G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Quantum cascade laser based hybrid dual comb spectrometer

Four-wave-mixing-based quantum cascade laser frequency combs (QCL-FC) are a powerful photonic tool, driving a recent revolution in major molecular fingerprint regions, i.e. mid- and far-infrared domains. Their compact and frequency-agile design, together with their high optical power and spectral purity, promise to deliver an all-in-one source for the most challenging spectroscopic applications. Here, we demonstrate a metrological-grade hybrid dual comb spectrometer, combining the advantages of a THz QCL-FC with the accuracy and absolute frequency referencing provided by a free-standing, optically-rectified THz frequency comb. A proof-of-principle application to methanol molecular transitions is presented. The multi-heterodyne molecular spectra retrieved provide state-of-the-art results in line-center determination, achieving the same precision as currently available molecular databases. The devised setup provides a solid platform for a new generation of THz spectrometers, paving the way to more refined and sophisticated systems exploiting full phase control of QCL-FCs, or Doppler-free spectroscopic schemes

Effect of coffee silver skin and brewers’ spent grain in the control of root-knot nematodes

Plant parasitic nematodes (PPN) are important pests of numerous agricultural crops especially vegetables, able to cause remarkable yield losses correlated to soil nematode population densities at sowing or transplant. The concern on environmental risks, stemming from the use of chemical pesticides acting as nematicides, compels to their replacement with more sustainable pest control strategies. To verify the effect of aqueous extracts of the agro-industry waste coffee silverskin (CS) and brewers’ spent grain (BSG) on the widespread root-knot nematode Meloidogyne incognita, and on the physiology of tomato plants, a pot experiment was carried out in a glasshouse at 25 ± 2 °C. The possible phytotoxicity of CS and BSG extracts was assessed on garden cress seeds. Tomato plants (landrace of Apulia Region) were transplanted in an artificial nematode infested soil with an initial population density of 3.17 eggs and juveniles/mL soil. CS and BSG were applied at rates of 50 and 100 % (1L/pot). Untreated and Fenamiphos EC 240 (nematicide) (0.01 μL a.i./mL soil) treated plants were used as controls. Reactive oxygen species (ROS) and chlorophyll content of tomato plants were estimated during the experiment. CS extract, at both doses, significantly reduced nematode population in comparison to the untreated control, although it was less effective than Fenamiphos. BSG extract did not reduce final nematode population compared to the control. Ten days after the first treatment, CS 100 %, BSG 50 % and BSG 100% elicited the highest ROS values, which considerably affected the growth of tomato plants in comparison to the untreated plants. The control of these pests is meeting with difficulties because of the current national and international regulations in force, which are limiting the use of synthetic nematicides. Therefore, CS extracts could assume economic relevance, as alternative products to be used in sustainable strategies for nematode management