RESUMO
Background: Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective: research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods: In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result: It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuringzone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion: Findings from current study would help[...].
Antecedentes: Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo: O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos: No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado: Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão: As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de, [...].
Assuntos
Humanos , Escarro , Farmacorresistência Bacteriana , Fatores de Risco , Infecções por Pseudomonas/patologia , Infecções por Pseudomonas/sangue , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/virologia , Sistema Respiratório , Técnicas In VitroRESUMO
Abstract Background Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.
Resumo Antecedentes Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de P. aeruginosa e, também, a sequência do gene rhl R pode ser usada como sequência de diagnóstico para identificar a sequência virulenta do gene rhl R das amostras quando isoladas do escarro de pacientes com pneumonia.
RESUMO
Background: Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective: research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods: In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result: It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion: Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.
Antecedentes: Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo: O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos: No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado: Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCUSG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão: As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de P. aeruginosa e, também, a sequência do gene rhl R pode ser usada como sequência de diagnóstico para identificar a sequência virulenta do gene rhl R das amostras quando isoladas do escarro de pacientes com pneumonia.
Assuntos
Humanos , Masculino , Feminino , Pneumonia , Pseudomonas aeruginosa/genética , RNA Ribossômico 16S , Glicolipídeos , Regulação Bacteriana da Expressão GênicaRESUMO
Sex differences in whole-body fat storage exist in many species. For example, Drosophila females store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood. Here, we identify a key role for sex determination gene transformer (tra) in regulating the male-female difference in fat storage. Normally, a functional Tra protein is present only in females, where it promotes female sexual development. We show that loss of Tra in females reduced whole-body fat storage, whereas gain of Tra in males augmented fat storage. Tra's role in promoting fat storage was largely due to its function in neurons, specifically the Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis of Akh pathway regulation revealed a male bias in APC activity and Akh pathway function, where this sex-biased regulation influenced the sex difference in fat storage by limiting triglyceride accumulation in males. Importantly, Tra loss in females increased Akh pathway activity, and genetically manipulating the Akh pathway rescued Tra-dependent effects on fat storage. This identifies sex-specific regulation of Akh as one mechanism underlying the male-female difference in whole-body triglyceride levels, and provides important insight into the conserved mechanisms underlying sexual dimorphism in whole-body fat storage.
Assuntos
Proteínas de Drosophila/genética , Gorduras/metabolismo , Hormônios de Inseto/metabolismo , Proteínas Nucleares/genética , Oligopeptídeos/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Feminino , Masculino , Proteínas Nucleares/metabolismo , Ácido Pirrolidonocarboxílico/metabolismo , Processos de Determinação Sexual , Fatores SexuaisRESUMO
BACKGROUND: Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. OBJECTIVE: research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. METHODS: In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. RESULT: It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. CONCLUSION: Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.
Assuntos
Pneumonia , Pseudomonas aeruginosa , Feminino , Regulação Bacteriana da Expressão Gênica , Glicolipídeos , Humanos , Masculino , Pseudomonas aeruginosa/genética , RNA Ribossômico 16SRESUMO
OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.
Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Adolescente , Anticolesterolemiantes/uso terapêutico , Criança , LDL-Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Estudos Transversais , Suplementos Nutricionais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Estilo de Vida , Masculino , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.
Assuntos
Proteínas de Drosophila/fisiologia , Drosophila/genética , Drosophila/metabolismo , Lipase/fisiologia , Metabolismo dos Lipídeos/genética , Lipólise/genética , Caracteres Sexuais , Animais , Animais Geneticamente Modificados , Metabolismo Energético/genética , Feminino , Lipase/genética , Lipase/metabolismo , Masculino , Micronutrientes/metabolismo , Triglicerídeos/metabolismoRESUMO
BACKGROUND AND AIMS: There are limited data from the US on outcomes of patients in specialty care for familial hypercholesterolemia (FH). METHODS: CASCADE FH Registry data were analyzed to assess longitudinal changes in medication usage, in low density lipoprotein cholesterol (LDL-C) levels, and the rate of major adverse cardiovascular events (MACE (myocardial infarction, coronary revascularization, stroke or transient ischemic attack) in adults with FH followed in US specialty clinics. RESULTS: The cohort consisted of 1900 individuals (61% women, 87% Caucasian), with mean age of 56⯱â¯15 years, 37% prevalence of ASCVD at enrollment, mean pretreatment LDL-C 249⯱â¯68â¯mg/dl, mean enrollment LDL-C 145â¯mg/dl and 93% taking lipid lowering therapy. Over follow up of 20⯱â¯11 months, lipid lowering therapy use increased (mean decrease in LDL-C of 32â¯mg/dl (p < 0.001)). Only 48% of participants achieved LDL-C < 100â¯mg/dl and 22% achieved LDL-C < 70â¯mg/dl; ASCVD at enrollment was associated with greater likelihood of goal achievement. MACE event rates were almost 6 times higher among patients with prior ASCVD compared to those without (4.6 vs 0.8/100 patient years). Also associated with incident MACE were markers of FH severity and conventional ASCVD risk factors. CONCLUSIONS: With care in FH specialized clinics, LDL-C decreased, but LDL-C persisted >100â¯mg/dl in 52% of patients. High ASCVD event rates suggest that adults with FH warrant designation as having an ASCVD risk equivalent. Earlier and more aggressive therapy of FH is needed to prevent ASCVD events.
Assuntos
LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Adulto , Idoso , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Cardiologia/normas , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Feminino , Seguimentos , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Resultado do TratamentoRESUMO
Objective The goal of this study was to evaluate the diagnostic yield of B-mode ultrasound and ultrasound elastography used alone and in combination for differentiating breast lesions into benign and malignant. Materials and methods Eighty-five patients were investigated with B-mode ultrasonography and elastography and provided a Breast Imaging Reporting, and Data System (BI-RADS) score based on ultrasonography, strain ratio, and elastography score (ES) based on elastography. Each lesion was then evaluated by a combination method, combining BI-RADS with strain ratio and BI-RADS with elastography score. Each modality was assessed for the successful detection and characterization of the lesion and whether combining ultrasonography B-mode imaging with strain elastography improves diagnosis and is reliable enough to replace invasive procedures such as biopsy that have been the mainstay of diagnosis. Results Of 85 lesions, 23 lesions (27%) were found to be malignant, and 62 lesions (72.9%) were benign. When used alone, BI-RADS had 100.0% sensitivity, 13% specificity, 50% and 100% positive and negative predictive values (respectively), and 72.9% accuracy. BI-RADS results were then combined with strain ratio (SR) and ES. BI-RADS with SR had 91.3% sensitivity, 95.2% specificity, 87.5% and 96.7% positive and negative predictive values (respectively), and 94.1% accuracy. Similarly, BI-RADS with ES had 91.3% sensitivity, 93.5% specificity, 84.0% and 96.7% positive and negative predictive values, and 92.9% accuracy. Conclusions The combination method performs better at diagnosing breast lesions than BI-RADS alone and can be used as an early and preliminary basis for diagnosis and in settings where invasive procedures cannot be performed. Combining strain elastography and BI-RADS also help characterize which lesions are better suited for biopsy, leading to a decline in unnecessary invasive procedures.
RESUMO
We describe a rare case of ectopic papillary thyroid cancer in the thyroglossal duct tract invading the floor-of-mouth musculature. The postablative defect was reconstructed with a bone-anchored tensor fascia lata graft to resuspend the floor of mouth to the mandible as a neogeniohyoid sling, enabling maintenance of a functional tongue position for normal speech and swallowing. This reconstruction should be considered when suprahyoid musculature is resected without breaching the oral lining.
Assuntos
Carcinoma Papilar/cirurgia , Coristoma/cirurgia , Fascia Lata/transplante , Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Cisto Tireoglosso/cirurgia , Glândula Tireoide , Adulto , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Coristoma/diagnóstico , Coristoma/patologia , Feminino , Humanos , Osso Hioide/cirurgia , Imageamento por Ressonância Magnética , Soalho Bucal/diagnóstico por imagem , Soalho Bucal/cirurgia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Esvaziamento Cervical/efeitos adversos , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Retalhos Cirúrgicos/transplante , Cisto Tireoglosso/diagnóstico , Cisto Tireoglosso/patologia , Tireoidectomia/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
We describe a rare case of cervical necrotising fasciitis caused by mastoiditis and Bezold's abscess. This case was complicated by a tracheostomy delaying wound healing. A novel strategy to repair the tracheotomy defect using Permacol™, an acellular porcine dermal substitute, and a local muscle flap not previously reported in the literature is described to allow the use of negative pressure wound therapy dressing. This technique may be employed in similar applications for non-healing tracheotomy wounds.
Assuntos
Abscesso/complicações , Fasciite Necrosante/etiologia , Pescoço , Tratamento de Ferimentos com Pressão Negativa/métodos , Abscesso/cirurgia , Materiais Biocompatíveis/uso terapêutico , Colágeno/uso terapêutico , Fasciite Necrosante/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Infecção da Ferida Cirúrgica/terapia , Traqueotomia/efeitos adversos , Traqueotomia/métodosRESUMO
Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
Assuntos
Prova Pericial/métodos , Aconselhamento Genético/métodos , Testes Genéticos/métodos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Apolipoproteínas B/sangue , Apolipoproteínas B/genética , Prova Pericial/normas , Aconselhamento Genético/normas , Testes Genéticos/normas , Humanos , Hiperlipoproteinemia Tipo II/sangue , Pró-Proteína Convertase 9/sangue , Pró-Proteína Convertase 9/genética , Receptores de LDL/sangue , Receptores de LDL/genéticaRESUMO
BACKGROUND AND AIMS: Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. METHODS: We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. RESULTS: In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90). CONCLUSIONS: In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.
Assuntos
LDL-Colesterol/sangue , Disparidades nos Níveis de Saúde , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/etnologia , Adulto , Negro ou Afro-Americano , Idoso , Asiático , Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Etnicidade , Feminino , Disparidades em Assistência à Saúde , Humanos , Hiperlipoproteinemia Tipo II/sangue , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Razão de Chances , Fenótipo , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. OBJECTIVE: To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. METHODS: We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: "clinical diagnosis," MEDPED, Simon Broome, DLCN, and other. RESULTS: Most adults enrolled in CASCADE FH (55.0%) received a "clinical diagnosis." The most commonly used formal criteria was Simon-Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P < .0001. Of the patients with only a "clinical diagnosis," 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. CONCLUSIONS: Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention.
Assuntos
Hiperlipoproteinemia Tipo II/diagnóstico , Adulto , LDL-Colesterol/sangue , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Sistema de Registros , Estados UnidosRESUMO
BACKGROUND: Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. METHODS AND RESULTS: We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08-2.82) and hypertension (2.48; 1.92-3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86-28.86) and use of >1 LDL-lowering medication (1.80; 1.34-2.41). CONCLUSIONS: FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.
Assuntos
Doença das Coronárias/prevenção & controle , Heterozigoto , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Padrões de Prática Médica , Lacunas da Prática Profissional , Adulto , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , LDL-Colesterol/sangue , Comorbidade , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Estudos Transversais , Diabetes Mellitus/epidemiologia , Regulação para Baixo , Diagnóstico Precoce , Feminino , Predisposição Genética para Doença , Fidelidade a Diretrizes , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fenótipo , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Valor Preditivo dos Testes , Prevalência , Lacunas da Prática Profissional/normas , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Sleep deprivation among junior physicians (house officers) is of growing concern. In developed countries, duty hours are now mandated, but in developing countries, junior physicians are highly susceptible to develop sleep impairment due to long working hours, on-call duties and shift work schedule. AIM: We undertook the study to assess sleep quality among Pakistani junior physicians. SUBJECTS AND METHODS: A cross-sectional study was conducted at private and public hospitals in Karachi, Pakistan, from June 2012 to January 2013. The study population comprised of junior doctors (house physicians and house surgeons). A consecutive sample of 350 physicians was drawn from the above-mentioned study setting. The subject underwent two validated self-administered questionnaires, that is, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). RESULTS: A total of 334 physicians completely filled out the questionnaire with a response rate of 95.4% (334/350). Of 334 physicians, 36.8% (123/334) were classified as "poor sleepers" (global PSQI score > 5). Poor sleep quality was associated with female gender (P = 0.01), excessive daytime sleepiness (P < 0.01), lower total sleep time (P < 0.001), increased sleep onset latency (P < 0.001), and increased frequency of sleep disturbances (P < 0.001). Abnormal ESS scores (ESS > 10) were more prevalent among poor sleepers (P < 0.01) signifying increased level of daytime hypersomnolence. CONCLUSION: Sleep quality among Pakistani junior physicians is significantly poor. Efforts must be directed towards proper sleep hygiene education. Regulations regarding duty hour limitations need to be considered.
RESUMO
Numerous studies have provided evidence regarding the involvement of protein S-nitrosylation in the progression of Alzheimer's disease (AD) pathology and its implication in the formation and accumulation of misfolded protein aggregates. The identification of S-nitrosylated proteins can be a major step toward the understanding of mechanisms leading to neuronal degeneration. The present study targeted S-nitrosylated proteins in AD hippocampus, substantia nigra and cortex using the following work-flow that combines S-nitrosothiol-specific antibody detection, classical biotin switch method labeled with fluorescence dye followed by electrospray ionization quadrupole time of flight tandem MS (ESI-QTOF MS/MS) identification. Endogenous nitrosocysteines were identified in 45 proteins, mainly involved in metabolism, signaling pathways, apoptosis and redox regulation as assigned by REACTOME and KEGG pathway database analysis. Superoxide dismutase (SOD2) [Mn], fructose-bisphosphate aldolase C (ALDOC) and voltage-dependent anion-selective channel protein 2 (VDAC2) showed differential S-nitrosylation signal, not previously reported in AD regions. Extensive neuronal atrophy with increased protein S-nitrosylation in AD regions is also evident from immunofluorescence studies using S-nitrosocysteine antibody. A number of plausible cysteine modification sites were predicted via Group-based Prediction System-S-nitrosothiols (GPS-SNO) 1.0 while STRING 8.3 analysis revealed functional annotations in the modified proteins. The findings are helpful in characterization of functional abnormalities and may facilitate the understanding of molecular mechanisms and biological function of S-nitrosylation in AD pathology.
Assuntos
Doença de Alzheimer/patologia , Encéfalo/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , S-Nitrosotióis/metabolismo , Superóxido Dismutase/metabolismo , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Idoso , Biotina/metabolismo , Estudos de Casos e Controles , Cisteína/análogos & derivados , Eletroforese em Gel Bidimensional , Feminino , Humanos , Masculino , Proteômica , Espectrometria de Massas em TandemRESUMO
Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.
Assuntos
Sistemas de Liberação de Medicamentos , Otopatias/tratamento farmacológico , Administração Oral , Administração Tópica , Animais , Orelha/anatomia & histologia , HumanosRESUMO
INTRODUCTION: Controversy still surrounds the use of drains after total knee replacement (TKR). We compared closed suction drains, reinfusion drains and no drains by studying haemoglobin (Hb) levels, blood transfusion requirements and functional knee outcome scores in a single surgeon series. METHODS: A total of 102 consecutive primary TKRs were performed by the senior author between September 2006 and July 2008. All were cemented fixed bearing devices with patellar resurfacing. Of the 102 patients, 30 had closed suction drainage, 33 had an unwashed reinfusion drainage system and 39 had no drains. Data regarding pre and post-operative Hb and units transfused were gathered retrospectively. Pre and post-operative American Knee Society scores (AKSS) and Oxford knee scores (OKS) were recorded prospectively. RESULTS: The pre-operative Hb levels were comparable among the groups. There was no statistically significant difference in Hb level reduction or autologous transfusion rates among the groups. Pre-operative AKSS and OKS were statistically comparable in each group. There was no statistical difference between the improvement in AKSS knee and function scores in all three groups. There was a slightly smaller improvement in the OKS of the 'no drain' group. There were no complications of drain usage and no deep infections. No patient required manipulation under anaesthesia and range of movement outcomes were the same for each group. CONCLUSIONS: Our study does not support the use of either closed suction drains or reinfusion drains in primary elective TKR.