Impedance Rhythms in Human Limbic System.

The impedance is a fundamental electrical property of brain tissue, playing a crucial role in shaping the characteristics of local field potentials, the extent of ephaptic coupling, and the volume of tissue activated by externally applied electrical brain stimulation. We tracked brain impedance, sleep-wake behavioral state, and epileptiform activity in five people with epilepsy living in their natural environment using an investigational device. The study identified impedance oscillations that span hours to weeks in the amygdala, hippocampus, and anterior nucleus thalamus. The impedance in these limbic brain regions exhibit multiscale cycles with ultradian (∼1.5-1.7 h), circadian (∼21.6-26.4 h), and infradian (∼20-33 d) periods. The ultradian and circadian period cycles are driven by sleep-wake state transitions between wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Limbic brain tissue impedance reaches a minimum value in NREM sleep, intermediate values in REM sleep, and rises through the day during wakefulness, reaching a maximum in the early evening before sleep onset. Infradian (∼20-33 d) impedance cycles were not associated with a distinct behavioral correlate. Brain tissue impedance is known to strongly depend on the extracellular space (ECS) volume, and the findings reported here are consistent with sleep-wake-dependent ECS volume changes recently observed in the rodent cortex related to the brain glymphatic system. We hypothesize that human limbic brain ECS changes during sleep-wake state transitions underlie the observed multiscale impedance cycles. Impedance is a simple electrophysiological biomarker that could prove useful for tracking ECS dynamics in human health, disease, and therapy.SIGNIFICANCE STATEMENT The electrical impedance in limbic brain structures (amygdala, hippocampus, anterior nucleus thalamus) is shown to exhibit oscillations over multiple timescales. We observe that impedance oscillations with ultradian and circadian periodicities are associated with transitions between wakefulness, NREM, and REM sleep states. There are also impedance oscillations spanning multiple weeks that do not have a clear behavioral correlate and whose origin remains unclear. These multiscale impedance oscillations will have an impact on extracellular ionic currents that give rise to local field potentials, ephaptic coupling, and the tissue activated by electrical brain stimulation. The approach for measuring tissue impedance using perturbational electrical currents is an established engineering technique that may be useful for tracking ECS volume.

Pharmacist Intervention Lowers HgbA1c in Diabetic Patients Regardless of HIV Status.

AIM: Compare glycemic control in human immunodeficiency (HIV)-positive patients on antiretroviral therapy to HIV-negative patients following pharmacist interventions. METHODS/RESULTS: This retrospective observational cohort study conducted at a Federally Qualified Health Center included adults with type II diabetes mellitus who attended at least two clinical pharmacy appointments between January 1, 2018 and July 31, 2019. Exclusion criteria included missing pre- or post-hemoglobin A1c (HgbA1c) values, type 1 diabetes, pregnancy, breastfeeding, deceased, or untreated HIV. The primary endpoint was change in HgbA1c from baseline to month 3. Secondary endpoints were change in HgbA1c at 6, 9, and 12 months, and time to goal. Additional endpoints included changes in number of anti-diabetic agents, blood pressure, body mass index, hypoglycemic events, percent of patients on a sodium-glucose co-transporter-2 (SGLT-2) inhibitor or glucagon-like peptide (GLP-1) agonist. This study was exempt from the University of California, Davis Institutional Review Board as a continuous quality improvement study.Seventy-eight patients were included, 17 of whom were HIV-positive. At 3 months, HgbA1c was reduced by -1.7% and -1.2% (p =0.31) for HIV-positive and -negative patients, respectively. In the pooled cohort, HgbA1c was reduced from baseline at all time points, and 24% of patients achieved HgbA1c below 7.0%. The number of antidiabetic medications remained unchanged or was decreased in 60% of patients. CONCLUSION: The study demonstrated clinically important HgbA1c reductions without increasing the medication burden in most patients. There was no significant difference in glycemic management between HIV-positive and HIV-negative patients.

Computed Tomography Cholangiography Using the Magnetic Resonance Contrast Agent Gadoxetate Disodium: A Phantom Study.

OBJECTIVE: The purpose of this work is to determine whether low doses of gadoxetate disodium (Eovist; Bayer Healthcare LLC, Whippany, NJ), a gadolinium-based contrast agent used for magnetic resonance liver imaging, can be visualized for computed tomography (CT) cholangiography using a phantom setup. MATERIALS AND METHODS: Vials containing 4 concentrations of gadoxetate disodium (1.9, 3.4, 4.8, and 9.6 mg Gd/mL) were placed in a 35 × 26-cm water phantom and imaged on 2 CT scanners: Siemens Somatom Flash and Force (Siemens Healthcare, Erlangen, Germany). These concentrations correspond to the estimated concentration in the bile duct for a 40-, 70-, or 100-kg patient, and twice the concentration of a 100-kg patient, respectively. Single-energy (SE) scans were acquired at 70, 80, 90, 100, 120, and 140 kVp, and dual-energy scans were acquired at 90/150Sn (Force) and 100/150 (Flash) for 2 dose levels (CTDIvol 13 and 23 mGy). Virtual monoenergetic images at 50 keV were created (Mono+; Siemens Healthcare, Erlangen, Germany). The mean intensity and standard deviation for each concentration of gadoxetate disodium and the water background were extracted from each image set and used to compute the contrast and contrast-to-noise ratio (CNR). To determine whether the signal provided by gadoxetate disodium was clinically sufficient, the measures were compared with those acquired from 12 clinical CT cholangiography examinations performed with iodine-containing iodipamide meglumine. RESULTS: From the retrospective clinical cohort, mean contrast (± standard deviation) of 239 ± 107 HU and CNR of 12.8 ± 4.2 were found in the bile duct relative to the liver. Comparing these metrics to the gadoxetate disodium samples, the highest concentration (9.6 mg Gd/mL) surpassed these thresholds at all energy levels. The 4.8 mg Gd/mL had sufficient CNR in the Force, but not in the Flash. The 3.4 mg Gd/mL had clinically relevant CNR at low kV of SE (<100 kVp) and 50 keV of dual energy in the Force but was insufficient in the Flash. Images acquired by the Force had a lower noise level and greater CNR compared with the Flash. Similar trends were seen at both dose levels. CONCLUSIONS: Gadoxetate disodium shows promise as a viable contrast agent for CT cholangiography, with CNR similar to those seen clinically with an iodine-based contrast agent. Dual-energy CT or low kV SE-CT is helpful to enhance the signal.

Making choices impairs subsequent self-control: a limited-resource account of decision making, self-regulation, and active initiative.

The current research tested the hypothesis that making many choices impairs subsequent self-control. Drawing from a limited-resource model of self-regulation and executive function, the authors hypothesized that decision making depletes the same resource used for self-control and active responding. In 4 laboratory studies, some participants made choices among consumer goods or college course options, whereas others thought about the same options without making choices. Making choices led to reduced self-control (i.e., less physical stamina, reduced persistence in the face of failure, more procrastination, and less quality and quantity of arithmetic calculations). A field study then found that reduced self-control was predicted by shoppers' self-reported degree of previous active decision making. Further studies suggested that choosing is more depleting than merely deliberating and forming preferences about options and more depleting than implementing choices made by someone else and that anticipating the choice task as enjoyable can reduce the depleting effect for the first choices but not for many choices.