Project description:The SMILES trial was the first intervention study to test dietary improvement as a treatment strategy for depression. Molendijk et al. propose that expectation bias and difficulties with blinding might account for the large effect size. While we acknowledge the issue of expectation bias in lifestyle intervention trials and indeed discuss this as a key limitation in our paper, we observed a strong correlation between dietary change and change in depression scores, which we argue is consistent with a causal effect and we believe unlikely to be an artefact of inadequate blinding. Since its publication, our results have been largely replicated and our recent economic evaluation of SMILES suggests that the benefits of our approach extend beyond depression. We argue that the SMILES trial should be considered an important, albeit preliminary, first step in the field of nutritional psychiatry research.
Project description:The antiviral agent remdesivir (Veklury®; Gilead Sciences), nucleotide analogue prodrug, has broad-spectrum activity against viruses from several families. Having demonstrated potent antiviral activity against coronaviruses in preclinical studies, remdesivir emerged as a candidate drug for the treatment of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during the current global pandemic. Phase III evaluation of remdesivir in the treatment of COVID-19 commenced in early 2020 and has thus far yielded promising results. In late May 2020, Taiwan conditionally approved the use of remdesivir in patients with severe COVID-19. This was followed by a rapid succession of conditional approvals in various countries/regions including the EU and Canada. Preceding these conditional approvals, an emergency use authorization for remdesivir had been granted in the USA (on 1 May 2020) and a special approval for emergency use was granted in Japan (on 7 May 2020). This article summarizes the milestones in the development of remdesivir leading to its first conditional approval for the treatment of COVID-19.
Project description:Circulating Tumor Cells (CTCs) from metastatic breast cancer patients were harvested and grown in vitro for 30+ days in a novel short-term culture method. Additionally, RNA from the buffy coat of 5 healthy donors were sequenced and subjected to culture conditions; 0/5 cultures successfully grew. This new culture method is highly efficient and allows for the molecular characterization of CTCs and identification of potential targets for therapy against tumor metastasis. Using this method, we established 12/12 cultures of CTCs.
Project description:Pedometer step count improves with pulmonary rehabilitation and deteriorates with time. The MCID for improvement and deterioration is 427 and -456 steps, respectively, but there is uncertainty about the reliability of these estimates. https://bit.ly/3ci97Jh.
Project description:IntroductionWhile various surgical techniques have been reported for open and minimally invasive treatment of upper tract urothelial cancer (UTUC), the procedure of robot-assisted nephroureterectomy (NU) with bladder cuff has never been reported using only retroperitoneum without entering abdominal cavity. We developed a novel port placement and technique allowing to perform robot-assisted NU by a unique retroperitoneal approach.MethodsBetween February and June 2021 patients with history of UTUC were treated by robot-assisted NU completely restricted to retroperitoneal space using a singular trocar placement and a two-step docking without relocation of the surgical robot. Patient characteristics, perioperative outcomes and short-term follow-up were prospectively analyzed.ResultsThe analysis included five patients [median age: 73 years; BMI: 27.2 kg/m2; Charlson comorbidity index 5]. All five patients had UTUC with a mean tumor size of 3.02 cm (range 0.9-6.0). UTUC was localized to distal ureter in two and to kidney in three cases. No positive surgical margins were noted for all patients with UTUC [1 low-grade and 4 high-grade]. Retroperitoneal lymphadenectomy in three patients did not reveal positive nodes. No intraoperative adverse events exceeding EAUiaiC classification ≥ 2 were observed, while median EBL was 150 ml (IQR 100-250). No patient experienced postoperative complications exceeding Clavien-Dindo classification ≥ 3a. Median hospital stay was 5.4d without any 30-d readmission.ConclusionWe demonstrate safety and feasibility of the first entire robot-assisted retroperitoneal nephroureterectomy (RRNU) with bladder cuff. This surgical technique is easily reproducible, while surgical outcomes are similar to other established techniques.
Project description:Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of "virulence factors" important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis.
Project description:Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, mutations are found in ITGB2, the gene that encodes the ? subunit of the ?(2) integrins. This syndrome is characterized directly after birth by delayed separation of the umbilical cord. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Le(a) and Le(b) blood group antigens. Finally, in LAD-III (also called LAD-I/variant) the conformational activation of the hematopoietically expressed ? integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells that is involved in the regulation of ? integrin conformation.
Project description:IntroductionSpain was one of the most affected countries during the first wave of COVID-19, having the highest mortality rate in Europe. The aim of this retrospective study is to estimate the impact that remdesivir-the first drug for COVID-19 approved in the EU-would have had in the first wave.MethodsThis study simulated the impact that remdesivir could have had on the Spanish National Health System (SNHS) capacity (bed occupancy) and the number of deaths that could have been prevented, based on two scenarios: a real-life scenario (without remdesivir) and an alternative scenario (with remdesivir). It considered the clinical results of the ACTT-1 trial in hospitalized patients with COVID-19 and pneumonia who required supplemental oxygen. The occupancy rates in general wards and ICUs were estimated in both scenarios.ResultsRemdesivir use could have prevented the admission of 2587 patients (43.75%) in the ICUs. It could have also increased the SNHS capacity in 5656 general wards beds and 1700 ICU beds, showing an increase in the number of beds available of 17.53% (95% CI 3.98%-24.42%) and 23.98% (95% CI 21.33%-28.22%), respectively, at the peak of the occupancy rates. Furthermore, remdesivir use could have prevented 7639 deaths due to COVID-19, which implies a 27.51% reduction (95% CI 14.25%-34.07%).ConclusionsRemdesivir could have relieved the pressure on the SNHS and could have reduced the death toll, providing a better strategy for the management of COVID-19 during the first wave.