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1.
Circulation ; 148(21): 1691-1704, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37850394

RESUMO

BACKGROUND: Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. ß-Adrenergic receptor antagonists (ß-blockers) are the first-line therapy for HCM. However, ß-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown. METHODS: We screened 21 ß-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure-volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (Myh6R403Q/+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (MYH7R403Q/+). RESULTS: We identified that carvedilol, a ß-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a ß1-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α1-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of ß-blocking effect, retains the ability to inhibit both α1-receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7R403Q/+ iPSC-derived cardiomyocytes. CONCLUSIONS: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.


Assuntos
Cardiomiopatia Hipertrófica , Metoprolol , Humanos , Camundongos , Animais , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Metoprolol/uso terapêutico , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/tratamento farmacológico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Miócitos Cardíacos/metabolismo , Verapamil/uso terapêutico , Receptores Adrenérgicos/metabolismo
2.
J Healthc Manag ; 69(1): 12-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38175533

RESUMO

GOAL: Clinician stress and resilience have been the subjects of significant research and interest in the past several decades. We aimed to understand the factors that contribute to clinician stress and resilience in order to appropriately guide potential interventions. METHODS: We conducted a scoping review (n = 42) of published reviews of research on clinician distress and resilience using the methodology of Peters and colleagues (2020). Our team examined these reviews using the National Academy of Medicine's framework for clinician well-being and resilience. PRINCIPAL FINDINGS: We found that organizational factors, learning/practice environment, and healthcare responsibilities were three of the top four factors identified in the reviews as contributing to clinician distress. Learning/practice environment and organizational factors were two of the top four factors identified in the reviews as contributing to their resilience. PRACTICAL APPLICATIONS: Clinicians continue to face numerous external challenges that complicate their work. Further research, practice, and policy changes are indicated to improve practice environments for healthcare clinicians. Healthcare leaders need to promote resources for organizational and system-level changes to improve clinician well-being.


Assuntos
Pessoal de Saúde , Estresse Ocupacional , Resiliência Psicológica , Humanos , Pessoal de Saúde/psicologia
3.
New Phytol ; 240(3): 1202-1218, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37559429

RESUMO

A prophage tail-like protein (Bg_9562) of Burkholderia gladioli strain NGJ1 possesses broad-spectrum antifungal activity, and it is required for the bacterial ability to forage over fungi. Here, we analyzed whether heterologous overexpression of Bg_9562 or exogenous treatment with purified protein can impart disease tolerance in tomato. The physiological relevance of Bg_9562 during endophytic growth of NGJ1 was also investigated. Bg_9562 overexpressing lines demonstrate fungal and bacterial disease tolerance. They exhibit enhanced expression of defense genes and activation of mitogen-activated protein kinases. Treatment with Bg_9562 protein induces defense responses and imparts immunity in wild-type tomato. The defense-inducing ability lies within 18-51 aa region of Bg_9562 and is due to sequence homology with the bacterial flagellin epitope. Interaction studies suggest that Bg_9562 is perceived by FLAGELLIN-SENSING 2 homologs in tomato. The silencing of SlSERK3s (BAK1 homologs) prevents Bg_9562-triggered immunity. Moreover, type III secretion system-dependent translocation of Bg_9562 into host apoplast is important for elicitation of immune responses during colonization of NGJ1. Our study emphasizes that Bg_9562 is important for the endophytic growth of B. gladioli, while the plant perceives it as an indirect indicator of the presence of bacteria to mount immune responses. The findings have practical implications for controlling plant diseases.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Burkholderia gladioli , Solanum lycopersicum , Flagelina , Burkholderia gladioli/metabolismo , Prófagos/metabolismo , Arabidopsis/genética , Imunidade Vegetal/genética , Proteínas de Arabidopsis/metabolismo , Doenças das Plantas/microbiologia
4.
EMBO Rep ; 22(6): e51857, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33786997

RESUMO

Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Here, we report that Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. RNase activity is prominent on NGJ1 as well as other bacterial RNA while DNase activity is pertinent to only other bacteria. The associated immunity (TsiTBg) proteins harbor non-canonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxin-antitoxin (TA) systems. Genome analysis reveals that homologs of TseTBg are either encoded as TA or T6SS effectors in diverse bacteria. Our results indicate that a new ORF (encoding a hypothetical protein) has evolved as a result of operonic fusion of TA type TseTBg homolog with certain T6SS-related genes by the action of IS3 transposable elements. This has potentially led to the conversion of a TA into T6SS effector in Burkholderia. Our study exemplifies that bacteria can recruit toxins of TA systems as T6SS weapons to diversify its arsenal to dominate during inter-bacterial competitions.


Assuntos
Proteínas de Bactérias , Sistemas de Secreção Tipo VI , Antibacterianos , Bactérias , Proteínas de Bactérias/genética , Desoxirribonucleases , Sistemas de Secreção Tipo VI/genética
5.
Environ Microbiol ; 24(6): 2781-2796, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34766435

RESUMO

Bacteria utilize RpoN, an alternative sigma factor (σ54) to grow in diverse habitats, including nitrogen-limiting conditions. Here, we report that a rice-associated mycophagous bacterium Burkholderia gladioli strain NGJ1 encodes two paralogues of rpoN viz. rpoN1 and rpoN2. Both of them are upregulated during 24 h of mycophagous interaction with Rhizoctonia solani, a polyphagous fungal pathogen. Disruption of either one of rpoNs renders the mutant NGJ1 bacterium defective in mycophagy, whereas ectopic expression of respective rpoN genes restores mycophagy in the complementing strains. NGJ1 requires rpoN1 and rpoN2 for efficient biocontrol to prevent R. solani to establish disease in rice and tomato. Further, we have identified 17 genes having RpoN regulatory motif in NGJ1, majority of them encode potential type III secretion system (T3SS) effectors, nitrogen assimilation, and cellular transport-related functions. Several of these RpoN regulated genes as well as certain previously reported T3SS apparatus (hrcC and hrcN) and effector (Bg_9562 and endo-ß-1,3-glucanase) encoding genes are upregulated in NGJ1 but not in ΔrpoN1 or ΔrpoN2 mutant bacterium, during mycophagous interaction with R. solani. This highlights that RpoN1 and RpoN2 modulate T3SS, nitrogen assimilation as well as cellular transport systems in NGJ1 and thereby promote bacterial mycophagy.


Assuntos
Burkholderia gladioli , Fator sigma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Burkholderia gladioli/metabolismo , Regulação Bacteriana da Expressão Gênica , Nitrogênio/metabolismo , Fator sigma/genética , Fator sigma/metabolismo
6.
Proc Natl Acad Sci U S A ; 115(10): E2338-E2347, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29463717

RESUMO

Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1 million people in the United States, but the underlying mechanisms remain poorly understood. In this study, we aimed to determine the biomechanical and structural causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain. Transgenic D94A (aspartic acid-to-alanine) mice were created and investigated by echocardiography and invasive hemodynamic and molecular structural and functional assessments. Consistent with the DCM phenotype, a significant reduction of the ejection fraction (EF) was observed in ∼5- and ∼12-mo-old male and female D94A lines compared with respective WT controls. Younger male D94A mice showed a more pronounced left ventricular (LV) chamber dilation compared with female counterparts, but both sexes of D94A lines developed DCM by 12 mo of age. The hypocontractile activity of D94A myosin motors resulted in the rightward shift of the force-pCa dependence and decreased actin-activated myosin ATPase activity. Consistent with a decreased Ca2+ sensitivity of contractile force, a small-angle X-ray diffraction study, performed in D94A fibers at submaximal Ca2+ concentrations, revealed repositioning of the D94A cross-bridge mass toward the thick-filament backbone supporting the hypocontractile state of D94A myosin motors. Our data suggest that structural perturbations at the level of sarcomeres result in aberrant cardiomyocyte cytoarchitecture and lead to LV chamber dilation and decreased EF, manifesting in systolic dysfunction of D94A hearts. The D94A-induced development of DCM in mice closely follows the clinical phenotype and suggests that MYL2 may serve as a new therapeutic target for dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Cadeias Leves de Miosina/metabolismo , Sarcômeros/metabolismo , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Cadeias Leves de Miosina/genética , Sarcômeros/genética
7.
Skeletal Radiol ; 50(5): 927-936, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33026478

RESUMO

INTRODUCTION: Clinically measured Quadriceps angle (Q-angle) has low reliability. Measurement of angle between femoral shaft and patellar tendon (FSPT angle) on routine knee MRI was described in this study to represent the lateral vector forces of quadriceps mechanism. The cross-sectional study was designed to compare this angle between subjects with objective patellofemoral instability (PFI) versus those without PFI, to assess its reliability, and to assess its validity in terms of its ability to differentiate between PFI and non-PFI subjects using the "Receiver Operating Characteristic" (ROC) curve. MATERIALS AND METHODS: MRI scans of 20 subjects with PFI and 20 without PFI were obtained. FSPT angle was measured in each MRI by three different raters. In addition, the clinical Q-angle was also measured in the control group. RESULTS: The FSPT angle was significantly higher in PFI group as compared with the non-PFI group (p < 0.001). It had substantial inter-rater reliability of 0.82 (95% CI = 0.67-0.92) in the non-PFI group and 0.89 (95% CI = 0.78-0.95) in the PFI group. Test-retest reliability was more than 0.90. The AUC for the ROC curve was 0.86 (95% CI = 0.74-0.97). The clinical Q-angle measured in non-PFI subjects had inter-rater reliability of only 0.48 (95% CI = 0.21-0.72), and showed a fair correlation of 0.58 with the MRI angle. CONCLUSION: Measurement of FSPT angle was described on MRI with substantial intra-rater and inter-rater reliability. The angle was significantly higher in PFI versus non-PFI subjects and also showed a good ability to differentiate between these two groups in the ROC curve.


Assuntos
Ligamento Patelar , Articulação Patelofemoral , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética , Ligamento Patelar/diagnóstico por imagem , Articulação Patelofemoral/diagnóstico por imagem , Reprodutibilidade dos Testes
8.
J Craniofac Surg ; 32(4): e369-e373, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33235168

RESUMO

ABSTRACT: A prospective cohort study composed of 43 patients treated for unilateral mandibular fracture. The primary study variables were the post-traumatic IAN neurosensory score and the score after fracture reduction in two different groups on the basis of time lapse between presentation and treatment and displacement of mandible fracture. Appropriate descriptive and bivariate statistics were computed. The sample was analyzed over a one year period. It was observed that the recovery percentage (80%) was good in Group-A (n = 20) patients as compared to Group-B (n = 23) patients (43.47%) with significant P value of 0.015. Patients with displacement of ≥9 mm have neurosensory deficit of 80% while fracture displacement ≥ 5 mm to 8 mm have the neurosensory deficit of 34.21% which is significant with P value of 0.049. With each millimeter increase of displacement of fracture segments, more neurosensory deficit will be manifested. Delay in seeking in the treatment increases the risk because of continued movement. Where the injury is more severe, excessive displacement with increased time lapse from injury to surgical intervention, there is a higher possibility neurosensory deficit or no recovery. Early management can reduce the risk of permanent neurosensory deficits.


Assuntos
Fraturas Mandibulares , Traumatismos do Nervo Trigêmeo , Humanos , Fraturas Mandibulares/cirurgia , Nervo Mandibular , Estudos Prospectivos , Imagem com Lapso de Tempo
9.
Dent Traumatol ; 37(2): 321-329, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33217220

RESUMO

BACKGROUND/AIM: Pediatric mandibular distal fractures present unique treatment challenges which are usually managed with open reduction and internal fixation (ORIF) with the risk of developing tooth bud injuries. Conservative management through maxillomandibular fixation (MMF) with orthodontic bracket-elastic as an out-patient department (OPD) service has been used for these fractures presenting with derangement of occlusion. The aim of this study was to retrospectively analyze MMF with orthodontic bracket-elastic as a treatment method and its outcome for management of pediatric mandibular distal fractures. METHODOLOGY: Data of seventeen pediatric cases diagnosed with displaced mandibular distal fractures managed with MMF with orthodontic bracket-elastic over a period of 5 years were analyzed. In this technique, two weeks of immobilization and one week for guiding elastics were used. RESULTS: The mean age of patients was 7.6 ± 1.6 years with a mean follow-up of 24 months. All fractures healed uneventfully with satisfactory occlusion. The cases included 23.5% minimally displaced, and 64.7% moderately displaced and 11.8% significantly displaced fractures with step deformity with successful remodeling of the lower border contours over a duration of 18 months ± 1 month. The developing tooth buds in the fracture line showed no complications except for root dilacerations/malformation (n = 3). CONCLUSION: MMF with orthodontic bracket-elastic is a viable and conservative technique for the management of pediatric mandibular distal fractures which need to be verified through randomized trials for generalization of the results.


Assuntos
Tratamento Conservador , Fraturas Mandibulares , Criança , Fixação Interna de Fraturas , Humanos , Técnicas de Fixação da Arcada Osseodentária , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
10.
BMC Microbiol ; 20(1): 216, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689944

RESUMO

BACKGROUND: A rice associated bacterium Burkholderia gladioli strain NGJ1 demonstrates mycophagy, a phenomenon wherein bacteria feed on fungi. Previously, we have reported that NGJ1 utilizes type III secretion system (T3SS) to deliver a prophage tail-like protein (Bg_9562) into fungal cells to establish mycophagy. RESULTS: In this study, we report that calcium ion concentration influences the mycophagous ability of NGJ1 on Rhizoctonia solani, an important fungal pathogen. The calcium limiting condition promotes mycophagy while high calcium environment prevents it. The expression of various T3SS apparatus encoding genes of NGJ1 was induced and secretion of several potential T3SS effector proteins (including Bg_9562) into extracellular milieu was triggered under calcium limiting condition. Using LC-MS/MS proteome analysis, we identified several calcium regulated T3SS effector proteins of NGJ1. The expression of genes encoding some of these effector proteins was upregulated during mycophagous interaction of NGJ1 with R. solani. Further, mutation of one of these genes (endo-ß-1, 3- glucanase) rendered the mutant NGJ1 bacterium defective in mycophagy while complementation with full length copy of the gene restored its mycophagous activity. CONCLUSION: Our study provides evidence that low calcium environment triggers secretion of various T3SS effectors proteins into the extracellular milieu and suggests the importance of cocktail of these proteins in promoting mycophagy.


Assuntos
Burkholderia gladioli/fisiologia , Cálcio/metabolismo , Rhizoctonia/fisiologia , Sistemas de Secreção Tipo III/metabolismo , Regulação para Cima , Antibiose , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Celulase/genética , Celulase/metabolismo , Cromatografia Líquida , Regulação Bacteriana da Expressão Gênica , Mutação , Proteômica , Espectrometria de Massas em Tandem , Sistemas de Secreção Tipo III/genética
11.
FASEB J ; 33(3): 3152-3166, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30365366

RESUMO

Myosin light chain 2 ( MYL2) gene encodes the myosin regulatory light chain (RLC) simultaneously in heart ventricles and in slow-twitch skeletal muscle. Using transgenic mice with cardiac-specific expression of the human R58Q-RLC mutant, we sought to determine whether the hypertrophic cardiomyopathy phenotype observed in papillary muscles (PMs) of R58Q mice is also manifested in slow-twitch soleus (SOL) muscles. Skinned SOL muscles and ventricular PMs of R58Q animals exhibited lower contractile force that was not observed in the fast-twitch extensor digitorum longus muscles of R58Q vs. wild-type-RLC mice, but mutant animals did not display gross muscle weakness in vivo. Consistent with SOL muscle abnormalities in R58Q vs. wild-type mice, myosin ATPase staining revealed a decreased proportion of fiber type I/type II only in SOL muscles but not in the extensor digitorum longus muscles. The similarities between SOL muscles and PMs of R58Q mice were further supported by quantitative proteomics. Differential regulation of proteins involved in energy metabolism, cell-cell interactions, and protein-protein signaling was concurrently observed in the hearts and SOL muscles of R58Q mice. In summary, even though R58Q expression was restricted to the heart of mice, functional similarities were clearly observed between the hearts and slow-twitch skeletal muscle, suggesting that MYL2 mutated models of hypertrophic cardiomyopathy may be useful research tools to study the molecular, structural, and energetic mechanisms of cardioskeletal myopathy associated with myosin RLC.-Kazmierczak, K., Liang, J., Yuan, C.-C., Yadav, S., Sitbon, Y. H., Walz, K., Ma, W., Irving, T. C., Cheah, J. X., Gomes, A. V., Szczesna-Cordary, D. Slow-twitch skeletal muscle defects accompany cardiac dysfunction in transgenic mice with a mutation in the myosin regulatory light chain.


Assuntos
Miosinas Cardíacas/genética , Miosinas Cardíacas/fisiologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/fisiopatologia , Fibras Musculares de Contração Lenta/fisiologia , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/fisiologia , Substituição de Aminoácidos , Animais , Cardiomiopatia Hipertrófica/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Contração Muscular/genética , Contração Muscular/fisiologia , Fibras Musculares de Contração Lenta/patologia , Mutação de Sentido Incorreto , Contração Miocárdica/genética , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia , Músculos Papilares/patologia , Músculos Papilares/fisiopatologia , Proteômica
12.
J Muscle Res Cell Motil ; 41(4): 313-327, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31131433

RESUMO

The activity of cardiac and skeletal muscles depends upon the ATP-coupled actin-myosin interactions to execute the power stroke and muscle contraction. The goal of this review article is to provide insight into the function of myosin II, the molecular motor of the heart and skeletal muscles, with a special focus on the role of myosin II light chain (MLC) components. Specifically, we focus on the involvement of myosin regulatory (RLC) and essential (ELC) light chains in striated muscle development, isoform appearance and their function in normal and diseased muscle. We review the consequences of isoform switching and knockout of specific MLC isoforms on cardiac and skeletal muscle function in various animal models. Finally, we discuss how dysregulation of specific RLC/ELC isoforms can lead to cardiac and skeletal muscle diseases and summarize the effects of most studied mutations leading to cardiac or skeletal myopathies.


Assuntos
Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Cadeias Leves de Miosina/metabolismo , Animais , Humanos , Camundongos
13.
Pflugers Arch ; 471(5): 683-699, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30706179

RESUMO

Genetic cardiomyopathies, a group of cardiovascular disorders based on ventricular morphology and function, are among the leading causes of morbidity and mortality worldwide. Such genetically driven forms of hypertrophic (HCM), dilated (DCM), and restrictive (RCM) cardiomyopathies are chronic, debilitating diseases that result from biomechanical defects in cardiac muscle contraction and frequently progress to heart failure (HF). Locus and allelic heterogeneity, as well as clinical variability combined with genetic and phenotypic overlap between different cardiomyopathies, have challenged proper clinical prognosis and provided an incentive for identification of pathogenic variants. This review attempts to provide an overview of inherited cardiomyopathies with a focus on their genetic etiology in myosin regulatory (RLC) and essential (ELC) light chains, which are EF-hand protein family members with important structural and regulatory roles. From the clinical discovery of cardiomyopathy-linked light chain mutations in patients to an array of exploratory studies in animals, and reconstituted and recombinant systems, we have summarized the current state of knowledge on light chain mutations and how they induce physiological disease states via biochemical and biomechanical alterations at the molecular, tissue, and organ levels. Cardiac myosin RLC phosphorylation and the N-terminus ELC have been discussed as two important emerging modalities with important implications in the regulation of myosin motor function, and thus cardiac performance. A comprehensive understanding of such triggers is absolutely necessary for the development of target-specific rescue strategies to ameliorate or reverse the effects of myosin light chain-related inherited cardiomyopathies.


Assuntos
Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Restritiva/genética , Cadeias Leves de Miosina/genética , Animais , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Restritiva/etiologia , Cardiomiopatia Restritiva/patologia , Modelos Animais de Doenças , Humanos , Mutação
14.
Planta ; 249(6): 1987-1996, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30903269

RESUMO

MAIN CONCLUSION: Amino acid sequence and crystal structure analyses of Tma12, an insecticidal protein isolated from the fern Tectaria macrodonta, identify it as a carbohydrate-binding protein belonging to the AA10 family of lytic polysaccharide monooxygenases, and provide the first evidence of AA10 proteins in plants. Tma12, isolated from the fern Tectaria macrodonta, is a next-generation insecticidal protein. Transgenic cotton expressing Tma12 exhibits resistance against whitefly and viral diseases. Beside its insecticidal property, the structure and function of Tma12 are unknown. This limits understanding of the insecticidal mechanism of the protein and targeted improvement in its efficacy. Here we report the amino acid sequence analysis and the crystal structure of Tma12, suggesting that it is possibly a lytic polysaccharide monooxygenase (LPMO) of the AA10 family. Amino acid sequence of Tma12 shows 45% identity with a cellulolytic LPMO of Streptomyces coelicolor. The crystal structure of Tma12, obtained at 2.2 Å resolution, possesses all the major structural characteristics of AA10 LPMOs. A H2O2-based enzymatic assay also supports this finding. It is the first report of the occurrence of LPMO-like protein in a plant. The two facts that Tma12 possesses insecticidal activity and shows structural similarity with LPMOs collectively advocate exploration of microbial LPMOs for insecticidal potential.


Assuntos
Gleiquênias/enzimologia , Hemípteros/efeitos dos fármacos , Inseticidas/metabolismo , Oxigenases de Função Mista/metabolismo , Polissacarídeos/metabolismo , Sequência de Aminoácidos , Animais , Gleiquênias/química , Gleiquênias/genética , Gossypium/enzimologia , Gossypium/genética , Gossypium/fisiologia , Peróxido de Hidrogênio/metabolismo , Inseticidas/farmacologia , Oxigenases de Função Mista/química , Oxigenases de Função Mista/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Alinhamento de Sequência
15.
Environ Monit Assess ; 191(9): 576, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31428877

RESUMO

Evolution of submicron particles in terms of particle number concentration and mobility-equivalent diameter was measured during Diwali festival-specific intensive pyrotechnic displays in Varanasi over central Indo-Gangetic Plain (IGP). A scanning mobility particle sizer coupled with an optical particle sizer was used to fit in an overlapping size range, and particle number concentration was analyzed to have an insight into the new particle formation and subsequent evolution of particles from nucleation to accumulation mode. Further, variation in black carbon (BC) concentration and aerosol ionic composition was measured simultaneously. Frequent fluctuation in particle number concentration in and around Diwali festival was evidenced, primarily influenced by local emission sources and meteorology, with three distinct peaks in number concentrations (dN/dlogDp, 3.1-4.5 × 104 cm3) coinciding well with peak firework emission period (18:00-23:00 h). Submicron particle size distribution revealed a single peak covering a size range of 80-130 nm, and for all instances, number concentration maximum coincided with geometric mean minimum, indicating the emission primarily in the ultrafine range (< 0.1 µm). Interestingly, during peak firework emissions, besides rise in accumulation mode, an event of new particle formation was identified with increase in nucleation and small Aitken mode, before being dispersed to background aerosols. On an integral scale, a clear distinction was noted between a normal and an episodic event, with a definite shift in the formation of ultrafine particles compared with the accumulation mode. The BC diurnal profile was typical, with a prominent nocturnal peak (12.0 ± 3.9 µg m-3) corresponding to a decrease in the boundary layer height. A slight variation in maximum BC concentration (16.8 µg m-3) was noted in the night of the event coinciding well with firework emissions. An increase in some specific ionic species was also noted in combination with an increase in the overall cation to anion ratio, which was explained in terms of heterogeneous transformation of NOx and catalytic conversion of SO2. Graphical abstract Time-resolved evolution of particle size distribution during normal and episodic events.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Substâncias Explosivas , Material Particulado/análise , Férias e Feriados , Índia , Tamanho da Partícula , Fuligem/análise , Fatores de Tempo
17.
J Med Syst ; 41(4): 49, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28210832

RESUMO

To investigate the effectiveness, efficiency and cost gains in collecting patient eye health information from remote rural villages of India by trained field investigators through an Android Based Tablet Application namely 'Sankara Electronic Remote Vision Information System (SERVIS)". During January and March 2016, a population based cross-sectional study was conducted in three Indian states employing SERVIS and manual method. The SERVIS application has a 48-items survey instrument programed into the application. Data on 281 individuals were collected for each of these methods as part of screening. The demographic details of individuals between both screening methods were comparable (P>0.05). The mean time (in minutes) to screen an individual by SERVIS was significantly less when compared to manual method (6.57±1.46 versus 11.93±1.53) (P<0.0001). The efficiency of SERVIS in screening was significantly evident as 26% (n = 73) of the patients screened have been referred to campsite and 69.8% (n = 51) of those referred were visited the campsite for a detailed eye examination by an ophthalmologist. The cost of screening through SERVIS is significantly less when compared to manual method; INR 7,633 (USD 113.9) Versus INR 24,780 (USD 370). SERVIS is an effective and efficient tool in terms of patients' referral conversion to the camp site leading to timely detection of potential blinding eye conditions and their appropriate treatment. This ensures timely prevention of avoidable blindness and visual impairment. In addition, the storage and access of eye health epidemiological quality data is helpful to plan appropriate blindness prevention initiatives in rural India.


Assuntos
Computadores de Mão , População Rural , Transtornos da Visão/diagnóstico , Testes Visuais/instrumentação , Idoso , Cegueira/diagnóstico , Custos e Análise de Custo , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Testes Visuais/economia
18.
Chin J Traumatol ; 20(4): 216-221, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28330802

RESUMO

PURPOSE: Orofacial trauma is becoming a leading medical problem worldwide. Most of the studies pertaining to orofacial trauma have been done in urban areas but very little scientific literature is available for rural areas. METHODS: A prospective medical institute-based study of orofacial injury patients was carried out from May 2013 to April 2016 (36 Months). Data regarding incidence, age and sex distribution, causes, types and site of injury, treatment modalities and trauma associated complications were collected and analysed. RESULTS: A total of 784 patients were studied. Males outnumbered females by a ratio of 2.9:1. Age range was 9 months-75 years with the peak incidence in the age-group of 18-34 years. Most injuries were caused by road-side accidents (72.7%), followed by assault and falls in 11.6% and 8% respectively. Soft tissue injuries and mandibular fractures were the most common type of injuries. Head/neck (50.29%) and limb injuries (27.2%) were the most prevalent associated injuries. Surgical debridement and soft tissue suturing was the most common emergency procedure. Closed reduction was performed in 61% of patients and open reduction and internal fixation in 30% of cases and 9% were managed conservatively. Complications occurred in 6.88% of patients, mainly due to infection and malocclusion. The mean duration of hospital stay was (10.12 ± 6.24) days. CONCLUSION: This study highlights the importance of department of dental surgery along with other disciplinaries in the management of orofacial injuries. Road-side accident remains the major etiological factor of orofacial injuries in our setting.


Assuntos
Traumatismos Maxilofaciais/epidemiologia , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Tempo de Internação , Masculino , Fraturas Mandibulares/epidemiologia , Traumatismos Maxilofaciais/terapia , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões dos Tecidos Moles/epidemiologia , Adulto Jovem
19.
J Craniofac Surg ; 27(7): e665-e667, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27536919

RESUMO

Oral focal mucinosis is considered as oral counterpart of cutaneous focal mucinosis. The preoperative diagnosis of mucinosis is almost impossible because of its rarity and clinical similarity to other lesions of various etiologies. The histological diagnosis of oral mucinosis is important to better understand the etiopathogenesis, treatment modalities, and any recurrence of the lesion besides differentiating from the other soft tissue lesions.The purpose of this paper is to report the first case of bimaxillary involvement with dome-shaped elevated, rounded, asymptomatic, normally colored swelling in left posterior palatal mucosa and left mandibular posterior region in a 25-year old woman who was diagnosed as oral focal mucinosis histopathologically.


Assuntos
Maxila/diagnóstico por imagem , Doenças da Boca/diagnóstico , Mucosa Bucal/patologia , Mucinoses/diagnóstico , Adulto , Biópsia , Feminino , Humanos , Radiografia
20.
J Craniofac Surg ; 25(1): e86-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24406613

RESUMO

The aim of the present article was to discuss an unusual case report of the odontogenic cutaneous sinus with emphasis on diagnosis and treatment. The causative factor in this case was diagnosed intraoperatively due to infected follicular space in absence of any sign and symptoms. Timely diagnosis of the case could have prevented significant morbidity due to mistreatment medically and surgically with eventual recurrence.


Assuntos
Fístula Cutânea/diagnóstico , Fístula Dentária/diagnóstico , Fístula Cutânea/etiologia , Fístula Cutânea/cirurgia , Fístula Dentária/etiologia , Fístula Dentária/cirurgia , Seguimentos , Humanos , Masculino , Dente Serotino , Sulco Nasogeniano , Cistos Odontogênicos/complicações , Cistos Odontogênicos/diagnóstico , Cistos Odontogênicos/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Radiografia Panorâmica , Extração Dentária , Dente Impactado/complicações , Dente Impactado/diagnóstico , Dente Impactado/cirurgia
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