Comprehensive Assessment of GPR68 Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody

GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved in cellular adaptations to pH changes during tumour development. Although expression of GPR68 has been described in many tumour cell lines, little is known about its presence in human tumour entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16 using various cell lines and tissue specimens. The antibody was then applied to a large series of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Antibody specificity was demonstrated in a Western blot analysis of GPR68-expressing cells using specific siRNAs. Immunocytochemical experiments revealed pH-dependent changes in subcellular localisation of the receptor and internalisation after stimulation with lorazepam. In normal tissue, GPR68 was present in glucagon-producing islet cells, neuroendocrine cells of the intestinal tract, gastric glands, granulocytes, macrophages, muscle layers of arteries and arterioles, and capillaries. GPR68 was also expressed in neuroendocrine tumours, where it may be a positive prognostic factor, in pheochromocytomas, cervical adenocarcinomas, and endometrial cancer, as well as in paragangliomas, medullary thyroid carcinomas, gastrointestinal stromal tumours, and pancreatic adenocarcinomas. Often, tumour capillaries were also strongly GPR68-positive. The novel antibody 16H23L16 will be a valuable tool for basic research and for identifying GPR68-expressing tumours during histopathological examinations

A Variable Stiffness Robotic Probe for Soft Tissue Palpation

During abdominal palpation diagnosis, a medical practitioner would change the stiffness of their fingers in order to improve the detection of hard nodules or abnormalities in soft tissue to maximize the haptic information gain via tendons. Our recent experiments using a controllable stiffness robotic probe representing a human finger also confirmed that such stiffness control in the finger can enhance the accuracy of detecting hard nodules in soft tissue. However, the limited range of stiffness achieved by the antagonistic springs variable stiffness joint subject to size constraints made it unsuitable for a wide range of physical examination scenarios spanning from breast to abdominal examination. In this letter, we present a new robotic probe based on a variable lever mechanism able to achieve stiffness ranging from 0.64 to 1.06 N ⋅m/rad that extends the maximum stiffness by around 16 times and the stiffness range by 33 times. This letter presents the mechanical model of the novel probe, the finite element simulation as well as experimental characterization of the stiffness response for lever actuation

Quantum \v{C}erenkov Radiation: Spectral Cutoffs and the Role of Spin and Orbital Angular Momentum

We show that the well-known \v{C}erenkov Effect contains new phenomena arising from the quantum nature of charged particles. The \v{C}erenkov transition amplitudes allow coupling between the charged particle and the emitted photon through their orbital angular momentum (OAM) and spin, by scattering into preferred angles and polarizations. Importantly, the spectral response reveals a discontinuity immediately below a frequency cutoff that can occur in the optical region. Specifically, with proper shaping of electron beams (ebeams), we predict that the traditional \v{C}erenkov radiation angle splits into two distinctive cones of photonic shockwaves. One of the shockwaves can move along a backward cone, otherwise considered impossible for \v{C}erenkov radiation in ordinary matter. Our findings are observable for ebeams with realistic parameters, offering new applications including novel quantum optics sources, and open a new realm for \v{C}erenkov detectors involving the spin and orbital angular momentum of charged particles.Comment: 27 pages, 3 figure

Exogenous Ketone Salt Supplementation and Whole-Body Cooling Do Not Improve Short-Term Physical Performance

Publisher Copyright: © Copyright © 2021 Clark, Munten, Herzig and Gagnon.Exogenous ketone supplementation and whole-body cooling (WBC) have shown to independently influence exercise metabolism. Whether readily available ketone salts, with and without WBC, would provide similar metabolic benefits during steady-state aerobic and time-trial performances was investigated. Nine active males (VO2peak: 56.3 ± 2.2 mL·kg−1·min−1) completed three single-blind exercise sessions preceded by: (1) ingestion of placebo (CON), (2) ketone supplementation (0.3 g·kg−1 β-OHB) (KET), and (3) ketone supplementation with WBC (KETCO). Participants cycled in steady-state (SS, 60% Wmax) condition for 30-min, immediately followed by a 15-min time trial (TT). Skin and core temperature, cardio-metabolic, and respiratory measures were collected continuously, whereas venous blood samples were collected before and after supplementation, after SS and TT. Venous β-OHB was elevated, while blood glucose was lower, with supplementation vs. CON (p < 0.05). TT power output was not different between conditions (p = 0.112, CON: 190 ± 43.5 W, KET: 185 ± 40.4 W, KETCO: 211 ± 50.7 W). RER was higher during KETCO (0.97 ± 0.09) compared to both CON (0.88 ± 0.04, p = 0.012) and KET (0.88 ± 0.05, p = 0.014). Ketone salt supplementation and WBC prior to short-term exercise sufficiently increase blood β-OHB concentrations, but do not benefit metabolic shifts in fuel utilization or improve time trial performance.Peer reviewe

The trail making test as a screening instrument for driving performance in older drivers; a translational research.

BACKGROUND: In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients' on-road driving performance in the context of cognitive decline. METHODS: This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers' licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance. RESULTS: The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%. CONCLUSION: In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors

CO2 isotope sensor using a broadband infrared source, a spectrally narrow 4.4 μm quantum cascade detector, and a Fourier spectrometer

We report a prototype CO2 gas sensor based on a simple blackbody infrared source and a spectrally narrow quantum cascade detector (QCD). The detector absorption spectrum is centered at 2260cm−1 (4.4μm) and has a full width at half maximum of 200cm−1 (25meV). It covers strong absorption bands of two spectrally overlapping CO2 isotopomers, namely the P-branch of 12CO2 and the R-branch of 13CO2. Acquisition of the spectral information and data treatment were performed in a Fourier transform infrared (FTIR) spectrometer. By flushing its sample compartment either with nitrogen, dry fresh air, ambient air, or human breath, we were able to determine CO2 concentrations corresponding to the different gas mixtures. Adetection limit of 500ppb was obtained in these experiment

The role of faith-based health professions schools in Cameroon’s health system

Faith-based health professions schools contribute to the training of staff in many Sub-Saharan African countries. Yet little is known about these actors, their role in the health system, potential comparative advantages and challenges faced. This is a qualitative study drawing on 24 qualitative interviews and 3 focus group discussions. Participants included faith-based health professions schools, staff at faith-based health professions schools, Ministry of Health officials and donors. Thematic analysis was used to analyse the data. The findings reveal that understanding of faith-based health professions schools held by donors and the Ministry of Health rest on a set of assumptions rather than evidence-backed knowledge and that knowledge on key aspects is missing (not least on the market share of such actors). This suggests that collaboration with and oversight of these non-state schools is limited, raising questions about the balance of state regulation and control in the public-private mix for training health workers. Linked to this weak oversight, the findings also raise concerns over a number of problematic activities at these schools, unaccredited training programmes and the presence of missionary volunteers whose presence and actions are rarely interrogated

(Neuro) Peptides, Physical Activity, and Cognition

Regular physical activity (PA) improves cognitive functions, prevents brain atrophy, and delays the onset of cognitive decline, dementia, and Alzheimer's disease. Presently, there are no specific recommendations for PA producing positive effects on brain health and little is known on its mediators. PA affects production and release of several peptides secreted from peripheral and central tissues, targeting receptors located in the central nervous system (CNS). This review will provide a summary of the current knowledge on the association between PA and cognition with a focus on the role of (neuro)peptides. For the review we define peptides as molecules with less than 100 amino acids and exclude myokines. Tachykinins, somatostatin, and opioid peptides were excluded from this review since they were not affected by PA. There is evidence suggesting that PA increases peripheral insulin growth factor 1 (IGF-1) levels and elevated serum IGF-1 levels are associated with improved cognitive performance. It is therefore likely that IGF-1 plays a role in PA induced improvement of cognition. Other neuropeptides such as neuropeptide Y (NPY), ghrelin, galanin, and vasoactive intestinal peptide (VIP) could mediate the beneficial effects of PA on cognition, but the current literature regarding these (neuro)peptides is limited.Peer reviewe