Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1

Our previous studies have shown that microRNA-383 (miR-383) expression is downregulated in the testes of infertile men with maturation arrest (MA). However, the underlying mechanisms of miR-383 involved in the pathogenesis of MA remain unknown. In this study, we showed that downregulation of miR-383 was associated with hyperactive proliferation of germ cells in patients with mixed patterns of MA. Overexpression of miR-383 in NT2 (testicular embryonal carcinoma) cells resulted in suppression of proliferation, G1-phase arrest and induction of apoptosis, whereas silencing of miR-383 reversed these effects. The effects of miR-383 were mediated through targeting a tumor suppressor, interferon regulatory factor-1 (IRF1), and miR-383 was negatively correlated with IRF1 protein expression in vivo. miR-383 inhibited IRF1 by affecting its mRNA stability, which subsequently reduced the levels of the targets of IRF1, namely cyclin D1, CDK2 and p21. Downregulation of IRF1 or cyclin D1, but not that of CDK2, enhanced miR-383-mediated effects, whereas silencing of p21 partially inhibited the effects of miR-383. Moreover, miR-383 downregulated CDK4 by increasing proteasome-dependent degradation of CDK4, which in turn resulted in an inhibition of phosphorylated retinoblastoma protein (pRb) phosphorylation. These results suggest that miR-383 functions as a negative regulator of proliferation by targeting IRF1, in part, through inactivation of the pRb pathway. Abnormal testicular miR-383 expression may potentiate the connections between male infertility and testicular germ cell tumor

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Life after Tracheostomy: Patient and Family Perspectives on Teaching, Transitions, and Multidisciplinary Teams.

OBJECTIVE: To report patient/family experiences and outcomes after tracheostomy STUDY DESIGN: International survey of patients and families with tracheostomy. SETTING: Collaboration of the Patient Safety and Quality Improvement Committee of the American Academy of Otolaryngology-Head and Neck Surgery and the Global Tracheostomy Collaborative. METHODS: A 50-item survey was developed with multistakeholder collaboration. The survey was disseminated via international social networks used by patients with a tracheostomy and their families. Qualitative and quantitative data were analyzed. RESULTS: Of 220 respondents, 90% cared for a pediatric patient with a tracheostomy. Only 48% of respondents felt very prepared at time of discharge, and 11% did not receive emergency preparedness training prior to discharge. Home nursing needs were inadequately met in 17% of families, with resulting difficulties shortly after discharge; 14% sought emergent care within 1 week of discharge. Nearly half of respondents indicated a desire to have met with a patient with a tracheostomy prior to surgery but were not offered that opportunity. Fragmented care or limited teamwork was reported by 32% of respondents, whereas tracheotomy care was described as integrated or maximally integrated for 67%. CONCLUSION: While many families report satisfaction with tracheostomy care, opportunities remain for improving care. This study highlights the importance of teaching, teamwork, and smoothing transition from the hospital. Potential quality improvement areas include standardizing tracheostomy teaching for routine and emergency needs and optimizing postdischarge support and coordination. Prior to surgery, connecting families to people with a tracheostomy may also be beneficial