Synchronizing pharmacotherapy in acne with review of clinical care

Acne is a chronic inflammatory skin disease that involves the pathogenesis of four major factors, such as androgen-induced increased sebum secretion, altered keratinization, colonization of Propionibacterium acnes, and inflammation. Several acne mono-treatment and combination treatment regimens are available and prescribed in the Indian market, ranging from retinoids, benzoyl peroxide (BPO), anti-infectives, and other miscellaneous agents. Although standard guidelines and recommendations overview the management of mild, moderate, and severe acne, relevance and positioning of each category of pharmacotherapy available in Indian market are still unexplained. The present article discusses the available topical and oral acne therapies and the challenges associated with the overall management of acne in India and suggestions and recommendations by the Indian dermatologists. The experts opined that among topical therapies, the combination therapies are preferred over monotherapy due to associated lower efficacy, poor tolerability, safety issues, adverse effects, and emerging bacterial resistance. Retinoids are preferred in comedonal acne and as maintenance therapy. In case of poor response, combination therapies BPO-retinoid or retinoid-antibacterials in papulopustular acne and retinoid-BPO or BPO-antibacterials in pustular-nodular acne are recommended. Oral agents are generally recommended for severe acne. Low-dose retinoids are economical and have better patient acceptance. Antibiotics should be prescribed till the inflammation is clinically visible. Antiandrogen therapy should be given to women with high androgen levels and are added to regimen to regularize the menstrual cycle. In late-onset hyperandrogenism, oral corticosteroids should be used. The experts recommended that an early initiation of therapy is directly proportional to effective therapeutic outcomes and prevent complications

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome 2 . We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2 's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals. </p