Renal tubular function in children and adolescents with Gitelnian's syndrome, the hypocalciuric variant of Bartter's syndrome

Renal tubular function was studied in 14 patients with Gitelman's syndrome and 14 control subjects. Apart from the biochemical hallmarks of Gitelman's syndrome, namely alkalaemia, hyperbi carbonataemia, hypokalaemia, hypomagnesaemia (with increased magnesium over creatinine ratio), increased urinary chloride over creatinine ratio, and low urinary calcium over creatinine, the patients were found to have hyperproteinaemia, hypochloraemia, high total plasma calcium concentration, reduced plasma ionized calcium concentration, and high urinary sodium excretion. A statistically significant negative linear relationship between plasma magnesium concentration and magnesium excretion corrected for glomerular filtration was observed in patients. The fractional calcium clearance and the urinary excretion of calcium corrected for glomerular filtration was significantly decreased in patients. In patients the urin ary osmolality after overnight water deprivation ranged from 526 to 1067 mmol/kg. Glucosuria and aminoacid uria were similar in patients and controls. The results of the study demonstrate the renal origin of hypomag nesaemia and hypocalciuria in Gitelman's syndrome. The failure to demonstrate hyperaminoaciduria, hyperglucosuria, hyperphosphaturia, hyperuricosuria, and severely impaired urinary concentrating ability provide evidence for a defect residing in the distal convoluted tubul

Critical speed estimated by statistically appropriate fitting procedures.

Intensity domains are recommended when prescribing exercise. The distinction between heavy and severe domains is made by the critical speed (CS), therefore requiring a mathematically accurate estimation of CS. The different model variants (distance versus time, running speed versus time, time versus running speed, and distance versus running speed) are mathematically equivalent. Nevertheless, error minimization along the correct axis is important to estimate CS and the distance that can be run above CS (d'). We hypothesized that comparing statistically appropriate fitting procedures, which minimize the error along the axis corresponding to the properly identified dependent variable, should provide similar estimations of CS and d' but that different estimations should be obtained when comparing statistically appropriate and inappropriate fitting procedure. Sixteen male runners performed a maximal incremental aerobic test and four exhaustive runs at 90, 100, 110, and 120% of their peak speed on a treadmill. Several fitting procedures (a combination of a two-parameter model variant and regression analysis: weighted least square) were used to estimate CS and d'. Systematic biases (P < 0.001) were observed between each pair of fitting procedures for CS and d', even when comparing two statistically appropriate fitting procedures, though negligible, thus corroborating the hypothesis. The differences suggest that a statistically appropriate fitting procedure should be chosen beforehand by the researcher. This is also important for coaches that need to prescribe training sessions to their athletes based on exercise intensity, and their choice should be maintained over the running seasons

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Albendazole and mebendazole are presently used for chemotherapeutical treatment. However, these benzimidazoles do not appear to be parasiticidal in vivo against AE. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported. New drugs are needed to cure AE and CE, which are considered to be neglected diseases. Strategies currently being implemented to identify novel chemotherapeutical treatment options include (i) conventional primary in vitro testing of broad-spectrum anti-infective drugs, either in parallel with, or followed by, animal experimentation; (ii) studies of drugs which interfere with the proliferation of cancer cells and of Echinococcus metacestodes; (iii) exploitation of the similarities between the parasite and mammalian signalling machineries, with a special focus on targeting specific signalling receptors; (iv) in silico approaches, employing the current Echinococcus genomic database information to search for suitable targets for compounds with known modes of action. In the present article, we review the efforts toward obtaining better anti-parasitic compounds which have been undertaken to improve chemotherapeutical treatment of echinococcosis, and summarize the achievements in the field of host-parasite interactions which may also lead to new immuno-therapeutical option

Multi-scale measurements of mesospheric aerosols and electrons during the MAXIDUSTY campaign

We present in situ measurements of small-scale fluctuations in aerosol populations as recorded through a mesospheric cloud system from the Faraday cups DUSTY and MUDD during on the MAXIDUSTY-1 and 1B sounding rocket payloads launched in the summer of 2016. Two mechanically identical DUSTY probes mounted with an inter-spacing of ∼10&thinsp;cm recorded very different currents, with strong spin modulation, in certain regions of the cloud system. A comparison to auxiliary measurement show similar tendencies in the MUDD data. Fluctuations in the electron density are found to be generally anti-correlated to the negative aerosol charge density on all length scales; however, in certain smaller regions the correlation turns positive. We have also compared the spectral properties of the dust fluctuations, as extracted by wavelet analysis, to polar mesospheric summer echo (PMSE) strength. In this analysis, we find a relatively good agreement between the power spectral density (PSD) at the radar Bragg scale inside the cloud system; however the PMSE edge is not well represented by the PSD. A comparison of proxies for PMSE strength, constructed from a combination of derived dusty plasma parameters, shows that no simple proxy can reproduce PMSE strength well throughout the cloud system. Edge effects are especially poorly represented by the proxies addressed here.</p

The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions