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Glomerular disease: looking beyond pathology.

ABSTRACT: The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease.

SUBMITTER: Wiggins RC

PROVIDER: S-EPMC4046719 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Glomerular disease: looking beyond pathology.

Wiggins Roger C RC Alpers Charles E CE Holzman Lawrence B LB He John C JC Salant David J DJ Chugh Sumant S SS Natarajan Rama R Trachtman Howard H Brasile Lauren L Star Robert A RA Rys-Sikora Krystyna E KE Moxey-Mims Marva M MM Flessner Michael F MF

Clinical journal of the American Society of Nephrology : CJASN 20140403 6

The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic scienc ...[more]

PMID: 24700796

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Project description:Pantomime has a long tradition in clinical neuropsychology of apraxia. It has been much more used by researchers and clinicians to assess tool-use disorders than real tool use. Nevertheless, it remains incompletely understood and has given rise to controversies, such as the involvement of the left inferior parietal lobe or the nature of the underlying cognitive processes. The present article offers a comprehensive framework, with the aim of specifying the neural and cognitive bases of pantomime. To do so, we conducted a series of meta-analyses of brain-lesion, neuroimaging and behavioural studies about pantomime and other related tasks (i.e. real tool use, imitation of meaningless postures and semantic knowledge). The first key finding is that the area PF (Area PF complex) within the left inferior parietal lobe is crucially involved in both pantomime and real tool use as well as in the kinematics component of pantomime. The second key finding is the absence of a well-defined neural substrate for the posture component of pantomime (both grip errors and body-part-as-tool responses). The third key finding is the role played by the intraparietal sulcus in both pantomime and imitation of meaningless postures. The fourth key finding is that the left angular gyrus seems to be critical in the production of motor actions directed towards the body. The fifth key finding is that performance on pantomime is strongly correlated with the severity of semantic deficits. Taken together, these findings invite us to offer a neurocognitive model of pantomime, which provides an integrated alternative to the two hypotheses that dominate the field: The gesture-engram hypothesis and the communicative hypothesis. More specifically, this model assumes that technical reasoning (notably the left area PF), the motor-control system (notably the intraparietal sulcus), body structural description (notably the left angular gyrus), semantic knowledge (notably the polar temporal lobes) and potentially theory of mind (notably the middle prefrontal cortex) work in concert to produce pantomime. The original features of this model open new avenues for understanding the neurocognitive bases of pantomime, emphasizing that pantomime is a communicative task that nevertheless originates in specific tool-use (not motor-related) cognitive processes. <Please insert Graphical abstract here>.

Project description:Key pointsPeak oxygen uptake, a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD), with mounting evidence supporting an important role for peripheral dysfunction, particularly within skeletal muscle. In patients with severe COPD and activity-matched controls, muscle oxygen transport and utilization were assessed at peak effort during single-leg knee-extensor exercise (KE), where ventilation is assumed to be submaximal. This strategy removes ventilation as the major constraint to exercise capacity in COPD, allowing maximal muscle function to be attained and evaluated. During maximal KE, both convective arterial oxygen delivery to the skeletal muscle microvasculature and subsequent diffusive oxygen delivery to the mitochondria were diminished in patients with COPD compared to control subjects. These findings emphasize the importance of factors, beyond the lungs, that influence exercise capacity in this patient population and may, ultimately, influence the prognosis, mortality and quality of life for patients with COPD.AbstractPeak oxygen uptake ( V?O2peak ), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminished V?O2peak with COPD. However, the peripheral determinants of V?O2peak have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle convective and diffusive oxygen (O2 ) transport, and therefore skeletal muscle peak O2 uptake ( V?MO2peak ), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O2 transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV1 ) ± SEM = 0.9 ± 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l min-1 , P < 0.05) and muscle diffusive O2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml min-1 mmHg-1 , P < 0.05) were ?1/3 lower in patients with COPD than controls, resulting in an attenuated V?MO2peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l min-1 , P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants of V?MO2peak , at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.

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Glomerular disease: looking beyond pathology.

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Glomerular disease: looking beyond pathology.

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