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Background: As a disorder of brain dysfunction, migraine has been associated with cognitive decline. However, no consistent results with respect to the attention function in migraineurs have been found, and the relationship between attentional inhibition and migraine is also unclear. In this study, the attentional inhibition function was evaluated using event-related potentials (ERPs) while migraine patients and healthy controls were performing the color–word Stroop task. Methods: In this study, 75 migraine patients and 41 age-, gender-, and education-matched healthy controls were enrolled. The Stroop task was performed, and both behavioral and ERP data were analyzed. Results: As to the behavioral data, the migraine group had a longer reaction time compared to the control group, but no difference in Stroop effect was observed. With respect to ERP components, the amplitudes of both early and late medial frontal negativity (MFN) were decreased in the migraine group. Additionally, obvious differences in the early MFN and sustained potential (SP) amplitudes were found between patients with and without allodynia. Conclusions: At the behavioral level, migraine patients exhibited decreased executive ability but no obvious decline in inhibition. By contrast, a decline in attentional inhibition during the migraine interictal phase was confirmed by the analysis of ERP components, mainly those associated with changes in the conflict-monitoring stage, independent of confounding factors such as age, education, medication and mood disorders. Migraine patients with allodynia exhibited some significant differences in early MFN and SP compared to those without, supporting the hypothesis that migraine chronification aggravates the decline in attentional inhibition. [ABSTRACT FROM AUTHOR]

Background: As COVID-19 vaccines become available, screening individuals for prior COVID-19 infection and vaccine response in point-of-care (POC) settings has renewed interest. We prospectively screened at-risk individuals for SARS-CoV-2 spike and nucleocapsid protein antibodies in a POC setting to determine if it was a feasible method to identify antibody from prior infection. Methods: Three EUA-approved lateral flow antibody assays were performed on POC finger-stick blood and compared with serum and a CLIA nucleocapsid antibody immunoassay. Variables including antibody class, time since PCR, and the assay antigen used were evaluated. Results: 512 subjects enrolled, of which 104 had a COVID-19 history and positive PCR. Only three PCR-positive subjects required hospitalization, with one requiring mechanical ventilation. The POC results correlated well with the immunoassay (93–97% sensitivity) and using serum did not improve the sensitivity or specificity. Conclusions: Finger-stick, POC COVID-19 antibody testing was highly effective in identifying antibody resulting from prior infections in mildly symptomatic subjects. Using high-complexity serum immunoassays did not improve the screening outcome. Almost all individuals with COVID-19 infection produced detectable antibodies to the virus. POC antibody testing is useful as a screen for prior COVID-19 infection, and should be useful in assessing vaccine response. [ABSTRACT FROM AUTHOR]

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31–60 days PSO. By 61–90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1–4 days PSO with 86% positivity observed at 5–7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection. [ABSTRACT FROM AUTHOR]

Among pain researchers there is a growing interest in the relationship between psychological resilience and pain experience. Whereas much of this work has focused on individual differences in pain perception or sensitivity, an equally important dimension of resilience is the capacity to persist with goal-directed activity despite experiencing pain. Consistent with this latter focus, the current study examined how pain resilience and pain catastrophizing combine to moderate the effects of ischemic pain on short-term memory task performance. Using a within-subjects design, 121 healthy participants completed four trials of a Corsi block-tapping task with pain exposure during the second and fourth trials. Results indicated that a combination of high pain resilience and low pain catastrophizing was associated with better task performance during the second pain exposure. These findings confirm existing evidence that resilience can moderate performance during pain, and offer new evidence that resilience and catastrophizing interact to shape this effect. [ABSTRACT FROM AUTHOR]

Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM. [ABSTRACT FROM AUTHOR]

Synthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here we report our discovery that naphthyridine carbamate dimer (NCD) targets disease-causing r(UGGAA)n repeat RNAs in spinocerebellar ataxia type 31 (SCA31). Structural analysis of the NCD-UGGAA/UGGAA complex by nuclear magnetic resonance (NMR) spectroscopy clarifies the mode of binding that recognizes four guanines in the UGGAA/UGGAA pentad by hydrogen bonding with four naphthyridine moieties of two NCD molecules. Biological studies show that NCD disrupts naturally occurring RNA foci built on r(UGGAA)n repeat RNA known as nuclear stress bodies (nSBs) by interfering with RNA–protein interactions resulting in the suppression of nSB-mediated splicing events. Feeding NCD to larvae of the Drosophila model of SCA31 alleviates the disease phenotype induced by toxic r(UGGAA)n repeat RNA. These studies demonstrate that small molecules targeting toxic repeat RNAs are a promising chemical tool for studies on repeat expansion diseases. Synthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here the authors show the mechanism by which a small molecule targets the disease-causing r(UGGAA)n repeat RNAs in spinocerebellar ataxia type 31. [ABSTRACT FROM AUTHOR]

Background: Pain is the most common symptom in patients with neoplasm. It is a distressing experience that seriously destructs the quality-of-life of patients, with a high prevalence in clinical observations. However, only a few studies have applied bibliometric methods to analyze systematic works on the comorbidity of cancer and pain. Purpose: The aim of this work was to conduct a systematic analysis of the scientific studies worldwide on the comorbidity of cancer and pain in 2010– 2019. Methods: The Web of Science databases were searched for publications related to the comorbidity of cancer and pain from 2010 to 2019. Results: A total of 3,423 papers met the inclusion criteria in this research. The increase in the quantity of papers presented a significant growth from 2010 to 2019 (P< 0.001) by linear regression analysis. The research subject categories of the 3,423 papers mainly concentrated on oncology (28.57%), clinical neurology (25.62%), and healthcare science services (15.89%). The US had the highest number of published papers, followed by the People's Republic of China, and England. According to scientific statistics, breast cancer (20.36%) was by far the most predominant topic in the papers related to the comorbidity of cancer and pain. Conclusion: This bibliometric research provided a framework for visual and quantitative research to management scholars in favor of exploring a potential field related to hot issue and research frontiers. [ABSTRACT FROM AUTHOR]

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Background: Low back pain is a common reason for patients to seek medical care. Physician non-adherence to clinical guidelines has been observed. We investigated the extent to which patient expectations correspond to recommendations of the German national guideline for management of low back pain (G-LBP) and whether patient characteristics, history of LBP and previous treatment experience are associated with expectations. Methods: A cross-sectional study including patients from 13 general practices was conducted. Data were collected using a questionnaire. Inverse probability weights were used to address non-response bias. Descriptive analysis and multivariate logistic regression models were performed. Results: A total of 977 patients were included in analyses (median age 57 years, 39% male). 75% of patients reported experiencing LBP currently or within the last year. More than 65% indicated they would agree to forgo further examinations if their LBP was judged by their physician to be of no serious concern. This was associated with the highest level of education and no prior imaging, and negatively associated with good-to-poor health status and moderate-to-severe pain intensity. 40% of participants expected imaging. The highest educational level, female gender and no prior imaging were associated with a decreased expectation of imaging. 70% expected prescriptions for massages. Females, participants with good-to-poor health status, current LBP or LBP in the last 12 months had an increased expectation for massages. Expectations for injection therapy (45%) were mainly associated with previous injections. Expectations for physiotherapy (64%) were associated with female gender, lower educational level, good-to-poor health status, current LBP or in the last 12 months. The perspective that daily activities should be continued (66%) was associated with female gender and higher educational level. Participants who agreed to the statement 'There is no effective treatment for LBP' (11%) had a poor health status, current LBP and a severe pain intensity. Conclusion: Patient views regarding LBP management are partially concordant with guideline recommendations and are strongly influenced by previous treatment experiences and education level. Exploration of patient expectations and experiences in LBP treatment may help minimize dissatisfaction of patients expecting treatments not endorsed by guidelines and simultaneously increase physician guideline adherence. [ABSTRACT FROM AUTHOR]

In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics. [ABSTRACT FROM AUTHOR]

Introduction: Fibromyalgia represents the most prevalent of the group of conditions that are known as central sensitivity syndromes. Approximately 2–5% of the adult population in the United States is affected by Fibromyalgia. This pain amplification syndrome has an enormous economic impact as measured by work absenteeism, decreased work productivity, disability and injury compensation, and over-utilization of healthcare resources. Multiple studies have shown that early diagnosis of this condition can improve patient outlook, and redirect valuable health care resources toward more appropriate targeted therapy. Efforts have been made toward improving diagnostic accuracy through updated criteria. Areas Covered: Reviewed here are 1) reasons for the need for more accurate diagnosis of Fibromyalgia, (2) a review of the evolution of Fibromyalgia to current times, and (3) the proliferation of currently available diagnostic criteria and problems related to each of them. From initial literature review until October 2020, PubMed, Embase, and Scopus were searched for applicable literature. Expert Opinion: A discussion of ongoing efforts to obtain a biomarker to enhance diagnostic accuracy concludes this review. A need to include rheumatologists as part of the care team of patients with Fibromyalgia is emphasized. [ABSTRACT FROM AUTHOR]

Introduction: Fibromyalgia (FM) is a chronic pain condition characterized by impaired emotional regulation. This study explored the brain response to pain-related fear as a potential brain signature of FM. Methods: We used a conditioned fear task and magnetoencephalography to record pain-related fear responses in patients with FM. Two blocks of 30 fear responses were collected to compute the response strength in the first block and the strength difference between the first and second blocks (fear habituation). These measurements were investigated for their clinical relevance and compared with measurements obtained from healthy controls and patients with chronic migraine (CM), a different chronic pain condition often comorbid with FM. Results: Pain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM (n = 52), patients with CM (n = 50), and the controls (n = 30); the response strength in the first block was consistent across groups. However, fear habituation in the right amygdala decreased in the FM group (vs. CM and control groups, both p ≤ 0.001, no difference between CM and control groups). At the 3-month follow-up, the patients with FM reporting < 30% improvement in pain severity (n = 15) after pregabalin treatment exhibited lower fear habituation in the left amygdala at baseline (vs. ≥ 30% improvement, n = 22, p = 0.019). Receiver operating characteristic analysis confirmed that amygdala fear habituation is a suitable predictor of diagnosis and treatment outcomes of FM (area under the curve > 0.7). Conclusions: Amygdala activation to pain-related fear is maladaptive and linked to treatment outcomes in patients with FM. Because the aberrant amygdala response was not observed in the CM group, this response is a potential brain signature of FM. Trial Registration: ClinicalTrials.gov Identifier, NCT02747940. [ABSTRACT FROM AUTHOR]

Ventriculoperitoneal shunt (VPS) is an adequate treatment for congenital hydrocephalus or chronic hydrocephalus in adults. Yet, it is a surgery associated with a significant rate of complications amongst neurosurgical procedures, with frequent shunt obstructions and infections. We report the first-ever case of peritonitis caused by Roseomonas mucosa, shortly after the revision of a VPS ventricular catheter. Hardware removal and proper antibiotic therapy led to the patient's recovery. Roseomonas mucosa is an opportunistic skin pathogen with an antibiotic resistance profile to many beta-lactamines and a tropism for indwelling catheters and post-operative period. Nowadays, it should be taken into account in case of infection of indwelling catheters and for some implantable medical devices. [ABSTRACT FROM AUTHOR]

Background: Homozygous protein C (PC) deficiency is a potentially fatal disease with ocular blinding presentation or sequela.Case Presentation: A 5 month-old boy was presented for evaluation of leukocoria. He had a history of frequent bruises and PC deficiency, treated with warfarin. His intraocular pressure was normal. In the left eye leukoma with anterior segment dysgenesis, shallow anterior chamber, and cataract were observed. Fundus was not visible. B-scan revealed a closed funnel retinal detachment. His right eye had a normal anterior segment and a thin retina with anomalous retinal vascular branching at equator and peripheral retina. A fibrovascular tuft on the optic nerve head with induced traction on superior arcade was visible. Total loss of a and b wave of both were appreciated in electroretinography (ERG). Fluorescein angiography (FA) showed very severe leakage at the junction of the vascularized and non-vascularized retina and optic nerve head. Favorable outcome was achieved with lasering of avascular retina in the right eye.Conclusion: The potential for protein C deficiency should be assessed in all infants with leukocoria, anterior segment dysgenesis, retinal detachment and retinal dysplasia. Early diagnosis could save the child's life and vision. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is commonly associated with anxiety and depression, making it more challenging to be managed. Psychological interventions are suggested for such complicated issues which are well evident in the United States and Europe. However, generalizing the evidence to Iranian population - as a Middle Eastern society - might be questionable. We aimed to synthesize our evidence on the effectiveness of these interventions among Iranian populations. Methods: This was a systematic review and meta-analysis. Persian and English literature were searched through Iran-doc, Elm-net, and PubMed until March 2019 using the following terms (or its Persian synonyms): chronic pain; persistent pain; chronic fatigue; fibromyalgia; neuropath*; LBP; irritable bowel; CFS; psycho*; cogniti*; acceptance; meaning; mindfulness; relaxation; biopsychosocial; rehabilitation; educat*. Eligible trials were randomized trials that evaluated the effectiveness of psychological interventions on Iranian adults with chronic pain. No setting restriction was considered. Risk of bias for each trial was assessed, and the random-effect model was used to pool summary effect across trials. Results: In all 30 eligible RCTs, the risk of bias for randomization was low except for one study. The pooled standardized mean difference (SMD) for depression and anxiety were 1.33 (95% CI: -1.42 to -0.68) and 1.25 (95% CI: -1.55 to -0.96), respectively. Conclusion: This study suggests that psychological interventions are highly effective in reducing depression and anxiety in Iranian patients with chronic pain, compared to what observed in the U.S. and European studies. However, there are still some methodological issues to be addressed. Future research should focus on high-quality trials with considerations on the methodological issues reported in the present study. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is characterized by chronic pain and fatigue, among other manifestations, thus advising interventions that do not aggravate these symptoms. The main purpose of this study is to analyse the effect of low-pressure hyperbaric oxygen therapy (HBOT) on induced fatigue, pain, endurance and functional capacity, physical performance and cortical excitability when compared with a physical exercise program in women with FM. Methods: A total of 49 women with FM took part in this randomized controlled trial. They were randomly allocated to three groups: physical exercise group (PEG, n = 16), low-pressure hyperbaric oxygen therapy group (HBG, n = 17) and control group (CG, n = 16). Induced fatigue, perceived pain, pressure pain threshold, endurance and functional capacity, physical performance and cortical excitability were assessed. To analyse the effect of the interventions, two assessments, that is, pre and post intervention, were carried out. Analyses of the data were performed using two-way mixed multivariate analysis of variance. Results: The perceived pain and induced fatigue significantly improved only in the HBG (p < 0.05) as opposed to PEG and CG. Pressure pain threshold, endurance and functional capacity, and physical performance significantly improved for both interventions (p < 0.05). The cortical excitability (measured with the resting motor threshold) did not improve in any of the treatments (p > 0.05). Conclusions: Low-pressure HBOT and physical exercise improve pressure pain threshold, endurance and functional capacity, as well as physical performance. Induced fatigue and perceived pain at rest significantly improved only with low-pressure HBOT. Trial registration: ClinicalTrials.gov identifier NCT03801109. [ABSTRACT FROM AUTHOR]

Pain is evolutionarily hardwired to signal potential danger and threat. It has been proposed that altered pain-related associative learning processes, i.e., emotional or fear conditioning, might contribute to the development and maintenance of chronic pain. Pain in or near the face plays a special role in pain perception and processing, especially with regard to increased pain-related fear and unpleasantness. However, differences in pain-related learning mechanisms between the face and other body parts have not yet been investigated. Here, we examined body-site specific differences in associative emotional conditioning using electrical stimuli applied to the face and the hand. Acquisition, extinction, and reinstatement of cue-pain associations were assessed in a 2-day emotional conditioning paradigm using a within-subject design. Data of 34 healthy subjects revealed higher fear of face pain as compared to hand pain. During acquisition, face pain (as compared to hand pain) led to a steeper increase in pain-related negative emotions in response to conditioned stimuli (CS) as assessed using valence ratings. While no significant differences between both conditions were observed during the extinction phase, a reinstatement effect for face but not for hand pain was revealed on the descriptive level and contingency awareness was higher for face pain compared to hand pain. Our results indicate a stronger propensity to acquire cue-pain-associations for face compared to hand pain, which might also be reinstated more easily. These differences in learning and resultant pain-related emotions might play an important role in the chronification and high prevalence of chronic facial pain and stress the evolutionary significance of pain in the head and face. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to test the validity of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome, to assess the psoriasis severity within the scope of rheumatology. Methods: Within the PsA international database (PSART-ID), 571 patients had PSI, while 322 of these also showed body surface area (BSA). Correlations between PSI, BSA, and other patient- and physician- reported outcomes were investigated. Results: There was a good correlation between PSI and BSA (r=0.546, p<0.001), which was even higher for mild psoriasis (BSA<3 (n=164): r=0.608, p<0.001). PSI significantly correlated with fatigue, pain, and patient and physician global parameters (p<0.001). Conclusion: PSI has a good correlation with other patient- and physician-reported outcomes, and our findings support its use in rheumatology practice. [ABSTRACT FROM AUTHOR]

Pharmacokinetic data regarding ceftaroline fosamil (CPT) penetration into cerebrospinal fluid (CSF) are limited to a rabbit model (15% inflamed) and adult case reports. We describe serum and CSF CPT concentrations in a 21-year-old, 34.8 kg female, medically complex patient presented with a 4-day history of fevers (Tmax 39.2°C), tachypnea, tachycardia, fatigue, and a 1-week history of pus and blood draining from the ventriculopleural (VPL) shunt. A head CT and an ultrasound of the neck revealed septated complex fluid collection surrounding the shunt. Therapy was initiated with vancomycin and ceftriaxone. Blood and CSF cultures from hospital day (HD) 1 were positive for methicillin-resistant Staphylococcus aureus with a CPT MIC of 0.5 mg/L and a vancomycin MIC range of 0.5 to 1 mg/L. On HD 3, CPT was added. On HD 7, simultaneous serum (69.4, 44, and 30.2 mg/L) and CSF (1.7, 2.3, and 2.3 mg/L) concentrations were obtained at 0.25, 1.5, and 4.75 hours from the end of an infusion. Based on these concentrations, CPT CSF penetration ratio ranged from 2.4% to 7.6%. After addition of CPT, the blood and CSF cultures remained negative on a regimen of vancomycin plus CPT. On HD 14, a new left-sided VPL shunt was placed. The patient continued on CPT for a period of 7 days after the new VPL shunt placement. This case demonstrated CPT CSF penetration in a range of 2.4% to 7.6%, approximately half of the rabbit model. This allowed for CSF concentrations at least 50% free time > 4 to 6× MIC of the dosing interval with a dosing regimen of 600 mg IV every 8 hours in a 34.8 kg chronic patient and resulted in a successful clinical outcome with no identified adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month). Methods: We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity. Results: Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008). Conclusions: Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM. [ABSTRACT FROM AUTHOR]

A small pond in Hinewai Reserve, Banks Peninsula, Canterbury has revealed a phytoplankton bloom consisting of an unusually minute desmid which has consequently been difficult to observe. It is described, assigned to the genus Cosmarium and compared with superficially similar species. It has unique features which justify assigning it to a new species Cosmarium wilsonii David B. Williamson & C.F. Carter. It is named after the Reserve kaitiaki (manager) Dr H. D. Wilson. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the possible drug-drug interactions between ceftiofur sodium and famotidine on co-administration. These studies were carried out at normal as well as elevated temperature at pH corresponding to blood pH of 7.4. Spectrophotometric method was used to study the dissolution of each drug individually and in the presence of the other drug. Change in the rate of dissolution of ceftiofur sodium in the presence of cimetidine as compared to the rate of dissolution in the absence of cimetidine supported the possible interactions between the two drugs. [ABSTRACT FROM AUTHOR]

Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use. Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases. Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking. Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects. [ABSTRACT FROM AUTHOR]

Microorganisms are ubiquitous and thought to regulate host populations. Although microorganisms can be pathogenic and affect components of fitness, few studies have examined their effects on wild plant populations. As individual traits might not contribute equally to changes in population growth rate, it is essential to examine the entire life cycle to determine how microorganisms affect host population dynamics. In this study, we used data from common garden experiments with plants from three Cucurbita pepo populations exposed to three virus treatments. These data were used to parameterize a deterministic matrix model, which allowed us to estimate the effect of virus on components of fitness and population growth rate. Virus did not reduce fruit number, but population growth rates varied among virus treatments and wild C. pepo populations. The effect of virus on population growth rate depended on virus species and wild C. pepo population. Contributions of life-history transitions and life-history traits to population growth rates varied among populations and virus treatments. However, this population-virus interaction was not evident when examining individual components of fitness. Thus, caution must be used when interpreting the effects of changes in individual traits, as single traits do not always predict population-level change accurately., (© 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.)

Background: The recognition of chronic pain as a biopsychosocial phenomenon has led to the establishment of multidisciplinary pain treatment facilities, such as pain centres. Previous studies have focussed on inpatient, group-based or time-limited multidisciplinary pain programmes. The aim was to investigate variation in patients' experiences of attending individual outpatient multidisciplinary treatment at pain centres in Norway.Methods: This was a qualitative study using semi-structured individual interviews with 19 informants. The informants were recruited among persons who after referral by their general practitioners 12 months prior had attended multidisciplinary pain treatment at a pain centre. The data were analysed thematically using systematic text condensation.Results: The informants had received different treatments at the pain centres. Some had undergone only one multidisciplinary assessment in which a physician, a psychologist and a physiotherapist had been present, whereas others had initially been to a multidisciplinary assessment and then continued treatment by one or more of the professionals at the centre. Their experiences ranged from the pain centre as being described as a lifebuoy by some informants who had attended treatment over time, to being described as a waste of time by others who had only attended one or two multidisciplinary sessions. Prominent experiences included being met with understanding and a perception of receiving the best possible treatment, but also included disappointment over not being offered any treatment and perceiving the multidisciplinary approach as unnecessary.Conclusions: There were large variations in the informants' experiences in the pain centres. The findings indicate that the pain centres' multidisciplinary approach can represent a new approach to living with chronic pain but may also not provide anything new. Efforts should be devoted to ensuring that the pain centres' multidisciplinary treatment approach is aligned with their patients' actual needs. [ABSTRACT FROM AUTHOR]

The repressive states of nuclear receptors (i.e., apo or bound to antagonists or inverse agonists) are poorly defined, despite the fact that nuclear receptors are a major drug target. Most ligand bound structures of nuclear receptors, including peroxisome proliferator-activated receptor γ (PPARγ), are similar to the apo structure. Here we use NMR, accelerated molecular dynamics and hydrogen-deuterium exchange mass spectrometry to define the PPARγ structural ensemble. We find that the helix 3 charge clamp positioning varies widely in apo and is stabilized by efficacious ligand binding. We also reveal a previously undescribed mechanism for inverse agonism involving an omega loop to helix switch which induces disruption of a tripartite salt-bridge network. We demonstrate that ligand binding can induce multiple structurally distinct repressive states. One state recruits peptides from two different corepressors, while another recruits just one, providing structural evidence of ligand bias in a nuclear receptor. The repressive states of peroxisome proliferator-activated receptor γ (PPARγ) are ill-defined, despite nuclear receptors being a major drug target. Here authors demonstrate multiple structurally distinct repressive states, providing a structural rationale for ligand bias in a nuclear receptor. [ABSTRACT FROM AUTHOR]

Background: Current treatment options for chronic pain and depression are largely medication-based, which may cause adverse side effects. Integrative Medical Group Visits (IMGV) combines mindfulness techniques, evidence based integrative medicine, and medical group visits, and is a promising adjunct to medications, especially for diverse underserved patients who have limited access to non-pharmacological therapies. Objective: Determine the effectiveness of IMGV compared to a Primary Care Provider (PCP) visit in patients with chronic pain and depression. Design: 9-week single-blind randomized control trial with a 12-week maintenance phase (intervention—medical groups; control—primary care provider visit) Setting: Academic tertiary safety-net hospital and 2 affiliated federally-qualified community health centers. Participants: 159 predominantly low income racially diverse adults with nonspecific chronic pain and depressive symptoms. Interventions: IMGV intervention– 9 weekly 2.5 hour in person IMGV sessions, 12 weeks on-line platform access followed by a final IMGV at 21 weeks. Measurements: Data collected at baseline, 9, and 21 weeks included primary outcomes depressive symptoms (Patient Health Questionnaire 9), pain (Brief Pain Inventory). Secondary outcomes included pain medication use and utilization. Results: There were no differences in pain or depression at any time point. At 9 weeks, the IMGV group had fewer emergency department visits (RR 0.32, 95% CI: 0.12, 0.83) compared to controls. At 21 weeks, the IMGV group reported reduction in pain medication use (Odds Ratio: 0.42, CI: 0.18–0.98) compared to controls. Limitations: Absence of treatment assignment concealment for patients and disproportionate group attendance in IMGV. Conclusion: Results demonstrate that low-income racially diverse patients will attend medical group visits that focus on non-pharmacological techniques, however, in the attention to treat analysis there was no difference in average pain levels between the intervention and the control group. Trial registration: clinicaltrials.gov NCT02262377. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal pain conditions incur high costs and produce significant personal and public health consequences, including disability and opioid-related mortality. Persistence of high-cost health care utilization for musculoskeletal pain may help identify system inefficiencies that could limit value of care. The objective of this study was to identify factors associated with persistent high-cost utilization among individuals seeking health care for musculoskeletal pain. Methods: This was a retrospective cohort study of Medical Expenditure Panel Survey data (2008–2013) that included a non-institutionalized, population-based sample of individuals seeking health care for a musculoskeletal pain condition (n = 12,985). Expenditures associated with musculoskeletal pain conditions over two consecutive years were analyzed from prescribed medicine, office-based medical provider visits, outpatient department visits, emergency room visits, inpatient hospital stays, and home health visits. Persistent high-cost utilization was defined as being in the top 15th percentile for annual musculoskeletal pain-related expenditures over 2 consecutive years. We used multinomial regression to determine which modifiable and non-modifiable sociodemographic, health, and pain-related variables were associated with persistent high-cost utilization. Results: Approximately 35% of direct costs for musculoskeletal pain were concentrated among the 4% defined as persistent high-cost utilizers. Non-modifiable variables associated with expenditure group classification included age, race, poverty level, geographic region, insurance status, diagnosis type and total number of musculoskeletal pain diagnoses. Modifiable variables associated with increased risk of high expenditure classification were higher number of missed work days, greater pain interference, and higher use of prescription medication for pain, while higher self-reported physical and mental health were associated with lower risk of high expenditure classification. Conclusions: Health care delivery models that prospectively identify these potentially modifiable factors may improve the costs and value of care for individuals with musculoskeletal pain prone to risk for high-cost care episodes. [ABSTRACT FROM AUTHOR]

Objective: Use an established quality improvement method, Lean A3, to improve the process of opioid prescribing in an academic rheumatology ambulatory clinic. Methods: This retrospective pre‐postintervention analysis of rheumatology records included patients prescribed opioids at least once during the study period. Lean A3 was used to develop a Controlled Substance Visit Protocol to standardize eight recommended elements of the opioid prescribing workflow. Analyses included changes in the recommended workflow elements and changes in opioid prescribing volume. Results: Improvements were observed in seven of the eight recommended elements. Patient education, including treatment agreements and consent forms (39% completion for both preimplementation) increased to 78% and 80%, respectively (P < 0.001 for both). Risk assessment, as measured by the Current Opioid Misuse Measure, increased from 0.5% to 76% (P < 0.001). Best practices in prescribing, including prescribing in multiples of seven to avoid weekend refill requests, increased from 1% to 79% (P < 0.001). Monitoring parameters, including standardized functional assessment (0% vs. 86%), prescription drug monitoring program queries (49% vs. 84%), and urine testing (1% vs. 32%) all increased (P < 0.001). Visits scheduled at least quarterly for patients on chronic opioids did not change (P = 0.18). Overall, the number of patients prescribed opioids (185 vs. 160; P < 0.001) and annual prescription opioid morphine milligram equivalents (MMEs) (1 933 585 MME vs. 1 386 368 MME; P < 0.001) decreased. Conclusion: The Lean A3 method is a successful quality improvement tool for improving and sustaining opioid prescribing within a single academic rheumatology clinic. This method has potential applicability to similar clinics interested in improving opioid prescribing. [ABSTRACT FROM AUTHOR]

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction—gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose–were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose. [ABSTRACT FROM AUTHOR]

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Objectives: Therapeutic virtual reality (VR) has emerged as an effective, drug-free tool for pain management, but there is a lack of randomized, controlled data evaluating its effectiveness in hospitalized patients. We sought to measure the impact of on-demand VR versus “health and wellness” television programming for pain in hospitalized patients. Methods: We performed a prospective, randomized, comparative effectiveness trial in hospitalized patients with an average pain score of ≥3 out of 10 points. Patients in the experimental group received a library of 21 VR experiences administered using the Samsung Gear Oculus headset; control patients viewed specialized television programming to promote health and wellness. Clinical staff followed usual care; study interventions were not protocolized. The primary outcome was patient-reported pain using a numeric rating scale, as recorded by nursing staff during usual care. Pre- and post-intervention pain scores were compared immediately after initial treatment and after 48- and 72-hours. Results: There were 120 subjects (61 VR; 59 control). The mean within-subject difference in immediate pre- and post-intervention pain scores was larger in the VR group (-1.72 points; SD 3.56) than in the control group (-0.46 points; SD 3.01); this difference was significant in favor of VR (P < .04). When limited to the subgroup of patients with severe baseline pain (≥7 points), the effect of VR was more pronounced vs. control (-3.04, SD 3.75 vs. -0.93, SD 2.16 points; P = .02). In regression analyses adjusting for pre-intervention pain, time, age, gender, and type of pain, VR yielded a .59 (P = .03) and .56 (P = .04) point incremental reduction in pain versus control during the 48- and 72-hour post-intervention periods, respectively. Conclusions: VR significantly reduces pain versus an active control condition in hospitalized patients. VR is most effective for severe pain. Future trials should evaluate standardized order sets that interpose VR as an early non-drug option for analgesia. [ABSTRACT FROM AUTHOR]

aim was to assess the psychometric properties (including internal consistency, construct validity, criterion validity, criterion-group validity and responsiveness) of the Fear of Pain Questionnaire (FOPQ) for adolescents (FOPQ-A) and parents (FOPQ-P) translated to Brazilian Portuguese (BrP). The secondary aim was to analyze the factor structures and their ability to identify subjects with chronic pain conditions and identify the relationship of the BrP FOPQ-A with saliva brain-derived neurotrophic-factor (BDNF). Methods: A cross-sectional study was conducted with 286 adolescents aged 11 to 18 (257 healthy adolescents [157 females] and 29 adolescents with chronic pain [16 females]). Parents and adolescents completed the BrP-FOPQ. A team of experts translated the FOPQ according to international guidelines. Convergent validity and factor analysis were performed. Later, a subsample (n=146) was used to correlate the BrP-FOPQ-A with saliva BDNF. Results: The BrP-FOPQ for adolescents and parents presented strong psychometric properties (Cronbach's α equal to 0.92 and 0.91, respectively). BrP-FOPQ-A confirmatory factor analysis yielded a two-factor structure while the factorial analyses of BrP-FOPQ-P demonstrated that the best solution was a three-structure factorial. The BrP-FOPQ-P scores in healthy adolescents and those in chronic pain conditions was 34.13 (16.71) vs 43.14 (18.08), respectively. A generalized mixed model demonstrated that the scores in the BrP-FOPQ-A are higher in those with chronic pain conditions compared to healthy subjects (29.20 [12.77] vs 33.80 [10.76], respectively; Wald χ2= 17.80; df=1, P<0.0001). The model revealed that the BDNF was positively correlated with the score of BrP-FOPQ-A and subjects with chronic pain showed higher levels of BDNF. Conclusion: The BrP-FOPQ scores for adolescents and parents were found to be psychometrically robust and reliable instruments, with primary evidence of validity. Higher scores on the BrP-FOPQ-A were correlated positively with saliva BDNF and permitted the identification of subjects with chronic pain conditions. [ABSTRACT FROM AUTHOR]

Cucurbita pepo is an economically important crop, which consists of cultivated C. pepo ssp. pepo, and two wild taxa (C. pepo ssp. fraterna and C. pepo ssp. ovifera). We aimed at understanding the domestication and the diversity of C. pepo in Mexico. We used two chloroplast regions and nine nuclear microsatellite loci to assess the levels of genetic variation and structure for C. pepo ssp. pepo's landraces sampled in 13 locations in Mexico, five improved varieties, one C. pepo ssp. fraterna population and ornamental C. pepo ssp. ovifera. We tested four hypotheses regarding the origin of C. pepo ssp. pepo's ancestor through approximate Bayesian computation: C. pepo ssp. ovifera as the ancestor; C. pepo ssp. fraterna as the ancestor; an unknown extinct lineage as the ancestor; and C. pepo ssp. pepo as hybrid from C. pepo ssp. ovifera and C. pepo ssp. fraterna ancestors. Cucurbita pepo ssp. pepo showed high genetic variation and low genetic differentiation. Cucurbita pepo ssp. fraterna and C. pepo ssp. pepo shared two chloroplast haplotypes. The three subspecies were well differentiated for microsatellite loci. Cucurbita pepo ssp. fraterna was probably C. pepo ssp. pepo's wild ancestor, but subsequent hybridization between taxa complicate defining C. pepo ssp. pepo's ancestor. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this systematic review was to identify the characteristics of physicians who prescribe opioids to adults with chronic pain. This review was limited to studies examining fully-trained physicians, as relevant characteristics of resident physicians and non-physician clinicians may differ. Methods: A comprehensive search of databases from January 1, 1980 to December 5, 2017 was conducted. Eligible study designs included (1) randomized trials; (2) nonrandomized prospective and retrospective studies; and (3) cross-sectional observational studies. The risk of bias in the included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. A total of 2508 records were screened and 22 studies met inclusion criteria. The majority of studies were cross-sectional (n=20) and the total number of participants was 8433. Results: The risk of bias was high overall. The majority of physicians were confident managing and prescribing opioids for chronic pain but had high levels of dissatisfaction. Physicians reported high awareness of the potential for opioid misuse and were concerned about inadequate prior training in pain management. The majority of physicians were less likely to prescribe for patients with a history of substance abuse and reported major concerns about regulatory scrutiny. Conclusion: This systematic review provides the foundation for the development of prospective studies aimed at further elucidating the constellation of mechanisms that influence physicians who manage pain and prescribe opioids. [ABSTRACT FROM AUTHOR]

Objective: To evaluate feasibility and acceptability of a sub-threshold exercise program with minimal in-person visits to treat youth with persistent sport-related concussion, and explore efficacy for improving concussive symptoms, health-related quality of life, and fear-avoidance. Study design: We conducted a pilot randomized controlled trial comparing a 6 week sub-threshold exercise program requiring only two in-person visits to active control (stretching) for 12–18 year old youth with persistent sport-related concussion. We measured moderate-to-vigorous physical activity pre- and post-intervention using accelerometry, and increased goals weekly via phone contact. We examined feasibility and acceptability using qualitative interviews. We used exponential regression to model differences in trajectory of concussive symptoms by experimental group, and linear regression to model differences in trajectory of health-related quality of life and fear-avoidance of pain by experimental group. Results: Thirty-two subjects randomized, 30 completed the study (n = 11 control, n = 19 intervention), 57 % female. Youth and parents reported enjoying participating in the study and appreciated the structure and support, as well as the minimal in-person visits. Exponential regression modeling indicated that concussive symptoms declined more rapidly in intervention youth than control (p = 0.02). Health-related quality of life and fear-avoidance of pain improved over time, but were not significantly different by group. Conclusions: This study indicates feasibility and potential benefit of a 6 week subthreshold exercise program with minimal in-person visits for youth with persistent concussion. Potential factors that may play a role in improvement such as fear-avoidance deserve further study. [ABSTRACT FROM AUTHOR]