Real-world evidence of heparin and citrate use in extracorporeal photopheresis: A hypothesis-generating data review of device settings and performance.

Extracorporeal photopheresis (ECP) is widely used for the treatment of cutaneous T-cell lymphoma, graft-vs-host disease, and other immune-related conditions. To avoid clotting during treatment, the ECP system used must be effectively primed with an anticoagulant. Heparin is the recommended anticoagulant for the THERAKOS CELLEX System, but acid citrate dextrose-A (ACDA) is often used. We compared system performance between these two anticoagulants for this ECP system. Deidentified data for ECP device performance were obtained at each treatment session, from automatically logged Smart Cards or labels completed by device operators. We compared the effects of ACDA or heparin on overall treatment duration, buffy coat (leukocyte) collection time, photoactivation time and the number of alarms and warnings. The variability in these parameters was also assessed. Data from 23 334 treat sessions were analyzed; ACDA was used in 34.4% and heparin in 65.6%. Overall, the ECP procedure duration, buffy coat collection time and photoactivation time were numerically similar regardless of whether ACDA or heparin was used, and regardless of needle mode. Photoactivation time variability was lower with ACDA compared with heparin in all needle modes. Among treatments that were completed automatically without any operator intervention, total treatment duration and photoactivation time were significantly reduced with ACDA use in both the double- and single-needle modes. The data presented indicate that, in both double- and single-needle modes, the THERAKOS® CELLEX® integrated ECP system performed similarly with ACDA compared to heparin, although ACDA demonstrated potential benefits in reducing variability in photoactivation time.

Severities in persistent mild traumatic brain injury related headache is associated with changes in supraspinal pain modulatory functions.

Emerging evidence suggests mild traumatic brain injury related headache (MTBI-HA) is a form of neuropathic pain state. Previous supraspinal mechanistic studies indicate patients with MTBI-HA demonstrate a dissociative state with diminished levels of supraspinal prefrontal pain modulatory functions and enhanced supraspinal sensory response to pain in comparison to healthy controls. However, the relationship between supraspinal pain modulatory functional deficit and severity of MTBI-HA is largely unknown. Understanding this relationship may provide enhanced levels of insight about MTBI-HA and facilitate the development of treatments. This study assessed pain related supraspinal resting states among MTBI-HA patients with various headache intensity phenotypes with comparisons to controls via functional magnetic resonance imaging (fMRI). Resting state fMRI data was analyzed with self-organizing-group-independent-component-analysis in three MTBI-HA intensity groups (mild, moderate, and severe) and one control group (n = 16 per group) within a pre-defined supraspinal pain network based on prior studies. In the mild-headache group, significant increases in supraspinal function were observed in the right premotor cortex (T = 3.53, p < 0.001) and the left premotor cortex (T = 3.99, p < 0.0001) when compared to the control group. In the moderate-headache group, a significant (T = -3.05, p < 0.01) decrease in resting state activity was observed in the left superior parietal cortex when compared to the mild-headache group. In the severe-headache group, significant decreases in resting state supraspinal activities in the right insula (T = -3.46, p < 0.001), right premotor cortex (T = -3.30, p < 0.01), left premotor cortex (T = -3.84, p < 0.001), and left parietal cortex (T = -3.94, p < 0.0001), and an increase in activity in the right secondary somatosensory cortex (T = 4.05, p < 0.0001) were observed when compared to the moderate-headache group. The results of the study suggest that the increase in MTBI-HA severity may be associated with an imbalance in the supraspinal pain network with decline in supraspinal pain modulatory function and enhancement of sensory/pain decoding.

Teacher feedback and student learning: A quantitative study.

INTRODUCTION: Feedback plays a significant role in informing students about the outcome of their assessments and contributes to their ongoing learning. The aim of this study was to investigate feedback currently given by clinical teachers to dental students throughout Europe. METHODS: This study used a piloted questionnaire, delivered on-line to members of the Association for Dental Education in Europe (ADEE). A largely quantitative approach was adopted with multiple-choice, single answer, open text boxes and Likert scale type questions. These data were collected via Google Forms, transferred to an excel spreadsheet and analysed using SPSS software Version 24. RESULTS: Data were collected from 223 questionnaires completed by respondents from 42 countries. Students received feedback following: (i) formative assessment (70%; n = 155), (ii) summative assessment (88%; n = 196) and iii) informally at any time (85%; n = 188). Feedback was delivered by different people including administrative staff (15%; n = 25). Several methods were used to deliver feedback, including written, oral/spoken, email and individually or as a group. 85% (n = 184) of teachers reported that their teaching had changed following feedback they had received from students. CONCLUSION: The study showed a strong ethos of delivering feedback from teachers to dental students following both assessment and non-assessment related activities. Teachers should understand/appreciate the individualistic nature of feedback and the importance of cultivating a congenial environment for feedback delivery. Challenges remain in delivering them to a high standard and in a timely manner.

Customizing TMS Applications in Traumatic Brain Injury Using Neuroimaging.

Optimizing transcranial magnetic stimulation (TMS) treatments in traumatic brain injury (TBI) and co-occurring conditions may benefit from neuroimaging-based customization. PARTICIPANTS: Our total sample (N = 97) included 58 individuals with TBI (49 mild, 8 moderate, and 1 severe in a state of disordered consciousness), of which 24 had co-occurring conditions (depression in 14 and alcohol use disorder in 10). Of those without TBI, 6 individuals had alcohol use disorder and 33 were healthy controls. Of our total sample, 54 were veterans and 43 were civilians. DESIGN: Proof-of-concept study incorporating data from 5 analyses/studies that used multimodal approaches to integrate neuroimaging with TMS. MAIN MEASURES: Multimodal neuroimaging methods including structural magnetic resonance imaging (MRI), MRI-guided TMS navigation, functional MRI, diffusion MRI, and TMS-induced electric fields. Outcomes included symptom scales, neuropsychological tests, and physiological measures. RESULTS: It is feasible to use multimodal neuroimaging data to customize TMS targets and understand brain-based changes in targeted networks among people with TBI. CONCLUSIONS: TBI is an anatomically heterogeneous disorder. Preliminary evidence from the 5 studies suggests that using multimodal neuroimaging approaches to customize TMS treatment is feasible. To test whether this will lead to increased clinical efficacy, studies that integrate neuroimaging and TMS targeting data with outcomes are needed.

Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation.

BACKGROUND: While transcranial magnetic stimulation (TMS) has been studied for the treatment of psychiatric disorders, emerging evidence supports its use for pain and headache by stimulating either motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). However, its clinical implementation is hindered due to a lack of consensus in the quality of clinical evidence and treatment recommendation/guideline(s). Thus, working collaboratively, this multinational multidisciplinary expert panel aims to: 1) assess and rate the existing outcome evidence of TMS in various pain/headache conditions; 2) provide TMS treatment recommendation/guidelines for the evaluated conditions and comorbid depression; and 3) assess the cost-effectiveness and technical issues relevant to the long-term clinical implementation of TMS for pain and headache. METHODS: Seven task groups were formed under the guidance of a 5-member steering committee with four task groups assessing the utilization of TMS in the treatment of Neuropathic Pain (NP), Acute Pain, Primary Headache Disorders, and Posttraumatic Brain Injury related Headaches (PTBI-HA), and remaining three assessing the treatment for both pain and comorbid depression, and the cost-effectiveness and technological issues relevant to the treatment. RESULTS: The panel rated the overall level of evidence and recommendability for clinical implementation of TMS as: 1) high and extremely/strongly for both NP and PTBI-HA respectively; 2) moderate for postoperative pain and migraine prevention, and recommendable for migraine prevention. While the use of TMS for treating both pain and depression in one setting is clinically and financially sound, more studies are required to fully assess the long-term benefit of the treatment for the two highly comorbid conditions, especially with neuronavigation. CONCLUSIONS: After extensive literature review, the panel provided recommendations and treatment guidelines for TMS in managing neuropathic pain and headaches. In addition, the panel also recommended more outcome and cost-effectiveness studies to assess the feasibility of the long-term clinical implementation of the treatment.

Addressing chronic persistent headaches after MTBI as a neuropathic pain state.

An increasing number of patients with chronic persistent post-traumatic headache (PPTH) after mild traumatic brain injury (MTBI) are being referred to headache or pain specialists as conventional treatment options for primary headache disorders have not been able to adequately alleviate their debilitating headache symptoms. Evolving clinical and mechanistic evidences support the notation that chronic persistent MTBI related headaches (MTBI-HA) carry the hallmark characteristics of neuropathic pain. Thus, in addition to conventional treatment options applicable to non-traumatic primary headache disorders, other available treatment modalities for neuropathic pain should be considered. In this comprehensive review article, the author reveals the prevalence of MTBI-HA and its clinical manifestation, discusses existing clinical and mechanistic evidence supporting the classification of chronic persistent MTBI-HA as a neuropathic pain state, and explores current available treatment options and future directions of therapeutic research related to MTBI-HA.

The impact of confidence on clinical dental practice.

INTRODUCTION: Increasing confidence through learning has the potential to change General Dental Practitioners' (GDPs) perceptions of clinical practice. By examining how changes in confidence influence the clinical practice of two cohorts of GDPs, during and following an extended period of postgraduate training, we show the importance of confidence to GDPs and that a lack of confidence is a primary reason why GDPs attend postgraduate training courses. METHODS: A mixed-method approach was adopted for this study. Quantitative data were collected via a series of linked questionnaires; qualitative data were collected using focus group discussions, interviews and contemporaneous field notes. Analysis was undertaken using SPSS software and a phenomenological approach, respectively. FINDINGS: Participants indicated an increase in confidence in their ability to undertake dental procedures, which led to an increase in confidence in communication skills, and their ability to undertake complex restorative procedures. This led to greater treatment acceptance by patients resulting in better "job satisfaction." DISCUSSION: A sense of confidence is central to personal development and ongoing study, leading to first, an improved capability to perform tasks (competence); second, confidence is a product of the relationship and trust of those people associated with the individual/professional and third, the correct level of challenge is important to confidence. CONCLUSIONS: The issue of confidence has not been looked at in postgraduate dentistry, but it is well recognised in medical education fields.

Pain-related white matter tract abnormalities in mild traumatic brain injury patients with persistent headache.

BACKGROUND: The occurrence of debilitating chronic persistent (24/7) headache after mild traumatic brain injury represents a central neuropathic pain state. Previous studies suggest that this chronic headache state can be attributed to altered supraspinal modulatory functional connectivity in both resting and evoked pain states. Abnormalities in the myelin sheaths along the supraspinal superior longitudinal fasciculus and anterior thalamic radiation are frequently associated with alteration in pain modulation related to functional connectivity deficit with the prefrontal cortex. This study assessed the correlated axonal injury-related white matter tract abnormality underlying these previously observed prefrontal functional connectivity deficits by comparing the fractional anisotropy, axial diffusivity, and radial diffusivity of brain white matter in patients with mild traumatic brain injury-related headache to healthy controls. RESULT: Diffusion tensor imaging data from patients ( N = 12, average age ± SD = 35.0 ± 8.0 years old, 10 male) with mild traumatic brain injury-headache were compared with images acquired from healthy controls. The mild traumatic brain injury cohort demonstrated two areas of significant ( P < 0.01, F value >16, cluster size >50 voxels) white matter tract abnormalities closely related to pain affective and modulatory functions in (1) the left superior longitudinal fasciculus which connects the prefrontal cortices with the parietal cortices and (2) the right anterior thalamic radiation connecting the prefrontal cortices with the anterior cingulate cortex. In addition, a significant ( P < 0.01) decrease in axial diffusivity and increase in radial diffusivity at the superior longitudinal fasciculus cluster were noted in the mild traumatic brain injury cohort. CONCLUSION: The identified white matter tract abnormalities may represent a state of Wallerian degeneration which correlates with the functional connectivity deficit in pain modulation and can contribute to the development of the chronic persistent headache in the patients with mild traumatic brain injury.

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms.

OBJECTIVE: Persistent mild traumatic brain injury related headache (MTBI-HA) represents a neuropathic pain state. This study tested the hypothesis that repetitive transcranial magnetic stimulation (rTMS) at the left prefrontal cortex can alleviate MTBI-HA and associated neuropsychological dysfunctions. METHODS AND MATERIALS: Veterans with MTBI-HA were randomized to receive four sessions of either real (REAL group) or sham (SHAM group) high frequency rTMS delivered at 10 Hz, 80% of resting motor threshold and 2000 pulses per session at >24 and <72 hours apart. Pre-treatment, post-treatment 1-week and 4-week headache and neuropsychological assessments were conducted. RESULTS: Twenty nine out of forty-four consented subjects completed the study. A two-factor (visit × treatment) repeated measures ANOVA showed a significant (p = 0.002, F = 11.63, df = 1) interaction for the average daily persistent headache intensity with the REAL group exhibiting a significant (p < 0.0001) average reduction (±SD) of 25.3 ± 16.8% and 23.0 ± 17.7% reduction in their numerical rating scale at the one-week and four-week post-treatment assessments in comparison to <1 ± 11.7% and 2.3 ± 14.5% reduction found in the SHAM group. In addition, a significant (p < 0.01) 50% and 57% reduction was found in the prevalence of persistent headache in the REAL group at the one-week and four-week assessments in comparison to 7% and 20% reduction found in the SHAM group. Furthermore, the REAL group demonstrated a significant (p = 0.033) improvement (from 22.3 ± 6.4 at pre-treatment to 19.0 ± 5.0 at post-treatment one-week) in the Hamilton Rating Scale for Depression score, while the SHAM group's score remained largely unchanged (from 25.33 ± 8.43 to 24.64 ± 5.03) in the same time frame. This trend of improvement, although not statistically significant, continues to the post-treatment four-week assessment. CONCLUSION: A short-course rTMS at the left DLPFC can alleviate MTBI-HA symptoms and provide a transient mood enhancing benefit. Further studies are required to establish a clinical protocol balancing both treatment efficacy and patient compliance.

Diminished supraspinal pain modulation in patients with mild traumatic brain injury.

BACKGROUND: Chronic pain conditions are highly prevalent in patients with mild traumatic brain injury. Supraspinal diffuse axonal injury is known to dissociate brain functional connectivity in these patients. The effect of this dissociated state on supraspinal pain network is largely unknown. A functional magnetic resonance imaging study was conducted to compare the supraspinal pain network in patients with mild traumatic brain injury to the gender and age-matched healthy controls with the hypothesis that the functional connectivities of the medial prefrontal cortices, a supraspinal pain modulatory region to other pain-related sensory discriminatory and affective regions in the mild traumatic brain injury subjects are significantly reduced in comparison to healthy controls. RESULTS: The mild traumatic brain injury group (N = 15) demonstrated significantly (P < 0.01, cluster threshold > 150 voxels) less activities in the thalamus, pons, anterior cingulate cortex, insula, dorsolateral prefrontal cortex, and medial prefrontal cortices than the healthy control group (N = 15). Granger Causality Analyses (GCA) indicated while the left medial prefrontal cortices of the healthy control group cast a noticeable degree of outward (to affect) causality inference to multiple pain processing related regions, this outward inference pattern was not observed in the mild traumatic brain injury group. On the other hand, only patients' bilateral anterior cingulate cortex received multiple inward (to be affected) causality inferences from regions including the primary and secondary somatosensory cortices and the inferior parietal lobe. Resting state functional connectivity analyses indicated that the medial prefrontal cortices of the mild traumatic brain injury group demonstrated a significantly (P < 0.01, F = 3.6, cluster size > 150 voxels) higher degree of functional connectivity to the inferior parietal lobe, premotor and secondary somatosensory cortex than the controls. Conversely, the anterior cingulate cortex of the healthy group demonstrated significantly (P < 0.01, F = 3.84, cluster size > 150 voxels) less degree of functional connectivities to the inferior parietal lobe and secondary somatosensory cortex than their mild traumatic brain injury counterparts. CONCLUSIONS: In short, the current study demonstrates that patients with mild traumatic brain injury and headaches appear to have an altered state of supraspinal modulatory and affective functions related to pain perception.

Cathepsin K Inhibition: A New Mechanism for the Treatment of Osteoporosis.

Cathepsin K (CatK), a cysteine protease, is highly expressed by osteoclasts and very efficiently degrades type I collagen, the major component of the organic bone matrix. Robust genetic and pharmacological preclinical studies consistently demonstrate that CatK inhibition increases bone mass, improves bone microarchitecture and strength. Recent advances in the understanding of the molecular and cellular mechanisms involved in bone modeling and remodeling suggest that inhibition of CatK decreases bone resorption, but increases the number of cells of osteoclast lineage. This in turn maintains the signals for bone formation, and perhaps may even increase bone formation on some cortical surfaces. Several CatK inhibitors, including relacatib, balicatib, odanacatib and ONO-5334 had entered clinical development for metabolic bone disorders with increased bone resorption, such as postmenopausal osteoporosis. However, odanacatib (ODN) is the only candidate continuing in development. ODN is a highly selective oral CatK inhibitor dosed once-weekly in humans. In a Phase 2 clinical trial, postmenopausal women treated with ODN had sustained reductions of bone resorption markers, while bone formation markers returned to normal after an initial decline within the first 2 years on treatment. In turn areal bone mineral density increased continuously at both spine and hip for up to 5 years. ODN has also been demonstrated to improve bone mass in women with postmenopausal osteoporosis previously treated with alendronate and in men with osteoporosis. ODN is currently in a worldwide Phase 3 fracture outcome trial for the treatment of postmenopausal osteoporosis with interim results supporting its anti-fracture efficacy at the spine, hip and non-vertebral sites.

Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial.

BACKGROUND: The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. METHODS: We conducted a randomized parallel-group assessor-blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. RESULTS: Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] -0.20, 95% confidence interval [CI] -0.36 to -0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD -6.72, 95% CI -10.9 to -2.57), function (Functional Status Scale score MD -0.22, 95% CI -0.38 to -0.05), dexterity (time to complete blinded pick-up test MD -6.13 seconds, 95% CI -10.6 to -1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale -0.70, 95% CI -1.34 to -0.06), and not significant for sensation (first finger monofilament test -0.08 mm, 95% CI -0.22 to 0.06). INTERPRETATION: For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. TRIAL REGISTRATION: Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655).

The antibacterial effect of sinoporphyrin sodium photodynamic therapy on Staphylococcus aureus planktonic and biofilm cultures.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus (S. aureus) are important causes of nosocomial and medical-device-related infections. Photodynamic treatment (PDT) has been proposed as an alternative approach for the inactivation of bacteria. Sinoporphyrin sodium (DVDMS) is a newly identified photosensitizer and has high photo-sensitivity when used in PDT. This study aims to evaluate the antibacterial effect of DVDMS mediated PDT on S. aureus planktonic and biofilm cultures. STUDY DESIGN/MATERIALS AND METHODS: The uptake of DVDMS in S. aureus was evaluated according to photometry after alkali lysis. Then bacteria were incubated with DVDMS and exposed to light treatment. After PDT treatment, counting colony-forming units (CFU) was applied to estimate the bactericidal effect. Intracellular reactive oxygen species (ROS) production was detected by flow cytometry. Scanning electron microscope (SEM) was performed to assess the disruption of biofilm. RESULTS: With the incubation time increased, the relative fluorescence intensity of DVDMS in bacteria increased and reached peak at 75 minutes. DVDMS alone did not produce significant toxicity compared with the untreated group, while, remarkable survival decrease was observed in PDT groups in a dose-dependent manner. More than 90% of the bacteria were effectively killed by the combined treatment of 2 µM DVDMS with 10 J/cm2 light irradiation, and 4-log reduction in CFU was observed after 5 µM DVDMS treatment followed by 100 J/cm2 light irradiation. Intracellular ROS level was significantly enhanced after PDT treatment. The disruption of biofilm was confirmed by SEM, suggesting DVDMS-PDT effectively damaged the biofilm. CONCLUSION: These results indicate DVDMS-PDT presents significant bactericidal activity.

Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX.

Sonodynamic therapy (SDT) is expected to be a novel therapeutic strategy for tumor. The protoporphyrin IX disodium salt (PpIX), a photosensitizer, can be activated by ultrasound. The present study aims to investigate apoptosis of HL-60 cells induced by PpIX-mediated SDT. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to examine cell toxicity. Apoptosis was detected using Annexin V-PE/7-amino-actinomycin D (7-AAD) double staining. Detection of apoptotic bodies was examined by Hoechst33342 (HO) staining. Western blotting was used to analyze the protein of caspase-3 and poly ADP-ribose polymerase (PARP). Intracellular reactive oxygen species (ROS) was detected by a flow cytometer after exposures. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound were significantly boosted. In addition, as determined by Annexin V-PE/7-AAD staining, SDT significantly induced HL-60 cell apoptosis, the obvious nuclear condensation was also found with HO staining at 4 hours post-SDT treatment. Furthermore, Western blotting showed visible enhancement of caspase-3 and PARP cleavage in this process. Besides, intracellular ROS production was significantly enhanced after SDT. Our findings demonstrate that PpIX-mediated SDT could induce apoptosis on HL-60 cells, suggesting that apoptosis is an important mechanism of cell death induced by PpIX-mediated SDT.

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches.

OBJECTIVE: Headache is one of the most common debilitating chronic pain conditions in either active or retired military personnel with mild traumatic brain injury (MTBI). This study assessed the effect of repetitive transcranial magnetic stimulation (rTMS) in alleviating MTBI-related headache (MTBI-HA). MATERIALS AND METHOD: Veterans with MTBI-HA were randomized to receive either real rTMS (REAL group) at 10 hz for a total of 2000 pulses divided into 20 trains with one-sec inter-train interval or sham rTMS (SHAM group) at the left motor cortex (LMC) with brain magnetic resonance imaging neuronavigation guidance. Pretreatment, posttreatment one-week and four-week headache and neuropsychological assessments were conducted. RESULT: Thirty veterans were screened and twenty four (21 men and 3 women with average year-old ± SD at 14.3 ± 12.6) subjects' data were analyzed. A two-factor (visit × treatment) repeated measures analysis of variance (RM-ANOVA) indicated a close to significant (p = 0.06) trend of interaction between pretreatment and posttreatment one-week assessment with the intensity of the persistent daily headache decreasing from 5.7 ± 1.9 to 2.2 ± 2.7 and 4.6 ± 1.3 to 3.5 ± 2.0 for the REAL and SHAM groups, respectively. Subsequent analyses indicated REAL group demonstrated a significantly (p = 0.041) higher % of reduction in persistent headache intensity than the SHAM group (56.3 ± 48.2% vs.15.4 ± 43.6%) at the posttreatment one-week assessment and the trend continued to the four-week assessment. Overall, a significantly (p = 0.035) higher percentage of the subjects in the REAL group (58.3%) demonstrated at least a 50% headache intensity reduction at posttreatment one-week assessment compared with the SHAM group (16.6%). The overall composite score of functionally debilitating headache exacerbation is significantly (p = 0.017) reduced in REAL group at the posttreatment four-week assessment in comparison with the SHAM group. No major sustained change in neuropsychological assessments was noted. CONCLUSION: The studied rTMS protocol appears to be a clinically feasible and effective treatment option in managing MTBI-HA.

Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for osteoporosis in Europe and Canada.

OBJECTIVES: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. METHODS: MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women ≥50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. RESULTS: Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. CONCLUSIONS: The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.

Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission.

Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P < 0.05) elevates sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers.

Sonodynamic action of hypocrellin B on biofilm-producing Staphylococcus epidermidis in planktonic condition.

Staphylococcus epidermidis is an opportunistic pathogen causing biofilm-associated infections. To investigate sonodynamic action of hypocrellin B on biofilm-producing Staphylococcus epidermidis in planktonic culture, a biofilm-producing strain Staphylococcus epidermidis (ATCC 35984) was incubated with hypocrellin B and then exposed to ultrasound at intensity (ISATA) of 1.56 W/cm(2) with a frequency of 1 MHz in continuous mode for 5 min. After sonodynamic treatment of hypocrellin B, the bacterial growth was measured using the colony counting method. Bacterial membrane integrity was investigated using a flow cytometry with propidium iodide staining. Intracellular reactive oxygen species (ROS) level was measured using a flow cytometry with DCFH-DA staining. The results showed that sonodynamic action of hypocrellin B significantly induced survival reduction of Staphylococcus epidermidis in a hypocrellin B dose-dependent manner, and a 4-log reduction was observed after the combined treatment of hypcorellin B (40 µM) and ultrasound sonication with the intensity of 1.56 W/cm(2) for 5 min. Bacterial membrane integrity was notably damaged and the level of intracellular ROS level was remarkably increased after sonodynamic treatment. The findings demonstrated that sonodynamic action of hypocrellin B had significant antibacterial activity on biofilm-producing Staphylococcus epidermidis in planktonic condition probably through increasing intracellular ROS level to cause damage to bacterial membrane integrity.

Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter.

Preclinical Research Schisandrae Chinensis Fructus (SCF), the fruit of Schisandra chinensis (Turcz.) Baill. (family Schisandraceae) is traditionally used as a tonic and antidiabetic agent in Asia. In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS-7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay-guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1 mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [14 C]-α-methyl-d-glucopyranoside ([14 C]-AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, of which F8, at a concentration of 1 mg/mL, was specific in inhibiting SGLT 2 (42% inhibition, P < 0.001), without inhibiting SGLT 1. Using LC/MS-MS, three compounds, deoxyschisandrin, schisandrin B (γ-schisandrin) and schisandrin were identified in F8 and their amounts quantified. However, subsequent evaluation in the [14 C]-AMG uptake assay showed that these three compounds failed to inhibit SGLT 2 activity indicating that the SGLT active component(s) from SCF have yet to be identified. Drug Dev Res 76 : 1-8, 2015.