Blimp-1/PRDM1 and Hr3/RORß specify the blue-sensitive photoreceptor subtype in Drosophila by repressing the hippo pathway.

During terminal differentiation of the mammalian retina, transcription factors control binary cell fate decisions that generate functionally distinct subtypes of photoreceptor neurons. For instance, Otx2 and RORß activate the expression of the transcriptional repressor Blimp-1/PRDM1 that represses bipolar interneuron fate and promotes rod photoreceptor fate. Moreover, Otx2 and Crx promote expression of the nuclear receptor Nrl that promotes rod photoreceptor fate and represses cone photoreceptor fate. Mutations in these four transcription factors cause severe eye diseases such as retinitis pigmentosa. Here, we show that a post-mitotic binary fate decision in Drosophila color photoreceptor subtype specification requires ecdysone signaling and involves orthologs of these transcription factors: Drosophila Blimp-1/PRDM1 and Hr3/RORß promote blue-sensitive (Rh5) photoreceptor fate and repress green-sensitive (Rh6) photoreceptor fate through the transcriptional repression of warts/LATS, the nexus of the phylogenetically conserved Hippo tumor suppressor pathway. Moreover, we identify a novel interaction between Blimp-1 and warts, whereby Blimp-1 represses a warts intronic enhancer in blue-sensitive photoreceptors and thereby gives rise to specific expression of warts in green-sensitive photoreceptors. Together, these results reveal that conserved transcriptional regulators play key roles in terminal cell fate decisions in both the Drosophila and the mammalian retina, and the mechanistic insights further deepen our understanding of how Hippo pathway signaling is repurposed to control photoreceptor fates for Drosophila color vision.

Difficult airway consultation service for children: steps to implement and preliminary results.

BACKGROUND: Failed airway management remains one of the most common causes of cardiopulmonary arrest in the pediatric population. Practice guidelines addressing the difficult airway (DAW) in adults provide anesthesiologists a framework for managing the airway during the perioperative period; however, similar consensus guidelines are lacking in the pediatric population. Many of the adverse events associated with difficult pediatric airway management occur outside the perioperative setting and often result in worse outcomes. The lower frequency of DAW management required in children, lesser awareness of pediatric health care professionals about DAW management, and the need for guiding principles led us to develop a DAW consultative service. This report outlines the steps to establish the Difficult Airway Service (DAS) and the initial experiences with this new consultation service. METHODS: The mission of the DAS is to identify children with known or anticipated DAWs, communicate the diagnosis and collaborate with referring medical and surgical services, and to manage children in those settings that airway management might be required in the context of the patient's ongoing medical care. RESULTS: The initial 3-month experience confirmed that a majority of pediatric DAW events are associated with congenital or acquired abnormalities. Through appropriate consultation and leadership, the DAS was able to physically and electronically identify pediatric patients with a DAW and provide management. Hospital-wide participation was instrumental in the success and exponential growth of DAS: planned preoperative tracheostomy in complicated posterior spinal fusion candidates, participation in EXIT procedures, standardization of airway carts, and implementation of education forums. CONCLUSION: In developing the DAS, our goal was to provide a more comprehensive approach to caring for a child with a DAW that included their entire hospital stay and follow-up care. We believe this approach has improved health care professional awareness as well as the safe management of routine and difficult pediatric airway. Additional studies are needed to determine whether measurable changes in morbidity and mortality are observed over time.

The relationship of alexithymia to emotional dysregulation within an alcohol dependent treatment sample.

Difficulties regulating emotions have implications for the development, maintenance, and recovery from alcohol problems. One construct thought to impede the regulation of emotion is alexithymia. Alexithymia is characterized by difficulties identifying, differentiating and expressing feelings, a limited imagination and fantasy life, and an externally-oriented thinking style (e.g., prefer talking about daily activities rather than feelings). Given that poor emotion regulation skills have been found to predict posttreatment levels of alcohol use, and that several defining characteristics of alexithymia bear similarity to deficits in emotion regulation skills, it is possible that alexithymia may predict poorer alcohol treatment outcomes. Thus, the present study first examined the relationship of alexithymia to several other emotion regulation measures and then investigated the impact of alexithymia on attrition and alcohol treatment outcomes in men and women (N=77) enrolled in a 12-week cognitive-behavioral intervention for alcohol dependence. At baseline, higher scores on alexithymia were associated poorer emotion regulation skills, fewer percent days abstinent, greater alcohol dependence severity, and several high-risk drinking situations. Alexithymia was unrelated to attrition and to level of alcohol consumption at posttreatment. Overall, the construct of alexithymia is shown to be related to several theoretically-related constructs (e.g., emotion regulation, mindfulness) but demonstrated a limited relationship to drinking outcomes in those seeking treatment for alcohol dependence.