The Global Threat of Counterfeit Drugs: Why Industry and Governments Must Communicate the Dangers

The production of substandard and fake drugs is a vast and underreported problem, particularly affecting poorer countries. Cockburn and colleagues argue that the pharmaceutical industry and governments must both take actio

A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries

The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo- oxygenase inhibitors). The effects of barium and ouabain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery : Combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). Results: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.Peer reviewedFinal Published versio

Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System

Background: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. Methods: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. Results: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7–8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. Conclusions: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.

Comparative cytogenetics of Auchenorrhyncha (Hemiptera, Homoptera): a review

A comprehensive review of cytogenetic features is provided for the large hemipteran suborder Auche norrhyncha, which currently contains approximately 42,000 valid species. This review is based on the analysis of 819 species, 483 genera, and 31 families representing all presently recognized Auchenorrhyn cha superfamilies, e.i. Cicadoidea (cicadas), Cercopoidea (spittle bugs), Membracoidea (leafhoppers and treehoppers), Myerslopioidea (ground-dwelling leafhoppers), and Fulgoroidea (planthoppers). History and present status of chromosome studies are described, as well as the structure of chromosomes, chro mosome counts, trends and mechanisms of evolution of karyotypes and sex determining systems, their variation at different taxonomic levels and most characteristic (modal) states, occurrence of partheno genesis, polyploidy, B-chromosomes and chromosome rearrangements, and methods used for cytoge netic analysis of Auchenorrhyncha.info:eu-repo/semantics/publishedVersio

Dynamics of a Quantum Phase Transition and Relaxation to a Steady State

We review recent theoretical work on two closely related issues: excitation of an isolated quantum condensed matter system driven adiabatically across a continuous quantum phase transition or a gapless phase, and apparent relaxation of an excited system after a sudden quench of a parameter in its Hamiltonian. Accordingly the review is divided into two parts. The first part revolves around a quantum version of the Kibble-Zurek mechanism including also phenomena that go beyond this simple paradigm. What they have in common is that excitation of a gapless many-body system scales with a power of the driving rate. The second part attempts a systematic presentation of recent results and conjectures on apparent relaxation of a pure state of an isolated quantum many-body system after its excitation by a sudden quench. This research is motivated in part by recent experimental developments in the physics of ultracold atoms with potential applications in the adiabatic quantum state preparation and quantum computation.Comment: 117 pages; review accepted in Advances in Physic

Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity

Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation.Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as nextgeneration cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAstowards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these leadSSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cellmembrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediatedcytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus eitheragent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhancethe cytotoxic activity of a chemotherapeutic drug in human cancer cells

Gamma Power Is Phase-Locked to Posterior Alpha Activity

Neuronal oscillations in various frequency bands have been reported in numerous studies in both humans and animals. While it is obvious that these oscillations play an important role in cognitive processing, it remains unclear how oscillations in various frequency bands interact. In this study we have investigated phase to power locking in MEG activity of healthy human subjects at rest with their eyes closed. To examine cross-frequency coupling, we have computed coherence between the time course of the power in a given frequency band and the signal itself within every channel. The time-course of the power was calculated using a sliding tapered time window followed by a Fourier transform. Our findings show that high-frequency gamma power (30–70 Hz) is phase-locked to alpha oscillations (8–13 Hz) in the ongoing MEG signals. The topography of the coupling was similar to the topography of the alpha power and was strongest over occipital areas. Interestingly, gamma activity per se was not evident in the power spectra and only became detectable when studied in relation to the alpha phase. Intracranial data from an epileptic subject confirmed these findings albeit there was slowing in both the alpha and gamma band. A tentative explanation for this phenomenon is that the visual system is inhibited during most of the alpha cycle whereas a burst of gamma activity at a specific alpha phase (e.g. at troughs) reflects a window of excitability