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STUDY DESIGN.: An in vitro and in vivo experimental study. OBJECTIVE.: This study was undertaken to evaluate differences in the capability of inducing an implant-centered infection between Staphylococcus aureus and Mycobacterium tuberculosis. SUMMARY OF BACKGROUND DATA.: Bacterial infection is still one of the most serious and devastating complications after orthopedic implant surgery despite the advent of new antibiotics and treatment methods. METHODS.: S. aureus and M. tuberculosis were separately cultured with titanium plates. The bacteria colonized on the plates were isolated and cultured on culture medium. They were evaluated and compared by colony-forming units enumeration. Scanning electron microscopy was used to evaluate the difference in the colonization features of the 2 pathogens. In the in vivo experiment, 22 dogs were used to assess the susceptibility to infection after a local bacterial challenge with either S. aureus or M. tuberculosis. RESULTS.: S. aureus showed heavy adhesion and multiplication on the surface of titanium plates in vitro, whereas M. tuberculosis rarely adhered to the surface of the plates. Under scanning electron microscopy, S. aureus colonization was observed: the coccoid was widespread on the surface of the plates but only a few M. tuberculosis cells scattered on the surface of the plates. In in vivo test, the infection rateforthe S. aureus inoculation was higher than that for the M. tuberculosis challenge. The infection rate for the entire test population (n = 44 sites) was 39.58% (19/48). The infection rates were 54.17% (13/24) for the S. aureus challenge and 25% (6/24) for the M. tuberculosis challenge, respectively (P < 0.05). CONCLUSION.: It is less likely for M. tuberculosis to adhere and form a biofilm on an implant surface than S. aureus. Under otherwise identical conditions, M. tuberculosis contamination following instrumented spine surgery might lead to less occurrence of infection than S. aureus contamination. [ABSTRACT FROM AUTHOR]

Objectives: Hyperphenylalaninemia predicts poor outcomes in patients with cardiovascular disease. However, the prognostic value and factors associated with stress hyperphenylalaninemia (SHP) were unknown in critical patients in the cardiac ICU., Design: Prospective observational study., Setting: Single-center, cardiac ICU in Taiwan., Patients: Patients over 20 years old with Acute Physiology And Chronic Health Evaluation II scores greater than or equal to 15 and/or ventilatory support in the cardiac ICU., Interventions: We measured plasma phenylalanine levels serially during patients' stays in the ICU to investigate their prognostic value for 90-day mortality. Gene array was performed to identify genetic polymorphisms associated with SHP (phenylalanine level ≥ 11.2 μmol/dL) and to develop a Genetic Risk Score (GRS). We analyzed the associations between SHP and clinical factors and genetic variants and identified the correlation between pteridines and genetic variants., Measurements and Main Results: The study enrolled 497 patients. Increased phenylalanine concentration was independently associated with increased mortality risk. Patients with SHP had a higher mortality risk compared with those without SHP (log rank = 41.13; p < 0.001). SHP was associated with hepatic and renal dysfunction and with genetic polymorphisms on the pathway of tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2). Higher GRSs were associated with lower BH4 bioavailability in response to stress ( p < 0.05). In patients without SHP at baseline, those with GRSs gretaer than or equal to 2 had a higher frequency of developing SHP during the ICU stay (31.5% vs 16.1%; p = 0.001) and a higher mortality risk ( p = 0.004) compared with those with GRSs less than 2. In patients with SHP at baseline, genetic variants did not provide additional prognostic value., Conclusions: SHP in patients admitted to the ICU was associated with a worse prognosis. In patients without SHP, genetic polymorphisms associated with SHP measured using a GRS of greater than or equal to 2 was associated with the subsequent SHP and higher mortality risk., Competing Interests: Dr. Wu disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Abstract: Chronic pain is often accompanied by anxiety and depression disorders. Amygdala nuclei play important roles in emotional responses, fear, depression, anxiety, and pain modulation. The exact mechanism of how amygdala neurons are involved in pain and anxiety is not completely understood. The central nucleus of the amygdala contains 2 major subpopulations of GABAergic neurons that express somatostatin (SOM+) or protein kinase Cδ (PKCδ+). In this study, we found about 70% of phosphorylated ERK-positive neurons colocalized with PKCδ+ neurons in the formalin-induced pain model in mice. Optogenetic activation of PKCδ+ neurons was sufficient to induce mechanical hyperalgesia without changing anxiety-like behavior in naïve mice. Conversely, chemogenetic inhibition of PKCδ+ neurons significantly reduced the mechanical hyperalgesia in the pain model. By contrast, optogenetic inhibition of SOM+ neurons induced mechanical hyperalgesia in naïve mice and increased phosphorylated ERK-positive neurons mainly in PKCδ+ neurons. Optogenetic activation of SOM+ neurons slightly reduced the mechanical hyperalgesia in the pain model but did not change the mechanical sensitivity in naïve mice. Instead, it induced anxiety-like behavior. Our results suggest that the PKCδ+ and SOM+ neurons in the central amygdala exert different functions in regulating pain-like and anxiety-like behaviors in mice., (Copyright © 2021 International Association for the Study of Pain.)

DNA-damaging chemotherapy is a major component of therapy for high-risk neuroblastoma, and patients often relapse with treatment-refractory disease. We hypothesized that DNA repair genes with increased expression in alkylating agent resistant models would provide therapeutic targets for enhancing chemotherapy. In-vitro cytotoxicity of alkylating agents for 12 patient-derived neuroblastoma cell lines was assayed using DIMSCAN, and mRNA expression of 57 DNA repair, three transporter, and two glutathione synthesis genes was assessed by TaqMan low-density array (TLDA) with further validation by qRT-PCR in 26 cell lines. O6-methylguanine-DNA methyltransferase (MGMT) mRNA was upregulated in cell lines with greater melphalan and temozolomide (TMZ) resistance. MGMT expression also correlated significantly with resistance to TMZ+irinotecan (IRN) (in-vitro as the SN38 active metabolite). Forced overexpression of MGMT (lentiviral transduction) in MGMT non-expressing cell lines significantly increased TMZ+SN38 resistance. The MGMT inhibitor O6-benzylguanine (O6BG) enhanced TMZ+SN38 in-vitro cytotoxicity, H2AX phosphorylation, caspase-3 cleavage, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling. TMZ+IRN+O6BG delayed tumor growth and increased survival relative to TMZ+IRN in two of seven patient-derived xenografts established at time of death from progressive neuroblastoma. We demonstrated that high MGMT expression was associated with resistance to alkylating agents and TMZ+IRN in preclinical neuroblastoma models. The MGMT inhibitor O6BG enhanced the anticancer effect of TMZ+IRN in vitro and in vivo. These results support further preclinical studies exploring MGMT as a therapeutic target and biomarker of TMZ+IRN resistance in high-risk neuroblastoma., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitors and the synthetic cytotoxic retinoid fenretinide have achieved durable clinical responses in T-cell lymphomas as single agents, and patients who failed prior HDAC inhibitor treatment have responded to fenretinide. We have previously shown fenretinide synergized with the class I HDAC inhibitor romidepsin in preclinical models of TCLMs. There exist some key differences between HDAC inhibitors. Therefore, we determined if the pan-HDAC inhibitor vorinostat synergizes with fenretinide. We demonstrated cytotoxic synergy between vorinostat and fenretinide in nine TCLM cell lines at clinically achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells). In vivo, vorinostat + fenretinide + ketoconazole (enhances fenretinide exposures by inhibiting fenretinide metabolism) showed greater activity in subcutaneous TCLM xenograft models than other groups. Fenretinide + vorinostat increased reactive oxygen species (ROS, measured by 2',7'-dichlorodihydrofluorescein diacetate dye), resulting in increased apoptosis (via transferase dUTP nick end labeling assay) and histone acetylation (by immunoblotting). The synergistic cytotoxicity, apoptosis, and histone acetylation of fenretinide + vorinostat was abrogated by the antioxidant vitamin C. Like romidepsin, vorinostat combined with fenretinide achieved synergistic cytotoxic activity and increased histone acetylation in preclinical models of TCLMs, but not in non-malignant cells. As vorinostat is an oral agent and not a P-glycoprotein substrate it may have advantages in such combination therapy. These data support conducting a clinical trial of vorinostat combined with fenretinide in relapsed and refractory TCLMs., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aims to provide the best possible evidence-based information on the efficacy and safety of sifalimumab for treatment of skin injury (SI) caused by systemic lupus erythematosus (SLE)., Methods: In this study, electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Social Care Online, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched comprehensively from inceptions to June 30, 2019 without language restrictions. We will include randomized controlled trials (RCTs) on evaluating the efficacy and safety of sifalimumab for SI caused by SLE. Two investigators will conduct study selection, data extraction, and risk of bias assessment independently. We will use RevMan 5.3 Software to perform statistical analysis., Results: This study will lie in the exhaustive and systematic nature of the literature search and its methods for evaluating quality and analyzing RCTs data. Considering the controversial efficacy of the treatment for sifalimumab, this study is responsible for improving the existing evidence on the efficacy and safety of sifalimumab for SI caused by SLE., Conclusion: The results of this study will provide latest evidence for judging whether sifalimumab is an effective intervention for patients with SI caused by SLE or not., Study Registration: CRD42019148225.

Background: To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG)., Methods: Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis., Results: Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] -0.37; 95% CI -0.56, -0.19; P < .0001), stomachache (standardized MD [SMD] -0.80; 95% CI -1.45, -0.14; P = .02), and belching (SMD -2.00; 95% CI -3.80, -0.20; P = .03). However, acid regurgitation (SMD -0.71; 95% CI -1.69, 0.28; P = .16) and anorexia (SMD -0.75; 95% CI -2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups., Conclusion: Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.

This retrospective cohort study evaluated the effects of different frequencies of physical therapy intervention on the total knee arthroplasty (TKA) and total hip arthroplasty (THA) risk of osteoarthritis (OA) patients.We sampled 438,833 insurants from Taiwan National Health Insurance Research Database for patients diagnosed as having OA during 2000 to 2013. OA who received physical therapy within in the first year of OA diagnosis were divided based on the number of sessions they received in that first year: >24, 13-23, and <12 sessions.The results revealed that the TKA and THA incidence rates among patients aged 60 to 80 years were respectively 3.5% and 0.9% in the >24 cohort and 4.9% and 1.4% (all P < .001) in the comparison cohort. Moreover, the HRs of TKA and THA in the >24 cohort were 0.77 (0.67-0.87, P < .001) and 0.71 (0.53-0.96, P = .024), respectively. By contrast, no significant differences were noted between the 13-23 and <12 cohorts and their respective comparison cohorts.In conclusion, our study results indicated that elderly patients aged 60 to 80 years who underwent >24 physical therapy sessions within 1 year of receiving an OA diagnosis exhibited reduced of TKA and THA risks.

Pain-related diseases are the top leading causes of life disability. Identifying brain regions involved in persistent neuronal changes will provide new insights for developing efficient chronic pain treatment. Here, we showed that anterior nucleus of paraventricular thalamus (PVA) plays an essential role in the development of mechanical hyperalgesia in neuropathic and inflammatory pain models in mice. Increase in c-Fos, phosphorylated extracellular signal-regulated kinase, and hyperexcitability of PVA neurons were detected in hyperalgesic mice. Direct activation of PVA neurons using optogenetics and pharmacological approaches were sufficient to induce persistent mechanical hyperalgesia in naive animals. Conversely, inhibition of PVA neuronal activity using DREADDs (designer receptors exclusively activated by designer drugs) or inactivation of PVA extracellular signal-regulated kinase at the critical time window blunted mechanical hyperalgesia in chronic pain models. At the circuitry level, PVA received innervation from central nucleus of amygdala, a known pain-associated locus. As a result, activation of right central nucleus of amygdala with blue light was enough to induce persistent mechanical hyperalgesia. These findings support the idea that targeting PVA can be a potential therapeutic strategy for pain relief.

Chronic pain can be initiated by one or more acute stimulations to sensitize neurons into the primed state. In the primed state, the basal nociceptive thresholds of the animal are normal, but, in response to another hyperalgesic stimulus, the animal develops enhanced and prolonged hyperalgesia. The exact mechanism of how primed state is formed is not completely understood. Here, we showed that spinal protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signal pathway is required for neuronal plasticity change, hyperalgesic priming formation, and the development of chronic hyperalgesia using acid-induced muscle pain model in mice. We discovered that phosphorylated extracellular signal-regulated kinase-positive neurons in the amygdala, spinal cord, and dorsal root ganglion were significantly increased after first acid injection. Inhibition of the phosphorylated extracellular signal-regulated kinase activity intrathecally, but not intracerebroventricularly or intramuscularly before first acid injection, prevented the development of chronic pain induced by second acid injection, which suggests that hyperalgesic priming signal is stored at spinal cord level. Furthermore, intrathecal injection of PKC but not protein kinase A blocker prevented the development of chronic pain, and PKC agonist was sufficient to induce prolonged hyperalgesia response after acid injection. We also found that mammalian target of rapamycin-dependent protein synthesis was required for the priming establishment. To test whether hyperalgesic priming leads to synaptic plasticity change, we recorded field excitatory postsynaptic potentials from spinal cord slices and found enhanced long-term potentiation in mice that received one acid injection. This long-term potentiation enhancement was prevented by inhibition of extracellular signal-regulated kinase. These findings show that the activation of PKC/ERK signal pathway and downstream protein synthesis is required for hyperalgesic priming and the consolidation of pain singling.

Objectives: Spontaneous orgasm is characterized by a spontaneous onset of orgasm without any preceding sexual or nonsexual trigger. It sheds insight on the mechanisms underlying orgasms and the sexual response cycle in humans., Methods: We report a male patient of repetitive spontaneous orgasm under trazodone treatment and systematically review the literature on drug-associated spontaneous orgasm (DASO)., Results: A total of 25 patients (18 women and 7 men), including our reported case, experienced 27 DASO events. Over half of them were under 50 years of age during the DASO event. Depression was the leading morbidity for these patients, and a limited list of antidepressants and antipsychotics were involved in 92.5% of all DASO events. Although offending drugs possess variable pharmacological properties, their common effect is an augmentation of serotonin-1A (5HT1A) neurotransmission. Offending drugs seemingly increase personal susceptibility to DASO. Over half of the patients, especially men, did not concurrently experience sexual arousal or desire during the DASO event. In the remaining patients, the orgasm was accompanied by or ensued with arousal or desire. A reduction of dose or discontinuation of the offending drug usually abolished DASO., Conclusions: It appears that 5HT1A has a key role in generating orgasm. Orgasms may be activated through arousal-independent or arousal-dependent pathways, and both orgasms and sexual arousal are bidirectionally activated. This double-bidirectional model of sexual response cycle may promote the success of sexual procreation and recreation, and further research on this pathway could offer an innovative method to manage anorgasmia in the future.

In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL).We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex.Twenty-four students got positive postbooster anti-HBs status (10-100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1.552 and 2.959, and the P value was less than 0.001.Prebooster anti-HBs level can be the powerful predictive factor for positive postbooster anti-HBs status (≧10 mIU/mL) and protective postbooster anti-HBs status (≧100 mIU/mL). According to the result of this study, if someone received complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels around 2 decades later, 1 booster dose of HBV vaccine could help him or her to regain positive postbooster anti-HBs status (≧10 mIU/mL) under the strong predictive factor of prebooster anti-HBs level higher than 1 mIU/mL. The other 2 HBV vaccines could be saved and the case could also save money and time., Competing Interests: There is no competing interest for the authors.

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

Single-port video-assisted thoracoscopic surgery (VATS) has been widely applied recently. However, there are still only few reports describing its use in mediastinum tumor resection. We present the technique of single-port video-assisted thoracoscopic mediastinum tumor resection and compare it with conventional VATS with regard to short-term outcome.We retrospectively enrolled 105 patients who received mediastinum surgery in Chang Gung Memorial Hospital. Sixteen patients received sternotomy or thoracotomy, 29 patients received single-port VATS, and 60 patients received conventional VATS (3 ports). The operative time, blood loss, postoperation day 1 pain score, discharge day pain score, and postoperative hospital stay were compared. In order to establish a well balanced cohort study, we also use propensity scores match (1:1) to compare the short-term clinical outcome in 2 groups.No operative deaths occurred in this study. Single-port VATS was associated with shorter operative time, lower postoperation day 1 pain score, and shorter postoperation hospital stay in our cohort study (P = 0.001, <0.001, and 0.039), and propensity scores matched cohort study (P = 0.003, <0.001, and <0.001).Single-port VATS for mediastinum tumor appears to be a safe and promising technique with short-term outcome not inferior to conventional VATS in our cohort study. The long-term oncology outcome may require time and more enrolled patients to be further evaluated.

Purpose: This study was designed to evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare the surgical results of VATS with the standard median sternotomy (MS) approach., Materials and Methods: Between April 2010 and April 2012, the data of 245 patients who underwent thymectomy for thymic tumors were prospectively collected. Among them, 93 patients with clinical stage I-II disease were retrospectively reviewed., Results: Resection was planned for VATS in 49 cases, and for MS in 44 cases. During operation, there were 3 conversions to open surgery because of local invasion (conversion to thoracotomy in 1 patient, and sternotomy in 2). No transfusion was required in any patient. There was no significant difference in duration or amount of postoperative chest tube drainage between the 2 groups (P>0.05). Operative time, blood loss during operation, average length of the intensive care unit stay, and length of hospital stay were significantly less in the VATS group than the MS group (P<0.05). There were no major perioperative complications or mortality. No recurrence was detected during a median follow-up of 27 months (range, 12 to 36 mo)., Conclusions: VATS thymectomy for early-stage thymic tumors is safe and feasible. In comparison with standard MS, the VATS approach was associated with a shorter intensive care unit stay and hospital stay. Prospective randomized multi-institutional trials with long-term follow-up are needed to compare the oncological outcomes.

Objectives: To describe rates of pain and pain interference in a large sample of adults aging with long-standing physical disabilities, relative to a normative US population sample., Methods: Self-report survey data was collected for a sample of 1877 individuals with spinal cord injury, neuromuscular disease, postpolio syndrome, or multiple sclerosis. Rates of pain severity and pain interference in these samples were then compared with those taken from a large normative sample (>20,000) collected through the NIH Patient Reported Outcomes Measurement Information System (PROMIS)., Results: Individuals with long-standing physical disabilities reported higher levels of pain and pain interference across the lifespan as compared with individuals in the normative sample. In general, individuals with disability did not experience an age-related decrease in pain and pain impact in contrast to those in the normative sample. For 3 disability groups (neuromuscular disease, postpolio syndrome, and multiple sclerosis), pain interference remained elevated and significantly higher than national norms in the "postretirement" period (ie, age 65 to 74)., Discussion: Results from this study provide a large scale data on prevalence rates of pain and pain interference in this population. Findings underscore the prevalence and impact of pain in persons with disabilities and suggest that individuals with disability may not experience the same degree of decrease in pain interference in later life that is typical of the US population. Those aging with disability may be especially at risk for pain-related impairment in later life.

Changing intracellular pH (pHi) exerts considerable influence on many cellular functions. Different pHi regulators, such as the Na-H exchanger (NHE), Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger (CHE), have been identified in mature mammalian cells. The aims of the present study were to investigate the physiological mechanisms of pHi recovery and to further explore the effects of alcohol on the pHi in human umbilical cord blood CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH-sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi. In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 ± 0.02; (2) 2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and are functional; (3) alcohol functions in a concentration-dependent manner to reduce pHi and increase NHE activity, but it does not affect CHE activity; and (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1, 2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs. Additionally, the intracellular acidosis is mainly caused by catalase-mediated alcohol metabolites, which provoke the activity of NHE.

This paper describes the psychometric properties of the PROMIS-pain interference (PROMIS-PI) bank. An initial candidate item pool (n=644) was developed and evaluated based on the review of existing instruments, interviews with patients, and consultation with pain experts. From this pool, a candidate item bank of 56 items was selected and responses to the items were collected from large community and clinical samples. A total of 14,848 participants responded to all or a subset of candidate items. The responses were calibrated using an item response theory (IRT) model. A final 41-item bank was evaluated with respect to IRT assumptions, model fit, differential item function (DIF), precision, and construct and concurrent validity. Items of the revised bank had good fit to the IRT model (CFI and NNFI/TLI ranged from 0.974 to 0.997), and the data were strongly unidimensional (e.g., ratio of first and second eigenvalue=35). Nine items exhibited statistically significant DIF. However, adjusting for DIF had little practical impact on score estimates and the items were retained without modifying scoring. Scores provided substantial information across levels of pain; for scores in the T-score range 50-80, the reliability was equivalent to 0.96-0.99. Patterns of correlations with other health outcomes supported the construct validity of the item bank. The scores discriminated among persons with different numbers of chronic conditions, disabling conditions, levels of self-reported health, and pain intensity (p<0.0001). The results indicated that the PROMIS-PI items constitute a psychometrically sound bank. Computerized adaptive testing and short forms are available., (Copyright 2010 International Association for the Study of Pain. All rights reserved.)

Study Design: A cross-sectional control-matched study in adolescents with idiopathic scoliosis (IS)., Objective: To evaluate whether subjects with IS had shoulder dysfunction and associated impairment in shoulder kinematics and muscular activation., Summary of Background Data: Evidence indicates that shoulder kinematics are related to shoulder pain and dysfunction. Despite the degree of morbidity associated with altered shoulder kinematics likely to occur in subjects with IS, no report has been published to address this hypothesis., Methods: In this investigation, shoulder kinematics (scapular tipping, scapular upward rotation, and scapulohumeral rhythm) and associated muscular activities [upper trapezius (UT), lower trapezius (LT), serrantus anterior (SA), and middle deltoid (MD)] were evaluated with a 3-dimensional electromagnetic tracking device and electromyography during arm elevations in 13 female subjects with IS and 13 age-gender-dominant hand-matched controls. Additionally, self-reported Flexilevel Scale of Shoulder Function (FLEX-SF) was evaluated between the 2 groups., Results: Subjects with IS demonstrated lower FLEX-SF scores than the controls (P = 0.01). For the convex side, more anterior tilt of the scapula in resting position was identified (P = 0.006). For the concave side, more scapular upward rotation in resting position was identified (P = 0.01). For the EMG amplitude, higher LT contraction activity on the convex side and lower LT and SA contraction activity on the concave side were established (P = 0.007 and less than 0.01, respectively). A moderate positive association was found between scapular posterior tipping during movement and FLEX-SF functional score (R = 0.51). A moderate negative association was found between LT muscular activity and FLEX-SF functional score (R = -0.54)., Conclusion: Given the progressive nature of IS and kinematic linkage among the thoracic spine, scapula, and arm, inadequate posterior tipping movement and high LT muscular activity on the convex side of IS are important to consider in rehabilitation programs for subjects with IS.

The measurement of pain behavior is a key component of the assessment of persons with chronic pain; however, few self-reported pain behavior instruments have been developed. We developed a pain behavior item bank as part of the Patient-Reported Outcome Measurement Information System (PROMIS). For the Wave I testing, because of the large number of PROMIS items, a complex sampling approach was used where participants were randomly assigned to either respond to two full-item banks or to multiple 7-item blocks of items. A web-based survey was designed and completed by 15,528 members of the general population and 967 individuals with different types of chronic pain. Item response theory (IRT) analysis models were used to evaluate item characteristics and to scale both items and individuals on the pain behavior domain. The pain behavior item bank demonstrated good fit to a unidimensional model (Comparative Fit Index = 0.94). Several iterations of IRT analyses resulted in a final 39-item pain behavior bank, and different IRT models were fit to the total sample and to those participants who experienced some pain. The results indicated that these items demonstrated good coverage of the pain behavior construct. Pain behavior scores were strongly related to pain intensity and moderately related to self-reported general health status. Mean pain behavior scores varied significantly by groups based on pain severity and general health status. The PROMIS pain behavior item bank can be used to develop static short-form and dynamic measures of pain behavior for clinical studies.

Objective: To determine whether a combination of topical anesthetic (EMLA) and local injection with lidocaine is better than lidocaine alone for pain relief after Ferguson hemorrhoidectomy., Methods: Sixty patients scheduled for hemorrhoidectomy were randomized into 2 groups: (1) control group (CG, n=30) received neomycin ointment (5 g), and (2) EMLA group (EG, n=30) received EMLA (5 g), both agents applied topically after surgery. Before the surgical incision was made, lidocaine (10 mL of a 1% solution) was locally injected into all 60 patients. After surgery, analgesics were provided when necessary. The visual analog scale score was recorded at 4 time points: (1) upon arrival in the postanesthesia room, (2) 2 hours after arriving in the postanesthesia room, (3) between 9 and 10 PM on the first postoperative evening, and (4) on the first postoperative morning. The frequency of meperidine requests, 1-time catheterizations for urinary retention, and patient satisfaction with postoperative pain management, were also recorded., Results: The median visual analog scale scores and cumulative dosages of meperidine were significantly lower in the EG than the CG (P<0.05). Patient satisfaction with postoperative pain control was also significantly higher in the EG than the CG (P<0.01). No systemic complications occurred., Discussion: EMLA is considered a breakthrough in cutaneous analgesia, capable of reducing pain in many cutaneous procedures. Because Ferguson hemorrhoidectomy has been performed for years with ongoing concerns over postoperative pain, we felt that using EMLA could lower postoperative pain intensity and the number of requests for additional medication.

Study Design: The aim of this case report is to examine the devastating complication that may follow vertebroplasty., Objectives: To report 1 case of intradural cement leakage caused by percutaneous vertebroplasty with polymethyl methacrylate., Summary of Background Data: Cement leakage is not a rare complication of vertebroplasty. But intradural cement leakage is rare. We herein report a rare but devastating complication of vertebroplasty., Methods: A 90-year-old woman with a T12 and L1 osteoporotic compression fracture underwent percutaneous vertebroplasty using polymethyl methacrylate at local hospital. A literature search was performed to assess complications of vertebroplasty., Results: She was transferred to our hospital due to abdominal pain. Physical examination revealed distended abdomen with local tenderness and weakness of both legs (muscle power: Grade 2). Plain radiograph of abdomen showed ileus and intradural cement leakage. Conservative treatment with nasogastric decompression was done, and her abdominal pain subsided 1 week later., Conclusions: Percutaneous vertebroplasty with polymethyl methacrylate is relatively safe, but it still should be proceeded under careful safeguard. The needle tip should not cross the medial border of the pedicle on the anteroposterior view before it has crossed the posterior cortex of the vertebral body on the lateral view. Good quality of image monitoring and clear visualization of cement should be helpful to prevent complications.

The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.

The effects of copper on voltage-gated A-type potassium currents were investigated in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp technique. Extracellular application of various concentrations of copper (1-1000 microM) reversibly reduced the amplitude of voltage-gated A-type potassium currents in a dose-dependent manner with a 50% inhibitory concentration value of 130 microM. Copper (300 microM) increased the V1/2 of the activation curve and state-inactivation curve by 17.2 and 9.0 mV, respectively. Thus, copper slowed down the activation and inactivation process of voltage-gated A-type potassium currents. This study indicated that copper reversibly inhibits the hippocampal CA1 neuronal voltage-gated A-type potassium current in a dose-dependent and voltage-dependent manner, and such actions are likely involved in the regulation of the neuronal excitability and the pathophysiology of Wilson's disease.

Catatonia as a clozapine withdrawal syndrome has not been well documented. There is only 1 case of excited catatonia described with the diagnosis made according to strict criteria. The authors report a patient who developed a catatonic stuporous state following abrupt discontinuation of clozapine, associated with features of cholinergic and serotonergic hyperactivity. The catatonic state resolved within 1 week with reinstatement of clozapine. It is suggested that serotonergic hyperactivity was involved, contributed by cholinergic rebound, in the pathogenesis of this patient's clozapine withdrawal catatonic syndrome.

Background and Purpose: Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression., Methods: We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects., Results: CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P<0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P=0.024) and more substantially suppressed by clopidogrel (P<0.0001) on day 90. Furthermore, only clopidogrel treatment (P=0.0016) was significantly independently associated with decreased CD62p expression on day 90., Conclusions: Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugs; therefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead.

Two patients sought treatment for bilateral fatigable ptosis; one patient had a hematoma, and the other patient had an intracranial metastasis. Compression of the central caudal nucleus in the dorsal midbrain is proposed as the cause of this ptosis, and an alteration of central acetylcholine neurotransmission may contribute to ocular fatigability. Because symptoms that suggest fatigable ptosis can be similar to those that suggest ocular myasthenia gravis, a careful evaluation is necessary to avoid misinterpretation.

Background and Purpose: Chinese have been reported to have an extremely low prevalence rate of carotid and vertebral artery disease in comparison with whites. Previous studies, however, have been limited to general hospital stroke admission or postmortem series and were prone to selection bias. Extracranial cerebrovascular disease (ECCVD) is associated with coronary artery disease (CAD) in whites. Data associating ECCVD with CAD in Chinese patients are not available., Methods: We studied 153 consecutive Chinese patients with angiographically documented CAD. Duplex ultrasonography was performed to identify any underlying extracranial carotid and vertebral artery disease. Patient demographics; vascular risk factors; history of myocardial infarction, transient ischemic attack (TIA) or stroke; concomitant peripheral vascular disease (PVD); degree of left ventricular dysfunction; and extent and severity of CAD were also noted and analyzed., Results: Significant (> or = 50%) stenosis of one or more of the extracranial cerebral arteries was found in 32 patients (21%). The internal and external carotid arteries were involved in 17 of 153 patients (11%) and 19 of 153 patients (12%), respectively. The vertebral artery was involved in 9 of 153 patients (6%) and the common carotid artery in 3 of 153 (2%). Diabetes mellitus, hypertension, a history of TIA or stroke, and PVD were significantly associated with the presence of ECCVD., Conclusions: Significant ECCVD is not uncommon in Chinese patients with CAD, and the prevalence is comparable with that reported in white populations. Patients with a history of diabetes, hypertension, TIA, stroke, and PVD are more likely to have concomitant ECCVD.

The purpose of this study was to evaluate the effects of reperfusion or in vivo pretreatment with a lipid peroxidation inhibitor, lazaroid (U74389G), on attenuating systolic and diastolic alterations occurring during myocardial stunning in isolated rat hearts. Male Sprague-Dawley rats (350-400 g) were randomized into three groups: control animals (n = 13) received no drugs; hearts from reperfused animals (n = 11) received 5 microM U74389G in the reperfusion solution; pretreated animals (n = 11) received 6 mg/kg U74389G by i.v. infusion 30 min before killing. Isolated, isovolumic rat hearts were subjected to 20 min of ischemia at 37 degrees C and subsequent reperfusion for 30 min. Left ventricular isovolumic developed pressure (LVDP), its first derivative (LVDPdP/dt), end-diastolic pressure (LVEDP), and the time constant of diastolic relaxation (tau) were measured. At baseline, no statistically significant differences were detected in systolic or diastolic function in hearts of rats with or without U74389G treatment. After reperfusion, LVDP stabilized at 87 and 92% in both drug-treated groups compared with 52% in the control group (p < 0.01) and dP/dtmax recovered to 101 and 110% of baseline compared with 58% in the control group (p < 0.01). Diastolic dysfunction showed significant improvement in both U74389G pretreatment groups. The increases in LVEDP and tau were 2.0- and 1.2-fold in pretreated hearts and 2,8-fold and 1.5-fold in drug-reperfused hearts, respectively (compared with 6-fold increases in LVEDP and a 2.5-fold increase in tau in controls; p < 0.05). In conclusion, whether administered before ischemia or during reperfusion, U74389G effectively attenuated the systolic and diastolic dysfunction in this model of myocardial stunning, probably protecting cell membranes from peroxidation by oxygen-derived metabolites.

Typical bilateral cheiro-oral syndrome was encountered in a 74-year-old man who had bilateral subdural hematoma after a minor head injury. The delayed grave neurologic deficits occurred 1 month later without expansion of the hematoma. Removal of the lesions reversed both cheiro-oral syndrome and his late-onset neurological disabilities.

To evaluate function of the normal and pathologic esophageal body under more physiologic conditions than those utilized for traditional laboratory testing, manometry was performed before and during eating using a catheter assembly containing three peripheral transducers. Studies were evaluated from seven normal volunteers, 18 typical achalasia patients (eight before and 10 after esophagomyotomy), and eight patients with diffuse esophageal spasm (DES) as characterized by frequent simultaneous and repetitive contractions. In the preprandial period, all had similar frequencies of esophageal contractions, although there was a wide range. During eating, the frequency of contractions increased in all groups; however, the contraction frequency in unoperated achalasia patients, 12.7 +/- 5.0 contractions/min, significantly exceeded the frequency in normal volunteers of 4.9 +/- 1.3 contractions/min, p less than 0.01. The frequency was lower in operated achalasia patients, 9.4 +/- 6.5 contractions/min, but still exceeded that of normal volunteers, p less than 0.01. Patients with DES also had more frequent contractions, 10.5 +/- 9.7 contractions/min, than did the normal volunteers, p less than 0.01. The mean pressure of esophageal contractions for both achalasia groups was similar and was significantly lower than for the normal volunteers. Pressure in the DES patients was intermediate. It is concluded that patients with achalasia have lower pressure but more frequent contractions than normal volunteers during eating, and this spasm-like activity may be a more important pathophysiologic factor in their dysphagia than previously recognized. Esophagomyotomy does decrease the frequency of these contractions. Frequency, but not pressure, of contractions differs from normal in patients with DES.