Exploring the brain in pain: Activations,deactivations and their relation

The majority of neuroimaging studies on pain focuses on the study of BOLD activations, and more rarely on deactivations. In this study, in a relatively large cohort of subjects (N = 61), we assess (a) the extent of brain activation and deactivation during the application of two different heat pain levels (HIGH and LOW) and (b) the relations between these two directions of fMRI signal change. Furthermore, in a subset of our subjects (N = 12), we assess (c) the functional connectivity of pain-activated or -deactivated regions during resting states. As previously observed, we find that pain stimuli induce intensity dependent (HIGH pain > LOW pain) fMRI signal increases across the pain matrix. Simultaneously, the noxious stimuli induce activity decreases in several brain regions, including some of the ‘core structures’ of the default network (DMN). In contrast to what we observe with the signal increases, the extent of deactivations is greater for LOW than HIGH pain stimuli. The functional dissociation between activated and deactivated networks is further supported by correlational and functional connectivity analyses. Our results illustrate the absence of a linear relationship between pain activations and deactivations, and therefore suggest that these brain signal changes underlie different aspects of the pain experience.     

Effect of axial load on anterior tibial translation when transitioning from non-weight bearing to weight bearing

Background

While the application of compressive joint loads and thigh muscle activity are associated with anterior tibial translation in vitro, less is known during early load acceptance in vivo. We investigated the effects of increasing axial loads on anterior tibial translation and thigh muscle activity in healthy knees during transition from non-weight bearing to early weight bearing.

Methods

Participants (11 males, 11 females) underwent 20%, 40%, and 60% body weight acceptance trials at 20° knee flexion while electromagnetic sensors measured anterior tibial translation (mm), and surface electromyography recorded quadriceps and hamstring muscle onset times (ms) and amplitudes (% maximal voluntary isometric contraction). Repeated measures ANOVA compared values across loads. Pearson correlations examined relationships between anterior tibial translation and muscle onset times and amplitudes within each load.

Findings

As load increased, anterior tibial translation (Mean (standard deviation)) (20% = 4.7 (1.7) mm < 40% = 7.1 (1.9) mm < 60% = 8.8 (2.1) mm), and quadriceps (20% = 23.6 (14.9)% maximal voluntary isometric contraction <40% = 32.7 (11.8)% maximal voluntary isometric contraction <60% = 41.1 (13.5)% maximal voluntary isometric contraction) and hamstring (20% = 15.5 (15.7)% maximal voluntary isometric contraction <40% = 23.0 (16.4)% maximal voluntary isometric contraction <60% = 27.6 (19.1)% maximal voluntary isometric contraction) activation increased, while quadriceps (20% = 96.7 (28.4) ms > 60% 80.2 (21.8) ms) and hamstring (20% = 141.5 (65.0) ms and 40% = 126.3 (68.8) > 60% 107.6 (28.4) ms) onset times decreased (P ? 0.05). There were no relationships between anterior tibial translation and muscle activation amplitudes (R = 0.033–0.294) or onset times (R = −0.031–0.374) (P > 0.09).

Interpretation

Greater axial loads near full knee extension during early weight acceptance result in greater anterior tibial translation, regardless of faster and stronger activation amplitudes. These findings support injury prevention programs aimed to reduce impact forces as they may in turn reduce anterior tibial translation and corresponding ligamentous strain during dynamic activity.     

Understanding Risky Behavior Engagement Amongst Chinese Adolescents

The goal of the current study is to examine whether neuroticism, cognitive emotional regulation deficits, and/or their interaction predict increased engagement in risky behaviors following increases in symptoms of depression. At Time 1, 411 Chinese adolescents from Yue Yang, Hunan completed self-report measures assessing cognitive emotion regulation, depressive symptoms, and risky behavior engagement. Follow-up assessments occurred once a month for 6 months, and participants completed measures assessing depressive symptoms and risky behavior engagement. In line with our hypotheses, results of idiographic, multilevel modeling analyses indicated that individuals who exhibited high levels of neuroticism and a tendency to utilize maladaptive cognitive emotional regulation strategies were more likely than individuals possessing only one or neither of these vulnerability factors to report greater engagement in risky behaviors following increases in symptoms of depression.     

The Impact of Placebo,Psychopathology, and Expectations on the Response to Acupuncture Needling in Patients With Chronic Low Back Pain

Comorbid psychopathology is a variable not explored in the acupuncture RCTs that could explain whether subgroups of patients with chronic low back pain have differential responses to acupuncture or placebo treatments. This was a controlled, blinded, crossover trial of verum acupuncture and validated sham acupuncture in 40 CLBP patients, with a Low or High level of psychiatric comorbidity. They completed a 0 to 10 rating scale for pain at the beginning and end of each treatment session, and rated their expectations for change in pain. Verum acupuncture was performed at Large Intestine 4 on the dorsal right hand for 30 minutes by a licensed acupuncturist. Data analysis used percent improvement in pain as the primary outcome for each of the treatment sessions. Both groups (21 Low and 19 High) reported significant analgesia with verum acupuncture needling, mean 33%, P = .9 for difference between groups; and with placebo, 26%, P = .09. In both groups, expectations were only a significant predictor of verum acupuncture response, P = .002, such that those with greater expectations had greater pain relief. Psychiatric comorbidity does not significantly impact acupuncture or placebo acupuncture analgesia in CLBP. It does not affect the positive impact of expectations on reported pain relief from real acupuncture.PerspectivePsychiatric comorbidity may predict differences between acupuncture and placebo responses, not otherwise seen in the RCTs for low back pain. Using a blinded, crossover design, we report that it does not predict outcome, nor does it seem to modify the effect of expectancy (a known predictor) on acupuncture response.     

Perfectionism, Anxiety, and Depression: Are the Relationships Independent?

The present study examined the relationship between perfectionism and various features of anxiety to determine whether these features of anxiety were related to perfectionism independent of depression. A factor analysis of various measures of anxiety symptoms reduced the measures to three factors: obsessive-compulsive disorder, social anxiety/trait anxiety/worry, and posttraumatic stress disorder (PTSD) symptoms. All three factors were significantly related to maladaptive perfectionism, but the social/trait/worry factor was the only factor found to be related to maladaptive perfectionism independent of depression. The PTSD factor was the only factor related to the adaptive component of perfectionism, and this relationship remained significant even after controlling for depression. Perfectionism was related to depression after controlling for the three anxiety factors; maladaptive perfectionism was positively related to depression and adaptive perfectionism was negatively related to depression. These findings indicate that there appears to be an aspect of perfectionism that is related to anxiety independent of depression and a separate aspect of perfectionism that is related to depression independent of anxiety.     

A vertebrate fatty acid desaturase with Δ5 and Δ6 activities

Delta5 and Delta6 fatty acid desaturases are critical enzymes in the pathways for the biosynthesis of the polyunsaturated fatty acids arachidonic, eicosapentaenoic, and docosahexaenoic acids. They are encoded by distinct genes in mammals and Caenorhabditis elegans. This paper describes a cDNA isolated from zebrafish (Danio rerio) with high similarity to mammalian Delta6 desaturase genes. The 1,590-bp sequence specifies a protein that, in common with other fatty acid desaturases, contains an N-terminal cytochrome b(5) domain and three histidine boxes, believed to be involved in catalysis. When the zebrafish cDNA was expressed in Saccharomyces cerevisiae it conferred the ability to convert linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) to their corresponding Delta6 desaturated products, 18:3n-6 and 18:4n-3. However, in addition it conferred on the yeast the ability to convert di-homo-gamma-linoleic acid (20:3n-6) and eicosatetraenoic acid (20:4n-3) to arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), respectively, indicating that the zebrafish gene encodes an enzyme having both Delta5 and Delta6 desaturase activity. The zebrafish Delta5/Delta6 desaturase may represent a component of a prototypic vertebrate polyunsaturated fatty acids biosynthesis pathway.     

Are surgery training programs ready for virtual reality? a survey of program directors in general surgery

BACKGROUND:

The use of advanced technology, such as virtual environments and computer-based simulators (VR/CBS), in training has been well established by both industry and the military. In contrast the medical profession, including surgery, has been slow to incorporate such technology in its training. In an attempt to identify factors limiting the regular incorporation of this technology into surgical training programs, a survey was developed and distributed to all general surgery program directors in the United States.

STUDY DESIGN:

A 22-question survey was sent to 254 general surgery program directors. The survey was designed to reflect attitudes of the program directors regarding the use of computer-based simulation in surgical training. Questions were scaled from 1 to 5 with 1 = strongly disagree and 5=strongly agree.

RESULTS:

A total of 139 responses (55%) were returned. The majority of respondents (58%) had seen VR/CBS, but only 19% had “hands-on” experience with these systems. Respondents strongly agreed that there is a need for learning opportunities outside of the operating room and a role for VR/CBS in surgical training. Respondents believed both staff and residents would support this type of training. Concerns included VR/CBS’ lack of validation and potential requirements for frequent system upgrades.

CONCLUSIONS:

Virtual environments and computer-based simulators, although well established training tools in other fields, have not been widely incorporated into surgical education. Our results suggest that program directors believe this type of technology would be beneficial in surgical education, but they lack adequate information regarding VR/CBS. Developers of this technology may need to focus on educating potential users and addressing their concerns.     

MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large-cell morphology and terminal B-cell differentiation. The differential diagnosis from Burkitt lymphoma, plasma cell myeloma and some variants of diffuse large B-cell lymphoma may be challenging because of the overlapping morphological, genetic and immunophenotypic features. Furthermore, the genomic landscape in PBL is not well known. To characterize the genetic and molecular heterogeneity of these tumors, we investigated 34 cases of PBL using an integrated approach, including fluorescence in situ hybridization, targeted sequencing of 94 B-cell lymphoma-related genes, and copy-number arrays. PBL were characterized by high genetic complexity including MYC translocations (87%), gains of 1q21.1-q44, trisomy 7, 8q23.2- q24.21, 11p13-p11.2, 11q14.2-q25, 12p and 19p13.3-p13.13, losses of 1p33, 1p31.1-p22.3, 13q and 17p13.3-p11.2, and recurrent mutations of STAT3 (37%), NRAS and TP53 (33%), MYC and EP300 (19%) and CARD11, SOCS1 and TET2 (11%). Pathway enrichment analysis suggested a cooperative action between MYC alterations and MAPK (49%) and JAK-STAT (40%) signaling pathways. Of note, Epstein-Barr virus (EBV)-negative PBL cases had higher mutational and copy-number load and more frequent TP53, CARD11 and MYC mutations, whereas EBVpositive PBL tended to have more mutations affecting the JAK-STAT pathway. In conclusion, these findings further unravel the distinctive molecular heterogeneity of PBL identifying novel molecular targets and the different genetic profile of these tumors in relation to EBV infection.     

Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth

AIM： To investigate the functional significance of insulin-like growth factor binding protein-5 （IGFBP-5） overexpression in pancreatic cancer （PaC）.
METHODS： The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses. Changes in cell survival and signal transduction were evaluated after mitogen and phosphatidylinositol activated protein kinase 3-kinase （PI3K） inhibitor treatment.
RESULTS： After serum deprivation, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 （ERK1/2） activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival.
CONCLUSION： These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.