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BACKGROUND: Decreasing rates of assisted vaginal birth have been paralleled with increasing rates of cesarean deliveries over the last 40 years. The OdonAssist is a novel device for assisted vaginal birth. Iterative changes to clinical parameters, device design, and technique have been made to improve device efficacy and usability. OBJECTIVE: This study aimed to determine if the feasibility, safety, and efficacy of the OdonAssist device were sufficient to justify conducting a future randomized controlled trial. STUDY DESIGN: An open-label nonrandomized study of 104 participants having a clinically indicated assisted vaginal birth using the OdonAssist was undertaken at Southmead Hospital, Bristol, United Kingdom. Data were also collected from participants who consented to participate in the study but for whom trained OdonAssist operators were not available, providing a nested cohort. The primary clinical outcome was the proportion of births successfully expedited with the OdonAssist. Secondary outcomes included clinical, patient-reported, operator-reported, device and health care utilization. Neonatal outcome data were reviewed at day 28, and maternal outcomes were investigated up to day 90. Given that the number of successful OdonAssist births was ≥61 out of 104, the hypothesis of a poor rate of 50% was rejected in favor of a good rate of ≥65%. RESULTS: Between August 2019 and June 2021, 941 (64%) of the 1471 approached, eligible participants consented to participate. Of these, 104 received the OdonAssist intervention. Birth was assisted in all cephalic vertex fetal positions, at all stations ≥1 cm below the ischial spines (with or without regional analgesia). The OdonAssist was effective in 69 of the 104 (66%) cases, consistent with the hypothesis of a good efficacy rate. There were no serious device-related maternal or neonatal adverse reactions, and there were no serious adverse device effects. Only 4% of neonatal soft tissue bruising in the successful OdonAssist group was considered device-related, as opposed to 20% and 23% in the unsuccessful OdonAssist group and the nested cohort, respectively. Participants reported high birth perception scores. All practitioners found the device use to be straightforward. CONCLUSION: Recruitment to an interventional study of a new device for assisted vaginal birth is feasible; 64% of eligible participants were willing to participate. The success rate of the OdonAssist was comparable to that of the Kiwi OmniCup when introduced in the same unit in 2002, meeting the threshold for a randomized controlled trial to compare the OdonAssist with current standard practice. There were no disadvantages of study participation in terms of maternal and neonatal outcomes. There were potential advantages of using the OdonAssist, particularly reduced neonatal soft tissue injury. The same application technique is used for all fetal positions, with all operators deeming the device straightforward to use. This study provides important data to inform future study design.
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Cesárea , Cabeça , Feminino , Recém-Nascido , Gravidez , Humanos , Reino Unido , VaginaRESUMO
The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1 persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH.
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Tecido Adiposo/citologia , Células-Tronco Adultas/metabolismo , Ciclo-Oxigenase 1/metabolismo , Hipertensão Pulmonar/terapia , Transplante de Células-Tronco , Células-Tronco Adultas/citologia , Células-Tronco Adultas/transplante , Animais , Diferenciação Celular , Ciclo-Oxigenase 1/genética , Vetores Genéticos/genética , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Lentivirus/genética , Monocrotalina/toxicidade , Ratos , Ratos Sprague-DawleyRESUMO
Introduction: COVID-19 diagnosis was one of the most pressing needs during the early stages of the pandemic. Its entire procedure has inherent biosafety risks that if not properly managed and mitigated can be life threatening. Cognizant of this vital aspect, the Department of Health (DOH) imposed a biosafety training requirement to all laboratories and institutions before they could perform COVID-19 diagnostic testing. But with the mandatory lockdown, conventional face-to-face training could not be conducted. To address this need, the Biosafety Education and Awareness Training COVID-19 Online Program was offered by the National Training Center for Biosafety and Biosecurity of the University of the Philippines Manila. Methods and Materials: This online training program implemented a distance learning approach made available through the Canvas Learning Management System. It consisted of seven modules on biosafety that were sufficient enough to capacitate the participants with information for them to effectively implement a biorisk management system. The participants were evaluated based on quiz, examination, and case analysis. Certificates of completion were awarded to participants who passed all evaluation methods. Results: A total of 3371 trainees from various medical professions passed and obtained the certificate. This resulted in >100 DOH-accredited COVID-19 testing laboratories by the end of 2020. Discussion and Conclusion: The online availability of this program proved to be an effective innovative solution to a unique problem. Therefore, this training program demonstrated that biosafety training can be effectively conducted online and in a distance learning approach.
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INTRODUCTION: The objective of this study is to evaluate the performance of OraQuick HCV Rapid Antibody Test against a "gold-standard", FDA-approved, laboratory-based serum immunoassay (SI) in postmortem blood. To date, OraQuick HCV Rapid Antibody Test has not been evaluated for use in postmortem testing. This OraQuick test is a manually performed, visually interpreted, single use immunoassay for the qualitative detection of antibodies to the hepatitis C virus (HCV). METHODS: Blood was collected from 51 decedents whose deaths were investigated in the jurisdiction of the Knox and Anderson County Medical Examiner's Office (MEO) January 2017 through April 2017. For each consented case, blood was tested using both the OraQuick HCV Rapid Antibody Test and a laboratory-based hepatitis C serum immunoassay ("gold standard" reference assay). Results from the OraQuick HCV Rapid Antibody Test were compared against a laboratory-based hepatitis C serum immunoassay. RESULTS: Using the laboratory-based serum immunoassay (SI) as the "gold standard" for assessing true HCV antibody positivity, and comparing SI against OraQuick rapid test, sensitivity for the OraQuick rapid test was 95.65% and specificity was 96.15% in postmortem blood. DISCUSSION: Our results demonstrate that OraQuick HCV rapid antibody test is reliable for diagnosis of hepatitis C infection in postmortem blood with a relatively short (less than approximately 21.5 hours) postmortem sample acquisition time. The OraQuick in some cases may be superior to traditional, laboratory-based HCV SI due to potential increased viscosity of postmortem blood.
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BACKGROUND: Metolachlor [(RS)-2-Chloro-N-(2-ethyl-6-methyl-phenyl)-N-(1-methoxypropan-2-yl)acetamide] and two degradates (metolachlor ethane-sulfonic acid and metolachlor oxanilic acid) are commonly observed in surface and groundwater. The behavior and fate of these compounds were examined over a 12-year period in seven agricultural watersheds in the United States. They were quantified in air, rain, streams, overland flow, groundwater, soil water, subsurface drain water, and water at the stream/groundwater interface. The compounds were frequently detected in surface and groundwater associated with agricultural areas. A mass budget approach, based on all available data from the study and literature, was used to determine a percentage-wise generalized distribution and fate of applied parent metolachlor in typical agricultural environments. RESULTS: In these watersheds, about 90% of applied metolachlor was taken up by plants or degraded, 10% volatilized, and 0.3% returned as rainfall. One percent was transported to surface water, while an equal amount infiltrated into the unsaturated zone soil water. <0.02% reached the groundwater. Subsurface flow paths resulted in greater degradation of metolachlor because degradation reactions had more time to proceed. CONCLUSIONS: An understanding of the residence times of water in the different environmental compartments, and the important processes affecting metolachlor as it is transported along flowpaths among the environmental compartments allows for a degree of predictability of metolachlor's fate. Degradates with long half-lives can be used (in a limited capacity) as tracers of metolachlor, because of their persistence and widespread occurrence in the environment.
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Calcitonin gene-related peptide (CGRP) has a beneficial effect in pulmonary hypertension and is a target for cardiovascular gene therapy. Marrow stromal cells (MSCs), also known as mesenchymal stem cells, hold promise for use in adult stem cell-based ex vivo gene therapy. To test the hypothesis that genetically engineered MSCs secreting CGRP can inhibit vascular smooth muscle cell proliferation, rat MSCs were isolated, ex vivo expanded, and transduced with adenovirus containing CGRP. Immunocytochemical analysis demonstrated that wild type rat MSCs express markers specific for stem cells, endothelial cells, and smooth muscle cells including Thy-1, c-Kit, von Willebrand Factor and alpha-smooth muscle actin. Immunocytochemistry confirmed the expression of CGRP by the transduced rat MSCs. The transduced rat MSCs released 10.3+/-1.3 pmol CGRP/1 x 10(6) cells/48 h (mean+/-S.E.M., n=3) into culture medium at MOI 300 and the CGRP-containing culture supernatant from the transduced cells inhibited the proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and rat aortic smooth muscle cells (ASMCs) in culture. Co-culture of the transduced rat MSCs with rat PASMCs or rat ASMCs also inhibited smooth muscle cell proliferation. These findings suggest that this novel adult stem cell-based CGRP gene therapy has potential for the treatment of cardiovascular diseases including pulmonary hypertension.
Assuntos
Células da Medula Óssea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Proliferação de Células , Células-Tronco Mesenquimais/fisiologia , Músculo Liso Vascular/citologia , Actinas/metabolismo , Adenoviridae/genética , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Técnicas de Cocultura , Engenharia Genética , Masculino , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Sprague-Dawley , Células Estromais , Antígenos Thy-1/metabolismo , Fator de von Willebrand/metabolismoRESUMO
OBJECTIVE: To implement parent-oriented discharge planning (Train-to-Home) for preterm infants in neonatal care. DESIGN: Before and after study, investigating the effects of the intervention during two 11-month periods before and after implementation. SETTING: Four local neonatal units (LNUs) in South West England. PARTICIPANTS: Infants without major anomalies born at 27-33 weeks' gestation admitted to participating units, and their parents. TRAIN-TO-HOME INTERVENTION: A family-centred discharge package to increase parents' involvement and understanding of their baby's needs, comprising a train graphic and supporting care pathways to facilitate parents' understanding of their baby's progress and physiological maturation, combined with improved estimation of the likely discharge date. MAIN OUTCOME MEASURES: Perceived Maternal Parenting Self-Efficacy (PMP S-E) scores, infant length of stay (LOS) and healthcare utilisation for 8 weeks following discharge. RESULTS: Parents reported that the Train-to-Home improved understanding of their baby's progress and their preparedness for discharge. Despite a lack of change in PMP S-E scores with the intervention, the number of post-discharge visits to emergency departments (EDs) fell from 31 to 20 (p<0.05), with a significant reduction in associated healthcare costs (£3400 to £2200; p<0.05) after discharge. In both study phases, over 50% of infants went home more than 3 weeks before their estimated date of delivery (EDD), though no reduction in LOS occurred. CONCLUSIONS: Despite the lack of measurable effect on the parental self-efficacy scores, the reduction in ED attendances and associated costs supports the potential value of this approach.
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Instituições de Assistência Ambulatorial/estatística & dados numéricos , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação , Pais/educação , Alta do Paciente , Adulto , Inglaterra , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Recent studies have suggested the potential use of vasoactive intestinal peptide (VIP) in the treatment of pulmonary arterial hypertension (PAH). An understanding of the mechanism of action of VIP is important for the development of new therapies for PAH. The biological effects of VIP are mediated by two type II guanine nucleotide binding protein (G-protein)-coupled receptors VIP/PACAP (pituitary adenylate cyclase activating peptide) receptor type1 (VPAC1) and VIP/PACAP receptor type 2 (VPAC2). In the present study, the distribution and role of these receptors were investigated and compared in cultured smooth muscle cells from rat aorta and pulmonary artery, as well as in fixed tissue sections of the aorta and pulmonary artery. Western blot analysis, RT-PCR and immunohistochemistry showed the expression of both VIP receptors in tissue sections of the aorta and pulmonary artery as well as in cultured smooth muscle cells from these vessels. The application of a specific antagonist of VPAC1 resulted in a small release from VIP induced inhibition of cell proliferation. In contrast (VIP 6-28; 300nM) which is an antagonist against both receptors resulted in a significant restoration of proliferation. The expression of cAMP was reduced in the presence of VIP 6-28 and slightly decreased by VPAC1 antagonist. These findings suggest a dual role for VPAC1 and VPAC2 receptors in mediating the antiproliferative effects of VIP with VPAC2 appearing to play a more dominant role.
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Aorta/metabolismo , Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Artéria Pulmonar/metabolismo , Receptores Tipo II de Peptídeo Intestinal Vasoativo/fisiologia , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/fisiologia , Peptídeo Intestinal Vasoativo/fisiologia , Animais , Aorta/citologia , Western Blotting , Células Cultivadas , AMP Cíclico/metabolismo , Expressão Gênica , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Imuno-Histoquímica , Masculino , Fragmentos de Peptídeos/farmacologia , Artéria Pulmonar/citologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Tipo II de Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Receptores Tipo II de Peptídeo Intestinal Vasoativo/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/antagonistas & inibidores , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We studied the effect of a synthetic GLP-1 receptor agonist, exenatide, a drug approved for the treatment of type 2 diabetes, on the recovery from vascular injury in Zucker (non-diabetic) fatty rats. Exenatide 5.0 microg/kg per day or saline was administered for seven days before, and 21 days after balloon catheter mediated carotid injury. A pair feeding experiment helped differentiate between the drug itself and the known effects of the drug on decreased food intake. Body weight and glucose (weekly), carotid artery I/M ratio, aortic protein eNOS and NFkappaB-p65 were measured. Body weight gain in exenatide rats was significantly lower (53+/-5 vs. 89+/-8 g) than controls. Blood glucose did not change significantly. The I/M ratio in the exenatide group was 0.2+/-0.1 vs. 0.9+/-0.1 in controls (p<0.05). The expression of aortic eNOS was unchanged in exenatide treated rats and a small decrease seen in NFkappaB-p65 expression was not statistically significant. We conclude that exenatide attenuates intimal hyperplasia following balloon catheter induced vascular injury independently of glucose regulation and food intake. Our findings provide additional support for cardiovascular benefits of exenatide, especially in obese and pre-diabetic patients. Further research is needed to elucidate the mechanism underlying these effects.
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Lesões das Artérias Carótidas/tratamento farmacológico , Resistência à Insulina , Peptídeos/uso terapêutico , Receptores de Glucagon/agonistas , Túnica Íntima/efeitos dos fármacos , Peçonhas/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Ingestão de Alimentos/efeitos dos fármacos , Exenatida , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hiperplasia/prevenção & controle , Óxido Nítrico Sintase Tipo III/metabolismo , Peptídeos/farmacologia , Ratos , Ratos Zucker , Fator de Transcrição RelA/metabolismo , Túnica Íntima/patologia , Peçonhas/farmacologiaRESUMO
OBJECTIVE: Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury. RESEARCH DESIGN AND METHODS: Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied. RESULTS: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats. CONCLUSIONS: The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Lesões das Artérias Carótidas/tratamento farmacológico , Salicilatos/uso terapêutico , Animais , Western Blotting , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/patologia , Cateterismo/efeitos adversos , Feminino , Imuno-Histoquímica , Óxido Nítrico Sintase Tipo III/genética , Ratos , Ratos Zucker , Superóxido Dismutase/genética , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Vasoactive intestinal peptide (VIP), a 28 amino acid peptide, has been shown to inhibit proliferation of vascular smooth muscle cells. In previous studies VIP and VIP analogs have been used to study the effects of the peptide on vascular smooth muscle cell function. In this study an adenovirus encoding the VIP gene was used to investigate the mechanism of the antiproliferative action of VIP in vascular smooth muscle cells. Primary cultures of aortic and pulmonary artery smooth muscle cells from male Sprague-Dawley rats were transfected with varying concentrations of serotype 5 adenovirus encoding human VIP (Ad5CMVhVIP). Transfection efficiency and subsequently VIP gene expression were confirmed by western blot analysis and immunohistochemistry. In this study a decrease in vascular smooth muscle cell proliferation at vector concentrations of 150, 300 and 600MOI (multiplicity of infection) was observed. In addition, there was increased production of cAMP in pulmonary artery and aortic smooth muscle cells transfected with VIP. Treatment of cells with a PKA inhibitor (Rp-8-BrcAMPs) restored proliferation to about 80% of control whereas treatment with the PKG inhibitor Rp-8-BrcGMPs had no significant effect suggesting the involvement of the PKA pathway in the antiproliferative actions of VIP.