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1.
Hepatology ; 74(4): 2102-2117, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33982322

RESUMO

BACKGROUND AND AIMS: Induced pluripotent stem cells (iPSCs) provide an important tool for the generation of patient-derived cells, including hepatocyte-like cells, by developmental cues through an endoderm intermediate. However, most iPSC lines fail to differentiate into endoderm, with induction resulting in apoptosis. APPROACH AND RESULTS: To address this issue, we built upon published methods to develop an improved protocol. We discovered that doxycycline dramatically enhances the efficiency of iPSCs to endoderm differentiation by inhibiting apoptosis and promoting proliferation through the protein kinase B pathway. We tested this protocol in >70 iPSC lines, 90% of which consistently formed complete sheets of endoderm. Endoderm generated by our method achieves similar transcriptomic profiles, expression of endoderm protein markers, and the ability to be further differentiated to downstream lineages. CONCLUSIONS: Furthermore, this method achieves a 4-fold increase in endoderm cell number and will accelerate studies of human diseases in vitro and facilitate the expansion of iPSC-derived cells for transplantation studies.


Assuntos
Apoptose/efeitos dos fármacos , Doxiciclina/farmacologia , Endoderma , Células-Tronco Pluripotentes Induzidas/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antibacterianos/farmacologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/fisiologia , Endoderma/citologia , Endoderma/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
2.
J Neurosci ; 38(3): 631-647, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29217690

RESUMO

New dentate granule cells (DGCs) are continuously generated, and integrate into the preexisting hippocampal network in the adult brain. How an adult-born neuron with initially simple spindle-like morphology develops into a DGC, consisting of a single apical dendrite with further branches, remains largely unknown. Here, using retroviruses to birth date and manipulate newborn neurons, we examined initial dendritic formation and possible underlying mechanisms. We found that GFP-expressing newborn cells began to establish a DGC-like morphology at ∼7 d after birth, with a primary dendrite pointing to the molecular layer, but at this stage, with several neurites in the neurogenic zone. Interestingly, the Golgi apparatus, an essential organelle for neurite growth and maintenance, was dynamically repositioning in the soma of newborn cells during this initial integration stage. Two weeks after birth, by which time most neurites in the neurogenic zone were eliminated, a compact Golgi apparatus was positioned exclusively at the base of the primary dendrite. We analyzed the presence of Golgi-associated genes using single-cell transcriptomes of newborn DGCs, and among Golgi-related genes, found the presence of STK25 and STRAD, regulators of embryonic neuronal development. When we knocked down either of these two proteins, we found Golgi mislocalization and extensive aberrant dendrite formation. Furthermore, overexpression of a mutated form of STRAD, underlying the disorder polyhydramnios, megalencephaly, and symptomatic epilepsy, characterized by abnormal brain development and intractable epilepsy, caused similar defects in Golgi localization and dendrite formation in adult-born neurons. Together, our findings reveal a role for Golgi repositioning in regulating the initial integration of adult-born DGCs.SIGNIFICANCE STATEMENT Since the discovery of the continuous generation of new neurons in the adult hippocampus, extensive effort was directed toward understanding the functional contribution of these newborn neurons to the existing hippocampal circuit and associated behaviors, while the molecular mechanisms controlling their early morphological integration are less well understood. Dentate granule cells (DGCs) have a single, complex, apical dendrite. The events leading adult-born DGCs' to transition from simple spindle-like morphology to mature dendrite morphology are largely unknown. We studied establishment of newborn DGCs dendritic pattern and found it was mediated by a signaling pathway regulating precise localization of the Golgi apparatus. Furthermore, this Golgi-associated mechanism for dendrite establishment might be impaired in a human genetic epilepsy syndrome, polyhydramnios, megalencephaly, and symptomatic epilepsy.


Assuntos
Dendritos/ultraestrutura , Complexo de Golgi/ultraestrutura , Neurogênese/fisiologia , Neurônios/citologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Dendritos/metabolismo , Complexo de Golgi/metabolismo , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
3.
J Arthroplasty ; 34(4): 710-716.e3, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30527896

RESUMO

BACKGROUND: Polymicrobial hip arthroplasty infections are a subset of periprosthetic joint infection (PJI) with distinct challenges representing 10%-47% of PJI. METHODS: Records were reviewed from all PJIs involving partial or total hip arthroplasty with positive hip cultures between 2005 and 2015 in order to determine baseline characteristics and outcomes including treatment success, surgeries for infection, and days in hospital for infection. Analysis was restricted to patients who had at least 2 years of follow-up after their final surgery or hospitalization for infection. Factors with P-value less than .05 in univariate outcomes analysis were included in multivariable models. RESULTS: After multivariable analysis, 28 of 95 hip arthroplasty PJIs which were polymicrobial were associated with significantly lower treatment success, more surgery, and longer hospitalizations compared to PJIs which were not polymicrobial. Patients diagnosed with polymicrobial infection later in treatment (4 of 28) had the lowest treatment success rate, underwent the most surgery, and spent the longest time in hospital. CONCLUSION: Polymicrobial periprosthetic hip infection is a particularly devastating complication of hip arthroplasty associated with decreased likelihood of treatment success, increased surgery for infection, and greater time in hospital. Patients with late polymicrobial infection had the worst outcomes. This investigation further characterizes the natural history of periprosthetic hip infections with more than one infectious organism. Patients who present with a subsequent polymicrobial infection should be educated that they have a particularly difficult treatment course and treatment success may not be possible.


Assuntos
Artrite Infecciosa/microbiologia , Artroplastia de Quadril/efeitos adversos , Coinfecção/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Adulto , Idoso , Artrite Infecciosa/cirurgia , Coinfecção/cirurgia , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
4.
Br J Community Nurs ; 23(Sup9): S16-S22, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30156875

RESUMO

Diabetes is a global disease, and its prevalence has increased rapidly in the last century. Many complications are associated with diabetes, and diabetic foot ulcers (DFU) are common. There is a variety of different treatments for DFU, and the aim of this article is to discuss the factors responsible for delayed wound healing in patients with diabetes, and the treatment strategies that are available.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Higiene da Pele/enfermagem , Cicatrização/fisiologia , Bandagens , Terapia Baseada em Transplante de Células e Tecidos , Desbridamento , Terapia por Estimulação Elétrica , Humanos , Oxigenoterapia Hiperbárica , Tratamento de Ferimentos com Pressão Negativa , Ozônio/uso terapêutico , Transplante de Pele
5.
Cureus ; 15(5): e38841, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37303357

RESUMO

INTRODUCTION:  Endodontic and restorative treatment goal is to restore occlusion and normal function of a tooth and provide stability to the dental arch. Root canal bacterial infection and apical periodontitis profoundly impact the management and outcome of endodontic treatments. The crucial goal of nonsurgical root canal therapy (NSRCT) is the mechanical removal of infected tissues and the chemical killing of bacteria. The present study assessed the outcomes and factors associated with the failure of primary endodontic treatment. METHODS:  A total of 250 teeth from 219 patients (104 male and 146 female) were examined in the Conservative Dentistry and Endodontics department, who reported symptomatic root canal-treated teeth. Data through clinical examination and radiographic examination was recorded on a proforma designed for the study of each patient regarding endodontic failure. RESULTS:  According to the type of tooth maximum number of teeth that were reported with failure are the molars (67.6%), followed by premolar (14.0%), incisor (12.8%), and lastly, canines (5.6%). Based on the location of affected teeth, the maximum teeth that presented with failed root canal treatment were from mandibular posteriors (51.2%), followed by maxillary posteriors (31.60%), maxillary anterior (13.2%), mandibular anterior (4.0%). CONCLUSION:  Endodontic failures were mostly found in underfilled root canals and poorly sealed post-endodontic coronal restoration and strong association with peri-apical radiolucency.

6.
Hand Clin ; 39(4): 489-503, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37827602

RESUMO

In this article, we discuss the use of three-dimensional (3-D) printed patient-specific implants in the management of upper extremity fractures. Traditional fracture fixation methods involve the use of standard-sized implants, which may not adequately address the needs of every patient, particularly those who have complications related to fracture nonunion or malunion and those who have significant bone loss. The benefits and limitations of this technology are also discussed, along with considerations for implementation in clinical practice. Overall, the use of 3-D printed patient-specific implants holds promise for improving the accuracy and efficacy of upper extremity fracture management.


Assuntos
Traumatismos do Braço , Fraturas Ósseas , Humanos , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Fraturas Ósseas/cirurgia , Extremidade Superior/cirurgia
7.
Addict Health ; 15(1): 45-52, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37560076

RESUMO

Background: Chronic alcoholism is a multifactorial condition predisposed by environmental, social, and psychological factors. Alcohol dependence syndrome (ADS) can present with varied cutaneous and systemic manifestations. The effects of alcohol use include cutaneous infections, infestations, features of malnutrition, exacerbation of pre-existing dermatoses, and alcohol-related dermatoses. This study aimed to analyze and document cutaneous manifestations secondary to infections, infestations, malnutrition, and modifications of pre-existing dermatoses in ADS patients and investigate the correlation between the presence of cutaneous manifestations and duration and quantity of alcohol intake. Methods: The present observational study was carried out in the Department of Dermatology for a period of one year. A total of 172 male patients with ADS presenting with skin manifestations were included in the study. Detailed analysis of history, clinical examination, and relevant investigations were conducted. Findings: Out of 172 male patients with ADS, the most common dermatoses noted were infections (166, 96.5%) and features of malnutrition (161, 93.6%). Exacerbation of pre-existing dermatoses (101, 58.7%) and alcohol-related dermatoses (85, 49.4%) were also observed. Conclusion: Most of the dermatoses were significantly correlated with the quantity of alcohol intake than with its duration, implying that higher quantity of alcohol intake has more impact on cutaneous and systemic manifestations. Identifying the cutaneous manifestations in ADS patients plays an important role in recognizing the underlying systemic disorders which in turn facilitates early intervention and thereby prevents complications.

8.
bioRxiv ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37873382

RESUMO

Adults and children afflicted with the 22q11.2 deletion syndrome (22q11.2DS) exhibit cognitive, social, and emotional impairments, and are at significantly heightened risk for schizophrenia (SCZ). The impact of this deletion on early human brain development, however, has remained unclear. Here we harness organoid models of the developing human cerebral cortex, cultivated from subjects with 22q11.2DS and SCZ, as well as unaffected control samples, to identify cell-type-specific developmental abnormalities arising from this genomic lesion. Leveraging single-cell RNA-sequencing in conjunction with experimental validation, we find that the loss of genes within the 22q11.2 locus leads to a delayed development of cortical neurons. This compromised development was reflected in an elevated proportion of actively proliferating neural progenitor cells, coupled with a decreased fraction of more mature neurons. Furthermore, we identify perturbed molecular imprints linked to neuronal maturation, observe the presence of sparser neurites, and note a blunted amplitude in glutamate-induced Ca2+ transients. The aberrant transcription program underlying impaired development contains molecular signatures significantly enriched in neuropsychiatric genetic liability. MicroRNA profiling and target gene investigation suggest that microRNA dysregulation may drive perturbations of genes governing the pace at which maturation unfolds. Using protein-protein interaction network analysis we define complementary effects stemming from additional genes residing within the deleted locus. Our study uncovers reproducible neurodevelopmental and molecular alterations due to 22q11.2 deletions. These findings have the potential to facilitate disease modeling and promote the pursuit of therapeutic interventions.

9.
J Clin Anesth ; 85: 111040, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36549035

RESUMO

BACKGROUND: Immediate postoperative extubation (IPE) can reduce perioperative complications and length of stay (LOS), however it is performed variably after liver transplant across institutions and has historically excluded high-risk recipients from consideration. In late 2012, we planned and implemented a single academic institution structured quality improvement (QI) initiative to standardize perioperative care of liver transplant recipients without exceptions. We hypothesized that such an approach would lead to a sustained increase in IPE after primary (PAC) and delayed abdominal closure (DAC). METHODS: We retrospectively studied 591 patients from 2013 to 2018 who underwent liver transplant after initiative implementation. We evaluated trends in incidence of IPE versus delayed extubation (DE), and reintubation, LOS, and mortality. RESULTS: Overall, 476/591 (80.5%) recipients underwent PAC (278 IPE, 198 DE) and 115/591 (19.5%) experienced DAC (39 IPE, 76 DE). When comparing data from 2013 to data from 2018, the incidence of IPE increased from 9/67 (13.4%) to 78/90 (86.7%) after PAC and from 1/12 (8.3%) to 16/23 (69.6%) after DAC. For the same years, the incidence of IPE after PAC for recipients with MELD scores ≥30 increased from 0/19 (0%) to 12/17 (70.6%), for recipients who underwent simultaneous liver-kidney transplant increased from 1/8 (12.5%) to 4/5 (80.0%), and for recipients who received massive transfusion (>10 units of packed red blood cells) increased from 0/17 (0%) to 10/13 (76.9%). Reintubation for respiratory considerations <48 h after IPE occurred in 3/278 (1.1%) after PAC and 1/39 (2.6%) after DAC. IPE was associated with decreased intensive care unit (HR of discharge: 1.92; 95% CI: 1.58, 2.33; P < 0.001) and hospital LOS (HR of discharge: 1.45; 95% CI: 1.20, 1.76; P < 0.001) but demonstrated no association with mortality. CONCLUSION: A structured QI initiative led to sustained high rates of IPE and reduced LOS in all liver transplant recipients, including those classified as high risk.


Assuntos
Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Extubação/efeitos adversos , Fígado , Período Pós-Operatório , Tempo de Internação
10.
J Biol Chem ; 286(18): 15989-97, 2011 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-21454701

RESUMO

The metabolism of the amyloid precursor protein (APP) has been extensively investigated because its processing generates the amyloid-ß-peptide (Aß), which is a likely cause of Alzheimer disease. Much prior research has focused on APP processing using transgenic constructs and heterologous cell lines. Work to date in native neuronal cultures suggests that Aß is produced in very large amounts. We sought to investigate APP metabolism and Aß production simultaneously under more physiological conditions in vivo and in vitro using cultured rat cortical neurons and live pigs. We found in cultured neurons that both APP and Aß are secreted rapidly and at extremely high rates into the extracellular space (2-4 molecules/neuron/s for Aß). Little APP is degraded outside of the pathway that leads to extracellular release. Two metabolic pools of APP are identified, one that is metabolized extremely rapidly (t1/2;) = 2.2 h), and another, surface pool, composed of both synaptic and extrasynaptic elements, that turns over very slowly. Aß release and accumulation in the extracellular medium can be accounted for stoichiometrically by the extracellular release of ß-cleaved forms of the APP ectodomain. Two α-cleavages of APP occur for every ß-cleavage. Consistent with the results seen in cultured neurons, an extremely high rate of Aß production and secretion from the brain was seen in juvenile pigs. In summary, our experiments show an enormous and rapid production and extracellular release of Aß and the soluble APP ectodomain. A small, slowly metabolized, surface pool of full-length APP is also identified.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Amiloide/metabolismo , Neurônios/metabolismo , Animais , Células Cultivadas , Humanos , Neurônios/citologia , Estrutura Terciária de Proteína , Ratos
11.
Drug Deliv Transl Res ; 12(11): 2838-2855, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35445942

RESUMO

Diabetic wound management is a serious health care challenge due to higher rates of relapse, expensive treatment approaches, and poor healing outcomes. Among cell-based therapies, use of platelet-rich plasma (PRP) has been shown to be effective for diabetic wounds, but its poor shelf-life limits its clinical use. Here, we demonstrate a simple but effective polymer system to increase the shelf-life of PRP by developing a polyelectrolyte complex with dropwise addition of chitosan solution containing PRP by simple mixing at room temperature. Thus, prepared chitosan-fucoidan (CF) carrier complex encapsulated more than 95% of the loaded PRP. The resulting CF/PRP colloids were spherical in shape and ensured extended PRP release up to 72 h at 37 °C. Routine characterization (FT-IR, XRD, SEM) showed the material properties. The biological assays showed that CF complexes were biocompatible while CF/PRP enhanced the proliferation of fibroblasts and keratinocytes via higher Ki67 expression and fibroblast migration. Further investigations using a diabetic mouse model demonstrated significantly higher wound contraction and histopathological observations showed increased fibroblast migration, and collagen and cytokeratin deposition in treatment groups. The results are suggestive of the efficacy of CF/PRP as a cost-effective topical formulation for the sustained delivery of growth factors in treating chronic diabetic wounds.


Assuntos
Quitosana , Diabetes Mellitus Experimental , Plasma Rico em Plaquetas , Animais , Proliferação de Células , Colágeno/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Queratinas/metabolismo , Antígeno Ki-67/metabolismo , Camundongos , Plasma Rico em Plaquetas/metabolismo , Polieletrólitos , Polissacarídeos , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização
12.
GeoJournal ; 87(6): 4879-4899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34744264

RESUMO

As the United States leads COVID-19 cases on global charts, its spatial distribution pattern offers a unique opportunity for studying the social and ecological factors that contribute to the pandemic's scale and size. We use a GIS-data-based approach to evaluate four American cities-Anchorage (Alaska), Atlanta (Georgia), Phoenix (Arizona), and Portland (Oregon) characterized by the significant composition of different racial and ethnic group populations. Building upon previous studies that investigated urban spatial inequalities using the environmental justice framework, we examine: (1) the relative racial vulnerability of Census Block Groups (CBG) and ZIP Code Tabulation Areas (ZCTA) to COVID-19 (2) green space distribution at CBG and ZCTA scale. Using standard normalization methods, we ranked racial vulnerability against % available green space for each city. Our results highlight the legacy of past and present urban planning injustices. The project is useful from environmental justice, public health management, and urban planning perspectives. Supplementary Information: The online version contains supplementary material available at 10.1007/s10708-021-10538-8.

13.
Exp Clin Transplant ; 20(8): 782-785, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33272160

RESUMO

We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intra-operative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.


Assuntos
Doença da Artéria Coronariana , Coração Auxiliar , Transplante de Fígado , Infarto do Miocárdio , Disfunção Ventricular Esquerda , Idoso , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Balão Intra-Aórtico/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/cirurgia , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicações
14.
Nat Commun ; 13(1): 3340, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680927

RESUMO

Advances in 3D neuronal cultures, such as brain spheroids and organoids, are allowing unprecedented in vitro access to some of the molecular, cellular and developmental mechanisms underlying brain diseases. However, their efficacy in recapitulating brain network properties that encode brain function remains limited, thereby precluding development of effective in vitro models of complex brain disorders like schizophrenia. Here, we develop and characterize a Modular Neuronal Network (MoNNet) approach that recapitulates specific features of neuronal ensemble dynamics, segregated local-global network activities and a hierarchical modular organization. We utilized MoNNets for quantitative in vitro modelling of schizophrenia-related network dysfunctions caused by highly penetrant mutations in SETD1A and 22q11.2 risk loci. Furthermore, we demonstrate its utility for drug discovery by performing pharmacological rescue of alterations in neuronal ensembles stability and global network synchrony. MoNNets allow in vitro modelling of brain diseases for investigating the underlying neuronal network mechanisms and systematic drug discovery.


Assuntos
Encefalopatias , Esquizofrenia , Encéfalo , Histona-Lisina N-Metiltransferase , Humanos , Neurônios/fisiologia , Organoides , Esquizofrenia/genética
15.
Cancer Med ; 11(1): 194-206, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837341

RESUMO

INTRODUCTION: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS. METHODS: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years. DISCUSSION AND CONCLUSION: We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.


Assuntos
Terapia Neoadjuvante , Sarcoma/patologia , Sarcoma/terapia , Idoso , Intervalo Livre de Doença , Feminino , Fibrose , Humanos , Hialina/metabolismo , Infarto/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Necrose , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sarcoma/metabolismo , Sarcoma/cirurgia
16.
Epilepsy Behav ; 20(1): 95-102, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21146461

RESUMO

To examine atomoxetine's tolerability in patients with epilepsy, we reviewed medical records of all patients with epilepsy who were treated with atomoxetine in a tertiary care pediatric psychopharmacology practice. Twenty-seven patients (10.1 ± 4.2 years, 63% male) with an average seizure frequency at baseline of 7 ± 24 per month (median: 0, range: 0-90) were found. Symptoms of attention-deficit/hyperactivity disorder in twenty-five patients (92.5%) had previously not responded to stimulants. Atomoxetine, average dose 35.2 ± 24.4 mg, was given for a median of 26 weeks (range: 4-141). Seventeen patients (63%) discontinued atomoxetine due to: inadequate response (n=7, 26%), worsening behavior such as increased irritability/activation (n = 7, 26%), nonadherence (n=1, 4%), emerging psychotic-like symptoms (n=1, 4%), and appetite decrease and tremor (n=1, 4%). There were no discontinuations because of seizure exacerbation. Atomoxetine dose, epilepsy etiology, seizure type, and comorbid psychiatric disorders did not predict discontinuation. No safety problems of sufficient magnitude to preclude prospective studies of atomoxetine in children with epilepsy were found.


Assuntos
Inibidores da Captação Adrenérgica/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Epilepsia/complicações , Propilaminas/efeitos adversos , Adolescente , Cloridrato de Atomoxetina , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prontuários Médicos , Estudos Retrospectivos , Resultado do Tratamento
17.
Sci Rep ; 11(1): 1749, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462335

RESUMO

Halomonas malpeensis strain YU-PRIM-29T is a yellow pigmented, exopolysaccharide (EPS) producing halophilic bacterium isolated from the coastal region. To understand the biosynthesis pathways involved in the EPS and pigment production, whole genome analysis was performed. The complete genome sequencing and the de novo assembly were carried out using Illumina sequencing and SPAdes genome assembler (ver 3.11.1) respectively followed by detailed genome annotation. The genome consists of 3,607,821 bp distributed in 18 contigs with 3337 protein coding genes and 53% of the annotated CDS are having putative functions. Gene annotation disclosed the presence of genes involved in ABC transporter-dependent pathway of EPS biosynthesis. As the ABC transporter-dependent pathway is also implicated in the capsular polysaccharide (CPS) biosynthesis, we employed extraction protocols for both EPS (from the culture supernatants) and CPS (from the cells) and found that the secreted polysaccharide i.e., EPS was predominant. The EPS showed good emulsifying activities against the petroleum hydrocarbons and its production was dependent on the carbon source supplied. The genome analysis also revealed genes involved in industrially important metabolites such as zeaxanthin pigment, ectoine and polyhydroxyalkanoate (PHA) biosynthesis. To confirm the genome data, we extracted these metabolites from the cultures and successfully identified them. The pigment extracted from the cells showed the distinct UV-Vis spectra having characteristic absorption peak of zeaxanthin (λmax 448 nm) with potent antioxidant activities. The ability of H. malpeensis strain YU-PRIM-29T to produce important biomolecules makes it an industrially important bacterium.


Assuntos
Halomonas/genética , Halomonas/metabolismo , Polissacarídeos/metabolismo , Zeaxantinas/biossíntese , Vias Biossintéticas , Genes Bacterianos , Genoma Bacteriano , Halomonas/isolamento & purificação , Redes e Vias Metabólicas , Anotação de Sequência Molecular/métodos , Filogenia , Tolerância ao Sal , Sequenciamento Completo do Genoma/métodos
18.
Epilepsy Behav ; 18(3): 229-37, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20493783

RESUMO

OBJECTIVE: The goal of this study was to pilot a randomized controlled trial of OROS methylphenidate (OROS-MPH) to treat attention deficit hyperactivity disorder (ADHD) plus epilepsy. METHODS: Thirty-three patients, 6-18years of age, taking antiepileptic drugs and with a last seizure 1-60months prior were assigned to a maximum daily dose of 18, 36, or 54mg of OROS-MPH in a double-blind placebo-controlled crossover trial. RESULTS: There were no serious adverse events and no carryover effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than did placebo treatment. There were too few seizures during the active (5) and placebo arms (3) to confidently assess seizure risk; however, considering exposure time, we observed an increased daily risk of seizures with increasing dose of OROS-MPH, suggesting that potential safety concerns require further study. CONCLUSION: A larger study to assess the effect of OROS-MPH on seizure risk is needed. A crossover design including subjects with frequent seizures could maximize power and address high patient heterogeneity and recruitment difficulties.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Estimulantes do Sistema Nervoso Central/uso terapêutico , Epilepsia/complicações , Metilfenidato/uso terapêutico , Adolescente , Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Criança , Intervalos de Confiança , Estudos Cross-Over , Método Duplo-Cego , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde
19.
Case Rep Anesthesiol ; 2020: 8670102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082638

RESUMO

ASA closed claims from 2000 to 2009 have shown that adverse respiratory events are more common in nonoperating room locations like endoscopy suite than in the operating room (44% v/s 20%). Here, we report a case of lung atelectasis which resulted in hypoxemia in a malnourished patient undergoing endoscopic procedure. It is crucial to identify the high-risk patients and monitor them appropriately in the postoperative phase. Continuous capnometry may offer additional benefit by identifying hypercapnia, hypoventilation at the earliest in the recovery area, thus preventing serious complications.

20.
Int J Biol Macromol ; 163: 745-755, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32599248

RESUMO

Silver nanoparticles (AgNPs) have gained attention due to their exceptional physicochemical properties and biological activities, owing to which they are extensively used in biomedical field. We synthesized AgNPs by rapid microwave-assisted method using fucoidan as a reducing agent. The synthesized fucoidan-AgNPs (F-AgNPs) were characterized for the structural and functional properties. The bactericidal effect and mode of action of F-AgNPs on the pathogenic bacteria and biofilm formation were investigated along with the cytotoxicity studies. The UV-Visible spectra of the F-AgNPs showed the surface resonance peak at 419 nm. The nanoparticles were spherical in shape with particle size of 59.5 ± 1.46 nm and polydispersity index (PDI) of 0.3 ± 0.01. Capping of fucoidan on AgNPs was confirmed by FTIR with characteristic peaks of sulfate group. Silver content of F-AgNPs was 87% with 13% contribution from the fucoidan moieties. The F-AgNPs showed antimicrobial activity against common pathogenic bacteria and was able to inhibit biofilm formation in Pseudomonas aeruginosa at 20 µg/mL concentration. The oxidative stress and intracellular protein leakage were observed due to the F-AgNP interaction with the cell bringing about bactericidal effect. The results highlight the synthesis and bioactivity of AgNPs doped with organic moieties for applications as antimicrobials.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/química , Nanopartículas Metálicas/química , Micro-Ondas , Polissacarídeos/química , Prata/química , Técnicas de Química Sintética , Química Verde , Estresse Oxidativo , Tamanho da Partícula , Espécies Reativas de Oxigênio , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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