pinecone/core-2020-05-10-deduplication huggingface dataset:
Molecular Transformation of 2-Methylazulenes: An Efficient and Practical Synthesis of 2-Formyl- and 2-Ethynylazulenes

First published: 09 Jan 20182-Formylazulene derivatives have been obtained in good yields by the reactions of 2-methylazulenes with N,N-dimethylformamide dimethyl acetal, followed by oxidative cleavage of the intermediately formed enamines with NaIO4. Vilsmeier formylation of 1-phenyl-3-methylazulenes also afforded the corresponding 2-formylazulenes in moderate yields. The treatment of a 2-methylazulene derivative bearing a formyl group at the 1-position with sodium methoxide led, through a self-condensation reaction, to a trans-1-(azulen-1-yl)-2-(azulen-2-yl)ethylene derivative, the structure of which was verified by single-crystal X-ray diffraction analysis. The 2-formylazulenes obtained were transformed into 2-ethynylazulenes in good yields by a modified Seyferth-Gilbert reaction. The reactivity of a 1-iodoazulene bearing a 2-formyl function in palladium-catalyzed cross-coupling reactions has also been examined
Rapid Synthesis of L-Idosyl Glycosyl Donors from α-\ud
Thioglucosides for the Preparation of Heparin Disaccharides

A new methodology for the synthesis of the most\ud
challenging heparin building block has been developed.\ud
Orthogonally protected L-idosyl glycosyl donors were prepared by\ud
C5 epimerization of the corresponding thioglucosides using the\ud
hydroboration/oxidation method followed by a 4,6-acetal formation.\ud
The -anomeric configuration was crucial and the bulky C4\ud
substituent was advantageous for the high L-ido diastereoselectivity.\ud
The 4,6-arylmethylene group proved to be a directing element in\ud
glycosylation thereby stereoselective -idosylation could be\ud
achieved by using idosyl donors without a C-2 participating group
Approaches to styrenyl building blocks for the synthesis of polyene xanthomonadin and its analogues.

A number of aryl building blocks for the synthesis of two xanthomonadin natural product pigments, as well as a related analogue, were accessed using a divergent hydroboration/bromoboration approach from a key alkynyl intermediate. A new approach towards substitution patterns around the ring was adopted following the isolation of an unexpected regioisomer from the bromination reaction. Potential coupling reactions onto these building blocks were explored, with a successful Sonogashira coupling performed on the key alkynyl intermediate, and with the key debrominated styrenyl boronate ester intermediate functionalised both by preliminary Suzuki–Miyaura coupling and by iododeboronation/Heck–Mizoroki coupling. Coupling reactions with brominated styrenyl intermediates proved much more challenging due to the instability of the intermediates to cross‐coupling, but some studies have shown promise
Acupuncture and electro-acupuncture for people diagnosed with subacromial pain syndrome: A multicentre randomized trial.

This is the peer-reviewed version of the following article: J. Lewis, J. Sim, and P. Barlas, Acupuncture and electro-acupuncture for people diagnosed with subacromial pain syndrome: A multicentre randomized trial, European Journal of Pain, first published 20 January 2017, available online at doi 10.1002/ejp.1001. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. ?? 2017 European Pain Federation - EFIC??Background Musculoskeletal disorders have been identified globally as the second most common healthcare problem for ???years lived with disability???, and of these shoulder conditions are amongst the most common, frequently associated with substantial pain and morbidity. Exercise and acupuncture are often provided as initial treatments for musculoskeletal shoulder conditions but their clinical effectiveness is uncertain. This study compared group exercise with group exercise plus either acupuncture or electro-acupuncture in patients with subacromial pain syndrome. Methods Two hundred and twenty-seven participants were recruited to a three-arm parallel-group randomized clinical trial. The primary outcome measure was the Oxford Shoulder Score. Follow-up was post treatment, and at 6 and 12 months. Between-group differences (two comparisons: the exercise group versus each of the acupuncture groups) were analysed at 6 months. A similar comparison across all follow-up time points was also conducted. Data were analysed on intention-to-treat principles with imputation of missing values. Results Treatment groups were similar at baseline, and all treatment groups demonstrated an improvement over time. Between-group estimates at 6 months were, however, small and non-significant, for both of the comparisons. The analyses across all follow-up time points yielded similar conclusions. There was a high rate of missing values (22% for the Oxford Shoulder Score). A sensitivity analysis using complete data gave similar conclusions to the analysis with missing values imputed. Conclusions In the current investigation, neither acupuncture nor electro-acupuncture were found to be more beneficial than exercise alone in the treatment of subacromial pain syndrome. These findings may support clinicians with treatment planning. Significance Shoulder pain is common and associated with substantial morbidity. Acupuncture is a popular treatment for shoulder pain. The findings suggest that acupuncture and electro-acupuncture offer no additional benefit over exercise in the treatment of shoulder pain of musculoskeletal origin
Brain changes associated with cognitive and emotional factors in chronic pain : a systematic review

An emerging technique in chronic pain research is MRI, which has led to the understanding that chronic pain patients display brain structure and function alterations. Many of these altered brain regions and networks are not just involved in pain processing, but also in other sensory and particularly cognitive tasks. Therefore, the next step is to investigate the relation between brain alterations and pain related cognitive and emotional factors. This review aims at providing an overview of the existing literature on this subject. Pubmed, Web of Science and Embase were searched for original research reports. Twenty eight eligible papers were included, with information on the association of brain alterations with pain catastrophizing, fear-avoidance, anxiety and depressive symptoms. Methodological quality of eligible papers was checked by two independent researchers. Evidence on the direction of these associations is inconclusive. Pain catastrophizing is related to brain areas involved in pain processing, attention to pain, emotion and motor activity, and to reduced top-down pain inhibition. In contrast to pain catastrophizing, evidence on anxiety and depressive symptoms shows no clear association with brain characteristics. However, all included cognitive or emotional factors showed significant associations with resting state fMRI data, providing that even at rest the brain reserves a certain activity for these pain-related factors. Brain changes associated with illness perceptions, pain attention, attitudes and beliefs seem to receive less attention in literature. 
Significance: This review shows that maladaptive cognitive and emotional factors are associated with several brain regions involved in chronic pain. Targeting these factors in these patients might normalize specific brain alterations
Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain

Background: Motivational and behavioral models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses. \ud
Methods: We examined changes in motivation, coping and acceptance among 78 men with chronic hemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioral changes, and one in which behavioral changes influence motivational changes. \ud
Results: Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioral component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioral model of pain acceptance. \ud
Conclusions: Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain
Conditioned pain modulation is affected by occlusion cuff conditioning stimulus intensity, but not duration

Background:
Various conditioned pain modulation (CPM) methodologies have been used to investigate diffuse noxious inhibitory control pain mechanisms in healthy and clinical populations. Occlusion cuff parameters have been poorly studied. We aimed to investigate whether occlusion cuff intensity and/or duration influenced CPM magnitudes. We also investigated the role of physical activity levels on CPM magnitude.

Methods:
Two studies were performed to investigate the role of intensity and duration of occlusion cuff conditioning stimulus on test stimulus (tibialis anterior pressure pain thresholds). In Study 1, conditioning stimulus intensity of 2/10 or 5/10 (duration <20 s) was evaluated using a paired‐samples t‐test. In Study 2, duration of 2/10 conditioning stimulus was 3 min. One‐way repeated‐measures ANOVA was used to investigate the effect of time (0, 1, 2 and 3 min) on CPM magnitude.

Results:
In Study 1, 27 healthy volunteers (mean ± SD: 24.9 years (±4.5); eight female) demonstrated that an occlusion cuff applied to the upper arm eliciting 5/10 local pain resulted in a significant (mean ± SD: 17% ± 46%) increase in CPM magnitude, when compared to 2/10 intensity (−3% ± 38%, p = 0.026), whereas in Study 2, 25 healthy volunteers (22.5 years (±2.7); 13 female) demonstrated that 3 min of 2/10 CS intensity did not result in a significant change in CPM (p = 0.21). There was no significant relationship between physical activity levels and CPM in either study (p > 0.22).

Conclusions:
This study demonstrated that an occlusion cuff of 5/10 conditioning stimulus intensity, when compared to 2/10, significantly increased CPM magnitude. Maintaining 2/10 conditioning stimulus for 3 min did not increase CPM magnitude.

Significance:
Dysfunctional conditioned pain modulation (CPM) has been associated with poor health outcomes. Various factors can influence CPM outcomes. The role of occlusion cuff conditioning stimulus intensity and duration has not been previously investigated. Intensity (5/10), but not duration of lower intensity (2/10) conditioning stimulus, affects CPM magnitude.Griffith Health, School of Applied PsychologyFull Tex
The MOBID-2 pain scale: Reliability and responsiveness to pain in patients with dementia

<p>Background: Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) pain scale is a staff-administered pain tool for patients with dementia. This study explores MOBID-2&rsquo;s test&ndash;retest reliability, measurement error and responsiveness to change.</p>
<p>Methods: Analyses are based upon data from a cluster randomized trial including 352 patients with advanced dementia from 18 Norwegian nursing homes. Test&ndash;retest reliability between baseline and week 2 (n = 163), and weeks 2 and 4 (n = 159) was examined in patients not expected to change (controls), using intraclass correlation coefficient (ICC2.1), standard error of measurement (SEM) and smallest detectable change (SDC). Responsiveness was examined by testing six priori-formulated hypotheses about the association between change scores on MOBID-2 and other outcome measures.</p>
<p>Results: ICCs of the total MOBID-2 scores were 0.81 (0&ndash;2 weeks) and 0.85 (2&ndash;4 weeks). SEM and SDC were 1.9 and 3.1 (0&ndash;2 weeks) and 1.4 and 2.3 (2&ndash;4 weeks), respectively. Five out of six hypotheses were confirmed: MOBID-2 discriminated (p &lt; 0.001) between change in patients with and without a stepwise protocol for treatment of pain (SPTP). Moderate association (r = 0.35) was demonstrated with Cohen-Mansfield Agitation Inventory, and no association with Mini-Mental State Examination, Functional Assessment Staging and Activity of Daily Living. Expected associations between change scores of MOBID-2 and Neuropsychiatric Inventory &ndash; Nursing Home version were not confirmed.</p>
<p>Conclusion: The SEM and SDC in connection with the MOBID-2 pain scale indicate that the instrument is responsive to a decrease in pain after a SPTP. Satisfactory test&ndash;retest reliability across test periods was demonstrated. Change scores &ge; 3 on total and subscales are clinically relevant and are beyond measurement error.</p
Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: A cluster randomized trial

<p>Background: Pain is frequent and distressing in people with dementia, but no randomized controlled trials have evaluated the effect of analgesic treatment on pain intensity as a key outcome.</p>
<p>Methods: Three hundred fifty-two people with dementia and significant agitation from 60 nursing home units were included in this study. These units, representing 18 nursing homes in western Norway, were randomized to a stepwise protocol of treating pain (SPTP) or usual care. The SPTP group received acetaminophen, morphine, buprenorphine transdermal patch and pregabalin for 8 weeks, with a 4-week washout period. Medications were governed by the SPTP and each participant&rsquo;s existing prescriptions. We obtained pain intensity scores from 327 patients (intervention n = 164, control n = 163) at five time points assessed by the primary outcome measure, Mobilization-Observation-Behaviour- Intensity-Dementia-2 (MOBID-2) Pain Scale. The secondary outcome was activities of daily living (ADL). We used a linear intercept mixed model in a two-way repeated measures configuration to assess change over time and between groups.</p>
<p>Results: The SPTP conferred significant benefit in MOBID-2 scores compared with the control group [average treatment effect (ATE) &minus;1.388; p &lt; 0.001] at week 8, and MOBID-2 scores worsened during the washout period (ATE = &minus;0.701; p = 0.022). Examining different analgesic treatments, benefit was conferred to patients receiving acetaminophen compared with the controls at week 2 (ATE = &minus;0.663; p = 0.010), continuing to increase until week 8 (ATE = &minus;1.297; p &lt; 0.001). Although there were no overall improvements in ADL, an increase was seen in the group receiving acetaminophen (ATE = +1.0; p = 0.022).</p>
<p>Conclusion: Pain medication significantly improved pain in the intervention group, with indications that acetaminophen also improved ADL function.</p
Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

© 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®. Funding sources E.K.B. was funded by a BBSRC PhD studentship. A.N., A.S.C.R. and T.P. were funded by a Wellcome Trust Strategic Award (London Pain Consortium; ref. 083259). A.S.C.R. and W.H. were funded by the Innovative Medicines Initiative Joint Undertaking (Europain; grant agreement no. 115007). We thank Pfizer for providing stavudine. Conflicts of interest None declared. Funded by BBSRC PhD studentship Wellcome Trust Strategic Award. Grant Number: 083259 Innovative Medicines Initiative Joint Undertaking. Grant Number: 115007Peer reviewedPublisher PD
Hypervigilance for innocuous tactile stimuli in patients with fibromyalgia: an experimental approach

Background: Hypervigilance, i.e., excessive attention, is often invoked as a potential explanation for the observation that many individuals with fibromyalgia show a heightened sensitivity to stimulation in various sensory modalities, such as touch and hearing. Compelling evidence for this assumption is, however, lacking. The aim of the present study was to investigate the presence of somatosensory hypervigilance in patients with fibromyalgia.
Methods: Fibromyalgia patients (n=41) and a matched control group (n=40) performed a tactile change detection task in which they had to detect whether there was a change between two consecutively presented patterns of tactile stimuli presented to various body locations. The task was performed under two conditions: in the unpredictable condition, tactile changes occurred equally often at all possible body locations; in the predictable condition, the majority of tactile changes occurred at one specific body location.
Results: It was hypothesized that the fibromyalgia group would show better tactile change detection in the unpredictable condition and when changes ocurred at unexpected locations in the predictable condition. The results did not support this hypothesis. In neither condition was the fibromyalgia group better than the control group in detecting tactile changes.
Conclusions: No evidence was found to support the claim that patients with fibromyalgia display somatosensory hypervigilance. This finding challenges the idea of hypervigilance as a static feature of fibromyalgia and urges for a more dynamic view in which hypervigilance emerges in situations when bodily threat is experienced
Enhanced c-Fos expression in the central amygdala correlates with increased thigmotaxis in rats with peripheral nerve injury

Pain is associated with affective, cognitive and sensory dysfunction. Animal models can be used to observe ethologically relevant behaviours such as thigmotaxis, giving insight into how ongoing sensory abnormalities influence natural rodent behaviours. The amygdala is a complex group of nuclei implicated in the integration and generation of emotional behavioural responses, including those associated with pain, and a region known as the central amygdala is particularly associated with generation of behavioural responses, due to its links to the descending pain modulation pathways; as such, study of amygdalar c-Fos immunoreactivity can help identify the neuronal circuits involved.This study investigated changes in both nociceptive evoked responses and open field behaviour following spinal nerve transection (SNT) in male Wistar rats, and attempted to correlate these with changes in central amygdala c-Fos immunoreactivity.Fourteen days after SNT, mechanical hypersensitivity was present in the hind paw ipsilateral to site of injury. Thigmotactic behaviour was significantly increased in both SNT and sham surgery animals, with c-Fos immunoreactivity in the central amygdala significantly greater in SNT animals compared to both sham and naive groups. Activation was greatest in the capsular and lateral subnuclei of the central amygdala, and in the caudal-most regions. There was a strong correlation between thigmotactic behaviour and central amygdala activation following SNT surgery not seen in sham animals suggesting a role for the amygdala in behavioural responses to peripheral nerve injury.This study provides evidence to support the role of the amygdala in thigmotactic open field behaviour following SNT. WHAT DOES THIS STUDY ADD?: Thigmotaxis and amygdala activation are positively correlated in rats following spinal nerve transection. Behavioural changes seen in sham animals did not correlate with amygdala activation, suggesting amygdala activation is related to nociceptive input. Evoked measures, such as hindpaw withdrawal, are not correlated with either thigmotaxis or amygdala activation, emphasizing the importance of complex behaviours when studying pain
Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain

__Background:__ Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain.  \ud
__Methods:__ Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. Primary outcome measure: pain reduction. Secondary outcome measure: Global Perceived Effect.  \ud
__Results:__ No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found.  \ud
__Conclusions:__ The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction.  \ud
__Significance:__ Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected