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1.
Proc Natl Acad Sci U S A ; 120(42): e2305667120, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37812718

RESUMO

Deformation of all materials necessitates the collective propagation of various microscopic defects. On Earth, fracturing gives way to crystal-plastic deformation with increasing depth resulting in a "brittle-to-ductile" transition (BDT) region that is key for estimating the integrated strength of tectonic plates, constraining the earthquake cycle, and utilizing deep geothermal resources. Here, we show that the crossing of a BDT in marble during deformation experiments in the laboratory is accompanied by systematic increase in the frequency of acoustic emissions suggesting a profound change in the mean size and propagation velocity of the active defects. We further identify dominant classes of emitted waveforms using unsupervised learning methods and show that their relative activity systematically changes as the rocks cross the brittle-ductile transition. As pressure increases, long-period signals are suppressed and short-period signals become dominant. At higher pressures, signals frequently come in avalanche-like patterns. We propose that these classes of waveforms correlate with individual dominant defect types. Complex mixed-mode events indicate that interactions between the defects are common over the whole pressure range, in agreement with postmortem microstructural observations. Our measurements provide unique, real-time data of microscale dynamics over a broad range of pressures (10 to 200 MPa) and can inform micromechanical models for semi-brittle deformation.

2.
N Engl J Med ; 385(9): 803-814, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34379916

RESUMO

BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS. RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 µg per milliliter at the time of controlled human malaria infection. CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antimaláricos/uso terapêutico , Malária Falciparum/prevenção & controle , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Antiprotozoários/sangue , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Infusões Intravenosas/efeitos adversos , Injeções Subcutâneas/efeitos adversos , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Plasmodium falciparum/isolamento & purificação
3.
J Neurosci ; 42(11): 2190-2204, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35135857

RESUMO

Failure of CNS neurons to mount a significant growth response after trauma contributes to chronic functional deficits after spinal cord injury. Activator and repressor screening of embryonic cortical neurons and retinal ganglion cells in vitro and transcriptional profiling of developing CNS neurons harvested in vivo have identified several candidates that stimulate robust axon growth in vitro and in vivo Building on these studies, we sought to identify novel axon growth activators induced in the complex adult CNS environment in vivo We transcriptionally profiled intact sprouting adult corticospinal neurons (CSNs) after contralateral pyramidotomy (PyX) in nogo receptor-1 knock-out mice and found that intact CSNs were enriched in genes in the 3-phosphoinositide degradation pathway, including six 5-phosphatases. We explored whether inositol polyphosphate-5-phosphatase K (Inpp5k) could enhance corticospinal tract (CST) axon growth in preclinical models of acute and chronic CNS trauma. Overexpression of Inpp5k in intact adult CSNs in male and female mice enhanced the sprouting of intact CST terminals after PyX and cortical stroke and sprouting of CST axons after acute and chronic severe thoracic spinal contusion. We show that Inpp5k stimulates axon growth in part by elevating the density of active cofilin in labile growth cones, thus stimulating actin polymerization and enhancing microtubule protrusion into distal filopodia. We identify Inpp5k as a novel CST growth activator capable of driving compensatory axon growth in multiple complex CNS injury environments and underscores the veracity of using in vivo transcriptional screening to identify the next generation of cell-autonomous factors capable of repairing the damaged CNS.SIGNIFICANCE STATEMENT Neurologic recovery is limited after spinal cord injury as CNS neurons are incapable of self-repair post-trauma. In vitro screening strategies exploit the intrinsically high growth capacity of embryonic CNS neurons to identify novel axon growth activators. While promising candidates have been shown to stimulate axon growth in vivo, concomitant functional recovery remains incomplete. We identified Inpp5k as a novel axon growth activator using transcriptional profiling of intact adult corticospinal tract (CST) neurons that had initiated a growth response after pyramidotomy in plasticity sensitized nogo receptor-1-null mice. Here, we show that Inpp5k overexpression can stimulate CST axon growth after pyramidotomy, stroke, and acute and chronic contusion injuries. These data support in vivo screening approaches to identify novel axon growth activators.


Assuntos
Tratos Piramidais , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Feminino , Inositol/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/fisiologia , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Polifosfatos/metabolismo , Tratos Piramidais/fisiologia
4.
Am Nat ; 195(1): 82-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31868543

RESUMO

Stable cooperation requires plasticity whereby individuals are able to express competitive or cooperative behaviors depending on social context. To date, however, the physiological mechanisms that underlie behavioral variation in cooperative systems are poorly understood. We studied hormone-mediated behavior in the wire-tailed manakin (Pipra filicauda), a gregarious songbird whose cooperative partnerships and competition for status are both crucial for fitness. We used automated telemetry to monitor >36,000 cooperative interactions among male manakins over three field seasons, and we examined how circulating testosterone affects cooperation using >500 hormone samples. Observational data show that in nonterritorial floater males, high testosterone is associated with increased cooperative behaviors and subsequent ascension to territorial status. In territory-holding males, however, both observational and experimental evidence demonstrate that high testosterone antagonizes cooperation. Moreover, circulating testosterone explains significant variation (2%-8%) in social behavior within each status class. Collectively, our findings show that the hormonal control of cooperation depends on a male's social status. We propose that the status-dependent reorganization of hormone-regulatory pathways can facilitate stable cooperative partnerships and thus provide direct fitness benefits for males.


Assuntos
Comportamento Cooperativo , Passeriformes/fisiologia , Comportamento Social , Territorialidade , Testosterona/sangue , Animais , Masculino , Estações do Ano , Meio Social
5.
J Card Surg ; 35(7): 1653-1656, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32353904

RESUMO

BACKGROUND AND AIM: Atrial septal defects with anomalous venous connections are commonly repaired via sternotomy, requiring careful baffle reconstruction to redirect pulmonary venous return and ensure a durable result. The cosmetically appealing periareolar incision may provide an esthetically superior alternative to the anterolateral minithoracotomy incision used in minimally invasive cardiac surgery. METHODS: We describe a patient with a sinus venosus atrial septal defect and partial anomalous pulmonary venous connection who underwent successful minimally invasive, endoscopic repair with apical vein translocation and autologous pericardial baffle reconstruction through a periareolar approach. RESULTS: Post-operative echocardiography demonstrated excellent results with no residual shunt and a widely patent baffle and preserved biventricular function. At 1-year post-op, our patient has had a greatly improved quality of life and an excellent cosmetic result with normal nipple-areolar sensation. CONCLUSIONS: We believe that periareolar approaches should be considered for all adult patients with simple and complex atrial septal defects.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares/métodos , Endoscopia/métodos , Comunicação Interatrial/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Veias Pulmonares/anormalidades , Veias Pulmonares/cirurgia , Adulto , Ecocardiografia , Feminino , Comunicação Interatrial/diagnóstico por imagem , Humanos , Veias Pulmonares/diagnóstico por imagem , Qualidade de Vida , Esternotomia/métodos , Resultado do Tratamento
6.
Ecology ; 99(8): 1825-1835, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29802772

RESUMO

Transient species occur infrequently in a community over time and do not maintain viable local populations. Because transient species interact differently than non-transients with their biotic and abiotic environment, it is important to characterize the prevalence of these species and how they impact our understanding of ecological systems. We quantified the prevalence and impact of transient species in communities using data on over 19,000 community time series spanning an array of ecosystems, taxonomic groups, and spatial scales. We found that transient species are a general feature of communities regardless of taxa or ecosystem. The proportion of these species decreases with increasing spatial scale leading to a need to control for scale in comparative work. Removing transient species from analyses influences the form of a suite of commonly studied ecological patterns including species-abundance distributions, species-energy relationships, species-area relationships, and temporal turnover. Careful consideration should be given to whether transient species are included in analyses depending on the theoretical and practical relevance of these species for the question being studied.


Assuntos
Biota , Ecossistema , Prevalência
7.
J Cardiothorac Vasc Anesth ; 31(2): 575-581, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27745797

RESUMO

OBJECTIVES: The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, observational cohort study design. SETTING: Single center, university hospital. PARTICIPANTS: Thirty-eight consecutive adults who had undergone liver transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired arterial blood samples were collected before surgical incision, 5 minutes after administration of an average dose of 2,054±771 units of intravenous unfractionated heparin before caval cross-clamping, 5 minutes after portal reperfusion, 5 minutes after hepatic artery reperfusion, and 1 hour after hepatic artery reperfusion. The observations that heparin assay measurements were within the predetermined limits of agreement, strongly suggested the two heparin assays (Hepcon HMS plus and Anti-Xa assay) are interchangeable during prophylactic heparin dose therapy during OLT. Post-reperfusion, receiver operating characteristic curve analysis revealed high accuracy in measuring circulating heparin levels with both Anti-Xa and Hepcon HMS assays when compared with the TEG r time ratio assay. CONCLUSIONS: The point-of-care Hepcon HMS plus/Kaolin-ACT (activated clotting time) assay appeared to be a reliable alternative to the more expensive and laboratory-required Anti-Xa assay in monitoring the response to intravenous heparin in patients undergoing OLT.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Heparina/administração & dosagem , Transplante de Fígado/métodos , Preparações de Plantas/administração & dosagem , Profilaxia Pré-Exposição/métodos , Adulto , Idoso , Anticoagulantes/sangue , Testes de Coagulação Sanguínea/métodos , Estudos de Coortes , Feminino , Heparina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboelastografia/métodos
8.
Perfusion ; 32(6): 489-494, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28820033

RESUMO

OBJECTIVES: Unregulated intraoperative distension of human saphenous vein (SV) graft leads to supraphysiologic luminal pressures and causes acute physiologic and cellular injury to the conduit. The effect of distension on tissue viscoelasticity, a biophysical property critical to a successful graft, is not well described. In this investigation, we quantify the loss of viscoelasticity in SV deformed by distension and compare the results to tissue distended in a pressure-controlled fashion. MATERIALS AND METHODS: Unmanipulated porcine SV was used as a control or distended without regulation and distended with an in-line pressure release valve (PRV). Rings were cut from these tissues and suspended on a muscle bath. Force versus time tracings of tissue constricted with KCl (110 mM) and relaxed with sodium nitroprusside (SNP) were fit to the Hill model of viscoelasticity, using mean absolute error (MAE) and r2-goodness of fit as measures of conformity. RESULTS: One-way ANOVA analysis demonstrated that, in tissue distended manually, the MAE was significantly greater and the r2-goodness of fit was significantly lower than both undistended tissues and tissues distended with a PRV (p<0.05) in KCl-induced vasoconstriction and SNP-induced vasodilation. CONCLUSIONS: Unregulated manual distension of SV graft causes loss of viscoelasticity and such loss may be mitigated with the use of an in-line PRV.


Assuntos
Ponte de Artéria Coronária/métodos , Endotélio Vascular/fisiopatologia , Veia Safena/cirurgia , Animais , Humanos , Suínos , Vasoconstrição
9.
J Cardiothorac Vasc Anesth ; 30(4): 917-23, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27020101

RESUMO

OBJECTIVES: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN: Retrospective, observational, cohort study design. SETTING: Single-center, university hospital. PARTICIPANTS: The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.


Assuntos
Injúria Renal Aguda/etiologia , Ácido Aminocaproico/efeitos adversos , Antifibrinolíticos/efeitos adversos , Transplante de Fígado/efeitos adversos , Tromboembolia/etiologia , Ácido Aminocaproico/administração & dosagem , Antifibrinolíticos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
10.
J Am Mosq Control Assoc ; 32(2): 130-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27280351

RESUMO

The efficacy of a metofluthrin-impregnated net (MIN) known as the "Mushikonazu" on the house entry behavior of female Aedes aegypti and Anopheles dirus mosquitoes was evaluated using a semi-field 50-m tunnel setup. While the MIN is labeled for the control of chironomids and moth flies, this study determined the feasibility of using the device, given its current construction and metofluthrin formulation, as a spatial repellent against mosquitoes. Sentinel and cone bioassays were used to determine the insecticidal effect of the MIN. A spatial activity index (SAI) was calculated to evaluate responses of the mosquitoes. For the spatial repellent evaluation against Ae. aegypti, the overall mean of SAI was slightly less than 0 at wk 1 after the MIN application and then decreased for the last 4 wk showing a preference to treatment tent. For An. dirus, the mean SAI at wk 1 was positive, indicating a presumed repellent effect of the MIN against An. dirus. For the subsequent 4 wk, the SAI was negative, indicating a preference for the MIN. Results suggested that the MIN may not be a promising approach to repel Ae. aegypti and An. dirus under field conditions in Thailand. However, it remains probable that the MIN may be effective as a spatial repellent if modifications are made to the metofluthrin concentration or formulation and/or the construction of the device.


Assuntos
Aedes , Anopheles , Ciclopropanos , Fluorbenzenos , Inseticidas , Controle de Mosquitos , Mosquiteiros/normas , Animais , Feminino , Tailândia
11.
Emerg Infect Dis ; 21(12): 2117-21, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26584400

RESUMO

In 2011, the world was declared free from rinderpest, one of the most feared and devastating infectious diseases of animals. Rinderpest is the second infectious disease, after smallpox, to have been eradicated. However, potentially infectious rinderpest virus material remains widely disseminated among research and diagnostic facilities across the world and poses a risk for disease recurrence should it be released. Member Countries of the World Organisation for Animal Health and the Food and Agricultural Organization of the United Nations are committed to destroying remaining stocks of infectious material or ensuring that it is stored under international supervision in a limited number of approved facilities. To facilitate this commitment and maintain global freedom from rinderpest, World Organisation for Animal Health Member Countries must report annually on rinderpest material held in their countries. The first official surveys, conducted during 2013-2015, revealed that rinderpest material was stored in an unacceptably high number of facilities and countries.


Assuntos
Doenças Transmissíveis , Erradicação de Doenças , Vírus da Peste Bovina , Animais , Bovinos/virologia , Saúde Global , Inquéritos e Questionários
12.
Artigo em Inglês | MEDLINE | ID: mdl-23691625

RESUMO

The resurgence of dengue fever and the chikungunya epidemic make the control of Aedes aegypti mosquitoes, the vectors of these diseases, critically important. We developed and evaluated an Ae. aegypti control device that is visually-attractive to mosquitoes. This pyriproxyfen-treated device was evaluated for its impact on Ae. aegypti egg production and population dynamics in dengue-endemic areas in Thailand. The device consists of a "high rise" shaped ovitrap/ resting station covered with black cotton cloth. The device is easily collapsible and transportable. Ae. aegypti are generally drawn towards darker, shadier areas making this device physically attractive as a resting station to mosquitoes of all physiological stages. The results show this device suppressed Ae. aegypti populations after it was introduced into a village. The observed effect was primarily the result of the Ae. aegypti exposure to pyriproxyfen shortly after adult emergence or after taking a blood meal resulting in decreased egg production. We believe the device may be further improved physically and the formulation should be replaced to provide even better efficacy for controlling Ae. aegypti mosquito, populations.


Assuntos
Aedes/efeitos dos fármacos , Dengue/prevenção & controle , Controle de Insetos/métodos , Insetos Vetores/efeitos dos fármacos , Piridinas/farmacologia , Aedes/crescimento & desenvolvimento , Infecções por Alphavirus/prevenção & controle , Animais , Febre de Chikungunya , Humanos , Insetos Vetores/crescimento & desenvolvimento , Larva
13.
Front Cardiovasc Med ; 10: 1152124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063951

RESUMO

Background and aims: Fatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media. Methods: Three healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4-12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima. Results: High lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima. Conclusion: The arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

14.
ACS Nano ; 17(17): 16412-16431, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37582231

RESUMO

The complexity of CRISPR machinery is a challenge to its application for nonviral in vivo therapeutic gene editing. Here, we demonstrate that proteins, regardless of size or charge, efficiently load into porous silicon nanoparticles (PSiNPs). Optimizing the loading strategy yields formulations that are ultrahigh loading─>40% cargo by volume─and highly active. Further tuning of a polymeric coating on the loaded PSiNPs yields nanocomposites that achieve colloidal stability under cryopreservation, endosome escape, and gene editing efficiencies twice that of the commercial standard Lipofectamine CRISPRMAX. In a mouse model of arthritis, PSiNPs edit cells in both the cartilage and synovium of knee joints, and achieve 60% reduction in expression of the therapeutically relevant MMP13 gene. Administered intramuscularly, they are active over a broad dose range, with the highest tested dose yielding nearly 100% muscle fiber editing at the injection site. The nanocomposite PSiNPs are also amenable to systemic delivery. Administered intravenously in a model that mimics muscular dystrophy, they edit sites of inflamed muscle. Collectively, the results demonstrate that the PSiNP nanocomposites are a versatile system that can achieve high loading of diverse cargoes and can be applied for gene editing in both local and systemic delivery applications.


Assuntos
Sistemas CRISPR-Cas , Nanopartículas , Camundongos , Animais , Sistemas CRISPR-Cas/genética , Silício , Porosidade , Polímeros
15.
Australas Emerg Care ; 25(1): 84-87, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33879427

RESUMO

BACKGROUND: Emergency department patients presenting with acute abdominal pain are often prescribed a chest X-ray; however, the value of chest X-rays in acute abdominal pain is poorly understood. The aim of this study was to assess the value of chest X-rays in acute abdominal pain. METHODS: A retrospective analysis of 944 chest X-rays performed for acute abdominal pain was conducted. Patient clinical information, radiology reports, and findings of other diagnostic investigations were also collected. MedCal® software was used to calculate diagnostic performance of chest X-rays. A Chi-Square test was used to assess the association between positive chest X-ray findings and both age and gender. RESULTS: Of the 944 chest X-rays identified as satisfying inclusion factors, only 10 cases (approximately 1%) demonstrated pathology that was likely to be the cause of the abdominal pain. Further analysis demonstrated the following performance metrics at 95%CI: sensitivity (12.8; 8.78-17.72); specificity (100; 98.4-100); positive predictive value (100%); negative predictive value (52.76; 51.54-53.98); accuracy (55.82; 51.17-60.40). CONCLUSION: Chest X-ray has limited sensitivity and diagnostic value in patients presenting to the emergency department with abdominal pain and does not appear to be a useful diagnostic investigation for abdominal pain.


Assuntos
Dor Abdominal , Serviço Hospitalar de Emergência , Dor Abdominal/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Raios X
16.
Endocrinology ; 163(2)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34971379

RESUMO

Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum insulin-like growth factor-1 (IGF1) levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.


Assuntos
Fatores de Transcrição Forkhead/fisiologia , Somatotrofos/fisiologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Feminino , Proteína Forkhead Box O1/deficiência , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/fisiologia , Proteína Forkhead Box O3/deficiência , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/fisiologia , Expressão Gênica , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/análise , Masculino , Camundongos , Camundongos Knockout , Hipófise/química , Hipófise/fisiologia , RNA Mensageiro/análise , Somatotrofos/química
17.
Virol J ; 8: 449, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21943222

RESUMO

BACKGROUND: Japanese encephalitis virus (JEV) genotype V reemerged in Asia (China) in 2009 after a 57-year hiatus from the continent, thereby emphasizing a need to increase regional surveillance efforts. Genotypic characterization was performed on 19 JEV-positive mosquito pools (18 pools of Culex tritaeniorhynchus and 1 pool of Cx. bitaeniorhynchus) from a total of 64 positive pools collected from geographically different locations throughout the Republic of Korea (ROK) during 2008 and 2010. FINDINGS: Two regions of the JEV genome were sequenced from 19 pools; the envelope gene and the nonstructural protein 5 (NS5)/3'-untranslated region (UTR). Eighteen pools of Culex tritaeniorhynchus and one pool of Cx. bitaeniorhynchus were positive for genotype I and genotype V, respectively. Sequence alignment of the complete E gene from Cx. bitaeniorhynchus showed high amino acid similarity (98.8%) to the Muar strain, characterized as the first report of genotype V, isolated from an encephalitis patient in Malaysia in 1952. CONCLUSION: This study represents the first report of JEV genotype V in the ROK. The reemergence of genotype V in Asia (China and ROK) after more than a half-century and its discovery in Cx. bitaeniorhynchus, a mosquito species previously unknown to carry JEV in the ROK, emphasizes the need for enhanced JE surveillance to monitor the dynamics of JEV strains within the region. Future findings may have implications with regard to JEV vaccination/prevention strategies.


Assuntos
Culex/virologia , Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/virologia , Genoma Viral , Genótipo , RNA Viral/genética , Regiões 3' não Traduzidas/genética , Sequência de Aminoácidos , Animais , China , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/genética , Encefalite Japonesa/transmissão , Humanos , Insetos Vetores/virologia , Vacinas contra Encefalite Japonesa , Malásia , Dados de Sequência Molecular , Tipagem Molecular , Filogenia , Vigilância da População , RNA Viral/química , República da Coreia/epidemiologia , Alinhamento de Sequência , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
18.
J Med Entomol ; 48(6): 1250-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22238887

RESUMO

In total, 22,846 (17,793 culicines and 5,053 Anopheles spp.) female mosquitoes were captured by a Mosquito Magnet trap at Daeseongdong, a small village adjacent to the military demarcation line (center of the demilitarized zone) in northern Gyeonggi Province, Republic of Korea (ROK). Culicine mosquitoes were identified to species, placed in pools of up to 30 mosquitoes each, and screened for flavivirus using a SYBR Green I-based real-time polymerase chain reaction. In total, 51/660 pools positive for flaviviruses and confirmed by DNA sequencing of the NS5 region, were positive for Japanese encephalitis virus (family Flaviviridae, genus Flavivirus, JEV) (50 Culex tritaeniorhynchus Giles and one Culex bitaeniorhynchus Giles). The JEV maximum likelihood estimations (MLEs) (estimated number of viral RNA-positive mosquitoes per 1,000) for Cx. tritaeniorhynchus and Cx. bitaeniorhynchus were 9.7 and 0.9, respectively. This is the first report of a Cx. bitaeniorhynchus positive for JEV in the ROK. JEV is a local civilian and military health threat and a significant concern for nonimmune (unvaccinated) U.S. soldiers, civilians, and family members deployed to the ROK.


Assuntos
Culicidae/virologia , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Insetos Vetores/virologia , Animais , Densidade Demográfica , República da Coreia , Estações do Ano
20.
J Med Imaging Radiat Sci ; 52(4): 606-614, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34903354

RESUMO

BACKGROUND: Chest X-rays (CXRs) are often requested for patients who present to emergency with abdominal pain, but its benefit to patient management remains unclear. Several guidelines have been developed to ensure that imaging investigations have the highest diagnostic impact. This study aims to compare referral guidelines to establish their recommendations and circumstances for recommendations regarding CXRs for patients with abdominal pain. METHODS: A systematic search of the literature was performed using Medline (via OVID), PubMed, Google, and Google Scholar. Referral guidelines were included if they provided recommendations for imaging of abdominal pain, were based on published evidence, and were broadly utilised. Data related to their recommendations for CXR for abdominal pain was recorded and analysed. RESULTS: Three guidelines supported the use of CXRs in the case of suspected perforation. Two guidelines included CXR for patients presenting with blunt abdominal trauma and severe abdominal pain requiring admission. One of the guidelines included use of CXRs for patients presenting with suspected small bowel obstruction, cholecystitis, and penetrating trauma. Two guidelines recorded no circumstances where the use of CXRs were recommended. CONCLUSION: Published evidence-based guidelines allow for the use of CXRs for patients presenting with abdominal pain in very limited circumstances.


Assuntos
Dor Abdominal , Encaminhamento e Consulta , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Humanos , Radiografia , Raios X
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