Inactive Control Research Articles

New Evidence in the Booming Field of Online Mindfulness: An Updated Meta-analysis of Randomized Controlled Trials.

BackgroundThere is a need to regularly update the evidence base on the effectiveness of online mindfulness-based interventions (MBIs), especially considering how fast this field is growing and developing.ObjectiveThis study presents an updated meta-analysis of randomized controlled trials assessing the effects of online MBIs on mental health and the potential moderators of these effects.MethodsWe conducted a systematic literature search in PsycINFO, PubMed, and Web of Science up to December 4, 2020, and included 97 trials, totaling 125 comparisons. Pre-to-post and pre-to-follow-up between-group effect sizes (Hedges g) were calculated for depression, anxiety, stress, well-being, and mindfulness using a random effects model.ResultsThe findings revealed statistically significant moderate pre-to-post effects on depression (g=0.34, 95% CI 0.18-0.50; P<.001), stress (g=0.44, 95% CI 0.32-0.55; P<.001), and mindfulness (g=0.40, 95% CI 0.30-0.50; P<.001) and small effects on anxiety (g=0.26, 95% CI 0.18-0.33; P<.001). For well-being, a significant small effect was found only when omitting outliers (g=0.22, 95% CI 0.15-0.29; P<.001) or low-quality studies (g=0.26, 95% CI 0.12-0.41; P<.001). Significant but small follow-up effects were found for depression (g=0.25, 95% CI 0.12-0.38) and anxiety (g=0.23, 95% CI 0.13-0.32). Subgroup analyses revealed that online MBIs resulted in higher effect sizes for stress when offered with guidance. In terms of stress and mindfulness, studies that used inactive control conditions yielded larger effects. For anxiety, populations with psychological symptoms had higher effect sizes. Adherence rates for the interventions ranged from 35% to 92%, but most studies lacked clear definitions or cut-offs.ConclusionsOur findings not only demonstrate that online MBIs are booming but also corroborate previous findings that online MBIs are beneficial for improving mental health outcomes in a broad range of populations. To advance the field of online MBIs, future trials should pay specific attention to methodological quality, adherence, and long-term follow-up measurements.

Randomized Controlled Trials of Mindfulness and Acceptance-Based Interventions Over the Past Two Decades: A Bibliometric Analysis.

Introduction: The past several years have witnessed a significant increase in interest among the public in mindfulness with an unmistakable growth in the scientific literature investigating mindfulness-based therapies. A myriad of therapeutic uses of mindfulness have been studied. Given this burgeoning interest, the authors' objective was to conduct a broad-sweeping bibliometric analysis over the past two decades to describe overarching trends in the publications of randomized controlled trials (RCTs) investigating mindfulness to broadly identify both strengths and gaps in this field and inform a strategic plan for further advancing this research area. Materials and Methods: The authors retrieved mindfulness-focused RCTs available on PubMed in the past two decades (2000-2019). They synthesized the literature with respect to publication numbers, countries of publication, journal type, areas of research focus, characteristics of study designs, sample size, and trends in remote intervention delivery. Results: The resulting 1389 publications represent a near exponential growth trend over the past 20 years. Publications from the top three countries (the United States, the United Kingdom, and the Netherlands) with the highest productivity accounted for 60% of total number of publications. The most published modalities include acceptance-based therapy (n = 260), mindfulness-based stress reduction (n = 238), mindfulness-based cognitive therapy (n = 174), and dialectical behavior therapy (n = 82). Stress, depression, anxiety, pain, cancer, diet/healthy eating, and sleep were the most common major areas of focus. Studies included active (46%) or inactive controls (44%), and increasingly more studies with both types of controls (10%). The top 10 journals that published the most mindfulness RCTs were from behavioral sciences and psychiatry or psychology. There were 187 RCTs utilizing remote delivery, with 146 (87.1%) in the most recent 5 years. Conclusion: Publications of mindfulness-focused RCTs show a continuous increasing trend. Mindfulness research from non-Western countries and studies published in biomedical journals were less prevalent and potentially represent future opportunities. Trends of studies with both inactive and active controls support an overall advancement in research methodology. There has been a significant expansion of studies of remotely delivered mindfulness interventions. Future research might consider evaluation of a broader range of modalities and further examine optimal delivery formats.

DIAGNOSTIC VALUE OF INTERLEUKIN-6 AND D-DIMER IN INFLAMMATORY BOWEL DISEASES

The article deals with the diagnostic value of changes in the content of interleukin-6 and D-dimer in patients with inflammatory bowel diseases (IBD) - Ulcerative Colitis (UC) and Crohn Disease (CD).&#x0D; Materials and methods: We have studied 34 patients with UC and 18 people with CD with continuously recurrent course. There are also analysed data of 15 patients with UC and 15 patients with CD in period of the remission. The control group included 30 healthy volunteers. Clinical, endoscopic examination, an immunoassay determination of the content of interleukin-6 (IL-6) and D-dimer, was carried out. CD activity was assessed using the Chron’s disease activity index. The localization of CD was established according to the Montreal classification. The clinical activity of the disease in patients with UC was determined using the classification according to Truelove-Witts. The value of the index consisted of the sum of points for each indicator, which allowed determining the activity of the inflammatory process.&#x0D; Statistical processing was performed using STATISTICA 10.0 (StatSoft. Inc., USA), at p&lt;0.05, the discrepancies between the obtained data were considered statistically significant.&#x0D; Research results. According to the obtained data, mild activity was found in 7 patients with UC (20.6%) and 4 - with CD (22.3%), moderate severity - in 17 (50.0%) and 8 (44.4%) patients, severe - in 10 (29.4%) and 6 (33.3%) patients. In the remission stage, 15 patients with UC and 15 patients with CD were examined. According to the Montreal classification, lesions of the upper gastrointestinal tract (L4) were observed in 4 patients with CD (22.2%), terminal ileitis (L1) occurred in 10 patients (55.6%), 4 patients were diagnosed with ileocolitis (L3) - 22.2%.&#x0D; It has been established that patients with an active course of UC and CD had a higher level of proinflammatory markers and thrombosis markers (D-dimer and IL-6) compared with inactive course and control group (p&lt;0.05). The D-dimer content in UC was 690±315 pg/l. It is confirmed the increase of the content of this marker in 2.55 times compared to control group and in 1.43 times than inactive course of the disease respectively. The level of IL-6 at active in course of UC was 3.36±1.78 pg/ml, increasing in 2.07 times against control and in 1.72 times compared with group of remission.&#x0D; In the active course of CD, the level of D-dimer reached 720±267 pg/ml, increasing in 2.67 times in relation to control and in 1.60 times with respect to patients under remission. The content of IL-6 in the active course of CD reached 4.07±2.17 pg/ml, increasing in 2.85 times in comparison to healthy individuals and in 2.83 times relatively patients with remission.&#x0D; While using the ROC-analysis, the most sensitive value as a “cut point” for the diagnosis of the active process in the course of IBD can be considered the content of the D-dimer in an amount of more than 650 pg/l. The calculated AUC in ROC-analysis for the IL-6 content was 73.7%±6.14% (61.7 - 85.7, p&lt;0.001), indicating the prognostic value of the model. The values of the IL-6 content of more than 2.80 pg/ml are diagnostically significant to predict the active process in IBD.

Effects of school-based mindfulness intervention on health-related quality of life: moderating effect of gender, grade, and independent practice in cluster randomized controlled trial

ObjectWe investigated the impact of a school-based 9-week mindfulness program vs. active control program (relaxation) and inactive control group on children’s self-reported Health-Related Quality of Life (HRQoL) moderated by gender, grade, and independent practice.MethodIn total 3519 (50/50% boys/girls) Finnish students aged 12–15 years from 56 schools were randomized into mindfulness intervention, active, and inactive control groups. HRQoL was measured at baseline, at 9 weeks, and at 26 weeks and analyzed with multilevel linear modeling.ResultsSignificant improvement on HRQoL was found (β = mean difference) (β = 1.587, 95% CI 0.672–2.502, p < 0.001) after 9 weeks and at 26 weeks of follow-up among students in the mindfulness group as compared to the active control group. Moderating effects on HRQoL were found for gender, grade, and independent practice: girls, 7th and 8th grade students, and students with regular independent mindfulness practice benefited most.ConclusionsGender and developmental stage may moderate the effects of mindfulness interventions on HRQoL and offer guidance in designing effective promotive interventions for children and adolescents.Trial Registration InformationHealthy Learning Mind—a school-based mindfulness and relaxation program: a study protocol for a cluster randomized controlled trial (RCT) ISRCTN18642659 retrospectively registered on 13 October 2015. The full trial protocol can be accessed at http://rdcu.be/t57S.

Effect of physical activity and exercise on telomere length: Systematic review with meta-analysis.

To compare a physically active lifestyle or structured exercise program to physically inactive lifestyle or control groups on telomere length (TL). We searched PubMed, EMBASE, Cochrane Library, and Open Gray databases up to March 31, 2020. We calculated standardized mean differences (SMD) with 95% confidence intervals (CI) of TL comparing physically active to physically inactive individuals and exercise intervention to control groups. Risk of bias was judged using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) for physical activity (PA) studies and the Cochrane risk-of-bias (RoB2) for exercise intervention studies. Certainty of evidence was judged using Grading of Recommendations Assessment, Development and Evaluation (GRADE). We included 30 studies (24 assessing the effects of PA and 6 assessing the effects of exercise interventions) comprising 7418 individuals. Physically active individuals had longer telomeres (SMD=0.70, 95% CI 0.12-1.28, very-low certainty), especially in middle-aged individuals (SMD=0.90, 95% CI 0.08-1.72, very-low certainty) and when considering only athletes (SMD=0.54, 95% CI 0.18-0.90, very-low certainty). Trim-and-fill analyses revealed that most of the pooled effects were overestimated. Exercise interventions did not yield any significant effect on TL. There is very-low certainty that physically active individuals have longer telomeres with a moderate effect, but this effect is probably overestimated.

Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with iβARK

Astrocytes respond to neurotransmitters and neuromodulators using G-protein-coupled receptors (GPCRs) to mediate physiological responses. Despite their importance, there has been no method to genetically, specifically, and effectively attenuate astrocyte Gq GPCR pathways to explore consequences of this prevalent signaling mechanism invivo. We report a 122-residue inhibitory peptide from β-adrenergic receptor kinase 1 (iβARK; and inactive D110A control) to attenuate astrocyte Gq GPCR signaling. iβARK significantly attenuated Gq GPCR Ca2+ signaling in brain slices and, invivo, altered behavioral responses, spared other GPCR responses, and did not alter astrocyte spontaneous Ca2+ signals, morphology, electrophysiological properties, or gene expression in the striatum. Furthermore, brain-wide attenuation of astrocyte Gq GPCR signaling with iβARK using PHP.eB adeno-associated viruses (AAVs), when combined with c-Fos mapping, suggested nuclei-specific contributions to behavioral adaptation and spatial memory. iβARK extends the toolkit needed to explore functions of astrocyte Gq GPCR signaling within neural circuits invivo.

A rapid benchtop method to assess biofilm on marine fouling control coatings

A rapid benchtop method to measure the torque associated with minidiscs rotating in water using a sensitive analytical rheometer has been used to monitor the drag caused by marine fouling on coated discs. The method was calibrated using sandpaper surfaces of known roughness. Minidiscs coated with commercial fouling control coatings, plus an inactive control, were exposed in an estuarine harbour. After 176 days the drag on the fouling control-coated discs, expressed as a moment coefficient, was between 73% and 90% less than the drag on the control coating. The method has potential use as a screen for novel antifouling and drag reducing coatings and surfaces. Roughness functions derived using Granville’s indirect similarity law are similar to patterns found in the general hydrodynamics literature, and so rotational minidisc results can be considered with reference to other fouling drag datasets. Supplemental data for this article is available online at https://doi.org/10.1080/08927014.2021.1929937 .

Mindfulness-based interventions among people of color: A systematic review and meta-analysis

Objective In the United States, people of color (POC) are disproportionately affected by various sources of stress and prevalent mental and physical health issues that may benefit from Mindfulness-based Interventions (MBIs). However, effects of MBIs for POC are unclear. This meta-analysis examines the efficacy of MBIs through randomized controlled trials (RCTs) that included predominately POC (≥75% of the sample). Method: Random effects models were used to synthesize effect sizes. A total of 24 RCT samples were analyzed. Results: Samples were on average 94.4% POC and predominantly from low-income backgrounds (total N = 2,156). At post-treatment, MBIs yielded small but statistically superior outcomes to active controls (Hedges’ g = 0.11) and inactive controls (g = 0.26). Compared to active controls, MBIs’ effects on well-being were smaller than their effects on other outcome types. Compared to inactive controls, MBIs that focused on non-clinical populations and had higher proportion of POC had larger effect sizes. Attrition rates of MBIs did not differ from other active conditions in outpatient settings. Conclusion: Findings provide modest, preliminary empirical support for MBIs among POC. We discuss main findings, limitations, and implications for future MBI research for health promotion among POC.

Experiences and effectiveness of occupational therapy interventions delivered in the acute setting: a mixed methods systematic review protocol.

The objective of this review is to synthesize and integrate the best available evidence on the experiences and effectiveness of occupational therapy interventions delivered in the acute setting. Occupational therapy is a client-centered health profession promoting health and well-being through occupation. In acute hospital settings, occupational therapy interventions are provided to patients to maximize function, prevent readmission, and promote safe discharge. Recent studies have demonstrated that occupational therapy has modified its practice in acute settings to include advocacy, team facilitation, and rapid clinical reasoning. This review will investigate not only the effectiveness of occupational therapy interventions, but also the experiences of patients, caregivers, and clinicians in the acute setting. This review will consider qualitative, quantitative, and mixed methods studies on the experiences and effectiveness of occupational therapy interventions delivered in acute settings. For the qualitative component, the experiences of patients and caregivers receiving any occupational therapy intervention, and clinicians directly or indirectly involved in delivering occupational therapy interventions, will be investigated. For the quantitative component, occupational therapy interventions will be compared with non-occupational therapy interventions, no intervention, wait-list, or other inactive or active (usual care) control interventions. Patient outcomes will include impairment, activities of daily living, psychological outcomes, and quality of life, while health system outcomes will include health care utilization and patient flow. The databases to be searched include CINAHL, Cochrane Controlled Trials Register, MEDLINE (Ovid), OT Seeker, PsycINFO (Ovid), and Scopus. Study selection, critical appraisal, data extraction, and data synthesis and integration will utilize the JBI segregated approach to mixed methods systematic reviews. PROSPERO CRD42020206363.

The Efficacy and Safety of Local Anesthetic Techniques for Postoperative Analgesia After Cesarean Section: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

ObjectiveCesarean section (CS) is one of the most frequently performed major surgical interventions. Local anesthetic techniques, a universal component of perioperative multimodal analgesia, are reportedly effective in reducing pain scores and opioid requirements. However, the optimal local anesthetic technique for postoperative CS pain remains unclear.MethodsSix databases were searched, and a Bayesian network meta-analysis was performed. The outcomes included cumulative morphine consumption and pain scores at four time points, time to first analgesic request, postoperative nausea and vomiting, pruritus, and sedation.ResultsSixty-eight studies with 5039 pregnant women were included. Six local anesthetic techniques were involved, including transversus abdominis plane block (TAPB), ilioinguinal and iliohypogastric nerve block, quadratus lumborum blocks, transversalis fascia plane block, erector spinae block, and wound infiltration. Compared to inactive controls, TAPB reduced cumulative morphine consumption at 6, 12, 24, and 48 h, pain scores at 6, 12, and 24 h (with the exception of 24 h at rest), the risk of postoperative nausea and vomiting, and sedation. Compared with inactive controls, ilioinguinal and iliohypogastric nerve block reduced cumulative morphine consumption at 6 and 24 h and pain scores at 6, 12, and 24 h during movement. Compared with inactive controls, quadratus lumborum blocks reduced cumulative morphine consumption at 24 and 48 h and pain scores at 6 and 12 h and lengthened the time to first analgesic request. Compared with inactive controls, wound infiltration reduced cumulative morphine consumption at 12 and 24 h, pain scores at 12 and 24 h during movement, and risk of sedation. Compared with inactive controls, erector spinae block reduced pain scores at 6 and 12 h. Transversalis fascia plane block was found to have similar outcomes to inactive controls.ConclusionTAPB is the most comprehensive local anesthetic technique for postoperative CS analgesia in the absence of intrathecal morphine.

Benefits of Mindfulness Professional Development for Elementary Teachers

Using an embedded quasi-experimental mixed-method approach, this exploratory study aimed to understand the benefits of mindfulness training for elementary school teachers and leaders in one rural school district. After the delivery of two 90-minute mindfulness professional developments with on-the-job practice of strategies over 2 weeks, quantitative statistical comparisons of the intervention and inactive control groups were made using survey results from the Mindfulness in Teaching Scale (Frank et al., 2016). Qualitative analyses used intervention participant journal entry responses along with one-on-one interviews. After analyses, the results suggest mindfulness training can benefit teachers, specifically in the use of intrapersonal mindfulness practices, reshaping daily interactions with students, and reducing stress.

The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness.

Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can be noninvasively tracked by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness. The study population was a UK cohort of children with juvenile DM. Circulating endothelial cells (CECs) and microparticles (MPs) were identified using immunomagnetic bead extraction and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokine and chemokine levels were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as the median and interquartile range (IQR), and statistical significance was assessed using nonparametric analyses. Ninety patients with juvenile DM and 79 healthy control subjects were included. The median age of the patients was 10.21 years (IQR 6.68-13.40), and the median disease duration was 1.63 years (IQR 0.28-4.66). CEC counts were higher in all patients with juvenile DM compared to controls (median 96 cells/ml [IQR (40-192] and 12 cells/ml [IQR 8-24], respectively; P < 0.0001). Circulating MP numbers were also significantly higher in patients with active juvenile DM compared to controls (median 204.7 × 103 /ml [IQR 87.9-412.6] and 44.3 × 103 /ml [IQR 15.0-249.1], respectively; P < 0.0001). MPs were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in patients with active juvenile DM compared to those with inactive disease (P = 0.0003) and controls (P < 0.0001). Carotid-radial PWV adjusted for age was increased in patients with juvenile DM compared to controls (P = 0.003). We observed increased endothelial injury and increased levels of proinflammatory cytokines in patients with active juvenile DM. MP profiles reflected distinct disease activity status in juvenile DM and are markers of vascular pathology, platelet activation, and thrombotic propensity. Ongoing long-term vascular injury may result in increased arterial stiffness in patients with juvenile DM.

Resolvin D1 Improves the Treg/Th17 Imbalance in Systemic Lupus Erythematosus Through miR-30e-5p.

Resolvin D1 (RvD1) prompts inflammation resolution and regulates immune responses. We explored the effect of RvD1 on systemic lupus erythematosus (SLE) and investigated the correlation between RvD1 and Treg/Th17 imbalance, which is one of the major factors contributing to the pathogenesis of disease. SLE patients and healthy controls were recruited to determine plasma RvD1 levels. MRL/lpr lupus model was used to verify rescue of the disease phenotype along with Treg/Th17 ratio. Purified naive CD4+ T cells were used to study the effect of RvD1 on Treg/Th17 differentiation in vitro. Furthermore, small RNA Sequencing and transfection were performed successively to investigate downstream microRNAs. The result showed that the RvD1 level was significantly lower in active SLE patients compared with inactive status and controls. Moreover, The SLE disease activity index (SLEDAI) score had a significant negative correlation with RvD1 level. As expected, RvD1 treatment ameliorated disease phenotype and inflammatory response, improved the imbalanced Treg/Th17 in MRL/lpr mice. In addition, RvD1 increased Treg while reduced Th17 differentiation in vitro. Furthermore, miR-30e-5p was verified to modulate the Treg/Th17 differentiation from naïve CD4+ T cells as RvD1 downstream microRNA. In conclusion, RvD1 effectively ameliorates SLE progression through up-regulating Treg and down-regulating Th17 cells via miR-30e-5p.

Low vision rehabilitation in improving the quality of life for patients with impaired vision: A systematic review and meta-analysis of 52 randomized clinical trials.

Background & aim:Low vision rehabilitation optimizes the use of residual vision after severe vision loss, but also teaches skills to improve visual functioning in daily life. These skills promote independence and active participation in society. This meta-analysis was designed to evaluate the efficacy of low vision rehabilitation in improving the quality of life (QoL) in visually impaired adults.Methods:We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to January 1, 2020. Randomized controlled trials (RCTs) that compared rehabilitation interventions with active or inactive controls were included. The standardized mean difference (SMD) with a 95% confidence interval (CI) was estimated to compare outcomes. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2.Results:A total of 52 RCTs with 6,239 participants were included in this meta-analysis. Compared to inactive comparators including waiting list or no care, low vision rehabilitation improved vision-related QoL, visual functioning (QoL: psychological aspect), and self-efficacy or self-esteem (QoL: psychological aspect), with pooled SMDs of −0.61 (95% CI −0.95 to −0.26; P = .0006), -1.14 (95% CI −1.69 to −0.59; P < .0001), and −0.84 (95% CI −1.47 to −0.22; P < .0001), respectively. Compared to active comparators, low vision rehabilitation improved vision-related QoL (SMD −0.26; 95% CI −0.46 to −0.06; P = .01) and activities of daily living (QoL: physical aspect) (SMD −0.39; 95% CI −0.67 to −0.12 P < .0001). However, no significant difference in health-related QoL and adaptation to vision loss (QoL: psychological aspect) was found between low vision rehabilitation and inactive comparators.Conclusions:This meta-analysis indicated that low vision rehabilitation interventions, particularly psychological therapies and methods of enhancing vision, may improve vision-related QoL and visual functioning in people with sight loss compared to usual care. Further studies should explore longer maintenance effects and the costs of several types of low vision rehabilitation. Studies characterizing the mechanisms of rehabilitation interventions in different settings, including low-income countries, are also required.

An evidence-based approach for the development of a clinical practice guideline for the treatment of neck pain using traditional Korean medicine

IntroductionIn Korea, all traditional Korean medicine interventions for neck pain are actively used, including acupuncture, herbal medicine, Chuna, and pharmacopuncture; however, clinical practice guidelines do not exist. We aimed to develop a clinical practice guideline for treating neck pain in adults using traditional Korean medicine. MethodsA committee comprising clinical and methodological experts was formed, and clinical questions were developed. A systematic review was conducted for each clinical question. The selected studies were analyzed and assigned a quality of evidence grade based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Recommendations were formulated considering the benefits and harms. A formal consensus was reached among the experts using the Delphi method. The final recommendations were recognized by relevant professional societies. ResultsIn total, 25 recommendations were developed regarding traditional Korean medicine treatments (acupuncture, electroacupuncture, fire needling, miniscalpel acupuncture, herbal medicine, Chuna manual therapy, pharmacopuncture, bee-venom pharmacopuncture, cupping, thread-embedding acupuncture, and Doin therapy). Acupuncture (versus inactive control) and Chuna manual therapy and pharmacopuncture (versus usual care) are recommended for symptom alleviation in the clinical treatment of neck pain. Electroacupuncture (versus usual care) and cupping (versus inactive control) should be considered for the alleviation of symptoms in the clinical treatment of neck pain. ConclusionsThe guideline could assist traditional Korean medicine doctors in South Korea to provide evidence-based, standardized treatment for neck pain in adults. Consequently, implementing this guideline in traditional Korean- medicine practice could expand the scope of health-insurance coverage, thereby reducing the public burden of medical expenses.

Responding Fails to Extinguish During Human-Laboratory Experiments of Resurgence

Resurgence is observed when a previously extinguished behavior reemerges while a more recently reinforced behavior is extinguished. Resurgence is further defined as responding that is greater than an inactive control response that has never produced reinforcement. Recent studies of resurgence using neurotypical adults as participants in human-laboratory investigations have produced discrepant patterns of responding compared to nonhuman animal laboratory studies when comparing control response performance. Namely, human-laboratory investigations have produced no differences between target and control responding, and persistence of all response types across the resurgence-test phase. In the present study, we conducted two human-laboratory experiments to determine if these effects were a product of the history of reinforcement associated with the target response as well as the types of technology used in human-laboratory studies. For all participants, we found no differences in levels of resurgence and occurrence for the target and control response, respectively. Moreover, we observed persistence of all response types across the resurgence-test phase in a manner consistent with prior research. This finding was apparent even when the length of baseline (i.e., reinforcement for the target) was increased, when the length of extinction was increased, and when low-technology stimuli were used. We highlight the implications of this outcome in the context of recent human-laboratory studies that have used arbitrary responses to study resurgence, and discuss the possible role of verbal mediation in these investigations.

Analgesia and Prevention of Opioid Self‐Administration by Agmatine‐Based Analogues

Chronic pain is a debilitating condition that is a heightened health concern due to the concurrent pain and opioid epidemics. The currently available options for the treatment and management of chronic pain, opioids, are associated with risk of conversion to addiction and diversion from patients for whom use is intended. To this end, we have studied non-opioid interventions, specifically the inhibition of the glutamatergic system. The glutamatergic system is shown to play a central role in opioid addiction, therefore its inhibition has been shown to prevent the development of opioid-seeking behavior in a rodent model of drug-seeking. A decarboxylated form of L-arginine, agmatine, is able to prevent the development of fentanyl-seeking behavior in a model of mouse self-administration likely through its role as an N-methyl-D-aspartate antagonist. However, agmatine has shown limited penetration through the blood brain barrier (BBB) and a short systemic half-life, limiting its clinical utility. We have designed a strategically-substituted agmatine compound (SSA3) with the goal of improving its penetration through the BBB by increasing the lipophilicity of agmatine, potentially improving distribution across the BBB and increasing its half-life following systemic delivery. To this end, we have evaluated SSA3 as a more viable potential therapeutic for the treatment of opioid use disorders (OUD). Mice (F, 21-30g) were given access to operant chambers and allowed to press either for oral oxycodone reward or an inactive control. Daily, the mice were given either a pre-treatment of a strategically-substituted agmatine (SSA3) compound or vehicle control, i.p.. Daily lever-pressing was recorded as an indication of drug-seeking behavior. Additionally, this same cohort was allowed to lever press for food pellet reward following conclusion of oxycodone reinforcement. Area under the curve (AUC) was compared between SSA pre-treated and vehicle pre-treated groups. Pre-treatment with the SSA3 compound significantly decreased oxycodone seeking behavior, but had no impact on food-maintained responding. Additionally, SSA3 showed no impact on motor coordination or cardiovascular function, side effects of concern for glutamatergic compounds. These data indicate that a strategically-substituted agmatine compound is capable of significantly reducing opioid-seeking behavior with a wide therapeutic window, avoiding the motor impairment and cardiovascular impairment typical of drugs of this class. Our future work includes optimization of dosing regimen as well as modeling the prevention of opioid relapse.

Efeito do treinamento resistido na sobrevida de camundongos c57bl/6 com caquexia associada ao melanoma cutâneo

OBJETIVO: O objetivo desse estudo foi verificar o efeito do treinamento resistido na sobrevida de camundongos C57BL/6 com caquexia associada ao melanoma cutâneo. MATERIAL E MÉTODOS: A amostra foi constituída por 64 (camundongos C57BL/6 fêmeas, com idade entre 10 e 12 semanas, com cerca de 50 ± 5 gramas de peso corporal. Os camundongos foram distribuídos aleatoriamente em quatros grupos: i. camundongos controle, com indução de tumor, inativos fisicamente (Controle, n = 16); ii. camundongos submetidos ao treinamento resistido diario somente antes da indução tumoral (Treino 1, n = 16); iii. camundongos submetidos ao treinamento resistido diario antes e após da indução tumoral (Treino 2, n = 16); iv. camundongos submetidos ao treinamento resistido diario após a indução tumoral e apresentado quadro caquetico (Treino 3, n = 16). O procedimento para treinamento resistido (TR) com choque foi utilizada uma escada com 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. O procedimento para TR com choque foi utilizada uma escada 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. O exercício resistido baseia-se na subida dos camundongos, na plataforma de saída aplicava-se um choque elétrico como estímulo para subir as escadas, nesta etapa era aplicada o choque nas quatro patas do animal com uma tensão elétrica de 20 volts a uma frequência de 45 Hertz durante seis séries de oito repetições, cada uma com noventa segundos de intervalo entre as séries Os grupos de camundongos foram submetidos a acompanhamento por no máximo 15 dias após o diagnóstico da caquexia a fim de comparar a sobrevida geral relacionada ao câncer entre os grupos de estudo. As curvas de sobrevivência de Kaplan-Meier foram estimadas para cada evento e as curvas dos diferentes grupos foram comparadas usando o teste de Log-rank. O tempo de sobrevida proposta foi de 25 dias após inoculação RESULTADOS: Os resultados apresentados nesse estudo mostraram que não houve diferença significativa (p &lt;0,05) entre as propostas de treino. CONCLUSÃO: Não houve diferença na sobrevida de animais com caquexia associada ao modelo tumoral singênico de melanoma cutâneo com intervenção de exercício resistido ou sedentários.

Horse-riding simulators in treatment of chronic low back pain: A meta-analysis.

The use of horse-riding simulators in the treatment of chronic low back pain has drawn considerable attention for its efficacy and acceptability to reduce chronic low back pain; because of the similarities in movements provided by equine-assisted therapies and the possible accessibility advantages. However, the results are conflicting. This study aimed to perform a meta-analysis of randomised controlled trials to assess the impact of treatments based on horse-riding simulators on chronic low back pain. A systematic literature search up to January 2021 was performed and 11 studies were detected with 543 subjects with chronic low back pain at the baseline of the study, 257 of them were using horse-riding simulators, and 255 of them were inactive control group who continued their usual care, and similar kind of physical therapy (control). They reported a comparison between horse-riding simulators and control to reduce chronic low back pain. Mean differences (MD) with 95% confidence intervals (CIs) were calculated assessing the impact of treatments based on horse-riding simulators on chronic low back pain using the continuous method with a random or fixed-effect model. Significantly higher change-from-baseline pain outcomes was observed in Visual Analogue Scale (MD, -4.36; 95% CI, -6.24 to -2.30, P<.001), and Roland Morris Disability Questionnaire change-from-baseline (MD, -2.32; 95% CI, -3.52 to -1.12, P<.001) with horse-riding simulators compared with control. Using horse-riding simulators may lower the risk of chronic low back pain. This relationship forces us to recommend the use of horse-riding simulators to avoid any complications that could occur with chronic low back pain.

The relationship between vitamin D status, intake and exercise performance in UK University-level athletes and healthy inactive controls.

The potential ergogenic effects of vitamin D (vitD) in high performing athletes has received considerable attention in the literature and media. However, little is known about non-supplemented university athletes and students residing at a higher latitude. This study aimed to investigate the effects of vitD (biochemical status and dietary intake) on exercise performance in UK university athletes and sedentary students. A total of 34 athletes and 16 sedentary controls were studied during the spring and summer months. Serum vitD status and sunlight exposure were assessed using LC-MS/MS and dosimetry, respectively. Muscular strength of the upper and lower body was assessed using handgrip and knee extensor dynamometry (KE). Countermovement jump (CMJ) and aerobic fitness were measured using an Optojump and VO2max test, respectively. Statistical analysis was performed using paired/ independent t-tests, ANCOVA and Pearson/ Spearman correlations, depending on normality. VitD status increased significantly over the seasons, with athletes measuring higher status both in spring (51.7±20.5 vs. 37.2±18.9 nmol/L, p = 0.03) and summer (66.7±15.8 vs 55.6±18.8 nmol/L, p = 0.04) when compared to controls, respectively. Notably, 22% of the subjects recruited were vitD deficient during the spring term only (<25nmol/L, n 9). Subjects with ‘insufficient’ vitD status (<50nmol/L) elicited significantly lower CMJ when contrasted to the vitD ‘sufficient’ (>50nmol/l) group (p = 0.055) and a lower VO2 max (p = 0.05) in the spring and summer term (p = 0.05 and p = 0.01, respectively). However, an ANCOVA test showed no significant difference detected for either CMJ or VO2max following adjustments for co-variates. In conclusion, we provide novel information on the vitD status, dietary intake, physical fitness and sunlight exposure of UK young adults across two separate seasons, for which there is limited data at present.