Activity

Cerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, depending upon the anatomic location, can be surgically removed, there is currently no pharmaceutical therapy to treat CCMs. Several mouse models have been developed to better understand CCM pathogenesis and test therapeutics. The most common mouse models induce a large CCM burden that is anatomically restricted to the cerebellum and contributes to lethality in the early days of life. These inducible models thus have a relatively short period for drug administration. We developed an inducible CCM3 mouse model that develops CCMs after weaning and provides a longer period for potential therapeutic intervention. Using this new model, three recently proposed CCM therapies, fasudil, tempol, vitamin D3, and a combination of the three drugs, failed to substantially reduce CCM formation when treatment was administered for 5 weeks, from postnatal day 21 (P21) to P56. We next restricted Ccm3 deletion to the brain vasculature and provided greater time (121 days) for CCMs to develop chronic hemorrhage, recapitulating the human lesions. We also developed the first model of acute CCM hemorrhage by injecting mice harboring CCMs with lipopolysaccharide. These efficient models will enable future drug studies to more precisely target clinically relevant features of CCM disease CCM formation, chronic hemorrhage, and acute hemorrhage.Following intrathecal injection of fluorescent tracers, ex vivo imaging of brain vibratome slices has been widely used to study the glymphatic system in the rodent brain. Tracer penetration into the brain is usually quantified by image-processing, even though this approach requires much time and manual operation. Here, we illustrate a simple protocol for the quantitative determination of glymphatic activity using spectrophotofluorometry. At specific time-points following intracisternal or intrastriatal injection of fluorescent tracers, certain brain regions and the spinal cord were harvested and tracers were extracted from the tissue. The intensity of tracers was analyzed spectrophotometrically and their concentrations were quantified from standard curves. Using this approach, the regional and dynamic delivery of subarachnoid CSF tracers into the brain parenchyma was assessed, and the clearance of tracers from the brain was also determined. Furthermore, the impairment of glymphatic influx in the brains of old mice was confirmed using our approach. Our method is more accurate and efficient than the imaging approach in terms of the quantitative determination of glymphatic activity, and this will be useful in preclinical studies.There are an increasing number of children who are dependent on medical technology to sustain their lives. Although significant research on this issue is taking place, the terminology used is variable and the concept of technology dependence is ill-defined. A systematic concept analysis was conducted examining the attributes, antecedents, and consequences of the concept of technology dependent, as portrayed in the literature. We found that this concept refers to a wide range of clinical technology to support biological functioning across a dependency continuum, for a range of clinical conditions. It is commonly initiated within a complex biopsychosocial context and has wide ranging sequelae for the child and family, and health and social care delivery.Conclusion The term technology dependent is increasingly redundant. Selleckchem Resatorvid It objectifies a heterogenous group of children who are assisted by a myriad of technology and who adapt to, and function with, this assistance in numerous ways. What is Known • There are an increasing number of children who require medical technology to sustain their life, commonly referred to as technology dependent. This concept analysis critically analyses the relevance of the term technology dependent which is in use for over 30 years. What is New • Technology dependency refers to a wide range of clinical technology to support biological functioning across a dependency continuum, for a range of clinical conditions. It is commonly initiated within a complex biopsychosocial context and has wide-ranging sequelae for the child and family, and health and social care delivery. • The paper shows that the term technology dependent is generally portrayed in the literature in a problem-focused manner. • This term is increasingly redundant and does not serve the heterogenous group of children who are assisted by a myriad of technology and who adapt to, and function with, this assistance in numerous ways. More appropriate child-centred terminology will be determined within the TechChild project.This study aimed to investigate whether using lung ultrasound (LUS) scores in premature newborns with respiratory distress syndrome (RDS) allows for earlier surfactant therapy (within the first 3 h of life) than using FiO2 criteria. This was a randomised, non-blinded clinical trial conducted in a neonatal intensive care unit. The inclusion criteria were newborns with a gestational age of ≤ 32 weeks and RDS. Patients meeting the inclusion criteria were randomly assigned to two groups the ultrasound group, administered surfactant based on LUS score and/or FiO2 threshold, and the control group, guided by FiO2 only. Fifty-six patients were included. The ultrasound group received surfactant earlier (1 h of life vs. 6 h, p less then 0.001), with lower FiO2 (25% vs. 30%, p = 0.016) and lower CO2 (48 vs. 54, p = 0.011). After surfactant treatment, newborns in the ultrasound group presented a greater SpO2 (p = 0.001) and SpO2/FiO2 ratio (p = 0.012).Conclusions LUS score allowed an earlier surfactant therapy, reduced oxygen exposure early in life and a better oxygenation after the treatment. This early surfactant replacement may lead to reduced oxygen exposure. What is Known • Lung ultrasound scores predict the need for surfactant therapy in premature newborns. What is New • This study shows that using lung ultrasound scores improves the timeliness of surfactant replacement compared with using FiO2 alone.