scholarly journals Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178753 ◽  
Author(s):  
Susanne C. Beck ◽  
Yuxi Feng ◽  
Vithiyanjali Sothilingam ◽  
Marina Garcia Garrido ◽  
Naoyuki Tanimoto ◽  
...  
Author(s):  
Brennan J. Sullivan ◽  
Pavel A. Kipnis ◽  
Brandon M. Carter ◽  
Shilpa D. Kadam

AbstractNeonatal seizures pose a clinical challenge for their early detection, acute management, and mitigation of long-term comorbidities. A major cause of neonatal seizures is hypoxic-ischemic encephalopathy that results in seizures that are frequently refractory to the first-line anti-seizure medication phenobarbital (PB). One proposed mechanism for PB-inefficacy during neonatal seizures is the reduced expression and function of the neuron-specific K+/Cl− cotransporter 2 (KCC2), the main neuronal Cl− extruder that maintains chloride homeostasis and influences the efficacy of GABAergic inhibition. To determine if PB-refractoriness after ischemic neonatal seizures is dependent upon KCC2 hypofunction and can be rescued by KCC2 functional enhancement, we investigated the recently developed KCC2 functional enhancer CLP290 in a CD-1 mouse model of refractory ischemic neonatal seizures quantified with vEEG. We report that acute CLP290 intervention can rescue PB-resistance, KCC2 expression, and the development of epileptogenesis after ischemic neonatal seizures. KCC2 phosphorylation sites have a strong influence over KCC2 activity and seizure susceptibility in adult experimental epilepsy models. Therefore, we investigated seizure susceptibility in two different knock-in mice in which either phosphorylation of S940 or T906/T1007 was prevented. We report that KCC2 phosphorylation regulates both neonatal seizure susceptibility and CLP290-mediated KCC2 functional enhancement. Our results validate KCC2 as a clinically relevant target for refractory neonatal seizures and provide insights for future KCC2 drug development.


2009 ◽  
Vol 158 (6) ◽  
pp. 1503-1512 ◽  
Author(s):  
HH Clarice Yang ◽  
Jong Moo Kim ◽  
Elliott Chum ◽  
Cornelis van Breemen ◽  
Ada WY Chung

Hand ◽  
2021 ◽  
pp. 155894472110527
Author(s):  
Vinay Rao ◽  
William B. Ericson Jr

Pediatric trigger thumbs present a conundrum for hand surgeons. Surgery for trigger thumbs has inherent risks, such as infection, nerve injury, and the risks of anesthesia, but will reliably solve the problem. But is surgical intervention necessary? Would these cases resolve spontaneously, eventually, without intervention? If not, what are the long-term consequences of the inability to fully extend the thumb interphalangeal joint? We present a pediatric trigger thumb that was symptomatic for 22 years, with complete resolution of symptoms after surgical intervention. This report illustrates at least some pediatric trigger thumbs will not resolve without surgical intervention, but treatment, even after 21 years, can result in normal thumb motion and function.


2015 ◽  
Vol 23 (2) ◽  
pp. 47-59 ◽  
Author(s):  
Nadine Langguth ◽  
Tanja Könen ◽  
Simone Matulis ◽  
Regina Steil ◽  
Caterina Gawrilow ◽  
...  

During adolescence, physical activity (PA) decreases with potentially serious, long-term consequences for physical and mental health. Although barriers have been identified as an important PA correlate in adults, research on adolescents’ PA barriers is lacking. Thus reliable, valid scales to measure adolescents’ PA barriers are needed. We present two studies describing a broad range of PA barriers relevant to adolescents with a multidimensional approach. In Study 1, 124 adolescents (age range = 12 – 24 years) reported their most important PA barriers. Two independent coders categorized those barriers. The most frequent PA barriers were incorporated in a multidimensional questionnaire. In Study 2, 598 adolescents (age range = 13 – 21 years) completed this questionnaire and reported their current PA, intention, self-efficacy, and negative outcome expectations. Seven PA barrier dimensions (leisure activities, lack of motivation, screen-based sedentary behavior, depressed mood, physical health, school workload, and preconditions) were confirmed in factor analyses. A multidimensional approach to measuring PA barriers in adolescents is reliable and valid. The current studies provide the basis for developing individually tailored interventions to increase PA in adolescents.


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