In the central nervous system (CNS), myelin sheaths around axons are formed by glial cells named oligodendrocytes (OLs). In turn, OLs are generated by oligodendrocyte precursor cells (OPCs) during ...postnatal development and in adults, according to a process that depends on the proliferation and differentiation of these progenitors. The maturation of OL lineage cells as well as myelination by OLs are complex and highly regulated processes in the CNS. OPCs and OLs express an array of receptors for neurotransmitters, in particular for the two main CNS neurotransmitters glutamate and GABA, and are therefore endowed with the capacity to respond to neuronal activity. Initial studies in cell cultures demonstrated that both glutamate and GABA signaling mechanisms play important roles in OL lineage cell development and function. However, much remains to be learned about the communication of glutamatergic and GABAergic neurons with oligodendroglia in vivo. This review focuses on recent major advances in our understanding of the neuron–oligodendroglia communication mediated by glutamate and GABA in the CNS, and highlights the present controversies in the field. We discuss the expression, activation modes and potential roles of synaptic and extrasynaptic receptors along OL lineage progression. We review the properties of OPC synaptic connectivity with presynaptic glutamatergic and GABAergic neurons in the brain and consider the implication of glutamate and GABA signaling in activity‐driven adaptive myelination.
Main points
We describe recent advances in our understanding of 1) the roles of synaptic and extrasynaptic receptors of OL lineage cells, 2) the roles of OPC synaptic connectivity, and 3) the impact of glutamate and GABA signaling on activity‐driven adaptive myelination.
The practising clinician treating a patient with metastatic clear cell renal cell carcinoma (CCRCC) faces a difficult task of choosing the most appropriate therapeutic regimen in a rapidly developing ...field with recommendations derived from clinical trials. NCCN guidelines for kidney cancer initiated a major shift in risk categorization and now include emerging treatments in the neoadjuvant setting. Updates of European Association of Urology clinical guidelines also include immune checkpoint inhibition as the first-line treatment. Randomized trials have demonstrated a survival benefit for ipilimumab and nivolumab combination in the intermediate and poor-risk group, while pembrolizumab plus axitinib combination is recommended not only for unfavorable disease but also for patients who fit the favorable risk category. Currently vascular endothelial growth factor (VEGF) targeted therapy based on tyrosine kinase inhibitors (TKI), sunitinib and pazopanib is the alternative regimen for patients who cannot tolerate immune checkpoint inhibitors (ICI). Cabozantinib remains a valid alternative option for the intermediate and high-risk group. For previously treated patients with TKI with progression, nivolumab, cabozantinib, axitinib, or the combination of ipilimumab and nivolumab appear the most plausible alternatives. For patients previously treated with ICI, any VEGF-targeted therapy, not previously used in combination with ICI therapy, seems to be a valid option, although the strength of this recommendation is weak. The indication for cytoreductive nephrectomy (CN) is also changing. Neoadjuvant systemic therapy does not add perioperative morbidity and can help identify non-responders, avoiding unnecessary surgery. However, the role of CN should be investigated under the light of new immunotherapeutic interventions. Also, markers of response to ICI need to be identified before the optimal selection of therapy could be determined for a particular patient.
Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and ...how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars. Here we show that rodents exposed to the second most prevalent radiation type in space (i.e. helium ions) at low, realistic doses, exhibit significant hippocampal and cortical based cognitive decrements lasting 1 year after exposure. Cosmic-radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in cognitive flexibility and reduced rates of fear extinction, elevated anxiety and depression like behavior. At the circuit level, irradiation caused significant changes in the intrinsic properties (resting membrane potential, input resistance) of principal cells in the perirhinal cortex, a region of the brain implicated by our cognitive studies. Irradiation also resulted in persistent decreases in the frequency and amplitude of the spontaneous excitatory postsynaptic currents in principal cells of the perirhinal cortex, as well as a reduction in the functional connectivity between the CA1 of the hippocampus and the perirhinal cortex. Finally, increased numbers of activated microglia revealed significant elevations in neuroinflammation in the perirhinal cortex, in agreement with the persistent nature of the perturbations in key neuronal networks after cosmic radiation exposure. These data provide new insights into cosmic radiation exposure, and reveal that even sparsely ionizing particles can disrupt the neural circuitry of the brain to compromise cognitive function over surprisingly protracted post-irradiation intervals.
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•Low dose cosmic irradiation causes significant adverse effects on CNS function.•Functional CNS disruptions occur over times commensurate with a trip to Mars.•Impairments to cognition and neural circuitry persisted 1 year after exposure.•Prolonged functional deficits were associated with elevated neuroinflammation.
•Mechanical and thermal processes to produce high performance RCA have been analyzed.•We calculated, for different scenarios, fines generation, energy, and CO2 emissions.•The production of fines ...increases from 40% up to as much as 70%.•Energy consumption has resulted up to 62 times higher than conventional recycling.•CO2 emissions range from 1.5 to 4.5kgCO2/t, to around 200kgCO2/t.
The use of recycled concrete aggregates (RCA) in applications other than road sub-layers is limited by two factors: the high porosity of RCA in comparison with natural aggregates, and the restrictions set forth in standards and building codes. Research efforts aimed at alleviating these restrictions are focused on improving the quality of coarse RCAs by reducing the amount of adhered cement pastes, which is the weakest element in this system and influences the rheological behaviour.
This paper presents an analysis of the environmental impacts of the recent mechanical and thermo-mechanical processing techniques which produce high performance RCA by reducing the volume of adhered cement paste. Based on published data, processing scenarios were established. These scenarios permit making rough estimates of energy consumption, CO2 emissions, fines generation and product quality. Using these data and the available emission factors from several countries, an objective comparison was made between these innovating processes and conventional recycling.
The production of fines increases from 40% up to as much as 70% as the volume of adhered cement paste on the RCA is reduced. Fuel fed thermo-mechanical process energy consumption, per tonne of recycled aggregate, varies between 36 and 62 times higher than conventional recycling processes. Mechanical processing, combined with microwave heating, increases energy consumption from 3 to a little more than 4 times conventional recycling. Consequently, CO2 emissions released by conventional coarse aggregate production go from 1.5 to 4.5kgCO2/t, to around 200kgCO2/t, for that of fossil fuel fed thermo-mechanical treatments.
Mechanical and mechanical/microwave treatments appear to have the greatest environmental potential. Notwithstanding, the further development of markets for fines is crucial for reducing environmental loads.
A conditioning on the event of having selected one model from a set of possibly misspecified normal linear regression models leads to the construction of uniformly optimal conditional confidence ...distributions. They can be used for valid postselection inference. The constructed conditional confidence distributions are finite sample exact and encompass all information regarding the focus parameter in the selected model. This includes the construction of optimal postselection confidence intervals at all significance levels and uniformly most powerful hypothesis tests.
•Roughness measurement procedure by optical interferometry was defined for recycle aggregates.•A way to correct the water absorption kinetics of recycled aggregates was proposed.•The water repellents ...effect on the recycled aggregates is temporary.
Surface treatment techniques may improve the characteristics of recycled aggregates (RAs) for use in cementitious materials, possibly as an alternative to the energy and CO2 intensive high quality RA production process. In this paper, we investigate the effectiveness of two water repellent treatments (silane solution and paraffin wax) on the characteristics of different RAs in terms of porosity. We explored the relationship between roughness, porosity/surface area, and wettability of RAs on their water absorption (WA) kinetics. The long-term goal of the treatments is to reduce the water demand of concrete/mortar.
We proposed a method to measure the roughness of coarse aggregates by optical interferometry. Contrary to popular belief, recycled concrete aggregates are as rough as crushed natural aggregates, and only red ceramic aggregate is less rough than natural aggregates. This technique combined with mercury intrusion porosimetry identified microstructural changes in the treated RAs. Silane was incorporated into smaller pores (<100nm) and caused a slight reduction in the total porosity and specific surface area of RAs. Paraffin wax also intruded into the RAs, filling larger pores (>100nm), and the wax significantly reduced the total porosity. Paraffin treatment formed a smoother surface and a thicker paraffin layer around the particles.
We determined the water absorption kinetics using the standard 24h WA test with method adaptations in order to improve the accuracy and repeatability of the tests. Treated RA surfaces exhibited hydrophobic behavior but at the cost of efficiency. WA kinetics significantly changed after 2h.
Waste management solutions and reuse strategies for excavation soils from construction works are needed to increase the circularity of resources in urban areas. In this study, we assessed some reuse ...strategies for excavated soils, based on a geotechnical-environmental characterization study conducted with samples from an “inert” construction and demolition waste (CDW) landfill in Sao Paulo city. The geotechnical reuse of soil samples should be limited to applications where the material is confined (backfilling trenches, containing walls etc.), because of swelling and loss of bearing capacity after saturation. In addition, CDW-soil mixtures can be used in reinforcement of subgrades and sub-bases of pavements of low-volume roads. Gypsum/cementitious materials in contact with the leakage of sanitary effluents might result in sulfate concentrations that restrict the reuse of CDW due to quality requirements of superficial waters, however, without posing a significant risk to human health. They might also degrade neighboring concrete foundations. A methodological flowchart to support reuse strategies of soils for urban areas was proposed, based on current characterization tests.
•Flowchart to support reuse strategies of excavation soils in urban areas.•Geotechnical-environmental characterization of excavation soils.•Excavation soils complied requirements for backfill of trenches/containing walls.•CDW-soil mixtures can be used in subgrade reinforcement and subbases of pavements.
Urinary incontinence is one of the most serious complications of prostate cancer treatment. The objective of this study was to assess efficacy and safety of Adjustable Transobturator Male System ...(ATOMS) compared to Adjustable Continence Therapy (proACT) for male stress urinary incotinence according to literature findings.
A systematic review and meta-analysis on adjustable devices ATOMS and ProACT is presented. Studies on female or neurogenic incontinence were excluded. Differences between ATOMS and proACT in primary objective: dryness status (no-pad or one safety pad/day) after initial device adjustment, and in secondary objectives: improvement, satisfaction, complications and device durability, were estimated using random-effect model. Statistical heterogeneity among studies included in the meta-analysis was assessed using tau2, Higgins´s I2 statistics and Cochran´s Q test.
Combined data of 41 observational studies with 3059 patients showed higher dryness (68 vs. 55%; p = .01) and improvement (91 vs. 80%; p = .007) rate for ATOMS than ProACT. Mean pad-count (-4 vs. -2.5 pads/day; p = .005) and pad-test decrease (-425.7 vs. -211.4 cc; p < .0001) were also significantly lower. Satisfaction was higher for ATOMS (87 vs. 56%; p = .002) and explant rate was higher for proACT (5 vs. 24%; p < .0001). Complication rate for ProACT was also higher, but not statistically significant (17 vs. 26%; p = .07). Mean follow-up was 25.7 months, lower for ATOMS than ProACT (20.8 vs. 30.6 months; p = .02). The rate of working devices favoured ATOMS at 1-year (92 vs. 76; p < .0001), 2-years (85 vs. 61%; p = .0008) and 3-years (81 vs. 58%; p = .0001). Significant heterogeneity was evidenced, due to variable incontinence severity baseline, difficulties for a common reporting of complications, different number of adjustments and time of follow-up and absence of randomized studies.
Despite the limitations that studies available are exclusively descriptive and the follow-up is limited, literature findings confirm ATOMS is more efficacious, with higher patient satisfaction and better durability than ProACT to treat male stress incontinence.
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