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We aimed to investigate the clinical implication of suspended scattering particles in motion (SSPiM) using optical coherence tomography angiography (OCTA) among branch retinal vein occlusion disease (BRVO) cases with macular edema (ME). Medical records of BRVO patients were reviewed. Central retinal thickness (CRT), ME type, and cyst size on optical coherence tomography images were evaluated before and after intravitreal bevacizumab injection. Nonperfusion area, SSPiM, and microvascular abnormalities in OCTA images were evaluated using a Heidelberg machine. SSPiM was identified in 24 of 56 cases. There were no differences in baseline characteristics between groups with and without SSPiM. Disease duration, disease-free duration, previous injection number, microaneurysms in the superficial vascular complex, and microaneurysms in the deep vascular complex (DVC) (p = 0.003, 0.013, 0.028, 0.003, < 0.001, respectively) differed significantly between the two groups. After multivariate logistic analysis, microaneurysms in the DVC were the only different factor between the two groups (odds ratio [OR]: 0.091; p = 0.001). Furthermore, SSPiM in the DVC (OR 10.908; p = 0.002) and nonperfusion grade (OR 0.039; p < 0.001) were significantly associated with cyst response after intravitreal injection. SSPiM may be correlated with microaneurysms in the DVC and a poor anatomical response after intravitreal injection.

Human ether-a-go-go-related gene (hERG) potassium channel blockage by small molecules may cause severe cardiac side effects. Thus, it is crucial to screen compounds for activity on the hERG channels early in the drug discovery process. In this study, we collected 5299 hERG inhibitors with diverse chemical structures from a number of sources. Based on this dataset, we evaluated different machine learning (ML) and deep learning (DL) algorithms using various integer and binary type fingerprints. A training set of 3991 compounds was used to develop quantitative structure-activity relationship (QSAR) models. The performance of the developed models was evaluated using a test set of 998 compounds. Models were further validated using external set 1 (263 compounds) and external set 2 (47 compounds). Overall, models with integer type fingerprints showed better performance than models with no fingerprints, converted binary type fingerprints or original binary type fingerprints. Comparison of ML and DL algorithms revealed that integer type fingerprints are suitable for ML, whereas binary type fingerprints are suitable for DL. The outcomes of this study indicate that the rational selection of fingerprints is important for hERG blocker prediction.

Background: With demographic change, the number of noncommunicable diseases, chronic diseases and multimorbidity is increasing, and so is the demand for health services. This represents a further challenge for the healthcare system. An adequate and efficient treatment of multimorbid patients requires a well-structured, informed and cross-indicated treatment. Therefore, a new form of coordinated, managed and cross-sectoral care for multimorbid patients - the "MamBo" care model - has been developed. Along with the implementation of MamBo, a process and outcome evaluation will be carried out, which is described in this study protocol. The aim of the study is to evaluate the care model according to its implementation process and effectiveness., Methods: The MamBo-care model will be evaluated in multi-perspective terms. Thus, a process and outcome evaluation with several data sources will be conducted: (1) Annual focus groups and individual interviews with those involved in the process. (2) Various primary data, including surveys of patients, physicians and practice staff at the time of enrolment and 1 year later to enable pre-post comparison. (3) Claim data from the health insurance of the MamBo population in comparison to a comparative population, formed by the propensity score matching method. (4) Process data of the care management. The analysis of qualitative data will be carried out by content analysis according to Mayring. For the analysis of the quantitative data, multivariate analyses are planned., Discussion: A new form of coordinated care has been introduced to improve intersectoral care of multimorbid patients and reduce the workload on physicians. The effects of the MamBo care model are being investigated for patients, physicians and the cost units. The results will form the basis for the decision whether the care model should be transferred to standard care and what needs to be taken into account for implementation., Trial Registration: The study was retrospectively registered in the German Register for Clinical Studies (DRKS00014047) on June 28, 2019.

Background: Randomized controlled trials (RCTs) are regarded as the most internally valid means of estimating the effectiveness of complex public health interventions, but the recruitment of participants can be difficult. The aim of this study was to explore factors that may have affected the recruitment of employees with musculoskeletal disorders (MSDs) to a multicenter worksite health promotion program from the perspective of recruiting case managers., Methods: Factors in recruitment to the RCT were explored using three focus group discussions with case managers. Data were processed using MAXQDA and analyzed with a combination of content and sequence analysis., Results: Findings showed that randomization is a major challenge for recruitment. Case managers adapted their communication with, and approaches to possible participants because of the randomization design and employed coping strategies to compensate for allocation into the control arm of the study. Perceptions of the superiority of the intervention group over the control group, perceptions of the (mis)match of participants to one of the groups, as well as the understanding of the necessity of randomization for effectiveness evaluations, further affected recruitment. Perceived expectations of possible participants and their (emotional) reactions to the randomization allocation also complicated recruitment., Conclusion: We were able to gain insight into the challenges of randomization for the recruitment of participants to a multicenter RCT. This study assisted the development of strategies to overcome barriers in the ongoing implementation process of the trial (i.e., the adaption of best practice information sheets and newsletters). There remains a need to develop effective interventions to help those recruiting to trials.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and a widespread form of dementia. Aggregated forms of the amyloid β-peptide (Aβ) are identified as a toxic species responsible for neuronal damage in AD. Extensive research has been conducted to reveal the aggregation mechanism of Aβ. However, the structure of pathological aggregates and the mechanism of aggregation are not well understood. Recently, experimental studies have confirmed that the α-sheet structure in Aβ drives aggregation and toxicity in AD. However, how the α-sheet structure is formed in Aβ and how it contributes to Aβ aggregation remains elusive. In the present study, molecular dynamics simulations suggest that Aβ adopts the α-strand conformation by peptide-plane flipping. Multiple α-strands interact through hydrogen bonding to form α-sheets. This structure acts as a nucleus that initiates and promotes aggregation and fibrillation of Aβ. Our findings are supported by previous experimental as well as theoretical studies. This study provides valuable structural insights for the design of anti-AD drugs exploiting the α-strand/α-sheet structure.

We aimed to evaluate the relationship between the capillary abnormalities including nonperfusion area (NPA) in optical coherence tomography angiography (OCTA) images and the recurrence of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF; bevacizumab). The records of 40 patients who underwent intravitreal bevacizumab injection for ME secondary to BRVO and had at least six months of follow-up were reviewed. Central retinal thickness (CRT; μm) and macular edema type were evaluated prior to treatment. After ME resolution, nonperfusion areas in the 1 mm (NPA1) and 1-3 mm (NPA3) zones on the Early Treatment Diabetic Retinopathy Study (ETDRS) circle within the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured using OCTA images. Furthermore, other microvascular abnormalities in the both SCP and DCP were compared between groups. ME recurred in 25 of 40 (62.5%) eyes. The NPA1 of the SCP and DCP (p = 0.002, 0.004, respectively), NPA3 of the SCP and DCP (p = 0.002, 0.008, respectively), and initial CRT (p = 0.022) differed significantly between eyes with and without ME recurrence. In multivariate logistic regression analyses, the NPA1 of the DCP (OR: 344.718; p = 0.029) and NPA3 of the SCP (OR: 4.072; p = 0.018) were significantly associated with ME recurrence. Other microvascular abnormalities were not significantly different between two groups. The central NPA and parafoveal NPA of the SCP in OCTA images correlated strongly with ME recurrence in BRVO patients after intravitreal anti-VEGF injection.

Water molecules play a key role in protein stability, folding, function and ligand binding. Protein hydration has been studied using free energy perturbation algorithms. However, the study of protein hydration without free energy calculation is also an active field of research. Accordingly, topological water network (TWN) analysis has been carried out instead of free energy calculation in the present work to investigate hydration of proteins. Water networks around 20 amino acids in the aqueous solution were explored through molecular dynamics (MD) simulations. These simulation results were compared with experimental observations. Water molecules from the protein data bank structures showed TWN patterns similar to MD simulations. This work revealed that TWNs are effected by the surrounding environment. TWNs could provide valuable clues about the environment around amino acid residues in the proteins. The findings from this study could be exploited for TWN-based drug discovery and development.

Background: Distortion of taste sensations is a common chemotherapy-induced side effect; however, treatment evidence is limited. Pilot data indicated that acupuncture might be able to improve symptoms of dysgeusia. Thus, the aim of this study is to investigate the effects and side effects of hypoglossal acupuncture in the treatment of dysgeusia in patients with breast cancer undergoing chemotherapy., Methods/design: The study is a randomized controlled trial comparing a single verum acupuncture treatment with two active comparators: sham acupuncture and dietary recommendations. Sample size calculation revealed a total of 75 patients pending an alpha of 0.05, a power of 0.8, and an estimated effect size of 0.80. Patients with breast cancer undergoing platinum- or taxane-based chemotherapy will be included if they present with phantogeusia (abnormal taste sensations without an external oral stimulus) with an intensity of 4 points or above on an 11-point numeric rating scale (NRS). The primary outcome is phantogeusia; secondary outcomes include parageusia (abnormal taste of food), hypogeusia (reduced taste sensations), hypergeusia (increased taste sensations), xerostomia (dry mouth), stomatitis, appetite, and functional impairment. All outcomes will be assessed at baseline and prior to the next chemotherapy administration using an 11-point NRS for each. All adverse events will be recorded., Discussion: The results of this study will demonstrate the extent to which hypoglossal acupuncture may influence the intensity of and functional impairment due to chemotherapy-induced dysgeusia., Trial Registration: Clinical Trials.gov, NCT02304913 . Registered on 19 November 2014.

Due to the current digital transition, companies are under pressure to pursue digitalization and often initiate far-reaching transformation processes. As a result, managers must drive change within a company and are involved in important decision-making processes. In the present study, we focused on two cognitive job demands in managers related to change due to digital transformation: perceived choice overload and pressure from digitalization. We assumed that the extent of challenging cognitive demands at work is rising and negatively influencing managers' psychological well-being. We conducted an online survey with a sample of 368 upper-level managers from a large ICT-company, where, at the time of the study, extensive transformation processes were taking place. Using multivariate regression analysis, potential prognostic effects on well-being were tested. Results showed that lower well-being was significantly associated with higher choice overload, but not with perceived pressure from digitalization. In our explorative study, we investigated two potential job demands in managers that, to our knowledge, have not yet been scientifically tested. Given the unsettled state of the field, it is important to try to further understand when choice overload and pressure from digitalization occur and when these may trigger negative health consequences.

Objective: To test the efficacy of Gua Sha therapy in patients with chronic low back pain., Methods: 50 patients with chronic low back pain (78% female, 49.7 ± 10.0 years) were randomized to two Gua Sha treatments (n = 25) or waitlist control (n = 25). Primary outcome was current pain intensity (100-mm visual analog scale); secondary outcome measures included function (Oswestry Disability Index), pain on movement (Pain on Movement Questionnaire), perceived change in health status, pressure pain threshold, mechanical detection threshold, and vibration detection threshold., Results: After treatment, patients in the Gua Sha group reported lower pain intensity (p < 0.001) and better overall health status (p = 0.002) compared to the waitlist group. No further group differences were found. No serious adverse events occurred., Conclusions: Gua Sha appears to be an acceptable, safe, and effective treatment for patients with chronic low back pain. Further rigorous studies are needed to confirm and extend these results., (Copyright © 2018. Published by Elsevier Ltd.)

The α-synuclein is a major component of amyloid fibrils found in Lewy bodies, the characteristic intracellular proteinaceous deposits which are pathological hallmarks of neurodegenerative diseases such as Parkinson's disease (PD) and dementia. It is an intrinsically disordered protein that may undergo dramatic structural changes to form amyloid fibrils. Aggregation process from α-synuclein monomers to amyloid fibrils through oligomeric intermediates is considered as the disease-causative toxic mechanism. However, mechanism underlying aggregation is not well-known despite several attempts. To characterize the mechanism, we have explored the effects of pH and temperature on the structural properties of wild-type and mutant α-synuclein using molecular dynamics (MD) simulation technique. MD studies suggested that amyloid fibrils can grow by monomer. Conformational transformation of the natively unfolded protein into partially folded intermediate could be accountable for aggregation and fibrillation. An intermediate α-strand was observed in the hydrophobic non-amyloid-β component (NAC) region of α-synuclein that could proceed to α-sheet and initiate early assembly events. Water network around the intermediate was analyzed to determine its influence on the α-strand structure. Findings of this study provide novel insights into possible mechanism of α-synuclein aggregation and promising neuroprotective strategy that could aid alleviate PD and its symptoms.

Background: Neural Therapy (NT) is a common complementary treatment approach using injections with short-acting local anesthetics to treat pain and chronic diseases. However, little is known about the underlying mechanisms and the domains of treatment response. This study therefore analyzed patient experiences following NT injections with procaine., Methods: Maximum variation sampling was used to collect data from semi-structured interviews conducted with 22 hospital inpatients aged 59.6 ± 14.9 years (81.8% female). Each had multiple (9.4 ± 6.9) diagnoses. They were undergoing two weeks of integrative treatment, which included individualized NT. The interview data were analyzed in MAXQDA using qualitative content analysis., Results: With injection, patients first described local anesthetic effects including temporary blocking of pain and increased local warmth. Second, patients reported on vegetative reactions frequently leading to turmoil within the body like initial aggravation of existing symptoms or the appearance of new, concealed or phantom symptoms. This often required the need for rest to deal with the treatment stimulus. As a third step, many patients could gain physical and emotional release and relief in symptoms, mood and functioning. Emotional release was often accompanied by weeping and initially overwhelmed affected patients with dissociated memories. However, in cases where patients were able to experience those memories with a new distance, a fourth step of integration was achievable. It included reframing processes as well as a gain in pain perception and body-awareness. As a possible fifth step, patients experienced improved mood, increased pain acceptance and empowerment. Adverse events of NT included pain from the injections, vegetative complaints and emotional turmoil that lasted for minutes or hours, with a maximum of two days., Conclusions: Patients treated with procaine injections reported different psychophysiological outcomes contributing to the understanding of the mechanisms underlying NT. Further efficacy studies should separate specific NT from non-specific/placebo effects., Trial Registration: DRKS00004567 .

Objective: Chemoport-related thrombosis (CRT) is a serious complication that causes morbidities and interrupts administration of intravenous cancer therapy. We investigated the incidence and risk of CRT in colorectal cancer (CRC) patients treated with bevacizumab (BEV)., Methods: We retrospectively reviewed 1,534 CRC patients who received chemotherapy with or without BEV using a chemoport between 2014 and 2016., Results: The participants had a median age of 58 (18-85) years, and 60.3% were male. All participants were stratified into three groups: adjuvant chemotherapy (AC) (n=670), palliative chemotherapy (PC) without BEV (n=356), and PC with BEV (n=508). The median follow-up was 20.19 (interquartile range, 14.07-27.19) months. CRT occurred in 3.8% of all patients; incidence of symptomatic and asymptomatic CRT was 2.9% and 0.9%, respectively. CRT occurred more in patients with BEV (5.7%) than in patients without BEV (2.9%, P=0.008). The cumulative incidence of CRT in patients administered PC with BEV was significantly higher than that in those administered AC (P=0.011) and there was a trend toward increased CRT in patients administered PC with BEV compared with those administered PC without BEV (P=0.044). Multivariate analysis found that BEV treatment was the only variable that was significantly associated with CRT (hazard ratio, 2.06; 95% confidence interval, 1.24-3.43; P=0.006)., Conclusions: BEV treatment was significantly associated with increased incidence of CRT in CRC patients.

Heat shock protein 90 (Hsp90) is one of the most abundant cellular proteins and plays a substantial role in the folding of client proteins. The inhibition of Hsp90 has been regarded as an attractive therapeutic strategy for treating cancer because many oncogenic kinases are Hsp90 client proteins. In this study, we report new inhibitors that directly bind to N-terminal ATP-binding pocket of Hsp90. Optimized structure-based virtual screening predicted candidate molecules, which was followed by confirmation using biophysical and cell-based assays. Among the reported crystal structures, we chose the two structures that show the most favourable early enrichments of true-positives in the receiver operating characteristic curve. Four molecules showed significant changes in the signals of 2D [ 1 H, 15 N] correlation NMR spectroscopy. Differential scanning calorimetry analysis supported the results indicating direct binding. Quantified dissociation constant values of the molecules, determined by a series of 2D NMR experiments, lie in the range of 0.1-33 μM. Growth inhibition assay with breast and lung cancer cells confirmed the cellular activities of the molecules. Cheminformatics revealed that the molecules share limited chemical similarities with known inhibitors. Molecular dynamics simulations detailed the putative binding modes of the inhibitors.

Purpose: To evaluate the immediate effect of 3% diquafosol ophthalmic solution on tear MUC5AC concentration, periodic acid-Schiff (PAS)-positive goblet cells, and tear film stability in normal and keratoconjunctivitis sicca (KCS) rat models., Methods: Rats were divided into normal and KCS groups. 3% of diquafosol solution was instilled into the right eye and normal saline into the left eye in both groups. To determine the peak time of tear MUC5AC concentration, tears were collected after 3% diquafosol instillation every 5 min up to 20 min. The tear film stability and the numbers of PAS-positive goblet cells were compared in both models., Results: After diquafosol instillation, tear MUC5AC concentration increased steadily for 15 min, at which point the MUC5AC concentration reached its peak. In both normal and KCS groups, the MUC5AC concentration at 15 min was higher after instillation of 3% diquafosol solution (17.77 ± 2.09 ng/ml in the normal group, 9.65 ± 3.51 ng/ml in the KCS group) than that after saline instillation (13.74 ± 2.87 ng/ml in the normal group, 8.19 ± 3.99 ng/ml in the KCS group) (p = 0.018 for both). The corneal wetting ability was significantly longer after instillation of 3% diquafosol solution compared with that after instillation of normal saline in the normal group (p = 0.018). The percentage of PAS-positive goblet cells after the instillation of 3% diquafosol solution was significantly lower than that after instillation of normal saline in both models (p = 0.018 for both)., Conclusions: Diquafosol ophthalmic solution was effective in stimulating mucin secretion in both normal and KCS rat models, and the peak time of tear MUC5AC concentration was 15 min after diquafosol instillation. The increased tear MUC5AC concentration was accompanied by improved tear film stability and a decreased percentage of PAS-positive goblet cells.

Shivering is a common side effect of targeted temperature modulation and general anesthesia. Antishivering strategies often employ a stepwise approach involving both pharmacological and physical interventions. However, approaches to treat shivering are often empiric and vary widely across care environments. We evaluated the quality of published antishivering protocols and guidelines with respect to methodological rigor, reliability, and consistency of recommendations.Using 4 medical databases, we identified 4027 publications that addressed shivering therapy, and excluded 3354 due to lack of relevance. After applying predefined eligibility criteria with respect to minimal protocol standards, 18 protocols/guidelines remained. Each was assessed using a modified Appraisal of Guidelines for Research and Evaluation II (mAGREE II) instrument containing 23 quality items within 6 domains (maximal score 23). Among 18 protocols/guidelines, only 3 incorporated systematically reviewed recommendations, whereas 15 merely targeted practice standardization. Fifteen of 18 protocols/guidelines addressed shivering during therapeutic cooling in which skin counterwarming and meperidine were most commonly cited. However, their mAGREE II scores were within the lowest tertile (1 to 7 points) and the median for all 18 protocols was 5. The quality domains most commonly absent were stakeholder involvement, rigor of development, and editorial independence. Three of 18 protocols/guidelines addressed postanesthetic antishivering. Of these, the American Society of Anesthesiologists guidelines recommending forced-air warming and meperidine received the highest mAGREE II score (14 points), whereas the remaining 2 recommendations had low scores (<5 points).Current published antishivering protocols/guidelines lack methodological rigor, reliability, and strength, and even the highest scoring of the 18 protocols/guidelines fulfilled only 60% of quality items. To be consistent with evidence-based protocol/guideline development processes, future antishivering treatment algorithms should increase methodological rigor and transparency.

Purpose: To evaluate the effect of photobleaching on fundus autofluorescence (FAF) images in acute central serous chorioretinopathy., Methods: We obtained prephotobleaching and postphotobleaching images using an Optomap 200Tx, and photobleaching was induced with a Heidelberg Retina Angiograph 2. Degrees of photobleaching were assessed as grayscale values in Optomap images. Concordances among the three kinds of images were analyzed. Hyper-AF lesions in prephotobleaching images were classified as Type 1 (changed to normal-AF after photobleaching) and Type 2 (unchanged after photobleaching). The FAF composite patterns of central serous chorioretinopathy lesions were classified as diffuse or mottled. Initial and final best-corrected visual acuity, central retinal thickness, and disease duration were compared according to fovea FAF type., Results: Forty-one eyes of 41 patients were analyzed. The lesion brightness of postphotobleaching Optomap FAF showed greater concordance with Heidelberg Retina Angiograph 2 FAF (94.74%) than the prephotobleaching Optomap FAF (80.49%). Eyes with Type 1 fovea had greater initial and final best-corrected visual acuity (20/23 vs. 20/41, 20/21 vs. 20/32, P < 0.0001, P = 0.001, respectively) and shorter disease duration (19.68 ± 12.98 vs. 51.55 ± 44.98 days, P = 0.043) than those with Type 2 fovea. However, eyes with diffuse Type 2 fovea had only lower initial and final best-corrected visual acuity (20/23 vs. 20/45, 20/21 vs. 20/36, P < 0.0001, P < 0.0001, respectively) than those with Type 1 fovea., Conclusion: Understanding the photobleaching effect is necessary for the accurate interpretation of FAF images. Furthermore, comparing prephotobleaching and postphotobleaching FAF images may be helpful for estimation of lesion status in central serous chorioretinopathy.

Background: Chronic neck pain is a major public health burden with only limited evidence for the effectiveness of complementary therapies. This study aimed to test the efficacy of cupping massage in patients with neck pain., Patients and Methods: Patients with chronic non-specific neck pain were randomly assigned to cupping massage or a wait list control. The intervention group received 5 cupping massages on a twice-weekly basis while the control patients continued their usual treatments. The primary outcome measure was neck pain intensity (0-100 mm visual analogue scale (VAS)) after 3 weeks. Secondary outcomes included pain on movement, functional disability, health-related quality of life, mechanical detection and pain thresholds and adverse events., Results: 50 patients (52.6 ± 10.3 years, 92% female) were randomised to either cupping massage or a wait list (N = 25 each). Patients in the cupping group reported significantly less neck pain post intervention (difference per protocol -14.3 mm, 95% confidence interval (CI) -27.7 to -1.0, p = 0.037; difference intention-to-treat -10.8 mm, 95% CI -21.5 to -0.1, p = 0.047). Significant group differences in favour of the intervention were further found for pain on movement (p = 0.019) and functional disability (p < 0.001), the quality-of-life subscales pain (p = 0.002) and mental health (p = 0.003) and the mental component summary (p = 0.036). Changes were also found for pressure pain sensitivity at the site of maximal pain (p = 0.022). Five adverse events were reported., Conclusions: Cupping massage appears to be effective in reducing pain and increasing function and quality of life in patients with chronic non-specific neck pain. More rigorous studies are needed to confirm and extend these results., (© 2017 S. Karger GmbH, Freiburg.)

Background: Despite the fact that unaddressed delays in clinical trial operation could severely compromise the overall effort invested, there seems to be a lack of concerted effort in reforming such delays. This study evaluated the composite effect of initiatives in reforming trial operation efficiency., Methods: A high-volume academic medical center in Korea has implemented various initiatives to improve the trial operation efficiency by expediting times from institutional review board (IRB) submission to approval, from IRB submission to trial open for subject enrollment, and from trial open to first patient-in. The initiatives include implementation of the protocol preliminary review, parallel processing of the clinical trial agreement review in line with the protocol submission to the IRB, and involvement of project manager for operational risk management. Times from IRB submission to approval, from IRB submission to trial open, and from trial open to first patient-in before and after implementation of initiatives were compared., Results: The median time required in IRB approval was meaningfully shorter in the postinitiative group (19 vs 14 days; P < .001). The median times from IRB submission to trial open for subject enrollment and from trial open to first patient-in were reduced significantly in the postinitiative group (trial open: 25 vs 18 days, P < .001; first patient-in: 111.5 vs 100 days, P = .014)., Conclusions: The initiatives were effective in reforming trial operational efficiency. Additional studies to address the cause of operational delay and modifiable factors influencing subject enrollment are needed to further improve operational efficiency.

In the present study, we intended to report a clinical pediatric case of thelaziasis in Korea. In addition, we briefly reviewed the literature on pediatric cases of thelaziasis in Korea. In the present case, 3 whitish, thread-like eye-worms were detected in a 6-year-old-boy living in an urban area and contracted an ocular infection known as thelaziasis incidentally during ecological agritainment. This is the first report of pediatric thelaziasis in Seoul after 1995.

Background: Autism spectrum disorder (ASD) affects many children and juveniles. The pathogenesis of ASD is not well understood. Environmental factors may play important roles in the development of ASD. We examined a possible relationship of inflammatory pain in neonates and the development of ASD in juveniles., Methods: Acute inflammation pain was induced by 5 % formalin (5 μl/day) subcutaneous injection into two hindpaws of postnatal day 3 to 5 (P3-P5) rat pups. Western blot, immunohistochemical, and behavioral examinations were performed at different time points after the insult., Results: Formalin injection caused acute and chronic inflammatory responses including transient local edema, increased levels of inflammatory cytokines, TNF-α, and IL-1β in the blood as well as in the brain, and increased microglia in the brain. One day after the pain insult, there was significant cell death in the cortex and hippocampus. Two weeks later, although the hindpaw local reaction subsided, impaired axonal growth and demyelization were seen in the brain of P21 juvenile rats. The number of bromodeoxyuridine (BrdU) and doublecortin (DCX) double-positive cells in the hippocampal dentate gyrus of P21 rats was significantly lower than that in controls, indicating reduced neurogenesis. In the P21 rat's brain of the formalin group, the expression of autism-related gene neurexin 1 (NRXN1), fragile X mental retardation 1 (FMR1), and oxytocin was significantly downregulated, consistent with the gene alteration in ASD. Juvenile rats in the formalin group showed hyperalgesia, repetitive behaviors, abnormal locomotion, sleep disorder, and distinct deficits in social memory and social activities. These alterations in neuroinflammatory reactions, gene expression, and behaviors were more evident in male than in female rats. Importantly, an anti-inflammation treatment using indomethacin (10 mg/kg, i.p.) at the time of formalin injections suppressed inflammatory responses and neuronal cell death and prevented alterations in ASD-related genes and the development of abnormal behaviors., Conclusions: These novel observations indicate that severe inflammatory pain in neonates and persistent inflammatory reactions may predispose premature infants to development delays and psychiatric disorders including ASD. The prevention of pain stimuli and prompt treatments of inflammation during development appear vitally important in disrupting possible evolution of ASD syndromes.

Background: The purpose of this study was to investigate peripapillary choroidal thickness (CT) in eyes with neovascular age-related macular degeneration (AMD) and to assess whether peripapillary CT is affected by intravitreal injection of ranibizumab (IVR) in eyes with neovascular AMD., Methods: Peripapillary and subfoveal CT were measured in spectral domain optical coherence tomography images from 39 eyes of neovascular AMD patients and 39 eyes of age-matched controls retrospectively. The patients were treated with 0.5 mg IVR monthly for 3 months and retreated as needed. Peripapillary CT at baseline, 3 months and 6 months was measured at four locations (superior, nasal, inferior and temporal areas)., Results: The mean peripapillary and subfoveal baseline CTs of the eyes with neovascular AMD (153.3 ± 45.3 μm and 228.6 ± 78.6 μm) were not different from those of the controls (149.0 ± 42.3 μm and 221.4 ± 54.1 μm; P = 0.665 and P = 0.639, respectively). Subfoveal CT decreased at 3 months (213.8 ± 75.8 μm, P < 0.001) and 6 months (215.1 ± 72.8 μm, P = 0.002) following IVR treatment. Mean peripapillary CT did not show significant changes at 3 months (149.6 ± 43.8 μm, P = 0.156) or 6 months (150.0 ± 43.4 μm, P = 0.187). Subanalysis revealed that only temporal peripapillary CT decreased from baseline (167.1 ± 54.5 μm) to 3 months (159.4 ± 50.8 μm, P = 0.010) and was sustained at 6 months (160.6 ± 49.6, P = 0.026). However, superior, nasal and inferior peripapillary CT did not show significant changes after IVR., Conclusions: Changes in peripapillary CT after IVR were limited to the macular area. This result may suggest that IVR does not affect CT outside of the macula in the eyes of patients with neovascular AMD.

Objective: To test the efficacy of the Alexander Technique, local heat and guided imagery on pain and quality of life in patients with chronic non-specific neck pain., Design: A randomized controlled trial with 3 parallel groups was conducted., Setting: Outpatient clinic, Department of Internal and Integrative Medicine., Subjects: A total of 72 patients (65 females, 40.7±7.9 years) with chronic non-specific neck pain., Interventions: Patients received 5 sessions of the Alexander Technique--an educational method which aims to modify dysfunctional posture, movement and thinking patterns associated with musculoskeletal disorders. Control groups were treated with local heat application or guided imagery. All interventions were conducted once a week for 45 minutes each., Main Measures: The primary outcome measure at week 5 was neck pain intensity on a 100-mm visual analogue scale; secondary outcomes included neck disability, quality of life, satisfaction and safety., Statistics: Analyses of covariance were applied; testing ordered hypotheses., Results: No group difference was found for pain intensity for the Alexander Technique compared to local heat (difference 4.5mm; 95% CI:-8.1;17.1; p=0.48), but exploratory analysis revealed the superiority of the Alexander Technique over guided imagery (difference -12.9 mm; 95% CI:-22.6;-3.1, p=0.01). Significant group differences in favor of the Alexander Technique were also found for physical quality of life (P<0.05). Adverse events mainly included slightly increased pain and muscle soreness., Conclusion: The Alexander Technique was not superior to local heat application in treating chronic non-specific neck pain. It cannot be recommended as routine intervention at this time. Further trials are warranted for conclusive judgment., (© The Author(s) 2015.)

In this study, we report new classes of potent tyrosinase inhibitors identified by enhanced structure-based virtual screening prediction; the enzyme and melanin content assays were also confirmed. Tyrosinase, a type-3 copper protein, participates in two distinct reactions, hydroxylation of tyrosine to DOPA and conversion of DOPA to dopaquinone, in melanin biosynthesis. Although numerous inhibitors of this reaction have been reported, there is a lag in the discovery of the new functional moieties. In order to improve the performance of virtual screening, we first produced an ensemble of 10,000 structures using molecular dynamics simulation. Quantum mechanical calculation was used to determine the partial charges of catalytic copper ions based on the met and deoxy states. Second, we selected a structure showing an optimal receiver operating characteristic (ROC) curve with known direct binders and their physicochemically matched decoys. The structure revealed more than 10-fold higher enrichment at 1% of the ROC curve than those observed in X-ray structures. Third, high-throughput virtual screening with DOCK 3.6 was performed using a library consisting of approximately 400,000 small molecules derived from the ZINC database. Fourth, we obtained the top 60 molecules and tested their inhibition of mushroom tyrosinase. The extended assays included 21 analogs of the 21 initial hits to test their inhibition properties. Here, the moieties of tetrazole and triazole were identified as new binding cores interacting with the dicopper catalytic center. All 42 inhibitors showed inhibitory constant, Ki, values ranging from 11.1 nM and 33.4 μM, with a tetrazole compound exhibiting the strongest activity. Among the 42 molecules, five displayed more than 30% reduction in melanin production when treated in B16F10 melanoma cells; cell viability was >90% at 20 μM. Particularly, a thiosemicarbazone-containing compound reduced melanin content by 55%.

Purpose: To evaluate the type and cause of orbital blowout fractures in Korea., Design: Retrospective, observational case series., Methods: Patients who underwent reconstruction for blowout fracture from March 2004 to April 2013 at Korea University Guro and Ansan Hospitals were included in this study. Patient demographics and orbital computed tomography (CT) scans were reviewed. On CT, ethmoid air cell septa, blowout fracture type, and other combined fractures were analyzed. Blowout fracture was classified as affecting up to 4 areas: the floor lateral to the infraorbital canal, the floor medial to the canal, the maxilla-ethmoidal strut ("inferomedial" strut), and the medial wall. Furthermore, trauma type and associated injury were reviewed. The results of adolescent patients and adult patients were compared, as were those of males and females., Results: The study included 659 eyes of 659 patients; mean patient age was 31.01 ± 14.27 years. In total, 513 (77.85%) patients were male and 146 (22.15%) were female. The most common blowout fracture type was medial wall fracture, followed by floor wall, floor and medial wall without inferomedial strut, and floor and medial wall fracture with inferomedial strut, in that order. Interestingly, patients with floor wall blowout fracture were younger (26.87 ± 12.90 y) than other groups: medial wall fracture (32.35 ± 14.64 y, P < 0.0001), floor and medial wall fracture (35.22 ± 14.49 y, P < 0.0001), and floor and medial wall fracture involving the maxillaethmoidal strut (32.62 ± 13.75 y, P = 0.002). The number of ethmoidal air cell septa was lowest in the medial wall fracture group (3.62 ± 0.67): floor wall fracture (4.07 ± 0.69, P < 0.0001), floor and medial wall fracture (3.90 ± 0.78, P < 0.0001), and floor and medial wall fracture involving the maxilla-ethmoidal strut (4.05 ± 0.72, P = 0.001)., Conclusions: Our study demonstrated that the blowout fracture type distribution in Korea varied from the results of many other studies. Medial wall fracture is the most common among the 4 types, and anatomic variance, such as number of ethmoid air cell septa, could influence blowout fracture type, especially in medial wall fracture.

Objective: We performed a systematic review of the published evidence regarding nonpharmacologic antishivering interventions in various clinical settings., Data Sources: Studies through November 2014 were identified using predefined search terms in electronic databases, including PubMed, the Cochrane Library, EMBASE: Excerpta Medica (Ovid), and Web of Science., Study Selection: All identified articles were critically analyzed by applying prespecified criteria. We included experimental trials with comparable baseline data investigating the antishivering efficacy of nonpharmacological interventions in subjects without underlying thermoregulatory dysfunction., Data Extraction: Sixty-five publications (3,361 subjects) were analyzed by the type of clinical setting, intervention, comparison, and study design. In addition, each study underwent a standardized study quality assessment., Data Synthesis: Nonpharmacological interventions consisted of active cutaneous warming (forced-air warming, electric heating pad/blanket, radiant heating, and water-circulating mattress), body core warming (fluid or gas warming system), passive cutaneous warming (space blankets or towels), and electroacupuncture. Identified clinical settings included perioperative settings without induced hypothermia (60 of 77 comparisons), perioperative settings with induced hypothermia (8 of 77), and induced hypothermia without anesthesia (9 of 77). Active cutaneous warming was the most commonly studied intervention, and it was associated with the highest prevalence of positive results when compared with controls in all three clinical settings. In contrast, passive cutaneous warming and body core warming showed conflicting efficacy. Comparison evaluations among different antishivering interventions were limited due to the paucity and heterogeneity of studies directly comparing different interventions against one another., Conclusion: This systematic review of the effectiveness of nonpharmacological antishivering methods delineates active cutaneous warming as the most effective nonpharmacologic antishivering intervention in the perioperative and induced hypothermia settings.

Objective: Findings of existing functional MRI (fMRI) studies on the neural mechanisms that mediate effects of acupuncture analgesia are inconsistent. This study analyzes the effects of manual acupuncture on pain ratings and brain activation in response to experimental, electrical pain stimuli., Design: Fourteen healthy volunteers were examined by using a 1.5-T MRI scanner. The intensity of pain stimuli was adjusted to individual pain ratings on a numeric rating scale. Baseline fMRI was performed during electrical pain stimulation in a blocked design. For the second session, manual acupuncture with repeated stimulation was performed on contralateral acupoints-large intestine 4, liver 3, and stomach 36-before imaging. After imaging, subjective pain ratings and ratings of the de qi sensation were assessed., Results: Compared with baseline, volunteers showed modulated brain activity under pain conditions in the cingulate gyrus, insula, primary somatosensory cortex, and prefrontal areas after the acupuncture session. In accordance with the literature, anterior insular and prefrontal activity seemed to be correlated with acupuncture treatment., Conclusion: This study supports the existence of analgesic acupuncture effects that outlast the needling period. Pain-associated brain areas were modulated in direct response to a preceding acupuncture treatment.

Our previous findings have demonstrated that bee venom (BV) has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB) activity assay. BV (1-5 μg/mL) inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

Primary paranasal sinus lymphoma is an uncommon malignancy that accounts for only 0.17% of all lymphomas and is often difficult to diagnose. Initially, tumors in this area cause very few symptoms and are at an advanced stage at the time of diagnosis. Ophthalmologic signs and symptoms occur early in the disease process because of close proximity of the orbit to the paranasal sinuses. We report on a case of primary malignant lymphoma of the sphenoid and ethmoid sinuses with involvement of the cavernous sinus, initially presenting with ophthalmologic signs and symptoms in association with cavernous sinus syndrome.

Purpose: The aim of this study was to compare meibomian gland loss (MGL) and expressed meibum grade between upper and lower eyelids in patients with obstructive meibomian gland dysfunction (MGD) and to evaluate the correlation between these 2 parameters and other clinical measurements., Methods: Twenty-six eyes of 26 patients with obstructive MGD were enrolled. Upper and lower MGLs were evaluated using noncontact meibography. Expressed meibum quality was assessed in 8 glands of the central third area of the upper and lower eyelids on a scale of 0 to 3 for each gland (total score range, 0-24). Tear film stability was evaluated based on tear break-up time (TBUT), and corneal staining was graded according to the National Eye Institute scale (range, 0-15)., Results: The mean MGL in the lower eyelids (24.1% ± 10.8%) was significantly greater than that of the upper eyelids (11.2% ± 5.2%) (P < 0.001). The mean expressed meibum grade in the lower eyelids (16.5 ± 5.1) was also significantly larger than that of the upper eyelids (11.2 ± 5.2) (P < 0.001). MGL was significantly correlated with expressed meibum grade in both eyelids (r = 0.451, P = 0.021 in the upper eyelids; r = 0.626, P = 0.001 in the lower eyelids). The meibum grades of both the upper and lower eyelids were negatively correlated with TBUT and positively correlated with corneal staining score. However, the MGL in both the eyelids was not correlated with TBUT or with corneal staining score., Conclusions: In patients with obstructive MGD, MGL and meibum grade in the lower eyelids were significantly greater than those of the upper eyelids. Although MGL and meibum quality showed a positive correlation with each other, TBUT and corneal staining score were significantly correlated with only meibum grade, and not with MGL.

It has been known that myriocin inhibits melanoma growth. However, the effects and action mechanisms of myriocin on lung cancer cell growth have not been reported. In this study, we examined whether myriocin isolated from Mycelia sterilia inhibits cell growth of lung cancer cells (A549 and NCI-H460) as well as possible signaling pathways involved in cell growth inhibition. Different concentrations of myriocin inhibited the growth of lung cancer cells through the induction of apoptotic cell death. Consistent with cancer cell growth inhibition, myriocin induced the expression of death receptors (DRs) as well as p-JNK and p-p38 in both cell lines. Moreover, the combination of myriocin with DR4 ligand TRAIL, and other well known anti-tumor drugs (docetaxel and cisplatin) synergistically inhibited cancer cell growth, and induced DR4 expression. These results showed that myriocin inhibits lung cancer cells growth through apoptosis via the activation of DR4 pathways, and enhanced anti-cancer effects with well known drugs. Thus, our study indicates that myriocin could be effective for lung cancer cells as an anti-cancer drug and/or a conjunction agent with well known anti-cancers.

Antihypertensive medication treatment is one effective management strategy to prevent cardiovascular disease (CVD) and mortality. However, little research has been conducted on the rates of antihypertensive medication adherence and the effect of antihypertensive medication adherence on health outcomes in South Korea. We searched the Korean National Health Insurance Claims Database for records from 2003 to 2007. Patients in this study were 18 years of age or older and they were diagnosed with hypertension and newly prescribed antihypertensive medication in 2003. Adherence to antihypertensive medication was estimated as the medication possession ratio (MPR). Multivariate Cox regression was used to evaluate the association between medication adherence and adverse health outcomes after adjusting for patient demographics and clinical characteristics. Our study population consisted of 40,408 patients with a mean age of 51 years. Among the patients, 50.3% were men, 4.0% had Medicaid health insurance, 17.8% had diabetes, 20.9% had dyslipidemia and 42.4% were adherent (MPR ≥ 80%). Nonadherent patients (MPR<80%) were younger and more likely to have Medicaid health insurance; they had lower rates of diabetes and dyslipidemia compared with adherent patients. In the Cox multivariate analysis, nonadherence increased the risk of all adverse health outcomes, including all-cause mortality and hospitalization for CVD (hazard ratio: 1.57, confidence interval: 1.40-1.76). In conclusion, our study indicates that medication adherence is important for reducing hospitalization due to CVD and mortality.

Unlabelled: Background. Chronic fatigue is one of the most restricting symptoms following primary breast cancer treatment, but clinical studies on symptom management are rare. The objective was to evaluate the impact of a multimodal mind-body program (MMMT), including moderate physical activity as compared with a walking intervention alone, on chronic fatigue symptoms of women with stage I to IIIA breast cancer., Patients and Methods: Sixty-four women (mean age = 56.7 years) suffering from chronic fatigue after active tumor treatment were randomly assigned to either an experimental or a control (n = 32 each) intervention (10 weeks). Fatigue, quality of life (QoL), functional well-being, anxiety, and depression were measured with standard questionnaires at baseline, after 10 weeks, and after 3 months., Results: Compared with baseline, both groups had reduced fatigue scores after treatment without any significant difference between groups (posttreatment, Δ = -0.3, confidence interval = -1.6 to 1.0, P = .678; follow-up, Δ = -0.4, confidence interval = -1.8 to 0.9, P = .510). All patients also improved regarding QoL and general functional well-being., Conclusion: Since both interventions reduced fatigue symptoms and enhanced QoL to a similar extent, we observed no verifiable add-on effect of the MMMT regarding fatigue symptoms. Considering the higher costs with additional expenditure related to MMMT, home-based walking intervention is recommended.

To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) mice. We investigated the activation of nuclear factor-kappaB/STAT3 since these are implicated transcription factors in the regulation of genes involving tumor growth. Significant inhibition of DNA-binding activity of nuclear factor-kappaB and STAT3, and the translocation of p50 and p65 into the nucleus and the phosphorylation of IĸB were found in the lungs of CCR5(-/-) mice compared with the lungs of CCR5(+/+) mice. Expression of apoptotic protein such as cleaved caspase-3, cleaved PARP and Bax was elevated, whereas the expression levels of survival protein such as Bcl-2 and cIAP1 was decreased in the lungs of CCR5(-/-) mice. Interestingly, we found that the level of monocyte chemoattractant protein-1 (MCP-1), a tumor growth-promoting cytokine, was significantly reduced in the lung tumor tissue and blood of CCR5(-/-) mice compared with the level in CCR5(+/+) mice. In addition, CCR5 small interfering RNA (siRNA) and inhibitor of MCP-1 blocked lung cancer cell growth, which was abolished by the addition of MCP-1 protein in cultured lung cancer cells. Moreover, inactivation of CD8(+) cytotoxic T cell and dendritic cells was significantly increased in the blood, lung tumors and spleens of CCR5(-/-) mice compared with that of CCR5(+/+) mice. Therefore, these results showed that CCR5 deficiency suppressed lung tumor development through the inhibition of nuclear factor-kappaB/STAT3 pathways and the downregulation of MCP-1 in the carcinogen-induced lung tumor model.

This retrospective-medical-record review was conducted to evaluate effect of infliximab therapy, particularly with a top-down strategy, on the nutritional parameters of children with Crohns disease (CD). 42 patients who were diagnosed with Crohns disease at the Pediatric Gastroenterology center of a tertiary care teaching hospital and achieved remission at two months and one year after beginning of treatment were divided into four subgroups according to the treatment regimen; azathioprine group (n = 11), steroid group (n = 11), infliximab top-down group (n = 11) and step-up group (n = 9). Weight, height, and serum albumin were measured at diagnosis, and then at two months and one year after the initiation of treatment. At 2 months, the Z score increment for weight was highest in the steroid group, followed by the top-down, step-up, and azathioprine groups. At one year, the Z score increment was highest in top-down group, followed by steroid, azathioprine, and step-up group. There were no significant differences between the four groups in Z score increment for height and serum albumin during the study period. The top-down infliximab treatment resulted in superior outcome for weight gain, compared to the step-up therapy and other treatment regimens.

Background: Malignant breast neoplasms are among the most frequent forms of cancer in the Western world. Conventional treatment of breast cancer may include surgery, hormonal therapy, chemotherapy, radiation and/or immunotherapy, all of which are often accompanied by severe side effects. Complementary and alternative medicine (CAM) treatments have been shown to be effective in alleviating those symptoms. Furthermore, with patient survival rates increasing, oncologists, psychologists and other therapists have to become more sensitive to the needs of cancer survivors that go beyond than the mere alleviation of symptoms. Many CAM methods are geared to treat the patient in a holistic manner and thus are also concerned with the patient's psychological and spiritual needs., Discussion: The use of certain CAM methods may become problematic when, as frequently occurs, patients use them indiscriminately and without informing their oncologists. Herbal medicines and dietary supplements, especially, may interfere with primary cancer treatments or have other detrimental effects. Thus, expertise in this highly specialized field of integrative medicine should be available to patients so that they can be advised about the benefits and negative effects of such preparations and practices.Being a beneficial combination of conventional and CAM care, integrative oncology makes possible the holistic approach to cancer care. The concept of integrative oncology for breast cancer is jointly practiced by the Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, academic teaching hospital of the University of Duisburg-Essen, and the Breast Center at Kliniken Essen-Mitte in Germany. This model is introduced here; its scope is reviewed, and its possible implications for the practice of integrative medicine are discussed., Summary: Evidence-based integrative care is crucial to the field of oncology in establishing state-of-the-art care for breast cancer patients.

Western integrative oncology (IO) combines conventional mainstream medicine with complementary and alternative medicine (CAM) for the care of cancer patients. Since it includes patient orientation and the holistic approach of many CAM options, IO offers not only preventive measures, but also a wide spectrum of treatment modalities for all stages of illness, from the acute phases through the rehabilitation period. Many therapeutic methods of IO are supported by scientific evidence, for example, dietary and nutritional counseling, exercise, and mind-body medicine, among others. IO also includes therapeutic interventions of traditional Chinese medicine (TCM). At present acupuncture, qigong, and foot massage play an important role in the Western care of cancer patients. However, unlike in China, in Western countries herbal remedies are usually only used during those periods in which chemotherapy is not applied in order to avoid herb-drug interactions. Instead, acupuncture is widely used to manage the side-effects that often accompany chemotherapy. This paper focuses on the role of Chinese medicine in Western IO and reviews the scope and limitations of IO in the care of cancer patients today. The future challenges of IO will also be discussed in this paper.

Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5-2.5 mg/kg, i.p.) reduces body and brain temperature by 2-5°C in 15-30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ∼30-40% when PIH therapy is initiated either immediately after stroke induction or after 30-60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries.

Objectives: The hypoalgesic effect of electroacupuncture (EA) was directly compared with the analgesic effect of pharmacological interventions using the submaximum effort tourniquet technique (SETT)., Methods: 125 healthy subjects (mean age 24.44±4.46 years; 62.4% female, 37.6% male) performed SETT at baseline and under one of five experimental conditions (n=25 per group): EA (2 Hz with burst pulses in alternating one-phase-square wave pulses; burst length 180 μs, burst frequency 80 Hz, stimulation time/pulse width 3 s), tramadol (50 mg), ibuprofen (400 mg), placebo pill or non-treatment control. EA was performed at LI4 and LI10 contralaterally with stimulation beginning 20 min before SETT and lasting throughout SETT. The pharmacological interventions were given in a double-blind design 1 h before the SETT assessment., Results: Subjects showed a hypoalgesic effect of the opiate and of the EA for subjective pain rating (EA p=0.0051; tramadol p=0.0299), and pain tolerance index (time/rating) (EA p=0.043; tramadol p=0.047) analysed using analysis of covariance. More subjects reached the strict time limit of 30 min (analysed by logistic regression and adjusted OR as a post-hoc analysis) under EA compared with most other experimental conditions. Only EA and tramadol were not significantly different (95% Wald confidence limits: non-treatment control vs EA 0.011 to 0.542; placebo pill vs EA 0.009 to 0.438; ibuprofen vs EA 0.021 to 0.766; tramadol vs EA 0.065 to 1.436)., Conclusion: In a laboratory setting, an EA procedure was as effective as a single dose of an orally administered opiate in reducing experimentally induced ischaemic pain.

Gua Sha is a traditional East Asian healing technique where the body surface is "press-stroked" with a smooth-edged instrument to raise therapeutic petechiae that last 2-5 days. The technique is traditionally used in the treatment of both acute and chronic neck and back pain. This study aimed to measure the effects of Gua Sha therapy on the pain ratings and pressure pain thresholds of patients with chronic neck pain (CNP) and chronic low back pain (CLBP). A total of 40 patients with either CNP or CLBP (mean age 49.23 ± 10.96 years) were randomized to either a treatment group (TG) or a waiting list control group (WLC). At baseline assessment (T1), all patients rated their pain on a 10 cm visual analog scale (VAS). Patients' pressure pain thresholds (PPT) at a site of maximal pain (pain-maximum) and an adjacent (pain-adjacent) site were also established. The treatment group then received a single Gua Sha treatment. Post-intervention measurements were taken for both groups at T2, seven days after baseline assessment (T1), using the same VAS and PPT measurements in precisely the same locations as at T1. Final analysis were conducted with 21 patients with CNP and 18 patients with CLBP. The study groups were equally distributed with regard to randomization. Patients in both the CNP and the CLBP treatment groups reported pain reduction (p < 0.05) and improved health status from their one Gua Sha treatment, as compared to the waiting list group. Pain sensitivity improved in the TG in CNP, but not in CLBP patients, possibly due to higher pressure sensitivity in the neck area. No adverse events were reported. These results suggest that Gua Sha may be an effective treatment for patients with chronic neck and low back pain. Further study of Gua Sha is warranted.

Objectives. The objective was to investigate whether a treatment with a needle stimulation pad (NSP) changes perceived pain and/or sensory thresholds in patients with chronic neck (NP) and lower back pain (BP). Methods. 40 patients with chronic NP and 42 patients with chronic BP were equally randomized to either treatment or waiting list control group. The treatment group self-administered a NSP over a period of 14 days. Pain ratings were recorded on numerical rating scales (NRSs). Mechanical detection thresholds (MDTs) and pressure pain thresholds (PPTs) were determined at the site of maximal pain and in the adjacent region, vibration detection thresholds (VDT) were measured at close spinal processes. The Northwick Park Neck Pain Questionnaire (NPQ) and the Oswestry Disability Index (ODI) were utilized for the NP and BP study, respectively. Results. NRS ratings were significantly reduced for the treatment groups compared to the control groups (NP: P = .021 and BP: P < .001), accompanied by a significant increase of PPT at pain maximum (NP: P = .032 and BP: P = .013). There was no effect on VDT and MDT. The NPQ showed also a significant improvement, but not the ODI. Conclusions. The mechanical NSP seems to be an effective treatment method for chronic NP and BP.

Background: The aim of this study was to investigate the effects of proton pump inhibitors on symptomatic inflammatory esophagogastric polyps (IEPs) in a pediatric cohort and to determine the optimal duration of treatment., Methods: The 11 patients with IEPs were managed with lansoprazole. Follow-up endoscopies were performed at 2 and 6 months after the start of medication. Medication was discontinued when the clinical symptoms completely resolved and the polyp size was reduced by more than 50% compared to the initial size., Results: The initial polyp size was 13.7 ± 3.3 mm. After 2 months of medication, the polyp size was reduced to 8.0 ± 5.8 mm. At 6 months, the polyp size was 4.7 ± 2.2 mm. The mean duration of medication was 4.8 ± 2.1 months. The duration of medication and the change in the polyp size appeared to have a linear correlation (p < 0.001). According to the formula used to calculate polyp size, the optimal duration of treatment was more than 7 months for complete resolution of the polyps., Conclusions: Proton pump inhibitor was effective for the treatment of IEPs. About 5 months of lansoprazole was adequate to treat IEPs in children. The optimal duration for complete resolution of the polyp might be more than 7 months., (Copyright © 2012 S. Karger AG, Basel.)

Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n = 25) or waiting list control group (WL, n = 25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Index (NDI), mechanical detection (MDT), vibration detection (MDT), and pressure pain thresholds (PPT) were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi) during the study. Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: -17.9 mm VAS, 95%CI -29.2 to -6.6; PM: -19.7, 95%CI -32.2 to -7.2; PaDi: -1.5 points on NRS, 95%CI -2.5 to -0.4; all P < 0.05) and higher quality of life than WL (SF-36, Physical Functioning: 7.5, 95%CI 1.4 to 13.5; Bodily Pain: 14.9, 95%CI 4.4 to 25.4; Physical Component Score: 5.0, 95%CI 1.4 to 8.5; all P < 0.05). No significant effect was found for NDI, MDT, or VDT, but TG showed significantly higher PPT at pain-areas than WL (in lg(kPa); pain-maximum: 0.088, 95%CI 0.029 to 0.148, pain-adjacent: 0.118, 95%CI 0.038 to 0.199; both P < 0.01). Conclusion. A single application of traditional cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP.

In clarifying the pathogenesis of inflammatory bowel diseases, a dysregulation of the adaptive immune function was the main focus of research in the last decade. With increasing knowledge of antimicrobial peptides, a primary disturbed barrier function and the system of innate immunity has recently received increasing attention. Contrary to the common understanding of irritable bowel syndrome as a functional disorder, there is first evidence for an involvement of innate immunity for this condition. Peptides with high relevance seem to be the class of human defensins. This article will thus discuss current advances in immunologic research of inflammatory bowel disease and irritable bowel syndrome, focusing on defensins and their possible role as biomarkers of these diseases.

Background: In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated., Methods: Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100-mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF-36). In addition, the mechanical-detection thresholds (MDT), vibration-detection thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain-related and control areas., Results: Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001). There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006) and vitality (Δ10.2, p = 0.006). Group differences in PPT were significant at pain-related and control areas (all p < 0.05), but were not significant for MDT or VDT., Conclusions: A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing., Trial Registration: The trial was registered at clinicaltrials.gov (NCT01289964).

We report the first measurement of the parity-violating single-spin asymmetries for midrapidity decay positrons and electrons from W+ and W- boson production in longitudinally polarized proton-proton collisions at sqrt[s] = 500 GeV by the STAR experiment at RHIC. The measured asymmetries, A(L)(W+) = -0.27 ± 0.10(stat.) ± 0.02(syst.) ± 0.03(norm.) and A(L)(W-) = 0.14 ± 0.19(stat.) ± 0.02(syst.) ± 0.01(norm.), are consistent with theory predictions, which are large and of opposite sign. These predictions are based on polarized quark and antiquark distribution functions constrained by polarized deep-inelastic scattering measurements.