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AIM: To analyse the technical challenges, clinical success, and associated complications of endovascular and percutaneous embolisation of pancreatitis-related pseudoaneurysms. MATERIALS AND METHODS: A retrospective study of patients referred for embolisation of pancreatitis-related pseudoaneurysms between January 2014 and March 2019 was conducted. Computed tomography angiography (CTA) was performed to assess the morphology of the aneurysms prior to any intervention. Percutaneous or endovascular embolisation was performed. Details of CTA and methods of embolisation were recorded. Technical success, clinical success, and complications were reported. RESULTS: A total of 80 patients (mean age, 40.69 ± 13.41 years, 73 male) underwent embolisation during the study period. Pseudoaneurysms were related to chronic pancreatitis (CP) in 44 (55%) patients and acute pancreatitis (AP) in 36 (45%) patients. Pseudoaneurysms were detected in 65 (81.2%) patients on CTA. The most common site of pseudoaneurysms was gastroduodenal artery (GDA) followed by splenic artery. Seven patients were treated with percutaneous thrombin injection and five were treated with percutaneous glue injection under ultrasound/fluoroscopy guidance. The remaining patients (n=68) underwent catheter angiography with endovascular embolisation. Technical success was achieved in 4/7 (57%) percutaneous thrombin cases and in all the cases (5/5, 100%) with percutaneous glue or endovascular (68/68,100%) embolisation. CONCLUSION: Endovascular or percutaneous embolisation of pseudoaneurysms has high technical success with an excellent safety profile.
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Falso Aneurisma/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Pancreatite/complicações , Doença Aguda , Adolescente , Adulto , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Artérias/diagnóstico por imagem , Criança , Angiografia por Tomografia Computadorizada , Duodeno/irrigação sanguínea , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Adesivo Tecidual de Fibrina/administração & dosagem , Artéria Gástrica/diagnóstico por imagem , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/complicações , Recidiva , Estudos Retrospectivos , Artéria Esplênica/diagnóstico por imagem , Centros de Atenção Terciária , Trombina/administração & dosagem , Adulto JovemRESUMO
PURPOSE: To assess the efficacy and outcome of percutaneous thrombin injection in treatment of visceral arterial pseudoaneurysms (PAs) in a selective group of patients. MATERIAL AND METHODS: Retrospective review of the institutional database showed 19 cases of visceral arterial pseudoaneurysms that were treated with percutaneous ultrasound-guided thrombin injection between January 2014 and December 2019 (13 men and 6 women). Of the pseudoaneurysms, 36% were due to pancreatitis, 35% were iatrogenic, 21% were infective and 8% traumatic. Most of the pseudoaneurysms arose from the hepatic artery (27%) followed by the splenic artery (26%) and renal artery (21%). Mean sac size of the pseudoaneurysms was 23 mm (range, 8 -40 mm). Technical success was defined as absence of flow within the PAs on follow-up ultrasonography (USG) 24 h and 3 days after thrombin injection. RESULTS: Overall technical success was seen in 10/19 patients. Technical success of thrombin injection was higher in cases of distal branch PAs as compared to main vessel PAs (9/13 vs. 1/6). Success rates were higher with smaller (<23mm) pseudoaneurysms (7/12) as compared to larger ones (3/7). There were no procedure-related complications. CONCLUSION: Ultrasound-guided percutaneous thrombin injection is a novel method of treating visceral pseudoaneurysms as a painless, cheap and radiation-free procedure. However, further large-scale studies are needed to prove the efficacy in treating visceral pseudoaneurysms.
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Falso Aneurisma , Trombina , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/tratamento farmacológico , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Doença Iatrogênica , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cut-points for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5-83.8 cm) and 81.0 cm (95% CI 79.2-82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63-65) than in men (53%, 95% CI 51-55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4-2.9, for men and 2.2, 95% CI 2.0-2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240.
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Anatomical evidence indicates that midcervical interneurons can be synaptically coupled with phrenic motoneurons. Accordingly, we hypothesized that interneurons in the C3-C4 spinal cord can display discharge patterns temporally linked with inspiratory phrenic motor output. Anesthetized adult rats were studied before, during, and after a 4-min bout of moderate hypoxia. Neuronal discharge in C3-C4 lamina I-IX was monitored using a multielectrode array while phrenic nerve activity was extracellularly recorded. For the majority of cells, spike-triggered averaging (STA) of ipsilateral inspiratory phrenic nerve activity based on neuronal discharge provided no evidence of discharge synchrony. However, a distinct STA phrenic peak with a 6.83 ± 1.1 ms lag was present for 5% of neurons, a result that indicates a monosynaptic connection with phrenic motoneurons. The majority (93%) of neurons changed discharge rate during hypoxia, and the diverse responses included both increased and decreased firing. Hypoxia did not change the incidence of STA peaks in the phrenic nerve signal. Following hypoxia, 40% of neurons continued to discharge at rates above prehypoxia values (i.e., short-term potentiation, STP), and cells with initially low discharge rates were more likely to show STP (P < 0.001). We conclude that a population of nonphrenic C3-C4 neurons in the rat spinal cord is synaptically coupled to the phrenic motoneuron pool, and these cells can modulate inspiratory phrenic output. In addition, the C3-C4 propriospinal network shows a robust and complex pattern of activation both during and following an acute bout of hypoxia.
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Potenciais de Ação/fisiologia , Vértebras Cervicais , Hipóxia/fisiopatologia , Neurônios Motores/fisiologia , Nervo Frênico/fisiologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiopatologiaRESUMO
PURPOSE: Grayscale ultrasonography when complemented with shear wave elastography helps in better evaluation of treatment response of leprosy neuropathy and in guiding appropriate management of the patient. There is limited literature regarding the use of shear wave elastography in ulnar nerve neuropathy. Our purpose was to evaluate the role of shear wave elastography in assessing stiffness changes within the ulnar nerve during treatment of leprosy. METHODS: This was a prospective study which included 30 patients diagnosed with leprosy neuropathy. Recruited patients were followed up, during the course of treatment, i.e. for 1 year. Serial ultrasonography of these patients was done at 0, 3, 6 and 12 months interval. RESULTS: Significant (P < 0.05) decrease in elastography parameters was seen in transverse imaging plane between first and third, as well as first and fourth visits (mean stiffness and velocity pretreatment ~ 25.78 ± 18 kPa and 2.74 ± 0.98 m/s, mean stiffness and velocity post-treatment 15.67 ± 5.89 kPa and 2.24 ± 0.428 m/s). Although elastography parameters decreased during these visits in the long-axis imaging plane, they were not found to be statistically significant. However, gross morphology and cross-sectional area of the nerve did not change significantly across visits. Interestingly, elastography values were higher in patients with neuritis, though not statistically significant. CONCLUSION: Shear wave elastography is a novel, upcoming modality in musculoskeletal imaging especially in the evaluation of peripheral neuropathy. It can act as an adjunct to grey-scale imaging, which can help in early diagnosis and in guiding treatment of leprosy neuropathy.
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Técnicas de Imagem por Elasticidade , Hanseníase , Doenças do Sistema Nervoso Periférico , Infecções dos Tecidos Moles , Neuropatias Ulnares , Técnicas de Imagem por Elasticidade/métodos , Seguimentos , Humanos , Hanseníase/complicações , Hanseníase/diagnóstico por imagem , Hanseníase/terapia , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/terapia , Estudos ProspectivosRESUMO
A significant number of patients after initial recovery from COVID-19 continue to experience lingering symptoms of the disease that may last for weeks or even months. Lungs being the most commonly affected organ by COVID-19, bear the major brunt of the disease and thus it is imperative to be aware of the evolution of the pulmonary parenchymal changes over time. CT chest is the imaging modality of choice to evaluate post-COVID lungs. Persistent ground-glass opacities, septal thickening, parenchymal bands, crazy-paving, traction bronchiectasis and consolidation constitute the commonly encountered imaging patterns seen on CT in post-COVID-19 lungs. Few vulnerable patients can develop lung fibrosis and show honeycombing on CT. Additionally, many complications like superadded infections (bacterial and fungal), pulmonary thromboembolism and pseudoaneurysm formation are also being reported. In the present pictorial review, we have tried to show the entire CT spectrum of sequelae of COVID-19 pneumonia and commonly associated infections and vascular complications.
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Hydatid disease is a parasitic infestation caused by the larval stage of Echinococcus. It can infest any part of the body; however, aortic hydatid disease is rare. Involvement of the abdominal aorta is usually due to embolization from cardiac hydatid cysts or direct invasion and can be present at intravascular or intramural locations. Aortic hydatid disease may present with fatal complications, such as anaphylaxis, pseudoaneurysm formation, systemic embolism, and arterial occlusion.
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Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors increases phrenic motor output. Ampakines are a class of drugs that are positive allosteric modulators of AMPA receptors. We hypothesized that 1) ampakines can stimulate phrenic activity after incomplete cervical spinal cord injury (SCI), and 2) pairing ampakines with brief hypoxia could enable sustained facilitation of phrenic bursting. Phrenic activity was recorded ipsilateral (IL) and contralateral (CL) to C2 spinal cord hemisection (C2Hx) in anesthetized adult rats. Two weeks after C2Hx, ampakine CX717 (15 mg/kg, i.v.) increased IL (61 ± 46% baseline, BL) and CL burst amplitude (47 ± 26%BL) in 8 of 8 rats. After 90 min, IL and CL bursting remained above baseline (BL) in 7 of 8 rats. Pairing ampakine with a single bout of acute hypoxia (5-min, arterial partial pressure of O2 ~ 50 mmHg) had a variable impact on phrenic bursting, with some rats showing a large facilitation that exceeded the response of the ampakine alone group. At 8 weeks post-C2Hx, 7 of 8 rats increased IL (115 ± 117%BL) and CL burst amplitude (45 ± 27%BL) after ampakine. The IL burst amplitude remained above BL for 90-min in 7 of 8 rats; CL bursting remained elevated in 6 of 8 rats. The sustained impact of ampakine at 8 weeks was not enhanced by hypoxia exposure. Intravenous vehicle (10% 2-Hydroxypropyl-ß-cyclodextrin) did not increase phrenic bursting at either time point. We conclude that ampakines effectively stimulate neural drive to the diaphragm after cervical SCI. Pairing ampakines with a single hypoxic exposure did not consistently enhance phrenic motor facilitation.
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Isoxazóis/uso terapêutico , Neurônios Motores/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Vértebras Cervicais/lesões , Diafragma/efeitos dos fármacos , Diafragma/inervação , Diafragma/fisiologia , Isoxazóis/farmacologia , Masculino , Neurônios Motores/fisiologia , Técnicas de Cultura de Órgãos , Nervo Frênico/fisiologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
AIMS/HYPOTHESIS: We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies. METHODS: We analysed a case-control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis. RESULTS: In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03-2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum gamma-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66-1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54-1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I (2) = 52.8%, p = 0.007). CONCLUSIONS/INTERPRETATION: Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.
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Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
We examined the potential contribution of ventromedial (VM) tissue sparing to respiratory recovery following chronic (1 mo) unilateral C2 spinal cord injury (SCI) in rats. Preserved white matter ipsilateral to the injury was quantitatively expressed relative to contralateral white matter. The ipsilateral-to-contralateral white matter ratio was 0 after complete C2 hemisection (C2HS) and 0.23+/-0.04 with minimal VM sparing. Inspiratory (breath min(-1)) and phrenic frequency (burst min(-1)), measured by plethysmography (conscious rats) and phrenic neurograms (anesthetized rats) respectively, were both lower with minimal VM sparing (p<0.05 vs. C2HS). Tidal volume also was greater in minimal VM sparing rats during a hypercapnic challenge (p<0.05 vs. C2HS). In other C2 hemilesioned rats with more extensive VM matter sparing (ipsilateral-to-contralateral white matter ratio=0.55+/-0.05), respiratory deficits were indicated at 1 mo post-injury by reduced ventilation during hypercapnic challenge (p<0.05 vs. uninjured). Anterograde (ventral respiratory column-to-spinal cord) neuroanatomical tracing studies showed that descending respiratory projections from the brainstem are present in VM tissue. We conclude that even relatively minimal sparing of VM tissue after C2 hemilesion can alter respiratory outcomes. In addition, respiratory deficits can emerge in the adult rat after high cervical SCI even when relatively extensive VM sparing occurs.
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Neurônios Motores/fisiologia , Recuperação de Função Fisiológica/fisiologia , Mecânica Respiratória/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Vértebra Cervical Áxis , Masculino , Vias Neurais , Nervo Frênico/citologia , Nervo Frênico/fisiologia , Pletismografia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de DoençaRESUMO
Primary pleural liposarcoma (PPL) is a rare malignant tumor of the pleura. The diagnosis of PPL may be suspected on chest imaging based on radiologic features such as large pleural mass showing areas of fat with or without calcification. Herein, we present the case of a 32-year-old male whose contrast-enhanced computed tomography scan of the chest revealed a large, heterogeneous, hypodense, right pleural-based mass with small areas of fat and calcification within it. An ultrasound-guided biopsy was performed, which confirmed the diagnosis of a myxoid variant of pleural liposarcoma.
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BACKGROUND: The beta-3 adrenergic receptor gene (ADRB3) is part of the adrenergic system, which is known to play a key role in energy metabolism. The association between the Trp64Arg variant in the ADRB3 and body mass index (BMI) has been widely examined, but previous studies have been small and results have been inconsistent. METHODS: We assessed the association between the ADRB3 Trp64Arg variant and BMI in a large UK population-based cohort of 4854 middle-aged men and women. We also performed a meta-analysis of 97 studies, involving 44 833 individuals, to place our findings in context. RESULTS: Although we found no significant difference in BMI (0.20 kg/m(2), P=0.40) between the Trp64Trp homozygotes and Arg64 allele carriers in our UK population-based cohort, the meta-analysis showed significant association between the Arg64Trp variant and BMI, with Arg64-allele carriers having a 0.24 kg/m(2) (P=0.0002) higher BMI compared with noncarriers. However, we also found substantial heterogeneity among the studies (P=2.2 x 10(-14)). The difference in East Asians (0.31 kg/m(2), P=0.001) was 3.9 times larger than that in Europeans in whom no significant association was observed (0.08 kg/m(2), P=0.36). This was consistent with the chronological cumulative decrease in the effect size, which decreased steadily in Europeans and reached nonsignificance after 11 studies in 1996. In East Asians, the cumulative effect size decreased after the first reports, but reached a steady state at a significant effect size of 0.24 kg/m(2) in 2000. Although the funnel plot indicated no apparent publication bias, smaller studies tended to report greater differences in BMI, compared with larger studies. CONCLUSIONS: Collectively, these data suggest that the Trp64Arg ADRB3 genetic variant might be associated with BMI in East Asians, but not Europeans. More generally, our study shows the importance of meta-analyses in the field of genetic association studies for common traits. Each genetic variant makes only a small contribution to variation in BMI, and large sample sizes are needed to reliably assess and interpret gene-phenotype associations.
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Índice de Massa Corporal , Receptores Adrenérgicos beta 3/genética , Antropometria , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Receptores Adrenérgicos beta 3/fisiologiaRESUMO
Female sex hormones influence the neural control of breathing and may impact neurologic recovery from spinal cord injury. We hypothesized that respiratory recovery after C2 spinal hemisection (C2HS) differs between males and females and is blunted by prior ovariectomy (OVX) in females. Inspiratory tidal volume (VT), frequency (fR), and ventilation (VE) were quantified during quiet breathing (baseline) and 7% CO2 challenge before and after C2HS in unanesthetized adult rats via plethysmography. Baseline breathing was similarly altered in all rats (reduced VT, elevated fR) but during hypercapnia females had relatively higher VT (i.e. compared to pre-injury) than male or OVX rats (p<0.05). Phrenic neurograms recorded in anesthetized rats indicated that normalized burst amplitude recorded ipsilateral to C2HS (i.e. the crossed phrenic phenomenon) is greater in females during respiratory challenge (p<0.05 vs. male and OVX). We conclude that sex differences in recovery of VT and phrenic output are present at 2 weeks post-C2HS. These differences are consistent with the hypothesis that ovarian sex hormones influence respiratory recovery after cervical spinal cord injury.
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Nervo Frênico/fisiologia , Ventilação Pulmonar/fisiologia , Recuperação de Função Fisiológica/fisiologia , Transtornos Respiratórios/complicações , Traumatismos da Medula Espinal/complicações , Análise de Variância , Animais , Vértebras Cervicais , Estradiol/sangue , Potenciais Evocados/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Masculino , Análise por Pareamento , Nervo Frênico/fisiopatologia , Pletismografia Total , Progesterona/sangue , Ratos , Transtornos Respiratórios/fisiopatologia , Fatores Sexuais , Traumatismos da Medula Espinal/fisiopatologia , Estatísticas não ParamétricasRESUMO
BACKGROUND: Integration of biomarker data with information on health and lifestyle provides a powerful tool to enhance the scientific value of health research. Existing health and demographic surveillance systems (HDSSs) present an opportunity to create novel biodata resources for this purpose, but data and biological sample collection often presents challenges. We outline some of the challenges in developing these resources and present the outcomes of a biomarker feasibility study embedded within the South East Asia Community Observatory (SEACO) HDSS. METHODS: We assessed study-related records to determine the pace of data collection, response from potential participants, and feedback following data and sample collection. Overall and stratified measures of data and sample availability were summarised. Crude prevalence of key risk factors was examined. RESULTS: Approximately half (49.5%) of invited individuals consented to participate in this study, for a final sample size of 203 (161 adults and 42 children). Women were more likely to consent to participate compared with men, whereas children, young adults and individuals of Malay ethnicity were less likely to consent compared with older individuals or those of any other ethnicity. At least one biological sample (blood from all participants - finger-prick and venous [for serum, plasma and whole blood samples], hair or urine for adults only) was successfully collected from all participants, with blood test data available from over 90% of individuals. Among adults, urine samples were most commonly collected (97.5%), followed by any blood samples (91.9%) and hair samples (83.2%). Cardiometabolic risk factor burden was high (prevalence of elevated HbA1c among adults: 23.8%; of elevated triglycerides among adults: 38.1%; of elevated total cholesterol among children: 19.5%). CONCLUSIONS: In this study, we show that it is feasible to create biodata resources using existing HDSS frameworks, and identify a potentially high burden of cardiometabolic risk factors that requires further evaluation in this population.
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Following spinal cord injury (SCI), intraspinal transplantation of neural progenitor cells (NPCs) harvested from the forebrain sub-ventricular zone (SVZ) can improve locomotor outcomes. Cervical SCI often results in respiratory-related impairments, and here we used an established model cervical SCI (C2 hemisection, C2Hx) to confirm the feasibility of mid-cervical transplantation of SVZ-derived NPCs and the hypothesis that that this procedure would improve spontaneous respiratory motor recovery. NPCs were isolated from the SVZ of enhanced green fluorescent protein (GFP) expressing neonatal rats, and then intraspinally delivered immediately caudal to an acute C2Hx lesion in adult non-GFP rats. Whole body plethysmography conducted at 4 and 8wks post-transplant demonstrated increased inspiratory tidal volume in SVZ vs. sham transplants during hypoxic (P=0.003) or hypercapnic respiratory challenge (P=0.019). Phrenic nerve output was assessed at 8wks post-transplant; burst amplitude recorded ipsilateral to C2Hx was greater in SVZ vs. sham rats across a wide range of conditions (e.g., quiet breathing through maximal chemoreceptor stimulation; P<0.001). Stereological analyses at 8wks post-injury indicated survival of ~50% of transplanted NPCs with ~90% of cells distributed in ipsilateral white matter at or near the injection site. Peak inspiratory phrenic bursting after NPC transplant was positively correlated with the total number of surviving cells (P<0.001). Immunohistochemistry confirmed an astrocytic phenotype in a subset of the transplanted cells with no evidence for neuronal differentiation. We conclude that intraspinal transplantation of SVZ-derived NPCs can improve respiratory recovery following high cervical SCI.
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Ventrículos Laterais/citologia , Nervo Frênico/fisiologia , Transtornos Respiratórios/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Animais , Animais Recém-Nascidos , Antígeno CD11b/metabolismo , Vértebras Cervicais , Modelos Animais de Doenças , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipóxia , Masculino , Proteína Básica da Mielina/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Recuperação de Função Fisiológica/fisiologia , Transtornos Respiratórios/cirurgiaRESUMO
[This corrects the article DOI: 10.1017/gheg.2017.4.].
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Antimicrobial resistance (AMR) is a global public health threat. Emergence of AMR occurs naturally, but can also be selected for by antimicrobial exposure in clinical and veterinary medicine. Despite growing worldwide attention to AMR, there are substantial limitations in our understanding of the burden, distribution and determinants of AMR at the population level. We highlight the importance of population-based approaches to assess the association between antimicrobial use and AMR in humans and animals. Such approaches are needed to improve our understanding of the development and spread of AMR in order to inform strategies for the prevention, detection and management of AMR, and to support the sustainable use of antimicrobials in healthcare.
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BACKGROUND: The factor (F) XIII Val34Leu variant has been implicated in coronary artery disease (CAD). In vitro evidence suggests an interaction between this variant and fibrinogen concentrations in determining thrombus structure. OBJECTIVES: To test whether this interaction is relevant in influencing coronary risk in apparently healthy individuals. METHODS: In an 8-year prospective population study of 25 663 men and women, we compared 898 apparently healthy men and women developing incident CAD with 1580 matched controls. RESULTS: Overall, the FXIII Val34Leu variant was not associated with the risk of future CAD. However, a significant interaction existed between the Val34Leu variant and fibrinogen levels for the risk of future CAD (P = 0.004). Among people in the lowest tertile of fibrinogen concentrations, LeuLeu carriers had an odds ratio (OR) of 2.88 (95% confidence interval; CI 1.24-6.74) compared to wild-type individuals (P for linearity = 0.003). By contrast, among those in the highest fibrinogen tertile, LeuLeu carriers were had a lower risk than wild-type individuals (OR 0.47, 95% CI 0.18-1.17, P for linearity = 0.1). CONCLUSIONS: Our results suggest that a significant gene-covariate interaction exists between the FXIII Val34Leu variant and fibrinogen levels. Relationships between genotype and disease risk may be altered by biological covariates. Simplistic paradigms of gene or biomarker associations are unlikely to fully characterize disease risk in populations.