Generation of the induced pluripotent stem cell line IOCVi001-A from a patient with the MFRP-related retinitis pigmentosa-nanophthalmos syndrome.

Retinitis pigmentosa (RP) is the most common retinal degeneration in humans and is characterized by the progressive degeneration of rods and cones and retinal pigment epithelium. We generated the IOCVi001-A induced pluripotent stem cell (iPSC) line from dermal fibroblast of a patient with a homozygous c.498_499insC (p.(Asn167Glnfs⁎34) variant in the Membrane-type frizzled related protein (MFRP) gene, a genetic defect causing a syndrome characterized by RP and small eye size (nanophthalmos). IOCVi001-A displayed normal stemness, expressed pluripotent stem cell markers and displayed a normal karyotype. This iPSC line can be used for in vitro disease modeling for complex forms of RP.

Identification of Genetic Variants for Diabetic Retinopathy Risk Applying Exome Sequencing in Extreme Phenotypes.

Background: Diabetic retinopathy (DR) risk has been shown to vary depending on ethnic backgrounds, and thus, it is worthy that underrepresented populations are analyzed for the potential identification of DR-associated genetic variants. We conducted a case-control study for the identification of DR-risk variants in Mexican population. Methods: We ascertained 60 type 2 diabetes mellitus (T2DM) patients. Cases (n = 30) were patients with advanced proliferative DR (PDR) with less than 15 years after a T2DM diagnosis while controls (n = 30) were patients with no DR 15 years after the diagnosis of T2DM. Exome sequencing was performed in all patients, and the frequency of rare variants was compared. In addition, the frequency of variants occurring in a set of 169 DR-associated genes were compared. Results: Statistically significant differences were identified for rare missense and splice variants and for rare splice variants occurring more than once in either group. A strong statistical difference was observed when the number of rare missense variants with an aggregated prediction of pathogenicity and occurring more than once in either group was compared (p = 0.0035). Moreover, 8 variants identified more than once in either group, occurring in previously identified DR-associated genes were recognized. The p.Pro234Ser KIR2DS4 variant showed a strong protective effect (OR = 0.04 [0.001-0.36]; p = 0.04). Conclusions: Our study showed an enrichment of rare splice acceptor/donor variants in patients with PDR and identified a potential protective variant in KIR2DS4. Although statistical significance was not reached, our results support the replication of 8 previously identified DR-associated genes.

Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma.

SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss-of-function variants in SOX2 are identified in approximately 40% of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation-positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. In this report we describe six new cases, four of which carry novel pathogenic SOX2 variants. Four cases presented with bilateral anophthalmia in addition to extraocular involvement. Another individual presented with only unilateral anophthalmia. One individual did not have any eye findings but presented with a suprasellar teratoma in infancy and was found to have the recurrent c.70del20 mutation in SOX2 (c.70_89del, p.Asn24Argfs*65). This is this first time this tumor type has been reported in the context of a de novo SOX2 mutation. Notably, individuals with hypothalamic hamartomas and slow-growing hypothalamo-pituitary tumors have been reported previously, but it is still unclear how SOX2 loss contributes to their formation.

Respuestas humanas del profesional de enfermería ante la contaminación acústica / Human responses of the nursing professional to acoustic contamination

El ruido es considerado uno de los principales contaminantes ambientales, su estudio no se ha desarrollado con profundidad en el ámbito de enfermería, hay evidencia científica que demuestra cambios fisiopatológicos y comportamentales en los individuos que están expuestos durante un tiempo prolongado; predisponiendo cambios en su vida cotidiana. El profesional de enfermería no es la excepción, el desarrollo de sus actividades se ejerce en un ambiente de ruido continuo, por lo que es de interés analizar que respuestas humanas genera en el profesional de enfermería, de un hospital de segundo nivel de atención. Se trata de un estudio observacional, descriptivo y transversal, en el que buscó identificar las respuestas humanas del profesional de enfermería ante la contaminación acústica. La población se conformó por 35 profesionales de enfermería. Se aplicó el test confort auditivo de María Gómez-Cano Alfaro del Instituto Nacional de Seguridad e Higiene en el Trabajo (RD286/ 2006); tiene una composición mixta de 36 ítems divididos en seis dimensiones. Las variables sociodemográficas demostraron clínica y estadísticamente significancia, por lo que son un factor de riesgo para en la presencia de respuestas humanas (molestia, ansiedad, angustia y estrés) (RM=3.500, IC.95% .372-32.978; p>0.250). El ambiente laboral donde se desenvuelven los profesionales de enfermería analizados, determinó que la contaminación acústica a la que se exponen aumenta significativamente con relación al ruido de interferencia y, en menor grado, con el ruido propio de la atmósfera laboral, lo que se tradujo en la presencia de respuestas humanas negativas como el estrés y el enojo *p< (0.015). Por lo consiguiente el ruido es un factor generador de respuestas humanas negativas, en el profesional de enfermería, cuando es sometido por un periodo prolongado generándole molestia, estrés, ansiedad y enojo, pudiendo ser este un factor de distracción durante la jornada laboral. Palabras claves: respuestas humanas, profesional de enfermería, contaminación acústica y ruido.

In-office bleaching with a two- and seven-day intervals between clinical sessions: A randomized clinical trial on tooth sensitivity.

OBJECTIVES: In-office bleaching is usually performed in 2-3 sessions with one-week interval. The impact of shorter interval times on tooth sensitivity has not been evaluated. This study aimed to compare the absolute risk of tooth sensitivity (TS) and colour change after in-office bleaching with a two- and seven-day intervals between sessions. METHODS: We selected for this randomized, single-blind study, 40 patients with colour C2 or darker. We performed two bleaching sessions with a 35% hydrogen peroxide gel with either a 1-week or 2-day interval. We recorded the TS up to 48 h with a VAS scale and the colour at baseline and 30 days after bleaching with a value-oriented shade guide and a spectrophotometer. The risk and intensity of TS were compared with the Fisher's exact test and two-way repeated measures ANOVA. Colour change (ΔSGU and ΔE) were evaluated by Student's t-test (alpha=5%). RESULTS: Approximately 60% of the participants reported TS (65% and 55% for the 7 and 2-day groups). A significant whitening of approximately 6 shade guide units was detected for both groups. No difference was detected between groups. CONCLUSIONS: The reduction of the interval between bleaching sessions from seven to two days reduced the treatment time without increasing the bleaching-induced TS (clinicaltrials.gov identifier: NCT1959789). CLINICAL SIGNIFICANCE: In-office bleaching with a 2-day interval did not increase the risk and intensity of bleaching-induced tooth sensitivity.