Dysbiotic Bacterial and Fungal Communities Not Restricted to Clinically Affected Skin Sites in Dandruff.

Dandruff is a prevalent chronic inflammatory skin condition of the scalp that has been associated with Malassezia yeasts. However, the microbial role has not been elucidated yet, and the etiology of the disorder remains poorly understood. Using high-throughput 16S rDNA and ITS1 sequencing, we characterized cutaneous bacterial and fungal microbiotas from healthy and dandruff subjects, comparing scalp and forehead (lesional and non-lesional skin sites). Bacterial and fungal communities from dandruff analyzed at genus level differed in comparison with healthy ones, presenting higher diversity and greater intragroup variation. The microbial shift was observed also in non-lesional sites from dandruff subjects, suggesting that dandruff is related to a systemic process that is not restricted to the site exhibiting clinical symptoms. In contrast, Malassezia microbiota analyzed at species level did not differ according to health status. A 2-step OTU assignment using combined databases substantially increased fungal assigned sequences, and revealed the presence of highly prevalent uncharacterized Malassezia organisms (>37% of the reads). Although clinical symptoms of dandruff manifest locally, microbial dysbiosis beyond clinically affected skin sites suggests that subjects undergo systemic alterations, which could be considered for redefining therapeutic approaches.

Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants.

Sequence alterations in the pendrin gene (SLC26A4) leading to functionally affected protein variants are frequently involved in the pathogenesis of syndromic and nonsyndromic deafness. Considering the high number of SLC26A4 sequence alterations reported to date, discriminating between functionally affected and unaffected pendrin protein variants is essential in contributing to determine the genetic cause of deafness in a given patient. In addition, identifying molecular features common to the functionally affected protein variants can be extremely useful to design future molecule-directed therapeutic approaches. Here we show the functional and molecular characterization of six previously uncharacterized pendrin protein variants found in a cohort of 58 Brazilian deaf patients. Two variants (p.T193I and p.L445W) were undetectable in the plasma membrane, completely retained in the endoplasmic reticulum and showed no transport function; four (p.P142L, p.G149R, p.C282Y and p.Q413R) showed reduced function and significant, although heterogeneous, expression levels in the plasma membrane. Importantly, total expression levels of all of the functionally affected protein variants were significantly reduced with respect to the wild-type and a fully functional variant (p.R776C), regardless of their subcellular localization. Interestingly, reduction of expression may also reduce the transport activity of variants with an intrinsic gain of function (p.Q413R). As reduction of overall cellular abundance was identified as a common molecular feature of pendrin variants with affected function, the identification of strategies to prevent reduction in expression levels may represent a crucial step of potential future therapeutic interventions aimed at restoring the transport activity of dysfunctional pendrin variants.

Newborn hearing screening and genetic testing in 8974 Brazilian neonates.

OBJECTIVE: An early diagnosis has been a priority in the audiological practice. Identifying hearing loss until 3 months old through Universal Newborn Hearing Screening and intervention before 6 months old, minimize the impact of auditory loss in the health and communication development of these children. However, in the clinical practice, despite the help of the risk indicators in the audiological and etiological diagnosis, the integrated services have come up against the challenge of determining the causes of auditory loss, bearing in mind that approximately 50% of the subjects who have congenital loss do not show risk factors in their clinical history. The current research aims introduce together etiologic and audiological diagnosis of newborns. METHODS: We eluted dried blood spots from paper and performed genetic testing for 35delG mutation in 8974 newborns that were also screened for transient otoacoustic emissions (TOAE). In addition, the A1555G and A827G mutations in the MTRNR1 mitochondrial gene were screened in all newborns. RESULTS: We have found 17 individuals who failed in TOAE. Among them, we detected 4 homozygous newborns for 35delG mutation and 3 individuals with A827G mutation in the MTRNR1 mitochondrial gene. The frequency of 35delG carriers was 0.94% [84/8974]. In all 17 individuals who failed in OAE no other mutation besides those mentioned above was found. CONCLUSIONS: The results greatly contribute to the public health area indicating the etiologic diagnosis, allowing family counseling as well as the early rehabilitation treatment or surgical intervention. Over time that will help to reduce the costs of rehabilitation considerably.