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But Gysi’s scientific influence was by no means limited to prosthetics. Rather, he also provided important studies on caries and the dental pulp. Moreover, he published fundamental work on dental histopathology and microphotography. The current image of Gysi therefore needs to be revised. In view of the thematic breadth of his scientific contributions, Gysi is not only the most important prosthodontist of his time, but also one of the most versatile and innovative representatives in the history of Swiss dentistry.

Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling.

is a repressor of γ-globin expression and HbF production in adult erythrocytes. Its down-regulation is a promising therapeutic strategy for induction of HbF.

We enrolled patients with sickle cell disease in a single-center, open-label pilot study. The investigational therapy involved infusion of autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector, which encodes a short hairpin RNA (shRNA) targeting

mRNA embedded in a microRNA (shmiR), allowing erythroid lineage-specific knockdown. Patients were assessed for primary end points of engraftment and safety and for hematologic and clinical responses to treatment.

As of October 2020, six patients had been followed for at least 6 months after receiving BCH-BB6rable risk-benefit profile in sickle cell disease. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT03282656).Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer. Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients – one with TDT and the other with SCD – received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer. More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.).Immune checkpoint blockade (ICB) has a limited effect on colorectal cancer, underlining the requirement of co-targeting the complementary mechanisms. Here, we identified prostaglandin E2 (PGE2 ) receptor 4 (EP4) as the master regulator of immunosuppressive myeloid cells (IMCs), which are the major driver of resistance to ICB therapy. PGE2 -bound EP4 promotes the differentiation of immunosuppressive M2 macrophages and myeloid-derived suppressor cells (MDSCs) and reduces the expansion of immunostimulated M1 macrophages. To explore the immunotherapeutic role of EP4 signaling, we developed a novel and selective EP4 antagonist TP-16. TP-16 effectively blocked the function of IMCs and enhanced cytotoxic T-cell-mediated tumor elimination in vivo. Cell co-culture experiments revealed that TP-16 promoted T-cell proliferation, which was impaired by tumor-derived CD11b+ myeloid cells. Notably, TP-16 and anti-PD-1 combination therapy significantly impeded tumor progression and prolonged mice survival. We further demonstrated that TP-16 increased responsiveness to anti-PD-1 therapy in an IMC-related spontaneous colorectal cancer mouse model. In summary, this study demonstrates that inhibition of EP4-expressing IMCs may offer a potential strategy for enhancing the efficacy of immunotherapy for colorectal cancer.

The rollout of antiretroviral therapy (ART) has been associated with reductions in HIV-related stigma, but pathways through which this reduction occurs are poorly understood. In the newer context of universal test and treat (UTT) interventions, where rapid diffusion of ART uptake takes place, there is an opportunity to understand the processes through which HIV-related stigma can decline, and how UTT strategies may precipitate more rapid and widespread changes in stigma. This qualitative study sought to evaluate how a UTT intervention influenced changes in beliefs, attitudes and behaviours related to HIV.

Longitudinal qualitative in-depth semi-structured interview data were collected within a community-cluster randomized UTT trial, the Sustainable East Africa Research in Community Health (SEARCH) study, annually over three rounds (2014 to 2016) from two cohorts of adults (n=32 community leaders, and n=112 community members) in eight rural communities in Uganda and Kenya. Data were inductively analysed to uced in response to the community viewing the healthy bodies of PLHIV successfully engaged in treatment, which lessens the fears that trigger enacted stigma; it becomes no longer socially normative to stigmatize PLHIV. SU11248 malate This process may be reinforced through public health messaging and anti-discrimination laws.

Declines in HIV-related stigma appear to underway and explained by social processes accelerated by UTT efforts. Widespread implementation of UTT shows promise for reducing multiple dimensions of stigma, which is critical for improving health outcomes among PLHIV.

Declines in HIV-related stigma appear to underway and explained by social processes accelerated by UTT efforts. Widespread implementation of UTT shows promise for reducing multiple dimensions of stigma, which is critical for improving health outcomes among PLHIV.This work shows the preparation of thin films, with thickness from 70 nm to 1 μm, of meta-polybenzimidazole (m-PBI) on polyimide P84 supports. Ethanolic solutions of m-PBI were used to coat flat and hollow fiber supports of asymmetric P84 with m-PBI in a process where the coating and drying was performed at room temperature. A solution of NaOH in EtOH allowed the dissolution of the m-PBI powder, providing the perfect coating solution to build thin films of m-PBI without damaging the polymeric support. It also meant a green alternative, avoiding the use of toxic solvents, such as dimethylacetamide. The resulting membranes have been tested for the separation of H2 mixtures at high temperature at different setups to allow checking their reproducibility. With 100 nm thickness the membranes showed their best gas separation performance. For flat membranes at 180 °C and 3 bar feed pressure a H2 permeance of 48.5 GPU was obtained, with respective H2 /CO2 and H2 /N2 selectivities of 33.3 and 55.8. Besides, the hollow fibers under a feed pressure of 6 bar and tested at the same temperature showed near 90 GPU of H2 with a H2 /CO2 selectivity of 13.