Highlights d NR supplementation in aged subjects augments the skeletal muscle NAD + metabolome d NR supplementation does not affect skeletal muscle mitochondrial bioenergetics d NR supplementation reduces levels of circulating inflammatory cytokines

IMPORTANCE Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse.OBJECTIVE To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. DESIGN, SETTING, AND PARTICIPANTSThis 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020.INTERVENTIONS Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). MAIN OUTCOMES AND MEASURESThe primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. RESULTSOf the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, −6.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, −9.5 to −2.4 cm CSF; P = .001) and at 24 months (adjusted mean [SE] difference, −8.2 [2.0] cm CSF; 95% CI, −12.2 to −4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, −7.2 [1.8] cm CSF; 95% CI, −10.6 to −3.7 cm CSF; P < .001) and at 24 months (adjusted mean [SE] difference, −8.7 [2.0] cm CSF; 95% CI, −12.7 to −4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, kg; 95% CI, −32.1 to −10.7 kg; P < .001) and at 24 months (adjusted mean [SE] difference, kg; 95% CI, −37.5 to −15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 year...

BackgroundThe cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation.MethodsUsing high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage.ResultsThe RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage.ConclusionThe cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

good correlation and concordance with the PCT assay on the Brahms Kryptor in a highly relevant patient group. Thus, the PCT assay from Roche allows easy and accurate measurement of serum PCT on an automated clinical immunochemistry analyzer that is fully integrated in standard hospital care. Role of Sponsor:The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript. Acknowledgments:We thank N. Ambrosius for excellent technical assistance.

The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low birth weight infants of mean (± SD) gestational age 25.6 ±0.5 weeks suffering bronchopulmonary dysplasia. A mean peak dexamethasone concentration of 250.5 ± 70.7 ng/ml was obtained following an intravenous bolus dose (0.369 ± 0.04 mg/kg dexamethasone) of dexamethasone sodium phosphate. Dexamethasone was measured in plasma by HPLC. Mean clearance (0.143 ± 0.028 litres/kg/h) was approximately half that reported previously in children and adults, while the half-life (9.26 ± 3.34 h) was 2- to 3-fold longer than in these patients. The volume of distribution (1.9 ± 0.483 litres/kg) was larger than reported in a previous study in adults, but was similar to that determined in pediatric and adult patients in another study.