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1.
PLoS Genet ; 19(5): e1010788, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37256900

RESUMO

Most non-spherical bacteria rely on the actin-like MreB cytoskeleton to control synthesis of a cell-shaping and primarily rod-like cell wall. Diverging from simple rod shape generally requires accessory cytoskeletal elements, which locally interfere with the MreB-guided cell wall synthesis. Conserved and widespread representatives of this accessory cytoskeleton are bactofilins that polymerize into static, non-polar bundles of filaments. Intriguingly, many species of the Actinobacteria and Rhizobiales manage to grow rod-like without MreB by tip extension, yet some of them still possess bactofilin genes, whose function in cell morphogenesis is unknown. An intricate representative of these tip-growing bacteria is Rhodomicrobium vannielii; a member of the hitherto genetically not tractable and poorly studied Hyphomicrobiaceae within the MreB-less Rhizobiales order. R. vannielii displays complex asymmetric cell shapes and differentiation patterns including filamentous hyphae to produce offspring and to build dendritic multicellular arrays. Here, we introduce techniques to genetically access R. vannielii, and we elucidate the role of bactofilins in its sophisticated morphogenesis. By targeted mutagenesis and fluorescence microscopy, protein interaction studies and peptidoglycan incorporation analysis we show that the R. vannielii bactofilins are associated with the hyphal growth zones and that one of them is essential to form proper hyphae. Another paralog is suggested to represent a novel hybrid and co-polymerizing bactofilin. Notably, we present R. vannielii as a powerful new model to understand prokaryotic cell development and control of multipolar cell growth in the absence of the conserved cytoskeletal element, MreB.


Assuntos
Rhodomicrobium , Rhodomicrobium/metabolismo , Forma Celular , Citoesqueleto/metabolismo , Parede Celular/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/genética
2.
J Mol Cell Cardiol ; 190: 1-12, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514002

RESUMO

BACKGROUND: Overexpression of the CREM (cAMP response element-binding modulator) isoform CREM-IbΔC-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF. PURPOSE: To identify key proteome signatures and biological processes accompanying the development of persistent AF through integrated proteomics and bioinformatics analysis. METHODS: Atrial tissue samples from three CREM-Tg mice and three wild-type littermates were subjected to unbiased mass spectrometry-based quantitative proteomics, differential expression and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. RESULTS: A total of 98 differentially expressed proteins were identified. Gene ontology analysis revealed enrichment for biological processes regulating actin cytoskeleton organization and extracellular matrix (ECM) dynamics. Changes in ITGAV, FBLN5, and LCP1 were identified as being relevant to atrial fibrosis and structural based on expression changes, co-expression patterns, and PPI network analysis. Comparative analysis with previously published datasets revealed a shift in protein expression patterns from ion-channel and metabolic regulators in young CREM-Tg mice to profibrotic remodeling factors in older CREM-Tg mice. Furthermore, older CREM-Tg mice exhibited protein expression patterns reminiscent of those seen in humans with persistent AF. CONCLUSIONS: This study uncovered distinct temporal changes in atrial protein expression patterns with age in CREM-Tg mice consistent with the progressive evolution of AF. Future studies into the role of the key differentially abundant proteins identified in this study in AF progression may open new therapeutic avenues to control atrial fibrosis and substrate development in AF.


Assuntos
Fibrilação Atrial , Modulador de Elemento de Resposta do AMP Cíclico , Fibrose , Átrios do Coração , Camundongos Transgênicos , Proteômica , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/genética , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Modulador de Elemento de Resposta do AMP Cíclico/genética , Proteômica/métodos , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Camundongos , Regulação da Expressão Gênica , Mapas de Interação de Proteínas , Proteoma/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Matriz Extracelular/metabolismo , Masculino
3.
BMC Public Health ; 24(1): 915, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549052

RESUMO

BACKGROUND: Studies estimate that at least 7.5% of adults are affected by long-term symptoms such as fatigue or cognitive impairment after the acute phase of COVID-19. COVID-19 vaccination may reduce the risk of long COVID. Rehabilitation can have a positive impact on recovery. This study aims to present the experiences of people with long COVID with COVID-19 vaccination and rehabilitation. Such research is important because perceptions of these measures can impact healthcare utilization and health status. METHODS: 48 adults with long COVID participated in this qualitative study, 25 of them in one-on-one interviews and 23 in focus groups. Participants were recruited via calls for participation on the websites and social media channels of two university hospitals and with the help of respondents' networks. The conversations were audio-recorded, transcribed, and analyzed using qualitative content analysis. Subsequently, the results were compared, interpreted, and discussed by scientific literature. RESULTS: 35 study participants reported that they had received a COVID-19 vaccination and 16 of them stated that they had utilized a rehabilitation service. These participants had varying experiences with COVID-19 vaccination and rehabilitation. Nine of them stated that they developed long COVID despite vaccination before COVID-19. Ten participants reported vaccine reactions, and two participants reported severe side effects. Two participants reported persistent deterioration of their long COVID symptoms after vaccination. This led to uncertainty about the safety, benefits, and handling of COVID-19 vaccination. However, most participants perceived the vaccine as effective regarding milder COVID-19 sequelae. Four participants felt their rehabilitation was helpful and four participants felt it was unhelpful. Two persons found the combination of inpatient rehabilitation and rehabilitation sport helpful. CONCLUSIONS: Several implications can be derived from this study: (1) researchers should explore the effects of COVID-19 vaccination on long COVID symptoms; (2) vaccination campaigns should be more responsive to the perspectives of people with long COVID on vaccination; (3) care planners should build rehabilitation facilities specialized in long COVID; (4) rehabilitation providers should train their professionals regarding long COVID and develop rehabilitation programs tailored to different clinical pictures. TRIAL REGISTRATION: German register for clinical trials DRKS00026007, 09 September 2021.


Assuntos
COVID-19 , Vacinas , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Síndrome de COVID-19 Pós-Aguda , Vacinação
4.
Artigo em Inglês | MEDLINE | ID: mdl-38992194

RESUMO

OBJECTIVE: To analyze the association of neurological disorders (ND) and head and neck cancer (HNC) with dysphagia severity and aspiration pneumonia occurrence. METHOD: Retrospective cohort study conducted at a university dysphagia center) for two consecutive years. Patients with ND or HNC were included if they had undergone a flexible endoscopic swallowing evaluation (FEES) at the dysphagia center, and at least one food consistency had been sampled and recorded. Outcomes of interest were swallowing safety, highest penetration-aspiration-score (PASmax), way of food intake, presence of a tracheal tube, and occurrence of pneumonia within the past two years. RESULTS: Of 257 consecutive patients, 199 were enrolled in the study and classified according to their underlying diagnosis into ND (120 patients) or HNC (79 patients). Forty-three HNC patients (54.4%) and 54 ND patients (45%) showed critical dysphagia in FEES (PAS ≥ 6). Binary logistic regression comparing both groups showed patients with ND to be 2.31 times more likely to develop pneumonia. However, if the 32 stroke patients were excluded from the calculation, PASmax remains the only significant variable affecting pneumonia risk in both groups. Liquids were the main challenge for ND patients, while aspirating HNC patients struggled with all consistencies. CONCLUSIONS: The study shows that patients with HNC and ND differ in pneumonia risk only if stroke patients are included in the ND group. If they are excluded, the PAS score is the only remaining risk factor for pneumonia. Thickening liquids may not be suitable for all dysphagic patients; individually tailored measures might be more helpful, especially for HNC patients.

5.
J Biol Chem ; 298(9): 102362, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35963431

RESUMO

The activity of protein phosphatase 2A (PP2A) is determined by the expression and localization of the regulatory B-subunits. PP2A-B56α is the dominant isoform of the B'-family in the heart. Its role in regulating the cardiac response to ß-adrenergic stimulation is not yet fully understood. We therefore generated mice deficient in B56α to test the functional cardiac effects in response to catecholamine administration versus corresponding WT mice. We found the decrease in basal PP2A activity in hearts of KO mice was accompanied by a counter-regulatory increase in the expression of B' subunits (ß and γ) and higher phosphorylation of sarcoplasmic reticulum Ca2+ regulatory and myofilament proteins. The higher phosphorylation levels were associated with enhanced intraventricular pressure and relaxation in catheterized KO mice. In contrast, at the cellular level, we detected depressed Ca2+ transient and sarcomere shortening parameters in KO mice at basal conditions. Consistently, the peak amplitude of the L-type Ca2+ current was reduced and the inactivation kinetics of ICaL were prolonged in KO cardiomyocytes. However, we show ß-adrenergic stimulation resulted in a comparable peak amplitude of Ca2+ transients and myocellular contraction between KO and WT cardiomyocytes. Therefore, we propose higher isoprenaline-induced Ca2+ spark frequencies might facilitate the normalized Ca2+ signaling in KO cardiomyocytes. In addition, the application of isoprenaline was associated with unchanged L-type Ca2+ current parameters between both groups. Our data suggest an important influence of PP2A-B56α on the regulation of Ca2+ signaling and contractility in response to ß-adrenergic stimulation in the myocardium.


Assuntos
Adrenérgicos , Proteína Fosfatase 2 , Adrenérgicos/metabolismo , Adrenérgicos/farmacologia , Animais , Cálcio/metabolismo , Isoproterenol/farmacologia , Camundongos , Camundongos Knockout , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Fosforilação , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Retículo Sarcoplasmático/metabolismo
6.
Amino Acids ; 55(9): 1173-1188, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37516715

RESUMO

In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography-mass spectrometry (GC-MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = - 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

7.
Prev Med ; 167: 107394, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563970

RESUMO

Language barriers pose a challenge to managing health conditions for various personal, interpersonal, and structural reasons. This study estimates the impact of limited English proficiency (LEP) on diabetes mellitus control and associated cardiovascular risk factors in a large representative sample of United States adults. Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, 2003-18) was used to estimate the impact of language proficiency on glycemic control (glycated hemoglobin [HbA1c]) and cardiovascular risk status (blood pressure [BP] and low-density lipoprotein [LDL]) in adult participants with known diabetes disease. The analysis included descriptive statistics and generalized linear models to adjust for sociodemographic characteristics. The study sample included 5017 participants with self-reported, physician-diagnosed diabetes mellitus. Most participants completed NHANES interview in English (90.8%), whereas some participants completed the interview in Spanish (LEP-Spanish; 6.6%) or requested an interpreter (LEP-interpreter; 2.6%). Compared to English-speaking participants, LEP-interpreter participants were more likely to have HbA1c ≥ 7% (OR = 1.6, 95% CI = 1.1, 2.4) or a combination of HbA1c ≥ 7%, LDL ≥ 2.6 mmol/L, and BP ≥ 130/80 mmHg (OR = 3.1; 95% CI = 1.2, 8.2). We observed no differences in the odds of diabetes control. between English-speaking and LEP-Spanish participants, whereas LEP-interpreter participants had worse diabetes control, possibly owing to the greater likelihood of patient-provider language discordance for non-English non-Spanish-speaking patients. Given that many patients, yet few providers, speak languages other than English or Spanish, innovative ways are needed to facilitate patient-provider communications (e.g., digital communication assistance tools).


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Proficiência Limitada em Inglês , Adulto , Humanos , Estados Unidos , Inquéritos Nutricionais , Estudos Transversais , Doenças Cardiovasculares/prevenção & controle , Hemoglobinas Glicadas , Fatores de Risco , Diabetes Mellitus/prevenção & controle , Barreiras de Comunicação
8.
BMC Pediatr ; 23(1): 312, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344777

RESUMO

BACKGROUND: In pediatric medical emergencies, paramedics and emergency physicians must often rely on the information of third parties, often caregivers, to gather information. Failing to obtain relevant information may lead to misinterpretation of symptoms and subsequent errors in decision making and clinical treatment. Thus, children and/or caregivers with limited proficiency of the locally spoken language may be at risk for medical errors. This study analyzes logs of rescue missions to determine whether paramedics could obtain essential information from German-speaking and foreign-language children and their caregivers. METHODS: We conducted a secondary data analysis based on retrospective data on pediatric patients of four emergency medical services (EMS) stations in Northern Germany. We defined language discordance with communication difficulties as main exposure. We used documentation quality as outcome defined as existing information on (a) pre-existing conditions, (b) current medication, and (c) events prior to the medical emergency. Statistical analyses include descriptive statistics, simple regression and multivariable regression. As multivariable regression model, a logistic regression was applied with documentation quality as dependent variable and language discordance with communication difficulties as independent variable adjusted for age, sex and Glasgow Coma Scale (GCS). RESULTS: Data from 1,430 pediatric rescue missions were analyzed with 3.1% (n = 45) having a language discordance with communication difficulties. Patients in the pediatric foreign-language group were younger compared to German-speaking patients. Thorough documentation was more frequent in German-speaking patients than in patients in the foreign-language group. Pre-existing conditions and events prior to the medical emergency were considerably more often documented in German-speaking than for foreign-language patients. Documentation of medication did not differ between these groups. The adjustment of sex, age and GCS in the multivariable analysis did not change the results. CONCLUSION: Language barriers are hindering paramedics to obtain relevant information in pediatric pre-hospital emergencies. This jeopardizes the safe provision of paramedic care to children who themselves or their caregivers are not fluent in German language. Further research should focus on feasible ways to overcome language barriers in pre-hospital emergencies. TRIAL REGISTRATION: This is a retrospective secondary data analysis of a study that was registered at the German Clinical Trials Register (No. DRKS00016719), 08/02/2019.


Assuntos
Emergências , Serviços Médicos de Emergência , Humanos , Criança , Estudos Retrospectivos , Barreiras de Comunicação , Alemanha , Hospitais , Inquéritos e Questionários
9.
BMC Health Serv Res ; 23(1): 1160, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884993

RESUMO

BACKGROUND: Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures. METHODS: Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz. RESULTS: Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers' lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID. CONCLUSIONS: Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment. TRIAL REGISTRATION: The study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).


Assuntos
COVID-19 , Adulto , Humanos , Grupos Focais , COVID-19/epidemiologia , COVID-19/terapia , Síndrome de COVID-19 Pós-Aguda , Pesquisa Qualitativa , Atenção à Saúde
10.
Proc Natl Acad Sci U S A ; 117(50): 32086-32097, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257551

RESUMO

Magnetotactic bacteria maneuver within the geomagnetic field by means of intracellular magnetic organelles, magnetosomes, which are aligned into a chain and positioned at midcell by a dedicated magnetosome-specific cytoskeleton, the "magnetoskeleton." However, how magnetosome chain organization and resulting magnetotaxis is linked to cell shape has remained elusive. Here, we describe the cytoskeletal determinant CcfM (curvature-inducing coiled-coil filament interacting with the magnetoskeleton), which links the magnetoskeleton to cell morphology regulation in Magnetospirillum gryphiswaldense Membrane-anchored CcfM localizes in a filamentous pattern along regions of inner positive-cell curvature by its coiled-coil motifs, and independent of the magnetoskeleton. CcfM overexpression causes additional circumferential localization patterns, associated with a dramatic increase in cell curvature, and magnetosome chain mislocalization or complete chain disruption. In contrast, deletion of ccfM results in decreased cell curvature, impaired cell division, and predominant formation of shorter, doubled chains of magnetosomes. Pleiotropic effects of CcfM on magnetosome chain organization and cell morphology are supported by the finding that CcfM interacts with the magnetoskeleton-related MamY and the actin-like MamK via distinct motifs, and with the cell shape-related cytoskeleton via MreB. We further demonstrate that CcfM promotes motility and magnetic alignment in structured environments, and thus likely confers a selective advantage in natural habitats of magnetotactic bacteria, such as aquatic sediments. Overall, we unravel the function of a prokaryotic cytoskeletal constituent that is widespread in magnetic and nonmagnetic spirilla-shaped Alphaproteobacteria.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Magnetossomos/metabolismo , Magnetospirillum/citologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/ultraestrutura , Divisão Celular , Microscopia Crioeletrônica , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/ultraestrutura , Citoesqueleto/genética , Citoesqueleto/ultraestrutura , Tomografia com Microscopia Eletrônica , Magnetossomos/ultraestrutura , Magnetospirillum/metabolismo , Magnetospirillum/ultraestrutura , Microscopia Eletrônica de Transmissão
11.
Eur Arch Otorhinolaryngol ; 280(3): 1329-1338, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36209319

RESUMO

PURPOSE: This study aimed to report on implementing flexible endoscopic evaluation of swallowing (FEES) in infants and toddlers with type 1 spinal muscular atrophy (SMA). In addition, a comparison of FEES results and clinical scores was carried out. METHODS: A prospective pilot study was conducted including ten symptomatic children with SMA type 1 (two SMN2 copies). They started treatment with one of the three currently approved therapies for SMA at a median age of 3.8 months (range 0.7-8.9). FEES was performed according to a standard protocol using Penetration-Aspiration Scale (PAS) and Murray Secretion Scale as a primary outcome. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) for motor function, Neuromuscular Disease Swallowing Status Scale (NdSSS), Oral and Swallowing Abilities Tool (OrSAT), and single clinical swallowing-related parameters were also assessed. RESULTS: Distinct swallowing disorders were already evident in eight children at inclusion. The most common findings from FEES were pharyngeal secretion pooling, penetration, and aspiration of saliva and food as well as delayed initiation of swallowing. Despite an average increase in motor function, no comparable improvement was found in swallowing function. None of the surveyed clinical scores showed a significant dependence on PAS in a mixed linear model. CONCLUSIONS: Valuable information regarding the status of dysphagia can be gathered endoscopically, particularly concerning secretion management and when oral intake is limited. Currently available clinical tools for children with type 1 may represent a change in nutritional status but are not yet mature enough to conclude swallowing ability. Further development is still required.


Assuntos
Transtornos de Deglutição , Atrofias Musculares Espinais da Infância , Lactente , Humanos , Recém-Nascido , Deglutição , Projetos Piloto , Estudos Prospectivos , Atrofias Musculares Espinais da Infância/complicações , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia
12.
Z Rheumatol ; 82(4): 342-354, 2023 May.
Artigo em Alemão | MEDLINE | ID: mdl-35523964

RESUMO

BACKGROUND: Immunocompromised people are less likely to be vaccinated, despite an increased benefit of many vaccinations in terms of benefit-risk assessment, including the vaccines against SARS CoV-2 (COVID-19). Attitudes, expectations, and experiences with previous vaccinations influence the decision to get vaccinated. OBJECTIVE: To explore the attitudes of immunocompromised people towards vaccinations in general and COVID-19 vaccination in particular and their experiences with COVID-19 vaccinations. MATERIAL AND METHODS: As part of the CoCo Immune study, immunocompromised participants were surveyed in the spring and summer of 2021 (1 November 2021-7 September 2021) using questionnaires. Initially, they were asked about their expectations concerning a COVID-19 vaccination and followed up about their experience after COVID-19 vaccination. In addition, sociodemographic data, general attitudes toward vaccinations and experiences with previous vaccinations were collected. Analysis was performed using descriptive and bivariate statistics. RESULTS: The 243 participants mostly approved vaccinations and expected the COVID-19 vaccination to be effective and well-tolerated. Women were more concerned about the safety of vaccinations and were more often worried about side effects. Older persons felt better informed than younger persons. Participants who reported subjective side effects of previous vaccinations were more skeptical about vaccinations as well as the government institutions that recommend vaccinations. They less often agreed with the statement "in retrospect, the COVID-19 vaccination has been harmless for me so far". DISCUSSION: The participants mostly expressed a positive attitude and anticipation towards COVID-19 vaccinations; however, the age and sex differences found suggest that there are different information needs which should be addressed when educating individuals about vaccinations or designing vaccination campaigns.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Estudos Longitudinais , Vacinas contra COVID-19/efeitos adversos , Motivação , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
13.
Am J Physiol Heart Circ Physiol ; 322(3): H427-H441, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35119335

RESUMO

Protein phosphatase 2A (PP2A) represents a heterotrimer that is responsible for the dephosphorylation of important regulatory myocardial proteins. This study was aimed to test whether the phosphorylation of PP2A-B56α at Ser41 by PKC is involved in the regulation of myocyte Ca2+ cycling and contraction. For this purpose, heart preparations of wild-type (WT) and transgenic mice overexpressing the nonphosphorylatable S41A mutant form (TG) were stimulated by administration of the direct PKC activator phorbol 12-myristate 13-acetate (PMA), and functional effects were studied. PKC activation was accompanied by the inhibition of PP2A activity in WT cardiomyocytes, whereas this effect was absent in TG. Consistently, the increase in the sarcomere length shortening and the peak amplitude of Ca2+ transients after PMA administration in WT cardiomyocytes was attenuated in TG. However, the costimulation with 1 µM isoprenaline was able to offset these functional deficits. Moreover, TG hearts did not show an increase in the phosphorylation of the myosin-binding protein C after administration of PMA but was detected in corresponding WT. PMA modulated voltage-dependent activation of the L-type Ca2+ channel (LTCC) differently in the two genotypes, shifting V1/2a by +1.5 mV in TG and by -2.4 mV in WT. In the presence of PMA, ICaL inactivation remained unchanged in TG, whereas it was slower in corresponding WT. Our data suggest that PKC-activated enhancement of myocyte contraction and intracellular Ca2+ signaling is mediated by phosphorylation of B56α at Ser41, leading to a decrease in PP2A activity.NEW & NOTEWORTHY The importance of the serine-41 phosphorylation site on B56α in reducing PP2A activity was demonstrated for the first time using a transgenic mutation model. Direct activation of PKC inhibits PP2A, leading to increased phosphorylation of MyBP-C in cardiomyocytes. The increased phosphorylation of contractile proteins is influenced by the PKC-phosphoB56α-PP2A signaling cascade resulting in improved intracellular Ca2+ handling and enhanced contractility and relaxation. PKC-mediated inhibition of PP2A also leads to modulation of the LTCC activation and inactivation kinetics.


Assuntos
Miócitos Cardíacos , Proteína Fosfatase 2 , Animais , Isoproterenol/farmacologia , Camundongos , Contração Muscular , Miócitos Cardíacos/metabolismo , Fosforilação , Proteína Fosfatase 2/metabolismo
14.
Oncology ; 100(7): 392-398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35609553

RESUMO

BACKGROUND: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. AIM: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. PATIENTS AND METHODS: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. RESULTS: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. CONCLUSION: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.


Assuntos
COVID-19 , Melanoma , Anticorpos Antivirais/metabolismo , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , SARS-CoV-2 , Vacinação
15.
BMC Infect Dis ; 22(1): 249, 2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35282824

RESUMO

BACKGROUND: Enteric parasites are endemic in many of the countries from which refugees originate. Clinical guidelines vary in approaches to screening for and treating intestinal parasites in refugee receiving countries. This study aims to investigate the prevalence and species of intestinal parasites identified in stool ova and parasite (O&P) specimens in a sample of newly arrived refugees in Toronto, Canada. METHODS: We conducted a retrospective chart review of 1042 refugee patients rostered at a specialized primary care clinic in Toronto from December 2011 to September 2016. Patients who completed recommended stool O&P analyses were included. Basic sociodemographic and clinical variables and results of stool O&P were examined. RESULTS: 419 patients (40.2%) had a stool O&P positive for any protozoan or helminth species. Sixty-nine patients (6.6%) had clinically significant parasite species (excluding B hominis, D fragilis, and E dispar, given their lower risk for causing symptoms/complications): 2.3% had clinically significant protozoans and 4.2% had helminths on stool analysis. CONCLUSION: Given the relatively low prevalence of clinically significant parasites identified, our findings do not support universal screening for enteric parasites with stool O&P among refugee claimants/asylum seekers. However, stool analysis should be considered in certain clinical situations, as part of a more tailored approach.


Assuntos
Parasitos , Refugiados , Animais , Canadá , Humanos , Atenção Primária à Saúde , Estudos Retrospectivos
16.
BMC Infect Dis ; 22(1): 403, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468758

RESUMO

BACKGROUND: Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to characterize the immune response to COVID-19 vaccination in immunocompromised, elderly people, and patients with hematological or oncological diseases. The study uses blood-based screenings to monitor the humoral and cellular immune response in these groups after vaccination. Questionnaires and qualitative interviews are used to describe the level of social participation. METHODS: The CoCo Immune Study is a mixed methods prospective, longitudinal, observational study at two large university hospitals in Northern Germany. Starting in March 2021, it monitors anti-SARS-CoV-2 immune responses and collects information on social participation in more than 600 participants, at least 18 years old. Inclusion criteria and subcohorts: Participants with (1) regularly intake of immunosuppressive medication (ICP-cohort) or (2) age ≥ 80 years (80 + -cohort). Additionally, patients with current or former (3) myeloid, (4) lymphatic disease or (5) solid tumor under checkpoint inhibition (3-5: HO-cohort). EXCLUSION CRITERIA: (1) refusal to give informed consent, (2) contraindication to blood testing, (3) inability to declare consent. Participants complete a questionnaire at four different time points: prior to full vaccination, and 1, 6 and 12 months after completed vaccination. In addition, participants draw blood samples themselves or through a local health care provider and send them with their questionnaires per post at the respective time points after vaccination. Patients of the HO cohort dispense additional blood samples at week 3 to 12 and at month 6 to 9 after 2nd vaccination to gain additional knowledge in B and T cell responses. Selected participants are invited to qualitative interviews about social participation. DISCUSSION: This observational study is designed to gain insight into the immune response of people with weakened immune systems and to find out how social participation is affected after COVID-19 vaccination. TRIAL REGISTRATION: This study was registered with German Clinical Trial Registry (registration number: DRKS00023972) on 30th December 2020.


Assuntos
COVID-19 , Doenças Hematológicas , Neoplasias , Adolescente , Idoso , Idoso de 80 Anos ou mais , Vacinas contra COVID-19 , Cocos , Humanos , Imunidade , Estudos Observacionais como Assunto , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento
17.
BMC Med Inform Decis Mak ; 22(1): 189, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854290

RESUMO

BACKGROUND: With the help of digital tools patients' medical histories can be collected quickly and transferred into their electronic medical records. This information can facilitate treatment planning, reduce documentation work, and improve care. However, it is still unclear whether the information collected from patients in this way is reliable. In this study, we assess the accuracy of the information collected by patients using an app for medical history taking by comparing it with the information collected in a face-to-face medical interview. We also study the app's usability from the patients' point of view and analysing usage data. METHODS: We developed a software application (app) for symptom-oriented medical history taking specialized for general practice. Medical history taking will take place involving patients with acute somatic or psychological complaints (1) using the app and (2) verbally with trained study staff. To assess the perceived usability, patients will complete a questionnaire for the System Usability Scale. We will collect sociodemographic data, information about media use and health literacy, and app usage data. DISCUSSION: Digital tools offer the opportunity to improve patient care. However, it is not self-evident that the medical history taken by digital tools corresponds to the medical history that would be taken in an interview. If simply due to a design flaw patients answer questions about signs and symptoms that indicate possible serious underlying conditions 'wrong', this could have severe consequences. By additionally assessing the app's usability as perceived by a diverse group of patients, potential weaknesses in content, design and navigation can be identified and subsequently improved. This is essential in order to ensure that the app meets the need of different groups of patients. Trial registration German Clinical Trials Register DRKS00026659 , registered Nov 03 2021. World Health Organization Trial Registration Data Set, https://trialsearch.who.int/Trial2.aspx? TrialID = DRKS00026659.


Assuntos
Aplicativos Móveis , Atenção à Saúde , Humanos , Atenção Primária à Saúde , Encaminhamento e Consulta , Inquéritos e Questionários
18.
Int J Audiol ; 61(5): 400-407, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34396881

RESUMO

OBJECTIVE: Exploring factors that predict a favourable clinical outcome in non-organic hearing loss (NOHL) in children. NOHL is defined as a subjective hearing loss without correlation in objective measures. DESIGN: Retrospective analysis of all childrens' data with the diagnosis NOHL seen between 2005 and 2017 at a tertiary referral centre. STUDY SAMPLE: Sixty-seven children (44 female, 23 male; mean age 11.26 years) were included. Statistical analyses included descriptive statistics, logistic regression, correlations, and Mann-Whitney U tests. RESULTS: A quarter of the children (17/67) had been provided previously with hearing aids without objective sensorineural hearing loss. Having been provided with hearing aids before the first visit to our clinic lowered the chance of normal hearing at the final visit by 76%. The prescription of hearing aids was significantly more likely in girls. Children provided with hearing aids were significantly older than those without and the time span between the first occurrence of the NOHL and first presentation at our department was longer than in children not provided with hearing aids. CONCLUSIONS: In cases of NOHL, hearing aid prescription is not indicated and significantly lowers a child's chance of full recovery and, thus, should not be prescribed unless NOHL is ruled out.


Assuntos
Surdez , Auxiliares de Audição , Perda Auditiva Neurossensorial , Perda Auditiva , Criança , Surdez/reabilitação , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
19.
Notf Rett Med ; 25(5): 341-347, 2022.
Artigo em Alemão | MEDLINE | ID: mdl-33903799

RESUMO

Background: As a response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, extensive contact restrictions were imposed by law in Germany as in other European countries. The present study intends to clarify the effect of these restrictions on emergency medical service (EMS) operations. Materials and methods: Retrospective chart review of EMS operation protocols over the first 6 months of 2020 (n = 6668 rescue missions) in four rescue stations in eastern Lower Saxony (Germany). Description and statistical comparison of operations 6 weeks before the restrictions with an equally long period after the order of the restrictions ("lockdown"). Results: During the 6 weeks after the lockdown the frequency of rescue operations decreased by 17.7%. In particular, there was a 40.6% (n = 91) decrease of emergency cases with respiratory diseases, mainly due to a decline of pneumonia and exacerbated chronic-obstructive pulmonary disease (COPD). At the same time, patients' mean age increased with fewer patients under 65 years. There were no changes in the frequency of psychiatric disorders, deceased or injured patients, or refusal of treatment and transport. A total of 67 patients with suspected or confirmed SARS-CoV­2 infection (1.0%) were observed during this period. Discussion: EMS experienced a reduction of operations as a result of contact restrictions, although not as pronounced as was recently described for emergency rooms. This supports the hypothesis that the reduction is particularly evident in less severe cases and in younger patients. The reduction in pneumonia and COPD cases is striking. On the one hand, this could indicate that contact restrictions reduce the incidence of other respiratory infections and their impact on chronic respiratory disorders, but it could also mean that patients try to avoid hospital treatment.

20.
Notf Rett Med ; 25(8): 570-577, 2022.
Artigo em Alemão | MEDLINE | ID: mdl-34230808

RESUMO

Background: Communication with foreign-speaking patients in emergency medical situations can be challenging. In contrast to the inpatient setting, adequate interpreters are often not readily available in emergency services. At the same time, however, emergency situations require rapid assessment as the basis for any treatment. Materials and methods: A smartphone app that enables basic communication in 18 languages using 600 different phrases was piloted over a period of 6 months in four emergency medical service stations. Finally, the usability of the app was evaluated by the whole rescue service staff in a questionnaire study using the System Usability Score and the AttrakDiff questionnaire. Results: The response rate was 48.5% and n = 48 questionnaires were evaluated. The average age of the respondents was 36 years and almost two-thirds were male. The System Usability Score showed a median of 67.5 points, indicating borderline good usability. The AttrakDiff questionnaire showed pragmatic quality with an average of 0.69 (SD 0.86), hedonic quality with 0.59 (SD 0.58), and attractiveness (ATT) with 0.64 points (SD 0.83). The average values show satisfying results above the neutral limit of 0. It was observed that those rescue workers who stated that they had already actively used the app with patients rated the app significantly better. Discussion: Given that the app studied is a complex work tool, its usability and attractiveness were rated as overall good, and paramedics who had already used the app rated it even more positively. This could indicate a hesitancy by some paramedics to use a complex digital tool in complex situations that are already characterized by language and cultural barriers.

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