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BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently to recurrent airway infections and bronchiectasis. QUESTION: How many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance? METHODS: To answer this question we exploited the molecular defects of the X-linked recessive PCD variant caused by pathogenic variants in DNAAF6 (PIH1D3), characterized by immotile cilia in the affected males. We carefully analyzed the clinical phenotype, molecular defect (immunofluorescence and transmission-electron microscopy) and performed in vitro (particle tracking in air-liquid interface cultures) and in vivo (radiolabeled tracer studies) studies to assess ciliary clearance of respiratory cells from females with heterozygous and males with hemizygous pathogenic DNAAF6 variants. RESULTS: PCD males with hemizygous pathogenic DNAAF6 variants displayed exclusively immotile cilia, absence of ciliary clearance and severe PCD symptoms. Due to random or skewed X-chromosome inactivation in six females with heterozygous pathogenic DNAAF6 variants, 54.3%±10 (range 38%-70%) of multiciliated cells were defective. Nevertheless, in vitro and in vivo assessment of the ciliary airway clearance was normal or slightly abnormal. Consistently, heterozygous female individuals showed no or only mild respiratory symptoms. CONCLUSIONS: Our findings indicate that 30%-62% of functioning multiciliated respiratory cells are able to generate either normal or slightly reduced ciliary clearance. Because heterozygous females displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine might be able to improve ciliary airway clearance in PCD individuals as well as clinical symptoms.
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BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age:â¯50â¯years, range:â¯2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spikeâ¯(S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+â¯CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Reinfecção , SARS-CoV-2 , Soroconversão , Humanos , SARS-CoV-2/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , Estudos Longitudinais , Alemanha/epidemiologia , Anticorpos Antivirais/sangue , Pessoa de Meia-Idade , Adulto , Masculino , Anticorpos Neutralizantes/sangue , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Idoso , Reinfecção/imunologia , Reinfecção/virologia , Reinfecção/prevenção & controle , Estudos Soroepidemiológicos , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Idoso de 80 Anos ou mais , VacinaçãoRESUMO
Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.
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Biomarcadores , Exercício Físico , Humanos , Masculino , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Feminino , Mucosa Intestinal/metabolismo , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Permeabilidade , Lactulose/urina , Lactulose/metabolismo , Ramnose/metabolismo , Adulto Jovem , Estresse Oxidativo , Cromogranina A/metabolismo , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Saliva/metabolismoRESUMO
Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis.
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Bronquiectasia , Pólipos Nasais , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Bronquiectasia/genética , Bronquiectasia/fisiopatologia , Pólipos Nasais/genética , Proteína 2 do Domínio Central WAP de Quatro DissulfetosRESUMO
BACKGROUND: While adverse impacts of climate change on physical health are well-known, research on its effects on mental health is still scarce. Thus, it is unclear whether potential impacts have already reached treatment practice. Our study aimed to quantify psychotherapists' experiences with patients reporting climate change-related concerns and their views on dealing with this topic in psychotherapy. METHODS: In a nationwide online survey, responses were collected from 573 psychotherapists from Germany. Therapists reported on the presence of such patients, their socio-demographic characteristics, and climate change-related reactions. Psychotherapists' views on dealing with this topic in psychotherapy were also assessed. Descriptive statistics were used to analyse the responses. RESULTS: About 72% (410/573) of psychotherapists indicated having had patients expressing concerns about climate change during treatment. Out of these therapists, 41% (166/410) stated that at least one patient sought treatment deliberately because of such concerns. Patients were mainly young adults with higher education. Most frequent primary diagnoses were depression, adjustment disorder, and generalized anxiety disorder. Psychotherapists having encountered such patients differed from those without such encounters in their views on potential functional impairment and the necessity to target the concerns in treatment. Although 79% (326/415) of all respondents felt adequately prepared by their current therapeutic skills, 50% (209/414) reported a lack of information on how to deal with such concerns in therapy. CONCLUSIONS: Results indicate that psychotherapists are frequently confronted with climate change-related concerns and regard the mental health impact of climate change on their patients as meaningful to psychotherapeutic care. Regular care could be improved by a continuous refinement of the conceptualization and knowledge of the mental health influences of climate change. This would allow providing tailored methods of assessing and addressing climate change-related concerns in practice.
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Mudança Climática , Psicoterapia , Adulto Jovem , Humanos , Psicoterapia/métodos , Inquéritos e Questionários , AlemanhaRESUMO
The efficacy of trauma-focused treatments for children and adolescents is well researched. However, less is known about the long-term and caregiver-reported effects. Searched databases were PsychInfo, MEDLINE, Cochrane Library, PTSDPubs, PubMed, Web of Science, and OpenGrey. Treatment effects of trauma-focused cognitive behavioral therapy (TF-CBT) were computed at 12-month follow-up with posttraumatic stress symptoms (PTSS) as primary outcome and symptoms of depression, anxiety, and grief as secondary outcomes. Concordance between participant and caregiver ratings were investigated. TF-CBT showed large improvements across all outcomes from pre-treatment to 12-month follow-up (PTSS: g = 1.71, CI 1.27-2.15) and favorable results compared to active treatments and treatment as usual at 12-month follow-up (PTSS: g = .35, CI .13-.56). More pronounced effects were found in group settings. No significant differences were detected between participant and caregiver ratings with high reliability across almost all outcomes and assessment points. TF-CBT is a reliable treatment for pediatric PTSS and secondary symptoms with stable results at 12-month follow-up.
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Terapia Cognitivo-Comportamental , Transtornos de Estresse Pós-Traumáticos , Humanos , Criança , Adolescente , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Cuidadores/psicologia , Reprodutibilidade dos Testes , Resultado do Tratamento , Terapia Cognitivo-Comportamental/métodosRESUMO
Currently, the effect of prenatal ultrasound on foetal development is intensively discussed and the guidelines for prenatal diagnostics have been changed. However, data supporting these concerns are scarce. Therefore, we used an established in ovo model of the chicken embryo to investigate cell proliferation and apoptosis within the retina. A total of 21 chicken eggs were fenestrated on Day 5 and allocated to either the control (n = 8) or exposition group (n = 13). The exposition group was treated with pulsed-wave Doppler ultrasound (PWD) for 10 min while controls remained without treatment. After subsequent incubation (6-48 h), the eggs were sacrificed, and chicken embryos were examined morphologically (HE-staining) and immunohistochemically. Counting of apoptotic and proliferating cells per retina was performed using antibodies specific for phospho-histone-H3 and active caspase-3 in combination with a biotin-labelled secondary antibody and peroxidase conjugated avidin-biotin complex for chromogenic detection. Due to a rather low number of specimens at each time point after ultrasound exposition, we neglected the effects of incubation time and focused on treatment effects. This approach revealed that the median number of proliferating cells is reduced after 10 min of exposure to PWD (569 vs. 766), while the number of apoptotic cells is fairly comparable between groups (5 vs. 6). Our data contribute to a better understanding of prenatal US on foetal development by suggesting that PWD could have an impact on the number of proliferating cells in the developing chicken retina and therefore justify further investigations.
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Biotina , Ultrassonografia Doppler , Embrião de Galinha , Animais , Feminino , Ultrassonografia , Ultrassonografia Doppler/veterinária , Angiografia , Apoptose , Galinhas , Retina/diagnóstico por imagemRESUMO
BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS. AIM: To assess the efficacy and safety of FMT for the treatment of IBS. METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence. RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision. CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
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Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/terapia , Síndrome do Intestino Irritável/etiologia , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Qualidade de Vida , Disbiose/terapia , Disbiose/etiologiaRESUMO
MR microscopy (MRM) is known as ultra-high-field (UHF) magnetic resonance imaging with an in-plane spatial resolution of <100 µm, yields highly resolved non-invasive anatomical imaging and allows longitudinal assessment of embryonic avian development. The aim of the present study was to evaluate the feasibility of in vivo anatomical MRI assessment of the developing upper extremity of the chicken. Thirty-eight fertilized chicken eggs were examined at 7 Tesla acquiring high-resolution T2-weighted images with an in-plane resolution of 74 × 74 µm. To reduce motion artefacts, the eggs were moderately cooled before and during MRI. Development of the upper extremity was anatomically and quantitatively assessed. Chondrification and ossification on MRI were correlated with histological examination. MRM allowed the identification of the embryo from stage D5 onwards. First chondrification of the upper extremity was visible at stage D7, and the differentiation of the forearm was possible from stage D9 throughout the developmental period with excellent correlation to histology. MRM also allowed the differentiation between cortical and medullary bone as well as the detection of chondrified areas. UHF MRM allows the in vivo and in ovo evaluation of the upper limb during embryonic development and provides non-invasive longitudinal anatomical information. This technique allows longitudinal studies of the same embryo during the developmental period and may therefore provide further insights into the development of the upper extremity. With improved coil technique and increasing availability of UHF MR systems, there is great potential regarding several research topics in experimental musculoskeletal radiology.
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Galinhas , Microscopia , Animais , Microscopia/veterinária , Imageamento por Ressonância Magnética/veterinária , Extremidade Superior , Estudos LongitudinaisRESUMO
Previous studies have suggested that performance-contingent reward can modulate cognitive control by biasing irrelevant location-response associations in the Simon task. However, the influence of reward in the case of irrelevant words (Stroop task) or irrelevant flankers (Eriksen Flanker task) remains unclear. Across two preregistered experiments, the present study investigated the influence of reward on conflict processing with different types of distractors. Conflict effects on mean reaction time (RT) were reduced in the Simon task (Experiments 1 and 2) when incongruent versus congruent trials were rewarded, and this modulating effect of reward on conflict processing was also observed in the Eriksen flanker task (Experiment 2), but not in the Stroop task (Experiment 1). We propose that cognitive control adjustments to distractor-specific reward contingencies can be generalized across distractor types producing both perceptual-related (Flanker task) and motor-related (Simon task) conflict, but, if any, to a limited degree when distractors produce additional higher-level task conflict (Stroop task). In addition, distributional RT analyses (delta plots) revealed that rewarded distractor-response associations modulate cognitive control not only via biasing the strength (Simon and Eriksen tasks) but also the time-course of suppressing distractor processing (Eriksen task). Overall, the present study dissociated distractor-general and distractor-specific effects of reward on cognitive control.
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Atenção , Conflito Psicológico , Humanos , Atenção/fisiologia , Tempo de Reação/fisiologia , Teste de StroopRESUMO
Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.
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Bifidobacterium longum , Lactobacillus helveticus , Probióticos , Encéfalo , Voluntários Saudáveis , Humanos , Probióticos/uso terapêuticoRESUMO
Robust population-wide immunity will help to curb the SARS-CoV-2 pandemics. To maintain the immunity at protective levels, the quality and persistence of the immune response elicited by infection or vaccination must be determined. We analyzed the dynamics of B cell response during 12 months following SARS-CoV-2 infection on an individual level. In contrast to antibodies, memory B cells specific for the spike (S) protein persisted at high levels throughout the period. These cells efficiently secreted neutralizing antibodies and correlated with IFN-γ-secreting CD4+ T cells. Interestingly, the CD27-CD21+ intermediate memory B cell phenotype was associated with high B cell receptor avidity and the production of neutralizing antibodies. Vaccination of previously infected individuals triggered a recall response enhancing neutralizing antibody and memory B cell levels. Collectively, our findings provide a detailed insight into the longevity of SARS-CoV-2-infection-induced B cell immunity and highlight the importance of vaccination among previously infected. IMPORTANCE To efficiently maintain immunity against SARS-CoV-2 infection, we must first determine the durability of the immune response following infection or vaccination. Here, we demonstrated that, unlike antibodies, virus-specific memory B cells persist at high levels for at least 12 months postinfection and successfully respond to a secondary antigen challenge. Furthermore, we demonstrated that vaccination of previously infected individuals significantly boosters B cell immunity.
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Vacinas contra COVID-19 , COVID-19 , Memória Imunológica , Células B de Memória , SARS-CoV-2 , Vacinação , Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Humanos , Interferon gama/imunologia , Células B de Memória/citologia , Células B de Memória/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de TempoRESUMO
Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited. Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task. Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed. Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention. Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].
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BACKGROUND: In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS: We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS: Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS: Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Necrose/terapia , Recidiva Local de Neoplasia/terapia , Estudos RetrospectivosRESUMO
Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.
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Bifidobacterium longum , Lactobacillus helveticus , Probióticos , Encéfalo/diagnóstico por imagem , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , MasculinoRESUMO
OBJECTIVE: To evaluate empirically the degree of content overlap between four self-report measures of fear of childbirth (FoC) identified as 'best in class' by a recent review. BACKGROUND: FoC and tokophobia is an area of increasing clinical concern and has been linked to poor maternal and neonatal outcomes. Clinical pathways have been established to improve care and interventions for FoC however, ambiguity and inconsistency remain regarding the most appropriate assessment measures. METHOD: A multi-rater and consensus content analysis was undertaken to determine the degree of overlap between four 'best in class' measures of FoC/tokophobia. RESULTS: The Slade-Pais expectations of childbirth scale (SPECS) was found to be the preferred measure in terms of symptom overlap of the tools evaluated, however, the overall level of overlap among these measures was weak. CONCLUSION: Limitations inherent to the current battery of preferred measures of FoC suggests both the desirability and urgency to develop a theoretically-grounded, psychometrically robust and accurate FoC assessment measure. Current measures of FoC are not interchangeable.
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Parto Obstétrico , Parto , Medo , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Healthcare workers (HCW) are among those most directly affected by the COVID-19 pandemic. Most research with this group has used ad hoc measures, which limits comparability across samples. The Stress and Anxiety to Viral Epidemics-9 scale (SAVE-9) is a nine-item scale first developed in Korea, and has since been translated into several languages. We report on data collected from 484 German HCW between November 2020 and March 2021, during the "second wave" of coronavirus infections. We conducted item analysis, confirmatory factor analysis on the previously found factor solutions of the SAVE-9, examined correlations with established measures of depression, generalized anxiety, and insomnia, and compared scores between different groups of HCW. The psychometric properties of the German SAVE-9 were satisfactory and comparable to previous findings from Korea and Russia. Correlations with mental health measures were positive, as expected. We found some significant differences between groups of HCW on the SAVE-9 which were consistent with the literature but did not appear on the other mental health measures. This suggests that the SAVE-9 taps into specifically work-related stress, which may make it a helpful instrument in this research area.
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COVID-19 , Pandemias , Ansiedade/epidemiologia , Estudos Transversais , Depressão , Pessoal de Saúde , Humanos , Idioma , SARS-CoV-2RESUMO
Background: The substantial number of young refugees who have arrived in Europe since 2015 requires rapid screening to identify those in need of treatment. However, translated versions of screening measures are not always available, necessitating the support of interpreters. The Child and Adolescent Trauma Screen (CATS) is a validated questionnaire for posttraumatic stress symptoms. Here, we report on the psychometric properties of the CATS in a sample of young refugees as a function of interpreter involvement. Methods: A total of N = 145 (Mage = 16.8, SD = 1.54; 93% male) were assessed with the CATS, with half of the screenings conducted with and half without interpreters. Post hoc analyses included calculating internal consistency using Cronbach's α. We used confirmative factor analysis to investigate the factor structure. Results: The CATS total scale showed good reliability (α = 0.84). Differences in psychometric properties between the interpreter vs. the no interpreter group were minor and tended to be in favor of the interpreter group. Results of a confirmatory factor analysis were acceptable after the exclusion of items with low item-scale correlations. Conclusions: The sample and the administration of the assessment represent the situation of young refugees in Germany, where resources are low and translated versions not always available. The CATS may be a helpful screening tool for clinicians working with young refugees, even when administered with an interpreter. Limitations include the post hoc design of the analysis without randomization of participants and the lack of a third comparison group using translated questionnaire versions.
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Refugiados , Transtornos de Estresse Pós-Traumáticos , Adolescente , Europa (Continente) , Feminino , Alemanha , Humanos , Masculino , Reprodutibilidade dos Testes , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIM: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. MATERIALS AND METHODS: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. RESULTS: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. DISCUSSION: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.