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Porocarcinoma Écrino , Perfilação da Expressão Gênica , Neoplasias das Glândulas Sudoríparas , Humanos , Porocarcinoma Écrino/genética , Porocarcinoma Écrino/patologia , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Transcriptoma/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Feminino , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Masculino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-IdadeRESUMO
We report an in-depth study of the thermodynamic and magnetocaloric properties of a strongly frustrated magnet, Cs2Fe2(MoO4)3. The underlying structure belongs to the double trillium lattice, which consists of two FeII (S = 2) sites with easy-axis and easy-plane single-ion anisotropy. Detailed 57Fe Mössbauer spectroscopic investigations along with ligand-field calculations support the existence of disparate ground states. The antiferromagnetic ordered structure is presented by the propagation vector k = (0,0,0) with noncollinear magnetic moments of 2.97 µB (Fe1) and 0.17 µB (Fe2), respectively. Strong and disordered magnetic correlations exist in the temperature regime between T N ≈ 1.0 K and |θCW| ≈ 22 K. The large degeneracy of the ground state is investigated in terms of its magnetocaloric response. Magnetization and specific heat measurements indicate a significant magnetocaloric cooling efficiency, making this rare-earth-free compound a promising candidate for cryogenic magnetic refrigeration applications, with refrigeration capacity of 79 J kg-1 for Δ(µ0 H) = 8 T.
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BACKGROUND AND OBJECTIVES: Malignant sweat gland tumors are rare, with the most common being eccrine porocarcinoma (EP). Approximately 18% of benign eccrine poroma (EPO) transit to EP. Previous research has provided first insights into the mutational landscape of EP. However, only few studies have performed gene expression analyses. This leaves a gap in the understanding of EP biology and potential drivers of malignant transformation from EPO to EP. METHODS: Transcriptome profiling of 23 samples of primary EP and normal skin (NS). Findings from the EP samples were then tested in 17 samples of EPO. RESULTS: Transcriptome profiling revealed diversity in gene expression and indicated biologically heterogeneous sub-entities as well as widespread gene downregulation in EP. Downregulated genes included CD74, NDGR1, SRRM2, CDC42, ANXA2, KFL9 and NOP53. Expression levels of CD74, NDGR1, SRRM2, ANXA2, and NOP53 showed a stepwise-reduction in expression from NS via EPO to EP, thus supporting the hypothesis that EPO represents a transitional state in EP development. CONCLUSIONS: We demonstrated that EP is molecularly complex and that evolutionary trajectories correspond to tumor initiation and progression. Our results provide further evidence implicating the p53 axis and the EGFR pathway. Larger samples are warranted to confirm our findings.
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Porocarcinoma Écrino , Perfilação da Expressão Gênica , Neoplasias das Glândulas Sudoríparas , Humanos , Porocarcinoma Écrino/genética , Porocarcinoma Écrino/patologia , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Feminino , Masculino , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Idoso , Pessoa de Meia-IdadeRESUMO
Ecotoxicology studies were performed in the earthworm Eisenia fetida with four different synthetic amorphous silica (SAS) (SYLOID® AL-1 FP, SYLOID® MX 107, LUDOX® P T-40â¯F, and HDK® N20) mixed into artificial soil to determine a NOEC/LOEC for effects on reproduction (56 days after application), mortality and biomass development (28 days after application) using a standardized artificial soil with 10% peat. The LC50 for test-item effects on adult mortality, and an EC10 and EC50 for reproduction were also determined. Furthermore, earthworms underwent histopathology evaluation, and the amount of silica in different organs from these organisms was evaluated using EDX (Energy Dispersive X-ray Spectroscopy). Histopathology revealed no findings in any organ of the earthworms, except for desiccated dissepiments in evaluated decedents at extremely high SAS doses. To measure SAS uptake into the organs, a fully quantitative method for silica was established and validated using standards containing known concentrations of silica to ensure the accuracy of the analyses undertaken. Results from EDX analysis demonstrated the negligible presence of silicon within the brain ganglia and gonads of adult earthworms comparable to controls. Therefore, any deposition of the test items within these two organs was excluded. In contrast, traces of silicon higher than in controls were found in the intestinal lumina of the earthworms due to ingestion of SAS with soil and feed, but not in other organs.
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BACKGROUND AND OBJECTIVES: In progressive multiple sclerosis (MS), compartmentalized inflammation plays a pivotal role in the complex pathology of tissue damage. The interplay between epigenetic regulation, transcriptional modifications, and location-specific alterations within white matter (WM) lesions at the single-cell level remains underexplored. METHODS: We examined intracellular and intercellular pathways in the MS brain WM using a novel dataset obtained by integrated single-cell multi-omics techniques from 3 active lesions, 3 chronic active lesions, 3 remyelinating lesions, and 3 control WM of 6 patients with progressive MS and 3 non-neurologic controls. Single-nucleus RNA-seq and ATAC-seq were combined and additionally enriched with newly conducted spatial transcriptomics from 1 chronic active lesion. Functional gene modules were then validated in our previously published bulk tissue transcriptome data obtained from 73 WM lesions of patients with progressive MS and 25 WM of non-neurologic disease controls. RESULTS: Our analysis uncovered an MS-specific oligodendrocyte genetic signature influenced by the KLF/SP gene family. This modulation has potential associations with the autocrine iron uptake signaling observed in transcripts of transferrin and its receptor LRP2. In addition, an inflammatory profile emerged within these oligodendrocytes. We observed unique cellular endophenotypes both at the periphery and within the chronic active lesion. These include a distinct metabolic astrocyte phenotype, the importance of FGF signaling among astrocytes and neurons, and a notable enrichment of mitochondrial genes at the lesion edge populated predominantly by astrocytes. Our study also identified B-cell coexpression networks indicating different functional B-cell subsets with differential location and specific tendencies toward certain lesion types. DISCUSSION: The use of single-cell multi-omics has offered a detailed perspective into the cellular dynamics and interactions in MS. These nuanced findings might pave the way for deeper insights into lesion pathogenesis in progressive MS.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Substância Branca , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Epigênese Genética , Multiômica , Esclerose Múltipla Crônica Progressiva/genética , Esclerose Múltipla Crônica Progressiva/patologia , Substância Branca/patologiaRESUMO
PURPOSE: The aim was to investigate the effect of aging by thermocycling and mechanical loading on forces and moments generated by orthodontic clear aligners made from different thermoplastic materials. METHODS: A total of 25 thermoformed aligners made from 5 different materials, i.e., Essix ACE® and Essix® PLUS™ (Dentsply Sirona, Bensheim, Germany), Invisalign® (Align Technology, San Jose, CA, USA), Duran®+ (Iserlohn, Germany), Zendura™ (Fremont, CA, USA), underwent a 14-day aging protocol involving mechanical loading (a 0.2â¯mm vestibular malalignment of the upper left second premolar [tooth 25]) and thermocycling in deionized water (temperature range 5-55⯰C). The 3D forces/moments exerted on tooth 25 of a resin model were measured at three time points: before aging (day 0), after 2 days and after 14 days of aging. RESULTS: Before aging, extrusion-intrusion forces were 0.6-3.0â¯N, orovestibular forces were 1.7-2.3â¯N, and moments as mesiodistal rotation were 0.3-42.1â¯Nmm. In all directions, multilayer Invisalign® exhibited the lowest force/moment magnitudes. After aging, all materials showed a significant force/moment decay within the first 2 days, except Invisalign® for orovestibular and vertical translation. However, following thermomechanical aging, Duran®+ and Zendura™ aligners had equivalent or even higher vestibular forces (direction of mechanical load). CONCLUSION: Thermomechanical aging significantly reduced forces and moments during the first 48â¯h. Multilayer aligner materials exhibit lower initial forces and moments than single-layer ones, and were less influenced by aging. Material hardening was observed after subjecting some of the aligner materials to mechanical loading. Thus, orthodontists should be aware of possible deterioration of orthodontic aligners over time. This work also sheds light on how material selection impacts the mechanical behavior of aligners and may provide valuable guidance regarding optimal timing for the aligner changing protocol.
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BACKGROUND: An increase in patients with multidrug-resistant organisms and associated outbreaks during the COVID-19 pandemic have been reported in various settings, including low-endemic settings. Here, we report three distinct carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in five intensive care units of a university hospital in Berlin, Germany during the COVID-19 pandemic. METHODS: A case-control study was conducted with the objective of identifying risk factors for CRAB acquisition in outbreak situations. Data utilized for the case-control study came from the investigation of three separate CRAB outbreaks during the COVID-19 pandemic (August 2020- March 2021). Cases were defined as outbreak patients with hospital-acquired CRAB. Controls did not have any CRAB positive microbiological findings and were hospitalized at the same ward and for a similar duration as the respective case. Control patients were matched retrospectively in a 2:1 ratio. Parameters routinely collected in the context of outbreak management and data obtained retrospectively specifically for the case-control study were included in the analysis. To analyze risk factors for CRAB acquisition, univariable and multivariable analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) were performed using a conditional logistic regression model. RESULTS: The outbreaks contained 26 cases with hospital-acquired CRAB in five different intensive care units. Two exposures were identified to be independent risk factors for nosocomial CRAB acquisition by the multivariable regression analysis: Sharing a patient room with a CRAB patient before availability of the microbiological result was associated with a more than tenfold increase in the risk of nosocomial CRAB acquisition (OR: 10.7, CI: 2.3-50.9), while undergoing bronchoscopy increased the risk more than six times (OR: 6.9, CI: 1.3-38.1). CONCLUSIONS: The risk factors identified, sharing a patient room with a CRAB patient and undergoing bronchoscopy, could point to an underperformance of basic infection control measure, particularly hand hygiene compliance and handling of medical devices. Both findings reinforce the need for continued promotion of infection control measures. Given that the outbreaks occurred in the first year of the COVID-19 pandemic, our study serves as a reminder that a heightened focus on airborne precautions should not lead to a neglect of other transmission-based precautions.
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Acinetobacter baumannii , COVID-19 , Infecção Hospitalar , Humanos , Estudos de Casos e Controles , Pandemias , Estudos Retrospectivos , Surtos de Doenças , Hospitais Universitários , CarbapenêmicosRESUMO
Background and study aims Perioperative hypothermia is associated with significant complications and can be prevented with forced-air heating systems (FAHS). Whether hypothermia occurs during prolonged endoscopic sedation is unclear and prevention measures are not addressed in endoscopic sedation guidelines. We hypothesized that hypothermia also occurs in a significant proportion of patients undergoing endoscopic interventions associated with longer sedation times such as endoscopic retrograde cholangiopancreaticography (ERCP), and that FAHS may prevent it. Patients and methods In this observational study, each patient received two consecutive ERCPs, the first ERCP following current standard of care without FAHS (SOC group) and a consecutive ERCP with FAHS (FAHS group). The primary endpoint was maximum body temperature difference during sedation. Results Twenty-four patients were included. Median (interquartile range) maximum body temperature difference was -0.9°C (-1.2; -0.4) in the SOC and -0.1°C (-0.2; 0) in the FAHS group ( P < 0.001). Median body temperature was lower in the SOC compared with the FAHS group after 20, 30, 40, and 50 minutes of sedation. A reduction in body temperature of > 1°C ( P < 0.001) and a reduction below 36°C ( P = 0.01) occurred more often in the SOC than in the FAHS group. FAHS was independently associated with reduced risk of hypothermia ( P = 0.006). More patients experienced freezing in the SOC group ( P = 0.004). Hemodynmaic and respiratory stability were comparable in both groups. Conclusions Hypothermia occurred in the majority of patients undergoing prolonged endoscopic sedation without active temperature control. FAHS was associated with higher temperature stability during sedation and better patient comfort.
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The regulation of gene expression by light enables the versatile, spatiotemporal manipulation of biological function in bacterial and mammalian cells. Optoribogenetics extends this principle by molecular RNA devices acting on the RNA level whose functions are controlled by the photoinduced interaction of a light-oxygen-voltage photoreceptor with cognate RNA aptamers. Here light-responsive ribozymes, denoted optozymes, which undergo light-dependent self-cleavage and thereby control gene expression are described. This approach transcends existing aptamer-ribozyme chimera strategies that predominantly rely on aptamers binding to small molecules. The optozyme method thus stands to enable the graded, non-invasive, and spatiotemporally resolved control of gene expression. Optozymes are found efficient in bacteria and mammalian cells and usher in hitherto inaccessible optoribogenetic modalities with broad applicability in synthetic and systems biology.
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RNA Catalítico , RNA , Animais , Motivos de Nucleotídeos , RNA/genética , RNA Catalítico/química , RNA Catalítico/genética , RNA Catalítico/metabolismo , Bactérias/metabolismo , Expressão Gênica , Mamíferos/metabolismoRESUMO
BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.
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Injúria Renal Aguda , Respiração Artificial , Recém-Nascido , Lactente , Humanos , Pré-Escolar , Incidência , Estudos Retrospectivos , Respiração Artificial/efeitos adversos , Recém-Nascido de muito Baixo Peso , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Fatores de RiscoRESUMO
Monolateral pin-to-bar-clamp fixators are commonly used to stabilize acute extremity injuries. Certain rules regarding frame geometry have been established that affect construct stability. The influence of sagittal pin angulation on construct stiffness and strength has not been investigated. The purpose of this biomechanical study was to demonstrate the effect of a pin angulation in the monolateral fixator using a composite cylinder model. Three groups of composite cylinder models with a fracture gap were loaded with different mounting variants of monolateral pin-to-bar-clamp fixators. In the first group, the pins were set parallel to each other and perpendicular to the specimen. In the second group, both pins were set convergent each in an angle of 15° to the specimen. In the third group, the pins were set each 15° divergent. The strength of the constructions was tested using a mechanical testing machine. This was followed by a cyclic loading test to produce pin loosening. A pull-out test was then performed to evaluate the strength of each construct at the pin-bone interface. Initial stiffness analyses showed that the converging configuration was the stiffest, while the diverging configuration was the least stiff. The parallel mounting showed an intermediate stiffness. There was a significantly higher resistance to pull-out force in the diverging pin configuration compared to the converging pin configuration. There was no significant difference in the pull-out strength of the parallel pins compared to the angled pin pairs. Convergent mounting of pin pairs increases the stiffness of a monolateral fixator, whereas a divergent mounting weakens it. Regarding the strength of the pin-bone interface, the divergent pin configuration appears to provide greater resistance to pull-out force than the convergent one. The results of this pilot study should be important for the doctrine of fixator mounting as well as for fixator component design.
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Ensuring data quality and protecting data are key requirements when working with health-related data. Re-identification risks of feature-rich data sets have led to the dissolution of the hard boundary between data protected by data protection laws (GDPR) and anonymized data sets. To solve this problem, the TrustNShare project is creating a transparent data trust that acts as a trusted intermediary. This allows for secure and controlled data exchange, while offering flexible datasharing options, considering trustworthiness, risk tolerance, and healthcare interoperability. Empirical studies and participatory research will be conducted to develop a trustworthy and effective data trust model.
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Blockchain , Pesquisa Empírica , Confiabilidade dos Dados , Instalações de Saúde , Disseminação de InformaçãoRESUMO
As they typically have limited direct contact, children's attitudes towards older adults have more opportunity to be shaped by other social influences such as their parents and children's literature. Children's books have been noted for their tendency to portray older adults in stereotypical ways and their tendencies to underrepresent older adults. We investigated how the portrayal of older adults as major versus supporting characters, as well as parents' age-related expectations were related to parental preference for children's books. We designed 24 children's book covers that depicted an older adult as a main character, a younger adult as a main character, or only children. One-hundred-seventy-five parents of children ages 0-12 rated their preference for the covers, their age-related expectations for the books' stories, and their personal aging expectations. Parents preferred covers featuring only children, and this preference was stronger for parents with more positive personal aging expectations. Cover preference was further predicted by age-related story expectations. When parents expected a book to conform to older-age stereotypes, they liked that particular cover less. Controlling for parents' age-related story expectations for each book resulted in near equal levels of preference for all types of book covers. Carefully designed children's books could provide an opportunity to increased vicarious intergenerational contact. These finding suggests that parents' interest in selecting these books for their children will be higher when they do not perceive the books to align with older-age stereotypes. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04298-6.
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The increase of Vancomycin-resistant Enterococcus faecium (VREfm) in recent years has been partially attributed to the rise of specific clonal lineages, which have been identified throughout Germany. To date, there is no gold standard for the interpretation of genomic data for outbreak analyses. New genomic approaches such as split k-mer analysis (SKA) could support cluster attribution for routine outbreak investigation. The aim of this project was to investigate frequent clonal lineages of VREfm identified during suspected outbreaks across different hospitals, and to compare genomic approaches including SKA in routine outbreak investigation. We used routine outbreak laboratory data from seven hospitals and three different hospital networks in Berlin, Germany. Short-read libraries were sequenced on the Illumina MiSeq system. We determined clusters using the published Enterococcus faecium-cgMLST scheme (threshold ≤20 alleles), and assigned sequence and complex types (ST, CT), using the Ridom SeqSphere+ software. For each cluster as determined by cgMLST, we used pairwise core-genome SNP-analysis and SKA at thresholds of ten and seven SNPs, respectively, to further distinguish cgMLST clusters. In order to investigate clinical relevance, we analysed to what extent epidemiological linkage backed the clusters determined with different genomic approaches. Between 2014 and 2021, we sequenced 693 VREfm strains, and 644 (93â%) were associated within cgMLST clusters. More than 74â% (n=475) of the strains belonged to the six largest cgMLST clusters, comprising ST117, ST78 and ST80. All six clusters were detected across several years and hospitals without apparent epidemiological links. Core SNP analysis identified 44 clusters with a median cluster size of three isolates (IQR 2-7, min-max 2-63), as well as 197 singletons (41.4â% of 475 isolates). SKA identified 67 clusters with a median cluster size of two isolates (IQR 2-4, min-max 2-19), and 261 singletons (54.9â% of 475 isolates). Of the isolate pairs attributed to clusters, 7â% (n=3064/45â596) of pairs in clusters determined by standard cgMLST, 15â% (n=1222/8500) of pairs in core SNP-clusters and 51â% (n=942/1880) of pairs in SKA-clusters showed epidemiological linkage. The proportion of epidemiological linkage differed between sequence types. For VREfm, the discriminative ability of the widely used cgMLST based approach at ≤20 alleles difference was insufficient to rule out hospital outbreaks without further analytical methods. Cluster assignment guided by core genome SNP analysis and the reference free SKA was more discriminative and correlated better with obvious epidemiological linkage, at least recently published thresholds (ten and seven SNPs, respectively) and for frequent STs. Besides higher overall discriminative power, the whole-genome approach implemented in SKA is also easier and faster to conduct and requires less computational resources.
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Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Humanos , Enterococos Resistentes à Vancomicina/genética , Berlim/epidemiologia , Polimorfismo de Nucleotídeo Único , Genoma Bacteriano , Infecções por Bactérias Gram-Positivas/epidemiologia , Surtos de Doenças , Hospitais , Alemanha/epidemiologiaRESUMO
BACKGROUND: Serratia marcescens may cause severe nosocomial infections, mostly in very low birth weight infants. Since S. marcescens exhibits by far the highest adjusted incidence rate for horizontal transmission, it can cause complex outbreak situations in neonatal intensive care units. OBJECTIVE: The aim of this study was to establish a fast and highly sensitive colonization screening for prompt cohorting and barrier nursing strategies. METHODS: A probe-based duplex PCR assay targeting the 16S rRNA gene of S. marcescens was developed and validated by using 36 reference strains, 14 S. marcescens outbreak- and nonoutbreak isolates, defined by epidemiological linkage and molecular typing, and applied in 1,347 clinical specimens from 505 patients. RESULTS AND CONCLUSIONS: The novel PCR assay proved to be highly specific and had an in vitro sensitivity of 100 gene copies per reaction (â¼15 bacteria). It showed a similar (in laryngeal/tracheal specimens) or even higher (in rectal/stoma swabs) in vivo sensitivity in comparison to routine microbial culture and was much quicker (<24 h vs. 2 days). By combining different oligonucleotide primers, there was robust detection of genetic variants of S. marcescens strains. PCR inhibition was low (1.6%) and observed with rectal swabs only. Cohort analysis illustrated applicability of the PCR assay as a quick tool to prevent outbreak scenarios by allowing rapid decisions on cohorting and barrier nursing. In summary, this novel molecular screening for colonization by S. marcescens is specific, highly sensitive, and substantially accelerates detection.
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Infecção Hospitalar , Infecções por Serratia , Recém-Nascido , Lactente , Humanos , Unidades de Terapia Intensiva Neonatal , Serratia marcescens/genética , RNA Ribossômico 16S , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia , Reação em Cadeia da Polimerase , Surtos de Doenças/prevenção & controle , Infecções por Serratia/diagnóstico , Infecções por Serratia/epidemiologia , Infecções por Serratia/prevenção & controleRESUMO
OBJECTIVES: Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonization. METHODS: From 2014 to 2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (prior multidrug-resistant organism detection, current/prior antibiotic consumption, prior hospital, rehabilitation or long-term care facility stay, international travel, animal contact and proton pump inhibitor [PPI]/antacid therapy). Genotype analysis was done using cgMLST typing. Multivariable analysis was performed. RESULTS: In 5 years, 265 of 17,349 included patients were colonized with VREfm (a prevalence of 1.5%). Risk factors for VREfm colonization were age (adjusted OR [aOR], 1.02; 95% CI, 1.01-1.03), previous (aOR, 2.71; 95% CI, 1.87-3.92) or current (aOR, 2.91; 95% CI, 2.60-3.24) antibiotic treatment, prior multidrug-resistant organism detection (aOR, 2.83; 95% CI, 2.21-3.63), prior stay in a long-term care facility (aOR, 2.19; 95% CI, 1.62-2.97), prior stay in a hospital (aOR, 2.91; 95% CI, 2.05-4.13) and prior consumption of PPI/antacids (aOR, 1.29; 95% CI, 1.18-1.41). Overall, the VREfm admission prevalence increased by 33% each year and 2% each year of life. 250 of 265 isolates were genotyped and 141 (53.2%) of the VREfm were the emerging ST117. Multivariable analysis showed that ST117 and non-ST117 VREfm colonized patients differed with respect to admission year and prior multidrug-resistant organism detection. DISCUSSION: Age, healthcare contacts and antibiotic and PPI/antacid consumption increase the individual risk of VREfm colonization. The VREfm admission prevalence increase in Germany is mainly driven by the emergence of ST117.
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Infecção Hospitalar , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Animais , Vancomicina/farmacologia , Hospitais Universitários , Estudos Transversais , Prevalência , Antiácidos , Antibacterianos/farmacologia , Fatores de Risco , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologiaRESUMO
Small fracture treatment includes the use of so-called "Herbert screws". In the past years, novel resorbable materials were introduced as an alternative to the classical titanium implants. The purpose of this study was to evaluate the influence of ongoing resorption/corrosion processes on the mechanical stability screws made from the magnesium alloy MgYREZr®. Our samples consisted of two partly resorbed screws, explanted due to medical reasons after 6 and 12 weeks, respectively, and five unused reference screws. We performed three-point bending tests to determine the stability of all screws. Additionally, with FE-models of the screws based on µCT-scans, we investigated whether any differences in the bending behavior of the screws can be attributed to the reduction of the material volume due to resorption alone. Both partly resorbed screws failed at a lower force than the reference screws (178.6 ± 5.5 N for the reference screws, 72.5 N and 74.5 N for the screw explanted after 6 and 12 weeks, respectively). FE simulations performed with the three different geometries and original material parameters (Young's modulus Enew = 45 GPa, yield limit σnew = 235 MPa) showed that the early fracture could not be attributed to the changed geometry alone. Material parameters for the partly resorbed screws were determined by fitting the numerical to the experimental force-displacement curves (E6week = 15 GPa, σ6week = 135 MPa and E12week = 8 GPa, σ12week = 135 MPa, respectively). Our results showed that both geometry of the screws and different material properties contribute to the overall stability. Understanding and controlling these two factors throughout the resorption process could enhance treatment options.
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Ligas , Magnésio , Parafusos Ósseos , Implantes Absorvíveis , TitânioAssuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Diagnóstico DiferencialRESUMO
Sensory photoreceptors mediate numerous light-dependent adaptations across organisms. In optogenetics, photoreceptors achieve the reversible, non-invasive, and spatiotemporally precise control by light of gene expression and other cellular processes. The light-oxygen-voltage receptor PAL binds to small RNA aptamers with sequence specificity upon blue-light illumination. By embedding the responsive aptamer in the ribosome-binding sequence of genes of interest, their expression can be downregulated by light. We developed the pCrepusculo and pAurora optogenetic systems that are based on PAL and allow to down- and upregulate, respectively, bacterial gene expression using blue light. Both systems are realized as compact, single plasmids that exhibit stringent blue-light responses with low basal activity and up to several 10-fold dynamic range. As PAL exerts light-dependent control at the RNA level, it can be combined with other optogenetic circuits that control transcription initiation. By integrating regulatory mechanisms operating at the DNA and mRNA levels, optogenetic circuits with emergent properties can thus be devised. As a case in point, the pEnumbra setup permits to upregulate gene expression under moderate blue light whereas strong blue light shuts off expression again. Beyond providing novel signal-responsive expression systems for diverse applications in biotechnology and synthetic biology, our work also illustrates how the light-dependent PAL-aptamer interaction can be harnessed for the control and interrogation of RNA-based processes.