATERIALS AND METHODS: Postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab with progressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. A receiver operating characteristic analysis was performed to define optimal ADC thresholds for differentiating tissue types. A retrospective population study was also performed comparing the overall survival of 64 patients with recurrent glioblastoma treated with bevacizumab. Patients were separated into 3 groups: no diffusion restriction, diffusion restriction that appeared and progressed within 5 months of bevacizumab initiation, and delayed or stable diffusion restriction. An additional analysis was performed assessing tumor O6-methylguanine-DNA-methyltransferase methylation. RESULTS: The optimal ADC threshold for differentiation of hypercellularity and necrosis was 0.736 × 10-3mm2/s. Progressively expanding diffusion restriction was pathologically confirmed to be coagulative necrosis surrounded by viable tumor. Progressive lesions were associated with the worst overall survival, while stable lesions showed the greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine-DNA-methyltransferase methylated tumors, none developed diffusion-restricted lesions. CONCLUSIONS: Progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. Stable lesions were, however, associated with increased overall survival. All lesions were associated with O6-methylguanine-DNA-methyltransferase unmethylated tumors.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos
19.
Schizophr Res ; 176(2-3): 151-157, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27567290

RESUMO

Schizophrenia is characterized by increased mortality for which suicidality is the decisive factor. An analysis of cortical thickness and folding to further elucidate neuroanatomical correlates of suicidality in schizophrenia has not yet been performed. We searched for relevant brain regions with such differences between patients with suicide-attempts, patients without any suicidal thoughts and healthy controls. 37 schizophrenia patients (14 suicide-attempters and 23 non-suicidal) and 50 age- and gender-matched healthy controls were included. Suicidality was documented through clinical interview and chart review. All participants underwent T1-weighted MRI scans. Whole brain node-by-node cortical thickness and folding were estimated (FreeSurfer Software) and compared. Additionally a three group comparison for prefrontal regions-of-interest was performed in SPSS using a multifactorial GLM. Compared with the healthy controls patients showed a typical pattern of cortical thinning in prefronto-temporal regions and altered cortical folding in the right medial temporal cortex. Patients with suicidal behavior compared with non-suicidal patients demonstrated pronounced (p<0.05) cortical thinning in the right DLPFC and the superior temporal cortex. Comparing cortical thickness in suicidal patients with non-suicidal patients significant (p<0.05) cortical thinning was additionally found in the right superior and middle temporal, temporopolar and insular cortex. Our findings extend the evidence for neuroanatomical underpinnings of suicidal behaviour in schizophrenia. We identified cortical thinning in a network strongly involved in regulation of impulsivity, emotions and planning of behaviour in suicide attempters, which might lead to neuronal dysregulation in this network and consequently to a higher risk of suicidal behavior.


Assuntos
Córtex Pré-Frontal/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Tentativa de Suicídio , Lobo Temporal/patologia , Adulto , Antipsicóticos/uso terapêutico , Análise por Conglomerados , Simulação por Computador , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Entrevista Psicológica , Imageamento por Ressonância Magnética , Masculino , Método de Monte Carlo , Tamanho do Órgão , Córtex Pré-Frontal/diagnóstico por imagem , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Software , Lobo Temporal/diagnóstico por imagem
20.
Child Care Health Dev ; 41(6): 865-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25980311

RESUMO

BACKGROUND: Childhood overweight and obesity remain major health conditions, affecting nearly one-third of children in the USA. Multiple factors have been identified that contribute to children becoming overweight; however, little is known regarding what low-income mothers perceive to be the causes of and the ways to prevent children from becoming overweight. METHODS: Low-income mothers (n = 286) with children aged 4-8 years participated in semi-structured interviews, during which they were asked for their opinions about the causes of and ways to prevent children from becoming overweight. After themes were identified, interviews were coded for the presence or absence of each theme. RESULTS: The majority of mothers were non-Hispanic White (69.2%) and overweight or obese (77.3%). Additionally, many of the children (41.9%) were overweight or obese. Six causes of children becoming overweight were identified by mothers: types or quantities of food eaten (90.9%); parenting behaviours (44.9%); lack of activity (42.3%); genetics, slow metabolism or medical issues (24.5%); stress or emotion (5.2%); and limited access to resources (3.5%). Five ways to prevent children from becoming overweight identified by mothers included the following: healthy eating (84.9%), more activity (54.8%), limiting screen time (19.9%), limiting sugar-sweetened beverages (12.2%) and drinking more water (6.6%). The majority of mothers (77.1%) reported that they carried out their suggestions to prevent their children from becoming overweight. CONCLUSION: Within this cohort with a high prevalence of maternal and child overweight, most mothers identified many of the evidence-based strategies for childhood obesity prevention. Future intervention development may benefit from focusing on content areas that were less commonly identified by mothers as well as helping mothers translate knowledge to implementation.


Assuntos
Atitude Frente a Saúde , Mães/psicologia , Sobrepeso/etiologia , Sobrepeso/prevenção & controle , Pobreza , Adulto , Criança , Pré-Escolar , Comportamento Alimentar , Humanos , Michigan/epidemiologia , Relações Mãe-Filho , Sobrepeso/epidemiologia , Poder Familiar , Fatores de Risco
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