The value-based price of transformative gene therapy for sickle cell disease: a modeling analysis.

Sickle cell disease (SCD) is an inherited, progressively debilitating blood disorder. Emerging gene therapies (GTx) may lead to a complete remission, the benefits of such can only be realized if GTx is affordable and accessible in the low-and middle-income countries (LMIC) with the greatest SCD burden. To estimate the health impacts and country-specific value-based prices (VBP) of a future gene therapy for SCD using a cost-utility model framework.

Discovery and Characterization of a Bicyclic Peptide (Bicycle) Binder to Thymic Stromal Lymphopoietin.

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that is difficult to drug with conventional small molecules due to the extended protein-protein interactions it forms with both receptors. The hit series was shown to bind to TSLP in a hotspot, that is also used by IL-7Rα.

The evolution of centriole degradation in mouse sperm.

Centrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometimes becoming dispensable, as in house mice.

Influence of concentration, irrigation method, and root canal third on intratubular penetration of sodium hypochlorite - a broad statistical analysis.

Background: The permanence of microorganisms in the root canal system represents the main cause of endodontic failure. Considering the impossibility of effective action of the endodontic files in ramifications of the main canal and mainly inside the dentinal tubules, a better understanding of the irrigation dynamics to enhance endodontic prognosis is essential. Objective: To evaluate the depth of intratubular penetration values of sodium hypochlorite (NaOCl) (dependent variable) by comparing different concentrations, methods of irrigation, and root canal thirds (independent variables) and to investigate the existence of interactions among them, capable of influencing the dependent variable.

Clinical determination of anatomical diameter in different dental groups correlating them with gender, age, tooth/canal and pulpoperiradicular diagnosis: an observational clinical study.

The aim of this observational clinical study (OCS) was to determine the clinical anatomical diameter (CAD) in several dental groups, thus correlating them with gender, age, tooth/canal and pulpoperiradicular diagnosis. Three-hundred fifty-nine teeth/584 vital or necrotic root canals from patients of both genders and different ages composed the sample. After performing the necessary previous procedures, K-Flexofiles were used to determine the CAD.