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Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species.
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Infecções Estafilocócicas , Staphylococcus aureus , Animais , Staphylococcus aureus/genética , Staphylococcus aureus/virologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Camundongos , Roedores/microbiologia , Roedores/virologia , Bacteriófagos/genética , Humanos , Filogenia , Genoma Bacteriano , Fagos de Staphylococcus/genéticaRESUMO
The rapid development of artificial intelligence (AI) has gained importance, with many tools already entering our daily lives. The medical field of radiation oncology is also subject to this development, with AI entering all steps of the patient journey. In this review article, we summarize contemporary AI techniques and explore the clinical applications of AI-based automated segmentation models in radiotherapy planning, focusing on delineation of organs at risk (OARs), the gross tumor volume (GTV), and the clinical target volume (CTV). Emphasizing the need for precise and individualized plans, we review various commercial and freeware segmentation tools and also state-of-the-art approaches. Through our own findings and based on the literature, we demonstrate improved efficiency and consistency as well as time savings in different clinical scenarios. Despite challenges in clinical implementation such as domain shifts, the potential benefits for personalized treatment planning are substantial. The integration of mathematical tumor growth models and AI-based tumor detection further enhances the possibilities for refining target volumes. As advancements continue, the prospect of one-stop-shop segmentation and radiotherapy planning represents an exciting frontier in radiotherapy, potentially enabling fast treatment with enhanced precision and individualization.
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Malignant melanoma remains the most lethal form of skin cancer, exhibiting poor prognosis after forming distant metastasis. Owing to their potential tumor-suppressive properties by regulating oncogenes and tumor suppressor genes, microRNAs are important player in melanoma development and progression. We defined the loss of miR-101-3p expression in melanoma cells compared with melanocytes and melanoblast-related cells as an early event in tumor development and aimed to understand the tumor suppressive role of miR-101-3p and its regulation of important cellular processes. Reexpression of miR-101-3p resulted in inhibition of proliferation, increase in DNA damage, and induction of apoptosis. We further determined the nuclear structure protein Lamin B1, which influences nuclear processes and heterochromatin structure, ATRX, CASP3, and PARP as an important direct target of miR-101-3p. RNA sequencing and differential gene expression analysis after miR-101-3p reexpression supported our findings and the importance of loss of mir-101-3p for melanoma progression. The validated functional effects are related to genomic instability, as recent studies suggest miRNAs plays a key role in mediating this cellular process. Therefore, we concluded that miR-101-3p reexpression increases the genomic instability, leading to irreversible DNA damage, which leads to apoptosis induction. Our findings suggest that the loss of miR-101-3p in melanoma serves as an early event in melanoma progression by influencing the genomic integrity to maintain the increased bioenergetic demand.
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Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Melanoma/genética , MicroRNAs/metabolismo , Neoplasias Cutâneas/genética , Apoptose/genética , Genômica , Instabilidade Genômica , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
AbstractFemale reproductive success is often limited by access to resources, and this can lead to social competition both within and between kin groups. Theory predicts that both resource availability and relatedness should influence the fitness consequences of social competition. However, testing key predictions requires differentiating the effects of these two factors. Here, we achieve this experimentally by manipulating the social environment of house mice, a facultative communal breeding species with known kin discrimination ability. This allows us to investigate (1) the reproductive costs of defending a limited resource in response to cues of social competition and (2) whether such costs, or their potential mitigation via cooperative behavior, are influenced by the relatedness of competitors. Our results support the hypothesis that resource defense can be costly for females, potentially trading off against maternal investment. When the availability of protected nest sites was limited, subjects (1) were more active, (2) responded more strongly to simulated territory intrusions via competitive signaling, and (3) produced smaller weaned offspring. However, we found no evidence that the propensity for kin to cooperate was influenced by the relatedness of rivals. Communal breeding between sisters occurred independently of the relatedness of competitors and communally breeding sisters weaned fewer offspring when competing with unrelated females, despite our study being designed to prevent infanticide between kin groups. Our findings thus demonstrate that female competition has fitness costs and that associating with kin is beneficial to avoid negative fitness consequences of competing with nonkin, in addition to more widely recognized kin-selected benefits.
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Comportamento Cooperativo , Comportamento Social , Animais , Camundongos , Feminino , Humanos , Meio Social , Irmãos , ReproduçãoRESUMO
The extent of how complex natural microbial communities contribute to metal corrosion is still not fully resolved, especially not for freshwater environments. In order to elucidate the key processes, we investigated rust tubercles forming massively on sheet piles along the river Havel (Germany) applying a complementary set of techniques. In-situ microsensor profiling revealed steep gradients of O2 , redox potential and pH within the tubercle. Micro-computed tomography and scanning electron microscopy showed a multi-layered inner structure with chambers and channels and various organisms embedded in the mineral matrix. Using Mössbauer spectroscopy we identified typical corrosion products including electrically conductive iron (Fe) minerals. Determination of bacterial gene copy numbers and sequencing of 16S rRNA and 18S rRNA amplicons supported a densely populated tubercle matrix with a phylogenetically and metabolically diverse microbial community. Based on our results and previous models of physic(electro)chemical reactions, we propose here a comprehensive concept of tubercle formation highlighting the crucial reactions and microorganisms involved (such as phototrophs, fermenting bacteria, dissimilatory sulphate and Fe(III) reducers) in metal corrosion in freshwaters.
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Bactérias , Compostos Férricos , Corrosão , RNA Ribossômico 16S/genética , Microtomografia por Raio-X , Bactérias/genética , Minerais , Água Doce , OxirreduçãoRESUMO
Various chalcidoid wasps can actively steer their terebra (= ovipositor shaft) in diverse directions, despite the lack of terebral intrinsic musculature. To investigate the mechanisms of these bending and rotational movements, we combined microscopical and microtomographical techniques, together with videography, to analyse the musculoskeletal ovipositor system of the ectoparasitoid pteromalid wasp Lariophagus distinguendus (Förster, 1841) and the employment of its terebra during oviposition. The ovipositor consists of three pairs of valvulae, two pairs of valvifers and the female T9 (9th abdominal tergum). The paired 1st and the 2nd valvulae are interlocked via the olistheter system, which allows the three parts to slide longitudinally relative to each other, and form the terebra. The various ovipositor movements are actuated by a set of nine paired muscles, three of which (i.e. 1st valvifer-genital membrane muscle, ventral 2nd valvifer-venom gland reservoir muscle, T9-genital membrane muscle) are described here for the first time in chalcidoids. The anterior and posterior 2nd valvifer-2nd valvula muscles are adapted in function. (1) In the active probing position, they enable the wasps to pull the base of each of the longitudinally split and asymmetrically overlapping halves of the 2nd valvula that are fused at the apex dorsally, thus enabling lateral bending of the terebra. Concurrently, the 1st valvulae can be pro- and retracted regardless of this bending. (2) These muscles can also rotate the 2nd valvula and therefore the whole terebra at the basal articulation, allowing bending in various directions. The position of the terebra is anchored at the puncture site in hard substrates (in which drilling is extremely energy- and time-consuming). A freely steerable terebra increases the chance of contacting a potential host within a concealed cavity. The evolution of the ability actively to steer the terebra can be considered a key innovation that has putatively contributed to the acquisition of new hosts to a parasitoid's host range. Such shifts in host exploitation, each followed by rapid radiations, have probably aided the evolutionary success of Chalcidoidea (with more than 500,000 species estimated).
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In malignant melanoma, a highly aggressive form of skin cancer, many microRNAs are aberrantly expressed contributing to tumorigenesis and progression. Further, deregulation of microRNA processing enzymes, like the miRNA-binding protein Argonaute 2, significantly impacts microRNA function. This study characterizes a novel splice variant of Argonaut 2, AGO2-ex1/3. AGO2-ex1/3 is substantially expressed in different melanoma cell lines and patient-derived tissue samples. It is a mature mRNA, which is translated into an N-terminally truncated Argonaute 2 protein form. Molecular dynamics simulations show that the PAZ, MID, and PIWI domain largely retain their structure in AGO2-ex1/3 and that the truncation of the N-terminus leads to an increased interdomain flexibility. Expression of AGO2-ex1/3 provides a survival advantage for melanoma cells while the knockdown causes significantly reduced proliferation and increases apoptosis. RNA-sequencing revealed that in cells lacking AGO2-ex1/3 expression many miRNA target genes are deregulated, implicating a considerable role of AGO2-ex1/3 for miRNA function. This study inaugurates insights into an important role of a so far unknown splice variant of Argonaute 2 for the miRNA pathway as well as the mechanisms which drive growth and survival of melanoma cells. This knowledge provides the basis for potential new promising therapeutic targets focusing on small RNA-mediated gene regulation in melanoma.
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Melanoma , MicroRNAs , Neoplasias Cutâneas , Apoptose/genética , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Humanos , Melanoma/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA , Neoplasias Cutâneas/genéticaRESUMO
Tracheobronchial stenoses consist of a spectrum of conditions that may result in focal or diffuse narrowing of the trachea or downstream bronchial system. The purpose of this paper is to provide an overview of the most commonly encountered conditions in terms of diagnosis and therapeutic options as well as the associated challenges for practitioners.
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Broncopatias , Humanos , Brônquios/cirurgia , Broncopatias/diagnóstico , Broncopatias/cirurgia , Broncoscopia , Constrição Patológica/cirurgia , Tomografia Computadorizada por Raios X , Traqueia/cirurgiaRESUMO
In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.
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Oxigenação por Membrana Extracorpórea , Choque , Humanos , Sociedades Científicas , Circulação Extracorpórea , Sociedades Médicas , AlemanhaRESUMO
The astonishing diversity of brain sizes observed across the animal kingdom is typically explained in the context of trade-offs: the benefits of a larger brain, such as enhanced cognitive ability, are balanced against potential costs, such as increased energetic demands. Several hypotheses have been formulated in this framework, placing different emphasis on ecological, behavioural, or physiological aspects of trade-offs in brain size evolution. Within this body of work, there exists considerable taxonomic bias towards studies of birds and mammals, leaving some uncertainty about the generality of the respective arguments. Here, we test three of the most prominent such hypotheses, the 'expensive tissue', 'social brain' and 'cognitive buffer' hypotheses, in a large dataset of fishes, derived from a publicly available resource (FishBase). In accordance with predictions from the 'expensive tissue' and the 'social brain' hypothesis, larger brains co-occur with reduced fecundity and increased sociality in at least some Classes of fish. Contrary to expectations, however, lifespan is reduced in large-brained fishes, and there is a tendency for species that perform parental care to have smaller brains. As such, it appears that some potential costs (reduced fecundity) and benefits (increased sociality) of large brains are near universal to vertebrates, whereas others have more lineage-specific effects. We discuss our findings in the context of fundamental differences between the classically studied birds and mammals and the fishes we analyse here, namely divergent patterns of growth, parenting and neurogenesis. As such, our work highlights the need for a taxonomically diverse approach to any fundamental question in evolutionary biology.
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Encéfalo , Peixes , Animais , Evolução Biológica , Aves , Análise Custo-Benefício , Mamíferos , Tamanho do ÓrgãoRESUMO
In permafrost peatlands, up to 20% of total organic carbon (OC) is bound to reactive iron (Fe) minerals in the active layer overlying intact permafrost, potentially protecting OC from microbial degradation and transformation into greenhouse gases (GHG) such as CO2 and CH4. During the summer, shifts in runoff and soil moisture influence redox conditions and therefore the balance of Fe oxidation and reduction. Whether reactive iron minerals could act as a stable sink for carbon or whether they are continuously dissolved and reprecipitated during redox shifts remains unknown. We deployed bags of synthetic ferrihydrite (FH)-coated sand in the active layer along a permafrost thaw gradient in Stordalen mire (Abisko, Sweden) over the summer (June to September) to capture changes in redox conditions and quantify the formation and dissolution of reactive Fe(III) (oxyhydr)oxides. We found that the bags accumulated Fe(III) under constant oxic conditions in areas overlying intact permafrost over the full summer season. In contrast, in fully thawed areas, conditions were continuously anoxic, and by late summer, 50.4 ± 12.8% of the original Fe(III) (oxyhydr)oxides were lost via dissolution. Periodic redox shifts (from 0 to +300 mV) were observed over the summer season in the partially thawed areas. This resulted in the dissolution and loss of 47.2 ± 20.3% of initial Fe(III) (oxyhydr)oxides when conditions are wetter and more reduced, and new formation of Fe(III) minerals (33.7 ± 8.6% gain in comparison to initial Fe) in the late summer under more dry and oxic conditions, which also led to the sequestration of Fe-bound organic carbon. Our data suggest that there is seasonal turnover of iron minerals in partially thawed permafrost peatlands, but that a fraction of the Fe pool remains stable even under continuously anoxic conditions.
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Pergelissolo , Compostos Férricos/metabolismo , Ferro/metabolismo , Oxirredução , Estações do Ano , SoloRESUMO
INTRODUCTION: The interval slide procedure (IS) has been introduced to improve mobility in massive, retracted rotator cuff tears. As clinical studies showed controversial results, the benefit of the IS is still widely discussed. AIM: Aim of this study was to analyze the effect of IS procedure on tendon mobility in a fresh porcine cadaver model. MATERIALS AND METHODS: In 30 fresh porcine cadaver shoulders with artificial supraspinatus defect tendon mobility was tested by measuring the load (in N) during tendon reduction to the footprint at the greater tubercle using a sensor enhanced arthroscopic grasper (t1). In intervention group (N = 15) anterior IS (t2), posterior IS (t3) and intraarticular capsule release (t4) were successively performed, each followed by tendon mobility assessment. Tendon mobility of the control group (N = 15) was measured in same time schedule without intervention. RESULTS: Mobility did not differ between groups for native tendons (CG 28.0 ± 11.2 N vs. IG 26.6 ± 11.6 N; P = 0.75). IS procedure significantly improves mobility at about 25.2% (t1 26.6 ± 11.6 N vs. t4 19.9 ± 12.3 N; P < 0.001) compared to the native tendon and 34.1% compared to CG (CG 30.2 ± 13.7 N vs. 19.9 ± 12.3 N; P = 0.026). In posthoc analyzes, anterior IS (P < 0.001) and capsule release (P = 0.005) significantly increased mobility, whereas the posterior IS did not (P = 0.778). CONCLUSION: The IS procedure results in increased supraspinatus tendon mobility in fresh porcine cadaver shoulders. However, performing the posterior IS subsequent to the anterior IS no significant improvement of mobility has been observed.
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Lesões do Manguito Rotador , Traumatismos dos Tendões , Animais , Fenômenos Biomecânicos , Cadáver , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Suínos , Traumatismos dos Tendões/cirurgiaRESUMO
BACKGROUND: High morbidity and mortality are frequently reported in intensive care patients suffering from severe sepsis with systemic inflammation. With the development of severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is often required. In this study, cytokine adsorption therapy in combination with ECMO is applied in patients with acute respiratory distress syndrome (ARDS) due to severe pneumogenic sepsis. The efficacy of this therapy is evaluated compared with a historical cohort without hemoadsorption therapy. METHODS: Between January and May 2018, combined high-flow venovenous ECMO and CytoSorb therapy (CytoSorb filter connected to ECMO circuit) was applied in patients (n = 13) with pneumogenic sepsis and ARDS. These patients were prospectively included (CytoSorb group). Data from patients (n = 7) with pneumogenic sepsis and ECMO therapy were retrospectively analyzed (control group). RESULTS: All patients survived in the CytoSorb group, where the 30-day mortality rate reached 57% in the control group. After CytoSorb therapy, we instantly observed a significant reduction in procalcitonin (PCT) and C-reactive protein (CRP) levels compared with the control group. Within 48 hours, the initial high doses of catecholamine could be weaned off only in the CytoSorb group. CONCLUSIONS: Our results indicate that CytoSorb in combination with ECMO is an effective therapy to prevent escalation of sepsis with rapid weaning off high-dose catecholamine infusions and quick reduction in PCT and CRP levels. Optimal timing of immunomodulatory therapy and impact on ECMO-related inflammation still need to be furtherly investigated.
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Citocinas/sangue , Oxigenação por Membrana Extracorpórea , Hemoperfusão , Síndrome do Desconforto Respiratório/terapia , Sepse/terapia , Adulto , Idoso , Proteína C-Reativa/metabolismo , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Hemoperfusão/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Prospectivos , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/diagnóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/diagnóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To examine whether robotic-assisted training as a supplement to usual therapy is safe, acceptable and improves function and patient reported outcome after proximal humeral fractures (PHF). DESIGN: Multicentre, assessor-blinded, randomised controlled prospective trial. SETTING: Three different rehabilitation hospitals in Germany. SUBJECTS: In total 928 PHF patients between 35 and 70 years were screened. Forty-eight participants were included in the study (intervention group n = 23; control group n = 25). INTERVENTION: The control group received usual occupational and physiotherapy over three weeks, and the intervention group received additional 12 robot-assisted training sessions at the ARMEO®-Spring. MAIN MEASURES: Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), the Wolf Motor Function Test-Orthopaedic, active range of motion and grip strength were determined before and after intervention period. The DASH was additionally obtained postal 6 and 13 months following surgery. RESULTS: The mean age of participants was 55 ± 10 years and was similar in both groups (p > 0.05). The change in DASH as the primary endpoint in the intervention group after intervention was -15 (CI = 8-22), at follow-up six month -7 (CI = -2 to 16) at follow up 13 month -9 (CI = 1-16); in control group -14 (CI = 11-18), at follow-up six month -13 (CI = 7-19) at follow up 13 month -6 (CI = -3 to 14). No difference in the change was found between groups (p > 0.05). None of the follow-up time points demonstrated an additional benefit of the robotic therapy. CONCLUSION: The additional robot-assisted therapy was safe, acceptable but showed no improvement in functional shoulder outcome compared to usual therapy only.
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Modalidades de Fisioterapia , Fraturas do Ombro/reabilitação , Adulto , Idoso , Análise Custo-Benefício , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional/métodos , Estudos Prospectivos , Amplitude de Movimento Articular , Robótica/métodos , Fraturas do Ombro/fisiopatologia , Fraturas do Ombro/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Molecular analyses of normal and diseased cells give insight into changes in gene expression and help in understanding the background of pathophysiological processes. Years after cDNA microarrays were established in research, RNA sequencing (RNA-seq) became a key method of quantitatively measuring the transcriptome. In this study, we compared the detection of genes by each of the transcriptome analysis methods: cDNA array, quantitative RT-PCR, and RNA-seq. As expected, we found differences in the gene expression profiles of the aforementioned techniques. Here, we present selected genes that exemplarily demonstrate the observed differences and calculations to reveal that a strong RNA secondary structure, as well as sample preparation, can affect RNA-seq. In summary, this study addresses an important issue with a strong impact on gene expression analysis in general. Therefore, we suggest that these findings need to be considered when dealing with data from transcriptome analyses.
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Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , RNA/química , Fatores de Transcrição SOX/genética , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Transcriptoma , Proteínas de Sinalização YAPRESUMO
In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.
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Oxigenação por Membrana Extracorpórea , Choque , Circulação Extracorpórea , Alemanha , Humanos , Sistemas de Manutenção da VidaRESUMO
Enantiopure (P)4- and (M)4-configured alleno-acetylenic cage (AAC) receptors offer a highly defined interior for the complexation and structure elucidation of small molecule fragments of the stereochemically complex chlorosulfolipid danicalipin A. Solution (NMR), solid state (X-ray), and theoretical investigations of the formed host-guest complexes provide insight into the conformational preferences of 14 achiral and chiral derivatives of the danicalipin A chlorohydrin core in a confined, mostly hydrophobic environment, extending previously reported studies in polar solvents. The conserved binding mode of the guests permits deciphering the effect of functional group replacements on Gibbs binding energies ΔG. A strong contribution of conformational energies toward the binding affinities is revealed, which explains why the denser packing of larger apolar domains of the guests does not necessarily lead to higher association. Enantioselective binding of chiral guests, with energetic differences ΔΔG293 K up to 0.7 kcal mol-1 between diastereoisomeric complexes, is explained by hydrogen- and halogen-bonding, as well as dispersion interactions. Calorimetric studies (ITC) show that the stronger binding of one enantiomer is accompanied by an increased gain in enthalpy ΔH but at the cost of a larger entropic penalty TΔS stemming from tighter binding.
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Alcadienos/química , Alcinos/química , Lipídeos/química , Receptores Artificiais/química , Cristalização , Cristalografia por Raios X , Estereoisomerismo , TermodinâmicaRESUMO
PURPOSE: Injection devices for administration of biopharmaceuticals enable subcutaneous self-administration by patients. To meet patient specific capabilities, injection forces need to be characterized. We address the open question of whether tissue resistance significantly contributes to overall injection forces, especially for large injection volumes. METHODS: Subcutaneous tissue resistance was systematically quantified for injection volumes up to 11 mL depending on viscosity (1-20 mPa·s) and injection rates (0.025-0.2 mL/s) using Göttingen Minipigs as the animal model. The contribution of an artificially applied external force at the injection site simulating autoinjector needle cover depression was tested between 2.5-7.5 N. RESULTS: Tissue resistance reached average values of ~120 mbar for injection volumes up to 11 mL independent of viscosity and injection rate, and maximum values of 300 mbar were determined. Artificially applied external forces led to higher values, independent of the absolute applied force - maximum values of 1 bar were obtained when injecting 4.5 mL of the 20 mPa·s solution at an injection rate of 0.1 mL/s with the application of an artificial 5 N force, corresponding to ~450 mbar. All conditions yield defined injection sites suggesting tissue resistance is defined by mechanical properties of the subcutaneous tissue. CONCLUSIONS: We set our results in relation to overall injection forces, concluding that maximum values in tissue resistance may cause challenges during subcutaneous injection when using injection devices. Graphical abstract.
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Injeções Subcutâneas , Tela Subcutânea/fisiologia , Animais , Fenômenos Biomecânicos , Dextranos , Agulhas , Suínos , Porco Miniatura , Seringas , ViscosidadeRESUMO
Table 2 of the article 'Tissue Resistance during Large-Volume Injections in Subcutaneous Tissue of Minipigs' encountered formatting errors in the (original) pdf version with misplacement of text and columns.
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Cooperative breeders feature the highest level of social complexity among vertebrates. Environmental constraints foster the evolution of this form of social organization, selecting for both well-developed social and ecological competences. Cooperative breeders pursue one of two alternative social trajectories: delaying reproduction to care for the offspring of dominant breeders or dispersing early to breed independently. It is yet unclear which ecological and social triggers determine the choice between these alternatives and whether diverging developmental trajectories exist in cooperative vertebrates predisposing them to dispersal or philopatry. Here we experimentally reared juveniles of cooperatively breeding cichlid fish by varying the social environment and simulated predation threat in a two-by-two factorial long-term experiment. First, we show that individuals develop specialized behavioral competences, originating already in the early postnatal phase. Second, these specializations predisposed individuals to pursue different developmental trajectories and either to disperse early or to extend philopatry in adulthood. Thus, our results contrast with the proposition that social specializations in early ontogeny should be restricted to eusocial species. Importantly, social and ecological triggers were both required for the generation of divergent life histories. Our results thus confirm recent predictions from theoretical models that organisms should combine relevant information from different environmental cues to develop integrated phenotypes.