Cutaneous nocardiosis with discharging sinus clinically mimicking tuberculosis diagnosed by cytology

Nocardiosis is primarily a pulmonary infection commonly seen in immunocompromised individuals. However, lymphocutaneous nocardiosis is observed in immunocompetent individuals often after trauma. The clinical and cytomorphological features of lymphocutaneous nocardiosis closely mimic the most common infections in India such as tuberculosis and mycetoma (very common cutaneous infection with discharging sinus). As it is crucial to differentiate nocardiosis from tuberculosis, to avoid unnecessary antitubercular treatment, special stains like modified Ziehl–Neelsen stain and Gram stain can be employed to differentiate the morphology of Nocardia from tuberculosis. Fine‐needle cytology from these cutaneous lesions helps in yielding adequate material for rapid and accurate diagnosis of immediate specific antibiotic treatment. We report a rare case that presented with clinical diagnosis of tuberculosis but turned out to be nocardiosis on cytomorphology with simple and most feasible fine‐needle aspiration method of tissue diagnosis and scrape cytology.     

CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials

Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient‐specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well‐studied. In advance of human therapeutic trials for CAPN5 vitreoretinopathy, genetic inactivation can be used to infer the effect of protein inhibition in vivo. We created a photoreceptor‐specific knockout (KO) mouse for Capn5 and compared the retinal phenotype to both wild‐type and an existing Capn5 KO mouse model. In humans, CAPN5 loss‐of‐function (LOF) gene variants were ascertained in large exome databases from 60,706 unrelated subjects without severe disease phenotypes. Ocular examination of the retina of Capn5 KO mice by histology and electroretinography showed no significant abnormalities. In humans, there were 22 LOF CAPN5 variants located throughout the gene and in all major protein domains. Structural modeling of coding variants showed these LOF variants were nearby known disease‐causing variants within the proteolytic core and in regions of high homology between human CAPN5 and 150 homologs, yet the LOF of CAPN5 was tolerated as opposed to gain‐of‐function disease‐causing variants. These results indicate that localized inhibition of CAPN5 is a viable strategy for hyperactivating disease alleles.     

Single‐nucleotide editing: From principle,optimization to application

Cytosine base editors (CBEs) and adenine base editors (ABEs), which are generally composed of an engineered deaminase and a catalytically impaired CRISPR‐Cas9 variant, are new favorite tools for single base substitution in cells and organisms. In this review, we summarize the principle of base‐editing systems and elaborate on the evolution of different platforms of CBEs and ABEs, including their deaminase, Cas9 variants, and editing outcomes. Moreover, we highlight their applications in mouse and human cells and discuss the challenges and prospects of base editors. The ABE‐ and CBE systems have been used in gene silencing, pathogenic gene correction, and functional genetic screening. Single base editing is becoming a new promising genetic tool in biomedical research and gene therapy.