RESUMO
BACKGROUND: The majority of the world's population is bilingual. Yet, therapy studies involving bilingual people with aphasia are rare and have produced conflicting results. One recent study suggested that therapy can assist word retrieval in bilingual aphasia, with effects generalizing to related words in the untreated language. However, this cross-linguistic generalisation only occurred into the person's stronger language (L1). While indicative, these findings were derived from just three participants, and only one received therapy in both languages. AIMS: This study addressed the following questions. Do bilingual people with aphasia respond to naming therapy techniques developed for the monolingual population? Do languages respond differently to therapy and, if so, are gains influenced by language dominance? Does cross-linguistic generalisation occur and does this depend on the therapy approach? Is cross-linguistic generalisation more likely following treatment in L2 or L1? METHODS & PROCEDURES: The study involved five aphasic participants who were bilingual in English and Bengali. Testing showed that their severity and dominance patterns varied, so the study adopted a case series rather than a group design. Each person received two phases of naming therapy, one in Bengali and one in English. Each phase treated two groups of words with semantic and phonological tasks, respectively. The effects of therapy were measured with a picture-naming task involving both treated and untreated (control) items. This was administered in both languages on four occasions: two pre-therapy, one immediately post-therapy and one 4 weeks after therapy had ceased. Testing and therapy in Bengali was administered by bilingual co-workers. OUTCOMES & RESULTS: Four of the five participants made significant gains from at least one episode of therapy. Benefits arose in both languages and from both semantic and phonological tasks. There were three instances of cross-linguistic generalisation, which occurred when items had been treated in the person's dominant language using semantic tasks. CONCLUSIONS & IMPLICATIONS: This study suggests that 'typical' naming treatments can be effective for some bilingual people with aphasia, with both L1 and L2 benefiting. It offers evidence of cross-linguistic generalisation, and suggests that this is most likely to arise from semantic therapy approaches. In contrast to some results in the academic literature, the direction of generalisation was from LI to L2. The theoretical implications of these findings are considered. Finally, the results support the use of bilingual co-workers in therapy delivery.
Assuntos
Anomia/reabilitação , Afasia de Broca/reabilitação , Afasia de Wernicke/reabilitação , Terapia da Linguagem/métodos , Multilinguismo , Reabilitação do Acidente Vascular Cerebral , Adolescente , Adulto , Anomia/diagnóstico , Afasia de Broca/diagnóstico , Afasia de Wernicke/diagnóstico , Feminino , Generalização Psicológica , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos , Semântica , Medida da Produção da Fala , Acidente Vascular Cerebral/diagnósticoRESUMO
Infections with respiratory viruses can spread via liquid droplets and aerosols, and cause diseases such as influenza and COVID-19. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of respiratory droplets containing these viruses. However, influenza A viruses and coronaviruses are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as absorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here we used polyamide 6.6 (PA66) fibers that had zinc ions embedded during the polymerisation process and systematically investigated if these fibers can absorb and inactivate pandemic SARS-CoV-2 and influenza A virus H1N1. We find that these viruses are readily absorbed by PA66 fabrics and inactivated by zinc ions embedded into this fabric. The inactivation rate (pfu·gram-1·min-1) exceeds the number of active virus particles expelled by a cough and supports a wide range of viral loads. Moreover, we found that the zinc content and the virus inactivating property of the fabric remain stable over 50 standardized washes. Overall, these results provide new insight into the development of "pathogen-free" PPE and better protection against RNA virus spread.
RESUMO
Influenza A viruses (IAV) and SARS-CoV-2 can spread via liquid droplets and aerosols. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. However, IAV and SARS-CoV-2 are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as adsorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here, we used polyamide 6.6 (PA66) fibers containing embedded zinc ions and systematically investigated if these fibers can adsorb and inactivate SARS-CoV-2 and IAV H1N1 when woven into a fabric. We found that our PA66-based fabric decreased the IAV H1N1 and SARS-CoV-2 titer by approximately 100-fold. Moreover, we found that the zinc content and the virus inactivating property of the fabric remained stable over 50 standardized washes. Overall, these results provide insights into the development of reusable PPE that offer protection against RNA virus spread.
Assuntos
Vírus da Influenza A/fisiologia , Nylons/farmacologia , SARS-CoV-2/fisiologia , Têxteis , Inativação de Vírus/efeitos dos fármacos , Zinco/farmacologia , Adsorção , Animais , Chlorocebus aethiops , Fibra de Algodão , Cães , Células HEK293 , Humanos , Vírus da Influenza A/efeitos dos fármacos , Íons , Células Madin Darby de Rim Canino , Polipropilenos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Células Vero , Carga Viral , Óxido de Zinco/farmacologiaRESUMO
Amphotericin B (AMB) is used to treat fungal infections of the central nervous system (CNS). However, AMB shows poor penetration into the CNS and little is known about the factors affecting its permeation through the blood-brain barrier (BBB). Therefore, we studied immunomodulatory and organism-associated molecules affecting the permeability of an in vitro BBB model to AMB. We examined the effects of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan (ZYM), dexamethasone (DEX), cyclosporine, and tacrolimus on transendothelial electrical resistance (TEER); endothelial tight junctions; filamentous actin; and permeability to deoxycholate AMB (DAMB), liposomal AMB (LAMB), and fluconazole. Proinflammatory cytokines and organism-associated molecules significantly decreased the mean TEER by 40.7 to 100% (P < or = 0.004). DEX increased the mean TEER by 18.2 to 26.4% (P < or = 0.04). TNF-alpha and LPS increased the permeability to AMB by 8.2 to 14.5% compared to that for the controls (1.1 to 2.4%) (P < or = 0.04). None of the other molecules affected the model's permeability to AMB. By comparison, the BBB model's permeability to fluconazole was >78% under all conditions studied, without significant differences between the controls and the experimental groups. LPS and TNF-alpha decreased tight-junction protein zona occludens 1 (ZO-1) between endothelial cells. In conclusion, IL-1beta, ZYM, and LTA increased the permeability of the BBB to small ions but not to AMB, whereas TNF-alpha and LPS, which disrupted the endothelial layer integrity, increased the permeability to AMB.
Assuntos
Anfotericina B/metabolismo , Antifúngicos/metabolismo , Barreira Hematoencefálica/fisiologia , Permeabilidade Capilar/fisiologia , Fluconazol/metabolismo , Fatores Imunológicos/farmacologia , Anfotericina B/farmacologia , Animais , Antifúngicos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Células Cultivadas , Citocinas/metabolismo , Citocinas/farmacologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Fluconazol/farmacologia , Ratos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismoRESUMO
High-level mupirocin resistance (H-Mu(r)) in S. aureus is associated with the mupA gene. The mupA Evigene test rapidly identifies this gene. This study assessed the performance of mupA Evigene compared to that of susceptibility disk testing. mupA Evigene detected H-Mu(r) in 6/179 S. aureus isolates, and the results were concordant with those of susceptibility disk testing.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Técnicas de Diagnóstico Molecular/métodos , Mupirocina/farmacologia , Proteínas Nucleares/genética , Kit de Reagentes para Diagnóstico , Staphylococcus aureus/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e EspecificidadeRESUMO
The peripheral-type benzodiazepine receptor (PBR), an 18-kDa high affinity drug and cholesterol binding protein, is expressed at high levels in various cancers. Its expression is positively correlated with aggressive metastatic behavior in human breast cancer cells. To determine the role of PBR in tumor progression, two human mammary carcinoma cell lines were utilized: the non-aggressive MCF-7 cell line, which expresses extremely low PBR levels, and the highly aggressive MDA-MB-231 cell line, which has much higher PBR levels. We have generated stably transfected lines of the tetracycline-repressible MCF-7 cell line (MCF-7 Tet-Off) with inducible human PBR cDNA. Induction of PBR expression in MCF-7 Tet-Off cells increased PBR ligand binding and cell proliferation. Transfection of MDA-MB-231 cells with multiple siRNAs complementary to PBR (PBR-siRNAs) led to different levels of PBR mRNA knockdown. Lentiviral-mediated PBR RNA interference in MDA-MB-231 cells decreased PBR levels by 50%. Decreased PBR expression was associated with cell cycle arrest at G2 phase, decreased cell proliferation, and significant increases in the protein levels of the cyclin-dependent kinase inhibitor p21(WAF/CIP1). These changes were accompanied by p53 activation seen as increased p53 phosphorylation (Ser15). In parallel, increased proteolytic activation of caspase-3 was also observed. Taken together these results suggest that PBR protein expression is directly involved in regulating cell survival and proliferation in human breast cancer cells by influencing signaling mechanisms involved in cell cycle control and apoptosis.
Assuntos
Apoptose/fisiologia , Proliferação de Células , Receptores de GABA-A/fisiologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caspase 3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ciclina A/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Doxiciclina/farmacologia , Fase G1/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Modelos Biológicos , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ensaio Radioligante , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Proteína do Retinoblastoma/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transfecção , Vimentina/biossínteseRESUMO
Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Amplificação de Genes/genética , Receptores de GABA-A/genética , Divisão Celular , DNA de Neoplasias/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Células Tumorais CultivadasRESUMO
BACKGROUND: Patients undergoing hemodialysis have experienced a 43% increase in rate of hospitalization due to infection during the past 20 years. Research in other industries has shown that safe systems are achieved by considering the entire system to enable performance specifications to be met. METHOD: A sociotechnical systems framework was applied through the Macroergonomic Analysis and Design method to evaluate a 54-chair ambulatory dialysis unit to decrease healthcare-associated infections. Fifty-seven system discrepancies across 6 healthcare-associated infection risk factors were identified. A multicomponent intervention was developed to address 44 of the variances across 4 of the risk factors. RESULTS: Access-related bloodstream infections and access site infections did not improve. Bacterial surface contamination decreased. Process measures for the individual components of the intervention demonstrated varying adherence to the intervention. CONCLUSIONS: Inconsistent compliance with interventions is hypothesized to be due to organizational and external environment factors.
Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Instituições de Assistência Ambulatorial , Bacteriemia/epidemiologia , Doenças Transmissíveis , Infecção Hospitalar/economia , Coleta de Dados , Fidelidade a Diretrizes , Departamentos Hospitalares , Hospitais , Humanos , Estilo de Vida , Melhoria de Qualidade , Diálise Renal/efeitos adversosRESUMO
The translocator protein (TSPO), formerly known as a peripheral benzodiazepine receptor, exerts pro-apoptotic function via regulation of mitochondrial membrane potential. We examined TSPO expression in human thyroid tumors (25 follicular adenomas (FA), 15 follicular cancers (FC), and 70 papillary cancers (PC)). The role of TSPO in the regulation of cell growth, migration, and apoptosis was examined in thyroid cancer cell lines after TSPO knockdown with siRNA and after treatment with TSPO antagonist (PK11195). Compared with normal thyroid, the level of TSPO expression was increased in FA, FC, and PC in 24, 26.6, and 55.7% of cases respectively. Thyroid cancer cell lines demonstrated variable levels of TSPO expression, without specific association with thyroid oncogene mutations. Treatment with inhibitors of PI3K/AKT or MEK/ERK signaling was not associated with changes in TSPO expression. Treatment with histone deacetylase inhibitor (valproic acid) increased TSPO expression in TSPO-deficient cell lines (FTC236 cells). TSPO gene silencing or treatment with PK11195 did not affect thyroid cancer cell growth and migration but prevented depolarization of mitochondrial membranes induced by oxidative stress. Induction of TSPO expression by valproic acid was associated with increased sensitivity of FTC236 to oxidative stress-inducible apoptosis. Overall, we showed that TSPO expression is frequently increased in PC. In vitro data suggested the role of epigenetic mechanism(s) in the regulation of TSPO in thyroid cells. Implication of TSPO in the thyroid cancer cell response to oxidative stress suggested its potential role in the regulation of thyroid cancer cell response to treatment with radioiodine and warrants further investigation.
Assuntos
Estresse Oxidativo/genética , Receptores de GABA/genética , Receptores de GABA/fisiologia , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular , Antineoplásicos/farmacologia , Carcinoma , Carcinoma Papilar , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Peróxido de Hidrogênio/farmacologia , Isoquinolinas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Receptores de GABA/metabolismo , Câncer Papilífero da Tireoide , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [(123)I]-(R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals (p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [(11)C]-(R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.
Assuntos
Inflamação/diagnóstico por imagem , Pulmão/química , Pulmão/patologia , Tomografia por Emissão de Pósitrons/métodos , Receptores de GABA/metabolismo , Animais , Biomarcadores/química , Biomarcadores/metabolismo , Radioisótopos de Carbono , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/metabolismo , Radioisótopos do Iodo , Lipopolissacarídeos/administração & dosagem , Pulmão/metabolismo , Camundongos , RadiografiaRESUMO
Peripheral-type benzodiazepine receptor (PBR) is an 18 kDa high-affinity drug ligand and cholesterol binding protein involved in various cell functions. Antisera for distinct PBR areas identified immunoreactive proteins of 18, 40, and 56 kDa and occasionally 72, 90, and 110 kDa in testicular Leydig and breast cancer cells. These sizes may correspond to PBR polymers and correlated to the levels of reactive oxygen species. Treatment of Leydig cells with human chorionic gonadotropin rapidly induced free radical, PBR polymer, and steroid formation. UV photoirradiation generates ROS species, which increased the size of intramembraneous particles of recombinant PBR reconstituted into proteoliposomes consistent with polymer formation, determined both by SDS-PAGE and by freeze-fracture electron microscopy. Spectroscopic analysis revealed the formation of dityrosines as the covalent cross-linker between PBR monomers. Moreover, photoirradiation increased PK 11195 drug ligand binding and reduced cholesterol binding capacity of proteoliposomes. Further addition of PK 11195 drug ligand to polymers increased the rate of cholesterol binding. These data indicate that reactive oxygen species induce in vivo and in vitro the formation of covalent PBR polymers. We propose that the PBR polymer might be the functional unit responsible for ligand-activated cholesterol binding and that PBR polymerization is a dynamic process modulating the function of this receptor in cholesterol transport and other cell-specific PBR-mediated functions.