Science translational medicine
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Randomized Controlled Trial
Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke.
Anodal transcranial direct current stimulation (tDCS) can boost the effects of motor training and facilitate plasticity in the healthy human brain. Motor rehabilitation depends on learning and plasticity, and motor learning can occur after stroke. We tested whether brain stimulation using anodal tDCS added to motor training could improve rehabilitation outcomes in patients after stroke. ⋯ Functional magnetic resonance imaging (MRI) showed increased activity during movement of the affected hand in the ipsilesional motor and premotor cortex in the anodal tDCS group compared to the sham treatment group. Structural MRI revealed intervention-related increases in gray matter volume in cortical areas, including ipsilesional motor and premotor cortex after anodal tDCS but not sham treatment. The addition of ipsilesional anodal tDCS to a 9-day motor training program improved long-term clinical outcomes relative to sham treatment in patients after stroke.
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Revitalizing the Oslerian ideal of the clinician-scientist-teacher may help in the training of the next generation of translational researchers.
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Blast exposure can cause mild traumatic brain injury (TBI) in mice and other mammals. However, there are important gaps in our understanding of the neuropathology underlying repetitive blast exposure in animal models compared to the neuroimaging abnormalities observed in blast-exposed veterans. Moreover, how an increase in the number of blast exposures affects neuroimaging endpoints in blast-exposed humans is not well understood. ⋯ Blast exposure caused reactive gliosis in mouse cerebellum, particularly in the deep cerebellar nuclei. Diffusion tensor imaging tractography of the cerebellum of blast-exposed veterans revealed that mean diffusivity correlated negatively with the number of blast-related mild TBIs. Together, these results argue that the cerebellum is vulnerable to repetitive mild TBI in both mice and humans.
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Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. ⋯ A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies.
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Sepsis is a leading cause of death in the United States, with mortality highest among patients who develop septic shock. Early aggressive treatment decreases morbidity and mortality. Although automated screening tools can detect patients currently experiencing severe sepsis and septic shock, none predict those at greatest risk of developing shock. ⋯ In comparison, the Modified Early Warning Score, which has been used clinically for septic shock prediction, achieved a lower AUC of 0.73 (95% CI, 0.71 to 0.76). A routine screening protocol based on the presence of two of the systemic inflammatory response syndrome criteria, suspicion of infection, and either hypotension or hyperlactatemia achieved a lower sensitivity of 0.74 at a comparable specificity of 0.64. Continuous sampling of data from the electronic health records and calculation of TREWScore may allow clinicians to identify patients at risk for septic shock and provide earlier interventions that would prevent or mitigate the associated morbidity and mortality.