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1.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35131859

RESUMO

Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde-fixed heterograft tissue, such as bovine pericardium (BP), are widely used for treating heart valve disease, a group of disorders that affects millions. Structural valve degeneration (SVD) of BHV due to both calcification and the accumulation of advanced glycation end products (AGE) with associated serum proteins limits durability. We hypothesized that BP modified with poly-2-methyl-2-oxazoline (POZ) to inhibit protein entry would demonstrate reduced accumulation of AGE and serum proteins, mitigating SVD. In vitro studies of POZ-modified BP demonstrated reduced accumulation of serum albumin and AGE. BP-POZ in vitro maintained collagen microarchitecture per two-photon microscopy despite AGE incubation, and in cell culture studies was associated with no change in tumor necrosis factor-α after exposure to AGE and activated macrophages. Comparing POZ and polyethylene glycol (PEG)-modified BP in vitro, BP-POZ was minimally affected by oxidative conditions, whereas BP-PEG was susceptible to oxidative deterioration. In juvenile rat subdermal implants, BP-POZ demonstrated reduced AGE formation and serum albumin infiltration, while calcification was not inhibited. However, BP-POZ rat subdermal implants with ethanol pretreatment demonstrated inhibition of both AGE accumulation and calcification. Ex vivo laminar flow studies with human blood demonstrated BP-POZ enhanced thromboresistance with reduced white blood cell accumulation. We conclude that SVD associated with AGE and serum protein accumulation can be mitigated through POZ functionalization that both enhances biocompatibility and facilitates ethanol pretreatment inhibition of BP calcification.


Assuntos
Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/terapia , Oxazóis/farmacologia , Pericárdio/efeitos dos fármacos , Animais , Materiais Biocompatíveis , Calcificação Fisiológica/efeitos dos fármacos , Calcinose/tratamento farmacológico , Calcinose/metabolismo , Calcinose/terapia , Linhagem Celular , Colágeno/metabolismo , Etanol/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Doenças das Valvas Cardíacas/metabolismo , Próteses Valvulares Cardíacas , Xenoenxertos/efeitos dos fármacos , Humanos , Masculino , Oxirredução/efeitos dos fármacos , Pericárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Células THP-1
2.
Emerg Infect Dis ; 30(6): 1193-1202, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781931

RESUMO

Chronic wasting disease (CWD) is a cervid prion disease with unknown zoonotic potential that might pose a risk to humans who are exposed. To assess the potential of CWD to infect human neural tissue, we used human cerebral organoids with 2 different prion genotypes, 1 of which has previously been associated with susceptibility to zoonotic prion disease. We exposed organoids from both genotypes to high concentrations of CWD inocula from 3 different sources for 7 days, then screened for infection periodically for up to 180 days. No de novo CWD propagation or deposition of protease-resistant forms of human prions was evident in CWD-exposed organoids. Some persistence of the original inoculum was detected, which was equivalent in prion gene knockout organoids and thus not attributable to human prion propagation. Overall, the unsuccessful propagation of CWD in cerebral organoids supports a strong species barrier to transmission of CWD prions to humans.


Assuntos
Organoides , Príons , Doença de Emaciação Crônica , Doença de Emaciação Crônica/transmissão , Humanos , Príons/metabolismo , Animais , Encéfalo/patologia , Genótipo
3.
Nature ; 558(7710): 425-429, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29925970

RESUMO

Molecular-scale manipulation of electronic and ionic charge accumulation in materials is the backbone of electrochemical energy storage1-4. Layered van der Waals (vdW) crystals are a diverse family of materials into which mobile ions can electrochemically intercalate into the interlamellar gaps of the host atomic lattice5,6. The structural diversity of such materials enables the interfacial properties of composites to be optimized to improve ion intercalation for energy storage and electronic devices7-12. However, the ability of heterolayers to modify intercalation reactions, and their role at the atomic level, are yet to be elucidated. Here we demonstrate the electrointercalation of lithium at the level of individual atomic interfaces of dissimilar vdW layers. Electrochemical devices based on vdW heterostructures 13 of stacked hexagonal boron nitride, graphene and molybdenum dichalcogenide (MoX2; X = S, Se) layers are constructed. We use transmission electron microscopy, in situ magnetoresistance and optical spectroscopy techniques, as well as low-temperature quantum magneto-oscillation measurements and ab initio calculations, to resolve the intermediate stages of lithium intercalation at heterointerfaces. The formation of vdW heterointerfaces between graphene and MoX2 results in a more than tenfold greater accumulation of charge in MoX2 when compared to MoX2/MoX2 homointerfaces, while enforcing a more negative intercalation potential than that of bulk MoX2 by at least 0.5 V. Beyond energy storage, our combined experimental and computational methodology for manipulating and characterizing the electrochemical behaviour of layered systems opens new pathways to control the charge density in two-dimensional electronic and optoelectronic devices.

4.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33443221

RESUMO

Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.


Assuntos
Ebolavirus/imunologia , Insuficiência Respiratória/virologia , Doenças dos Suínos/virologia , Animais , Anticorpos Antivirais/imunologia , Causalidade , Vírus de DNA/patogenicidade , Surtos de Doenças/prevenção & controle , Ebolavirus/metabolismo , Ebolavirus/patogenicidade , Filipinas/epidemiologia , Insuficiência Respiratória/veterinária , Sus scrofa/virologia , Suínos/virologia , Doenças dos Suínos/epidemiologia , Eliminação de Partículas Virais/imunologia
5.
J Am Chem Soc ; 145(11): 6371-6382, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36897933

RESUMO

The analysis at the single-molecule level of proteins and their interactions can provide critical information for understanding biological processes and diseases, particularly for proteins present in biological samples with low copy numbers. Nanopore sensing is an analytical technique that allows label-free detection of single proteins in solution and is ideally suited to applications, such as studying protein-protein interactions, biomarker screening, drug discovery, and even protein sequencing. However, given the current spatiotemporal limitations in protein nanopore sensing, challenges remain in controlling protein translocation through a nanopore and relating protein structures and functions with nanopore readouts. Here, we demonstrate that supercharged unstructured polypeptides (SUPs) can be genetically fused with proteins of interest and used as molecular carriers to facilitate nanopore detection of proteins. We show that cationic SUPs can substantially slow down the translocation of target proteins due to their electrostatic interactions with the nanopore surface. This approach enables the differentiation of individual proteins with different sizes and shapes via characteristic subpeaks in the nanopore current, thus facilitating a viable route to use polypeptide molecular carriers to control molecular transport and as a potential system to study protein-protein interactions at the single-molecule level.


Assuntos
Nanoporos , Peptídeos/química , Proteínas , Sequência de Aminoácidos , Nanotecnologia
6.
PLoS Pathog ; 17(1): e1009195, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465158

RESUMO

SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , COVID-19/patologia , Queratina-18/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , COVID-19/imunologia , COVID-19/virologia , Modelos Animais de Doenças , Feminino , Humanos , Queratina-18/imunologia , Pulmão/imunologia , Pulmão/patologia , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , SARS-CoV-2/fisiologia , Traqueia/imunologia , Traqueia/virologia
7.
Proc Natl Acad Sci U S A ; 117(12): 6771-6776, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32054787

RESUMO

The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Animais , Betacoronavirus , COVID-19 , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Pandemias , Pneumonia Viral , Profilaxia Pós-Exposição , SARS-CoV-2 , Carga Viral , Replicação Viral/efeitos dos fármacos
8.
Cogn Neuropsychol ; 38(3): 179-204, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34529546

RESUMO

The imaging genetics of specific reading disabilities (SRD) is an emerging field that aims to characterize the disabilities' neurobiological causes, including atypical brain structure and function and distinct genetic architecture. The present review aimed to summarize current imaging genetics studies of SRD, characterize the effect sizes of reported results by calculating Cohen's d, complete a Fisher's Combined Probability Test for genes featured in multiple studies, and determine areas for future research. Results demonstrate associations between SRD risk genes and reading network brain phenotypes. The Fisher's test revealed promising results for the genes DCDC2, KIAA0319, FOXP2, SLC2A3, and ROBO1. Future research should focus on exploratory approaches to identify previously undiscovered genes. Using comprehensive neuroimaging (e.g., functional and effective connectivity) and genetic (e.g., sequencing and epigenetic) techniques, and using larger samples, diverse stages of development, and longitudinal investigations, would help researchers understand the neurobiological correlates of SRD to improve early identification.


Assuntos
Dislexia , Proteínas do Tecido Nervoso , Encéfalo/diagnóstico por imagem , Dislexia/genética , Humanos , Proteínas Associadas aos Microtúbulos , Neuroimagem , Receptores Imunológicos
9.
Child Dev ; 92(1): 7-20, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32767770

RESUMO

Orphans and vulnerable children affected by HIV/AIDS (HIV OVC) are at risk for cognitive difficulties and lack of access to education. Interventions addressing cognitive or educational outcomes for HIV OVC worldwide were examined through systematic searches conducted from October 2016 to 2019. We examined the summative effectiveness of interventions and the specific effects of participant age and intervention length. Interventions targeting cognitive outcomes had a small, significant effect, with no effect of moderating variables. Interventions targeting educational outcomes had significant effects. Educational interventions over 1 year were effective, but effects of intervention length were not significant. Overall, this review provides support for the effectiveness of interventions targeting cognitive and educational outcomes for OVC and highlights the need for more research on such interventions.


Assuntos
Desenvolvimento Infantil , Proteção da Criança/psicologia , Crianças Órfãs/psicologia , Infecções por HIV/psicologia , Populações Vulneráveis/psicologia , Criança , Proteção da Criança/estatística & dados numéricos , Filho de Pais com Deficiência/psicologia , Crianças Órfãs/estatística & dados numéricos , Pré-Escolar , Escolaridade , Infecções por HIV/epidemiologia , Humanos , Masculino , Apoio Social , Populações Vulneráveis/estatística & dados numéricos
10.
Zentralbl Chir ; 146(1): 44-57, 2021 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-33296936

RESUMO

BACKGROUND: The surgical procedure for patients with colorectal cancer (CRC) in the palliative situation cannot be adequately standardised. The present study was initiated to identify criteria for the decision for resection of the malignancy with or without anastomosis. PATIENTS/MATERIAL AND METHODS: In a unicentric retrospective analysis, 103 patients after palliative resection with or without anastomosis due to CRC were examined. Using univariate and logistic regression analysis, the influence of a total of 40 factors on postoperative morbidity and mortality was assessed. RESULTS: In 46 cases, resection with primary anastomosis and in 57 cases a discontinuity resection was performed. Postoperative morbidity was 44.7% and mortality 17.5%. After one-stage resection with anastomosis, nicotine abuse (OR 4.2; p = 0.044), hypalbuminaemia (OR 4.0; p = 0.012), ASA score > 2 (OR 3.7; p = 0.030) and liver remodelling/cirrhosis (OR 3.6; p = 0.031) increased the risk for postoperative complications. Hypalbuminaemia (OR 1.8; p = 0.036), cachexia (OR 1.8; p = 0.043), anaemia (OR 1.5; p = 0.038) and known alcohol abuse (OR 1.9; p = 0.023) were identified as independent risk factors for early postoperative mortality. After discontinuity resection, renal failure (OR 2.1; p = 0.042) and cachexia (OR 1.5; p = 0.045) led to a significant increase in the risk of postoperative morbidity, alcohol abuse (OR 1.8; p = 0.041) in mortality. Hypalbuminaemia (OR 2.8; p = 0.019) and an ASA score > 2 (OR 2.6; p = 0.004) after resection and reconstruction increased the risk of major complications according to Clavien-Dindo, while pre-existing renal failure (OR 1.6; p = 0.023) increased the risk after discontinuity resection. In univariate analysis, an ASA score > 2 (p = 0.038) after simultaneous tumour resection and reconstruction, and urgent surgery in both groups with or without primary anastomosis were additionally identified as significant parameters with a negative influence on mortality (p = 0.010 and p = 0.017). CONCLUSION: Palliative resections of colorectal carcinomas have high morbidity and mortality. Especially in cases of pre-existing alcohol abuse and/or urgent indication for surgery, more intensive monitoring should be performed. In the case of anaemia, cachexia, hypalbuminemia and an ASA score > 2, discontinuity resection may be the more appropriate procedure.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Colorretais/cirurgia , Humanos , Cuidados Paliativos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco
11.
Psychiatr Danub ; 33(2): 147-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185734

RESUMO

Depression is the most prevalent mood disorder among pregnant women. Only 50% of women seek intervention during gestation. Untreated during pregnancy, depression can induce obstetric and neonatal complications, most commonly, anhedonia, suboptimal weight gain, suicidal behavior, pre-term birth, and/or spontaneous miscarriage. The babies more often suffer cognitive deficits, low birth weight, and growth delay. The mothers subsequently also experience an increased risk for significant degrees of postpartum depression. Those with relatively milder cases of depression should initially receive psychotherapy. Otherwise, there are many antidepressant medications available for the pharmacotherapy of depression. However, treating pregnant females with depression is a challenge because of potential teratogenic effects caused by many pharmaceuticals. Physicians should know the recommended guidelines for treating depressed women during a time of gestation. It is crucial to identify women suffering from depression during pregnancy, and electing those that warrant pharmacotherapy while picking the best and safest medication is a complex process with paramount significance. Before prescribing an antidepressant drug, explain the advantages and disadvantages of the interventions. Whenever prescribing during these circumstances, more than conventionally close obstetric, emotional, and medication monitoring is to be provided. This would also include an emphasis on diet, exercise, psychotherapy, and avoidance of any non-critical medicinal or other substance exposures.


Assuntos
Depressão Pós-Parto , Complicações na Gravidez , Antidepressivos/efeitos adversos , Exercício Físico , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Gestantes
12.
J Virol ; 93(18)2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31292241

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV) is a cause of severe hemorrhagic fever. Its tick reservoir and vector are widely distributed throughout Africa, Southern and Eastern Europe, the Middle East, and Asia. Serological evidence suggests that CCHFV can productively infect a wide variety of species, but only humans develop severe, sometimes fatal disease. The role of the host adaptive immunity in control or contribution to the severe pathology seen in CCHF cases is largely unknown. Studies of adaptive immune responses to CCHFV have been limited due to lack of suitable small animal models. Wild-type mice are resistant to CCHFV infection, and type I interferon-deficient mice typically develop a rapid-onset fatal disease prior to development of adaptive immune responses. We report here a mouse model in which type I interferon-deficient mice infected with a clinical isolate of CCHFV develop a severe inflammatory disease but ultimately recover. Recovery was coincident with development of CCHFV-specific B- and T-cell responses that were sustained for weeks postinfection. We also found that recovery from a primary CCHFV infection could protect against disease following homologous or heterologous reinfection. Together this model enables study of multiple aspects of CCHFV pathogenesis, including convalescence, an important aspect of CCHF disease that existing mouse models have been unsuitable for studying.IMPORTANCE The role of antibody or virus-specific T-cell responses in control of acute Crimean-Congo hemorrhagic fever virus infection is largely unclear. This is a critical gap in our understanding of CCHF, and investigation of convalescence following severe acute CCHF has been limited by the lack of suitable small animal models. We report here a mouse model of CCHF in which infected mice develop severe disease but ultimately recover. Although mice developed an inflammatory immune response along with severe liver and spleen pathology, these mice also developed CCHFV-specific B- and T-cell responses and were protected from reinfection. This model provides a valuable tool to investigate how host immune responses control acute CCHFV infection and how these responses may contribute to the severe disease seen in CCHFV-infected humans in order to develop therapeutic interventions that promote protective immune responses.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo , Interferon Tipo I/genética , Imunidade Adaptativa/imunologia , Animais , Convalescença , Modelos Animais de Doenças , Vírus da Febre Hemorrágica da Crimeia-Congo/fisiologia , Febre Hemorrágica da Crimeia/metabolismo , Febre Hemorrágica da Crimeia/virologia , Interferon Tipo I/metabolismo , Fígado/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Baço/virologia
13.
Ann Behav Med ; 54(11): 853-866, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525205

RESUMO

BACKGROUND: Worldwide, there are more than 13.3 million orphans and vulnerable children affected by Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (HIV OVC), defined as individuals below the age of 18 who have lost one or both parents to HIV/AIDS or have been made vulnerable by HIV/AIDS; they are at risk for negative psychosocial and cognitive outcomes. PURPOSE: This meta-analysis aimed to examine the scientific literature on available interventions for HIV OVC, with a focus on community-based interventions (CBI). METHODS: Systematic electronic searches were conducted from four databases between October 2016 and April 2017 to identify articles investigating the effectiveness of interventions for HIV OVC. Effect sizes were calculated for each article which provided enough information and data points for analyses. RESULTS: Seventy-four articles were reviewed, including psychosocial interventions (d = 0.30), cognitive interventions (d = 0.14), social protection interventions (d = 0.36), and community-based interventions (CBI; d = 0.36). Study-specific effect sizes varied widely, ranging from -1.09 to 2.26, that is, from a negative effect to an impressively large positive one, but the majority of studies registered small to medium effects (the overall effect size for all studies was 0.32, SE = 0.03, 95% CI: 0.26-0.37). Social protection interventions had the highest positive outcomes whereas CBI tended to have the fewest significant positive outcomes, with some outcomes worsening instead of improving. CONCLUSIONS: Overall, interventions provided to OVC have potential for improving cognitive, psychosocial, and risk-behavior outcomes. Social protection interventions and CBI had the highest effect sizes, but CBI had positive effects on fewer outcomes and demonstrated some negative effects. CBI warrant scrutiny for improvement, as they represent an important form of culturally embedded services with potentially long-term benefits to OVC, yet appear to be differentially effective. Successful components of other types of intervention were identified, including cash grants, mentorship, and family therapy. In addition, more research is needed that attends to which interventions may be more effective for specific populations, or that studies cost-effectiveness.


Assuntos
Filho de Pais com Deficiência/psicologia , Crianças Órfãs/psicologia , Terapia Cognitivo-Comportamental , Serviços de Saúde Comunitária , Intervenção Psicossocial , Apoio Social , Populações Vulneráveis/psicologia , Síndrome da Imunodeficiência Adquirida/psicologia , Adolescente , Criança , Pré-Escolar , Cognição , Infecções por HIV/psicologia , Comportamentos de Risco à Saúde , Humanos , Política Pública/economia
14.
J Surg Res ; 242: 318-322, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31129240

RESUMO

BACKGROUND: Laparoscopic intraoperative cholangiogram (IOC) with common bile duct exploration (CBDE) and endoscopic retrograde cholangiopancreatography (ERCP) are two therapeutic techniques for choledocholithiasis. The preferred technique is unclear. MATERIALS AND METHODS: We identified subjects who underwent laparoscopic cholecystectomy (LC) and IOC/CBDE or ERCP from July 1, 2006, to December 31, 2016. We retrospectively reviewed 81 patients (≤ 18 y) who received these interventions for suspected choledocholithiasis. Main outcomes analyzed were success of intervention and complications. RESULTS: Of the 81 patients, 21 ERCPs and three endoscopic ultrasounds (EUSs) were performed before LC. Eighteen of 21 (85.7%) patients had stones or sludge cleared by ERCP, whereas 3 (14.3%) had normal common bile ducts without evidence of stones. Five of 24 (20.8%) had significant post-ERCP complications. Seven of 24 (29.2%) had more than one admission. Sixty of 81 patients underwent LC with IOC ± CBDE. Twenty one of 60 (36.2%) were found to have abnormal IOC. Eight of 15 (53.3%) attempted laparoscopic CBDE were successful. Eleven of 21 (52.4%) patients with abnormal IOC had post-LC ERCP (10) and EUS (1). Patients admitted to the Pediatric Surgery service were more likely to undergo LC first than ERCP/EUS (OR 3.46, 95% CI 1.26 to 9.45, P = 0.016). Patients undergoing LC first had a shorter length of stay (mean LOS 5.13 d versus 4.07, median 5.0 versus 3.0 d, P-value < 0.05). CONCLUSIONS: Successful and safe laparoscopic treatment of choledocholithiasis is possible in the pediatric patient. A laparoscopic-first approach to suspected choledocholithiasis may reduce the number of procedures needed in this patient population.


Assuntos
Colangiografia/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Coledocolitíase/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Coledocolitíase/diagnóstico por imagem , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Dev Psychobiol ; 61(2): 304-310, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471082

RESUMO

This study aimed to examine whether the relationship between mothers' DNA methylation profiles and offspring's depression is modulated by negative parenting. The participants were 35 African-American mother-offspring dyads. Young adult offspring (19 females; age = 17-29.5 years) were assessed on depressive symptoms, and mothers (36-51 years) were assessed on negative parenting. Methyl-binding domain (MBD) sequencing was used to assay genome-wide DNA methylation in peripheral T lymphocytes. Controlling for the effect of offspring's DNA methylation, mothers' DNA methylation was positively associated with offspring's depression. Hypermethylation of a subset of the epigenetic markers was associated with increased negative parenting. Negative parenting was positively correlated with offspring's depression as well, suggesting that negative parenting may be a modulator between the mother's epigenome and offspring's depression. This study is one of the first investigations of the modulating role of parenting behavior in associations between the mother's epigenome and offspring's depression.


Assuntos
Metilação de DNA , Depressão , Epigênese Genética , Relações Mãe-Filho/psicologia , Poder Familiar/psicologia , Adolescente , Adulto , Depressão/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
J Infect Dis ; 218(suppl_5): S458-S465, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30215737

RESUMO

Filoviruses are among the most pathogenic infectious agents known to human, with high destructive potential, as evidenced by the recent Ebola virus epidemic in West Africa. As members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers. In this study we compare the pathogenesis of Ravn virus (RAVV) and Marburg virus (MARV) strains Angola, Musoke, and Ozolin in rhesus and cynomolgus macaques, the 2 nonhuman primate species most commonly used in filovirus research. Our results reveal the most pathogenic MARV strain to be Angola, followed by Musoke, whereas Ozolin is the least pathogenic. We also demonstrate that RAVV is highly pathogenic in cynomolgus macaques but less pathogenic in rhesus macaques. Our results demonstrate a preferential infection of endothelial cells by MARVs; in addition, analysis of tissue samples suggests that lymphocyte and hepatocyte apoptosis might play a role in MARV pathogenicity. This information expands our knowledge about pathogenicity and virulence of marburgviruses.


Assuntos
Doença do Vírus de Marburg/etiologia , Marburgvirus/patogenicidade , Animais , Apoptose , Hepatócitos/patologia , Macaca fascicularis , Macaca mulatta , Macrófagos/patologia , Masculino , Doença do Vírus de Marburg/imunologia , Doença do Vírus de Marburg/patologia , Fenótipo
17.
Am J Pathol ; 186(3): 630-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26724387

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV-infected humans, which will aid in investigating MERS-CoV disease pathogenesis.


Assuntos
Antígenos Virais/sangue , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/imunologia , Replicação Viral/imunologia , Animais , Antígenos Virais/análise , Callithrix , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Macaca mulatta , Macrófagos Alveolares/classificação , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Neutrófilos/imunologia , Coelhos , Carga Viral , Virulência
18.
Pediatr Surg Int ; 33(1): 15-21, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27722897

RESUMO

PURPOSE: Surgical procedures for high imperforate anus have ranged from the posterior sagittal anorectoplasty (PSARP) to laparoscopic-assisted anorectoplasty (LAARP). PSARP bisects the sphincter muscle complex, introducing muscle injury and scarring. LAARP uses a straight trocar to traverse an often non-linear sphincter muscle complex. MRI-assisted LAARP (MRI-LAARP) guides the neorectum precisely through the middle of the entire sphincter complex along its trajectory. We present our experience utilizing MRI intraoperatively during LAARP. METHODS/PROCEDURE: Ten children underwent MRI-LAARP procedures. Intraoperative MRI was performed to delineate the sphincter complex, and to guide the advancement of an MRI-compatible needle through the center of the complex from skin to the peritoneal cavity. The remainder of the procedure was completed using the standard LAARP technique. RESULTS: All had successful MRI needle placement through the sphincter complex. Nine patients had successful laparoscopic pull-through procedures; one was converted to open due to severe intraperitoneal adhesions. Postoperative stay averaged 5.4 ± 4.4 days. Out of the ten patients, one child had mild dehiscence of the anal anastomosis requiring revision 11 days postoperatively. CONCLUSION: The theoretical advantage of the MRI-LAARP is placing the neorectum through the entire sphincter complex without transecting the muscle. Follow-up of these patients shows good short-term results; however, long-term follow-up will be needed to best assess sphincter and bowel function.


Assuntos
Canal Anal/cirurgia , Anus Imperfurado/cirurgia , Laparoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Procedimentos de Cirurgia Plástica/métodos , Reto/cirurgia , Cirurgia Assistida por Computador/métodos , Canal Anal/diagnóstico por imagem , Anus Imperfurado/diagnóstico , Feminino , Humanos , Lactente , Masculino , Cavidade Peritoneal , Reto/diagnóstico por imagem , Resultado do Tratamento
19.
Pediatr Surg Int ; 32(11): 1053-1057, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27590475

RESUMO

BACKGROUND: Neonates commonly require central access, and in those with very low or extremely low birthweight this can be challenging. Described here is a technique that uses ultrasound guidance in the placement of peripherally inserted central catheters (PICC) in neonates and an analysis of outcomes. METHODS: A retrospective chart review was conducted of all patients below 1500 g that underwent placement of a peripherally inserted central catheter under ultrasound guidance between January 1, 2012, and December 31, 2014 at a single center. All patients had multiple previous attempts at PICC placement by experienced NICU vascular access nurses prior to referral. Complications were determined based on clinical and procedural notes. RESULTS: A total of ten patients were found during the study period. The average estimated gestational age was 29.8 weeks (range 26-38 weeks).The average weight at the time of PICC insertion was 968 g (range 485-1390 g). All attempts at placement were successful. There were no complications directly related to PICC insertion. CONCLUSION: Ultrasound guided PICC line placements using ultrasound is an effective technique, which can be applied to very low and extremely low birth weight infants, with excellent success rates and a low risk of complications.


Assuntos
Cateterismo Periférico/instrumentação , Cateterismo Periférico/métodos , Ultrassonografia de Intervenção/métodos , Cateteres de Demora , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Retrospectivos
20.
Pediatr Surg Int ; 32(3): 301-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26602208

RESUMO

BACKGROUND: MRI-guided laparoscopic assisted anorectoplasty (MRI-LAARP), a new approach for surgical correction of high imperforate anus, does not bisect the sphincter complex as in the PSARP and is able to pull the neorectum through the entire sphincter complex unlike the LAARP. There is no available MRI-compatible device to position and transport patients during this procedure. We report on the design of such a device here. METHODS AND DEVICE: The device was constructed from 1.0″ polyvinylchloride tubing and poly-methyl methacrylate (Plexiglass(®)) platform. The device has a stable, rigid base on which platform is secure. An adjustable and removable superstructure is secured to this base to suspend legs for lithotomy position. RESULTS: MRI-LAARP has been performed on 6 patients. The device has performed well and meets requirements set forth in development including construction with MRI-compatible materials, size fitting in the MRI bore, ability to hold patient in lithotomy position, ability to position and support MRI flex coils, and providing stability while transporting to a separate OR with needle in position. CONCLUSIONS: This device provides a stable structure to position and transport a patient with a needle in a tenuous position without dislodgement allowing this procedure, and potentially other procedures, to be done in hospitals without MROR capability.


Assuntos
Anus Imperfurado/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Laparoscopia/instrumentação , Imagem por Ressonância Magnética Intervencionista/instrumentação , Posicionamento do Paciente/instrumentação , Transferência de Pacientes/métodos , Canal Anal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Desenho de Equipamento , Humanos , Lactente , Laparoscopia/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Salas Cirúrgicas , Polimetil Metacrilato , Polivinil , Reto/cirurgia , Resultado do Tratamento
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