Delineating genotype and parent-of-origin effect on the phenotype in MSH6-associated Lynch syndrome.

Background: This study investigates the potential influence of genotype and parent-of-origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease-causing MSH6 germline variants.

Patients And Methods: A cohort of 1615 MSH6 variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant.

Discordant Staining Patterns and Microsatellite Results in Tumors of MSH6 Pathogenic Variant Carriers.

Diagnosis of Lynch syndrome (LS) caused by a pathogenic germline MSH6 variant may be complicated by discordant immunohistochemistry (IHC) and/or by a microsatellite stable (MSS) phenotype. This study aimed to identify the various causes of the discordant phenotypes of colorectal cancer (CRC) and endometrial cancer (EC) in MSH6-associated LS. Data were collected from Dutch family cancer clinics.

Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma.

Background: Type 2 endotype asthma is driven by IL-4 and IL-13 signaling via IL-4Ra, which is highly expressed on airway epithelium, airway smooth muscle, and immunocytes in the respiratory mucosa, suggesting potential advantages of an inhalable antagonist. Lipocalin 1 (Lcn1), a 16 kDa protein abundant in human periciliary fluid, has a robust drug-like structure well suited to protein engineering, but it has never been used to make an inhaled Anticalin protein therapeutic.

Objectives: We sought to reengineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile.

Identification of Medicinal Products: Providing an Educational Framework.

The ISO standards for the Identification of Medicinal Products (IDMP) prove to be difficult to implement. Guidance needs to be provided to those using and further developing IDMP-related standards and terminologies. Providing fitting and structured education would be a step forward.

Birt-Hogg-Dubé syndrome in apparent primary spontaneous pneumothorax patients; results and recommendations for clinical practice.

Background: Birt-Hogg-Dubé syndrome (BHD) is an inherited disease caused by pathogenic variants in the FLCN gene. One of the characteristics is the increased risk for spontaneous pneumothorax, likely due to the presence of pulmonary cysts mainly distributed under the carina. Due to variable expression and lack of awareness, BHD is likely to be underdiagnosed.