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1.
J Int Neuropsychol Soc ; 30(1): 27-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37154103

RESUMO

OBJECTIVE: Loneliness is a concern for patients with schizophrenia. However, the correlates of loneliness in patients with schizophrenia are unclear; thus, the aim of the study is to investigate neuro- and social cognitive mechanisms associated with loneliness in individuals with schizophrenia. METHOD: Data from clinical, neurocognitive, and social cognitive assessments were pooled from two cross-national samples (Poland/USA) to examine potential predictors of loneliness in 147 patients with schizophrenia and 103 healthy controls overall. Furthermore, the relationship between social cognition and loneliness was explored in clusters of patients with schizophrenia differing in social cognitive capacity. RESULTS: Patients reported higher levels of loneliness than healthy controls. Loneliness was linked to increased negative and affective symptoms in patients. A negative association between loneliness and mentalizing and emotion recognition abilities was found in the patients with social-cognitive impairments, but not in those who performed at normative levels. CONCLUSIONS: We have elucidated a novel mechanism which may explain previous inconsistent findings regarding the correlates of loneliness in individuals with schizophrenia.


Assuntos
Disfunção Cognitiva , Mentalização , Esquizofrenia , Teoria da Mente , Humanos , Esquizofrenia/complicações , Solidão , Emoções , Disfunção Cognitiva/complicações , Cognição , Percepção Social
2.
Schizophr Res ; 256: 72-78, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37163867

RESUMO

While considerable emphasis has been put on investigating the mechanisms that drive reduced social connection in patients with schizophrenia (SCZ), recent studies have increasingly focused on the issue of loneliness in SCZ. As both social cognitive bias and self-reported empathy predict loneliness in non-clinical populations, the current study aims to examine the relationship between loneliness, reduced social connection and social cognitive biases, and self-reported empathy in SCZ. Ninety-three adult SCZ and sixty-six matched healthy individuals completed a battery of questionnaires measuring loneliness and social connection (Revised-UCLA Loneliness Scale, Lubben-Social Network Scale, Social Disconnectedness Scale), cognitive biases (Ambiguous Intentions Hostility Questionnaire, Davos Assessment of Cognitive Biases Scale, Cognitive Biases Questionnaire for psychosis) and self-reported empathy (Interpersonal Reactivity Index). Significant predictors of loneliness in SCZ were entered into two latent variables ("Social Threat Bias", "Social Connection"), and structural equation modeling was used to explore the direct and indirect relationships between Social Threat Bias, symptoms. and loneliness in SCZ. Patients reported higher levels of loneliness, cognitive biases and personal distress compared to controls. Furthermore, SCZ reported less social connection and perspective taking compared to controls. Structural equation modeling revealed that Social Threat Bias was linked to increased loneliness in SCZ both directly and indirectly via decreased social connection. Negative symptoms were directly linked with loneliness, while the association between affective symptoms and loneliness was mediated via Social Threat Bias. The results of the current study suggest that social threat bias should be considered while planning the interventions aimed to reduce loneliness in schizophrenia.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Adulto , Humanos , Esquizofrenia/diagnóstico , Solidão/psicologia , Transtornos Psicóticos/psicologia , Viés , Cognição
3.
J Card Surg ; 37(7): 1877-1884, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35249236

RESUMO

BACKGROUND: Closed-chest transapical valve implantations (aortic, mitral, and tricuspid) and cardiac structural procedures requiring large-sized introducer sheaths cannot be safely performed with the available technology. We tested a self-expanding apical closure device in a closed-chest animal model, using large-sized introducer sheaths and human-sized animals to establish the technique for future tests in humans. METHODS: Six human-sized pigs (mean weight: 89.7 ± 3.7 kg) received general anesthesia, intubation, and full heparinization (15,000 IU/animal; expected activated clotting time >200 s). Under fluoroscopy and multimodality imaging guidance with next-generation fusion imaging prototypes, a 15-cm long needle and a standard guidewire were percutaneously inserted under the xiphoidal aponeurosis and into the ventricular apex. After the exchange with a stiff guidewire, a 21-Fr introducer sheath for transapical procedures (outer diameter: 25-Fr) was placed in the left ventricle through the apex. The self-expanding closure device was inserted and deployed under fluoroscopic guidance while the 21-Fr sheath was gently removed. Hemodynamic conditions were monitored for 30 min and then the chest was opened to inspect the closure device and quantify the blood loss in the pericardium. Animals were killed and the hearts were removed and inspected. RESULTS: All six apical closure devices were successfully deployed without adverse events. No death, hemodynamic collapse, or cardiac tamponade occurred during the 30-min observational period (mean systolic and diastolic pressures: 88 ± 11 and 58 ± 13 mmHg, respectively; mean heart rate: 60 ± 11 beats per minutes). Pre- and postdeployment (after protamine administration) mean activated clotting time was 541 ± 263 and 217 ± 62 s, respectively. The plugs provided good sealing with a mean of 27.2 ± 13.86 ml of blood lost in the pericardium. Postmortem inspection showed good plug fixation without myocardial damage. CONCLUSION: This self-expanding apical closure device successfully sealed the percutaneous access sites made with large-sized introducer sheaths in human-sized animals. This preclinical study suggests that transapical valve and structural procedures requiring large-sized introducer sheaths can be performed percutaneously.


Assuntos
Catéteres , Implante de Prótese de Valva Cardíaca , Animais , Cateterismo Cardíaco/métodos , Fluoroscopia , Implante de Prótese de Valva Cardíaca/métodos , Ventrículos do Coração/cirurgia , Hemodinâmica , Hemorragia/etiologia , Humanos , Suínos
4.
J Dent Res ; 101(3): 323-330, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34528480

RESUMO

Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell-derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3'RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration.


Assuntos
Fenda Labial , Fissura Palatina , MicroRNAs , Estudos de Casos e Controles , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , MicroRNAs/genética , Crista Neural , Polimorfismo de Nucleotídeo Único
5.
Perfusion ; 37(8): 773-784, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112048

RESUMO

OBJECTIVES: The main aim was a systematic evaluation of the current evidence on outcomes for patients undergoing right ventricular assist device (RVAD) implantation following left ventricular assist device (LVAD) implantation. METHODS: This systematic review was registered on PROSPERO (CRD42019130131). Reports evaluating in-hospital as well as follow-up outcome in LVAD and LVAD/RVAD implantation were identified through Ovid Medline, Web of Science and EMBASE. The primary endpoint was mortality at the hospital stay and at follow-up. Pooled incidence of defined endpoints was calculated by using random effects models. RESULTS: A total of 35 retrospective studies that included 3260 patients were analyzed. 30 days mortality was in favour of isolated LVAD implantation 6.74% (1.98-11.5%) versus 31.9% (19.78-44.02%) p = 0.001 in LVAD with temporary need for RVAD. During the hospital stay the incidence of major bleeding was 18.7% (18.2-19.4%) versus 40.0% (36.3-48.8%) and stroke rate was 5.6% (5.4-5.8%) versus 20.9% (16.8-28.3%) and was in favour of isolated LVAD implantation. Mortality reported at short-term as well at long-term was 19.66% (CI 15.73-23.59%) and 33.90% (CI 8.84-59.96%) in LVAD respectively versus 45.35% (CI 35.31-55.4%) p ⩽ 0.001 and 48.23% (CI 16.01-80.45%) p = 0.686 in LVAD/RVAD group respectively. CONCLUSION: Implantation of a temporary RVAD is allied with a worse outcome during the primary hospitalization and at follow-up. Compared to isolated LVAD support, biventricular mechanical circulatory support leads to an elevated mortality and higher incidence of adverse events such as bleeding and stroke.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Humanos , Coração Auxiliar/efeitos adversos , Disfunção Ventricular Direita/etiologia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia/etiologia
6.
Osteoporos Int ; 33(1): 177-183, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34350492

RESUMO

Craniocervical abnormalities in osteogenesis imperfecta (OI) such as basilar invagination or cervical kyphosis can cause severe neurological morbidity. These abnormalities may be more frequent in OI type V compared with other OI subtypes of similar disease severity, underlining the importance of screening in this group. INTRODUCTION: Craniocervical abnormalities in osteogenesis imperfecta (OI) can cause severe neurological morbidity. Although radiological cranial base abnormalities in OI have been well described in the literature, there are limited data on these abnormalities in OI type V and their association with clinical sequelae. METHODS: A retrospective case series on patients with craniocervical abnormalities in OI type V at our institution. RESULTS: Craniocervical abnormalities were present in 7 of 37 patients with OI type V (19%). For 5 patients (age at last follow-up: 5 to 26 years; 2 females), sufficient information was available for inclusion in the case series. All had genetically confirmed OI type V. Age range at diagnosis of the craniocervical abnormality was 1 day to 18 years. Basilar invagination was present in 3 patients; 2 had cervical kyphosis. Dysplasia of upper cervical vertebrae or base of skull was seen in 3 patients. The severity of the craniocervical abnormality did not clearly correlate with the severity of the OI phenotype. Three patients required surgical intervention (ages 7, 11, and 26 years) due to compression of the spinal cord or brainstem. Craniocervical abnormalities were detected incidentally or on screening in 3 patients, and only 2 had significant positive findings on neurological examination. CONCLUSION: A variety of craniocervical abnormalities are seen in OI type V including dysplasia of the cervical vertebrae. These cases highlight the importance of screening patients with OI type V with lateral skull and cervical spine x-rays throughout childhood and after skeletal maturity.


Assuntos
Cifose , Osteogênese Imperfeita , Platibasia , Vértebras Cervicais/diagnóstico por imagem , Criança , Feminino , Humanos , Lactente , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/genética , Estudos Retrospectivos
7.
J Cardiovasc Pharmacol Ther ; 26(6): 665-676, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33969747

RESUMO

Manipulation of nitric oxide (NO) may enable control of progression and treatment of pulmonary hypertension (PH). Several approaches may modulate the NO-cGMP pathway in vivo. Here, we investigate the effectiveness of 3 modulatory sites: (i) the amount of l-arginine; (ii) the size of plasma NO stores that stimulate soluble guanylate cyclase; (iii) the conversion of cGMP into inactive 5'-GMP, with respect to hypoxia, to test the effectiveness of the treatments with respect to hypoxia-induced PH. Male rats (n = 80; 10/group) maintained in normoxic (21% O2) or hypoxic chambers (10% O2) for 14 days were subdivided in 4 sub-groups: placebo, l-arginine (20 mg/ml), the NO donor molsidomine (15 mg/kg in drinking water), and phoshodiesterase-5 inhibitor sildenafil (1.4 mg/kg in 0.3 ml saline, i.p.). Hypoxia depressed homeostasis and increased erythropoiesis, heart and right ventricle hypertrophy, myocardial fibrosis and apoptosis inducing pulmonary remodeling. Stimulating anyone of the 3 mechanisms that enhance the NO-cGMP pathway helped rescuing the functional and morphological changes in the cardiopulmonary system leading to improvement, sometimes normalization, of the pressures. None of the treatments affected the observed parameters in normoxia. Thus, the 3 modulatory sites are essentially similar in enhancing the NO-cGMP pathway, thereby attenuating the hypoxia-related effects that lead to pulmonary hypertension.


Assuntos
GMP Cíclico/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Hipóxia/fisiopatologia , Óxido Nítrico/metabolismo , Citrato de Sildenafila/farmacologia , Animais , Arginina/metabolismo , Hipertensão Pulmonar/fisiopatologia , Masculino , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Vasodilatadores
8.
Perfusion ; 36(2): 183-189, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32567504

RESUMO

OBJECTIVE: The aim was to evaluate the performance of a newly developed magnetically suspended centrifugal pump head intended for use as a ventricular assistance device with a newly developed extracorporeal membrane oxygenator setup. METHODS: In an experimental setup, an extracorporeal membrane oxygenator circuit was established in three calves with a mean weight of 68.2 ± 2.0 kg. A magnetically levitated centrifugal pump was tested, along with a newly designed extracorporeal membrane oxygenator console, at three different flow ranges: (a) 0.0 to 5.2 L/min, (b) 0.0 to 7.1 L/min, and (c) 0.0 to 6.0 L/min. For each setup, the animals were supported by a circuit for 6 h. Blood samples were collected just before caridiopulmonary bypass (CPB) after 10 min on bypass and after 1, 2, 5, and 6 h of perfusion for hemolysis determination and biochemical tests. Values were recorded for blood pressure, mean flow, and pump rotational speed. Analysis of variance was used for repeated measurements. RESULTS: Mean pump flows achieved during the three 6 h pump runs for the three pump heads studied were as follows: (a) flow range 0.0 to 5.2 L/min, 3.6 ± 1.5 L/min, (b) flow range 0.0 to 7.1 L/min, 4.9 ± 1.3 L/min, and (c) flow range 0.0 to 6.0 L/min, 3.8 ± 1.5 L/min. Blood trauma, evaluated by plasma hemoglobin and lactate dehydrogenase levels, did not help in detecting any significant hemolysis. Thrombocytes and white blood cell count profiles showed no significant differences between the groups at the end of the 6 h perfusion. At the end of testing, no clot deposition was found in the oxygenator, and there was no evidence of peripheral emboli. CONCLUSION: The results suggest that the newly developed magnetically suspended centrifugal pump head provides satisfactory hydrodynamic performance in an acute perfusion scenario without increasing hemolysis.


Assuntos
Oxigenação por Membrana Extracorpórea , Trombose , Animais , Bovinos , Hemólise , Hidrodinâmica , Oxigenadores de Membrana
9.
Acta Diabetol ; 57(10): 1245-1253, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32488499

RESUMO

AIMS: To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). METHODS: In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA-during follow-up according to the most recent episode-or ND. RESULTS: At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. CONCLUSIONS: HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/epidemiologia , Hiperglicemia/epidemiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Adolescente , Adulto , Idoso , Áustria/epidemiologia , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Cetoacidose Diabética/sangue , Cetoacidose Diabética/complicações , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Coma Hiperglicêmico Hiperosmolar não Cetótico/sangue , Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suíça/epidemiologia , Adulto Jovem
10.
Osteoarthritis Cartilage ; 28(9): 1235-1244, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32278071

RESUMO

OBJECTIVE: Evaluate articular cartilage by magnetic resonance imaging (MRI) T2∗ mapping within the distal femur and proximal tibia in adolescents with juvenile osteochondritis dissecans (JOCD). DESIGN: JOCD imaging studies acquired between August 2011 and February 2019 with clinical and T2∗ mapping MRI knee images were retrospectively collected and analyzed for 31 participants (9F/22M, 15.0 ± 3.8 years old) with JOCD lesions in the medial femoral condyle (MFC). In total, N = 32 knees with JOCD lesions and N = 14 control knees were assessed. Mean T2∗ values in four articular cartilage regions-of-interest (MFC, lateral femoral condyle (LFC), medial tibia (MT), and lateral tibia (LT)) and lesion volume were measured and analyzed using Wilcoxon-rank-sum tests and Spearman correlation coefficients (R). RESULTS: Mean ± standard error T2∗ differences observed between the lesion-sided MFC and the LFC in JOCD-affected knees (28.5 ± 0.9 95% confidence interval [26.8, 30.3] vs 26.3 ± 0.7 [24.8, 27.7] ms, P = 0.088) and between the affected- and control-knee MFC (28.5 ± 0.9 [26.8, 30.3] vs 28.5 ± 0.6 [27.1, 29.9] ms, P = 0.719) were nonsignificant. T2∗ was significantly increased in the lesion-sided MT vs the LT for the JOCD-affected knees (21.5 ± 0.7 [20.1, 22.9] vs 18.0 ± 0.7 [16.5, 19.5] ms, P = 0.002), but this same difference was also observed between the MT and LT in control knees (21.0 ± 0.6 [19.7, 22.3] vs 18.1 ± 1.1 [15.8, 20.4] ms, P = 0.037). There was no significant T2∗ difference between the affected- and control-knee MT (21.5 ± 0.7 [20.1, 22.9] vs 21.0 ± 0.6 [19.7, 22.3] ms, P = 0.905). T2∗ within the lesion-sided MFC was not correlated with patient age (R = 0.20, P = 0.28) or lesion volume (R = 0.06, P = 0.75). T2∗ values were slightly increased near lesions in later-stage JOCD subjects but without statistical significance. CONCLUSIONS: T2∗ relaxations times were not significantly different from control sites in the articular cartilage overlying JOCD lesions in the MFC or adjacent MT cartilage in early-stage JOCD.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Osteocondrite Dissecante/diagnóstico por imagem , Adolescente , Idade de Início , Criança , Feminino , Fêmur/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Adulto Jovem
11.
Ophthalmologe ; 117(12): 1198-1209, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-32221657

RESUMO

Subjective impairment of floater patients can only be partially quantified using ophthalmological test methods. In order to classify floater patients, patient-related characteristics associated with higher level of impairment should be identified. A data set of a prospective, multicenter single-arm primary study of 64 floater patients who underwent vitrectomy includes patient-related characteristics and information on subjective preoperative and postoperative (3 months after vitrectomy) impairment. Data on impairment were collected with a floater-specific questionnaire and condensed into self-rated impairment indices (SRI). Medians of the SRI were calculated for the manifestation of sociodemographic and ophthalmological parameters as well as for the classification of floaters on the study and second eye and tested for significance. Higher preoperative SRI were associated with professional activity, young age, reduced preoperative visual acuity, retinal alterations and higher refractive errors as well as floaters on the second eye. Higher postoperative SRI were found in combination with cataract and younger age. The SRI differences were only occasionally significant. Classification of floaters as documented by the surgeon and by SRI were significantly correlated only for patients without other visual comorbidities besides floaters. The primary study reported high preoperative subjective impairment and a significant decrease in SRI after vitrectomy for almost all patients. The current study showed that some individual patient-related characteristics tended to be associated with greater preoperative impairment and greater benefit from vitrectomy.


Assuntos
Oftalmopatias , Corpo Vítreo , Oftalmopatias/diagnóstico , Oftalmopatias/epidemiologia , Oftalmopatias/cirurgia , Humanos , Pacientes , Estudos Prospectivos , Vitrectomia
12.
Sci Rep ; 9(1): 11120, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366938

RESUMO

Bile acids are steroid compounds from the digestive tracts of vertebrates that enter agricultural environments in unusual high amounts with manure. Bacteria degrading bile acids can readily be isolated from soils and waters including agricultural areas. Under laboratory conditions, these bacteria transiently release steroid compounds as degradation intermediates into the environment. These compounds include androstadienediones (ADDs), which are C19-steroids with potential hormonal effects. Experiments with Caenorhabditis elegans showed that ADDs derived from bacterial bile acid degradation had effects on its tactile response, reproduction rate, and developmental speed. Additional experiments with a deletion mutant as well as transcriptomic analyses indicated that these effects might be conveyed by the putative testosterone receptor NHR-69. Soil microcosms showed that the natural microflora of agricultural soil is readily induced for bile acid degradation accompanied by the transient release of steroid intermediates. Establishment of a model system with a Pseudomonas strain and C. elegans in sand microcosms indicated transient release of ADDs during the course of bile acid degradation and negative effects on the reproduction rate of the nematode. This proof-of-principle study points at bacterial degradation of manure-derived bile acids as a potential and so-far overlooked risk for invertebrates in agricultural soils.


Assuntos
Ácidos e Sais Biliares/metabolismo , Caenorhabditis elegans/metabolismo , Esterco/microbiologia , Pseudomonas/metabolismo , Esteroides/metabolismo , Agricultura/métodos , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Receptores Androgênicos/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Solo , Transcriptoma/fisiologia
13.
Cardiovasc Drugs Ther ; 33(4): 407-414, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31264002

RESUMO

PURPOSE: In pulmonary hypertension (PH), hypoxia represents both an outcome and a cause of exacerbation. We addressed the question whether hypoxia adaptation might affect the mechanisms underlying PH alleviation through phosphodiesterase-5 (PDE5) inhibition. METHODS: Eight-week-old male Sprague-Dawley rats were divided into two groups depending on treatment (placebo or sildenafil, a drug inhibiting PDE5) and were exposed to hypoxia (10% O2) for 0 (t0, n = 9/10), 2 (t2, n = 5/5) or 4 (t4, n = 5/5) weeks. The rats were treated (0.3 mL i.p.) with either saline or sildenafil (1.4 mg/Kg per day). RESULTS: Two-week hypoxia changed the body weight (- 31% vs. - 27%, respectively, P = NS), blood hemoglobin (+ 25% vs. + 27%, P = NS) and nitrates+nitrites (+ 175% vs. + 261%, P = 0.007), right ventricle fibrosis (+ 814% vs. + 317%, P < 0.0001), right ventricle hypertrophy (+ 84% vs. + 49%, P = 0.007) and systolic pressure (+ 108% vs. + 41%, P = 0.001), pulmonary vessel density (+ 61% vs. + 46%, P = NS), and the frequency of small (< 50 µm wall thickness) vessels (+ 35% vs. + 13%, P = 0.0001). Most of these changes were maintained for 4-week hypoxia, except blood hemoglobin and right ventricle hypertrophy that continued increasing (+ 52% vs. + 42%, P = NS; and + 104% vs. + 83%, P = 0.04). To further assess these observations, small vessel frequency was found to be linearly related with the right ventricle-developed pressure independent of hypoxia duration. CONCLUSIONS: Thus, although hypoxia adaptation is not yet accomplished after 4 weeks, PH alleviation by PDE5 inhibition might nevertheless provide an efficient strategy for the management of this disease.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/complicações , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Pulmão/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
14.
Philos Trans A Math Phys Eng Sci ; 377(2151): 20180392, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31230573

RESUMO

The FLASHForward experimental facility is a high-performance test-bed for precision plasma wakefield research, aiming to accelerate high-quality electron beams to GeV-levels in a few centimetres of ionized gas. The plasma is created by ionizing gas in a gas cell either by a high-voltage discharge or a high-intensity laser pulse. The electrons to be accelerated will either be injected internally from the plasma background or externally from the FLASH superconducting RF front end. In both cases, the wakefield will be driven by electron beams provided by the FLASH gun and linac modules operating with a 10 Hz macro-pulse structure, generating 1.25 GeV, 1 nC electron bunches at up to 3 MHz micro-pulse repetition rates. At full capacity, this FLASH bunch-train structure corresponds to 30 kW of average power, orders of magnitude higher than drivers available to other state-of-the-art LWFA and PWFA experiments. This high-power functionality means FLASHForward is the only plasma wakefield facility in the world with the immediate capability to develop, explore and benchmark high-average-power plasma wakefield research essential for next-generation facilities. The operational parameters and technical highlights of the experiment are discussed, as well as the scientific goals and high-average-power outlook. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

15.
Swiss Med Wkly ; 149: w20054, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30995683

RESUMO

AIMS OF THE STUDY: An extracorporeal membrane oxygenation system (ECMO), as a bridge to either recovery, a ventricular assist device (VAD), or heart or lung transplantation, may be the only lifesaving option for critically ill patients suffering from refractory cardiac, respiratory or combined cardiopulmonary failure. As peripheral hospitals may not offer ECMO treatment, tertiary care centres provide specialised ECMO teams for on-site implantation and subsequent patient transfer on ECMO to the tertiary hospital. This study reports the results of the largest ECMO transportation programme in Switzerland and describes its feasibility and safety. METHODS: Patients transported on ECMO by our mobile ECMO team to our tertiary centre between 1 September 2009 and 31 December, 2016 underwent retrospective analysis. Implantation was performed by our specialised ECMO team (primary transport) or by the medical staff of the referring hospital (secondary transport) with subsequent transfer to our institution. Type of ECMO, transport data, patient baseline characteristics, operative variables and postoperative outcomes including complications and mortality were collected from medical records. RESULTS: Fifty-eight patients were included (three patients excluded: one repatriation, two with incomplete medical records). Thirty-five patients (60%) received veno-venous, 22 (38%) veno-arterial and one patient (2%) veno-venoarterial ECMO. Forty-nine (84%) patients underwent primary and nine (16%) secondary transport. Thirty-five (60%) patients were transferred by helicopter and 23 (40%) by ambulance, with median distances of 38.1 (13–225) km and 21 (3-71) km respectively. No clinical or technical complications occurred during transportation. During hospitalisation, three patients had ECMO-associated complications (two compartment syndrome of lower limb, one haemothorax after central ECMO upgrade). Median days on ECMO was 8 (<1–49) and median days in hospital was 17 (<1–122). ECMO weaning was successful in 41 patients (71%), on-transport survival was 100%, 40 patients survived to discharge (69%), and overall survival was 67% (39 patients) at a median follow-up of 58 days (<1–1441). Cumulative survival was significantly affected by cardiogenic shock vs. ARDS (p = 0.001), veno-arterial and veno-venoarterial vs. veno-venous ECMO (p = 0.001) and after secondary vs. primary transport (p <0.001). The ECMO weaning rate was significantly lower after secondary transfer (22%, two patients, both vaECMO) vs. primary transfer (80%, p = 0.002, 39 patients of which 35 (71%) had vvECMO). CONCLUSIONS: The first results of our ECMO transportation programme show its feasibility, safety and efficacy without on-site implant or on-transport complications or mortality. The favourable early survival may justify the large effort with respect to logistics, costs and manpower. With rising awareness, referring centres may increasingly consider this lifesaving option at an early stage, which may further improve outcomes.


Assuntos
Estado Terminal/mortalidade , Oxigenação por Membrana Extracorpórea/mortalidade , Hospitais/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Adulto , Oxigenação por Membrana Extracorpórea/métodos , Estudos de Viabilidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes/métodos , Estudos Retrospectivos , Suíça , Fatores de Tempo , Transporte de Pacientes/métodos , Transporte de Pacientes/estatística & dados numéricos , Resultado do Tratamento
16.
Eur Heart J ; 39(45): 3995-3997, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508101
18.
Perfusion ; 33(1_suppl): 18-23, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29788840

RESUMO

OBJECTIVE: The present study was designed to assess in vivo a new, optimized, virtually wall-less, dual-lumen, bi-caval cannula for veno-venous ECMO in comparison to a commercially available cannula. METHODS: Veno-venous extracorporeal membrane oxygenation (ECMO) was carried out in a bovine study (n=5, bodyweight 75±5kg). Following systemic heparinization, ECMO was established in a trans-jugular fashion through a calibrated 23F orifice, using a new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula (Smartcanula LLC, Lausanne, Switzerland) versus a commercially available 23F bi-caval, dual-lumen control cannula (Avalon Elite®, Maquet, Rastatt, Germany) in a veno-venous ECMO setup. Veno-venous ECMO was initiated at 500 revolutions per minute (RPM) and increased by incremental steps of 500 RPM up to 2500 RPM. Catheter outlet pressure, catheter inlet pressure, oxygen saturation and pump flow were recorded at each stage. RESULTS: Mean flow accounted for 0.37±0.04 L/min for wall-less versus 0.29± 0.07 L/min for control at 500 RPM, 0.97±0.12 versus 0.67±0.06 at 1000 RPM, 1.60±0.14 versus 1.16±0.08 at 1500 RPM, 2.31±0.13 versus 1.52±0.13 for 2000 RPM and 3.02±0.5 versus 2.11±0.18 (p<0.004). The mean venous suction required was 19±8 mmHg for wall-less versus 20±3 mmHg for control at 500 RPM, 7±3 versus 9±4 for 1000 RPM, -11±10 versus -12±8 at 1500 RPM, -39±15 versus -49±10 for 2000 RPM and -60±28 versus -94±7 for 2500 RPM. The mean venous injection pressure accounted for 29±7 mmHg for wall-less versus 27±5 mmHg for control at 500 RPM, 50±6 versus 61±7 at 1000 RPM, 89±10 versus 99±17 for 1500 RPM, 142±14 versus 161±9 at 2000 RPM and 211±41 versus 252 ±3 for 2500 RPM. CONCLUSION: Compared to the commercially available control cannula, the new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula allows for significantly higher blood flows, requires less suction and results in lower injection pressures in vivo.


Assuntos
Cânula/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea/métodos , Hemodinâmica/fisiologia , Animais , Bovinos , Humanos
20.
Innovations (Phila) ; 13(2): 104-107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29677020

RESUMO

OBJECTIVE: Inadequate peripheral venous drainage during minimally invasive cardiac surgery (MICS) is a challenge and cannot always be solved with increased vacuum or increased centrifugal pump speed. The present study was designed to assess the benefit of virtually wall-less transfemoral venous cannulas during MICS. METHODS: Transfemoral venous cannulation with virtually wall-less cannulas (3/8″ 24F 530-630-mm ST) was performed in 10 consecutive patients (59 ± 10 years, 8 males, 2 females) undergoing MICS for mitral (6), aortic (3), and other (4) procedures (combinations possible). Before transfemoral insertion of wall-less cannulas, a guidewire was positioned in the superior vena cava under echocardiographic control. The wall-less cannula was then fed over the wire and connected to a minimal extracorporeal system. Vacuum assist was used to reach a target flow of 2.4 l/min per m with augmented venous drainage at less than -80 mm Hg. RESULTS: Wall-less venous cannulas measuring either 630 mm (n = 8) in length or 530 mm (n = 2) were successfully implanted in all patients. For a body size of 173 ± 11 cm and a body weight of 78 ± 26 kg, the calculated body surface area was 1.94 ± 0.32 m. As a result, the estimated target flow was 4.66 ± 0.78 l/min, whereas the achieved flow accounted for 4.98 ± 0.69 l/min (107% of target) at a vacuum level of 21.3 ± 16.4 mm Hg. Excellent exposure and "dry" intracardiac surgical field resulted. CONCLUSIONS: The performance of virtually wall-less venous cannulas designed for augmented peripheral venous drainage was tested in MICS and provided excellent flows at minimal vacuum levels, confirming an increased performance over traditional thin wall cannulas. Superior results can be expected for routine use.


Assuntos
Cânula/normas , Procedimentos Cirúrgicos Cardíacos/instrumentação , Ponte Cardiopulmonar/instrumentação , Drenagem/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Idoso , Cânula/estatística & dados numéricos , Ponte Cardiopulmonar/métodos , Cateterismo , Drenagem/métodos , Ecocardiografia , Desenho de Equipamento , Feminino , Veia Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Vácuo , Veia Cava Superior/cirurgia
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