RepoMed (Medizinische Hochschule Hannover)
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Lactiplantibacillus plantarum inhibited the growth of primary liver cancer by inducing early apoptosis and senescence, in vitro
No full textAnalyse der Hart- und Weichgewebesymmetrie nach Mittelgesichtsfrakturen zur Bestimmung des Einflusses beider Faktoren auf das postoperative Ergebnis
No full textSoftware tools for systematic review literature screening and data extraction: qualitative user experiences from succinct formal tests
No full textSystematic reviews (SRs) are an important tool in implementing the 3Rs in preclinical research. With the ever-increasing amount of scientific literature, SRs require increasing time-investments. Thus, using the most efficient review tools is essential. Most available tools aid the screening process, tools for data-extraction and / or multiple review phases are relatively scarce. Using a single platform for all review phases allows for auto-transfer of references from one phase to the next, which enables work on multiple phases at the same time. We performed succinct formal tests of four multiphase review tools that are free or relatively affordable: Covidence, Eppi, SRDR+ and SYRF. Our tests comprised full-text screening, sham data extraction and discrepancy resolution in the context of parts of a systematic review. Screening was performed as per protocol. Sham data extraction comprised free text, numerical and categorial data. Both reviewers kept a log of their experiences with the platforms throughout. These logs were qualitatively summarized and supplemented with further user experiences. We show value of all tested tools in the SR process. Which tool is optimal depends on multiple factors, comprising previous experience with the tool, but also review type, review questions and review team member enthusiasm
Subcutaneous and orally self-administered high-dose carprofen shows favorable pharmacokinetic and tolerability profiles in male and female C57BL/6J mice
No full textIntroduction Surgical interventions in mice require appropriate pain relief to ensure animal welfare and to avoid influence of pain on research findings. Carprofen is a non-steroidal anti-inflammatory drug commonly used as an analgesic for interventions inducing mild to moderate pain in laboratory rodents. Despite its frequent use, species-specific data on pharmacokinetics (PK), side effects, and potential impact on behavioral pain indicators are limited. Methods We determined PK and tolerability profiles of carprofen in healthy male and female C57BL/6J mice (n = 42), administered at highest recommended doses via single subcutaneous (s.c.) injection (20 mg/kg) and oral self-administration (25 mg/kg/24 h) per drinking water (d.w.) for 5 days. Plasma concentrations were measured at various time points after the start of the treatment (n = 6 per time point), and side effects were evaluated using a modified Irwin test battery, hematology, and histopathology. Additionally, potential interference with cage-side behaviors commonly used for pain assessment, such as the mouse grimace scale, wheel running, burrowing, nesting, and grooming activity, was investigated. Results Maximum plasma concentrations of 133.4 ± 11.3 μg/ml were reached 1 h after single s.c. injection with an elimination half-life of 8.52 h. Intake from d.w. resulted in a steady state within 24 h after the start of the treatment with plasma levels of around 60 μg/ml over 5 days in both sexes. The medicated water was well-accepted, and increased d.w. intake was observed in the first 24 h after exposure (p < 0.0001). The Irwin test revealed only minor influence on tested behavior and physiological functions. However, during treatment via d.w., an increase in body temperature (p < 0.0001) was observed, as well as a reduction in voluntary wheel running activity by 49-70% in male mice. Moreover, grooming behavior was slightly affected. Hematology and histopathology were without pathological findings that could be attributed to carprofen treatment. High-dose carprofen can be considered safe and of favorable PK for both administration routes assessed in healthy C57BL/6J mice of both sexes. Further efficacy evaluation of carprofen as monoanalgesic or component of multimodal post-surgical regimens is clearly encouraged; however, the impact on behavioral markers used for pain assessment should be considered in this context
Physiotherapy interventions in post- and long-COVID-19: a scoping review protocol
No full textIntroduction Post- or long-COVID-19 conditions manifest with a spectrum of symptoms reminiscent of pulmonary, musculoskeletal, psychological and neurological disorders. Individuals with post- or long-COVID-19 syndrome often present with myalgia, pulmonary problems and fatigue, which significantly impact their daily functioning. Physiotherapy interventions are an accepted medical remedy for these symptoms. This scoping review aims to outline the evidence of physiotherapy interventions documented in the scientific literature, specifically focusing on hands-on therapy. Methods and analysis This scoping review conforms to the methodological framework established by the Joanna Briggs Institute (JBI). The procedure for drafting a scoping review involves several steps, starting with defining the research question and the inclusion and exclusion criteria. Eligible studies are those analysing physiotherapy treatment parameters for direct patient interaction in post- and long-COVID-19 patients. Telemedicine and entirely home-based workouts will be excluded aligning with the context of outpatient physiotherapy in Germany. The literature search will be conducted in PubMed, EBSCO research, Scopus, Web of Science, Embase, PEDRO, Cochrane and WISO databases by two independent researchers. Screening, data extraction and a critical appraisal will be performed by these researchers using assessment tools provided by the JBI. Extracted data will encompass demographic characteristics, definitions of post- or long-COVID-19 conditions, descriptions of interventions, their treatment parameters and treatment outcome. Subsequently, findings will be disseminated through a scoping review article or conference presentation. Ethics and dissemination Given that this review does not involve human participants, ethical committee approval is deemed unnecessary. The results will be published in peer-reviewed journals and presented at academic and physiotherapeutic conferences
JAK inhibitors to treat STAT3 gain-of-function: a single-center report and literature review
No full textObjective The signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) syndrome (STAT3-GOF) is an inborn error of immunity (IEI) characterized by diverse manifestations of immune dysregulation that necessitate systemic immunomodulatory treatment. The blockade of the interleukin-6 receptor and/or the inhibition of the Janus kinases has been commonly employed to treat diverse STAT3-GOF-associated manifestations. However, evidence on long-term treatment outcome, especially in the case of adult patients, is scarce. Methods Clinical data, including laboratory findings and medical imaging, were collected from all seven patients, diagnosed with STAT3-GOF, who have been treated at the Hannover University School, focusing on those who received a Janus kinase (JAK) inhibitor (JAKi). Previously published cases of STAT3-GOF patients who received a JAKi were evaluated, focusing on reported treatment efficacy with respect to diverse STAT3-GOF-associated manifestations of immune dysregulation and safety. Results Five out of seven patients diagnosed with STAT3-GOF were treated with a JAKi, each for a different indication. Including these patients, outcomes of JAKi treatment have been reported for a total of 41 patients. Treatment with a JAKi led to improvement of diverse autoimmune, inflammatory, or lymphoproliferative manifestations of STAT3-GOF and a therapeutic benefit could be documented for all except two patients. Considering all reported manifestations of immune dysregulation in each patient, complete remission was achieved in 10/41 (24.4%) treated patients. Conclusions JAKi treatment improved diverse manifestations of immune dysregulation in the majority of STAT3-GOF patients, representing a promising therapeutic approach. Long-term follow-up data are needed to evaluate possible risks of prolonged treatment with a JAKi
Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection
Get PDFIntroduction Serum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, the IL-6R exists in membrane-bound and soluble forms (sIL-6R), and the sIL-6R in combination with soluble glycoprotein 130 (sgp130) forms an IL-6-neutralizing buffer system capable of neutralizing small amounts of IL-6. Methods In this study, we analyzed serum levels of IL-6, sIL-6R and sgp130 in the serum of COVID-19 convalescent individuals with a history of mild COVID-19 disease and in acute severely ill COVID-19 patients compared to uninfected control subjects. Furthermore, we used single cell RNA sequencing data in order to determine which immune cell types are sources and targets of the individual cytokines and whether their expression is altered in severe COVID-19 patients. Results We find that sIL-6R levels are not only increased in acute severely ill patients, but also in convalescents after a mild COVID-19 infection. We show that this increase in sIL-6R results in an enhanced capacity of the sIL-6R/sgp130 buffer system, but that significantly enhanced free IL-6 is still present due to an overload of the buffer. Further, we identify IL-6 serum levels, age and the number of known pre-existing medical conditions as crucial determinants of disease outcome for the patients. We also show that IL-11 has no major systemic role in COVID-19 patients and that sCD25 is only increased in acute severely ill COVID-19 patients, but not in mild convalescent individuals. Discussion In conclusion, our study shows long-lasting alterations of the IL-6 system after COVID-19 disease, which might be relevant when applying anti-IL-6 or anti-IL-6R therapy