Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan–Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(–)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(–) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. © 1999 Cancer Research Campaig

Nanoelectropulse-driven membrane perturbation and small molecule permeabilization

BACKGROUND: Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization. RESULTS: In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to unipolar pulses, which perturb membrane phospholipid order, tracked with FM1-43 fluorescence, only at the anode side of the cell, bipolar pulses redistribute phospholipids at both the anode and cathode poles, consistent with migration of the anionic PS head group in the transmembrane field. In addition, we demonstrate that, as predicted by the membrane charging hypothesis, a train of shorter pulses requires higher fields to produce phospholipid scrambling comparable to that produced by a time-equivalent train of longer pulses (for a given applied field, 30, 4 ns pulses produce a weaker response than 4, 30 ns pulses). Finally, we show that influx of YO-PRO-1, a fluorescent dye used to detect early apoptosis and activation of the purinergic P2X(7 )receptor channels, is observed after exposure of Jurkat T lymphoblasts to sufficiently large numbers of pulses, suggesting that membrane poration occurs even with nanosecond pulses when the electric field is high enough. Propidium iodide entry, a traditional indicator of electroporation, occurs with even higher pulse counts. CONCLUSION: Megavolt-per-meter electric pulses as short as 3 ns alter the structure of the plasma membrane and permeabilize the cell to small molecules. The dose responses of cells to unipolar and bipolar pulses ranging from 3 ns to 30 ns duration support the hypothesis that a field-driven charging of the membrane dielectric causes the formation of pores on a nanosecond time scale, and that the anionic phospholipid PS migrates electrophoretically along the wall of these pores to the external face of the membrane

Effects of fungicides and bactericides on orchid seed germination and shoot tip cultures in vitro

Amphotericin B, benomyl, gentamycin, nystatin, quintozene penicillin G, sodium omadine, and vancomycin singly and in several combinations have no deleterious effects on the germination of orchid seeds, but inhibit the growth in vitro of shoot tip explants. © 1981 Martinus Nijhoff/Dr W. Junk Publishers

Integrating anaerobic digestion and pyrolysis for treating digestates derived from sewage sludge and fat wastes

P. 32603-32614The coupling of biological and thermal technologies allows for the complete conversion of wastes into energy and biochar eliminating the problem of sludge disposal. The valorisation of fatty residues as co-substrate in a mesophilic digester of a wastewater treatment plant was studied considering an integrated approach of co-digestion and pyrolysis. Four digested samples obtained from co-digestion of sewage sludge and butcher’s fat waste were studied by thermogravimetric analysis. The activation energy corresponding to the sludge pyrolysis was calculated by a non-isothermal kinetic. Arrhenius activation energy was lower for the pyrolysis of a digested grease sample (92 kJ mol−1 obtained by OFW and 86 kJ mol−1 obtained by Vyazovkin) than for the pyrolysis of sewage sludge and its blends (164–190 kJ mol−1 obtained by OFW and 162–190 kJ mol−1 obtained by Vyazovkin). The analysis of the integrated approach of anaerobic co-digestion and pyrolysis of digestates demonstrated that the addition of 3% (w/v) of fat to the feeding sludge results in a 25% increase in the electricity obtained from biogas (if a combined heat and power unit is considered for biogas valorisation) and increasing the fat content to 15% allows for covering all thermal needs for drying of digestate and more than doubles (2.4 times) the electricity production when the scenario of digestion and pyrolysis is contemplated.S

JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging

JWST has revolutionized the field of extragalactic astronomy with its sensitive and high-resolution infrared view of the distant Universe. Adding to the new legacy of JWST observations, we present the first NIRCam imaging data release from the JWST Advanced Deep Extragalactic Survey (JADES), providing nine filters of infrared imaging of ∼25 arcmin2 covering the Hubble Ultra Deep Field and portions of Great Observatories Origins Deep Survey South. Utilizing 87 on-sky dual-filter hours of exposure time, these images reveal the deepest ever near-infrared view of this iconic field. We supply carefully constructed nine-band mosaics of the JADES bands, as well as matching reductions of five additional bands from the JWST Extragalactic Medium-band Survey. Combining with existing Hubble Space Telescope imaging, we provide 23-band space-based photometric catalogs and photometric redshifts for ≈47,500 sources. To promote broad engagement with JADES, we have created an interactive FitsMap website to provide an interface for professional researchers and the public to experience these JWST data sets. Combined with the first JADES NIRSpec data release, these public JADES imaging and spectroscopic data sets provide a new foundation for discoveries of the infrared Universe by the worldwide scientific community

Social media in undergraduate medical education: A systematic review.

INTRODUCTION: There are over 3.81 billion worldwide active social media (SoMe) users. SoMe are ubiquitous in medical education, with roles across undergraduate programmes, including professionalism, blended learning, well being and mentoring. Previous systematic reviews took place before recent explosions in SoMe popularity and revealed a paucity of high-quality empirical studies assessing its effectiveness in medical education. This review aimed to synthesise evidence regarding SoMe interventions in undergraduate medical education, to identify features associated with positive and negative outcomes. METHODS: Authors searched 31 key terms through seven databases, in addition to references, citation and hand searching, between 16 June and 16 July 2020. Studies describing SoMe interventions and research on exposure to existing SoMe were included. Title, abstract and full paper screening were undertaken independently by two reviewers. Included papers were assessed for methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and/or the Standards for Reporting Qualitative Research (SRQR) instrument. Extracted data were synthesised using narrative synthesis. RESULTS: 112 studies from 26 countries met inclusion criteria. Methodological quality of included studies had not significantly improved since 2013. Engagement and satisfaction with SoMe platforms in medical education are described. Students felt SoMe flattened hierarchies and improved communication with educators. SoMe use was associated with improvement in objective knowledge assessment scores and self-reported clinical and professional performance, however evidence for long term knowledge retention was limited. SoMe use was occasionally linked to adverse impacts upon mental and physical health. Professionalism was heavily investigated and considered important, though generally negative correlations between SoMe use and medical professionalism may exist. CONCLUSIONS: Social media is enjoyable for students who may improve short term knowledge retention and can aid communication between learners and educators. However, higher-quality study is required to identify longer-term impact upon knowledge and skills, provide clarification on professionalism standards and protect against harms

Leipzig 2003

The 46th Leipzig International Festival for Documentary and Animation Films (14-19 October 2003) - the tenth under retiring festival director Fred Gehler - went down in the books as one of the best so far as politically relevant programming was concerned. Rithy Panh's S21 - La machine de mort Khm&egrave;re Rouge (S21 - The Khmer Rouge Killing Machine, France) was awarded both the Golden Dove for Best Long Doc&shy;umentary by the International Jury and the FIPRESCI Prize by the Inter&shy;national Critics. First seen at Cannes in the Official Program as a Special Screening, S21 is currently making the rounds of key international film festivals - after Leipzig it was booked for the Viennale and the London Film Festival. Running at 100 minutes, its plodding pace demands the complete attention of the viewer and makes for a quite horrifying experience as the story unfolds. S21 refers to the site of the..