N-(Phenoxyalkyl)amides as MT1 and MT2 ligands: Antioxidant properties and inhibition of Ca2+/CaM-dependent kinase II

Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT(1) and MT(2) melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H(2)O(2)-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, to

IR-correlated 31 GHz radio emission from Orion East

Lynds dark cloud LDN1622 represents one of the best examples of anomalous dust emission, possibly originating from small spinning dust grains. We present Cosmic Background Imager (CBI) 31 GHz data of LDN1621, a diffuse dark cloud to the north of LDN1622 in a region known as Orion East. A broken ring with diameter g\approx 20 arcmin of diffuse emission is detected at 31 GHz, at \approx 20-30 mJy beam$^{-1}$ with an angular resolution of \approx 5 arcmin. The ring-like structure is highly correlated with Far Infra-Red emission at $12-100 \mu$m with correlation coefficients of r \approx 0.7-0.8, significant at $\sim10\sigma$. Multi-frequency data are used to place constraints on other components of emission that could be contributing to the 31 GHz flux. An analysis of the GB6 survey maps at 4.85 GHz yields a $3\sigma$ upper limit on free-free emission of 7.2 mJy beam$^{-1}$ (\la 30 per cent of the observed flux) at the CBI resolution. The bulk of the 31 GHz flux therefore appears to be mostly due to dust radiation. Aperture photometry, at an angular resolution of 13 arcmin and with an aperture of diameter 30 arcmin, allowed the use of IRAS maps and the {\it WMAP} 5-year W-band map at 93.5 GHz. A single modified blackbody model was fitted to the data to estimate the contribution from thermal dust, which amounts to \sim$10 per cent at 31 GHz. In this model, an excess of 1.52\pm 0.66 Jy (2.3\sigma) is seen at 31 GHz. Future high frequency$\sim$100-1000 GHz data, such as those from the {\it Planck} satellite, are required to accurately determine the thermal dust contribution at 31 GHz. Correlations with the IRAS$100 \mu$m gave a coupling coefficient of$18.1\pm4.4 \mu$K (MJy/sr)$^{-1}$, consistent with the values found for LDN1622.Comment: 8 pages, 3 figures, 3 tables, submitted to MNRA

Systemic treatment of malignant gastrointestinal neuroectodermal tumour after childhood neuroblastoma: chemotherapy in malignant gastrointestinal neuroectodermal tumour

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in youngaged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m2/day on days 1–5, vincristine 1,5 mg/m2/ day on days 1 and 5, and doxorubicin 60 mg/m2/day on day 5; CVP: cisplatin 40 mg/m2/day on days 1–5 and etoposide 100 mg/m2/day on days 1–5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustineteniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies

Liquid baits with Oenococcus oeni increase captures of Drosophila suzukii

The spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), native to Eastern Asia, is an invasive alien species in Europe and the Americas, where it is a severe pest of horticultural crops, including soft fruits and wine grapes. The conventional approach to controlling infestations of SWD involves the use of insecticides, but the frequency of application for population management is undesirable. Consequently, alternative strategies are urgently needed. Effective and improved trapping is important as an early risk detection tool. This study aimed to improve Droskidrink® (DD), a commercially available attractant for SWD. We focused on the chemical and behavioral effects of adding the bacterium Oenococcus oeni (Garvie) to DD and used a new trap design to enhance the effects of attractive lures. We demonstrate that microbial volatile compounds produced by O. oeni are responsible for the increase in the attractiveness of the bait and could be later utilized for the development of a better trapping system. Our results showed that the attractiveness of DD was increased up to two-fold by the addition of commercially available O. oeni when combined with an innovative trap design. The new trap-bait combination increased the number of male and especially female catches at low population densitie

Chromatic Pupillometry Findings in Alzheimer's Disease

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function. We have previously described, in post-mortem investigations of AD retinas, a loss of mRGCs, and in the remaining mRGCs, we demonstrated extensive morphological abnormalities. We noted dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization. In this study, we evaluated, with chromatic pupillometry, the PLR in a cohort of mild-moderate AD patients compared to controls. AD and controls also underwent an extensive ophthalmological evaluation. In our AD cohort, PIPR did not significantly differ from controls, even though we observed a higher variability in the AD group and 5/26 showed PIPR values outside the 2 SD from the control mean values. Moreover, we found a significant difference between AD and controls in terms of rod-mediated transient PLR amplitude. These results suggest that in the early stage of AD there are PLR abnormalities that may reflect a pathology affecting mRGC dendrites before involving the mRGC cell body. Further studies, including AD cases with more severe and longer disease duration, are needed to further explore this hypothesis

Preclinical development of HIvax: human survivin Highly Immunogenic vaccines

Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization.

Purpose: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. Methods: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. Results: A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P \u3c 0.05, respectively). Conclusions: En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV