Fluid restriction versus volume expansion in children with diarrhea-associated HUS: a retrospective observational study.

BACKGROUND: Fifty percent of patients with typical diarrhea-associated hemolytic uremic syndrome (D+HUS) require kidney replacement therapy (KRT). In these patients, dehydration worsens disease prognosis. We evaluated dialysis requirement, presence of seizures, and mortality rate among patients diagnosed with D+HUS treated with volume expansion (VE) versus fluid restriction (FR). METHODS: Thirty-five patients with D+HUS were enrolled; 16 received VE and 19 were historical patients who received conventional FR. RESULTS: Upon admission or during treatment, neither group presented evidence of fluid overload. The VE group received higher volumes of saline (VE 27 ml/kg [10-30] over a 3-h period vs. FR 0 ml), had higher urine output after 12 h (VE vs. FR: OR 6.2 [1.2-41.6], P = 0.03), and required less dialysis (VE 2 [12.5%, CI 95% 0-29] vs. FR 9 [47.4%, CI 95% 24-70], P = 0.035). The VE group had an absolute risk reduction of 0.34 (CI 95% 0.07-0.63); hence, three patients treated with VE were required to avoid one KRT. VE also corrected initial hyponatremia and maintained serum sodium within normal ranges. No statistical differences were observed regarding number of patients with seizures (P = 0.08) or mortality (P = 1.0). CONCLUSIONS: VE markedly reduces the number of patients requiring KRT and keeps serum sodium within a normal range. We propose to initially hydrate every patient with D+HUS and without signs of fluid overload, with 10 ml/kg/h 0.9% saline solution IV, over a 3-h period. Afterwards, if urine output is ≥ 0.5 ml/kg/h, it is recommended to not dialyze and continue IV hydration schedule with isotonic (D5) saline solution, according to their needs.

Disynaptic inhibition shapes tuning of OFF-motion detectors in Drosophila.

The circuitry underlying the detection of visual motion in Drosophila melanogaster is one of the best studied networks in neuroscience. Lately, electron microscopy reconstructions, algorithmic models, and functional studies have proposed a common motif for the cellular circuitry of an elementary motion detector based on both supralinear enhancement for preferred direction and sublinear suppression for null-direction motion. In T5 cells, however, all columnar input neurons (Tm1, Tm2, Tm4, and Tm9) are excitatory. So, how is null-direction suppression realized there? Using two-photon calcium imaging in combination with thermogenetics, optogenetics, apoptotics, and pharmacology, we discovered that it is via CT1, the GABAergic large-field amacrine cell, where the different processes have previously been shown to act in an electrically isolated way. Within each column, CT1 receives excitatory input from Tm9 and Tm1 and provides the sign-inverted, now inhibitory input signal onto T5. Ablating CT1 or knocking down GABA-receptor subunit Rdl significantly broadened the directional tuning of T5 cells. It thus appears that the signal of Tm1 and Tm9 is used both as an excitatory input for preferred direction enhancement and, through a sign inversion within the Tm1/Tm9-CT1 microcircuit, as an inhibitory input for null-direction suppression.

The connectome of the adult Drosophila mushroom body provides insights into function.

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory, and activity regulation. Here, we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

Modulation of auditory percepts by transcutaneous electrical stimulation.

Transcutaneous, electrical stimulation with electrodes placed on the mastoid processes represents a specific way to elicit vestibular reflexes in humans without active or passive subject movements, for which the term galvanic vestibular stimulation was coined. It has been suggested that galvanic vestibular stimulation mainly affects the vestibular periphery, but whether vestibular hair cells, vestibular afferents, or a combination of both are excited, is still a matter of debate. Galvanic vestibular stimulation has been in use since the late 18th century, but despite the long-known and well-documented effects on the vestibular system, reports of the effect of electrical stimulation on the adjacent cochlea or the ascending auditory pathway are surprisingly sparse. The present study examines the effect of transcutaneous, electrical stimulation of the human auditory periphery employing evoked and spontaneous otoacoustic emissions and several psychoacoustic measures. In particular, level growth functions of distortion product otoacoustic emissions were recorded during electrical stimulation with alternating currents (2 Hz, 1-4 mA in 1 mA-steps). In addition, the level and frequency of spontaneous otoacoustic emissions were followed before, during, and after electrical stimulation (2 Hz, 1-4 mA). To explore the effect of electrical stimulation on the retrocochlear level (i.e. on the ascending auditory pathway beyond the cochlea), psychoacoustic experiments were carried out. Specifically, participants indicated whether electrical stimulation (4 Hz, 2 and 3 mA) induced amplitude modulations of the perception of a pure tone, and of auditory illusions after presentation of either an intense, low-frequency sound (Bounce tinnitus) or a faint band-stop noise (Zwicker tone). These three psychoacoustic measures revealed significant perceived amplitude modulations during electrical stimulation in the majority of participants. However, no significant changes of evoked and spontaneous otoacoustic emissions could be detected during electrical stimulation relative to recordings without electrical stimulation. The present findings show that cochlear function, as assessed with spontaneous and evoked otoacoustic emissions, is not affected by transcutaneous electrical stimulation, at the currents used in this study. Psychoacoustic measures like pure tone perception, but also auditory illusions, are affected by electrical stimulation. This indicates that activity of the retrocochlear ascending auditory pathway is modulated during transcutaneous electrical stimulation.