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1.
Nature ; 595(7866): 233-238, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234335

RESUMO

Quantum simulation using synthetic systems is a promising route to solve outstanding quantum many-body problems in regimes where other approaches, including numerical ones, fail1. Many platforms are being developed towards this goal, in particular based on trapped ions2-4, superconducting circuits5-7, neutral atoms8-11 or molecules12,13. All of these platforms face two key challenges: scaling up the ensemble size while retaining high-quality control over the parameters, and validating the outputs for these large systems. Here we use programmable arrays of individual atoms trapped in optical tweezers, with interactions controlled by laser excitation to Rydberg states11, to implement an iconic many-body problem-the antiferromagnetic two-dimensional transverse-field Ising model. We push this platform to a regime with up to 196 atoms manipulated with high fidelity and probe the antiferromagnetic order by dynamically tuning the parameters of the Hamiltonian. We illustrate the versatility of our platform by exploring various system sizes on two qualitatively different geometries-square and triangular arrays. We obtain good agreement with numerical calculations up to a computationally feasible size (approximately 100 particles). This work demonstrates that our platform can be readily used to address open questions in many-body physics.

2.
Osteoporos Int ; 35(5): 785-794, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38246971

RESUMO

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur. We developed a global FEA-computed fracture risk index to increase the prediction accuracy of hip fracture incidence. PURPOSE: Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. METHODS: We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. RESULTS: We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). CONCLUSIONS: The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males.


Assuntos
Fraturas do Quadril , Fraturas Proximais do Fêmur , Masculino , Humanos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Densidade Óssea , Fêmur/diagnóstico por imagem , Curva ROC , Análise de Elementos Finitos
3.
Psychother Psychosom ; 93(5): 328-339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39168112

RESUMO

INTRODUCTION: There is a significant demand for interventions that reduce distress related to auditory verbal hallucinations (AVHs). AVH distress is associated with the way voice hearers relate with AVHs. We aimed to establish the feasibility of a randomized controlled trial to demonstrate that adding "Relating Therapy" (RT) to treatment as usual (TAU) is superior to TAU in reducing AVH distress. METHODS: We conducted a multicenter, parallel, single-blind, randomized controlled feasibility trial in five mental health centers in Germany. Participants were ≥19 years of age, had persistent and distressing AVHs, and had a diagnosis of a schizophrenia-spectrum disorder. RT was delivered over a maximum of 16 sessions within 5 months. Blind assessments were conducted at baseline and at 5 and 9 months. Feasibility outcomes were the number of patients recruited and retained, and safety and therapist adherence. The primary endpoint was the distress factor score of the AVH subscale of the Psychotic Symptoms Rating Scales at 9 months. RESULTS: Eighty-five of 177 enrolled participants were randomized into RT + TAU (n = 43) or TAU (n = 42). Feasibility was excellent with 87% retention at 9 months, 86% reaching treatment uptake criteria, 98% therapist adherence, and no unexpected serious adverse reactions. Compared to TAU, RT + TAU showed nonsignificant trends toward less AVH distress (b = -2.40, SE = 1.52, p = 0.121, 90% CI (-4.94 to 0.15) and stronger improvement on all but one of the secondary outcomes. CONCLUSION: A randomized controlled trial of RT is feasible, safe, and well accepted. Our results provide an encouraging basis to further test the efficacy of RT in a definitive multicenter trial.


Assuntos
Estudos de Viabilidade , Alucinações , Esquizofrenia , Humanos , Alucinações/terapia , Método Simples-Cego , Masculino , Feminino , Adulto , Esquizofrenia/terapia , Pessoa de Meia-Idade , Resultado do Tratamento , Alemanha , Angústia Psicológica , Estresse Psicológico/terapia
4.
BMC Nephrol ; 25(1): 220, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987671

RESUMO

BACKGROUND: Hemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments. METHODS: This prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was ß2-microglobulin removal rate (ß2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety. RESULTS: 82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest ß2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety. CONCLUSIONS: The novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints. TRIAL REGISTRATION: eMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).


Assuntos
Estudos Cross-Over , Hemodiafiltração , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hemodiafiltração/instrumentação , Hemodiafiltração/métodos , Estudos Prospectivos , Microglobulina beta-2/sangue , Falência Renal Crônica/terapia
5.
Artigo em Inglês | MEDLINE | ID: mdl-39032518

RESUMO

Adequate and transparent reporting is necessary for critically appraising research. Yet, evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-empaneled a group of authors to develop methodological and statistical reporting guidelines identifying the minimum information needed to document and evaluate observational studies and clinical trials in oral health: the Oral Health Statistics Guidelines. Drafts were circulated to the editors of 85 oral health journals and to task force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The final version was subsequently approved by the task force in September 2021, submitted for journal review in 2022, and revised in 2023. The checklist consists of 48 guidelines: 5 for introductory information, 17 for methods, 13 for statistical analysis, 6 for results, and 7 for interpretation; 7 are specific to clinical trials. Each of these guidelines identifies relevant information, explains its importance, and often describes best practices. The checklist was published in multiple journals. The article was published simultaneously in Journal of Dental Research Clinical and Translational Research, the Journal of the American Dental Association, and the Journal of Oral and Maxillofacial Surgery. Completed checklists should accompany manuscripts submitted for publication to these and other oral health journals to help authors, journal editors, and reviewers verify that the manuscript provides the information necessary to adequately document and evaluate the research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39033786

RESUMO

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the Oral Health Statistical (OHStat) Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials, Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and Consolidated Standards for Reporting Trials harms guidelines and incorporate the Statistical Analysis and Methods in Published Literature guidelines for reporting statistics, the Clinical and Laboratory Images in Publications principles for documenting images, and the Grading of Recommendations Assessment, Development and Evaluation indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental researches into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.

7.
Mol Psychiatry ; 27(11): 4464-4473, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35948661

RESUMO

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.


Assuntos
Transtorno do Espectro Autista , Transtorno Depressivo Maior , Transtornos Mentais , Animais , Camundongos , Humanos , Transtorno do Espectro Autista/genética , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Transtornos Mentais/genética , Camundongos Knockout , Fatores de Processamento de RNA/genética
8.
Ann Hematol ; 102(3): 547-561, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36695874

RESUMO

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60-87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45-64)) and the study group arms (53% (95%CI: 47-60) and 59% (95%CI: 58-63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7-14.0) in the CSA, 7.6% (95%CI: 4.5-12.8) in study group A and 11.1% (95%CI: 9.0-13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0-26.9), 17.0% (95%CI: 2.0-23.9), and 19.5% (95%CI: 16.7-22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.


Assuntos
Leucemia Mieloide Aguda , Mitoxantrona , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/efeitos adversos , Intervalo Livre de Doença , Leucemia Mieloide Aguda/tratamento farmacológico , Mitoxantrona/efeitos adversos , Prognóstico , Indução de Remissão
9.
Klin Padiatr ; 235(2): 90-97, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36758576

RESUMO

BACKGROUND: Foreign body ingestion in children is a clinically important reason for presentation to the emergency department. The individual outcome ranges from benign spontaneous courses to severe complications. Fatal outcomes occur rarely and complications are related to patient's age as well as type and location of the foreign body. The aim of our present study was to evaluate the outcome of children and adolescents with foreign body ingestion with a focus on complications, which mainly occurred after button battery ingestion. METHODS: We reviewed medical records of patients between 0 and 18 years of age who had presented to the paediatric emergency department of our hospital with suspected foreign body ingestion between January 2011 and March 2021 (123 months). Clinical, imaging, and endoscopic data as well as treatment modalities were analysed. RESULTS: In the ten10 year period under review, a total of 1,162 children and adolescents (6 months - 18 years) presented to our emergency room with suspected foreign body ingestion. Among those, 398 ingestions (34%) could be verified radiologically and/or endoscopically, while in the remaining 764 cases (66%) the suspicion could not be confirmed. The majority of patients with verified ingestion (n=324; 81%) presented with ingestion of a metallic foreign body. We observed 55 cases with verified ingestion of a button battery. Five of these cases had severe complications, with a near-fatal course in two patients who developed an oesophageal-tracheal fistula. CONCLUSION: In contrast to all other ingestions of foreign bodies in children, button battery ingestions lead to mucosal damage and severe complications in a significant number of children.


Assuntos
Esôfago , Corpos Estranhos , Criança , Adolescente , Humanos , Lactente , Esôfago/diagnóstico por imagem , Fontes de Energia Elétrica , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/terapia , Hospitais , Ingestão de Alimentos , Estudos Retrospectivos
10.
Mol Psychiatry ; 26(8): 4179-4190, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-31712720

RESUMO

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.


Assuntos
Transtorno Depressivo Maior , Neuroticismo , Transtorno de Pânico , Dinamarca , Depressão/genética , Transtorno Depressivo Maior/genética , Estônia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Alemanha , Humanos , Transtorno de Pânico/genética , Polimorfismo de Nucleotídeo Único , Suécia
11.
Artif Organs ; 46(7): 1318-1327, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35192209

RESUMO

BACKGROUND: Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated time-resolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial. METHODS: In plasma recirculation experiments over 240 min, sieving coefficients (SC) for ß2-microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun). Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data. RESULTS: SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: ß2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%). For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg). CONCLUSIONS: Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers.


Assuntos
Diálise Renal , Microglobulina beta-2 , Albuminas , Membranas Artificiais , Peso Molecular , Mioglobina , Diálise Renal/métodos
12.
J Vasc Surg ; 74(6): 1894-1903.e3, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34182035

RESUMO

BACKGROUND: Acute abdominal aortic occlusion (AAO) is a rare vascular emergency associated with high morbidity and mortality. In the present study, we analyzed the clinical management and outcomes for a consecutive patient series during a 16-year period. METHODS: We included all patients with an acute AAO and bilateral acute limb ischemia who had been treated between 2004 and 2019. Patients with dissection, aneurysm rupture, or chronic occlusive disease were excluded. The patient characteristics, surgical procedures, and outcomes were extracted retrospectively from a prospective aortic database, electronic patient files, and outpatient examination records. The extent of ischemia was classified according to the TASC II (Inter-Society Consensus for the Management of Peripheral Arterial Disease) section on acute limb ischemia. The primary endpoints were 30-day mortality (safety endpoint) and the combined 6-month amputation and/or death rate (efficacy endpoint). The follow-up outcomes, amputation rates, and 30-day complications were evaluated as secondary endpoints. The patient cohort was divided into four 4-year groups (2004-2007, 2008-2011, 2012-2015, 2016-2019) to assess the outcome changes over time. Statistical analysis included χ2 tests and univariate and linear regression analyses. RESULTS: A total of 74 patients (57% male; median age, 64.5 years) with an acute AAO were identified. Arterial thrombosis was the most common etiology (66%). The extent of ischemia was TASC I, IIa, IIb, and III in 7%, 39%, 40%, and 14%, respectively. The patient numbers had increased significantly over time (P = .016). Of the patients, 42% had undergone open transfemoral recanalization (including hybrid procedures), 35% open aortic surgery, 15% extra-anatomic bypass surgery, and 5% (four patients) endovascular therapy alone. The overall 30-day mortality rate was 23%, and the 6-month amputation and/or death rate was 43%. The 30-day mortality rate had declined significantly from 54% for 2004 to 2007 to 10% for 2011 to 2015 (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.001-0.52) and 20% for 2016 to 2019 (OR, 0.21; 95% CI, 0.05-0.90), a statistically nonsignificant trend showing that the relative decline in the use of open aortic procedures was associated with decreased 30-day mortality (P = .06). Univariate analysis indicated that elevated serum lactate on admission (OR, 3.33; 95% CI, 1.06-10.48) and an advanced stage of limb ischemia (OR, 4.33), were strongly associated with an increased 30-day mortality rate. The incidence of severe postoperative systemic complications also indicated a greater incidence of both primary endpoints. The 6-month amputation and/or mortality rates were also affected by the presence of atrial fibrillation (OR, 3.63; 95% CI, 1.34-9.79) and increased patient age (OR, 3.96; 95% CI, 1.49-10.53). CONCLUSIONS: Acute AAO remains a life-threatening emergency. Immediate transfemoral open or endovascular techniques should be preferred, if technically possible and proper intraoperative imaging is available.


Assuntos
Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Procedimentos Endovasculares , Isquemia/cirurgia , Procedimentos Cirúrgicos Vasculares , Doença Aguda , Idoso , Amputação Cirúrgica , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/mortalidade , Doenças da Aorta/fisiopatologia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/mortalidade , Arteriopatias Oclusivas/fisiopatologia , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
13.
Support Care Cancer ; 29(9): 5399-5408, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33694088

RESUMO

PURPOSE: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL. METHODS: We retrospectively reviewed patients seen at the University of California San Francisco lymphoma clinic from January 1, 2016, to March 31, 2017 who had (1) aggressive B-cell NHL, (2) received first-line therapy with R-CHOP-like regimens, and had (3) CT scans pre- and post-treatment available for review. Associations between clinical variables and vertebral, rib, and pelvic fracture outcomes were assessed, and multivariate logistic regression models were used to identify predictors of prevalent and incident fractures. RESULTS: We identified 162 patients who met the inclusion criteria. Median age at diagnosis was 60 years. Of the 162 patients, 38 patients (28%) had prevalent fractures prior to receiving chemotherapy. Within 1 year after treatment, 16 patients (10%) developed new fractures. Having a prevalent fracture strongly predicted developing a new fracture after treatment, with incident fractures occurring in 12 of 38 patients with prevalent fractures versus 4 of 124 without prevalent fractures (odds ratio 10.45, p<0.0005). CONCLUSION: Our results suggest that patients with aggressive B-cell NHL who receive R-CHOP-like therapy should be screened for fractures prior to treatment and those with existing fractures should be considered for therapy to decrease risk of new fractures.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfócitos B , Pré-Escolar , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Humanos , Incidência , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/epidemiologia , Prednisona/efeitos adversos , Estudos Retrospectivos , Vincristina/efeitos adversos
14.
Environ Monit Assess ; 193(12): 788, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757592

RESUMO

Dumped munitions contain various harmful substances which can affect marine biota like fish. One of them is mercury (Hg), included in the common explosive primer Hg fulminate. There is still a lack of knowledge whether dumped munitions impact the Hg concentrations in the Baltic Sea environment. This study aims to answer the question if dab caught at the dump site Kolberger Heide show higher Hg concentrations released from munition sources and whether Hg in fish is a usable marker for munition exposure. Therefore, a total of 251 individual dab (Limanda limanda) were analysed including 99 fish from the dump site. In fish from the Kolberger Heide, no elevated Hg concentrations were found compared to reference sites when age-dependent bioaccumulation of mercury was considered. Therefore we conclude that Hg in fish is no suitable indicator for exposure to munition dumping, e.g. in the frame of possible future monitoring studies as Hg exposure originating from dumped munition is only a small contributor to overall Hg exposure of fish.


Assuntos
Linguado , Mercúrio , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Peixes , Mercúrio/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
15.
J Neural Transm (Vienna) ; 127(11): 1527-1537, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32468273

RESUMO

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Transtorno de Pânico , Ansiedade/genética , Transtornos de Ansiedade/genética , Metilação de DNA , DNA Metiltransferase 3A , Humanos , Transtorno de Pânico/genética , Fenótipo , DNA Metiltransferase 3B
16.
Pediatr Allergy Immunol ; 31(5): 560-564, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319131

RESUMO

With increasing number of SARS-CoV-2 infections and COVID-19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20% of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3000 births per year, an outbreak of COVID-19 occurred in March 2020, affecting 36 staff members, including doctors, nurses, and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS-CoV-2. Apart from massive testing of personnel in pre-defined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pessoal de Saúde , Pandemias/prevenção & controle , Assistência Perinatal/métodos , Pneumonia Viral/prevenção & controle , COVID-19 , Feminino , Alemanha , Higiene das Mãos , Maternidades , Humanos , Máscaras , Gravidez , Quarentena , SARS-CoV-2 , Isolamento Social
17.
Nicotine Tob Res ; 22(6): 935-941, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-31091312

RESUMO

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed. RESULTS: Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with ß= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and ß = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, ß = -0.08, 95% CI = -0.16 to -0.01 and ß = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (ß = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.


Assuntos
Fumar Cigarros/efeitos adversos , Músculo Esquelético/patologia , Músculo Quadríceps/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Estudos Prospectivos , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/efeitos dos fármacos , Fumantes , Tomografia Computadorizada por Raios X
18.
J Clin Densitom ; 23(2): 155-164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31558405

RESUMO

INTRODUCTION: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response. METHODOLOGY: QCT and DXA scans of both hips were performed on 10 astronauts: once preflight and twice postflight about 1 wk and 1 yr after return. If trabecular BMD had not returned to baseline (i.e., within QCT measurement error) in 1 or both hips 1 yr after flight, then another QCT hip scan was obtained at 2 yr after flight. RESULTS: Areal BMD by DXA recovered in 9 of 10 astronauts at 1 yr postflight while incomplete recovery of trabecular BMD by QCT was evident in 5 of 10 astronauts and persisted in 4 of the 5 astronauts 2 yr postflight. CONCLUSION: As an adjunct to DXA, QCT is needed to detect changes to hip trabecular BMD after spaceflight and to confirm complete recovery. Incomplete recovery at 2 yr should trigger the need for further evaluation and possible intervention to mitigate premature fragility and fractures in astronauts following long-duration spaceflight.


Assuntos
Astronautas , Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Quadril/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Voo Espacial , Tomografia Computadorizada por Raios X , Adulto , Remodelação Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Projetos Piloto , Fatores de Risco
19.
Appetite ; 151: 104686, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234530

RESUMO

Because of inconsistencies in the field of attentional bias to food cues in eating behavior, this study aimed to re-examine the assumption that hungry healthy weight individuals have an attentional bias to food cues, but satiated healthy weight individuals do not. Since attentional engagement and attentional disengagement have been proposed to play a distinct role in behavior, we used a performance measure that is specifically designed to differentiate between these two attentional processes. Participants were healthy weight women who normally eat breakfast. In the satiated condition (n = 54), participants were instructed to have breakfast just before coming to the lab. In the fasted condition (n = 50), participants fasted on average 14 h before coming into the lab. Satiated women showed no stronger attentional engagement or attentional disengagement bias to food cues than to neutral cues. Fasted women did show stronger attentional engagement to food cues than to neutral cues that were shown briefly (100 ms). They showed no bias in attentional engagement to food cues that were shown longer (500 ms) or in attentional disengagement from food cues. These findings are in line with the assumption that healthy weight individuals show an attentional bias to food cues when food stimuli are motivationally salient. Furthermore, the findings point to the importance of differentiating between attentional engagement and attentional disengagement.


Assuntos
Viés de Atenção , Sinais (Psicologia) , Atenção , Feminino , Alimentos , Humanos , Fome
20.
Clin Psychol Psychother ; 27(4): 548-558, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32103569

RESUMO

Repetitive negative thought plays an important role in the maintenance of mental health problems following bereavement. To date, bereavement researchers have primarily focused on rumination (i.e., repetitive thought about negative events and/or negative emotions), yet the interest in worry (i.e., repetitive thought about uncertain future events) is increasing. Both cognitive processes potentially lead to poorer adaptation to bereavement by contributing to loss-related avoidance and behavioural avoidance of activities. The current study aims to establish the differential associations of rumination and worry with symptoms of depression and prolonged grief and clarify if avoidance processes mediate the associations of rumination and worry with symptom levels. Four hundred seventy-four recently bereaved adults (82% female) filled out questionnaires assessing rumination, worry, loss-related and behavioural avoidance, and depression and prolonged grief symptoms. Rumination and worry were both uniquely associated with depression and prolonged grief symptoms. Compared with worry, rumination related more strongly to prolonged grief symptoms, whereas correlations of both cognitive styles with depression symptoms did not differ. Loss-related avoidance and behavioural avoidance partially mediated the associations of rumination and worry with prolonged grief symptoms. Behavioural avoidance partially mediated the associations of rumination and worry with depression symptoms. Findings suggest that exposure and behavioural activation may be effective interventions to reduce repetitive thinking and psychopathology after bereavement.


Assuntos
Ansiedade/psicologia , Aprendizagem da Esquiva , Luto , Ruminação Cognitiva , Pensamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Pesar , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
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