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1.
Sensors (Basel) ; 23(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37571666

RESUMO

Deep learning has become increasingly common in aerial imagery analysis. As its use continues to grow, it is crucial that we understand and can explain its behavior. One eXplainable AI (XAI) approach is to generate linguistic summarizations of data and/or models. However, the number of summaries can increase significantly with the number of data attributes, posing a challenge. Herein, we proposed a hierarchical approach for generating and evaluating linguistic statements of black box deep learning models. Our approach scores and ranks statements according to user-specified criteria. A systematic process was outlined for the evaluation of an object detector on a low altitude aerial drone. A deep learning model trained on real imagery was evaluated on a photorealistic simulated dataset with known ground truth across different contexts. The effectiveness and versatility of our approach was demonstrated by showing tailored linguistic summaries for different user types. Ultimately, this process is an efficient human-centric way of identifying successes, shortcomings, and biases in data and deep learning models.

2.
Emerg Med Australas ; 35(2): 194-199, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36200454

RESUMO

OBJECTIVE: To investigate patients presenting to EDs following the recent introduction of a shared electric scooter (e-scooter) scheme in Northern Territory (NT). METHODS: We conducted a prospective observational cohort study in Darwin, a regional city in NT, Australia with a population of approximately 150 000. Any patient who disclosed involvement of an e-scooter in the reason for their presentation to the ED was included. A descriptive analysis was derived for age, sex, triage time, alcohol level, injury type and the requirement of operating theatre, inpatient stay or ED discharge. Categorical variables were analysed using χ2 -tests, with odds ratios (ORs), 95% confidence intervals (CIs) and P-values reported. Costing analysis to ED of attendances and inpatient hospital admissions was undertaken. RESULTS: There were 111 presentations over the 8-month study period (January-September 2021). Forty-nine percent (n = 51) of patients were male and 51% (n = 54) were female. Extremity (n = 70) and craniofacial (n = 61) injuries were most common and approximately a quarter of patients (n = 24) required operative management for injuries sustained. Approximately half (n = 51) of patients were intoxicated and the average alcohol level of those tested was 0.18% (range 0.05-0.49%). The average cost per ED attendance was AU$777 and total cost of inpatient admissions being AU$352 255. All inpatient admissions were a result of injury while intoxicated. CONCLUSION: Harm minimisations strategies targeting implementation of alcohol testing and penalties for riders may be able to reduce the effect that the introduction of e-scooters on the strained health system in the NT.


Assuntos
Hospitalização , Alta do Paciente , Humanos , Masculino , Feminino , Northern Territory/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Acidentes de Trânsito , Dispositivos de Proteção da Cabeça , Serviço Hospitalar de Emergência
3.
Res Dev Disabil ; 128: 104298, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35816978

RESUMO

BACKGROUND: Self-report is important for measuring health outcomes; however, most research in intellectual disability (ID) relies on proxy report. The lack of cognitively accessible measures is one barrier to accurate self-reporting by individuals with ID. AIMS: This paper describes the process of adapting self-report measures of health status, health-related quality of life, and environment for use by individuals with ID and presents evidence on their usability (accessibility), usefulness (independent self-report), and reliability (internal consistency and test-retest). METHODS AND PROCEDURES: We used an inclusive research approach, in which we collaborated with adults with ID to revise, cognitively test, and pilot test cognitively accessible self-report measures. Technology supported the independent completion of measures. We assessed usability, usefulness, and reliability of these measures in 41 adults with ID. OUTCOMES AND RESULTS: The resulting measures are useful (independently completed) and usable (elicit a range of responses), with modest reliability (internal consistency and test-retest). CONCLUSIONS AND IMPLICATIONS: Self- report by adults with ID is feasible. A key element of this measure adaptation process was engaging adults with ID. More research is needed to understand the reliability and validity of the adapted measures and the characteristics of the population for whom they are most usable.


Assuntos
Deficiência Intelectual , Adulto , Nível de Saúde , Humanos , Deficiência Intelectual/diagnóstico , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Autorrelato
4.
J Endod ; 48(4): 527-534, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35077752

RESUMO

INTRODUCTION: This study investigated a colloidal microgel for angiogenic and odontogenic differentiation of cells in the presence of cell-derived extracellular matrix (ECM) proteins using a 3-dimensional culture model. METHODS: Viscoelastic properties of human dental pulp were determined to understand the native ECM environment. ECM proteins were extracted from dental pulp stem cell (DPSC) cultures, and MaxGel (Millipore Sigma, Burlington, MA) was used as a commercially available ECM protein. DPSCs were incubated in colloidal microgels in the presence of ECM proteins or gelatin methacryloyl (GelMA) as a bulk hydrogel (n = 9/group). The viability and odontogenic differentiation of DPSCs within hydrogels was determined using viability assays, mineralization staining, calcium and alkaline phosphatase assays, and quantitative polymerase chain reaction for odontogenic gene expression. Angiogenic properties of endothelial cells were determined using tubule formation assays and quantitative polymerase chain reaction to detect angiogenic gene expression. RESULTS: Dental pulp had a higher elastic modulus than the viscous modulus, showing a solidlike response similar to hydrogels. DPSC-derived ECM showed higher collagen and GAG than MaxGel (P < .05). The viability of DPSCs was similar in colloidal microgels, whereas higher cell viability, calcium deposition, and alkaline phosphatase activity were observed in GelMA (P < .05). Colloidal microgels allowed tubule-like structures by endothelial cells, whereas no tubular formation was observed in GelMA. DPSC-derived ECM in colloidal microgel up-regulated odontogenic gene expression, whereas MaxGel up-regulated angiogenic gene expression (P < .05). CONCLUSIONS: Colloidal microgels allowed cellular organization that can improve penetration and nutritional supply in a full-length root canal system. The bioactivity of cell-derived ECM proteins can be modified depending on the external stimulus.


Assuntos
Microgéis , Endodontia Regenerativa , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Polpa Dentária , Células Endoteliais , Matriz Extracelular , Proteínas da Matriz Extracelular/metabolismo , Gelatina , Humanos , Hidrogéis , Metacrilatos , Células-Tronco/fisiologia
5.
Res Dev Disabil ; 114: 103985, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34049229

RESUMO

BACKGROUND: Individuals with intellectual and developmental disabilities (IDD) may be especially vulnerable to changes associated with the COVID-19 pandemic given an increased likelihood of health concerns, low socioeconomic status, and difficulty accessing services. AIMS: The purpose of this study was to explore mental health problems and services in individuals with IDD during the pandemic. We explored whether number of mental health problems differed by disability, age, gender, living situation, physical health, and access to services. METHODS AND PROCEDURES: An online survey about experiences during the pandemic was administered to adults with IDD and their caregivers in the United States and in Chile. OUTCOMES AND RESULTS: In both Chile and the United States, few people endorsed increased health problems. Half of the sample in Chile and 41 % of the sample in the United States endorsed increased mental health problems. Approximately 15 % of the sample in the US reported no longer receiving state developmental disability services. CONCLUSIONS AND IMPLICATIONS: Healthcare and disability-specific agencies should consider strategies to tailor supports to improve mental health functioning and access to community.


Assuntos
COVID-19 , Deficiências do Desenvolvimento , Deficiência Intelectual , Saúde Mental , Adulto , Chile , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/terapia , Acessibilidade aos Serviços de Saúde , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/terapia , Pandemias , Estados Unidos/epidemiologia
6.
IEEE Trans Neural Netw Learn Syst ; 32(11): 4826-4838, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021943

RESUMO

While most deep learning architectures are built on convolution, alternative foundations such as morphology are being explored for purposes such as interpretability and its connection to the analysis and processing of geometric structures. The morphological hit-or-miss operation has the advantage that it considers both foreground information and background information when evaluating the target shape in an image. In this article, we identify limitations in the existing hit-or-miss neural definitions and formulate an optimization problem to learn the transform relative to deeper architectures. To this end, we model the semantically important condition that the intersection of the hit and miss structuring elements (SEs) should be empty and present a way to express Don't Care (DNC), which is important for denoting regions of an SE that are not relevant to detecting a target pattern. Our analysis shows that convolution, in fact, acts like a hit-to-miss transform through semantic interpretation of its filter differences. On these premises, we introduce an extension that outperforms conventional convolution on benchmark data. Quantitative experiments are provided on synthetic and benchmark data, showing that the direct encoding hit-or-miss transform provides better interpretability on learned shapes consistent with objects, whereas our morphologically inspired generalized convolution yields higher classification accuracy. Finally, qualitative hit and miss filter visualizations are provided relative to single morphological layer.


Assuntos
Algoritmos , Aprendizado Profundo/tendências , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão/tendências , Humanos , Reconhecimento Automatizado de Padrão/métodos
7.
Injury ; 50(5): 1009-1016, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30898389

RESUMO

BACKGROUND: Reviewing prehospital trauma deaths provides an opportunity to identify system improvements that may reduce trauma mortality. The objective of this study was to identify the number and rate of potentially preventable trauma deaths through expert panel reviews of prehospital and early in-hospital trauma deaths. METHODS: We conducted a retrospective review of prehospital and early in-hospital (<24 h) trauma deaths following a traumatic out-of-hospital cardiac arrest that were attended by Ambulance Victoria (AV) in the state of Victoria, Australia, between 2008 and 2014. Expert panels were used to review cases that had resuscitation attempted by paramedics and underwent a full autopsy. Patients with a mechanism of hanging, drowning or those with anatomical injuries deemed to be unsurvivable were excluded. RESULTS: Of the 1183 cases that underwent full autopsies, resuscitation was attempted by paramedics in 336 (28%) cases. Of these, 113 cases (34%) were deemed to have potentially survivable injuries and underwent expert panel review. There were 90 (80%) deaths that were not preventable, 19 (17%) potentially preventable deaths and 4 (3%) preventable deaths. Potentially preventable or preventable deaths represented 20% of those cases that underwent review and 7% of cases that had attempted resuscitation. CONCLUSIONS: The number of potentially preventable or preventable trauma deaths in the pre-hospital and early in-hospital resuscitation phase was low. Specific circumstances were identified in which the trauma system could be further improved.


Assuntos
Comitês Consultivos , Autopsia/estatística & dados numéricos , Serviços Médicos de Emergência/normas , Medicina de Emergência/educação , Prova Pericial/estatística & dados numéricos , Parada Cardíaca Extra-Hospitalar/mortalidade , Ressuscitação/mortalidade , Adulto , Feminino , Primeiros Socorros , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Parada Cardíaca Extra-Hospitalar/terapia , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Análise de Sobrevida , Vitória/epidemiologia , Ferimentos e Lesões
8.
Diagn Cytopathol ; 44(12): 964-968, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27546053

RESUMO

BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for evaluating cervical lymph nodes for metastases from thyroid carcinomas. Reports have illustrated that with application of standardized technique and appropriate cutoffs, thyroglobulin (TG) washout studies increase the sensitivity and specificity of FNAC in identifying lymph node metastases. This project describes our experience at an academic medical center utilizing needle wash thyroglobulin analyses as an ancillary to FNAC. MATERIALS AND METHODS: We reviewed cases at our institution where thyroglobulin analysis was performed in conjunction with FNA of lymph nodes in patients with thyroid carcinoma. Thyroglobulin levels were measured on needle rinses from each FNA biopsy that appeared negative or equivocal at the time of immediate assessment. These results were compared with surgical pathology results from neck dissections, when performed. RESULTS: 168 FNA biopsies were performed on suspicious lymph nodes from 97 patients with known or suspected thyroid malignancy between April 2013 and present. Using a cutoff of 1.0 ng TG/ml, thyroglobulin studies performed at our institution were found to have sensitivity and specificity results of 0.95. Surgical pathology results were used as the gold standard. When surgical pathology results are not available, FNAC is used as the mode of comparison. False positive Tg results occurred in two prethyroidectomy patients suggesting that sample contamination with blood may influence this method's specificity. A false-negative Tg result occurred in a lymph node with <1 mm focus of metastatic PTC, indicating that Tg results may not be sensitive in cases with few tumor cells. CONCLUSIONS: Our results suggest that thyroglobulin washout studies improve the quality of our biopsy diagnoses when used in conjunction with FNA in the assessment of metastatic disease in the context of established thyroid malignancy in post-thyroidectomy patients. Thyroglobulin values close to the cutoff of 1.0 ng/ml should be interpreted with caution, as these may represent a minute focus of metastatic tumor. Tg values in prethyroidectomy patients should also be interpreted with caution, as contamination with blood may cause its elevation. Diagn. Cytopathol. 2016;44:964-968. © 2016 Wiley Periodicals, Inc.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/patologia , Tireoglobulina/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma Papilar/metabolismo , Criança , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/metabolismo
9.
Ultrasound Med Biol ; 42(6): 1251-62, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26947445

RESUMO

Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Imageamento Tridimensional/métodos , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Razão Sinal-Ruído
11.
Ultrason Imaging ; 37(1): 22-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25060914

RESUMO

Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in the United States and the second leading cause of cancer-related death. Multi-parametric magnetic resonance imaging (mpMRI) has gained recent popularity to characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the potential to aid PCa diagnosis and management by using tissue stiffness to evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging datasets were compared with one another and with gross pathology measurements made immediately after radical prostatectomy. Images were manually segmented in 3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging modalities showed good correlation between estimated organ volume and gross pathologic weights. Ultrasound and MR total prostate volumes were well correlated (R(2) = 0.77), but B-mode images yielded prostate volumes that were larger (16.82% ± 22.45%) than MR images, due to overestimation of the lateral dimension (18.4% ± 13.9%), with less significant differences in the other dimensions (7.4% ± 17.6%, anterior-to-posterior, and -10.8% ± 13.9%, apex-to-base). ARFI and MR CG volumes were also well correlated (R(2) = 0.85). CG volume differences were attributed to ARFI underestimation of the apex-to-base axis (-28.8% ± 9.4%) and ARFI overestimation of the lateral dimension (21.5% ± 14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were well correlated with MR T2-weighted image (T2WI) estimates, with biases in the lateral dimension due to poor contrast caused by extraprostatic fat. B-mode combined with ARFI imaging is a promising low-cost, portable, real-time modality that can complement mpMRI for PCa diagnosis, treatment planning, and management.


Assuntos
Técnicas de Imagem por Elasticidade , Próstata/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Próstata/patologia
12.
Am J Dermatopathol ; 37(4): 305-10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24614207

RESUMO

Cutaneous toxoplasmosis is a rare and diagnostically challenging entity. Today, the acquired form occurs predominantly in immunocompromised patients with human immunodeficiency virus or after hematopoietic stem cell transplantation. We report a case of cutaneous toxoplasmosis in a 6-year-old girl after allogeneic stem cell transplantation for immune-mediated encephalopathy, first manifesting at 16 months of age. In the post-transplant setting, she developed a rash consisting of approximately 8 scattered 3­4-mm round, erythematous macules and papules on her back, abdomen, and right shoulder. Sections from a biopsy of a lesion on the back revealed numerous spherules tightly packed within small cystic structures in the epidermis. The diagnosis of cutaneous toxoplasmosis was confirmed by an immunohistochemical stain for Toxoplasma gondii and polymerase chain reaction on the peripheral blood for the T. gondii genome. This case should raise awareness that acquired toxoplasmosis with cutaneous involvement can occur in the pediatric population, particularly in immunocompromised patients after stem cell transplantation. Early diagnosis and treatment of this life-threatening opportunistic infection may improve patient outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções Oportunistas/parasitologia , Dermatopatias Parasitárias/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose/parasitologia , Antiprotozoários/uso terapêutico , Biópsia , Criança , DNA de Protozoário/genética , Quimioterapia Combinada , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Reação em Cadeia da Polimerase , Dermatopatias Parasitárias/diagnóstico , Dermatopatias Parasitárias/imunologia , Fatores de Tempo , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Resultado do Tratamento
15.
J Clin Aesthet Dermatol ; 5(1): 36-46, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22328958

RESUMO

Hypocomplementemic urticarial vasculitis syndrome, as opposed to urticarial vasculitis or urticarial vasculitis syndrome, is a rare disease process where the exact pathophysiology remains unknown. This article discusses the case of a 34-year-old Hispanic man with an ongoing history of chronic urticaria comprising episodes induced by low ambient temperatures, emotional stress, and spontaneous occurrences. This article serves as a consolidated reference for specialists to comprehensively review the plethora of systemic manifestations that may accompany urticarial vasculitis and highlights new systemic complications reported in association with this disease which are also observed in this case.

16.
Biophys J ; 99(9): 2803-11, 2010 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-21044577

RESUMO

It is well established that bacteria are able to respond to temporal gradients (e.g., by chemotaxis). However, it is widely held that prokaryotes are too small to sense spatial gradients. This contradicts the common observation that the vast majority of bacteria live on the surface of a solid substrate (e.g., as a biofilm). Herein we report direct experimental evidence that the nonmotile bacterium Staphylococcus aureus possesses a tactile response, or primitive sense of touch, that allows it to respond to spatial gradients. Attached cells recognize their substrate interface and localize adhesins toward that region. Braille-like avidity maps reflect a cell's biochemical sensory response and reveal ultrastructural regions defined by the actual binding activity of specific proteins.


Assuntos
Staphylococcus aureus/fisiologia , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/fisiologia , Aderência Bacteriana/fisiologia , Biofilmes/crescimento & desenvolvimento , Fenômenos Biofísicos , Fibronectinas/química , Fibronectinas/genética , Fibronectinas/fisiologia , Microscopia de Força Atômica , Modelos Biológicos , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Staphylococcus aureus/genética , Propriedades de Superfície
17.
Langmuir ; 26(13): 10764-70, 2010 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-20218549

RESUMO

Bacterial cell-wall-associated fibronectin binding proteins A and B (FnBPA and FnBPB) form bonds with host fibronectin. This binding reaction is often the initial step in prosthetic device infections. Atomic force microscopy was used to evaluate binding interactions between a fibronectin-coated probe and laboratory-derived Staphylococcus aureus that are (i) defective in both FnBPA and FnBPB (fnbA fnbB double mutant, DU5883), (ii) capable of expressing only FnBPA (fnbA fnbB double mutant complemented with pFNBA4), or (iii) capable of expressing only FnBPB (fnbA fnbB double mutant complemented with pFNBB4). These experiments were repeated using Lactococcus lactis constructs expressing fnbA and fnbB genes from S. aureus. A distinct force signature was observed for those bacteria that expressed FnBPA or FnBPB. Analysis of this force signature with the biomechanical wormlike chain model suggests that parallel bonds form between fibronectin and FnBPs on a bacterium. The strength and covalence of bonds were evaluated via nonlinear regression of force profiles. Binding events were more frequent (p < 0.01) for S. aureus expressing FnBPA or FnBPB than for the S. aureus double mutant. The binding force, frequency, and profile were similar between the FnBPA and FnBPB expressing strains of S. aureus. The absence of both FnBPs from the surface of S. aureus removed its ability to form a detectable bond with fibronectin. By contrast, ectopic expression of FnBPA or FnBPB on the surface of L. lactis conferred fibronectin binding characteristics similar to those of S. aureus. These measurements demonstrate that fibronectin-binding adhesins FnBPA and FnBPB are necessary and sufficient for the binding of S. aureus to prosthetic devices that are coated with host fibronectin.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Fibronectinas/química , Fibronectinas/metabolismo , Lactococcus lactis/metabolismo , Staphylococcus aureus/metabolismo , Biofilmes/crescimento & desenvolvimento , Lactococcus lactis/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento
18.
PLoS One ; 2(11): e1187, 2007 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-18000554

RESUMO

The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Hipocampo/metabolismo , Adulto , Regulação para Baixo , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Análise de Sequência com Séries de Oligonucleotídeos
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