Exercise-Associated Hyponatremia: The Effects of Carbohydrate and Hydration Status on IL-6, ADH, and Sodium Concentrations

Exercise-associated hyponatremia (serum sodium \u3c 135 mmol/L) is a rare, but serious condition that has been identified in those engaging in prolonged, physical activity conducted in the heat. PURPOSE: The purpose of this study was to evaluate the effect of hydration status and glycogen level on plasma IL-6, ADH, and sodium concentrations during and after prolonged exercise in the heat. METHODS: Ten male participants completed four trials: a glycogen depleted, euhydrated condition (DE); a glycogen depleted, dehydrated condition (DD); a glycogen loaded, euhydrated condition (LE); and a glycogen loaded, dehydrated condition (LD) consisting of cycling 90 minutes at 60% VO2 max in a 35˚C environment followed by a 3-h rehydration (RH) period. During RH, subjects received either 150% of fluid lost (DD & LD) or an additional 50% of fluid lost (DE & LE). Exercise and RH blood samples were analyzed for glucose, IL-6, ADH, and Na+. Sweat and urine samples were analyzed for [Na+]. RESULTS: Post-exercise to post-rehydration [Na+] changes for LD, DD, DE and LE were -6.85, -6.7, -1.45 and 0.10 mM, respectively. Post-exercise [IL-6] for DD, LD, DE, and LE were 5.4, 4.0, 3.7, and 3.49 pg/mL, respectively. Post-exercise [ADH] for LD, DD, DE, and LE were 21.5, 12.8, 7.6, and 1.9 pg/mL, respectively. The number of hyponatremic measurements for all RH samples was 5, 5, 20, and 10 for LD, DD, DE, and LE, respectively. CONCLUSION: Despite our glycogen and hydration manipulations, no regulatory effects of IL-6 and ADH on plasma sodium were observed. The timing of fluid intake did alter plasma sodium since euhydration during exercise combined with an additional 50% intake during RH, and a post-exercise RH volume of 150% of fluid lost both resulted in sodium concentrations below initial levels. Supported by a grant from the Gatorade Sports Science Institute

Decay-accelerating factor expression in the rat kidney is restricted to the apical surface of podocytes

Decay-accelerating factor expression in the rat kidney is restricted to the apical surface of podocytes.BackgroundDecay-accelerating factor (DAF) has inhibitory activity toward complement C3 and C5 convertases. DAF is present in human glomeruli and on cultured human glomerular visceral epithelial cells (GEC). We studied the distribution and function of rat DAF.MethodsFunction-neutralizing antibodies (Abs) were raised against DAF. The distribution of DAF in vivo was determined by immunoelectron microscopy. Functional studies were performed in cultured GEC and following IV injection of anti-DAF Abs into rats.ResultsDAF was present exclusively on the apical surfaces of GEC, and was not present on the basal surfaces of GEC, nor other glomerular or kidney cells. DAF was functionally active on cultured GEC, and served to limit complement activation in concert with CD59, an inhibitor of C5b-9 formation. Upon injection into normal rats, anti-DAF F(ab′)2 Abs bound to GEC in vivo, yet there was no evidence for complement activation and animals did not develop abnormal albuminuria. Anti-megalin complement-activating IgG Abs were “planted” on GEC, which activated complement as evidenced by the presence of C3d on GEC. Attempts to inhibit DAF function with anti-DAF Abs did not affect the quantity of complement activation by these anti-megalin Abs, nor did it lead to development of abnormal albuminuria. In contrast, in the puromycin aminonucleoside model of GEC injury and proteinuria, anti-DAF Abs slowed the recovery from renal failure that occurs in this model.ConclusionIn cultured rat GEC, DAF is an effective complement regulator. In vivo, DAF is present on GEC apical surfaces. Yet, it appears that DAF is not essential to prevent complement activation from occurring under normal circumstances and in those cases in which complement-activating Abs are present on the basal surfaces of GEC in vivo. However, in proteinuric conditions, DAF appears to be protective to GEC

Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services

Background: Emergency department (ED) data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. Methods: A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172) over a three-year period (31st March 2008 to 30th March 2011) to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Results: Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P < 0.001); with male:female ratios increasing on more violent nights. Risks peak at age 18 years. Deprived individuals have greater risks of presenting across all ages (AOR 3.87, 95% CIs 3.82-3.92; P < 0.001). Proportions of assaults from deprived communities increase midweek. Female presentations in affluent areas peak aged 20 years. By age 13, females from deprived communities exceed this peak. Presentations peak on Friday and Saturday nights and the eves of public holidays; the largest peak is on New Year’s Eve. Assaults increase over summer with a nadir in January. Impacts of annual celebrations without holidays vary. Some (Halloween, Guy Fawkes and St Patrick’s nights) see increased assaults while others (St George’s and Valentine’s Day nights) do not. Home nation World Cup football matches are associated with nearly a three times increase in midweek assault presentation. Other football and rugby events examined show no impact. The 2008 Olympics saw assaults fall. The overall calendar model strongly predicts observed presentations (R2 = 0.918; P < 0.001). Conclusions: To date, the role of ED data has focused on helping target nightlife police activity. Its utility is much greater; capable of targeting and evaluating multi-agency life course approaches to violence prevention and optimising frontline resources. National ED data are critical for fully engaging health services in the prevention of violence

On Radio Detection of Ultra-High Energy Neutrinos in Antarctic Ice

Interactions of ultrahigh energy neutrinos of cosmological origin in large volumes of dense, radio-transparent media can be detected via coherent Cherenkov emission from accompanying electromagnetic showers. Antarctic ice meets the requirements for an efficient detection medium for a radio frequency neutrino telescope. We carefully estimate the sensitivity of realistic antennas embedded deep in the ice to 100 MHz - 1 GHz signals generated by predicted neutrino fluxes from active galactic nuclei. Our main conclusion is that a {\it single radio receiver} can probe a $\sim 1$ ${\rm km}^3$ volume for events with primary energy near 2 PeV and that the total number of events registered would be roughly 200 to 400 ${\rm year}^{-1}$ in our most conservative estimate. An array of such receivers would increase sensitivity dramatically. A radio neutrino telescope could directly observe and test our understanding of the most powerful particle accelerators in the universe, simultaneously testing the standard theory of particle physics at unprecedented energies.Comment: 45 pages, 21 figures, uuencoded, gzipped, submitted to Phys. Rev. D, also available at http://poincare.math.ukans.edu/~frichter/radio.html (Shading in Figure 21 fixed

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression

Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial

Objective To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. Methods We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. Results Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95$79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. Significance Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia