Temporal Aspects of Endogenous Pain Modulation During a Noxious Stimulus Prolonged for 1 Day

Background This study investigated (a) if a prolonged noxious stimulus (24‐hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and (b) if acute pain relief or exacerbation (cooling and heating the capsaicin patch) during the prolonged noxious stimulus would affect central pain modulation. Methods Twenty‐eight participants (26.2 ± 1.0 years; 12 women) wore a transdermal 8% capsaicin patch on the forearm for 24 hr. Data were collected at baseline (Day 0), 1 hr, 3 hr, Day 1 (post‐capsaicin application) and Day 3/4 (post‐capsaicin removal) that included capsaicin‐evoked pain intensity, heat pain thresholds (HPTs), TSP (10 painful cuff pressure stimuli on leg) and CPM (cuff pressure pain threshold on the leg prior vs. during painful cuff pressure conditioning on contralateral leg). After 3 hr, cold (12°C) and heat (42°C) stimuli were applied to the capsaicin patch to transiently increase and decrease pain intensity. Results Participants reported moderate pain scores at 1 hr (2.5 ± 2.0), 3 hr (3.7 ± 2.4), and Day 1 (2.4 ± 1.8). CPM decreased 3‐hr post‐capsaicin (p = .001) compared to Day 0 and remained diminished while the capsaicin pain score was reduced (0.4 ± 0.7, p \u3c .001) and increased (6.6 ± 2.2, p \u3c .001) by patch cooling and heating. No significant differences occurred for CPM during patch cooling or heating compared to initial 3HR; however, CPM during patch heating was reduced compared with patch cooling (p = .01). TSP and HPT did not change. Conclusions This prolonged experimental pain model is useful to provide insight into subacute pain conditions and may provide insight into the transition from acute to chronic pain. Significance During the early hours of a prolonged noxious stimulus in healthy adults, CPM efficacy was reduced and did not recover by temporarily removing the ongoing pain indicating a less dynamic neuroplastic process

A review of the NE Atlantic conjugate margins based on seismic refraction data

The NE Atlantic region evolved through several rift episodes, leading to break-up in the Eocene that was associated with voluminous magmatism along the conjugate margins of East Greenland and NW Europe. Existing seismic refraction data provide good constraints on the overall tectonic development of the margins, despite data gaps at the NE Greenland shear margin and the southern Jan Mayen microcontinent. The maximum thickness of the initial oceanic crust is 40 km at the Greenland–Iceland–Faroe Ridge, but decreases with increasing distance to the Iceland plume. High-velocity lower crust interpreted as magmatic underplating or sill intrusions is observed along most margins but disappears north of the East Greenland Ridge and the Lofoten margin, with the exception of the Vestbakken Volcanic Province at the SW Barents Sea margin. South of the narrow Lofoten margin, the European side is characterized by wide margins. The opposite trend is seen in Greenland, with a wide margin in the NE and narrow margins elsewhere. The thin crust beneath the basins is generally underlain by rocks with velocities of >7 km s−1 interpreted as serpentinized mantle in the Porcupine and southern Rockall basins; while off Norway, alternative interpretations such as eclogite bodies and underplating are also discussed

Moho and basement depth in the NE Atlantic Ocean based on seismic refraction data and receiver functions

Seismic refraction data and results from receiver functions were used to compile the depth to the basement and Moho in the NE Atlantic Ocean. For interpolation between the unevenly spaced data points, the kriging technique was used. Free-air gravity data were used as constraints in the kriging process for the basement. That way, structures with little or no seismic coverage are still presented on the basement map, in particular the basins off East Greenland. The rift basins off NW Europe are mapped as a continuous zone with basement depths of between 5 and 15 km. Maximum basement depths off NE Greenland are 8 km, but these are probably underestimated. Plate reconstructions for Chron C24 (c. 54 Ma) suggest that the poorly known Ammassalik Basin off SE Greenland may correlate with the northern termination of the Hatton Basin at the conjugate margin. The most prominent feature on the Moho map is the Greenland–Iceland–Faroe Ridge, with Moho depths >28 km. Crustal thickness is compiled from the Moho and basement depths. The oceanic crust displays an increased thickness close to the volcanic margins affected by the Iceland plume

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q< 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

Clar Sextet Analysis of Triangular, Rectangular and Honeycomb Graphene Antidot Lattices

Pristine graphene is a semimetal and thus does not have a band gap. By making a nanometer scale periodic array of holes in the graphene sheet a band gap may form; the size of the gap is controllable by adjusting the parameters of the lattice. The hole diameter, hole geometry, lattice geometry and the separation of the holes are parameters that all play an important role in determining the size of the band gap, which, for technological applications, should be at least of the order of tenths of an eV. We investigate four different hole configurations: the rectangular, the triangular, the rotated triangular and the honeycomb lattice. It is found that the lattice geometry plays a crucial role for size of the band gap: the triangular arrangement displays always a sizable gap, while for the other types only particular hole separations lead to a large gap. This observation is explained using Clar sextet theory, and we find that a sufficient condition for a large gap is that the number of sextets exceeds one third of the total number of hexagons in the unit cell. Furthermore, we investigate non-isosceles triangular structures to probe the sensitivity of the gap in triangular lattices to small changes in geometry

Preoperative neuropathic pain like symptoms and central pain mechanisms in knee osteoarthritis predicts poor outcome 6 months after total knee replacement surgery

Preoperative pain characteristics in osteoarthritis (OA) patients may explain persistent pain after total knee replacement (TKR). Fifty patients awaiting TKR and 22 asymptomatic controls were recruited to evaluate the degree of neuropathic pain symptoms and pain sensitisation. OA patients were pain phenotyped into two groups based on the PainDETECT questionnaire: High PainDETECT group (scores ≥19) indicating neuropathic pain-like symptoms, Low PainDETECT group (scores 19) indicating nociceptive or mixed pain.Cuff algometry assessing pain detection thresholds (PDT) and pain tolerance (PTT) was conducted on the lower legs. Temporal summation of pain (TSP) was assessed using ten sequential cuff stimulations and a von Frey stimulator. Conditioning pain modulation was assessed by cuff pain conditioning on one leg and parallel assessment of PDT on the contralateral leg. Pressure pain thresholds (PPTs) were recorded by pressure handheld algometry local and distant to the knee. Knee pain intensity (VAS) and pain assessment were collected before and 6 months post-TKR. 30% of patients demonstrated neuropathic pain-like symptoms (High PainDETECT group). Facilitated TSP and reduced PPTs distant to the knee were found in High PainDETECT group compared to Low PainDETECT group and healthy controls groups (

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice