MR-Phasenbilder ultraschallinduzierter Verschiebungsfelder an Brustläsionen

In dieser Arbeit wurde eine Methode erforscht, die die Uktraschalstrahlungskraft mit der MRT kombiniert. Durch die Schallstrahlungskraft werden im Gewebe Verschiebungen hervorgerufen. Diese lieferten einen Kontrast in MR-Phasenbildern, welche mit einer bewegungssensitiven Spin-Echo-Sequenz aufgenommen wurden. Aus den Phasenbildern konnte pixelweise die Verschiebung in Schallausbreitungsrichtung berechnet werden, welche maßgeblich von der Schallabsorption und den elastischen Eigenschaften des Gewebes abhängt. In vorbereitenden Messungen an einem kommerziellen Phantom und mehreren selbst hergestellten wurde das Verhalten von homogenem Gewebe, weichen und festen Einschlüssen sowie Kalkeinschlüssen unter Einfluss der Schallstrahlungskraft von Ultraschall untersucht. Die Einschlüsse wurden lokalisiert und das charakteristische Verhalten erklärt. Da im Rahmen dieser Arbeit ein Ethik-Antrag bei den zuständigen Ethikkommissionen erfolgreich gestellt wurde, konnten die Erkenntnisse aus den Phantommessungen auf Messungen an Versuchspersonen übertragen werden. Es wurden drei Patientinnen mit verschiedenen Pathologien (eine Zyste und zwei Fibroadenome) untersucht. In allen Messungen kam es im Gewebe zunächst zu einem Anstieg der Verschiebung mit anschließendem Abfall, was auf die Randbedingungen zurückzuführen ist. Beim Übergang ins zystische Gewebe kam es erneut zu einem Anstieg der Verschiebung, da es weicher als das umliegende Gewebe ist. Obwohl das Gewebe des Fibroadenoms fester als das umliegende Gewebe ist, wird es als Ganzes stärker verschoben als die Umgebung. Dieses Verhalten lässt sich mit medizinischem Hintergrundwissen erklären. Bei Fibroadenomen handelt es sich zwar um Verhärtungen, diese sind allerdings abgekapselt und im umliegenden Gewebe leicht verschieblich. Trifft der Ultraschall auf das Fibroadenom, so kommt es zur Reflektion an der Grenzfläche zwischen dem Drüsengewebe und dem Fibroadenom. Der so erzeugte erhöhte Kraftübertrag führt zur gesteigerten Verschiebung des gesamten Fibroadenoms. Parallel zu den Messungen an Patientinnen wurde eine Störungsanalyse an gesunden Versuchspersonen durchgeführt. Diese ergab, dass die auftretenden Bildstörungen maßgeblich durch ungewollte Bewegungen des Messvolumens hervorgerufen werden. Die Ergebnisse zeigen, dass die vorgestellte Methode erfolgreich an Patientinnen angewendet werden kann und das Potenzial hat, ohne jegliches Gesundheitsrisiko das Spektrum der Vorsorgeuntersuchungen zu erweitern. Vorhandene Befunde wurden bestätigt, was darauf hoffen lässt, dass diese Methode, nach einer Weiterentwicklung und in Kombination mit den Standard-Techniken, zur Verbesserung der Brustkrebsdiagnostik beitragen kann und damit falsch-positive Befunde und Biopsieuntersuchungen reduziert werden können

Emergency infection prevention and control training in fragile, conflict-affected or vulnerable settings: A scoping review

Background: It is uncertain what could be the best training methods for infection prevention and control when an infectious disease threat is active or imminent in especially vulnerable or resource-scarce settings. Methods: A scoping review was undertaken to find and summarise relevant information about training modalities, replicability and effectiveness of IPC training programmes for clinical staff as reported in multiple study designs. Eligible settings were conflict-affected or in countries classified as low-income or lower-middle income (World Bank 2022 classifications). Search terms for LILACS and Scopus were developed with input of an expert working group. Initially found articles were dual-screened independently, data were extracted especially about infection threat, training outcomes, needs assessment and teaching modalities. Backwards and forwards citation searches were done to find additional studies. Narrative summary describes outcomes and aspects of the training programmes. A customised quality assessment tool was developed to describe whether each study could be informative for developing specific future training programmes in relevant vulnerable settings, based on six questions about replicability and eight questions about other biases. Findings: Included studies numbered 29, almost all (n=27) were pre-post design, two were trials. Information within the included studies to enable replicability was low (average score 3.7/6). Nearly all studies reported significant improvement in outcomes suggesting that the predominant study design (pre-post) is inadequate to assess improvement with low bias, that any and all such training is beneficial, or that publication bias prevented reporting of less successful interventions and thus a informative overview. Conclusion: It seems likely that many possible training formats and methods can lead to improved worker knowledge, skills and / or practice in infection prevention and control. Definitive evidence in favour of any specific training format or method is hard to demonstrate due to incomplete descriptions, lack of documentation about unsuccessful training, and few least-biased study designs (experimental trials). Our results suggest that there is a significant opportunity to design experiments that could give insights in favour of or against specific training methods. “Sleeping” protocols for randomised controlled trials could be developed and then applied quickly when relevant future events arise, with evaluation for outcomes such as knowledge, practices, skills, confidence, and awareness

Antidepressant and antipsychotic drug prescribing and diabetes outcomes:a systematic review of observational studies

Aims: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. Methods: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. Results: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. Conclusions: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Antidepressant and antipsychotic drug prescribing and diabetes outcomes: A systematic review of observational studies

AIMS: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. METHODS: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. RESULTS: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. CONCLUSIONS: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Disruption to Functional Networks in Neonates With Perinatal Brain Injury Predicts Motor Skills at 8 Months

Objective: Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Methods: Infants ( Results: Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. Conclusion: fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies

Antidepressant and antipsychotic drug prescribing and diabetes outcomes: A systematic review of observational studies

Aims: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. Methods: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. Results: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. Conclusions: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogen