Citations

We used whole‐exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in‐silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole‐brain analysis and meta‐analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next‐generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. Ann Neurol 2015;77:547–552

The ability of oral antibiotic treatment to control diabetic diarrhea was documented by a double-blind study involving a patient with this condition. When the patient was given Mysteclin-F, the diarrhea subsided promptly, only to recur when a placebo was substituted,. The erratic behavior of diabetic diarrhea is indicated, however, by the fact that a remission eventually occurred, and no further treatment was required. Although not all patients with diabetic diarrhea respond to antibiotic treatment, its trial merits consideration forthose patients who are refractory to the simpler forms of treatment.

Background The Carotid Revascularization Endarterectomy Versus Stenting Trial ( CREST ) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors. Methods and Results Management was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low‐density lipoprotein, cholesterol <100 mg/dL, systolic blood pressure <140 mm Hg, fasting blood glucose <126 mg/dL, and nonsmoking status. Optimal control was defined as achieving all 4 goals concurrently. Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow‐up visits for up to 48 months. In the analysis cohort of 2210, significant improvements in risk‐factor control were observed across risk factors for all follow‐up visits compared with baseline. At 48 months, achievement of the low‐density lipoprotein cholesterol goal improved from 59.1% to 73.6% ( P <0.001), achievement of the systolic blood pressure goal improved from 51.6% to 65.1% ( P <0.001), achievement of the glucose goal improved from 74.9% to 80.7% ( P =0.0101), and nonsmoking improved from 74.4% to 80.9% ( P <0.0001). The percentage with optimal risk‐factor control also improved significantly, from 16.7% to 36.2% ( P <0.001), but nearly 2 of 3 study participants did not achieve optimal control during the study. Conclusions Site‐based risk‐factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal. Intensive medical management should be considered for future trials of carotid revascularization. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00004732.

Green’s functions effectively simulate shear waves produced by an applied acoustic radiation force in elastic and viscoelastic soft tissue. In an effort to determine the optimal parameters for these simulations, the convergence of Green's function-based calculations is evaluated for realistic spatial distributions of the initial radiation force “push.” The input to these calculations is generated by FOCUS, the “Fast Object-oriented C + + Ultrasound Simulator,” which computes the approximate intensity fields generated by a Phillips L7-4 ultrasound transducer array for both focused and unfocused beams. The radiation force in the simulation model, which is proportional to the simulated intensity, is applied for 200 μs, and the resulting displacements are calculated with the Green's function model. Simulation results indicate that, for elastic media, convergence is achieved when the intensity field is sampled at roughly one-tenth of the wavelength of the compressional component that delivers the radiation force “push.” Aliasing and oscillation artifacts are observed in the model for an elastic medium at lower sampling rates. For viscoelastic media, spatial sampling rates as low as two samples per compressional wavelength are sufficient due to the low-pass filtering effects of the viscoelastic medium. [Supported in part by NIH Grants R01EB012079 and R01DK092255.]