Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study

Objective The aims of this study were to examine (i) base line pressure pain thresholds in patients with chronic fatigue syndrome and those with chronic low back pain compared with healthy subjects, (ii) the change in mean pain threshold in response to exercise, and (iii) associations with exercise induced increase in nitric oxide Participants Twenty six patients with chronic fatigue syndrome suffering of chronic pain, 21 patients with chronic low back pain and 31 healthy subjects Methods Participants underwent a submaximal aerobic exercise protocol on a bicycle ergometer, preceded and followed by venous blood sampling (nitric oxide) and algometry (hand arm calf low back) Results Patients with chronic fatigue syndrome presented overall lower pain thresholds compared with healthy sub jects and patients with chronic low back pain (p<0 05) No significant differences were found between healthy subjects and patients with chronic low back pain After submaximal aerobic exercise, mean pain thresholds decreased in patients with chronic fatigue syndrome and increased in the others (p<0 01) At baseline nitric oxide levels were significantly higher in the chronic low back pain group After controlling for body mass index no significant differences were seen be tween the groups at baseline or in response to exercise Nitric oxide was not related to pain thresholds in either group Conclusion The results suggest hyperalgesia and abnormal central pain processing during submaximal aerobic exercise in chronic fatigue syndrome, but not in chronic low back pain Nitric oxide appeared to be unrelated to pain processin

Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial.

&lt;b&gt;Objective&lt;/b&gt;: It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with Chronic Fatigue Syndrome (CFS). &lt;b&gt;Design&lt;/b&gt;: An uncontrolled clinical trial (semi-experimental design). &lt;b&gt;Setting&lt;/b&gt;: Outpatient clinic of a university department. &lt;b&gt;Subjects&lt;/b&gt;: 24 patients with CFS. &lt;b&gt;Interventions&lt;/b&gt;: Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an &lt;i&gt;intensity&lt;/i&gt; where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio =1.0 derived from a previous sub-maximal exercise test and for a duration calculated from how long each patient felt they were able to walk. &lt;b&gt;Main outcome measures&lt;/b&gt;: The Short Form 36 Health Survey or SF-36, the CFS Symptom List, and the CFS-Activities and Participation Questionnaire were filled in prior to, immediately and 24 hours post-exercise. &lt;b&gt;Results&lt;/b&gt;: The fatigue increase observed immediately post-exercise (p=0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (p=0.03). Fourteen of 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score ³10). Six of 24 participants indicated that the exercise bout had slightly worsened their health status, and 2 of 24 had a clinically meaningful decrease in vitality (change of SF-36 vitality score ³20). There was no change in activity limitations/participation restrictions. &lt;b&gt;Conclusion&lt;/b&gt;: It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with CFS, but was unable to prevent short-term symptom increases

Nanometer control in plasmonic systems through discrete layer-by-layer macrocycle-cation deposition.

In this work, we demonstrate that coordination interactions between Fe3+ and cucurbit[7]uril (CB[7]) can be utilised to build up defined nanoscale spacing layers in metallic nanosystems. We begin by characterising the layer-by-layer deposition of CB[7] and FeCl3·6H2O coordination layers through the use of a Quartz-Crystal Microbalance (QCM) and contact angle measurements. We then apply this layered structure to accurately control the spacing, and thus optical properties, of gold nanoparticles in a Nanoparticle-on-Mirror (NPoM) structure, which is demonstrated via normalising plasmon resonance spectroscopy.European Commission for a Marie Curie Fellowship (NANOSPHERE, 658360) ERC starting investigator grant (ASPiRe 240629) RC acknowledges support from the Dr. Manmohan Singh scholarship from St. John’s College BdN acknowledges support from the Leverhulme Trust and the Isaac Newton trust ECF

Single-molecule strong coupling at room temperature in plasmonic nanocavities

Emitters placed in an optical cavity experience an environment that changes their coupling to light. In the weak-coupling regime light extraction is enhanced, but more profound effects emerge in the single-molecule strong-coupling regime where mixed light-matter states form [1,2] . Individual two-level emitters in such cavities become non-linear for single photons, forming key building blocks for quantum information systems as well as ultra-low power switches and lasers [3–6] . Such cavity quantum electrodynamics has until now been the preserve of low temperatures and complex fabrication, severely compromising their use [5,7,8] . Here, by scaling the cavity volume below 40 nm^3 and using host-guest chemistry to align 1-10 protectively-isolated methylene-blue molecules, we reach the strong-coupling regime at room temperature and in ambient conditions. Dispersion curves from >50 plasmonic nanocavities display characteristic anticrossings, with Rabi frequencies of 300 meV for 10 molecules decreasing to 90 meV for single molecules, matching quantitative models. Statistical analysis of vibrational spectroscopy time-series and dark-field scattering spectra provide evidence of single-molecule strong coupling. This dressing of molecules with light can modify photochemistry, opening up the exploration of complex natural processes such as photosynthesis [9] and pathways towards manipulation of chemical bonds [10].We acknowledge financial support from EPSRC grants EP/G060649/1 and EP/I012060/1, and ERC grant LINASS 320503. RC acknowledges support from the Dr. Manmohan Singh scholarship from St. John’s College. FB acknowledges support from the Winton Programme for the Physics of Sustainability. SJB acknowledges support from the European Commission for a Marie Curie Fellowship (NANOSPHERE, 658360).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature17974

Single-molecule strong coupling at room temperature in plasmonic nanocavities.

Photon emitters placed in an optical cavity experience an environment that changes how they are coupled to the surrounding light field. In the weak-coupling regime, the extraction of light from the emitter is enhanced. But more profound effects emerge when single-emitter strong coupling occurs: mixed states are produced that are part light, part matter1, 2, forming building blocks for quantum information systems and for ultralow-power switches and lasers. Such cavity quantum electrodynamics has until now been the preserve of low temperatures and complicated fabrication methods, compromising its use. Here, by scaling the cavity volume to less than 40 cubic nanometres and using host–guest chemistry to align one to ten protectively isolated methylene-blue molecules, we reach the strong-coupling regime at room temperature and in ambient conditions. Dispersion curves from more than 50 such plasmonic nanocavities display characteristic light–matter mixing, with Rabi frequencies of 300 millielectronvolts for ten methylene-blue molecules, decreasing to 90 millielectronvolts for single molecules—matching quantitative models. Statistical analysis of vibrational spectroscopy time series and dark-field scattering spectra provides evidence of single-molecule strong coupling. This dressing of molecules with light can modify photochemistry, opening up the exploration of complex natural processes such as photosynthesis and the possibility of manipulating chemical bonds.We acknowledge financial support from EPSRC grants EP/G060649/1 and EP/I012060/1, and ERC grant LINASS 320503. RC acknowledges support from the Dr. Manmohan Singh scholarship from St. John’s College. FB acknowledges support from the Winton Programme for the Physics of Sustainability. SJB acknowledges support from the European Commission for a Marie Curie Fellowship (NANOSPHERE, 658360).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature17974

A new method for fine-scale assessments of the average urban Heat island over large areas and the effectiveness of nature-based solutions

People living in cities experience extra heat stress due to the so-called Urban Heat Island (UHI) effect. To gain an insight into the spatial variability of the UHI for the Netherlands, a detailed map (10 m horizontal resolution) has been calculated that shows the summer-averaged daily maximal UHI situation. The map is based on a relationship between the UHI, mean wind speed at 10 m height and the number of people living within a distance of 10 km, derived from simulations of over 100 European cities with the extensively validated urban climate model UrbClim. The cooling effect of green and blue infrastructure is also taken into account in the map, based on these simulation results. The presented map will help local authorities in defining target areas for climate adaptation measures and estimate the impact of nature-based solutions

Pharmacokinetics of Etravirine Combined with Atazanavir/Ritonavir and a Nucleoside Reverse Transcriptase Inhibitor in Antiretroviral Treatment-Experienced, HIV-1-Infected Patients

Objectives. TEACH (NCT00896051) was a randomized, open-label, two-arm Phase II trial to investigate the pharmacokinetic interaction between etravirine and atazanavir/ritonavir and safety and efficacy in treatment-experienced, HIV-1-infected patients. Methods. After a two-week lead-in of two nucleoside reverse transcriptase inhibitors (NRTIs) and atazanavir/ritonavir 300/100 mg, 44 patients received etravirine 200 mg bid with one NRTI, plus atazanavir/ritonavir 300/100 mg or 400/100 mg qd (n=22 each group) over 48 weeks. Results. At steady-state etravirine with atazanavir/ritonavir 300/100 mg qd or 400/100 mg qd decreased atazanavir Cmin⁡ by 18% and 9%, respectively, with no change in AUC24 h or Cmax⁡ versus atazanavir/ritonavir 300/100 mg qd alone (Day −1). Etravirine AUC12 h was 24% higher and 16% lower with atazanavir/ritonavir 300/100 or 400/100 mg qd, respectively, versus historical controls. At Week 48, no significant differences were seen between the atazanavir/ritonavir groups in discontinuations due to adverse events (9.1% each group) and other safety parameters, the proportion of patients with viral load <50 copies/mL (intent-to-treat population, noncompleter = failure) (50.0%, atazanavir/ritonavir 300/100 mg qd versus 45.5%, 400/100 mg qd), and virologic failures (31.8% versus 27.3%, resp.). Conclusions. Etravirine 200 mg bid can be combined with atazanavir/ritonavir 300/100 mg qd and an NRTI in HIV-1-infected, treatment-experienced patients without dose adjustment

Plasmon-induced optical control over dithionite-mediated chemical redox reactions.

External-stimuli controlled reversible formation of radical species is of great interest for synthetic and supramolecular chemistry, molecular machinery, as well as emerging technologies ranging from (photo)catalysis and photovoltaics to nanomedicine. Here we show a novel hybrid colloidal system for light-driven reversible reduction of chemical species that, on their own, do not respond to light. This is achieved by the unique combination of photo-sensitive plasmonic aggregates and temperature-responsive inorganic species generating radicals that can be finally accepted and stabilised by non-photo-responsive organic molecules. In this system Au nanoparticles (NPs) self-assembled via sub-nm precise molecular spacers (cucurbit[n]urils) interact strongly with visible light to locally accelerate the decomposition of dithionite species (S2O42-) close to the NP interfaces. This light-driven process leads to the generation of inorganic radicals whose electrons can then be reversibly picked up by small organic acceptors, such as the methyl viologen molecules (MV2+) used here. During light-triggered plasmon- and heat-assisted generation of radicals, the S2O42- species work as a chemical 'fuel' linking photo-induced processes at the NP interfaces with redox chemistry in the surrounding water environment. By incorporating MV2+ as a Raman-active reporter molecule, the resulting optically-controlled redox processes can be followed in real-time.European commision: Marie Skłodowska-Curie funding, ERC, EPSRC, Leverhulme Trust, Newton Trust

Primary hemiarthroplasty versus conservative treatment for comminuted fractures of the proximal humerus in the elderly (ProCon): A Multicenter Randomized Controlled trial

Background. Fractures of the proximal humerus are associated with a profound temporary and sometimes permanent, impairment of function and quality of life. The treatment of comminuted fractures of the proximal humerus like selected three-or four-part fractures and split fractures of the humeral head is a demanding and unresolved problem, especially in the elderly. Locking plates appear to offer improved fixation; however, screw cut-out rates ranges due to fracture collapse are high. As this may lead to higher rates of revision surgery, it may be preferable to treat comminuted fractures in the elderly primarily with a prosthesis or non-operatively. Results from case series and a small-sample randomized controlled trial (RCT) suggest improved function and less pain after primary hemiarthroplasty (HA); however these studies had some limitations and a RCT is needed. The primary aim of this study is to compare the Constant scores (reflecting functional outcome and pain) at one year after primary HA versus non-operative treatment in elderly patients who sustained a comminuted proximal humeral fracture. Secondary aims include effects on functional outcome, pain, complications, quality of life, and cost-effectiveness. Methods/Design. A prospective, multi-center RCT will be conducted in nine centers in the Netherlands and Belgium. Eighty patients over 65 years of age, who have sustained a three-or four part, or split head proximal humeral fracture will be randomized between primary hemiarthroplasty and conservative treatment. The primary outcome is the Constant score, which indicates pain and function. Secondary outcomes include the Disability of the Arm and Shoulder (DASH) score, Visual Analogue Scale (VAS) for pain, radiographic healing, health-related quality of life (Short-form-36, EuroQol-5D) and healthcare consumption. Cost-effectiveness ratios wi

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK