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Find video protocols related to scientific articles indexed in Pubmed.
Increased Pain Sensitivity in Chronic Pain Subjects on Opioid Therapy: A Cross-Sectional Study Using Quantitative Sensory Testing.
Pain Med
PUBLISHED: 11-08-2014
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The aim of this study was to compare the sensitivity to experimental pain of chronic pain patients on opioid therapy vs chronic pain patients on non-opioid therapy and healthy subjects by quantitative sensory testing (QST).
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A leptin-mediated central mechanism in analgesia-enhanced opioid reward in rats.
J. Neurosci.
PUBLISHED: 07-18-2014
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Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1? in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management.
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Persistent nociception induces anxiety-like behavior in rodents: role of endogenous neuropeptide S.
Pain
PUBLISHED: 03-10-2014
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Anxiety disorder is a comorbid condition of chronic pain. Analgesics and anxiolytics, subject to addiction and abuse, are currently used to manage pain and anxiety symptoms. However, the cellular mechanism underlying chronic pain and anxiety interaction remains to be elucidated. We report that persistent nociception following peripheral nerve injury induced anxiety-like behavior in rodents. Brain expression and release of neuropeptide S (NPS), a proposed endogenous anxiolytic peptide, was diminished in rodents with coexisting nociceptive and anxiety-like behaviors. Intracerebroventricular administration of exogenous NPS concurrently improved both nociceptive and anxiety-like behaviors. At the cellular level, NPS enhanced intra-amygdaloidal inhibitory transmission by increasing presynaptic gamma-aminobutyric acid (GABA) release from interneurons. These findings indicate that the interaction between nociceptive and anxiety-like behaviors in rodents may be regulated by the altered NPS-mediated intra-amygdaloidal GABAergic inhibition. The data suggest that enhancing the brain NPS function may be a new strategy to manage comorbid pain and anxiety.
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'Do UC the melanoma?' Recognising the importance of different lesions displaying unevenness or having a history of change for early melanoma detection.
Australas. J. Dermatol.
PUBLISHED: 02-19-2014
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Many melanomas are of a diameter smaller than 6?mm and may lack classical asymmetry, border irregularity and colour variegation (ABCD). The objectives of this article are to characterise the fidelity of melanomas diagnosed in a high-risk clinic to the ABCD and to review potential methods for early clinical detection of melanoma.
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Buprenorphine-naloxone therapy in pain management.
Anesthesiology
PUBLISHED: 02-11-2014
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Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.
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Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury.
Brain Res.
PUBLISHED: 01-13-2014
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Midazolam and morphine are often used in pediatric intensive care unit (ICU) for analgesia and sedation. However, how these two drugs interact behaviorally remains unclear. Here, we examined whether (1) co-administration of midazolam with morphine would exacerbate morphine tolerance and morphine-induced hyperactive behaviors, and (2) protein kinase C (PKC) would contribute to these behavioral changes. Male rats of 3-4 weeks old were exposed to a hindpaw burn injury. In Experiment 1, burn-injured young rats received once daily saline or morphine (10mg/kg, subcutaneous, s.c.), followed 30min later by either saline or midazolam (2mg/kg, intraperitoneal, i.p.), for 14 days beginning 3 days after burn injury. In Experiment 2, young rats with burn injury were administered with morphine (10mg/kg, s.c.), midazolam (2mg/kg, i.p.), and chelerythrine chloride (a non-specific PKC inhibitor, 10nmol, intrathecal) for 14 days. For both experiments, cumulative morphine anti-nociceptive dose-response (ED50) was tested and hyperactive behaviors such as jumping and scratching were recorded. Following 2 weeks of each treatment, ED50 dose was significantly increased in rats receiving morphine alone as compared with rats receiving saline or midazolam alone. The ED50 dose was further increased in rats receiving both morphine and midazolam. Co-administration of morphine and midazolam also exacerbated morphine-induced hyperactive behaviors. Expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor and PKC? in the spinal cord dorsal horn (immunohistochemistry; Western blot) was upregulated in burn-injured young rats receiving morphine alone or in combination with midazolam, and chelerythrine prevented the development of morphine tolerance. These results indicate that midazolam exacerbated morphine tolerance through a spinal NMDA/PKC-mediated mechanism.
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Update on neuropathic pain treatment: ion channel blockers and gabapentinoids.
Curr Pain Headache Rep
PUBLISHED: 07-27-2013
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Neuropathic pain is a debilitating chronic pain condition, which remains difficult to treat. The current mainstays of treatment include physical therapy, interventional procedures and medications. Among medications, ion channel blockers and gabapentinoids are the 2 classes of drugs commonly used to treat neuropathic pain. It has been suggested that these medications may be useful to treat a variety of neuropathic pain conditions. This article provides several updates on the utility of both ion channel blockers and gabapentinoids for the treatment of neuropathic pain.
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Racial parities in outcomes after radiotherapy for head and neck cancer.
Cancer
PUBLISHED: 07-10-2013
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Although black patients experience worse outcomes after treatment for squamous cell carcinoma of the head and neck (HNSCC), these conclusions were based on populations in which blacks comprised a minority of patients. The objective of the current study was to determine the impact of race on outcomes in patients with HNSCC who received radiotherapy at an institution in which blacks comprised the majority of patients.
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Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer.
Oral Oncol.
PUBLISHED: 06-18-2013
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In head and neck squamous cell carcinoma (HNSCC), docetaxel, cisplatin and 5-fluorouracil (TPF) has become an accepted induction chemotherapy regimen. However, carboplatin-paclitaxel (CT) regimens have shown comparable outcomes. Here, we compared the outcomes of patients treated with either TPF or CT as induction chemotherapy followed by definitive chemoradiation.
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Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats.
Brain Res.
PUBLISHED: 06-05-2013
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Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that (1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; (2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; (3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; (4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and (5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain.
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Lack of correlation between opioid dose adjustment and pain score change in a group of chronic pain patients.
J Pain
PUBLISHED: 02-26-2013
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Despite the increasing use of opioid analgesics for chronic pain management, it is unclear whether opioid dose escalation leads to better pain relief during chronic opioid therapy. In this study, we retrospectively analyzed clinical data collected from the Massachusetts General Hospital Center for Pain Medicine over a 7-year period. We examined 1) the impact of opioid dose adjustment (increase or decrease) on clinical pain score; 2) gender and age differences in response to opioid therapy; and 3) the influence of clinical pain conditions on the opioid analgesic efficacy. A total of 109 subjects met the criteria for data collection. We found that neither opioid dose increase, nor decrease, correlated with point changes in clinical pain score in a subset of chronic pain patients over a prolonged course of opioid therapy (an average of 704 days). This lack of correlation was consistent regardless of the type of chronic pain including neuropathic, nociceptive, or mixed pain conditions. Neither gender nor age differences showed a significant influence on the clinical response to opioid therapy in these subjects. These results suggest that dose adjustment during opioid therapy may not necessarily alter long-term clinical pain score in a group of chronic pain patients and that individualized opioid therapy based on the clinical effectiveness should be considered to optimize the treatment outcome.
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Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: immunohistochemical marker of perisinusoidal basement membrane formation.
Anat Rec (Hoboken)
PUBLISHED: 01-28-2013
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Liver sinusoids are lined by a fenestrated endothelium that lacks a basement membrane. Formation of perisinusoidal basement membranes beneath the endothelium is an integral feature of capillarization of sinusoids that is a significant pathology found in advanced fibrosis. Liver fibrosis is prevalent in elderly cadavers; however, basement membrane formation in these liver samples has yet to be studied. Collagen type IV and laminin are major basement membrane proteins and their codistribution around sinusoids provides an immunohistochemical marker of basement membrane formation. Here, we examined the intralobular sites of perisinusoidal basement membrane formation in elderly cadaveric livers having various stages of fibrosis. Collagen IV and laminin codistributed in basement membranes of portal and septal ductular and vascular structures, providing a positive control. In the parenchyma, collagen IV immunostaining of sinusoids was panlobular in all stages of fibrosis, and the stain was continuous along the sinusoids. In contrast, laminin was not detected in livers, showing minimal fibrotic change. It was rarely seen in perisinusoidal/pericellular fibrosis, but frequently in septa formation, bridging fibrosis, and cirrhosis. The laminin stain was patchy, occurring principally in sinusoids of periportal and periseptal areas, less commonly in mid-lobular and rarely in centrilobular areas. Consecutive sections revealed that laminin codistributed with collagen IV in these sinusoidal locations, thus marking the sites of perisinusoidal basement membrane formation in aged fibrotic livers. This development is presumably related to aging of the liver and exacerbated by liver injury caused by advanced liver fibrosis, possibly resulting in sinusoidal capillarization.
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Clinical and dermoscopic characteristics of desmoplastic melanomas.
JAMA Dermatol
PUBLISHED: 01-18-2013
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To describe and analyze the clinical and dermoscopic characteristics of desmoplastic melanoma (DM) as a function of pathologic subtype and phenotypic traits.
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Does pain score in response to a standardized subcutaneous local anesthetic injection predict epidural steroid injection outcomes in patients with lumbosacral radiculopathy? A prospective correlational study.
Pain Med
PUBLISHED: 01-07-2013
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Epidural steroid injections (ESI) are the most commonly performed pain procedures. Despite numerous studies, controversy continues to surround their effectiveness. The purpose of this study is to determine whether a standard, clinical local anesthetic injection can predict outcomes for ESI.
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Redefining the number needed to excise.
Australas. J. Dermatol.
PUBLISHED: 01-05-2013
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The number needed to excise (NNE) is a metric used to convey the efficiency of dermatological practice by serving as a gauge for the diagnostic accuracy of melanoma. Rather than an NNE for melanoma alone, we assert that the NNE should measure all skin cancer types and we present data on NNE from two clinical sites demonstrating the utility and trends in NNE over time.
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Disruption of persistent nociceptive behavior in rats with learning impairment.
PLoS ONE
PUBLISHED: 01-01-2013
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Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed A? solution, whereas persistent nociception produced in these rats by complete Freunds adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of A?, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase C? was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain.
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Combination therapy for neuropathic pain: a review of current evidence.
CNS Drugs
PUBLISHED: 12-03-2011
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Neuropathic pain is a debilitating chronic condition that remains very difficult to treat. Recently, a number of clinical studies have compared the effectiveness of combination drug therapy with monotherapy for neuropathic pain treatment. In this article, we summarize up-to-date clinical studies of combination therapy for the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a relatively small number of clinical studies on this topic, several positive indications have emerged. First, clinical studies using gabapentin (five positive trials) and pregabalin (five positive trials and one negative trial) in combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have shown positive responses greater than the respective monotherapies for pain related to diabetic neuropathy and postherpetic neuropathy. Second, high-concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be effective add-on therapies (a modality of combination therapy) for various neuropathic pain conditions. Third, combination therapy for cancer-related neuropathic pain has yielded only limited success based on a number of small-scale clinical studies. While there are benefits of using combination therapy for neuropathic pain treatment, including better pain relief and reduced adverse effects, more clinical studies are required in order to (i) make head-to-head comparisons between combination and single-drug therapies, (ii) identify symptom-specific combination therapies for distinctive clinical neuropathic pain conditions, (iii) explore combination therapies that include non-drug modalities such as physical therapy, psychological coping and biofeedback to facilitate functional restoration and (iv) develop new and objective evaluation tools for clinical outcome assessment.
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Opioid therapy for chronic pain: physicians attitude and current practice patterns.
J Opioid Manag
PUBLISHED: 10-01-2011
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Although opioid therapy is widely used for the treatment of chronic pain conditions, there is a lack of consensus on a number of practical issues related to the use of prescription opioids. The authors conducted a comprehensive practice-oriented survey to examine physicians attitudes, knowledge, experience, and practice patterns regarding opioid therapy for chronic pain management. The survey was conducted during 2007 and 2008 through nationwide direct mails and e-mails to physicians who are currently practicing in the United States. The survey contained 23 questions divided into six categories: (1) physicians overall view on opioid therapy for chronic pain management; (2) clinical indications for opioid therapy; (3) patient-related factors influencing the decision to begin opioid therapy; (4) effectiveness of opioid therapy; (5) choice of opioid regimen; and (6) opioid agreement and opioid abuse behavior. The survey results suggest that opioid therapy remains as an important treatment option for chronic malignant and nonmalignant pain. However, the survey results should be viewed in the context of a low response rate (18.2 percent). These results also suggest that by improving the clinical knowledge of physicians participating in opioid therapy through education and collaboration, including a team approach with consultation from pain specialists, psychologists, and others, a better outcome for opioid therapy in patients with chronic pain conditions could be achieved.
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New strategies in head and neck cancer: understanding resistance to epidermal growth factor receptor inhibitors.
Clin. Cancer Res.
PUBLISHED: 04-20-2010
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The epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma of the head and neck (HNSCC). However, despite high expression of EGFR in these cancers, EGFR inhibitor monotherapy has only had modest activity. Potential mechanisms of resistance to EGFR-targeted therapies involve EGFR and Ras mutations, epithelial-mesenchymal transition, and activation of alternative and downstream pathways. Strategies to optimize EGFR-targeted therapy in head and neck cancer involve not only the selection for patients most likely to benefit but also the use of combination therapies to target the network of pathways involved in tumor growth, invasion, angiogenesis, and metastasis.
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A survey of selected physician views on acupuncture in pain management.
Pain Med
PUBLISHED: 03-01-2010
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To collect information on the role of acupuncture in pain management from pain physicians and referral physicians who manage clinical pain conditions.
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An intravenous ketamine test as a predictive response tool in opioid-exposed patients with persistent pain.
J Pain Symptom Manage
PUBLISHED: 07-16-2009
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Chronic pain patients who are treated with opioid therapy represent a significant challenge to medical professionals. When pain recurs in the face of a previously effective opioid regimen, treatment options include dose escalation, opioid rotation, drug holidays, and the addition of adjuvants. Some experts advocate the use of N-methyl-D-aspartate receptor (NMDA-R) antagonists to combat tolerance. Recently, the use of an intravenous (i.v.) ketamine infusion to predict the response to a dextromethorphan (DX) treatment trial has been described. In this study, 56 opioid-exposed patients with recurrent pain were treated with a low-dose (0.1mg/kg) i.v. ketamine test followed by a DX treatment course. Using previously designated cutoff values for a positive response to ketamine (67% or more pain relief) and DX (50% or more pain relief), the sensitivity, specificity, positive predictive value, and negative predictive value for an i.v. ketamine infusion to predict subsequent response to DX treatment were 72%, 68%, 52%, and 85%, respectively. The observed agreement between analgesic responses was 78%, indicating a highly significant correlation (r=0.54, P=0.0001). Subgroup classification revealed no significant differences in the response to either ketamine or DX treatment based on pain classification (i.e., nociceptive, neuropathic, or mixed) or placebo response. In contrast, a weaker correlation between ketamine and DX response was found in subjects requiring high-dose rather than low-dose opioid therapy. A significant correlation also was noted between the development of side effects for the two NMDA-R antagonists. Based on these results, we conclude that an i.v. ketamine test may be a valuable tool in predicting subsequent response to DX treatment in opioid-exposed patients. with persistent pain.
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Alcohol consumption and health status in older adults: a longitudinal analysis.
J Aging Health
PUBLISHED: 07-06-2009
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Objective. This longitudinal study examines the relationship of alcohol consumption to mortality and changes in mental and functional health in older adults. Method.In a national population health survey, 4,187 participants aged 50 and older at baseline provided information on alcohol consumption, potential confounders, and follow-up vital status. Logistic regression estimated the odds ratio for mortality, increase in psychological distress, and decline in functional health 10 years later. Results. Compared with lifelong abstainers, light and moderate drinkers were at nonsignificantly lower risk of mortality. Among survivors, alcohol consumption showed no consistent relationship with increases in psychological distress. Occasional and light drinkers had significantly reduced risk of a substantial functional health decline, whereas moderate drinkers had nonsignificantly reduced risk. Discussion. Findings suggest that light-to-moderate alcohol consumption reduces the risk of substantial functional health decline in older middle-aged drinkers.
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Insights into pilus assembly and secretion from the structure and functional characterization of usher PapC.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-20-2009
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Ushers constitute a family of bacterial outer membrane proteins responsible for the assembly and secretion of surface organelles such as the pilus. The structure at 3.15-A resolution of the usher pyelonephritis-associated pili C (PapC) translocation domain reveals a 24-stranded kidney-shaped beta-barrel, occluded by an internal plug domain. The dimension of the pore allows tandem passage of individual folded pilus subunits in an upright pilus growth orientation, but is insufficient for accommodating donor strand exchange. The molecular packing revealed by the crystal structure shows that 2 PapC molecules in head-to-head orientation interact via exposed beta-strand edges, which could be the preferred dimer interaction in solution. In vitro reconstitution of fiber assemblies suggest that PapC monomers may be sufficient for fiber assembly and secretion; both the plug domain and the C-terminal domain of PapC are required for filament assembly, whereas the N-terminal domain is mainly responsible for recruiting the chaperone-subunit complexes to the usher. The plug domain has a dual function: gating the beta-pore and participating in pilus assembly.
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Altered quantitative sensory testing outcome in subjects with opioid therapy.
Pain
PUBLISHED: 01-08-2009
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Preclinical studies have suggested that opioid exposure may induce a paradoxical decrease in the nociceptive threshold, commonly referred as opioid-induced hyperalgesia (OIH). While OIH may have implications in acute and chronic pain management, its clinical features remain unclear. Using an office-based quantitative sensory testing (QST) method, we compared pain threshold, pain tolerance, and the degree of temporal summation of the second pain in response to thermal stimulation among three groups of subjects: those with neither pain nor opioid therapy (group 1), with chronic pain but without opioid therapy (group 2), and with both chronic pain and opioid therapy (group 3). We also examined the possible correlation between QST responses to thermal stimulation and opioid dose, opioid treatment duration, opioid analgesic type, pain duration, or gender in group 3 subjects. As compared with both group 1 (n=41) and group 2 (n=41) subjects, group 3 subjects (n=58) displayed a decreased heat pain threshold and exacerbated temporal summation of the second pain to thermal stimulation. In contrast, there were no differences in cold or warm sensation among three groups. Among clinical factors, daily opioid dose consistently correlated with the decreased heat pain threshold and exacerbated temporal summation of the second pain in group 3 subjects. These results indicate that decreased heat pain threshold and exacerbated temporal summation of the second pain may be characteristic QST changes in subjects with opioid therapy. The data suggest that QST may be a useful tool in the clinical assessment of OIH.
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Desmoplastic melanoma: a review.
J. Am. Acad. Dermatol.
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Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis, and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of DM and nondesmoplastic melanoma. This has led to the separation of DM into 2 histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors, and examine the current literature on disease progression and management.
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A functional relationship between trigeminal astroglial activation and NR1 expression in a rat model of temporomandibular joint inflammation.
Pain Med
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To examine the hypothesis that glial activation would regulate the expression of the N-methyl-D-aspartate receptor subunit 1 (NR1) in the trigeminal subnucleus caudalis (Sp5C) after temporomandibular joint (TMJ) inflammation.
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Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors.
Pain
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A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. As compared with Wistar rats, WKY rats showed a lower plasma melatonin level, downregulation of the melatonin MT1 receptor, but upregulation of the NR1 subunit of the NMDA receptor in the ipsilateral trigeminal subnucleus caudalis (Sp5C). Intracisternal administration of 6-chloromelatonin (250 ?g, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
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From the bottle to the skin: challenges in evaluating antioxidants.
Photodermatol Photoimmunol Photomed
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Endogenous production and ultraviolet-generated free radicals in the skin can lead to photoaging and even skin cancer. Topical antioxidants have been found to provide benefits against ultraviolet damage and these ingredients have been incorporated into various cosmetic products and claimed to have substantial effects. Currently, there is a lack in a standardized rating system to measure the concentration and activity levels of antioxidants in these products. As a result, it is difficult for consumers and clinicians to evaluate and select commercial products based on readily accessible evidence. In this review, we will describe four assays which have been used to measure antioxidants in various products, and the strengths and weaknesses of each test will be detailed. We will highlight key considerations for clinicians when interpreting the results of antioxidant tests when evaluating commercial products containing antioxidants.
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Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression.
J. Clin. Invest.
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Pain and depression are frequently comorbid disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in this comorbidity. We found that chronic pain in rats induced depressive behavior and IDO1 upregulation in the bilateral hippocampus. Upregulation of IDO1 resulted in the increased kynurenine/tryptophan ratio and decreased serotonin/tryptophan ratio in the bilateral hippocampus. We observed elevated plasma IDO activity in patients with both pain and depression, as well as in rats with anhedonia induced by chronic social stress. Intra-hippocampal administration of IL-6 in rats, in addition to in vitro experiments, demonstrated that IL-6 induces IDO1 expression through the JAK/STAT pathway. Further, either Ido1 gene knockout or pharmacological inhibition of hippocampal IDO1 activity attenuated both nociceptive and depressive behavior. These results reveal an IDO1-mediated regulatory mechanism underlying the comorbidity of pain and depression and suggest a new strategy for the concurrent treatment of both conditions via modulation of brain IDO1 activity.
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The role of antioxidants in photoprotection: a critical review.
J. Am. Acad. Dermatol.
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Free radicals have long been studied as a contributor to aging and disease processes. Endogenous production of radicals from cellular metabolism and exogenous sources from ultraviolet radiation and pollution can damage the skin on the cellular and tissue levels. Although the body possesses an elegant defense system to prevent radical damage, this innate system can be overwhelmed and lead to a state of oxidative stress or immunosuppression, and can even trigger carcinogenesis. Topical supplementation of antioxidants can provide additional protection to neutralize reactive oxygen species from both endogenous and exogenous sources. This review will discuss our current understanding of the mechanisms of free radical damage and evaluate the potential benefit of topical antioxidants in sunscreens and skin care products.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.