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1.
Thorax ; 79(6): 524-537, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38286613

RESUMO

INTRODUCTION: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised. METHODS: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation. RESULTS: COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells. CONCLUSION: We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.


Assuntos
Células Epiteliais , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/etiologia , Células Epiteliais/metabolismo , Masculino , Pessoa de Meia-Idade , Células Cultivadas , Brônquios/patologia , Feminino , Idoso , Óxido de Zinco , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Cílios , Nanopartículas , Diferenciação Celular
2.
Am J Perinatol ; 41(S 01): e3305-e3312, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38154466

RESUMO

OBJECTIVE: Pneumothorax (PTX) is a potentially life-threatening condition that affects neonates, with an incidence of 0.05 to 2%. Its management includes conservative treatment, chest tube (CT) drainage, and needle aspiration (NA). Aims were to evaluate the incidence of PTX in a 10-hospital perinatal network, its clinical characteristics and risk factors, and to compare the different treatment options. STUDY DESIGN: All neonates diagnosed with PTX and hospitalized in the network were included in this retrospective observational trial over a period of 30 months. Primary outcome was the incidence of PTX. Secondary outcomes were the treatment modality, the length of stay (LOS), and the number of chest X-rays. RESULTS: Among the 173 neonates included, the overall incidence of PTX was 0.56 per 100 births with a large range among the hospitals (0.12-1.24). Thirty-nine percent of pneumothoraces were treated conservatively, 41% by CT drainage, 13% by NA, and 7% by combined treatment. Failure rate was higher for NA (37%) than for CT drainage (9%). However, the number of X-rays was lower for patients treated by NA, with a median of 6 (interquartile range [IQR] 4-6.25), than by CT drainage, with a median of 9 (IQR 7-12). LOS was shorter for NA than for CT drainage, with a median of 2 (IQR 1-4.25) and 6 days (IQR 3-15), respectively. Complications, including apnea and urinary retention, occurred in 28% of patients managed with CT drainage, whereas none was observed with NA. CONCLUSION: High variability of PTX incidence was observed among the hospitals within the network, but these values correspond to the literature. NA showed to reduce the number of X-rays, the LOS, and complications compared with CT drainage, but it carries a high failure rate. This study helped provide a new decisional management algorithm to harmonize and improve PTX treatment within our network. KEY POINTS: · Neonatal PTX is a frequent pathology with a high incidence requiring urgent management.. · We report a large variability of PTX incidence between different hospitals of the same network.. · Needle aspiration carries higher failure rate, shorter hospital stay duration without complications reported..


Assuntos
Tubos Torácicos , Drenagem , Tempo de Internação , Pneumotórax , Humanos , Pneumotórax/terapia , Pneumotórax/epidemiologia , Estudos Retrospectivos , Recém-Nascido , Feminino , Masculino , Suíça/epidemiologia , Incidência , Drenagem/métodos , Tempo de Internação/estatística & dados numéricos , Tratamento Conservador/métodos , Fatores de Risco
3.
J Pediatr ; 237: 213-220.e2, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34157348

RESUMO

OBJECTIVE: To assess patent ductus arteriosus treatment variation between Swiss perinatal centers and to determine its effect on outcome in a population-based setting. STUDY DESIGN: This was a retrospective cohort study of infants born less than 28 weeks of gestation between 2012 and 2017. Outcomes between surgically ligated and pharmacologically treated infants as well as infants born in centers performing ≤10% ligation ("low" group) and >10% ("high" group) were compared using logistic regression and 1:1 propensity score matching. Matching was based on case-mix and preligation confounders: intraventricular hemorrhages grades 3-4, necrotizing enterocolitis, sepsis, and ≥28 days' oxygen supply. RESULTS: Of 1389 infants, 722 (52%) had pharmacologic treatment and 156 (11.2%) received surgical ligation. Compared with infants who received pharmacologic treatment, ligated infants had greater odds for major morbidities (OR 2.09, 95% CI 1.44-3.04) and 2-year neurodevelopmental impairment (OR 1.81, 95% CI 1.15-2.84). Mortality was comparable after restricting the cohort to infants surviving at least until day 10 to avoid survival bias. In the "low" group, 34 (4.9%) of 696 infants were ligated compared with 122 (17.6%) of 693 infants in the "high" group. Infants in the "high" group had greater odds for major morbidities (OR 1.49, 95% CI 1.11-2.0). CONCLUSIONS: Our analysis identified a burden on infants receiving surgical ligation vs pharmacologic treatment in a population-based setting where there was no agreed-on common procedure. These results may guide a revision of patent ductus arteriosus treatment practice in Switzerland.


Assuntos
Permeabilidade do Canal Arterial/mortalidade , Permeabilidade do Canal Arterial/cirurgia , Doenças do Prematuro/mortalidade , Doenças do Prematuro/cirurgia , Ligadura/estatística & dados numéricos , Permeabilidade do Canal Arterial/complicações , Feminino , Hospitalização , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Razão de Chances , Utilização de Procedimentos e Técnicas , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Suíça , Resultado do Tratamento
4.
J Biol Chem ; 294(2): 644-661, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30455355

RESUMO

Ataxin-3 is a deubiquitinating enzyme and the affected protein in the neurodegenerative disorder Machado-Joseph disease (MJD). The ATXN3 gene is alternatively spliced, resulting in protein isoforms that differ in the number of ubiquitin-interacting motifs. Additionally, nonsynonymous SNPs in ATXN3 cause amino acid changes in ataxin-3, and one of these polymorphisms introduces a premature stop codon in one isoform. Here, we examined the effects of different ataxin-3 isoforms and of the premature stop codon on ataxin-3's physiological function and on main disease mechanisms. At the physiological level, we show that alternative splicing and the premature stop codon alter ataxin-3 stability and that ataxin-3 isoforms differ in their enzymatic deubiquitination activity, subcellular distribution, and interaction with other proteins. At the pathological level, we found that the expansion of the polyglutamine repeat leads to a stabilization of ataxin-3 and that ataxin-3 isoforms differ in their aggregation properties. Interestingly, we observed a functional interaction between normal and polyglutamine-expanded ATXN3 allelic variants. We found that interactions between different ATXN3 allelic variants modify the physiological and pathophysiological properties of ataxin-3. Our findings indicate that alternative splicing and interactions between different ataxin-3 isoforms affect not only major aspects of ataxin-3 function but also MJD pathogenesis. Our results stress the importance of considering isoforms of disease-causing proteins and their interplay with the normal allelic variant as disease modifiers in MJD and autosomal-dominantly inherited diseases in general.


Assuntos
Processamento Alternativo , Ataxina-3/genética , Ataxina-3/metabolismo , Doença de Machado-Joseph/genética , Agregação Patológica de Proteínas/genética , Ataxina-3/análise , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Doença de Machado-Joseph/metabolismo , Doença de Machado-Joseph/patologia , Polimorfismo de Nucleotídeo Único , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia , Mapas de Interação de Proteínas , Isoformas de Proteínas/análise , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estabilidade Proteica , Ubiquitina/metabolismo
5.
J Pediatr ; 226: 87-95.e3, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32454115

RESUMO

OBJECTIVES: To determine, in children born preterm, the association of mechanical ventilation duration with brainstem development, white matter maturation, and neurodevelopmental outcomes at preschool age. STUDY DESIGN: This prospective cohort study included 144 neonates born at <30 weeks of gestation (75 male, mean gestational age 27.1 weeks, SD 1.6) with regional brainstem volumes automatically segmented on magnetic resonance imaging at term-equivalent age (TEA). The white matter maturation was assessed by diffusion tensor imaging and tract-based spatial statistics. Neurodevelopmental outcomes were assessed at 4.5 years of age using the Movement Assessment Battery for Children, 2nd Edition, and the Wechsler Primary and Preschool Scale of Intelligence, 4th Edition, full-scale IQ. The association between the duration of mechanical ventilation and brainstem development was validated in an independent cohort of children born very preterm. RESULTS: Each additional day of mechanical ventilation predicted lower motor scores (0.5-point decrease in the Movement Assessment Battery for Children, 2nd Edition, score by day of mechanical ventilation, 95% CI -0.6 to -0.3, P < .0001). Prolonged exposure to mechanical ventilation was associated with smaller pons and medulla volumes at TEA in 2 independent cohorts, along with widespread abnormalities in white matter maturation. Pons and medulla volumes at TEA predicted motor outcomes at 4.5 years of age. CONCLUSIONS: In neonates born very preterm, prolonged mechanical ventilation is associated with impaired brainstem development, abnormal white matter maturation, and lower motor scores at preschool age. Further research is needed to better understand the neural pathological mechanisms involved.


Assuntos
Tronco Encefálico/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Doenças do Prematuro/terapia , Transtornos do Neurodesenvolvimento/epidemiologia , Respiração Artificial/efeitos adversos , Pré-Escolar , Estudos de Coortes , Imagem de Tensor de Difusão , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologia , Tamanho do Órgão , Estudos Prospectivos , Fatores de Tempo , Substância Branca/crescimento & desenvolvimento
6.
Med Mycol ; 57(6): 694-702, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445443

RESUMO

Biotyper analysis of Nannizziopsis guarroi, a fatal fungal pathogen in lizards, was described recently. Hypocrealean fungal infections in captive reptiles appear with an increasing frequency during the last decade. Therefore, the aim of this study was to proof Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) as diagnostic tool for the identification of reptile pathogenic hypocrealean fungi. Ten fungal isolates obtained from nine reptiles with fungal glossitis, disseminated visceral mycosis, pneumomycosis, and fungal keratitis were analyzed. Phylogeny consisted of fragments of the large subunit of nuclear encoded ribosomal DNA (D1/D2, LSU) and the internal transcribed spacer region 1 of nuclear encoded ribosomal DNA (ITS1) as well as the protein coding gene translation elongation factor 1 alpha (TEF). Results revealed unanimously two Metarhizium granulomatis genotypes in a total of three isolates, various M. viride genotypes (n = 3), two different Purpureocillium lilacinum isolates as well as one isolate of each P. lavendulum and Beauveria bassiana. Purpureocillium lilacinum and B. bassiana are likewise frequently employed as a mycoinsecticide and mycoacaricide in agriculture on a worldwide scale and have occasionally been reported in man, causing fungal keratitis, sclerokeratitis, nosocomial infections in immunosuppressed patients, as well as cavitary pulmonary disease and cutaneous hyalohyphomycosis in immunocompetent patients. According to the results establishment of Biotyper analysis for faster differentiation of reptile-associated fungal pathogens is entirely justified.


Assuntos
Fungos/classificação , Micoses/veterinária , Répteis/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Jacarés e Crocodilos/microbiologia , Animais , Animais de Zoológico/microbiologia , Beauveria/classificação , Beauveria/isolamento & purificação , DNA Espaçador Ribossômico/genética , Feminino , Fungos/isolamento & purificação , Lagartos/microbiologia , Masculino , Metarhizium/classificação , Metarhizium/isolamento & purificação , Paecilomyces/classificação , Paecilomyces/isolamento & purificação , Filogenia , Serpentes/microbiologia
7.
Med Mycol ; 56(5): 610-620, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29420823

RESUMO

Fungal infections in captive as well as in free-living reptiles caused by emerging obligate pathogenic fungi appear with increasing frequency and give occasion to establish new and fast methods for routine diagnostics. The so-called yellow fungus disease is one of the most important and common fungal dermatomycoses in central bearded dragons (Pogona vitticeps) and green iguanas (Iguana iguana) and is caused by Nannizziopsis guarroi. The aim of this study was to prove reliability in identification of N. guarroi with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in comparison to molecular biological analysis of ribosomal DNA genes. In seven lizards from three different species, including central bearded dragons, green iguanas, and a European green lizard (Lacerta viridis), dermatomycoses caused by N. guarroi were diagnosed by isolation of the fungal pathogen as well as histopathological confirmation of the granulomatous inflammatory reaction in deep skin biopsies. With this survey, we proved that MALDI-TOF MS is a diagnostic tool for accurate identification of N. guarroi. Besides small subunit 18S rDNA (SSU) and internal transcribed spacer (ITS)1-5.8S rDNA, a large fragment of the large subunit of the 28S rDNA (LSU), including the domain (D)1 and D2 have been sequenced, for phylogenetical analysis. Large fragment of the LSU from N. guarroi has been sequenced for the first time. Yellow fungus disease in a European lizard species is described for the first time to our knowledge as well, which could be of importance for free-ranging populations of European lizards.


Assuntos
Dermatomicoses/veterinária , Genômica , Lagartos/microbiologia , Onygenales/genética , Proteômica , Animais , DNA Ribossômico/genética , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Proteínas Fúngicas/metabolismo , Genoma Fúngico/genética , Técnicas de Tipagem Micológica , Onygenales/classificação , Onygenales/metabolismo , Filogenia , Análise de Componente Principal , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária
8.
J Clin Microbiol ; 55(3): 832-843, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28003420

RESUMO

Metarhizium viride has been associated with fatal systemic mycoses in chameleons, but subsequent data on mycoses caused by this fungus in reptiles are lacking. The aim of this investigation was therefore to obtain information on the presence of M. viride in reptiles kept as pets in captivity and its association with clinical signs and pathological findings as well as improvement of diagnostic procedures. Beside 18S ribosomal DNA (rDNA) (small subunit [SSU]) and internal transcribed spacer region 1 (ITS-1), a fragment of the large subunit (LSU) of 28S rDNA, including domain 1 (D1) and D2, was sequenced for the identification of the fungus and phylogenetic analysis. Cultural isolation and histopathological examinations as well as the pattern of antifungal drug resistance, determined by using agar diffusion testing, were additionally used for comparison of the isolates. In total, 20 isolates from eight inland bearded dragons (Pogona vitticeps), six veiled chameleons (Chamaeleo calyptratus), and six panther chameleons (Furcifer pardalis) were examined. Most of the lizards suffered from fungal glossitis, stomatitis, and pharyngitis or died due to visceral mycosis. Treatment with different antifungal drugs according to resistance patterns in all three different lizard species was unsuccessful. Sequence analysis resulted in four different genotypes of M. viride based on differences in the LSU fragment, whereas the SSU and ITS-1 were identical in all isolates. Sequence analysis of the SSU fragment revealed the first presentation of a valid large fragment of the SSU of M. viride According to statistical analysis, genotypes did not correlate with differences in pathogenicity, antifungal susceptibility, or species specificity.


Assuntos
Metarhizium/isolamento & purificação , Micoses/veterinária , Animais , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Feminino , Histocitoquímica , Masculino , Microscopia , Técnicas de Tipagem Micológica , Micoses/microbiologia , Micoses/patologia , Filogenia , RNA Ribossômico/genética , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética , Répteis , Análise de Sequência de DNA
9.
J Pediatr ; 181: 29-36.e1, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27837953

RESUMO

OBJECTIVES: To investigate the association between early nutritional intake and brain development assessed by magnetic resonance imaging (MRI). STUDY DESIGN: A cohort of neonates born at ≤30 weeks gestational age underwent MRI at term equivalent age. Brain maturation and injury were assessed using the Kidokoro score. Two groups were defined by severity of the scores. The associations between macronutrients intake during the first 2 weeks of life, clinical factors, and imaging scores were analyzed using logistic regression. RESULTS: MRI scores from group 1 patients (n = 27) were normal to mildly abnormal (0-5). Group 2 (n = 15) had more abnormal scores (6-12). The median gestational ages (IQR) were 27.4 (1.9) weeks in group 1 and 27.0 (2.9) weeks in group 2, with birth weights of 900 (318) g (group 1) and 844 (293) g (group 2). In group 2, energy, lipid, and carbohydrate intake were significantly lower than in group 1. Group 2 also showed higher rates of sepsis and clinical risk scores than group 1. After adjustments in bivariate models, higher energy and lipid intake remained significantly associated with improved scores on MRI. This association was stronger for the gray matter component of the score. CONCLUSIONS: Higher energy and lipid intake during the first 2 weeks after birth was associated with a lower incidence of brain lesions and dysmaturation at term equivalent age in preterm neonates.


Assuntos
Desenvolvimento Infantil/fisiologia , Dietoterapia/métodos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/crescimento & desenvolvimento , Imageamento por Ressonância Magnética/métodos , Análise de Variância , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Necessidades Nutricionais , Estudos Prospectivos , Valores de Referência , Medição de Risco , Nascimento a Termo
10.
Tumour Biol ; 37(5): 6275-83, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26619845

RESUMO

Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 µM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis.


Assuntos
Carcinoma/tratamento farmacológico , Éteres Fosfolipídicos/administração & dosagem , Canais de Potássio Ativados por Cálcio de Condutância Baixa/biossíntese , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Cálcio/metabolismo , Carcinoma/genética , Carcinoma/patologia , Movimento Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Urotélio/efeitos dos fármacos , Urotélio/patologia
11.
Stroke ; 46(11): 3274-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26382172

RESUMO

BACKGROUND AND PURPOSE: Occlusion of the internal carotid artery puts patients at risk of recurrent ischemic events because of hemodynamic compromise. Our goal was to characterize clinical and duplex parameters indicating patients at risk of recurrent ischemia. METHODS: We retrospectively identified patients with symptomatic internal carotid artery occlusion. Clinical characteristics and ultrasound parameters, including collateral networks, were analyzed. Predictors for recurrent ipsilateral ischemia were investigated by Cox regression analysis. RESULTS: Of 68 patients, at least 1 recurrent ischemic event within the same vascular territory was observed in 14 patients (20.6%) within 2 to 92 days (median, 29.5 days). The median follow-up period was 6 months. Diabetes mellitus and previous transient ischemic attack were associated with recurrence, as was activation of the maximum number of collateral pathways on transcranial ultrasound (28.6% versus 5.6%; P=0.03). Furthermore, flow in the posterior cerebral arteries was higher in patients with recurrence in ipsilateral and contralateral posterior cerebral artery P2 segments (76 IQR 37.5 versus 59, IQR 22.5 cm/s and 68, IQR 35.6 versus 52, IQR 21 cm/s; P<0.01 and 0.02). CONCLUSIONS: Flow increases in both posterior cerebral artery P2 segments suggest intensified compensatory efforts when other collaterals are insufficient. Together with the presence of diabetes mellitus and a history of transient ischemic attack, this duplex parameter indicates that patients with internal carotid artery are at particular risk of recurrent ischemia.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Artéria Carótida Interna/diagnóstico por imagem , Circulação Colateral , Ataque Isquêmico Transitório/epidemiologia , Oclusão da Artéria Retiniana/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Inibidores da Agregação Plaquetária/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Oclusão da Artéria Retiniana/etiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Ultrassonografia Doppler Transcraniana
12.
PLoS One ; 19(4): e0301594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662661

RESUMO

BACKGROUND: Parents of preterm infants in the Neonatal Intensive Care Unit (NICU) environment may experience psychological distress, decreased perceived self-efficacy, and/or difficulties in establishing an adaptive parent-infant relationship. Early developmental care interventions to support the parental role and infant development are essential and their impact can be assessed by an improvement of parental self-efficacy perception. The aims were to assess the effects of an early intervention provided in the NICU (the Joint Observation) on maternal perceived self-efficacy compared to controls (primary outcome) and to compare maternal mental health measures (perceived stress, anxiety, and depression), perception of the parent-infant relationship, and maternal responsiveness (secondary outcomes). METHODS: This study was a monocentric randomized controlled trial registered in clinicatrials.gov (NCT02736136), which aimed at testing a behavioural intervention compared with treatment-as-usual. Mothers of preterm neonates born 28 to 32 6/7 weeks gestation were randomly allocated to either the intervention or the control groups. Outcome measures consisted of self-report questionnaires completed by the mothers at 1 and 6 months after enrollment and assessing perceived self-efficacy, mental health, perception of the parent-infant relationship and responsiveness, as well as satisfaction with the intervention. RESULTS: No statistically significant group effects were observed for perceived maternal self-efficacy or the secondary outcomes. Over time, perceived maternal self-efficacy increased for mothers in both groups, while anxiety and depression symptoms decreased. High satisfaction with the intervention was reported. CONCLUSIONS: The joint observation was not associated with improved perceived maternal self-efficacy or other mental health outcomes, but may constitute an additional supportive measure offered to parents in a vulnerable situation during the NICU stay.


Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Saúde Mental , Mães , Autoeficácia , Humanos , Feminino , Recém-Nascido , Adulto , Mães/psicologia , Masculino , Ansiedade/psicologia , Depressão/psicologia , Estresse Psicológico
13.
Arch Dis Child Fetal Neonatal Ed ; 109(2): 151-158, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-37739774

RESUMO

OBJECTIVE: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). METHODS: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. RESULTS: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.


Assuntos
Infecções por Citomegalovirus , Perda Auditiva , Substância Branca , Lactente , Humanos , Substância Branca/diagnóstico por imagem , Estudos Retrospectivos , Neuroimagem , Imageamento por Ressonância Magnética/métodos , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico por imagem , Perda Auditiva/complicações
14.
Front Vet Sci ; 10: 1233118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601758

RESUMO

In 2021, a case of canine brucellosis diagnosed in a dog with orchitis was presented to a veterinary practice in Germany. Serological testing excluded Brucella (B.) canis as a causative agent, but molecular analysis revealed the presence of B. suis biovar 1. Since biovar 1 is not endemic in Europe and the dog had no history of travel to endemic areas, a comprehensive epidemiological investigation was conducted using whole genome sequence data to determine the source of infection. We describe the clinical progress of the animal and the potential infection of a veterinary clinic employee. The findings highlight the importance of considering less common Brucella species as possible causes of canine brucellosis. The data also emphasize that it is quite challenging to identify Brucella species in a routine diagnostic laboratory and to conduct epidemiological investigations to unveil possible transmission routes.

15.
Children (Basel) ; 10(8)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37628411

RESUMO

BACKGROUND: Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. AIM: To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). METHODS: In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24-29 weeks gestational age (GA) in Switzerland in 2002-2014, with G3-IVH and/or PVHI. RESULTS: Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002-2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. CONCLUSION: In 2002-2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results.

16.
Appl Neuropsychol Child ; : 1-12, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015558

RESUMO

While the survival rate of very preterm (VPT) infants has increased in the last decades, they are still at risk of developing long-term neurodevelopmental impairments, especially regarding self-regulatory abilities, and goal-directed behaviors. These skills rely on executive functions (EFs), an umbrella term encompassing the core capacities for inhibition, shifting, and working memory. Existing comprehensive tests are time-consuming and therefore not suitable for all pediatric neuropsychological assessments. The Flanker task is an experimental computer game having the advantage to last less than ten minutes while giving multiple EFs measures. Here, we tested the potency of this task in thirty-one VPT children aged 8-10 years during their clinical assessment. First, we found that VPT children performed in the norm for most clinical tests (i.e., WISC-V, BRIEF, and NEPSY) except for the CPT-3 where they were slower with more omission errors, which could indicate inattentiveness. Second, some Flanker task scores were correlated with standardized clinical testing without resisting to multiple comparisons correction. Finally, compared to full-term children, VPT children showed poorer performance in global EFs measure and lower accuracy in the Flanker task. These findings suggest that this child-friendly version of the Flanker task demonstrated a reasonable sensitivity in capturing EFs with good discrimination between VPT and term children despite VPT children's mild difficulties. It may represent a promising tool for neuropsychological assessments and be suitable as a screening test, providing further validating larger studies. Moreover, while VPT schoolchildren globally display normal intelligence, subtle difficulties that seem to relate to EFs are observed.

17.
Front Psychol ; 14: 1251049, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38314254

RESUMO

Introduction: Estimated 50,000 minor children in Germany experience a newly diagnosed cancer in one of their parents every year. Family resilience has proven to be an important concept against life crises. However, little research exists regarding family resilience in the context of parental cancer with minor children. Based on the "Family Resilience Framework," the aim of the study is to investigate the processes of family resilience of affected families. In addition, we explore which combinations of promoting family resilience processes can be characterized. Methods: As part of the mixed-method quasi-experimental interventional study "F-SCOUT," a qualitative content analysis was used to analyze the documentation of the "Family-Scouts" (a fixed contact person who advises, accompanies, and supports the families). Documentation was performed by families' study inclusion (T0), after 3 months (T1) and 9 months (T2) concerning current family situation, organization of everyday life, emotional coping, open communication within the family, and planned tasks. Results: The N = 73 families had between one and six children. In 58 (79%) families, the mother had cancer. In the course of the analysis, a category system with 10 main categories and 36 subcategories emerged. Family resilience processes were described to different extents. Combinations of categories promoting family resilience were characterized by the use of social resources, flexibility, economic resources, and open communication. Discussion: The findings are consistent with existing assumptions about family resilience in terms of the importance of social resources, family cohesion, mutual support, flexibility, open communication, and psychological well-being. In contrast to the findings of previous research, spirituality, and collaborative problem-solving indicate less centrality here. In turn, the findings on economic resources and information-seeking provide a valuable addition to the family resilience literature in the context of parental cancer with minor children. Clinical trial registration: ClinicalTrials.gov, identifier NCT04186923.

18.
Children (Basel) ; 9(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36138689

RESUMO

This study aimed to evaluate the impact of a standardised joint observation (JOIN) performed in the neonatal intensive care unit (NICU) on the neurodevelopment of preterm infants at six months corrected age (CA) compared with a preterm control group. In this monocentric interventional randomised controlled trial, we allocated 76 mothers and their preterm neonates to either JOIN, an early one-session intervention, or standard care during the NICU hospitalisation. The neurodevelopment of the preterm infants was assessed by standardised developmental tests at six months CA and compared between the intervention and the control groups. This randomised controlled trial was registered on clinicaltrials.gov (NCT02736136) in April 2016. Sixty-five infants underwent neurodevelopmental assessment at six months CA. There were no significant differences between the two groups in neurodevelopmental outcome measures. The JOIN intervention was not associated with significant improvement in neurodevelopment at six months CA in preterm infants.

19.
Swiss Med Wkly ; 152: w30174, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35748336

RESUMO

AIMS OF THE STUDY: To assess whether the COVID-19 pandemic caused by SARS-CoV-2 had an impact on incidence, treatment or major adverse short-term outcome of preterm-born infants in Switzerland. METHODS: Retrospective cohort study of preterm infants born in 2020 based on two independent data sources from the Swiss Federal Statistics Office (FSO) and SwissNeoNet. Based on FSO data, we calculated the odds ratios for extremely preterm (22-27 weeks gestation), very preterm (28-31 weeks gestation), and late preterm (32-36 weeks gestation) births during the pandemic. Based on SwissNeoNet data of infants born between 22 and 31 weeks gestation, we compared infants born during the Swiss lockdown period in 2020 with infants born during the same period between 2015 and 2019, all infants of 2020 with all infants between 2015 and 2019 and infants born to mothers tested SARS-CoV-2 positive and negative. Possible associations with the pandemic were tested using logistic regression adjusted for case-mix. As a control, we compared births of 2019 with those of 2015-2018. RESULTS: The FSO data revealed equivalent odds for extremely preterm births in 2020 (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.89-1.14), as well as somewhat lower odds ratios for very preterm (OR 0.9, 95% CI 0.82-1.00) and late preterm (OR 0.91, 95% CI 0.88-0.93) births in 2020. A comparison between 2019 and 2015-2018, however, revealed matching odds ratios rendering an association to the pandemic unlikely. In the SwissNeoNet data, 137 infants were born during lockdown in 2020 compared with 134 births per year during 2015-2019. When including all infants, 744 infants were compared to 845 births, respectively. The only difference observed in treatments and short term outcomes between 2020 and the reference years were a higher odds for respiratory distress syndrome (OR 1.6, 95% CI 1.08-2.37) and provision of continuous positive airway pressure (CPAP) (OR 1.39, 95% CI 1.05-1.84). CONCLUSIONS: Our Swiss population-based analysis did not identify the elsewhere reported association between the COVID-19 pandemic and a reduced preterm birth rate. However, we can confirm a possible link between the COVID-19 pandemic and higher odds of respiratory distress syndrome, possibly coupled with CPAP requirements. Further observation of potential effects of the pandemic on health and health care provision to newborns may however be indicated based on the literature available so far and that our data only covers the first 9 months of the current pandemic.


Assuntos
COVID-19 , Doenças do Prematuro , Nascimento Prematuro , Síndrome do Desconforto Respiratório , COVID-19/epidemiologia , Pré-Escolar , Estudos de Coortes , Controle de Doenças Transmissíveis , Feminino , Humanos , Incidência , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/epidemiologia , Pandemias , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Suíça/epidemiologia , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-35682131

RESUMO

Introduction: The COVID-19 pandemic generated a significant burden on the German health care system, affecting the mental health of health care workers (HCW) in particular. Resilience may serve as an essential protective factor for individuals' well-being. Objective: Our objective was to identify demographic and work-related correlates of individual resilience and to investigate the association between pandemic-related stress, resilience and mental health using different resilience models. Methods: Our sample comprised 1034 German HCW in different medical professions who completed an online survey from 20 April to 1 July 2020. Resilience was assessed using the Resilience Scale-5 (RS-5). The pandemic-related self-reported stress burden was captured by a single item, while depression and anxiety symptoms were measured with the PHQ-2 and GAD-2, respectively. Additionally, various sociodemographic and work-related factors were assessed. Results: Overall, we found high levels of resilience in the sample compared to a German sample before the pandemic, which were significantly associated only with the older age of participants and having children in both univariate and multivariate analyses. Regarding mechanisms of resilience, moderation analysis revealed that low individual resilience and high pandemic-related stress burden independently contributed to both anxiety and depression symptoms while resilience additionally moderated the relationship between stress burden and anxiety symptoms. The link between self-reported stress burden and mental health symptoms was also partially mediated by individual resilience. Conclusion: Taken together, the findings based on the present sample during the COVID-19 pandemic suggest that resilience plays a central role in the mental health of healthcare workers and that resilience-building interventions should be expanded, especially with a focus on younger employees.


Assuntos
COVID-19 , Resiliência Psicológica , Ansiedade/diagnóstico , Ansiedade/epidemiologia , COVID-19/epidemiologia , Criança , Depressão/diagnóstico , Depressão/epidemiologia , Pessoal de Saúde/psicologia , Humanos , Saúde Mental , Pandemias , SARS-CoV-2
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