One in every 3 patients admitted to the PICUs requires ventilatory support. The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%.
Rheumatoid arthritis (RA) is a debilitating autoimmune disease with grave physical, emotional and socioeconomic consequences. Despite advances in targeted biologic and pharmacologic interventions that have recently come to market, many patients with RA continue to have inadequate response to therapies, or intolerable side effects, with resultant progression of their disease. In this review, we detail multiple biomolecular pathways involved in RA disease pathogenesis to elucidate and highlight pathways that have been therapeutic targets in managing this systemic autoimmune disease. Here we present an up-to-date accounting of both emerging and approved pharmacological treatments for RA, detailing their discovery, mechanisms of action, efficacy, and limitations. Finally, we turn to the emerging fields of bioengineering and cell therapy to illuminate possible future targeted therapeutic options that combine material and biological sciences for localized therapeutic action with the potential to greatly reduce side effects seen in systemically applied treatment modalities.
Structural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength. Here, using two-photon glutamate uncaging to induce plasticity at individual dendritic spines on hippocampal CA1 neurons from mice and rats of both sexes, we demonstrate that p38 MAPK is generally required downstream of non-ionotropic NMDAR signaling to drive both spine shrinkage and LTD. In a series of pharmacological and molecular genetic experiments, we identify key components of the non-ionotropic NMDAR signaling pathway driving dendritic spine shrinkage, including the interaction between NOS1AP (nitric oxide synthase 1 adaptor protein) and neuronal nitric oxide synthase (nNOS), nNOS enzymatic activity, activation of MK2 (MAPK-activated protein kinase 2) and cofilin, and signaling through CaMKII. Our results represent a large step forward in delineating the molecular mechanisms of non-ionotropic NMDAR signaling that can drive shrinkage and elimination of dendritic spines during synaptic plasticity.
In the season of acute lower respiratory infections, one of every two children admitted to pediatric intensive care units requires mechanical ventilation. Acute respiratory failure was the most common reason for mechanical ventilation. The spontaneous breathing trial was the most commonly used method for liberation from mechanical ventilation.
The key messages of these guidelines on chronic kidney disease are: Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. CKD is a common condition, its prevalence being about 10%, and is treatable if it is detected on time. A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. The CKD risk groups are individuals with diabetes, hypertension and a family history of renal disease. The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. Therapy must emphasize the maximal reduction of cardiovascular risk. The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes.
DC reduces ICP in pediatric patients with traumatic brain injury. The mortality rate is low and long-term prognosis in survivors is good. Complications related to surgery are frequent. Wide craniectomy with duraplasty seems to be the most common technique. Defining the most appropriate indications and timing for DC in pediatric patients should be the objective of future prospective studies.
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