Light-sensitive Lipid-based Nanoparticles for Drug Delivery: Design Principles and Future Considerations for Biological Applications

PubMed Central

Yavlovich, Amichai; Smith, Brandon; Gupta, Kshitij; Blumenthal, Robert; Puri, Anu

2011-01-01

Radiation-based therapies aided by nanoparticles have been developed since decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details on the strategies to develop photo-triggerable designer liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic. PMID:20939770

Extracorporeal Shock Wave Therapy Versus Trigger Point Injection in the Treatment of Myofascial Pain Syndrome in the Quadratus Lumborum

PubMed Central

2017-01-01

Objective To compare the effectiveness of extracorporeal shock wave therapy (ESWT) and trigger point injection (TPI) for the treatment of myofascial pain syndrome in the quadratus lumborum. Methods In a retrospective study at our institute, 30 patients with myofascial pain syndrome in the quadratus lumborum were assigned to ESWT or TPI groups. We assessed ESWT and TPI treatment according to their affects on pain relief and disability improvement. The outcome measures for the pain assessment were a visual analogue scale score and pain pressure threshold. The outcome measures for the disability assessment were Oswestry Disability Index, Roles and Maudsley, and Quebec Back Pain Disability Scale scores. Results Both groups demonstrated statistically significant improvements in pain and disability measures after treatment. However, in comparing the treatments, we found ESWT to be more effective than TPI for pain relief. There were no statistically significant differences between the groups with respect to disability. Conclusion Compared to TPI, ESWT showed superior results for pain relief. Thus, we consider ESWT as an effective treatment for myofascial pain syndrome in the quadratus lumborum. PMID:28971042

Improvement in clinical outcomes after dry needling versus myofascial release on pain pressure thresholds, quality of life, fatigue, pain intensity, quality of sleep, anxiety, and depression in patients with fibromyalgia syndrome.

PubMed

Castro Sánchez, Adelaida M; García López, Hector; Fernández Sánchez, Manuel; Pérez Mármol, José Manuel; Aguilar-Ferrándiz, María Encarnación; Luque Suárez, Alejandro; Matarán Peñarrocha, Guillermo Adolfo

2018-04-23

To compare the effectiveness of dry needling versus myofascial release on myofascial trigger points pain in cervical muscles, quality of life, impact of symptoms pain, quality of sleep, anxiety, depression, and fatigue in patients with fibromyalgia syndrome. A single-blind randomized controlled trial was conducted. Sixty-four subjects with fibromyalgia were randomly assigned to a dry needling group or a myofascial release group. Pain pressure thresholds of myofascial trigger points were evaluated in the cervical muscles. In addition, quality of life, impact of fibromyalgia symptoms, quality of sleep, intensity of pain, anxiety and depression symptoms, impact of fatigue at baseline and post treatment after four weeks of intervention were evaluated. Significant improvement was found in most pain pressure thresholds of the myofascial trigger points in cervical muscles in the dry needling group compared to myofascial release (p < 0.05). Similarly, these differences between groups were found for the components of quality of life of physical function (F = 12.74, p = 0.001), physical role (F = 11.24, p = 0.001), body pain (F =30.26, p < 0.001), general health (F = 15.83, p < 0.001), vitality (F = 13.51, p = 0.001), social function (F = 4.73, p = 0.034), emotional role (F = 8.01, p = 0.006), and mental health (F = 4.95, p = 0.030). Similar results were achieved for total impact of FMS symptoms (F = 42.91, p < 0.001), quality of sleep (F = 11.96, p = 0.001), state anxiety (F = 7.40, p = 0.009), and trait anxiety (F = -14.63, p < 0.001), hospital anxiety and depression (F = 20.60, p < 0.001), general pain intensity (F = 29.59, p < 0.001), and fatigue (F = -25.73, p < 0.001). The dry needling therapy showed higher improvements in comparison with myofascial release therapy for pain pressure thresholds, the components of quality of life of physical role, body pain, vitality and social function, as well as the total impact of FMS symptoms, quality of sleep, state and trait anxiety, hospital anxiety-depression, general pain intensity and fatigue. Implications for rehabilitation Dry needling therapy reduces myofascial trigger point pain in the short term in patients with fibromyalgia syndrome. This therapeutic approach improves anxiety, depression, fatigue symptoms, quality of life, and sleep after treatment. Dry needling and myofascial release therapies decrease intensity of pain, and the impact of fibromyalgia symptoms in this population. These intervention approaches should be considered in an independent manner as complementary therapies within a multidisciplinary setting.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuccitelli, Richard, E-mail: rich@bioelectromed.com; Tran, Kevin; Athos, Brian

Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted tomore » determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.« less

Physical therapy in the treatment of fibromyalgia.

PubMed

Offenbächer, M; Stucki, G

2000-01-01

Fibromyalgia (FM) is a syndrome of unknown etiology characterized by chronic wide spread pain, increased tenderness to palpation and additional symptoms such as disturbed sleep, stiffness, fatigue and psychological distress. While medication mainly focus on pain reduction, physical therapy is aimed at disease consequences such as pain, fatigue, deconditioning, muscle weakness and sleep disturbances and other disease consequences. We systematically reviewed current treatment options in the treatment of fibromyalgia. Based on evidence from randomized controlled trials cardiovascular fitness training importantly improves cardiovascular fitness, both subjective and objective measures of pain as well as subjective energy and work capacity and physical and social activities. Based on anecdotal evidence or small observational studies physiotherapy may reduce overloading of the muscle system, improve postural fatigue and positioning, and condition weak muscles. Modalities and whole body cryotherapy may reduce localized as well as generalized pain in short term. Trigger point injection may reduce pain originating from concomitant trigger points in selected FM patient. Massage may reduce muscle tension and may be prescribed as a adjunct with other therapeutic interventions. Acupuncture may reduce pain and increase pain threshold. Biofeedback may positively influence subjective and objective disease measures. TENS may reduce localized musculoskeletal pain in fibromyalgia. While there seems to be no single best treatment option, physical therapy seem to reduce disease consequences. Accordingly a multidisciplinary approach combining these therapies in a well balanced program may be the most promising strategy and is currently recommended in the treatment of fibromyalgia.

Mechanisms of Myofascial Pain

PubMed Central

Jafri, M. Saleet

2014-01-01

Myofascial pain syndrome is an important health problem. It affects a majority of the general population, impairs mobility, causes pain, and reduces the overall sense of well-being. Underlying this syndrome is the existence of painful taut bands of muscle that contain discrete, hypersensitive foci called myofascial trigger points. In spite of the significant impact on public health, a clear mechanistic understanding of the disorder does not exist. This is likely due to the complex nature of the disorder which involves the integration of cellular signaling, excitation-contraction coupling, neuromuscular inputs, local circulation, and energy metabolism. The difficulties are further exacerbated by the lack of an animal model for myofascial pain to test mechanistic hypothesis. In this review, current theories for myofascial pain are presented and their relative strengths and weaknesses are discussed. Based on new findings linking mechanoactivation of reactive oxygen species signaling to destabilized calcium signaling, we put forth a novel mechanistic hypothesis for the initiation and maintenance of myofascial trigger points. It is hoped that this lays a new foundation for understanding myofascial pain syndrome and how current therapies work, and gives key insights that will lead to the improvement of therapies for its treatment. PMID:25574501

Trends in management of myofacial pain

PubMed Central

Pal, Uma Shanker; Kumar, Lakshya; Mehta, Gagan; Singh, Nimisha; Singh, Geeta; Singh, Mayank; Yadav, Hemant Kumar

2014-01-01

We systematically reviewed the myofascial pain publications in the literature. The aim of this article is to review the methods of management and their outcome and factors associated with prognosis. The topics of interest in the diagnostic process are myofascial trigger points electromyography, jaw tracking, joint sound recorder, sonography, and vibratography, exclusion of other orofacial pain and temporomandibular disorders. Management modalities are occlusal therapy, physiotherapy, multidimensional rehabilitation antinociceptive therapy, anti-inflammatory and analgesics, muscle relaxants, stretch, and spray technique, transcutaneous electric nerve stimulation, and in severe cases botulinum toxin may be tried. The disease required interdisciplinary interaction in terms of occlusal therapy, antinociceptive therapy and physiotherapy because management of the disease may be influenced by the specialist primarily treating the patients. PMID:25937719

Managing Pain Caused By Neurological Disease

PubMed Central

Tunks, Eldon

1985-01-01

Stabbing paroxysmal pain due to neurological disease can often be controlled by anticonvulsants, whereas steady burning pain is often responsive to tricyclic antidepressants, and to neuroleptics. Overuse of opiates may actually aggravate the pain, necessitating detoxification. Transcutaneous electrical nerve stimulation is helpful for conditions in which pain is localized, especially if there is a ‘trigger area’ or neuroma, or if paresthesias can be stimulated within the painful area. Local anesthetic injection, possibly with corticosteroid, relieves painful scars and neuromas, neuritis, and tender trigger points. Sympathetic blocks are used for post-herpetic neuralgia and sympathetic dystrophies. Relaxation therapy is a very useful psychological treatment. PMID:21274032

Disarmed by density

PubMed Central

Nasi, Aikaterini; Rethi, Bence

2013-01-01

We observed a cell concentration-dependent differentiation switch among cultured dendritic cells (DCs) triggered by lactic acid, a product of glycolytic metabolism. In particular, while interleukin (IL)-12, IL-23, and tumor necrosis factor α (TNFα)-producing, migratory DCs developed in sparse cultures, IL-10-producing, non-migratory DCs differentiated in dense cultures. This points to a novel opportunity for tailoring DC-based anticancer therapies through metabolism modulation in developing DCs. PMID:24575378

The short-term effects of trigger point therapy, stretching and medicine ball exercises on accuracy and back swing hip turn in elite, male golfers - A randomised controlled trial.

PubMed

Quinn, Samantha-Lynn; Olivier, Benita; Wood, Wendy-Ann

2016-11-01

This study aimed to compare the effect of myofascial trigger point therapy (MTPT) and stretching, MTPT and medicine ball exercises, and no intervention, on hip flexor length (HFL), golf swing biomechanics and performance in elite, male golfers. Single blind, randomised controlled trial with two experimental groups (stretch group: MTPT and stretching; and the ball group: MTPT, a single stretch and medicine ball exercises) and one control group (no intervention). Professional golf academy. One hundred, elite, male golfers aged 16-25 years. HFL, 3D biomechanical analysis of the golf swing, club head speed (CHS), smash ratio, accuracy and distance at baseline and after the interventions. Backswing hip turn (BSHT) improved in the ball group relative to the control group (p = 0.0248). Accuracy in the ball group and the stretch group improved relative to the control group (Fisher's exact = 0.016). Other performance parameters such as: smash ratio, distance and CHS were not compromised by either intervention. This study advocates the use of MTPT combined with medicine ball exercises over MTPT combined with stretching in the treatment of golfers with shortened hip flexors - even immediately preceding a tournament. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of shoulder strength in males with and without myofascial trigger points in the upper trapezius.

PubMed

Kim, H A; Hwang, U J; Jung, S H; Ahn, S H; Kim, J H; Kwon, O Y

2017-11-01

This study was conducted in order to compare the strength of scapular elevator and shoulder abductor with and without restricted scapular elevation between male subjects with and without myofascial trigger points in the upper trapezius. In total, 15 male subjects with myofascial trigger points, and 15age- and weight-matched male subjects without myofascial trigger points in the upper trapezius. Each subject was measured in the strength of maximum isometric scapular elevation and shoulder abduction with and without restricted scapular elevation. Maximum isometric contractions were measured using the Smart KEMA strength measurement system. Independent t-tests were used to compare shoulder strength values between the myofascial trigger points and non- myofascial trigger points groups. The results showed that shoulder abductor strength in the group with myofascial trigger points (5.64kgf) was significantly lower than in the group without myofascial trigger points (11.96kgf) when scapular elevation was restricted (p<0.05). However, there was no significant difference in the strength of the scapular elevator or shoulder abductor between groups (p>0.05). These findings suggest that decreased strength in the shoulder abductor with restricted scapular elevation should be considered in evaluating and treating individuals with myofascial trigger points of the upper trapezius. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in Clinical Parameters in Patients with Tension-type Headache Following Massage Therapy: A Pilot Study

PubMed Central

Moraska, Albert; Chandler, Clint

2008-01-01

Complementary and alternative medicine approaches to treatment for tension-type headache are increasingly popular among patients, but evidence supporting its efficacy is limited. The objective of this study was to assess short term changes on primary and secondary headache pain measures in patients with tension-type headache (TTH) receiving a structured massage therapy program with a focus on myofascial trigger point therapy. Participants were enrolled in an open label trial using a baseline control with four 3-week phases: baseline, massage (two 3-week phases) and follow-up. Twice weekly, 45-minute massage sessions commenced following the baseline phase. A daily headache diary was maintained throughout the study in which participants recorded headache incidence, intensity, and duration. The Headache Disability Index was administered upon study entry and at 3-week intervals thereafter. 18 subjects were enrolled with 16 completing all headache diary, evaluation, and massage assignments. Study participants reported a median of 7.5 years with TTH. Headache frequency decreased from 4.7±0.7 episodes per week during baseline to 3.7±0.9 during treatment period 2 (P<0.001); reduction was also noted during the follow-up phase (3.2±1.0). Secondary measures of headache also decreased across the study phases with headache intensity decreasing by 30% (P<0.01) and headache duration from 4.0±1.3 to 2.8±0.5 hours (P<0.05). A corresponding improvement in Headache Disability Index was found with massage (P<0.001). This pilot study provides preliminary evidence for reduction in headache pain and disability with massage therapy that targets myofascial trigger points, suggesting the need for more rigorously controlled studies. PMID:19119396

Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.

PubMed

Ramon, Silvia; Gleitz, Markus; Hernandez, Leonor; Romero, Luis David

2015-12-01

Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM). Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema.

PubMed

Suzuki, Atsushi; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Mori, Yuta; Kondoh, Yasuhiro

2018-01-01

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.

Disarmed by density: A glycolytic break for immunostimulatory dendritic cells?

PubMed

Nasi, Aikaterini; Rethi, Bence

2013-12-01

We observed a cell concentration-dependent differentiation switch among cultured dendritic cells (DCs) triggered by lactic acid, a product of glycolytic metabolism. In particular, while interleukin (IL)-12, IL-23, and tumor necrosis factor α (TNFα)-producing, migratory DCs developed in sparse cultures, IL-10-producing, non-migratory DCs differentiated in dense cultures. This points to a novel opportunity for tailoring DC-based anticancer therapies through metabolism modulation in developing DCs.

Muscle trigger point therapy in tension-type headache.

PubMed

Alonso-Blanco, Cristina; de-la-Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César

2012-03-01

Recent evidence suggests that active trigger points (TrPs) in neck and shoulder muscles contribute to tension-type headache. Active TrPs within the suboccipital, upper trapezius, sternocleidomastoid, temporalis, superior oblique and lateral rectus muscles have been associated with chronic and episodic tension-type headache forms. It seems that the pain profile of this headache may be provoked by referred pain from active TrPs in the posterior cervical, head and shoulder muscles. In fact, the presence of active TrPs has been related to a higher degree of sensitization in tension-type headache. Different therapeutic approaches are proposed for proper TrP management. Preliminary evidence indicates that inactivation of TrPs may be effective for the management of tension-type headache, particularly in a subgroup of patients who may respond positively to this approach. Different treatment approaches targeted to TrP inactivation are discussed in the current paper, focusing on tension-type headache. New studies are needed to further delineate the relationship between muscle TrP inactivation and tension-type headache.

Reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature.

PubMed

Lucas, Nicholas; Macaskill, Petra; Irwig, Les; Moran, Robert; Bogduk, Nikolai

2009-01-01

Trigger points are promoted as an important cause of musculoskeletal pain. There is no accepted reference standard for the diagnosis of trigger points, and data on the reliability of physical examination for trigger points are conflicting. To systematically review the literature on the reliability of physical examination for the diagnosis of trigger points. MEDLINE, EMBASE, and other sources were searched for articles reporting the reliability of physical examination for trigger points. Included studies were evaluated for their quality and applicability, and reliability estimates were extracted and reported. Nine studies were eligible for inclusion. None satisfied all quality and applicability criteria. No study specifically reported reliability for the identification of the location of active trigger points in the muscles of symptomatic participants. Reliability estimates varied widely for each diagnostic sign, for each muscle, and across each study. Reliability estimates were generally higher for subjective signs such as tenderness (kappa range, 0.22-1.0) and pain reproduction (kappa range, 0.57-1.00), and lower for objective signs such as the taut band (kappa range, -0.08-0.75) and local twitch response (kappa range, -0.05-0.57). No study to date has reported the reliability of trigger point diagnosis according to the currently proposed criteria. On the basis of the limited number of studies available, and significant problems with their design, reporting, statistical integrity, and clinical applicability, physical examination cannot currently be recommended as a reliable test for the diagnosis of trigger points. The reliability of trigger point diagnosis needs to be further investigated with studies of high quality that use current diagnostic criteria in clinically relevant patients.

Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

PubMed

Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

2015-01-01

A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

PubMed

Park, Amy J; Paraiso, Marie Fidela R

2009-08-01

Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

Contribution of myofascial trigger points to migraine symptoms.

PubMed

Giamberardino, Maria Adele; Tafuri, Emmanuele; Savini, Antonella; Fabrizio, Alessandra; Affaitati, Giannapia; Lerza, Rosanna; Di Ianni, Livio; Lapenna, Domenico; Mezzetti, Andrea

2007-11-01

This study evaluated the contribution of myofascial trigger points (TrPs) to migraine pain. Seventy-eight migraine patients with cervical active TrPs whose referred areas (RAs) coincided with migraine sites (frontal/temporal) underwent electrical pain threshold measurement in skin, subcutis, and muscle in TrPs and RAs at baseline and after 3, 10, 30, and 60 days; migraine pain assessment (number and intensity of attacks) for 60 days before and 60 days after study start. Fifty-four patients (group 1) underwent TrP anesthetic infiltration on the 3rd, 10th, 30th, and 60th day (after threshold measurement); 24 (group 2) received no treatment. Twenty normal subjects underwent threshold measurements in the same sites and time points as patients. At baseline, all patients showed lower than normal thresholds in TrPs and RAs in all tissues (P < .001). During treatment in group 1, all thresholds increased progressively in TrPs and RAs (P < .0001), with sensory normalization of skin/subcutis in RAs at the end of treatment; migraine pain decreased (P < .001). Threshold increase in RAs and migraine reduction correlated linearly (.0001 < P < .006). In group 2 and normal subjects, no changes occurred. Cervical TrPs with referred areas in migraine sites thus contribute substantially to migraine symptoms, the peripheral nociceptive input from TrPs probably enhancing the sensitization level of central sensory neurons. This article shows the beneficial effects of local therapy of active myofascial trigger points (TrPs) on migraine symptoms in patients in whom migraine sites coincide with the referred areas of the TrPs. These results suggest that migraine pain is often contributed to by myofascial inputs that enhance the level of central neuronal excitability.

[Anesthesia unrelated triggering of a fatal malignant hyperthermia crisis].

PubMed

Olthoff, D; Vonderlind, C

1997-12-01

For incidents of malignant hyperthermia (MH) outside the hospital, a high number of unrecorded cases must be reckoned with because of an insufficient knowledge of emergency services and poor identification and documentation that make it impossible to classify acute situations under the diagnosis of malignant hyperthermia crisis. As a result, there are no statistical data in this field, and only case reports with a broad spectrum of suspected trigger mechanisms have been published. The case described in this report is a proved example of a non-anesthesia-related triggering of MH in a 21-year-old man who had had an anesthetic-induced MH manifestation in childhood, which was confirmed with an in vitro contracture test. After visiting a restaurant, he became unconscious and convulsive after consuming a high level of alcohol (2.9/1000). The first cardiocirculatory arrest occurred directly before hospitalization. After admission, the patient showed a full-blown MH episode whose subsequent fatality was unavoidable in spite of adapted and optimal therapy. Suspected trigger mechanisms seem to be multifactoral (excessive alcohol consumption, over-heating, mental stress) as a forensic investigation did not point to any particular signs of typical trigger substances. The case demonstrates again that an MH attack might be triggered under certain non-anaesthesia-related situations. For patients with an MH disposition, additional information on their behavior outside the hospital is required.

Development and Applications of Photo-triggered Theranostic Agents

PubMed Central

Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

2010-01-01

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

PubMed

Wang, Peng; Yin, Lingshu; Zhang, Yawei; Kirk, Maura; Song, Gang; Ahn, Peter H; Lin, Alexander; Gee, James; Dolney, Derek; Solberg, Timothy D; Maughan, Richard; McDonough, James; Teo, Boon-Keng Kevin

2016-03-08

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

Assessment of pelvic floor muscles in women with deep endometriosis.

PubMed

Dos Bispo, Ana Paula Santos; Ploger, Christine; Loureiro, Alessandra Fernandes; Sato, Hélio; Kolpeman, Alexander; Girão, Manoel João Batista Castello; Schor, Eduardo

2016-09-01

To assess function and prevalence of spasms and trigger points of the pelvic floor muscles in women with deep endometriosis. One hundred and four (104) patients were assessed. Group 1 (G1) was composed of 52 subjects diagnosed with deep endometriosis proven by magnetic resonance imaging (MRI); Group 2 (G2) was composed of 52 women with no signs of endometriosis. Subjects from both G1 and G2 were seen at the Division of Pelvic Pain and Endometriosis and at Center for Prevention of Sexually Transmitted Diseases, both at Federal University of São Paulo (UNIFESP), respectively. A full physical therapy evaluation was carried out, including medical history, presence of dyspareunia and physical examination, which included detailed evaluation of pelvic floor muscles and occurrence of muscle spasm, trigger point and muscle function. The average age of the subjects in the study group was 36.4 and 30.9 years in the control group (p = 0.002). A greater prevalence of deep dyspareunia was found in the subjects in the endometriosis group when compared to the control group (p = 0.010). Women in G1 had higher prevalence of muscle spasms. In this group, 53.9 % had spasms-compared to only 17.3 % of women in G2 (p < 0.001). On the other hand, no significant difference between the groups (p = 0.153) was found while searching for the presence of trigger points. Women with deep endometriosis have increased prevalence of pelvic floor muscle spasms when compared to the control group.

Comparison of the Effectiveness of Transcutaneous Electrical Nerve Stimulation and Interferential Therapy on the Upper Trapezius in Myofascial Pain Syndrome: A Randomized Controlled Study.

PubMed

Dissanayaka, Thusharika Dilrukshi; Pallegama, Ranjith Wasantha; Suraweera, Hilari Justus; Johnson, Mark I; Kariyawasam, Anula Padma

2016-09-01

The aim of this study was to compare the effectiveness of transcutaneous electrical nerve stimulation and interferential therapy (IFT) both in combination with hot pack, myofascial release, active range of motion exercise, and a home exercise program on myofascial pain syndrome patients with upper trapezius myofascial trigger point. A total of 105 patients with an upper trapezius myofascial trigger point were recruited to this single-blind randomized controlled trial. Following random allocation of patients to three groups, three therapeutic regimens-control-standard care (hot pack, active range of motion exercises, myofascial release, and a home exercise program with postural advice), transcutaneous electrical nerve stimulation-standard care and IFT-standard care-were administered eight times during 4 wks at regular intervals. Pain intensity and cervical range of motions (cervical extension, lateral flexion to the contralateral side, and rotation to the ipsilateral side) were measured at baseline, immediately after the first treatment, before the eighth treatment, and 1 wk after the eighth treatment. Immediate and short-term improvements were marked in the transcutaneous electrical nerve stimulation group (n = 35) compared with the IFT group (n = 35) and the control group (n = 35) with respect to pain intensity and cervical range of motions (P < 0.05). The IFT group showed significant improvement on these outcome measurements than the control group did (P < 0.05). Transcutaneous electrical nerve stimulation with standard care facilitates recovery better than IFT does in the same combination.

Comparison of the Efficacy of Dry Needling and High-Power Pain Threshold Ultrasound Therapy with Clinical Status and Sonoelastography in Myofascial Pain Syndrome.

PubMed

Aridici, Rifat; Yetisgin, Alparslan; Boyaci, Ahmet; Tutoglu, Ahmet; Bozdogan, Erol; Sen Dokumaci, Dilek; Kilicaslan, Nihat; Boyaci, Nurefsan

2016-10-01

The aim of this study was to compare the therapeutic efficacy of high-power pain threshold (HPPT) ultrasound therapy applied to the trigger points and dry needling (DN) in myofascial pain syndrome. Sixty-one patients were randomly assigned to an HPPT (n = 30) and dry needling (n = 31) groups. The primary outcome measures were the Visual Analog Scale (VAS) and Neck Pain and Disability Scale (NPDS), both at 1 week and 4 weeks after treatment. The secondary outcome measures were the number of painful trigger points, range of the tragus-acromioclavicular joint, the Short Form-36, the Beck Depression Inventory, the Beck Anxiety Inventory, and sonoelastographic tests after a 1-week treatment. More improvement was seen in anxiety in the HPPT group (P < 0.05). However, no significant differences were found between the groups with regard to other parameters (P > 0.05). A decrease in tissue stiffness was only seen in the HPPT group (P < 0.05). Significant posttreatment improvements were seen on all clinical scales in both groups (P < 0.05). After a treatment period of 4 weeks, a significant improvement was also observed on the visual analog scale and NPDS (P < 0.05). Our study favors the efficacy of both treatment methods in myofascial pain syndrome. Although a significant decrease was shown in tissue stiffness with HPPT, neither of these treatments had an apparent superiority.

Effectiveness of Physical Therapy in Patients with Tension-type Headache: Literature Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Arbós-Berenguer, Teresa; González, Ángel Arturo López; Vicente-Herrero, Teófila

2014-01-01

Tension-type headache (TTH) is a disease with a great incidence on quality of life and with a significant socioeconomic impact. The aim of this review is to determine the effectiveness of physical therapy by using manual therapy (MT) for the relief of TTH. A review was done identifying randomized controlled trials through searches in MEDLINE, PEDro, Cochrane and CINAHL (January 2002 - April 2012). English-language studies, with adult patients and number of subjects not under 11, diagnosed with episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) were included. Initial search was undertaken with the words Effectiveness, Tension-type headache, and Manual therapy (39 studies). In addition, a search which included terms related to treatments such as physiotherapy, physical therapy, spinal manipulation was performed (25 studies). From the two searches 9 studies met the inclusion criteria and were analysed finding statistically significant results: 1) myofascial release, cervical traction, neck muscles trigger points in cervical thoracic muscles and stretching; 2) Superficial heat and massage, connective tissue manipulation and vertebral Cyriax mobilization; 3) cervical or thoracic spinal manipulation and cervical chin-occipital manual traction; 4) massage, progressive relaxation and gentle stretching, program of active exercises of shoulder, neck and pericranial muscles; 5) massage, passive rhythmic mobilization techniques, cervical, thoracic and lumbopelvic postural correction and cranio-cervical exercises; 6) progressive muscular relaxation combined with joint mobilization, functional, muscle energy, and strain/counterstrain techniques, and cranial osteopathic treatment; 7) massage focused on relieving myofascial trigger point activity; 8) pressure release and muscle energy in suboccipital muscles; 9) combination of mobilizations of the cervical and thoracic spine, exercises and postural correction. All studies used a combination of different techniques and none analyzed treatments separately, also all the studies have assessed aspects related to TTH beyond frequency and intensity of pain. The findings from these studies showed evidence that physiotherapy with articulatory MT, combined with cervical muscle stretching and massage are effective for this disease in different aspects related with TTH. No evidence was found of the effectiveness of the techniques applied separately.

Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

PubMed

Glover, Amanda L; Bennett, James B; Pritchett, Jeremy S; Nikles, Sarah M; Nikles, David E; Nikles, Jacqueline A; Brazel, Christopher S

2013-01-01

The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.

Can Ashi points stimulation have specific effects on shoulder pain? A systematic review of randomized controlled trials.

PubMed

Wang, Kang-Feng; Zhang, Li-Juan; Lu, Feng; Lu, Yong-Hui; Yang, Chuan-Hua

2016-06-01

To provide an evidence-based overview regarding the efficacy of Ashi points stimulation for the treatment of shoulder pain. A comprehensive search [PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Chongqing Weipu Database for Chinese Technical Periodicals (VIP) and Wanfang Database] was conducted to identify randomized or quasi-randomized controlled trials that evaluated the effectiveness of Ashi points stimulation for shoulder pain compared with conventional treatment. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. RevMan 5.0 was used for data synthesis. Nine trials were included. Seven studies assessed the effectiveness of Ashi points stimulation on response rate compared with conventional acupuncture. Their results suggested significant effect in favour of Ashi points stimulation [odds ratio (OR): 5.89, 95% confidence interval (CI): 2.97 to 11.67, P<0.01, heterogeneity: χ(2) =3.81, P=0.70, I (2) =0% ]. One trial compared Ashi points stimulation with drug therapy. The result showed there was a significantly greater recovery rate in group of Ashi points stimulation (OR: 9.58, 95% CI: 2.69 to 34.12). One trial compared comprehensive treatment on the myofascial trigger points (MTrPs) with no treatment and the result was in favor of MTrPs. Ashi points stimulation might be superior to conventional acupuncture, drug therapy and no treatment for shoulder pain. However, due to the low methodological quality of included studies, a firm conclusion could not be reached until further studies of high quality are available.

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

PubMed

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

Laser radiation in tennis elbow treatment: a new minimally invasive alternative

NASA Astrophysics Data System (ADS)

Paganini, Stefan; Thal, Dietmar R.; Werkmann, Klaus

1998-01-01

The epicondylitis humeri radialis (EHR) (tennis elbow), is a common disease in elbow joint pain syndromes. We treated patients with chronic pain for at least one year and no improvement with conservative or operative therapies with a new minimal invasive method, the EHR-Laser radiation (EHR- LR). With this method periepicondylar coagulations were applied to the trigger points of the patients. For this the previously established technique of facet joint coagulation with the Nd:Yag-laser was modified. In a follow-up study of between 6 weeks and 2 years all patients reported either a significant pain reduction or were symptom free. EHR-LR is a new method situated between conservative and surgical treatments for minimal invasive therapy of EHR. Several therapeutic rationales were discussed for the resulting pain reduction.

Trigger point-related sympathetic nerve activity in chronic sciatic leg pain: a case study.

PubMed

Skorupska, Elżbieta; Rychlik, Michał; Pawelec, Wiktoria; Bednarek, Agata; Samborski, Włodzimierz

2014-10-01

Sciatica has classically been associated with irritation of the sciatic nerve by the vertebral disc and consequent inflammation. Some authors suggest that active trigger points in the gluteus minimus muscle can refer pain in similar way to sciatica. Trigger point diagnosis is based on Travel and Simons criteria, but referred pain and twitch response are significant confirmatory signs of the diagnostic criteria. Although vasoconstriction in the area of a latent trigger point has been demonstrated, the vasomotor reaction of active trigger points has not been examined. We report the case of a 22-year-old Caucasian European man who presented with a 3-year history of chronic sciatic-type leg pain. In the third year of symptoms, coexistent myofascial pain syndrome was diagnosed. Acupuncture needle stimulation of active trigger points under infrared thermovisual camera showed a sudden short-term vasodilatation (an autonomic phenomenon) in the area of referred pain. The vasodilatation spread from 0.2 to 171.9 cm(2) and then gradually decreased. After needling, increases in average and maximum skin temperature were seen as follows: for the thigh, changes were +2.6°C (average) and +3.6°C (maximum); for the calf, changes were +0.9°C (average) and +1.4°C (maximum). It is not yet known whether the vasodilatation observed was evoked exclusively by dry needling of active trigger points. The complex condition of the patient suggests that other variables might have influenced the infrared thermovision camera results. We suggest that it is important to check if vasodilatation in the area of referred pain occurs in all patients with active trigger points. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Impact of identifying factors which trigger bothersome tinnitus on the treatment outcome in tinnitus retraining therapy.

PubMed

Molini, Egisto; Faralli, Mario; Calzolaro, Lucia; Ricci, Giampietro

2014-01-01

The aim of this work was to ascertain any differences in the effectiveness of rehabilitation therapy in relation to the presence or absence of a known negative reinforcement responsible for the tinnitus-related pathology. Between 1 January 2001 and 31 December 2008, we recruited 294 subjects suffering from incapacitating tinnitus and/or hyperacusis. The patients underwent tinnitus retraining therapy (TRT) according to the methods described by Jastreboff and Hazell [Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge, Cambridge University Press, 2004, pp 121-133]. We clinically assessed the presence or absence of known phenomena of associative learning, regarding the presence of adverse events temporally correlated with tinnitus and the treatment outcome. The separate analysis of the 2 subgroups shows a statistically significant difference in the improvement rate between the group with a known triggering factor and the group without a triggering factor, with a preponderance of the former with a 91% improvement rate versus approximately 56% for the latter. In our study, the inability to identify factors triggering bothersome tinnitus negatively affected the treatment outcome in TRT. © 2014 S. Karger AG, Basel.

The use of low-level laser therapy (LLLT) in the treatment of trigger points that are associated with rotator cuff tendonitis

NASA Astrophysics Data System (ADS)

Al-Shenqiti, A.; Oldham, J.

2003-12-01

The purpose of this study was to investigate the efficacy of LLLT in the treatment of trigger points (TrPs) that are associated with rotator cuff tendonitis. A double-blind randomized controlled trail was conducted. Sixty patients were randomly allocated to one of two groups: sham or laser therapy. The laser (Excel, Omega Universal Technologies Ltd, London, UK) parameters used were a wavelength of 820 nm, a power output of 100 mW, a frequency of 5000 Hz (modulated) and energy density of 32 J/cm2. The two groups received a course of 12 treatment sessions for four weeks (3 sessions per week). Pain, functional activities (as measured using the Shoulder Pain and Disability Index, SPADI), pressure pain threshold (PPT) and range of motion (ROM) were assessed pre and post treatment, with a three month follow-up assessment. Significant improvements in pain (p < 0.001) were observed for the laser group (6 cm median improvement on a 10 cm VAS) compared to the sham group (2 cm median improvement) immediately post treatment. The improvements in the laser group continued post treatment with a 7 cm median improvement observed at three month follow-up. Similar between group differences were observed for ROM (p < 0.01), functional activities (p <= 0.001) and PPT (p <= 0.05). The findings of the current study suggested that LLLT is effective in treating patients with TrPs associated with rotator cuff tendonitis, when using the parameters described. However, the mechanism of its action is not yet clear, and will require further investigation.

Splint therapy for trigger finger in children.

PubMed

Tsuyuguchi, Y; Tada, K; Kawaii, H

1983-02-01

During the last 9 years, 83 trigger digits in 65 children were treated using a modified coil spring splint which maintains the interphalangeal (IP) joint in neutral extension or hyperextension. Sixty-two digits (75%) were completely healed following splint therapy alone, after an average period of splinting for 9.4 months. Eight digits which did not improve with splinting were surgically treated. Splint therapy to maintain the IP joint in neutral extension or hyperextension proved markedly effective in our series.

Development of a clinical prediction rule for identifying women with tension-type headache who are likely to achieve short-term success with joint mobilization and muscle trigger point therapy.

PubMed

Fernández-de-las-Peñas, César; Cleland, Joshua A; Palomeque-del-Cerro, Luis; Caminero, Ana Belén; Guillem-Mesado, Amparo; Jiménez-García, Rodrigo

2011-02-01

To identify prognostic factors from the history and physical examination in women with tension-type headache (TTH) who are likely to experience self-perceived clinical improvement following a multimodal physical therapy session including joint mobilization and muscle trigger point (TrP) therapies. No definitive therapeutic intervention is available for TTH. It would be useful for clinicians to have a clinical prediction rule for selecting which TTH patients may experience improved outcomes following a multimodal physical therapy program. Women diagnosed with pure TTH by 3 experienced neurologists according to the International Headache Society criteria from different neurology departments were included. They underwent a standardized examination (neck mobility, pressure pain thresholds, total tenderness score, presence of muscle TrPs, Medical Outcomes Study 36-Item Short Form, the Neck Disability Index [NDI], the Beck Depression Inventory, and the Headache Disability Inventory) and then a multimodal physical therapy session including joint mobilization and TrP therapies. The treatment session included a 30-second grade III or IV central posterior-anterior nonthrust mobilization applied from T4 to T1 thoracic vertebrae, at C7-T1 cervico-thoracic junction and C1-C2 vertebrae for an overall intervention time of 5 minutes Different TrP techniques, particularly soft tissue stroke, pressure release, or muscle energy were applied to head and neck-shoulder muscles (temporalis, suboccipital, upper trapezius, splenius capitis, semispinalis capitis, sternocleidomastoid) to inactivate active muscle TrPs. Participants were classified as having achieved a successful outcome 1 week after the session based on their self-perceived recovery. Potential prognostic variables were entered into a stepwise logistic regression model to determine the most accurate set of variables for prediction of success. Data for 76 subjects were included in the analysis, of which 36 experienced a successful outcome (48%). Eight prognostic variables were retained in the regression model: mean age <44.5 years, presence of left sternocleidomastoid TrP, presence of suboccipital TrP, presence of left superior oblique muscle TrP, cervical rotation to the left > 69°, total tenderness score <20.5, NDI <18.5, referred pain area of right upper trapezius muscle TrP >42.23. The current clinical prediction rule may allow clinicians to make an a priori identification of women with TTH who are likely to experience short-term self-report improvement with a multimodal session including joint mobilizations and TrP therapies. Future studies are necessary to validate these findings. © 2010 American Headache Society.

Non-pharmacologic management of sickle cell pain.

PubMed

Bodhise, Paul Brown; Dejoie, Marjorie; Brandon, Zemoria; Simpkins, Stanley; Ballas, Samir K

2004-06-01

Patients with sickle cell disease (SCD) suffer from both acute and chronic pain. The latter includes avascular necrosis of the hip joints mostly in the adult population. It has a negative impact on the quality of life of affected individuals and is often associated with depression, disability, unemployment and dependence on opioid analgesics. In this study, we show that a non-pharmacologic approach to management with deep tissue/deep pressure massage therapy technique, including neuromuscular trigger point treatment with acupressure, in patients with SCD has a salutary effect on pain relief and quality of life. Copyright 2004 Taylor and Francis Ltd

Dry needling: a literature review with implications for clinical practice guidelines1

PubMed Central

Dunning, James; Butts, Raymond; Mourad, Firas; Young, Ian; Flannagan, Sean; Perreault, Thomas

2014-01-01

Background: Wet needling uses hollow-bore needles to deliver corticosteroids, anesthetics, sclerosants, botulinum toxins, or other agents. In contrast, dry needling requires the insertion of thin monofilament needles, as used in the practice of acupuncture, without the use of injectate into muscles, ligaments, tendons, subcutaneous fascia, and scar tissue. Dry needles may also be inserted in the vicinity of peripheral nerves and/or neurovascular bundles in order to manage a variety of neuromusculoskeletal pain syndromes. Nevertheless, some position statements by several US State Boards of Physical Therapy have narrowly defined dry needling as an ‘intramuscular’ procedure involving the isolated treatment of ‘myofascial trigger points’ (MTrPs). Objectives: To operationalize an appropriate definition for dry needling based on the existing literature and to further investigate the optimal frequency, duration, and intensity of dry needling for both spinal and extremity neuromusculoskeletal conditions. Major findings: According to recent findings in the literature, the needle tip touches, taps, or pricks tiny nerve endings or neural tissue (i.e. ‘sensitive loci’ or ‘nociceptors’) when it is inserted into a MTrP. To date, there is a paucity of high-quality evidence to underpin the use of direct dry needling into MTrPs for the purpose of short and long-term pain and disability reduction in patients with musculoskeletal pain syndromes. Furthermore, there is a lack of robust evidence validating the clinical diagnostic criteria for trigger point identification or diagnosis. High-quality studies have also demonstrated that manual examination for the identification and localization of a trigger point is neither valid nor reliable between-examiners. Conclusions: Several studies have demonstrated immediate or short-term improvements in pain and/or disability by targeting trigger points (TrPs) using in-and-out techniques such as ‘pistoning’ or ‘sparrow pecking’; however, to date, no high-quality, long-term trials supporting in-and-out needling techniques at exclusively muscular TrPs exist, and the practice should therefore be questioned. The insertion of dry needles into asymptomatic body areas proximal and/or distal to the primary source of pain is supported by the myofascial pain syndrome literature. Physical therapists should not ignore the findings of the Western or biomedical ‘acupuncture’ literature that have used the very same ‘dry needles’ to treat patients with a variety of neuromusculoskeletal conditions in numerous, large scale randomized controlled trials. Although the optimal frequency, duration, and intensity of dry needling has yet to be determined for many neuromusculoskeletal conditions, the vast majority of dry needling randomized controlled trials have manually stimulated the needles and left them in situ for between 10 and 30 minute durations. Position statements and clinical practice guidelines for dry needling should be based on the best available literature, not a single paradigm or school of thought; therefore, physical therapy associations and state boards of physical therapy should consider broadening the definition of dry needling to encompass the stimulation of neural, muscular, and connective tissues, not just ‘TrPs’. PMID:25143704

Research on the effects of laser-therapy application in low back pain of musculo-capsulo-ligaments disorders

NASA Astrophysics Data System (ADS)

Nica, Adriana S.; Teleki, N.; Vasiliu, Virgil V.

1995-03-01

Usually, lumbosacrat aria is a very mechanical stressed aria because of insufficient adaptation to the verticality and because of many other getting in professional field (high physical stress, sedentary profession) or in daily living. Because of all these facts and the other can develop `low back pain syndromes' in variable places dorsolumbar, lumbar or lumbosacrat aria, in different degree of disability interesting the muscles, fasciae, aponevrosis tendons, capsules and ligaments. Specially the muscular tissue is in high sufferings in paravertebral lumbosacrat place where we can find frequently contractor (usually secondary to the static vertebral troubles) or retractors; sometimes we discover morphopathological disorder in muscles with trigger and tender points--very painful and cause of a high percent of disability of lumbosacrat region. The aim of this research is to prove by clinic--functional tests the effects of laser- therapy and to notice the answer of all the soft tissue from lumbosacrat region and all the structures treated which respond after laser-therapy to kinetotherapy, comparing with the other kinds of physical therapy.

Subjective tinnitus assessment and treatment in clinical practice: the necessity of personalized medicine.

PubMed

Van de Heyning, Paul; Gilles, Annick; Rabau, Sarah; Van Rompaey, Vincent

2015-10-01

Subjective tinnitus can be triggered by a variety of causes, and therefore tinnitus patients constitute a very heterogeneous population difficult to manage. In this article, we reviewed the current literature to present our conceptual model of the conscious auditory percept and tinnitus - based on experimental research - in order to explain the clinical approach to the individual tinnitus patient. Fundamental research has provided evidence to support the neurophysiological model of tinnitus developed by Jastreboff. By manipulating the limbic, autonomic and auditory systems, tinnitus retraining therapy (TRT) aims to reduce the response to the abnormal stimulus. Evidence has confirmed the effectiveness of TRT and cognitive behavioral therapy in reducing the negative impact of subjective tinnitus on the patients' quality of life. Every patient with subjective tinnitus has its unique 'tinnitus profile' which provides a guide to the necessary combination of therapeutic actions. Evidence suggests the multidisciplinary approach combining etiological therapy as well as TRT, and cognitive behavioral therapy in specialized clinics is not only effective in reducing the patient's quality of life but also cost-effective from a healthcare and societal point of view.

Clinical presentation and manual therapy for upper quadrant musculoskeletal conditions

PubMed Central

Isabel de-la-Llave-Rincón, Ana; Puentedura, Emilio J; Fernández-de-las-Peñas, César

2011-01-01

In recent years, increased knowledge of the pathogenesis of upper quadrant pain syndromes has translated to better management strategies. Recent studies have demonstrated evidence of peripheral and central sensitization mechanisms in different local pain syndromes of the upper quadrant such as idiopathic neck pain, lateral epicondylalgia, whiplash-associated disorders, shoulder impingement, and carpal tunnel syndrome. Therefore, a treatment-based classification approach where subjects receive matched interventions has been developed and, it has been found that these patients experience better outcomes than those receiving non-matched interventions. There is evidence suggesting that the cervical and thoracic spine is involved in upper quadrant pain. Spinal manipulation has been found to be effective for patients with elbow pain, neck pain, or cervicobrachial pain. Additionally, it is known that spinal manipulative therapy exerts neurophysiological effects that can activate pain modulation mechanisms. This paper exposes some manual therapies for upper quadrant pain syndromes, based on a nociceptive pain rationale for modulating central nervous system including trigger point therapy, dry needling, mobilization or manipulation, and cognitive pain approaches. PMID:23115473

Know Your Options (to Manage Your Pain Without Opioids)

MedlinePlus

... behavioral, and emotional triggers of pain and stress Exercise therapy, including physical therapy Medications for depression or for seizures Interventional therapies (injections) Exercise and ...

Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.

PubMed

Skinner, Reagan T

2014-01-01

A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.

[The role of the cervical spine and the craniomandibular system in the pathogenesis of tinnitus. Somatosensory tinnitus].

PubMed

Biesinger, E; Reisshauer, A; Mazurek, B

2008-07-01

The causes of tinnitus, vertigo, and hearing disturbances may be pathological processes in the cervical spine and temporomaxillary joint. In these cases, tinnitus is called somatosensory tinnitus (SST). For afferences of the cervical spine, projections of neuronal connections in the cochlear nucleus were found. A reflex-like impact of the cervical spine on the cochlear nucleus can be assumed. The tinnitus treatment concept of the Charité University Hospital in Berlin involves the cooperation of ENT specialists with many other disciplines in an outpatient clinic. A standardized examination protocol has been established, and physical therapy has been integrated into the interdisciplinary tinnitus treatment. For tinnitus-modulating therapy of muscular trigger points, local anesthetics as well as self-massage or treatment by a physiotherapist or osteopath are useful.

A rational approach to the management of chronic migraine.

PubMed

Evans, Randolph W

2013-01-01

About 2% of the adult population has chronic migraine with only 20% diagnosed with this disorder. Those with medication overuse may improve with withdrawal of overuse medications. The intravenous dihydroergotamine regimen usually produces short-term benefit for those with medically refractory chronic migraine. OnabotulinumtoxinA and topiramate have shown efficacy in large placebo-controlled randomized trials. Sodium valproate, gabapentin, tizanidine, amitriptyline, fluoxetine, zonisamide, and possibly memantine may be alternative or possibly combined treatment options but with lesser levels of evidence supporting their use. Preliminary evidence suggests that nerve blocks might be beneficial. Acupuncture, biofeedback, relaxation therapy, and cognitive behavioral therapy might be of benefit. Surgical treatments including bariatric and deactivation of trigger points are of growing interest but not appropriate for most sufferers. Occipital nerve stimulation is a promising treatment with ongoing studies defining its use. © 2013 American Headache Society.

Compensatable muon collider calorimeter with manageable backgrounds

DOEpatents

Raja, Rajendran

2015-02-17

A method and system for reducing background noise in a particle collider, comprises identifying an interaction point among a plurality of particles within a particle collider associated with a detector element, defining a trigger start time for each of the pixels as the time taken for light to travel from the interaction point to the pixel and a trigger stop time as a selected time after the trigger start time, and collecting only detections that occur between the start trigger time and the stop trigger time in order to thereafter compensate the result from the particle collider to reduce unwanted background detection.

Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial).

PubMed

Ballard, Clive; Brown, Richard; Fossey, Jane; Douglas, Simon; Bradley, Paul; Hancock, Judith; James, Ian A; Juszczak, Edmund; Bentham, Peter; Burns, Alistair; Lindesay, James; Jacoby, Robin; O'Brien, John; Bullock, Roger; Johnson, Tony; Holmes, Clive; Howard, Robert

2009-09-01

Good practice guidelines state that a psychological intervention should usually precede pharmacotherapy, but there are no data evaluating the feasibility of psychological interventions used in this way. At the first stage of a randomized blinded placebo-controlled trial, 318 patients with Alzheimer disease (AD) with clinically significant agitated behavior were treated in an open design with a psychological intervention (brief psychosocial therapy [BPST]) for 4 weeks, preceding randomization to pharmacotherapy. The therapy involved social interaction, personalized music, or removal of environmental triggers. Overall, 318 patients with AD completed BPST with an improvement of 5.6 points on the total Cohen-Mansfield Agitation Inventory (CMAI; mean [SD], 63.3 [16.0] to 57.7 [18.4], t = 4.8, df = 317, p < 0.0001). Therapy worksheets were completed in six of the eight centers, with the key elements of the intervention delivered according to the manual for >95% of patients. More detailed evaluation of outcome was completed for the 198 patients with AD from these centers, who experienced a mean improvement of 6.6 points on the total CMAI (mean [SD], 62.2 [14.3] to 55.6 [15.8], t = 6.5, df = 197, p < 0.0001). Overall, 43% of participants achieved a 30% improvement in their level of agitation. The specific attributable benefits of BPST cannot be determined from an open trial. However, the BPST therapy was feasible and was successfully delivered according to an operationalized manual. The encouraging outcome indicates the need for a randomized controlled trial of BPST.

The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

PubMed

Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

2014-04-01

Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values <10 g/dL without an increase of ≥ 0.5 g/dL). The background, rationale and study design of the trial are presented here. The study has been completed and results are expected in late 2013. FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

Effectiveness of myofascial trigger point manual therapy combined with a self-stretching protocol for the management of plantar heel pain: a randomized controlled trial.

PubMed

Renan-Ordine, Rômulo; Alburquerque-Sendín, Francisco; de Souza, Daiana Priscila Rodrigues; Cleland, Joshua A; Fernández-de-Las-Peñas, César

2011-02-01

A randomized controlled clinical trial. To investigate the effects of trigger point (TrP) manual therapy combined with a self-stretching program for the management of patients with plantar heel pain. Previous studies have reported that stretching of the calf musculature and the plantar fascia are effective management strategies for plantar heel pain. However, it is not known if the inclusion of soft tissue therapy can further improve the outcomes in this population. Sixty patients, 15 men and 45 women (mean ± SD age, 44 ± 10 years) with a clinical diagnosis of plantar heel pain were randomly divided into 2 groups: a self-stretching (Str) group who received a stretching protocol, and a self-stretching and soft tissue TrP manual therapy (Str-ST) group who received TrP manual interventions (TrP pressure release and neuromuscular approach) in addition to the same self-stretching protocol. The primary outcomes were physical function and bodily pain domains of the quality of life SF-36 questionnaire. Additionally, pressure pain thresholds (PPT) were assessed over the affected gastrocnemii and soleus muscles, and over the calcaneus, by an assessor blinded to the treatment allocation. Outcomes of interest were captured at baseline and at a 1-month follow-up (end of treatment period). Mixed-model ANOVAs were used to examine the effects of the interventions on each outcome, with group as the between-subjects variable and time as the within-subjects variable. The primary analysis was the group-by-time interaction. The 2 × 2 mixed-model analysis of variance (ANOVA) revealed a significant group-by-time interaction for the main outcomes of the study: physical function (P = .001) and bodily pain (P = .005); patients receiving a combination of self-stretching and TrP tissue intervention experienced a greater improvement in physical function and a greater reduction in pain, as compared to those receiving the self-stretching protocol. The mixed ANOVA also revealed significant group-by-time interactions for changes in PPT over the gastrocnemii and soleus muscles, and the calcaneus (all P<.001). Patients receiving a combination of self-stretching and TrP tissue intervention showed a greater improvement in PPT, as compared to those who received only the self-stretching protocol. This study provides evidence that the addition of TrP manual therapies to a self-stretching protocol resulted in superior short-term outcomes as compared to a self-stretching program alone in the treatment of patients with plantar heel pain. Therapy, level 1b.

Comparison between newer local anesthetics for myofascial pain syndrome management.

PubMed

Zaralidou, A Th; Amaniti, E N; Maidatsi, P G; Gorgias, N K; Vasilakos, D F

2007-06-01

Myofascial pain syndromes are characterized by the presence of painful loci within muscles, tendons or ligaments, called trigger points. Infiltration of these points with local anesthetics is often used as a treatment modality. The aim of the study was to comparatively evaluate 0.25% levobupivacaine and 0.25% ropivacaine for trigger point injection regarding pain on injection, treatment efficacy and duration of symptoms remission. Sixty-eight patients, suffering from myofascial pain syndromes, were randomly assigned to two groups to receive either levobupivacaine or ropivacaine for trigger-point injection. After completion of the procedure, patients were asked to rate pain during injection and efficacy of the treatment, based on immediate relief. Two weeks later, they were asked about the duration of this relief. Statistical analysis did not reveal significant differences between groups with respect to pain during injection, efficacy of the treatment and duration of pain relief. The two local anesthetics seem to be equally effective for trigger point infiltration. (c) 2007 Prous Science. All rights reserved.

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy.

PubMed

Lin, Han; Chen, Yu; Shi, Jianlin

2018-03-21

Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient methodology for benefiting personalized biomedicine in combating cancer.

Botulinum Toxin for the Treatment of Myofascial Pain Syndromes Involving the Neck and Back: A Review from a Clinical Perspective

PubMed Central

Climent, José M.; Fenollosa, Pedro; Martin-del-Rosario, Francisco

2013-01-01

Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP) is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies. PMID:23533477

Reinvestigation of the dysfunction in neck and shoulder girdle muscles as the reason of cervicogenic headache among office workers.

PubMed

Huber, Juliusz; Lisiński, Przemysław; Polowczyk, Agnieszka

2013-05-01

Dysfunction of cervical and shoulder girdle muscles as reason of cervicogenic headache (CEH) was reinvestigated with clinical and neurophysiological studies. Forty office workers were randomized into two groups to verify efficiency of supervised kinesiotherapy (N = 20) aimed with improvement of muscle's activity and headache symptoms releasing. Headache intensity was evaluated with visual analog scale (VAS), range of cervical movement (ROM) with goniometer, trigger points (TrPs) incidence with palpation and muscle's strength with Lovett's scale. Reaction of patients for muscle's elongation was also evaluated. Surface electromyographical recordings were bilaterally analyzed at rest (rEMG) and during maximal contraction (mcEMG). Deficits of cervical flexion and muscles strength were found in all patients. TrPs occurred predominantly in painful trapezius muscle. Incidence of trigger points coexisted with intensity of CEH. Results indicated on muscles dysfunction which improved only after supervised therapy. Positive correlations between increase in rEMG amplitudes and high VAS scores, high-amplitude rEMG recordings incidence and increased number of TrPs were found. Negative correlation was detected between amplitude in mcEMG and amplitude of rEMG recordings. Dysfunction of trapezius muscle was most responsible for CEH etiology. Proposed algorithm of kinesiotherapy was effective as complementary method of the CEH patients treatment.

Construction of near-infrared light-triggered reactive oxygen species-sensitive (UCN/SiO2-RB + DOX)@PPADT nanoparticles for simultaneous chemotherapy and photodynamic therapy

NASA Astrophysics Data System (ADS)

Zhou, Fang; Zheng, Bin; Zhang, Ying; Wu, Yudong; Wang, Hanjie; Chang, Jin

2016-06-01

Combined therapy now plays a major role in cancer therapy due to the outcome of huge amounts of scientific experiments in recent years. However, all systems designed previously have been unable to simultaneously deliver therapy effects using several methods to produce a greater overall therapeutic effect. To solve the problem, we constructed a delivery system of near-infrared light (NIR)-triggered reactive oxygen species (ROS)-sensitive nanoparticles (NPs) for simultaneous chemotherapy and photodynamic therapy (PDT). The inner NP was assembled from a hydrophobic upconverting nanoparticle (UCN) core, with a thin silica shell linked with rose bengal (RB). Finally, a type of ROS-induced biodegradable polymer named poly-(1, 4-phenyleneacetone dimethylenethioketal) (PPADT) was self-assembled to form the NP as an outer shell to load the inner NP and doxorubicin (DOX). As the results show, the UCN core works as a transducer to convert deeply penetrating NIR to visible light for activating the photosensitizer RB for PDT under NIR excitation. In the meantime, the redundant ROS caused PPADT to biodegrade to release the loaded DOX, realizing simultaneous chemotherapy and PDT. Properties such as structure, size distribution, morphology, Fourier transform infrared spectroscopy, ROS production test, cell uptake test and combined therapy treatment effect in vitro were evaluated to prove NIR triggered ROS-sensitive (UCN/SiO2-RB + DOX)@PPADT NPs. Based on our data, this delivery system could provide an effective means to realize simultaneous chemotherapy and PDT through external NIR-triggered ROS sensitivity.

Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

PubMed

Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

2018-05-09

Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Myofascial pain syndrome--frequent occurrence and often misdiagnosed].

PubMed

Pongratz, D E; Späth, M

1998-09-30

Myofascial pain syndrome (MPS) is a very common localized--sometimes also polytopic--painful musculoskeletal condition associated with trigger points, for which, however, diagnostic criteria established in well-designed studies are still lacking. These two facts form the basis for differentiating between MPS and the fibromyalgia syndrome. The difference between trigger points (MPS) and tender points (fibromyalgia) is of central importance--not merely in a linguistic sense. A knowledge of the signs and symptoms typically associated with a trigger point often obviates the need for time-consuming and expensive technical diagnostic measures. The assumption that many cases of unspecific complaints affecting the musculoskeletal system may be ascribed to MPS makes clear the scope for the saving of costs.

Temporomandibular disorders. Part 2: conservative management

PubMed Central

Shaffer, Stephen M; Brismée, Jean-Michel; Sizer, Phillip S; Courtney, Carol A

2014-01-01

Appropriate management of temporomandibular disorders (TMD) requires an understanding of the underlying dysfunction associated with the temporomandibular joint (TMJ) and surrounding structures. A comprehensive examination process, as described in part 1 of this series, can reveal underlying clinical findings that assist in the delivery of comprehensive physical therapy services for patients with TMD. Part 2 of this series focuses on management strategies for TMD. Physical therapy is the preferred conservative management approach for TMD. Physical therapists are professionally well-positioned to step into the void and provide clinical services for patients with TMD. Clinicians should utilize examination findings to design rehabilitation programs that focus on addressing patient-specific impairments. Potentially appropriate plan of care components include joint and soft tissue mobilization, trigger point dry needling, friction massage, therapeutic exercise, patient education, modalities, and outside referral. Management options should address both symptom reduction and oral function. Satisfactory results can often be achieved when management focuses on patient-specific clinical variables. PMID:24976744

Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huai, Lei; Wang, Cuicui; Zhang, Cuiping

2012-06-08

Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acutemore » promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.« less

The relationship between latent trigger points and depression levels in healthy subjects.

PubMed

Celik, Derya; Kaya Mutlu, Ebru

2012-06-01

Our purpose was to study the relationship between latent trigger points (LTrP) and levels of depression in healthy subjects. A total of 76 healthy subjects consisting of 40 men and 36 women (mean age, 25.4 ± 4.8 years; age range, 19-42 years) from the School of Physical Therapy and Rehabilitation and the Orthopaedics and Traumatology Department of Istanbul University Medical Faculty were selected for the study. Latent trigger points on the scapular muscles of each subject were evaluated. The upper and middle trapezius, supraspinatus, serratus anterior, and rhomboideus muscles were examined respectively, by palpation with the thumb, to determine whether there was pain. The first group consisted of 30 subjects (20 men and 10 women; mean age, 24.2 ± 5.02 years) who had previously been diagnosed as negative after an LTrP examination (control group), while the second group consisted of 28 subjects (12 men and 16 women; mean age, 23.6 ± 2.24 years) who had been diagnosed with at least five LTrPs. The third group consisted of 18 subjects (8 men and 10 women; mean age, 26. 9 ± 7.23 years) who had been diagnosed with more than five LTrPs. All groups were assessed, using the Beck Depression Inventory (BDI). The mean BDI value was found to be 8.0 ± 4.2 in the first group, 10.3 ± 3.4 in the second, and 28.5 ± 4.8 in the third. A significant difference was found between the mean BDI values of the first and second groups and also between the first and third groups. The mean BDI values of the second and third groups were also found to be statistically significant (p = 0.042). We observed a close relationship between the presence of LTrPs and depression levels in healthy people.

Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: A controlled clinical trial

PubMed Central

Bablis, Peter; Pollard, Henry; Bonello, Rod

2008-01-01

Background Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Methods Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. Results The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P < 0.001). Conclusion After a short course of NET treatment, measurements of visual analog scale and pressure algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when compared to a control group which received a sham protocol of NET. Chronic neck pain sufferers may benefit from NET treatment in the relief of trigger point sensitivity. Further research including long-term randomised controlled trials for the effect of NET on chronic neck pain, and other chronic pain syndromes are recommended. Trial Registration This trial has been registered and allocated the Australian Clinical Trials Registry (ACTR) number ACTRN012607000358448. The ACTR has met the requirements of the ICMJE's trials registration policy and is an ICMJE acceptable registry. PMID:18495042

HSA/PSS coated gold nanorods as thermo-triggered drug delivery vehicles for combined cancer photothermal therapy and chemotherapy

NASA Astrophysics Data System (ADS)

Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: a randomized controlled trial [ISRCTN75722066].

PubMed

Bron, Carel; Wensing, Michel; Franssen, Jo Lm; Oostendorp, Rob Ab

2007-11-05

Shoulder disorders are a common health problem in western societies. Several treatment protocols have been developed for the clinical management of persons with shoulder pain. However available evidence does not support any protocol as being superior over others. Systematic reviews provide some evidence that certain physical therapy interventions (i.e. supervised exercises and mobilisation) are effective in particular shoulder disorders (i.e. rotator cuff disorders, mixed shoulder disorders and adhesive capsulitis), but there is an ongoing need for high quality trials of physical therapy interventions. Usually, physical therapy consists of active exercises intended to strengthen the shoulder muscles as stabilizers of the glenohumeral joint or perform mobilisations to improve restricted mobility of the glenohumeral or adjacent joints (shoulder girdle). It is generally accepted that a-traumatic shoulder problems are the result of impingement of the subacromial structures, such as the bursa or rotator cuff tendons. Myofascial trigger points (MTrPs) in shoulder muscles may also lead to a complex of symptoms that are often seen in patients diagnosed with subacromial impingement or rotator cuff tendinopathy. Little is known about the treatment of MTrPs in patients with shoulder disorders.The primary aim of this study is to investigate whether physical therapy modalities to inactivate MTrPs can reduce symptoms and improve shoulder function in daily activities in a population of chronic a-traumatic shoulder patients when compared to a wait-and-see strategy. In addition we investigate the recurrence rate during a one-year-follow-up period. This paper presents the design for a randomized controlled trial to be conducted between September 2007 - September 2008, evaluating the effectiveness of a physical therapy treatment for non-traumatic shoulder complaints. One hundred subjects are included in this study. All subjects have unilateral shoulder pain for at least six months and are referred to a physical therapy practice specialized in musculoskeletal disorders of the neck-, shoulder-, and arm. After the initial assessment patients are randomly assigned to either an intervention group or a control-group (wait and see). The primary outcome measure is the overall score of the Dutch language version of the DASH (Disabilities of Arm, Shoulder and Hand) questionnaire. Since there is only little evidence for the efficacy of physical therapy interventions in certain shoulder disorders, there is a need for further research. We found only a few studies examining the efficacy of MTrP therapy for shoulder disorders. Therefore we will perform a randomised clinical trial of the effect of physical therapy interventions aimed to inactivate MTrPs, on pain and impairment in shoulder function in a population of chronic a-traumatic shoulder patients. We opted for an intervention strategy that best reflects daily practice. Manual high velocity thrust techniques and dry-needling are excluded. Because in most physical therapy interventions, blinding of the patient and the therapist is not possible, we will perform a randomised, controlled and observer-blinded study. This randomized clinical trial is registered at current controlled trials ISRCTN75722066.

“We make choices we think are going to save us”: Debate and stance identification for online breast cancer CAM discussions

PubMed Central

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-01-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients’ conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients’ stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members’ stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients’ opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work. PMID:28967000

"We make choices we think are going to save us": Debate and stance identification for online breast cancer CAM discussions.

PubMed

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-04-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients' conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients' stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members' stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients' opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work.

Inhibition of the checkpoint protein PD-1 by the therapeutic antibody pembrolizumab outlined by quantum chemistry.

PubMed

Tavares, Ana Beatriz M L A; Lima Neto, José X; Fulco, Umberto L; Albuquerque, Eudenilson L

2018-01-30

Much of the recent excitement in the cancer immunotherapy approach has been generated by the recognition that immune checkpoint proteins, like the receptor PD-1, can be blocked by antibody-based drugs with profound effects. Promising clinical data have already been released pointing to the efficiency of the drug pembrolizumab to block the PD-1 pathway, triggering the T-lymphocytes to destroy the cancer cells. Thus, a deep understanding of this drug/receptor complex is essential for the improvement of new drugs targeting the protein PD-1. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT), we investigate in silico the binding energy features of the receptor PD-1 in complex with its drug inhibitor. Our computational results give a better understanding of the binding mechanisms, being also an efficient alternative towards the development of antibody-based drugs, pointing to new treatments for cancer therapy.

Synergy effects of combined multichannel EMG-triggered electrical stimulation and mirror therapy in subacute stroke patients with severe or very severe arm/hand paresis.

PubMed

Schick, Thomas; Schlake, Hans-Peter; Kallusky, Juliane; Hohlfeld, Günter; Steinmetz, Maria; Tripp, Florian; Krakow, Karsten; Pinter, Michaela; Dohle, Christian

2017-01-01

Neurorehabilitation requires the development of severity-dependent and successful therapies for arm/hand rehabilitation in stroke patients. To evaluate the effectiveness of adding mirror therapy to bilateral EMG-triggered multi-channel electrostimulation for the treatment of severe arm/hand paresis in stroke patients. The subjects of this randomized, controlled, multicentre study were stroke patients who had suffered their first insult between 1 and 6 months before study start and had severe or very severe arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly allocated to an intervention group (n = 16) or control group (n = 17). Both groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG-triggered multi-channel electrostimulation. The intervention group additionally received mirror feedback of the unaffected limb. The primary outcome measure was motor recovery of the upper extremities, as measured by the Fugl-Meyer Assessment. The Intervention Group with very severe paresis had significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at a medium effect size (Cohen) of d = 0.7, due to a significant recovery of shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A subtest. For subjects with severe paresis, additional mirror therapy did not significantly influence outcome. Additional mirror therapy in combination with EMG-triggered multi-channel electrostimulation is therapeutically beneficial for post-acute stroke patients with very severe arm/hand paresis.

ELECTRONIC TRIGGER CIRCUIT

DOEpatents

Russell, J.A.G.

1958-01-01

An electronic trigger circuit is described of the type where an output pulse is obtained only after an input voltage has cqualed or exceeded a selected reference voltage. In general, the invention comprises a source of direct current reference voltage in series with an impedance and a diode rectifying element. An input pulse of preselected amplitude causes the diode to conduct and develop a signal across the impedance. The signal is delivered to an amplifier where an output pulse is produced and part of the output is fed back in a positive manner to the diode so that the amplifier produces a steep wave front trigger pulsc at the output. The trigger point of the described circuit is not subject to variation due to the aging, etc., of multi-electrode tabes, since the diode circuit essentially determines the trigger point.

Injection therapy for subacute and chronic low back pain: an updated Cochrane review.

PubMed

Staal, J Bart; de Bie, Rob A; de Vet, Henrica C W; Hildebrandt, Jan; Nelemans, Patty

2009-01-01

A systematic review of randomized controlled trials (RCTs). To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low back pain. The effectiveness of injection therapy for low back pain is still debatable. Heterogeneity of target tissue, pharmacological agent, and dosage, generally found in RCTs, point to the need for clinically valid comparisons in a literature synthesis. We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases up to March 2007 for relevant trials reported in English, French, German, Dutch, and Nordic languages. We also screened references from trials identified. RCTs on the effects of injection therapy involving epidural, facet, or local sites for subacute or chronic low back pain were included. Studies that compared the effects of intradiscal injections, prolotherapy, or ozone therapy with other treatments were excluded unless injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded. Eighteen trials (1179 participants) were included in this review. The injection sites varied from epidural sites and facet joints (i.e. intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender-and trigger points). The drugs that were studied consisted of corticosteroids, local anesthetics, and a variety of other drugs. The methodologic quality of the trials was limited with 10 of 18 trials rated as having a high methodologic quality. Statistical pooling was not possible because of clinical heterogeneity in the trials. Overall, the results indicated that there is no strong evidence for or against the use of any type of injection therapy. There is insufficient evidence to support the use of injection therapy in subacute and chronic low-back pain. However, it cannot be ruled out that specific subgroups of patients may respond to a specific type of injection therapy.

Management of Myofascial Pain of Upper Trapezius: A Three Group Comparison Study

PubMed Central

Kannan, Priya

2012-01-01

It is important to identify the most effective therapeutic modality in the management of myofascial trigger points (MTPt). Thus we aimed to study the effect of therapeutic ultrasound, laser and ischemic compression in reducing pain and improving cervical range of motion among patients with MTPt. Experimental study comparing three groups was designed as a 5 days trial, a co-relational design was considered. Outcome measures: VAS for pain, provocative pain test using “soft tissue tenderness grading scheme” and active cervical lateral flexion using inch tape. Methods- Patients were divided into 3 groups, Gr 1 underwent treatment using therapeutic ultrasound, Gr 2 with therapeutic laserand Gr 3 with ischemic compression. Assessments were done on day 1 and day 5 of treatment respectively. Results: ANOVA revealed improvement among all 3 groups as statistically significant difference (p<0.05) between the start and end of trial. Analysis using Chi square test shows a statistically significant difference in the improvement between laser and the other 2 groups. Mean difference in the change of scores between the assessments showed laser therapy to have a tendency towards progressive improvement over the treatment period and a better improvement than the other 2 groups. Weconclude that laser can be used as an effective treatment regimen in the management of myofascial trigger points thereby reducing disability caused due to musculoskeletal pathology. PMID:22980377

Inhibiting the Epidermal Growth Factor Receptor | Center for Cancer Research

Cancer.gov

The Epidermal Growth Factor Receptor (EGFR) is a widely distributed cell surface receptor that responds to several extracellular signaling molecules through an intracellular tyrosine kinase, which phosphorylates target enzymes to trigger a downstream molecular cascade. Since the discovery that EGFR mutations and amplifications are critical in a number of cancers, efforts have been under way to develop and use targeted EGFR inhibitors. These efforts have met with some spectacular successes, but many patients have not responded as expected, have subsequently developed drug-resistant tumors, or have suffered serious side effects from the therapies to date. CCR Investigators are studying EGFR from multiple vantage points with the goal of developing even better strategies to defeat EGFR-related cancers.

Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction.

PubMed

de Haan, Judy B; Cooper, Mark E

2011-01-01

Although intensive glycaemic and blood pressure control have reduced the risks of micro- and macrovascular complications, diabetes remains a major cause of cardiovascular events, end-stage renal failure, blindness and neuropathy. It is therefore imperative to understand the underlying mechanisms and to establish effective treatments to prevent, retard or reverse diabetic complications. One area of increased focus is the diabetic vascular endothelium. Hyperglycaemia triggers a cascade of events, not least an increase in reactive oxygen species (ROS) leading to enhanced oxidative stress, with its negative impact on endothelial function. In this review, we explore a unifying hypothesis that increased glucose-mediated ROS leads to endothelial dysfunction as the underpinning causative event triggering accelerated micro- and macrovascular complications. In particular, the consequences of deficiencies in the antioxidant enzyme, glutathione peroxidase, on endothelial dysfunction as a trigger of diabetic micro- and macrovascular complications, will be reviewed. Furthermore, novel antioxidant therapies will be highlighted. Specifically, use of Gpx1-mimetics holds promise as a targeted antioxidant approach and an alternative adjunct therapy to reduce diabetic complications.

SiC/Si diode trigger circuit provides automatic range switching for log amplifier

NASA Technical Reports Server (NTRS)

1967-01-01

SiC/Si diode pair provides automatic range change to extend the operating range of a logarithmic amplifier-conversion circuit and assures stability at or near the range switch-over point. the diode provides hysteresis for a trigger circuit that actuates a relay at the desired range extension point.

Applying threshold concepts to conservation management of dryland ecosystems: Case studies on the Colorado Plateau

USGS Publications Warehouse

Bowker, Matthew A.; Miller, Mark E.; Garman, Steven L.; Belote, Travis; Guntenspergen, Glenn R.

2014-01-01

Ecosystems may occupy functionally distinct alternative states, some of which are more or less desirable from a management standpoint. Transitions from state to state are usually associated with a particular trigger or sequence of triggers, such as the addition or subtraction of a disturbance. Transitions are often not linear, rather it is common to see an abrupt transition come about even though the trigger increases only incrementally; these are examples of threshold behaviors. An ideal monitoring program, such as the National Park Service’s Inventory and Monitoring Program, would quantify triggers, and be able to inform managers when measurements of a trigger are approaching a threshold so that management action can avoid an unwanted state transition. Unfortunately, both triggers and the threshold points at which state transitions occur are generally only partially known. Using case studies, we advance a general procedure to help identify triggers and estimate where threshold dynamics may occur. Our procedure is as follows: (1) Operationally define the ecosystem type being considered; we suggest that the ecological site concept of the Natural Resource Conservation Service is a useful system, (2) Using all available a priori knowledge to develop a state-and-transition model (STM), which defines possible ecosystem states, plausible transitions among them and likely triggers, (3) Validate the STM by verifying the existence of its states to the greatest degree possible, (4) Use the STM model to identify transitions and triggers likely to be detectable by a monitoring program, and estimate to the greatest degree possible the value of a measurable indicator of a trigger at the point that a state transition is imminent (tipping point), and values that may indicate when management intervention should be considered (assessment points). We illustrate two different methods for attaining these goals using a data-rich case study in Canyonlands National Park, and a data-poor case study in Wupatki National Monument. In the data-rich case, STMs are validated and revised, and tipping and assessment points are estimated using statistical analysis of data. In the data-poor case, we develop an iterative expert opinion survey approach to validate the degree of confidence in an STM, revise the model, identify lack of confidence in specific model components, and create reasonable first approximations of tipping and assessment points, which can later be refined when more data are available. Our goal should be to develop the best set of models possible given the level of information available to support decisions, which is often not much. The approach presented here offers a flexible means of achieving this goal, and determining specific research areas in need of study.

Neutrophil cell surface receptors and their intracellular signal transduction pathways☆

PubMed Central

Futosi, Krisztina; Fodor, Szabina; Mócsai, Attila

2013-01-01

Neutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2 + signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases. PMID:23994464

Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.

PubMed

Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp

2017-09-25

Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

Friction massage versus kinesiotaping for short-term management of latent trigger points in the upper trapezius: a randomized controlled trial.

PubMed

Mohamadi, Marzieh; Piroozi, Soraya; Rashidi, Iman; Hosseinifard, Saeed

2017-01-01

Latent trigger points in the upper trapezius muscle may disrupt muscle movement patterns and cause problems such as cramping and decreased muscle strength. Because latent trigger points may spontaneously become active trigger points, they should be addressed and treated to prevent further problems. In this study we compared the short-term effect of kinesiotaping versus friction massage on latent trigger points in the upper trapezius muscle. Fifty-eight male students enrolled with a stratified sampling method participated in this single-blind randomized clinical trial (Registration ID: IRCT2016080126674N3) in 2016. Pressure pain threshold was recorded with a pressure algometer and grip strength was recorded with a Collin dynamometer. The participants were randomly assigned to two different treatment groups: kinesiotape or friction massage. Friction massage was performed daily for 3 sessions and kinesiotape was used for 72 h. One hour after the last session of friction massage or removal of the kinesiotape, pressure pain threshold and grip strength were evaluated again. Pressure pain threshold decreased significantly after both friction massage (2.66 ± 0.89 to 2.25 ± 0.76; P  = 0.02) and kinesiotaping (2.00 ± 0.74 to 1.71 ± 0.65; P  = 0.01). Grip strength increased significantly after friction massage (40.78 ± 9.55 to 42.17 ± 10.68; P  = 0.03); however there was no significant change in the kinesiotape group (39.72 ± 6.42 to 40.65 ± 7.3; P  = 0.197). There were no significant differences in pressure pain threshold (2.10 ± 0.11 & 1.87 ± 0.11; P  = 0.66) or grip strength (42.17 ± 10.68 & 40.65 ± 7.3; P  = 0.53) between the two study groups. Friction massage and kinesiotaping had identical short-term effects on latent trigger points in the upper trapezius. Three sessions of either of these two interventions did not improve latent trigger points. Registration ID in IRCT: IRCT2016080126674N3.

Probable Mechanisms of Needling Therapies for Myofascial Pain Control

PubMed Central

Chou, Li-Wei; Kao, Mu-Jung; Lin, Jaung-Geng

2012-01-01

Myofascial pain syndrome (MPS) has been defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs) clinically. MTrP is defined as the hyperirritable spot in a palpable taut band of skeletal muscle fibers. Appropriate treatment to MTrPs can effectively relieve the clinical pain of MPS. Needling therapies, such as MTrP injection, dry needling, or acupuncture (AcP) can effectively eliminate pain immediately. AcP is probably the first reported technique in treating MPS patients with dry needling based on the Traditional Chinese Medicine (TCM) theory. The possible mechanism of AcP analgesia were studied and published in recent decades. The analgesic effect of AcP is hypothesized to be related to immune, hormonal, and nervous systems. Compared to slow-acting hormonal system, nervous system acts in a faster manner. Given these complexities, AcP analgesia cannot be explained by any single mechanism. There are several principles for selection of acupoints based on the TCM principles: “Ah-Shi” point, proximal or remote acupoints on the meridian, and extra-meridian acupoints. Correlations between acupoints and MTrPs are discussed. Some clinical and animal studies of remote AcP for MTrPs and the possible mechanisms of remote effectiveness are reviewed and discussed. PMID:23346211

Three reasons for on-line remote telemonitoring of patients treated with high doses of radionuclide therapy. Our experience.

PubMed

Matovic, Milovan; Jeremic, Marija; Urosevic, Vlade; Ravlic, Miroslav; Vlajkovic, Marina

2015-01-01

Following radionuclide therapy, patients usually must remain hospitalised in special "restricted access area" 2-5 days, until radiation in their body drops below a certain level. During this period medical personnel can be faced with some challenges. Based on our previous experience, we used telemedicine approach as solution for it. We have developed comprehensive telemedicine system, which consists of three own developed hardware & software modules which are accessible remotely. Challenge #1 Some of patients can experiencing serious complications related to radionuclide therapy or related to co-morbidities, if they have any of it. In some of those cases audio-visual contact with patients and follow-up their vital functions can be of high importance in case of patient needs urgent intervention. Solution #1 System for on-line remote monitoring of patients' vital functions registered with bed side monitor and video surveillance of area which use patients during hospitalisation. This system is established by IP cameras and bedside patient monitor, equipped with appropriate network card and software. Using remote connection (LAN or internet), a physician can watch at personal computer or mobile phone the waves and vital signs patterns from the bedside monitor, as well as live video from surveillance cameras. It provides prompt intervention in case of emergency. Challenge #2 Having in mind the overall costs of radionuclide therapy and patients hospital stay on the one hand, and limited capacity of the hospital premises for radionuclide therapy, on the other, it is of high importance to estimate as early as possible the time period after which the radiation in a patient's body will drop below the limit imposed by the law. Solution #2 On-line remote radiation monitoring system, which measures the radiation exposure rate by means of a pancake probe, which is connected to a PTZ (Pan-tilt-zoom) device and DVR (Digital video recorder). Those devices enable precise positioning of the detector on target region of the patient's body. The positioning of the detector can be visually controlled by a micro camera, placed at the center of detector's plane. Furthermore, there are three LASER pointers placed around the detector in order to mark the area where it is directed. In addition, two ultrasound sensors placed on the edge of the detector holder in order to estimate the exact distance between the probe and the patient's body. All those devices are controlled by the DVR. The data collected by the detector are acquired and processed by a PC, using customized hardware/software system developed by Italian ThereminoR group. Using remote connection, a physician can watch on-line radiation exposure rate in any time and can use commands of PTZ and DVR device for proper positioning of probe during measurement and control it by micro camera, LASER pointers and US sensors. Physician demands from the patients to take the same position for 5 minutes on each hour, during first 10 hours. Those data we use as reference points for further processing by our software. Based on two exponential matematical model, our software estimates the whole process of elimination of radioactivity from the patient's body, using reference points collected during the first day after radionuclide therapy. Based on that, physician can predict (on first day after therapy!) when patient will be able to leave the restricted access area". Challenge #3 Despite strict instructions given to them by physician and nurse before administration of radionuclide therapy, some patients sometimes try to leave "restricted access area". Solution #3 We have developed a system which continuously monitors the corridor which a patient must use in case of an attempt to leave the "restricted access area". Our system consists of a survey meter equipped with pancake probe directed towards the corridor. The survey meter is connected to a trigger circuit which gives signal in the case when the measeured count rate exceeds previously adjusted value. Trigger circuit is connected to the programmable siren, blinking light, alarm device unit with SIM card and IP surveillance camera. On the siren we previously recorded the voice alarm. In the case when the system is triggered, the patient will hear warning message and see blinking light. When the alarm device is triggered it will call responsible physician and nurse on mobile phone and IP camera simultaneously records this event. System also sending via email appropriate data about each event, when it happens. From our experience gained over the past 4 years, our telemonitoring system dedicated for patients receiving radionuclide therapy ensures a high level of safety for the patient and medical staff.

Ischemic compression and joint mobilisation for the treatment of nonspecific myofascial foot pain: findings from two quasi-experimental before-and-after studies.

PubMed

Hains, Guy; Boucher, Pierre B; Lamy, Anne-Marie

2015-03-01

The aim of this study was to evaluate the efficacy of myofascial therapy involving ischemic compression on trigger points in combination with mobilization therapy on patients with chronic nonspecific foot pain. Two quasi-experimental before-and-after studies involving two different baseline states. Foot pain patients at a private clinic were divided into two separate cohorts: A, custom orthotic users; and B, non-users. In Study A, 31 users received 15 experimental treatments consisting of ischemic compressions on trigger points and mobilization of articulations through the foot immediately after study enrollment. In study B, ten non-users were prescribed a soft prefabricated insole and were monitored for five weeks before subsequently receiving 15 experimental treatments after the initial five-week delay. The Foot Function Index (FFI) and patients' perceived improvement score (PIS) on a scale from 0% to 100%. The Study A group (n=31) maintained a significant reduction in the FFI at all three follow-up evaluations. Mean improvement from baseline in FFI was 47%, 49% and 56% at 0, 1 and 6 months, respectively, post-treatment. Mean PIS was 58%, 57%, and 58%, again at 0, 1 and 6 months post-treatment. For the Study B group, mean improvement in FFI was only 19% after the monitoring period, and 64% after the experimental treatment period. Mean PIS was 31% after monitoring, and 78% after experimental treatment. In repeated measures analyses, experimental treatment was associated with a significant main effect in both of these before-and after studies (all P values<0.01). Combined treatment involving ischemic compression and joint mobilization for chronic foot pain is associated with significant improvements in functional and self-perceived improvement immediately and at up to six-months post-treatment. Further validation of this treatment approach within a randomized controlled trial is needed.

Targeting myofascial taut bands by ultrasound.

PubMed

Thomas, Kisha; Shankar, Hariharan

2013-07-01

Myofascial pain syndrome (MPS) is a frequent diagnosis in chronic pain and is characterized by tender, taut bands known as trigger points. The trigger points are painful areas in skeletal muscle that are associated with a palpable nodule within a taut band of muscle fibers. Despite the prevalence of myofascial pain syndrome, diagnosis is based on clinical criteria alone. A growing body of evidence that suggests that taut bands are readily visualized under ultrasound-guided exam, especially when results are correlated with elastography, multidimensional imaging, and physical exam findings such as local twitch response. The actual image characteristic in B mode appears to be controversial. Ultrasonography provides an objective modality to assist with diagnosis and treatment of trigger points in the future.

Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

NASA Astrophysics Data System (ADS)

Li, Zebin; Li, Ting

2018-02-01

Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

Mechanisms of chronic pain - key considerations for appropriate physical therapy management.

PubMed

Courtney, Carol A; Fernández-de-Las-Peñas, César; Bond, Samantha

2017-07-01

In last decades, knowledge of nociceptive pain mechanisms has expanded rapidly. The use of quantitative sensory testing has provided evidence that peripheral and central sensitization mechanisms play a relevant role in localized and widespread chronic pain syndromes. In fact, almost any patient suffering with a chronic pain condition will demonstrate impairments in the central nervous system. In addition, it is accepted that pain is associated with different types of trigger factors including social, physiological, and psychological. This rational has provoked a change in the understanding of potential mechanisms of manual therapies, changing from a biomechanical/medical viewpoint, to a neurophysiological/nociceptive viewpoint. Therefore, interventions for patients with chronic pain should be applied based on current knowledge of nociceptive mechanisms since determining potential drivers of the sensitization process is critical for effective management. The current paper reviews mechanisms of chronic pain from a clinical and neurophysiological point of view and summarizes key messages for clinicians for proper management of individuals with chronic pain.

A dangerous method? The German discourse on hypnotic suggestion therapy around 1900

PubMed Central

Maehle, Andreas-Holger

2017-01-01

In the late nineteenth century, German-speaking physicians and psychiatrists intensely debated the benefits and risks of treatment by hypnotic suggestion. While practitioners of the method sought to provide convincing evidence for its therapeutic efficacy in many medical conditions, especially nervous disorders, critics pointed to dangerous side effects, including the triggering of hysterical attacks or deterioration of nervous symptoms. Other critics claimed that patients merely simulated hypnotic phenomena in order to appease their therapist. A widespread concern was the potential for abuses of hypnosis, either by giving criminal suggestions or in the form of sexual assaults on hypnotized patients. Official inquiries by the Prussian Minister for Religious, Educational and Medical Affairs in 1902 and 1906 indicated that relatively few doctors practised hypnotherapy, whereas the method was increasingly used by lay healers. Although the Ministry found no evidence for serious harm caused by hypnotic treatments, whether performed by doctors or by lay healers, many German doctors seem to have regarded hypnotic suggestion therapy as a problematic method and abstained from using it.

PML–RARA-RXR Oligomers Mediate Retinoid and Rexinoid/cAMP Cross-Talk in Acute Promyelocytic Leukemia Cell Differentiation

PubMed Central

Kamashev, Dmitrii; Vitoux, Dominique; de Thé, Hugues

2004-01-01

PML–RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML–RARA homodimer–triggered repression. Here, we examined the nature of the PML–RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML–RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to highly relaxed structural constrains for DNA binding and identifying a major gain of function of this oncogene. PML–RARA-specific response elements were identified, which all conveyed a major transcriptional response to RA only in APL cells. In these cells, we demonstrate that PML–RARA oligomers are complexed to RXR. Directly probing PML–RARA function in APL cells, we found that the differentiation enhancer cyclic AMP (cAMP) boosted transcriptional activation by RA. cAMP also reversed the normal silencing (subordination) of the transactivating function of RXR when bound to RARA or PML–RARA, demonstrating that the alternate rexinoid/cAMP-triggered APL differentiation pathway also activates PML–RARA targets. Finally, cAMP restored both RA-triggered differentiation and PML–RARA transcriptional activation in mutant RA-resistant APL cells. Collectively, our findings directly demonstrate that APL cell differentiation parallels transcriptional activation through PML–RARA-RXR oligomers and that those are functionally targeted by cAMP, identifying this agent as another oncogene-targeted therapy. PMID:15096541

A new NIR-triggered doxorubicin and photosensitizer indocyanine green co-delivery system for enhanced multidrug resistant cancer treatment through simultaneous chemo/photothermal/photodynamic therapy.

PubMed

Yu, Yanna; Zhang, Zhipeng; Wang, Yun; Zhu, Hao; Li, Fangzhou; Shen, Yuanyuan; Guo, Shengrong

2017-09-01

It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. This nano-sized system was constructed by filling the interior of AuNCs with DOX, ICG and 1-tetradecanol, and modifying the surface with biotinylated poly (ethylene glycol) via Au-S bonds, termed as DOX/ICG@biotin-PEG-AuNC-PCM. The DOX and ICG co-release from DOX/ICG@biotin-PEG-AuNC-PCM was much faster in PBS at 40°C or under 808nm NIR irradiation at 2.5W/cm 2 than at 37°C (e.g. 67.27% or 80.31% vs. 5.57% of DOX, 76.08% vs. 3.83% of ICG for 20min). The flow cytometry and confocal laser scanning microscopy (CLSM) results showed, the AuNCs were taken up by MCF-7/ADR cells via endocytosis, thus enhancing DOX uptake; the biotin on AuNCs facilitated this endocytosis; NIR irradiation caused the heating of the AuNCs, triggering the DOX and ICG co-release and enhancing the distribution of DOX in nuclei, the released ICG generated ROS to take photodynamic therapy. Due to the above unique properties, DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC 50 against MCF-7/ADR cells was very low, only 0.48µg/mL, much smaller than that of free DOX (74.51μg/mL). A new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, was prepared, termed as DOX/ICG@biotin-PEG-AuNC-PCM, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC 50 against MCF-7/ADR cells was very low, only 0.48µg/mL, much smaller than that of free DOX (74.51μg/mL). Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

The diet factor in pediatric and adolescent migraine.

PubMed

Millichap, J Gordon; Yee, Michelle M

2003-01-01

Diet can play an important role in the precipitation of headaches in children and adolescents with migraine. The diet factor in pediatric migraine is frequently neglected in favor of preventive drug therapy. The list of foods, beverages, and additives that trigger migraine includes cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine withdrawal, and alcoholic drinks, especially red wine and beer. Underage drinking is a significant potential cause of recurrent headache in today's adolescent patients. Tyramine, phenylethylamine, histamine, nitrites, and sulfites are involved in the mechanism of food intolerance headache. Immunoglobulin E-mediated food allergy is an infrequent cause. Dietary triggers affect phases of the migraine process by influencing release of serotonin and norepinephrine, causing vasoconstriction or vasodilatation, or by direct stimulation of trigeminal ganglia, brainstem, and cortical neuronal pathways. Treatment begins with a headache and diet diary and the selective avoidance of foods presumed to trigger attacks. A universal migraine diet with simultaneous elimination of all potential food triggers is generally not advised in practice. A well-balanced diet is encouraged, with avoidance of fasting or skipped meals. Long-term prophylactic drug therapy is appropriate only after exclusion of headache-precipitating trigger factors, including dietary factors.

Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: a randomized clinical trial.

PubMed

Mejuto-Vázquez, María J; Salom-Moreno, Jaime; Ortega-Santiago, Ricardo; Truyols-Domínguez, Sebastián; Fernández-de-Las-Peñas, César

2014-04-01

Randomized clinical trial. To determine the effects of trigger point dry needling (TrPDN) on neck pain, widespread pressure pain sensitivity, and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle. TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes. Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed. Methods Seventeen patients (53% female) were randomly assigned to 1 of 2 groups: a single session of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5-6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain intensity; and cervical spine range-of-motion data were collected at baseline (pretreatment) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient. Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable. Patients treated with 1 session of TrPDN experienced greater decreases in neck pain, greater increases in pressure pain threshold, and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention (P<.01 for all comparisons). Between-group effect sizes were medium to large immediately after the TrPDN session (standardized mean score differences greater than 0.56) and large at the 1-week follow-up (standardized mean score differences greater than 1.34). The results of the current randomized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity, and also increase active cervical range of motion, in patients with acute mechanical neck pain. Changes in pain, pressure pain threshold, and cervical range of motion surpassed their respective minimal detectable change values, supporting clinically relevant treatment effects. Level of Evidence Therapy, level 1b-.

Recognizing Myofascial Pelvic Pain in the Female Patient with Chronic Pelvic Pain

PubMed Central

Pastore, Elizabeth Anne; Katzman, Wendy B.

2012-01-01

Myofascial pelvic pain (MFPP) is a major component of chronic pelvic pain (CPP) and often is not properly identified by healthcare providers. The hallmark diagnostic indicator of MFPP is myofascial trigger points in the pelvic floor musculature that refer pain to adjacent sites. Effective treatments are available to reduce MFPP, including myofascial trigger point release, PMID:22862153

The effectiveness of manual versus algometer pressure release techniques for treating active myofascial trigger points of the upper trapezius.

PubMed

Abu Taleb, Walaa; Rehan Youssef, Aliaa; Saleh, Amir

2016-10-01

Manual pressure release (MPR) is a popular treatment of trigger points. Yet, treatment response may be influenced by inconsistent application of pressure. Further, it may contribute to increased risk of work-related musculoskeletal disorders of the wrist and hand in therapists. Therefore, this study aimed at introducing a novel method to apply pressure using the algometer and to compare its effectiveness to MPR. Forty-five volunteers with active trigger points of the upper trapezius received algometer pressure release (APR), MPR, or sham ultrasound (US). Pain pressure threshold (PPT) and contralateral active and passive neck side-bending ranges were assessed at baseline and immediately after a single session. Results showed no significant differences in post-treatment PPT between the study groups (p > 0.05). The APR group showed a significant increase in passive side-bending range compared with the two other groups, whereas active range improved in the APR compared with the US group (p < 0.05). Our results show that using algometer to apply pressure release to upper trapezius trigger points is more effective compared with manual release and sham US. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tumor-triggered drug release from calcium carbonate-encapsulated gold nanostars for near-infrared photodynamic/photothermal combination antitumor therapy.

PubMed

Liu, Yanlei; Zhi, Xiao; Yang, Meng; Zhang, Jingpu; Lin, Lingnan; Zhao, Xin; Hou, Wenxiu; Zhang, Chunlei; Zhang, Qian; Pan, Fei; Alfranca, Gabriel; Yang, Yuming; de la Fuente, Jesús M; Ni, Jian; Cui, Daxiang

2017-01-01

Different stimulus including pH, light and temperature have been used for controlled drug release to prevent drug inactivation and minimize side-effects. Herein a novel nano-platform (GNS@CaCO 3 /ICG) consisting of calcium carbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars (GNSs) and the photodynamic properties of indocyanine green (ICG) in the photodynamic/photothermal combination therapy (PDT/PTT). In this study, the calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance, but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally. The application of GNS@CaCO 3 /ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation, which was superior to the single PDT or PTT. Meanwhile, the distinct pH-triggered drug release performance of GNS@CaCO 3 /ICG implemented the tumor-targeted NIR fluorescence imaging. In addition, we monitored the bio-distribution and excretion pathway of GNS@CaCO 3 /ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs, and the results proved that GNS@CaCO 3 /ICG had a great ability for tumor-specific and tumor-triggered drug release. We therefore conclude that the GNS@CaCO 3 /ICG holds great promise for clinical applications in anti-tumor therapy with tumor imaging or drug tracing.

Dual-triggered oxygen self-supply black phosphorus nanosystem for enhanced photodynamic therapy.

PubMed

Liu, Jintong; Du, Ping; Mao, Hui; Zhang, Lei; Ju, Huangxian; Lei, Jianping

2018-07-01

Nonspecific distribution of photosensitizer and the intrinsic hypoxic condition in the tumor microenvironment are two key factors limiting the efficacy of O 2 -dependent photodynamic therapy (PDT). Herein, a dual-triggered oxygen self-supported nanosystem using black phosphorus nanosheet (BPNS) as both photosensitizer and nanocarrier was developed to enhance PDT for tumors within hypoxic microenvironment. The BPNS platform was functionalized with folate and a blocker DNA duplex of 5'-Cy5-aptamer-heme/3'-heme labeled oligonucleotides. The resulting heme dimer could passivate its peroxidase activity. After specific recognition of aptamer-target, the quenched fluorescence is "turned" on by cellular adenosine triphosphate. The passivated nanosystem then activates the catalytic function towards excessive intracellular H 2 O 2 to generate O 2 essential to sustain BPNS-mediated PDT, leading to 8.7-fold and 7.5-fold increase of PDT efficacy in treating the hypoxic cell and tumor, respectively. Therefore, the dual-triggered oxygen self-supply nanosystem not only exerts tumor microenvironment-associated stimulus for enhanced PDT but also surmounts hypoxia-associated therapy resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multi-functional liposomes showing radiofrequency-triggered release and magnetic resonance imaging for tumor multi-mechanism therapy.

PubMed

Du, Bin; Han, Shuping; Li, Hongyan; Zhao, Feifei; Su, Xiangjie; Cao, Xiaohui; Zhang, Zhenzhong

2015-03-12

Recently, nanoplatforms with multiple functions, such as tumor-targeting drug carriers, MRI, optical imaging, thermal therapy etc., have become popular in the field of cancer research. The present study reports a novel multi-functional liposome for cancer theranostics. A dual targeted drug delivery with radiofrequency-triggered drug release and imaging based on the magnetic field influence was used advantageously for tumor multi-mechanism therapy. In this system, the surface of fullerene (C60) was decorated with iron oxide nanoparticles, and PEGylation formed a hybrid nanosystem (C60-Fe3O4-PEG2000). Thermosensitive liposomes (dipalmitoylphosphatidylcholine, DPPC) with DSPE-PEG2000-folate wrapped up the hybrid nanosystem and docetaxel (DTX), which were designed to combine features of biological and physical (magnetic) drug targeting for fullerene radiofrequency-triggered drug release. The magnetic liposomes not only served as powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agents, but also as powerful agents for photothermal ablation of tumors. Furthermore, a remarkable thermal therapy combined chemotherapy multi-functional liposome nanoplatform converted radiofrequency energy into thermal energy to release drugs from thermosensitive liposomes, which was also observed during both in vitro and in vivo treatment. The multi-functional liposomes also could selectively kill cancer cells in highly localized regions via their excellent active tumor targeting and magnetic targeted abilities.

[Non-pharmacological diabetes therapy].

PubMed

Martin, Stephan; Kolb, Hubert

2008-02-01

Diabetes mellitus type 2 is a life-style disease that is triggered by obesity and lack of physical activity. The pathophysiological basis of the disease is a reduction of insulin sensitivity, that is caused by the trigger factors. Glucose metabolic disorders appear if overproduction of insulin can not compensate the insulin resistance. In early phases postprandial blood glucose is increased, in late phases elevation of fasting blood glucose is noted. In the general awareness manifestation of type 2 diabetes is associated with an initiation of a pharmacological therapy. This is not the case, as described in detail in this review. Next to epidemiological studies, which indicate trigger factors, intervention trials will be discussed that led to a shift in paradigm in the diabetology. Non-pharmacological interventions are a therapeutical alternative in a lot of patients or are able to reduce the amount of antidiabetic agents significantly.

NIR-triggered high-efficient photodynamic and chemo-cascade therapy using caspase-3 responsive functionalized upconversion nanoparticles.

PubMed

Zhao, Na; Wu, Baoyan; Hu, Xianglong; Xing, Da

2017-10-01

Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photodynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nanoparticles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

ERIC Educational Resources Information Center

Bugg, Julie M.

2014-01-01

The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control…

Retrosternal abscess after trigger point injections in a pregnant woman: a case report.

PubMed

Usman, Faisal; Bajwa, Abubakr; Shujaat, Adil; Cury, James

2011-08-23

Although retrosternal abscess is a well known complication of sternotomy and intravenous drug abuse, to date it has not been described as a consequence of trigger point injections. There are reported cases of serious complications as a result of this procedure including epidural abscess, necrotizing fasciitis, osteomyelitis and gas gangrene. A 37-year-old African-American woman, who was 20 weeks pregnant, presented to our emergency room with complaints of progressively worsening chest pain and shortness of breath over the course of the last two months. She was undergoing trigger point injections at multiple different sites including the sternoclavicular joint for chest pain and dystonia. Two years previously she had developed a left-sided pneumothorax as a result of this procedure, requiring chest tube placement and subsequent pleurodesis. Her vital signs in our emergency room were normal except for resting tachycardia, with a pulse of 100 beats per minute. A physical examination revealed swelling and tenderness of the sternal notch with tenderness to palpation over the left sternoclavicular joint. Laboratory data was significant for a white blood count of 13.3 × 109/L with 82% granulocytes. A chest radiograph revealed left basilar scarring with blunting of the left costophrenic angle. A computed tomography angiogram showed a 4.7 cm abscess in the retrosternal region behind the manubrium with associated sclerosis and cortical irregularity of the manubrium and left clavicle. Trigger point injection is generally considered very safe. However, there are reported cases of serious complications as a result of this procedure. A computed tomography scan of the chest should strongly be considered in the evaluation of chest pain and shortness of breath of unclear etiology in patients with even a remote history of trigger point injections.

Injection therapy for subacute and chronic low-back pain.

PubMed

Staal, J Bart; de Bie, Rob; de Vet, Henrica Cw; Hildebrandt, Jan; Nelemans, Patty

2008-07-16

The effectiveness of injection therapy for low-back pain is still debatable. Heterogeneity of target tissue, pharmacological agent and dosage generally found in randomized controlled trials (RCTs) points to the need for clinically valid comparisons in a literature synthesis. To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low-back pain. We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases from January 1999 to March 2007 for relevant trials reported in English, French, German, Dutch and Nordic languages. We also screened references from trials identified. RCTs on the effects of injection therapy involving epidural, facet or local sites for subacute or chronic low-back pain were included. Studies which compared the effects of intradiscal injections, prolotherapy or Ozone therapy with other treatments, were excluded unless injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded. Two review authors independently assessed the quality of the trials. If study data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a best evidence synthesis to summarize the results. The evidence was classified into five levels (strong, moderate, limited, conflicting or no evidence), taking into account the methodological quality of the studies. 18 trials (1179 participants) were included in this updated review. The injection sites varied from epidural sites and facet joints (i.e. intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender- and trigger points). The drugs that were studied consisted of corticosteroids, local anesthetics and a variety of other drugs. The methodological quality of the trials was limited with 10 out of 18 trials rated as having a high methodological quality. Statistical pooling was not possible due to clinical heterogeneity in the trials. Overall, the results indicated that there is no strong evidence for or against the use of any type of injection therapy. There is insufficient evidence to support the use of injection therapy in subacute and chronic low-back pain. However, it cannot be ruled out that specific subgroups of patients may respond to a specific type of injection therapy.

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles.

PubMed

Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

2015-01-01

Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

PubMed Central

Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

2015-01-01

Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. PMID:26213469

Chronic pain in a patient with Ehlers-Danlos syndrome (hypermobility type): The role of myofascial trigger point injections.

PubMed

Tewari, Saipriya; Madabushi, Rajashree; Agarwal, Anil; Gautam, Sujeet K; Khuba, Sandeep

2017-01-01

Chronic widespread musculoskeletal pain is a cardinal symptom in hypermobility type of Ehler Danlos Syndrome (EDS type III). The management of pain in EDS, however, has not been studied in depth. A 30 year old female, known case of EDS, presented to the pain clinic with complaints of severe upper back pain for 6 months. Physical examination of the back revealed two myofascial trigger points over the left rhomboids and the left erector spinae. Local anaesthetic trigger point injections were given at these points, followed by stretching exercises under analgesic cover for the first week. After 1 week the patient reported 60-80% pain relief. This case highlights that we must keep a high index of suspicion for the more treatable causes of pain like myofascial pain syndrome in patients suffering from EDS, and should address it promptly and appropriately in order to maximise patient comfort. Copyright © 2016 Elsevier Ltd. All rights reserved.

Popular sweetner sucralose as a migraine trigger.

PubMed

Patel, Rajendrakumar M; Sarma, Rakesh; Grimsley, Edwin

2006-09-01

Sucralose (trichlorogalactosucrose, or better known as Splenda) is an artificial sweetener from native sucrose that was approved by the FDA on April 1, 1998 (April Fool's Day). This observation of a potential causal relationship between sucralose and migraines may be important for physicians to remember this can be a possible trigger during dietary history taking. Identifying further triggers for migraine headaches, in this case sucralose, may help alleviate some of the cost burden (through expensive medical therapy or missed work opportunity) as well as provide relief to migraineurs.

Hypothesizing the body's genius to trigger and self-organize its healing: 25 years using a standardized neurophysics therapy

PubMed Central

Ross, Sara N.; Ware, Ken

2013-01-01

We aim for this contribution to operate bi-directionally, both as a “bedside to bench” reverse-translational fractal physiological hypothesis and as a methodological innovation to inform clinical practice. In 25 years using gym equipment therapeutically in non-research settings, the standardized therapy is consistently observed to trigger universal responses of micro to macro waves of system transition dynamics in the human nervous system. These are associated with observably desirable impacts on disorders, injuries, diseases, and athletic performance. Requisite conditions are therapeutic coaching, erect posture, extremely slow movements in mild resistance exercises, and executive control over arousal and attention. To motivate research into the physiological improvements and in validation studies, we integrate from across disciplines to hypothesize explanations for the relationships among the methods, the system dynamics, and evident results. Key hypotheses include: (1) Correctly-directed system efforts may reverse a system's heretofore misdirected efforts, restoring healthier neurophysiology. (2) The enhanced information processing accompanying good posture is an essential initial condition. (3) Behaviors accompanying exercises performed with few degrees of freedom amplify information processing, triggering destabilization and transition dynamics. (4) Executive control over arousal and attention is essential to release system constraints, amplifying and complexifying information. (5) The dynamics create necessary and in many cases evidently sufficient conditions for the body to resolve or improve its own conditions within often short time periods. Literature indicates how the human system possesses material self-awareness. A broad explanation for the nature and effects of the therapy appears rooted in the cascading recursions of the systems' dynamics, which appear to trigger health-fostering self-reorganizing processes when this therapy provides catalytic initial conditions. PMID:24312056

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Prevalence of right atrial non-pulmonary vein triggers in atrial fibrillation patients treated with thyroid hormone replacement therapy.

PubMed

Kim, Ki-Hun; Mohanty, Sanghamitra; Mohanty, Prasant; Trivedi, Chintan; Morris, Eli Hamilton; Santangeli, Pasquale; Bai, Rong; Al-Ahmad, Amin; Burkhardt, John David; Gallinghouse, Joseph G; Horton, Rodney; Sanchez, Javier E; Bailey, Shane; Hranitzky, Patrick M; Zagrodzky, Jason; Kim, Soo G; Di Biase, Luigi; Natale, Andrea

2017-08-01

Thyroid hormone (TH) is known to enhance arrhythmogenicity, and high-normal thyroid function is related with an increased recurrence of atrial fibrillation (AF) after catheter ablation. However, the impact of thyroid hormone replacement (THR) on AF ablation is not well known. This study evaluated 1163 consecutive paroxysmal AF patients [160 (14%) on THR and 1003 (86%) without THR] undergoing their first catheter ablation. A total of 146 patients on THR and 146 controls were generated by propensity matching, based on calculated risk factor scores, using a logistic model (age, sex, body mass index, and left atrium size). The presence of non-pulmonary vein (PV) triggers was disclosed by a high-dose isoproterenol challenge (up to 30 μg/min) after PV isolation. Clinical characteristics were not different between the groups. When compared to the control, non-PV triggers were significantly greater in the THR patients [112 (77%) vs. 47 (32%), P < 0.001], and most frequently originated from the right atrium (95 vs. 56%, P < 0.001). Other sources of non-PV triggers were the interatrial septum (25 vs. 11%, P = 0.002), coronary sinus (70 vs. 52%, P = 0.01), left atrial appendage (47 vs. 34%, P = 0.03), crista terminalis/superior vena cava (11 vs. 8%, P = 0.43), and mitral valve annulus (7 vs. 5%, P = 0.45) (THR vs. control), respectively. After mean follow-up of 14.7 ± 5.2 months, success rate was lower in patients on THR therapy [94 (64.4%)] compared to patients not receiving THR therapy [110 (75.3%), log-rank test value = 0.04]. Right atrial non-PV triggers were more prevalent in AF patients treated with THR. Elimination of non-PV triggers provided better arrhythmia-free survival in the non-THR group.

Hemoglobin levels triggering erythropoiesis-stimulating agent therapy in patients with cancer: the shift after United States Food and Drug Administration policy changes.

PubMed

Stroupe, Kevin T; Tarlov, Elizabeth; Lee, Todd A; Weichle, Thomas W; Zhang, Qiuying L; Michaelis, Laura C; Ozer, Howard; Durazo-Arvizu, Ramon; Browning, Margaret M; Hynes, Denise M

2012-11-01

To determine whether the hemoglobin level at which health care providers prescribed erythropoiesis-stimulating agent (ESA) therapy (trigger hemoglobin level) for their patients receiving chemotherapy was lower after the United States Food and Drug Administration (FDA) mandated a black-box warning in March 2007. Retrospective analysis. U.S. Department of Veterans Affairs Healthcare System (VA) national databases. A total of 7450 patients who were diagnosed with cancer between 2002 and 2009, were undergoing chemotherapy, and who received an ESA within 12 months after their cancer diagnosis. Data were collected on patients' demographic, clinical, environmental, and treatment-related factors. After controlling for these factors, multivariable regression analyses were used to compare the trigger hemoglobin level before and after the FDA-mandated labeling change. The average trigger hemoglobin level was 0.73 g/dl lower after the labeling change (95% confidence interval [CI] -0.84 to -0.63). Moreover, the decline in trigger hemoglobin levels began in mid-2006, when the average trigger hemoglobin level fell from 10.50 g/dl in early 2006 (95% CI 10.36-10.63) to 9.30 g/dl by late 2009 (95% CI 9.10-9.49). Even before the 2007 FDA-mandated changes in ESA product labeling, hemoglobin levels that triggered ESA treatment began declining for patients receiving cancer care within the VA. This highlights the critical importance of dissemination of postmarketing safety data to impact shifts in ESA use for anemia management. © 2012 Pharmacotherapy Publications, Inc.

75 FR 34049 - Magnuson-Stevens Fishery Conservation and Management Act Provisions; Fisheries of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... limits, in season possession limit triggers, and other measures to improve management of the skate... given year, the possession limit trigger (80 percent in the wing fishery, 90 percent in the bait fishery... is exceeded by more than 5 percent, the trigger point at which the possession limit is reduced would...

Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers.

PubMed

Zeng, Leyong; Pan, Yuanwei; Tian, Ying; Wang, Xin; Ren, Wenzhi; Wang, Shouju; Lu, Guangming; Wu, Aiguo

2015-07-01

The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser. Copyright © 2015 Elsevier Ltd. All rights reserved.

'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

PubMed

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirigh, Conall; Chibanda, Dixon; Abas, Melanie

2015-07-01

To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy. © 2015 John Wiley & Sons Ltd.

The neurobiology of the human febrile response.

PubMed

Biddle, Chuck

2006-04-01

Fever is a normal adaptation in response to a pyrogenic stimulus resulting in the generation of cytokines and prostaglandins. Fever differs from hyperpyrexia and hyperthermia associated with hot environs and pharmacological triggers. Typically, pyrogens are infectious organisms or their direct products (toxins). The body produces a wide array of pyrogenic cytokines such as interleukins (IL-1, IL-6), interferon, and tumor necrosis factor. Tissue trauma can trigger the febrile response, as can infectious organisms, certain medications, and blood products. The circumventricular organ system (CVOS) is neuronal tissues lying outside the blood-brain barrier that has a key role in initiating the communication sequence responsible for the synthesis of febrile prostaglandins. When pyrogenic cytokines are detected by the CVOS, prostaglandin synthesis, especially cyclooxygenase-dependent prostaglandin E2, is induced, activating the febrile response. Once the appropriate signal is received by the hypothalamus, autonomic, endocrine, and behavioral processes are activated until the hypothalamic set-point is reset downward as a consequence of a reduction in pyrogen content or antipyretic therapy, with subsequent heat loss. There is little evidence that fever facilitates recovery from disease or assists the immune system in mounting a response. Antipyretics are used commonly to decrease the distressing manifestations associated with fever.

Triggering Factor of Strong Earthquakes and Its Prediction Verification

NASA Astrophysics Data System (ADS)

Ren, Z. Q.; Ren, S. H.

After 30 yearsS research, we have found that great earthquakes are triggered by tide- generation force of the moon. ItSs not the tide-generation force in classical view- points, but is a non-classical viewpoint tide-generation force. We call it as TGFR (Tide-Generation ForcesS Resonance). TGFR strongly depends on the tide-generation force at time of the strange astronomical points (SAP). The SAP mostly are when the moon and another celestial body are arranged with the earth along a straight line (with the same apparent right ascension or 180o difference), the other SAP are the turning points of the moonSs relatively motion to the earth. Moreover, TGFR have four different types effective areas. Our study indicates that a majority of earthquakes are triggering by the rare superimposition of TGFRsS effective areas. In China the great earthquakes in the plain area of Hebei Province, Taiwan, Yunnan Province and Sichuan province are trigger by the decompression TGFR; Other earthquakes are trig- gered by compression TGFR which are in Gansu Province, Ningxia Provinces and northwest direction of Beijing. The great earthquakes in Japan, California, southeast of Europe also are triggered by compression of the TGFR. and in the other part of the world like in Philippines, Central America countries, and West Asia, great earthquakes are triggered by decompression TGFR. We have carried out examinational immediate prediction cooperate TGFR method with other earthquake impending signals such as suggested by Professor Li Junzhi. The successful ratio is about 40%(from our fore- cast reports to the China Seismological Administration). Thus we could say the great earthquake can be predicted (include immediate earthquake prediction). Key words: imminent prediction; triggering factor; TGFR (Tide-Generation ForcesS Resonance); TGFR compression; TGFR compression zone; TGFR decompression; TGFR decom- pression zone

Reliability of different methodologies of infrared image analysis of myofascial trigger points in the upper trapezius muscle

PubMed Central

Dibai-Filho, Almir V.; Guirro, Elaine C. O.; Ferreira, Vânia T. K.; Brandino, Hugo E.; Vaz, Maíta M. O. L. L.; Guirro, Rinaldo R. J.

2015-01-01

BACKGROUND: Infrared thermography is recognized as a viable method for evaluation of subjects with myofascial pain. OBJECTIVE: The aim of the present study was to assess the intra- and inter-rater reliability of infrared image analysis of myofascial trigger points in the upper trapezius muscle. METHOD: A reliability study was conducted with 24 volunteers of both genders (23 females) between 18 and 30 years of age (22.12±2.54), all having cervical pain and presence of active myofascial trigger point in the upper trapezius muscle. Two trained examiners performed analysis of point, line, and area of the infrared images at two different periods with a 1-week interval. The intra-class correlation coefficient (ICC2,1) was used to assess the intra- and inter-rater reliability. RESULTS: With regard to the intra-rater reliability, ICC values were between 0.591 and 0.993, with temperatures between 0.13 and 1.57 °C for values of standard error of measurement (SEM) and between 0.36 and 4.35 °C for the minimal detectable change (MDC). For the inter-rater reliability, ICC ranged from 0.615 to 0.918, with temperatures between 0.43 and 1.22 °C for the SEM and between 1.19 and 3.38 °C for the MDC. CONCLUSION: The methods of infrared image analyses of myofascial trigger points in the upper trapezius muscle employed in the present study are suitable for clinical and research practices. PMID:25993626

Coupling of pulsed electromagnetic fields (PEMF) therapy to molecular grounds of the cell

PubMed Central

Funk, Richard HW

2018-01-01

In this review we compile results cited in reliable journals that show a ratio for the use of pulsed electromagnetic fields (PEMF) in therapy, indeed. This is true especially for chronically inflamed joints. Furthermore, we try to link this therapeutic approach to the molecular background of chronic inflammation and arthritis. At first we start with the clinical outcome of PEMF therapy. Then, we look for possible triggers and an electromagnetic counterpart that is endogenously inherent in cell biology and in the tissues of interest. Finally, we want to investigate causal molecular and cellular mechanisms of possible PEMF actions. It shows that there are endogenous mechanisms, indeed, which can act as triggers for PEMF like the resting membrane potential as well as resonance mechanisms in charged moieties like membrane transporters. Especially voltage-gated calcium channels can be triggered. These may lead into specific signaling pathways and also may elicit nitric oxide as well as moderate radical reactions, which can ultimately lead to e.g. NFκB-like reactions. Concerted in the right way, these reactions can cause a kind of cell protection and ultimately lead to a dampening of inflammatory signals like interleukins. PMID:29887943

Evaluation of dosimetric effect caused by slowing with multi-leaf collimator (MLC) leaves for volumetric modulated arc therapy (VMAT)

PubMed Central

Wang, Iris Z.; Kumaraswamy, Lalith K.; Podgorsak, Matthew B.

2016-01-01

Background This study is to report 1) the sensitivity of intensity modulated radiation therapy (IMRT) QA method for clinical volumetric modulated arc therapy (VMAT) plans with multi-leaf collimator (MLC) leaf errors that will not trigger MLC interlock during beam delivery; 2) the effect of non-beam-hold MLC leaf errors on the quality of VMAT plan dose delivery. Materials and methods. Eleven VMAT plans were selected and modified using an in-house developed software. For each control point of a VMAT arc, MLC leaves with the highest speed (1.87-1.95 cm/s) were set to move at the maximal allowable speed (2.3 cm/s), which resulted in a leaf position difference of less than 2 mm. The modified plans were considered as ‘standard’ plans, and the original plans were treated as the ‘slowing MLC’ plans for simulating ‘standard’ plans with leaves moving at relatively lower speed. The measurement of each ‘slowing MLC’ plan using MapCHECK®2 was compared with calculated planar dose of the ‘standard’ plan with respect to absolute dose Van Dyk distance-to-agreement (DTA) comparisons using 3%/3 mm and 2%/2 mm criteria. Results All ‘slowing MLC’ plans passed the 90% pass rate threshold using 3%/3 mm criteria while one brain and three anal VMAT cases were below 90% with 2%/2 mm criteria. For ten out of eleven cases, DVH comparisons between ‘standard’ and ‘slowing MLC’ plans demonstrated minimal dosimetric changes in targets and organs-at-risk. Conclusions For highly modulated VMAT plans, pass rate threshold (90%) using 3%/3mm criteria is not sensitive in detecting MLC leaf errors that will not trigger the MLC leaf interlock. However, the consequential effects of non-beam hold MLC errors on target and OAR doses are negligible, which supports the reliability of current patient-specific IMRT quality assurance (QA) method for VMAT plans. PMID:27069458

[Malassezia yeasts and their significance in dermatology].

PubMed

Hort, W; Nilles, M; Mayser, P

2006-07-01

Yeasts of the genus Malassezia belong to the normal microflora of the human skin. In addition they are known to cause a variety of skin diseases; the most frequent of which is pityriasis versicolor. Malassezia yeasts are also thought to be associated with seborrheic dermatitis, dandruff and Malassezia folliculitis. Recently the significance of Malassezia yeasts as a trigger factor for atopic dermatitis of the head and neck region has been pointed out. The role of the Malassezia yeasts in these different diseases has been controversial in the past and remains an issue because of difficulties in isolation, culture and differentiation of the organism. Thanks to molecular techniques, 10 species can actually be differentiated. The article presents the different Malassezia-associated diseases, their clinical picture, diagnosis and appropriate therapy. In addition the speciation of Malassezia is reviewed.

Intestinal alkaline phosphatase prevents metabolic syndrome in mice.

PubMed

Kaliannan, Kanakaraju; Hamarneh, Sulaiman R; Economopoulos, Konstantinos P; Nasrin Alam, Sayeda; Moaven, Omeed; Patel, Palak; Malo, Nondita S; Ray, Madhury; Abtahi, Seyed M; Muhammad, Nur; Raychowdhury, Atri; Teshager, Abeba; Mohamed, Mussa M Rafat; Moss, Angela K; Ahmed, Rizwan; Hakimian, Shahrad; Narisawa, Sonoko; Millán, José Luis; Hohmann, Elizabeth; Warren, H Shaw; Bhan, Atul K; Malo, Madhu S; Hodin, Richard A

2013-04-23

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.

Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

PubMed

Johnson, Alison C; Dugué, Audrey Emmanuelle; Silva, Marlon; Moise, Laura; Tillou, Xavier; Joly, Florence; Aide, Nicolas

2016-12-01

The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18 F-choline (CH) PET/CT after external beam radiation therapy (EBRT). In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18 F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18 F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.

Physiotherapy interventions for patients with chronic pelvic pain: A systematic review of the literature.

PubMed

Fuentes-Márquez, Pedro; Cabrera-Martos, Irene; Valenza, Marie Carmen

2018-05-14

To summarize the available scientific evidence on physiotherapy interventions in the management of chronic pelvic pain (CPP). A systematic review of randomized controlled trials was performed. An electronic search of MEDLINE, CINAHL, and Web of Science databases was performed to identify relevant randomized trials from 2010-2016. Manuscripts were included if at least one of the comparison groups received a physiotherapy intervention. Studies were assessed in duplicate for data extraction and risk of bias using the Physiotherapy Evidence Database scale PEDro. Eight of the studies screened met the inclusion criteria. Four manuscripts studied the effects of electrotherapy including intravaginal electrical stimulation, short wave diathermy, respiratory-gated auricular vagal afferent nerve stimulation, percutaneous tibial nerve stimulation, and sono-electro-magnetic therapy with positive results. Three studies focused on manual assessing the efficacy of myofascial versus massage therapy in two of them and ischemic compression for trigger points. Although physiotherapy interventions show some beneficial effects, evidence cannot support the results. Heterogeneity in terms of population phenotype, methodological quality, interpretation of results, and operational definition result in little overall evidence to guide treatment.

Is prolongation of corrected QT interval associated with seizures induced by electroconvulsive therapy reduced by atropine sulfate?

PubMed

Suzuki, Yoko; Miyajima, Miho; Ohta, Katsuya; Yoshida, Noriko; Omoya, Rie; Fujiwara, Mayo; Watanabe, Takafumi; Okumura, Masaki; Yamazaki, Hiroaki; Shintaku, Masayuki; Murata, Issei; Ozaki, Shigeru; Sasaki, Takeshi; Nakamura, Mitsuru; Suwa, Hiroshi; Sasano, Tetsuo; Kawara, Tokuhiro; Matsuura, Masato; Matsushima, Eisuke

2017-11-01

Electrocardiogram abnormalities have been reported during electroconvulsive therapy (ECT). A corrected QT interval (QTc) prolongation indicates delayed ventricular repolarization, which can trigger ventricular arrhythmias such as torsade de pointes (TdP). We examined the QTc changes during generalized tonic-clonic seizures induced by ECT, and the effects of atropine sulfate on these QTc changes. We analyzed heart rate, QT interval, and QTc in 32 patients with depression who underwent ECT (25 women, 67.4 ± 8.7 years of age). The QTc from -30 to 0 seconds prestimulation was used as baseline, which was compared with QTc at 20-30 seconds and 140-150 seconds poststimulus onset. QTc was significantly prolonged at 20-30 seconds poststimulus, then significantly decreased at 140-150 seconds poststimulus, compared with baseline. QTc prolongation induced by ECT was significantly decreased by atropine sulfate. These data suggest that the risk of TdP may be enhanced by ECT. Further, the risk of cardiac ventricular arrhythmias, including TdP, may be reduced by administration of atropine sulfate. © 2017 Wiley Periodicals, Inc.

Photodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus.

PubMed

Gomes-da-Silva, Lígia C; Zhao, Liwei; Bezu, Lucillia; Zhou, Heng; Sauvat, Allan; Liu, Peng; Durand, Sylvère; Leduc, Marion; Souquere, Sylvie; Loos, Friedemann; Mondragón, Laura; Sveinbjørnsson, Baldur; Rekdal, Øystein; Boncompain, Gaelle; Perez, Franck; Arnaut, Luis G; Kepp, Oliver; Kroemer, Guido

2018-05-28

Preclinical evidence depicts the capacity of redaporfin (Redp) to act as potent photosensitizer, causing direct antineoplastic effects as well as indirect immune-dependent destruction of malignant lesions. Here, we investigated the mechanisms through which photodynamic therapy (PDT) with redaporfin kills cancer cells. Subcellular localization and fractionation studies based on the physicochemical properties of redaporfin revealed its selective tropism for the endoplasmic reticulum (ER) and the Golgi apparatus (GA). When activated, redaporfin caused rapid reactive oxygen species-dependent perturbation of ER/GA compartments, coupled to ER stress and an inhibition of the GA-dependent secretory pathway. This led to a general inhibition of protein secretion by PDT-treated cancer cells. The ER/GA play a role upstream of mitochondria in the lethal signaling pathway triggered by redaporfin-based PDT Pharmacological perturbation of GA function or homeostasis reduces mitochondrial permeabilization. In contrast, removal of the pro-apoptotic multidomain proteins BAX and BAK or pretreatment with protease inhibitors reduced cell killing, yet left the GA perturbation unaffected. Altogether, these results point to the capacity of redaporfin to kill tumor cells via destroying ER/GA function. © 2018 The Authors.

AMPLITUDE DISCRIMINATOR HAVING SEPARATE TRIGGERING AND RECOVERY CONTROLS UTILIZING AUTOMATIC TRIGGERING

DOEpatents

Chase, R.L.

1962-01-23

A transistorized amplitude discriminator circuit is described in which the initial triggering sensitivity and the recovery threshold are separately adjustable in a convenient manner. The discriminator is provided with two independent bias components, one of which is for circuit hysteresis (recovery) and one of which is for trigger threshold level. A switching circuit is provided to remove the second bias component upon activation of the trigger so that the recovery threshold is always at the point where the trailing edge of the input signal pulse goes through zero or other desired value. (AEC)

Insights Into the Mechanism of OnabotulinumtoxinA in Chronic Migraine

PubMed Central

Durham, Paul L.; Cady, Roger

2012-01-01

OnabotulinumtoxinA has recently been approved by regulatory agencies in the UK and United States for treatment of chronic migraine based on data generated from the PREEMPT studies. As such, onabotulinumtoxinA is the only prophylactic therapy specifically approved for chronic migraine. Most headache clinicians would agree that acute episodic migraine and chronic migraine differ in their pathophysiology, etiology, diagnosis, and response to pharmacological as well as nonpharmacological therapies. Of the 7 botulinum neurotoxin serotypes, botulinum neurotoxin type A (onabotulinumtoxinA) has been the most thoroughly investigated in preclinical and clinical studies. Based on preclinical studies, onabotulinumtoxinA is known to inhibit the release of excitatory neurotransmitters from both motor and sensory neurons by preventing vesicle fusion to the cell membrane. In addition to the well-documented myorelaxant effects of this neurotoxin, onabotulinumtoxinA can exert a direct analgesic effect that likely involves inhibition of primary and secondary nociceptive neurons. The inhibitory effects of onabotulinumtoxinA are also likely to involve suppressing the activity of myogenic trigger points and decreasing the persistent nociceptive barrage that promotes and maintains central sensitization. This article describes possible mechanisms to explain how onabotulinumtoxinA functions as a therapy for chronic migraine and considers why treatment with the neurotoxin is not effective in some chronic migraineurs. PMID:22082429

Triggerable electro-optic amplitude modulator bias stabilizer for integrated optical devices

DOEpatents

Conder, A.D.; Haigh, R.E.; Hugenberg, K.F.

1995-09-26

An improved Mach-Zehnder integrated optical electro-optic modulator is achieved by application and incorporation of a DC bias box containing a laser synchronized trigger circuit, a DC ramp and hold circuit, a modulator transfer function negative peak detector circuit, and an adjustable delay circuit. The DC bias box ramps the DC bias along the transfer function curve to any desired phase or point of operation at which point the RF modulation takes place. 7 figs.

Triggerable electro-optic amplitude modulator bias stabilizer for integrated optical devices

DOEpatents

Conder, Alan D.; Haigh, Ronald E.; Hugenberg, Keith F.

1995-01-01

An improved Mach-Zehnder integrated optical electro-optic modulator is achieved by application and incorporation of a DC bias box containing a laser synchronized trigger circuit, a DC ramp and hold circuit, a modulator transfer function negative peak detector circuit, and an adjustable delay circuit. The DC bias box ramps the DC bias along the transfer function curve to any desired phase or point of operation at which point the RF modulation takes place.

Radial extracorporeal shockwave therapy for the treatment of finger tenosynovitis (trigger digit)

PubMed Central

Malliaropoulos, Nikos; Jury, Rosanna; Pyne, Debasish; Padhiar, Nat; Turner, Jennifer; Korakakis, Vasileios; Meke, Maria; Lohrer, Heinz

2016-01-01

Introduction Stenosing tenosynovitis that is characterized by the inability to flex the digit smoothly, usually leads to prolonged rehabilitation or surgery. Study design This case series is a retrospective cohort study. Purpose The aim of this case series was to evaluate the effectiveness of radial extracorporeal shockwave therapy (rESWT) for the treatment of stenosing tenosynovitis of the digital flexor tendon (trigger digit). Methods A retrospective analysis of 44 patients (49 fingers) treated with an individually adapted rESWT protocol was conducted. Trigger digit pain and function were evaluated at baseline and 1-, 3-, and 12-months posttreatment. Recurrence and pretreatment symptom duration were analyzed. Results Significant reductions in pain scores and functional improvement were found between baseline and all follow-up assessments (P<0.001). Pretreatment symptom duration was significantly correlated with the number of rESWT sessions required (r=0.776, P<0.001) and 1-year posttreatment pain score (r=0.335, P=0.019). Conclusion This study provides initial evidence that rESWT is an effective treatment for trigger digit, but randomised controlled trials are required to provide further evidence of this effect. PMID:27843364

Highly efficient drug delivery nanosystem via L-phenylalanine triggering based on supramolecular polymer micelles.

PubMed

Dong, Haiqing; Li, Yongyong; Wen, Huiyun; Xu, Meng; Liu, Lijian; Li, Zhuoquan; Guo, Fangfang; Shi, Donglu

2011-03-16

An intelligent drug delivery nanosystem has been developed based on biodegradable supramolecular polymer micelles (SMPMs). The drug release can be triggered from SMPMs responsively by a bioactive agent, L-phenylalanine in a controlled fashion. The SMPMs are constructed from ethylcellulose-graft-poly(ε-caprolactone) (EC-g-PCL) and α-cyclodextrin (α-CD) derivate via host-guest and hydrophobic interactions. It has been found that these SMPMs have disassembled rapidly in response to an additional L-phenylalanine, due to great affinity discrepancy to α-CD between L-phenylalanine and PCL. Experiments have been carried out on trigger-controlled in vitro drug release of the SMPMs loaded with a model porphyrin based photosensitizer THPP. The result shows that the SMPMs released over 85% THPP in 6 h, which is two orders magnitudes faster than that of control. Also investigated is the photodynamic therapy (PDT) of THPP-loaded SMPMs with and without L-phenylalanine on MCF-7 carcinoma cell line. An effective trigger-concentration dependent lethal effect has been found showing promise in clinical photodynamic therapy. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation.

PubMed

Nasr, Rihab; Guillemin, Marie-Claude; Ferhi, Omar; Soilihi, Hassan; Peres, Laurent; Berthier, Caroline; Rousselot, Philippe; Robledo-Sarmiento, Macarena; Lallemand-Breitenbach, Valérie; Gourmel, Bernard; Vitoux, Dominique; Pandolfi, Pier Paolo; Rochette-Egly, Cécile; Zhu, Jun; de Thé, Hugues

2008-12-01

Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers growth arrest of leukemia-initiating cells (LICs) ex vivo and their clearance in PML-RARA mouse APL in vivo. Retinoic acid treatment of mouse APLs expressing the fusion protein PLZF-RARA triggers full differentiation, but not LIC loss or disease remission, establishing that differentiation and LIC loss can be uncoupled. Although retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. A cyclic AMP (cAMP)-dependent phosphorylation site in PML-RARA is crucial for retinoic acid-induced PML-RARA degradation and LIC clearance. Moreover, activation of cAMP signaling enhances LIC loss by retinoic acid, identifying cAMP as another potential APL therapy. Thus, whereas transcriptional activation of PML-RARA is likely to control differentiation, its catabolism triggers LIC eradication and long-term remission of mouse APL. Therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells.

A comprehensive protocol to diagnose and treat pain of muscular origin may successfully and reliably decrease or eliminate pain in a chronic pain population.

PubMed

Marcus, Norman J; Gracely, Edward J; Keefe, Kelly O

2010-01-01

A comprehensive protocol is presented to identify muscular causes of regional pain syndromes utilizing an electrical stimulus in lieu of palpation, and combining elements of Prolotherapy with trigger point injections. One hundred seventy-six consecutive patients were evaluated for the presence of muscle pain by utilizing an electrical stimulus produced by the Muscle Pain Detection Device. The diagnosis of "Muscle Pain Amenable to Injection" (MPAI), rather than trigger points, was made if pain was produced for the duration of the stimulation. If MPAI was found, muscle tendon injections (MTI) were offered to patients along with post-MTI physical therapy, providing neuromuscular electrical stimulation followed by a validated exercise program [1]. A control group, evaluated 1 month prior to their actual consultation/evaluation when muscle pain was identified but not yet treated, was used for comparison. Forty-five patients who met criteria completed treatment. Patients' scores on the Brief Pain Inventory decreased an average of 62%; median 70% (P < 0.001) for pain severity and 68%; median 85% (P < 0.001) for pain interference one month following treatment. These changes were significantly greater (P < 0.001) than those observed in the untreated controls. A protocol incorporating an easily reproducible electrical stimulus to diagnose a muscle causing pain in a region of the body followed by an injection technique that involves the entirety of the muscle, and post injection restoration of muscle function, can successfully eliminate or significantly reduce regional pain present for years.

External triggering and triggered targeting strategies for drug delivery

NASA Astrophysics Data System (ADS)

Wang, Yanfei; Kohane, Daniel S.

2017-06-01

Drug delivery systems that are externally triggered to release drugs and/or target tissues hold considerable promise for improving the treatment of many diseases by minimizing nonspecific toxicity and enhancing the efficacy of therapy. These drug delivery systems are constructed from materials that are sensitive to a wide range of external stimuli, including light, ultrasound, electrical and magnetic fields, and specific molecules. The responsiveness conferred by these materials allows the release of therapeutics to be triggered on demand and remotely by a physician or patient. In this Review, we describe the rationales for such systems and the types of stimuli that can be deployed, and provide an outlook for the field.

Myofascial trigger points, pain, disability, and sleep quality in individuals with mechanical neck pain.

PubMed

Muñoz-Muñoz, Sonsoles; Muñoz-García, María T; Alburquerque-Sendín, Francisco; Arroyo-Morales, Manuel; Fernández-de-las-Peñas, César

2012-10-01

The purpose of this study was to investigate the presence of active myofascial trigger points (MTrPs) in a greater number of muscles than previous studies and the relation between the presence of MTrPs, the intensity of pain, disability, and sleep quality in mechanical neck pain. Fifteen patients with mechanical neck pain (80% women) and 12 comparable controls participated. Myofascial trigger points were bilaterally explored in the upper trapezius, splenius capitis, semispinalis capitis, sternocleidomastoid, levator scapulae, and scalene muscles in a blinded design. Myofascial trigger points were considered active if the subject recognized the elicited referred pain as a familiar symptom. Myofascial trigger points were considered latent if the elicited referred pain was not recognized as a symptom. Pain was collected with a numerical pain rate scale (0-10); disability was assessed with Neck Disability Index; and sleep quality, with the Pittsburgh Sleep Quality Index. Patients exhibited a greater disability and worse sleep quality than controls (P < .001). The Pittsburgh Sleep Quality Index score was associated with the worst intensity of pain (r = 0.589; P = .021) and disability (r = 0.552; P = .033). Patients showed a greater (P = .002) number of active MTrPs (mean, 2 ± 2) and similar number (P = .505) of latent MTrPs (1.6 ± 1.4) than controls (latent MTrPs, 1.3 ± 1.4). No significant association between the number of latent or active MTrPs and pain, disability, or sleep quality was found. The referred pain elicited by active MTrPs in the neck and shoulder muscles contributed to symptoms in mechanical neck pain. Patients exhibited higher disability and worse sleep quality than controls. Sleep quality was associated with pain intensity and disability. No association between active MTrPs and the intensity of pain, disability, or sleep quality was found. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Association of Chronic Pelvic Pain and Endometriosis With Signs of Sensitization and Myofascial Pain

PubMed Central

Stratton, Pamela; Khachikyan, Izabella; Sinaii, Ninet; Ortiz, Robin; Shah, Jay

2014-01-01

Objective To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis. Methods A cross-sectional prospective study of women aged 18 to 50 with pain suggestive of endometriosis and healthy, pain-free volunteers without history of endometriosis. Patients underwent a physiatric neuro-musculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All pain participants underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation. Results Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83% and 82%) but much lower among healthy volunteers (15%, p<0.001). Nearly all women with pain had myofascial trigger points (94% and 91%). Adjusting for study group, those with high anxiety (OR=1.05, 95% CI:1.004–1.099; p=0.031) and depression (OR=1.06, 95% CI:1.005–1.113; p=0.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared to the others (87% v 67% v 15%; p<0.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR=9.41, 95% CI:1.77–50.08, p=0.009). Conclusions Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates. PMID:25730237

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

PubMed Central

Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.

2010-01-01

ABSTRACT Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward. PMID:20725771

Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

PubMed

Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

2017-03-28

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

DNA repair mechanisms in cancer development and therapy.

PubMed

Torgovnick, Alessandro; Schumacher, Björn

2015-01-01

DNA damage has been long recognized as causal factor for cancer development. When erroneous DNA repair leads to mutations or chromosomal aberrations affecting oncogenes and tumor suppressor genes, cells undergo malignant transformation resulting in cancerous growth. Genetic defects can predispose to cancer: mutations in distinct DNA repair systems elevate the susceptibility to various cancer types. However, DNA damage not only comprises a root cause for cancer development but also continues to provide an important avenue for chemo- and radiotherapy. Since the beginning of cancer therapy, genotoxic agents that trigger DNA damage checkpoints have been applied to halt the growth and trigger the apoptotic demise of cancer cells. We provide an overview about the involvement of DNA repair systems in cancer prevention and the classes of genotoxins that are commonly used for the treatment of cancer. A better understanding of the roles and interactions of the highly complex DNA repair machineries will lead to important improvements in cancer therapy.

[The effect of floating-needle therapy combined with rehabilitation training for the hand function recovery of post-stroke patients].

PubMed

Yang, Jiangxia; Xiao, Hong

2015-08-01

To explore the improvement of hand motion function,spasm and self-care ability of daily life for stroke patients treated with floating-needle combined with rehabilitation training. Eighty hand spasm patients of post-stroke within one year after stroke were randomly divided into an observation group and a control group, 40 cases in each one. In the two groups, rehabilitation was adopted for eight weeks,once a day,40 min one time. In the observation group, based on the above treatment and according to muscle fascia trigger point, 2~3 points in both the internal and external sides of forearm were treated with floating-needle. The positive or passive flexion and extension of wrist and knuckle till the relief of spasm hand was combined. The floating-needle therapy was given for eight weeks, on the first three days once a day and later once every other day. Modified Ashworth Scale(MAS), activity of daily life(ADL, Barthel index) scores and Fugl-Meyer(FMA) scores were used to assess the spasm hand degree,activity of daily life and hand motion function before and after 7-day, 14-day and 8-week treatment. After 7-day, 14-day and 8-week treatment, MAS scores were apparently lower than those before treatment in the two groups(all P<0. 05), and Barthel scores and FMA scores were obviously higher than those before-treatment(all P<0. 05). After 14-day and 8-week treatment, FMA scores in the observation group were markedly higher than those in the control group(both P<0. 05). Floating-needle therapy combined with rehabilitation training and simple rehabilitation training could both improve hand spasm degree, hand function and activity of daily life of post-stroke patients, but floating-needle therapy combined with rehabilitation training is superior to simple rehabilitation training for the improvement of hand function.

THE USE OF TRIGGER POINT DRY NEEDLING AND INTRAMUSCULAR ELECTRICAL STIMULATION FOR A SUBJECT WITH CHRONIC LOW BACK PAIN: A CASE REPORT

PubMed Central

2013-01-01

Study Design: Case Report. Background and Purpose: Myofascial trigger points (MTrPs) are widely accepted by clinicians and researchers as a primary source of regional neuromusculoskeletal pain. Trigger point dry needling (TrP‐DN) is an invasive procedure that involves stimulation of MTrPs using an monofilament needle. The purpose of this case report is to report the outcomes of TrP‐DN and intramuscular electrical stimulation (IES) as a primary treatment intervention in a subject with chronic low back pain. Case Description: The subject was a 30‐year‐old female, active duty military, who was referred to physical therapy for low back and right posterolateral hip pain. She noticed symptoms after suffering a lumbar flexion injury while picking up a barbell during weight training. Physical examination demonstrated findings that supported the diagnosis of lumbar segmental instability with a right hip stability dysfunction. Objective findings included a multi‐segmental flexion movement pattern dysfunction and MTrPs in the right gluteus maximus and gluteus medius muscles with deep palpation. The subject was treated with TrP‐DN and IES for a total of two visits. Bilateral L3 and L5 multifidus and right gluteus maximus and medius muscles were treated, along with implementing a home exercise program consisting of core stability exercises. Outcomes: The subject reported no existing pain and disability on the Numerical Pain Rating Scale and Oswestry Disability Questionnaire and a large perceived change in recovery on the Global Rating of Change at final follow‐up. Physical examination was normal, demonstrating no observed impairments or functional limitations, including normal multi‐segmental flexion and no MTrPs with deep palpation. Discussion: The subject was able to return to full military active duty without any physical limitations and resumed pre‐injury activity levels, including the ability to resume all activities without pain. There is much promise regarding the use of TrP‐DN with IES intervention for the treatment of lumbar and/or hip stability dysfunction. Future research is recommended to determine if TrP‐DN intervention, with and without IES, is effective for other body regions and long‐term subject outcomes. Level of Evidence: Level 4. PMID:23593553

Killing two birds with one stone: successful opioid monotherapy in intractable migraine-triggered epilepsy, a case series

PubMed Central

Derakhshan, Iraj

2017-01-01

The novel concept explored in this case series is the primacy of headaches in generating seizures in those patients who suffer from migraine-triggered epilepsy. In this series, once the migraine headaches were fully suppressed, via daily scheduled opioid therapy, the seizures also stopped. Seizures returned, however, after the patients stopped the opiate regimen for any reason. The above pharmacological scenario is reminiscent of a similar but naturalistic course of events reported on the salutary effects of ketogenic diet, or changes in life style, in similar cases of migraine-triggered epilepsy. The primacy of migraine in treating what has been named ‘seizure headaches’ is seen in two other scenarios (i.e. the salutary effect of ketogenic diet and lifestyle changes resulting in restoration of one’s sleeping pattern) thus stopping the migraine as well as the seizures associated with the same. This case series recounts the same phenomenon via utilizing around-the-clock maintenance opioid therapy. PMID:28203347

Killing two birds with one stone: successful opioid monotherapy in intractable migraine-triggered epilepsy, a case series.

PubMed

Derakhshan, Iraj

2017-01-01

The novel concept explored in this case series is the primacy of headaches in generating seizures in those patients who suffer from migraine-triggered epilepsy. In this series, once the migraine headaches were fully suppressed, via daily scheduled opioid therapy, the seizures also stopped. Seizures returned, however, after the patients stopped the opiate regimen for any reason. The above pharmacological scenario is reminiscent of a similar but naturalistic course of events reported on the salutary effects of ketogenic diet, or changes in life style, in similar cases of migraine-triggered epilepsy. The primacy of migraine in treating what has been named 'seizure headaches' is seen in two other scenarios (i.e. the salutary effect of ketogenic diet and lifestyle changes resulting in restoration of one's sleeping pattern) thus stopping the migraine as well as the seizures associated with the same. This case series recounts the same phenomenon via utilizing around-the-clock maintenance opioid therapy.

Desensitization of triggers and urge reprocessing for pathological gambling: a case series.

PubMed

Bae, Hwallip; Han, Changwoo; Kim, Daeho

2015-03-01

This case series introduces the desensitization of triggers and urge reprocessing (DeTUR), as a promising adjunctive therapy in addition to comprehensive treatment package for pathological gambling. This addiction protocol of eye movement desensitization and reprocessing was delivered to four male inpatients admitted to a 10-week inpatient program for pathological gambling. The therapist gave three 60-min weekly sessions of the DeTUR using bilateral stimulation (horizontal eye movements or alternative tactile stimuli) focusing on the hierarchy of triggering situations and the urge to initiate gambling behaviors. After treatment, self-reported gambling symptoms, depression, anxiety, and impulsiveness were all improved, and all the participants reported satisfaction with the therapy. They were followed up for 6 months and all maintained their abstinence from gambling and their symptomatic improvements. Given the efficiency (i.e., brevity and efficacy) of the treatment, a controlled study to confirm the effects of the DeTUR on pathological gambling would be justified.

The food additive vanillic acid controls transgene expression in mammalian cells and mice.

PubMed

Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

2012-03-01

Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

Carpal Tunnel Syndrome: Effectiveness of Physical Therapy and Electrophysical Modalities. An Updated Systematic Review of Randomized Controlled Trials.

PubMed

Huisstede, Bionka M; Hoogvliet, Peter; Franke, Thierry P; Randsdorp, Manon S; Koes, Bart W

2017-09-20

To review scientific literature studying the effectiveness of physical therapy and electrophysical modalities for carpal tunnel syndrome (CTS). The Cochrane Library, PubMed, Embase, CINAHL, and Physiotherapy Evidence Database. Two reviewers independently applied the inclusion criteria to select potential eligible studies. Two reviewers independently extracted the data and assessed the methodologic quality using the Cochrane Risk of Bias Tool. A best-evidence synthesis was performed to summarize the results of the included studies (2 reviews and 22 randomized controlled trials [RCTs]). For physical therapy, moderate evidence was found for myofascial massage therapy versus ischemic compression on latent, or active, trigger points or low-level laser therapy in the short term. For several electrophysical modalities, moderate evidence was found in the short term (ultrasound vs placebo, ultrasound as single intervention vs other nonsurgical interventions, ultrasound vs corticosteroid injection plus a neutral wrist splint, local microwave hyperthermia vs placebo, iontophoresis vs phonophoresis, pulsed radiofrequency added to wrist splint, continuous vs pulsed vs placebo shortwave diathermy, and interferential current vs transcutaneous electrical nerve stimulation vs a night-only wrist splint). In the midterm, moderate evidence was found in favor of radial extracorporeal shockwave therapy (ESWT) added to a neutral wrist splint, in favor of ESWT versus ultrasound, or cryo-ultrasound, and in favor of ultrasound versus placebo. For all other interventions studied, only limited, conflicting, or no evidence was found. No RCTs investigating the long-term effects of physical therapy and electrophysical modalities were found. Because of heterogeneity in the treatment parameters used in the included RCTs, optimal treatment parameters could not be identified. Moderate evidence was found for several physical therapy and electrophysical modalities for CTS in the short term and midterm. Future studies should concentrate on long-term effects and which treatment parameters of physical therapy and electrophysical modalities are most effective for CTS. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Light dosimetry for focused and defocused beam irradiation in multi-layered tissue models

NASA Astrophysics Data System (ADS)

Petrova, Kremena S.; Stoykova, Elena V.

2006-09-01

Treatment of acupuncture points, trigger points, joint inflammations in low level laser therapy as well as various applications of lasers for treatment of soft tissues in dental medicine, require irradiation by a narrow converging laser beam. The aim of this study is to compare light delivery produced by focused or defocused narrow beam irradiation in a multi-layered skin tissue model at increasing depth of the target. The task is solved by 3-D Monte-Carlo simulation for matched and mismatched refractive indices at the tissue/ambient medium interface. The modeled light beams have a circular cross-section at the tissue entrance with uniform or Gaussian intensity distribution. Three are the tissue models used in simulation : i) a bloodless skin layer; ii) a bloodless skin layer with embedded scattering object; iii) a skin layer with small blood vessels of varying size, which are modeled as infinite cylinders parallel to the tissue surface located at different depths. Optical properties (absorption coefficient, scattering coefficient, anisotropy factor, g, and index of refraction) of different tissue constituents are chosen from the literature.

Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.

PubMed

Yu, Shuangjiang; Ding, Jianxun; He, Chaoliang; Cao, Yue; Xu, Weiguo; Chen, Xuesi

2014-05-01

Nanoscale carriers that stably load drugs in blood circulation and release the payloads in desirable sites in response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, a novel type of disulfide core cross-linked micelles, which are facilely fabricated by cross-linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic disulfide moieties via a thiol-disulfide exchange reaction, are developed. A broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles as a model drug. The drug release from the core cross-linked polyurethane micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer saline (PBS), whereas it is markedly accelerated with addition of an intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL-PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX-loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti-tumor efficacy and reduced toxic side effects are key aspects of efficient cancer therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a bio-triggered drug delivery system for cancer therapy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomimetic HDL nanoparticle mediated tumor targeted delivery of indocyanine green for enhanced photodynamic therapy.

PubMed

Wang, Yazhe; Wang, Cheng; Ding, Yang; Li, Jing; Li, Min; Liang, Xiao; Zhou, Jianping; Wang, Wei

2016-12-01

Photodynamic therapy has emerged as a promising strategy for cancer treatment. To ensure the efficient delivery of a photosensitizer to tumor for anticancer effect, a safe and tumor-specific delivery system is highly desirable. Herein, we introduce a novel biomimetic nanoparticle named rHDL/ICG (rHDL/I), by loading amphiphilic near-infrared (NIR) fluorescent dye indocyanine green (ICG) into reconstituted high density lipoproteins (rHDL). In this system, rHDL can mediate photoprotection effect and receptor-guided tumor-targeting transportation of cargos into cells. Upon NIR irradiation, ICG can generate fluorescent imaging signals for diagnosis and monitoring therapeutic activity, and produce singlet oxygen to trigger photodynamic therapy (PDT). Our studies demonstrated that rHDL/I exhibited excellent size and fluorescence stability, light-triggered controlled release feature, and neglectable hemolytic activity. It also showed equivalent NIR response compared to free ICG under laser irradiation. Importantly, the fluorescent signal of ICG loaded in rHDL/I could be visualized subcellularly in vitro and exhibited metabolic distribution in vivo, presenting superior tumor targeting and internalization. This NIR-triggered image-guided nanoparticle produced outstanding therapeutic outcomes against cancer cells, demonstrating great potential of biomimetic delivery vehicles in future clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Severely deranged vital signs as triggers for acute treatment modifications on an intensive care unit in a low-income country.

PubMed

Schell, Carl Otto; Castegren, Markus; Lugazia, Edwin; Blixt, Jonas; Mulungu, Moses; Konrad, David; Baker, Tim

2015-07-25

Critical care saves lives of the young with reversible disease. Little is known about critical care services in low-income countries. In a setting with a shortage of doctors the actions of the nurse bedside are likely to have a major impact on the outcome of critically ill patients with rapidly changing physiology. Identification of severely deranged vital signs and subsequent treatment modifications are the basis of modern routines in critical care, for example goal directed therapy and rapid response teams. This study assesses how often severely deranged vital signs trigger an acute treatment modification on an Intensive Care Unit (ICU) in Tanzania. A medical records based, observational study. Vital signs (conscious level, respiratory rate, oxygen saturation, heart rate and systolic blood pressure) were collected as repeated point prevalences three times per day in a 1-month period for all adult patients on the ICU. Severely deranged vital signs were identified and treatment modifications within 1 h were noted. Of 615 vital signs studied, 126 (18%) were severely deranged. An acute treatment modification was in total indicated in 53 situations and was carried out three times (6%) (2/32 for hypotension, 0/8 for tachypnoea, 1/6 for tachycardia, 0/4 for unconsciousness and 0/3 for hypoxia). This study suggests that severely deranged vital signs are common and infrequently lead to acute treatment modifications on an ICU in a low-income country. There may be potential to improve outcome if nurses are guided to administer acute treatment modifications by using a vital sign directed approach. A prospective study of a vital sign directed therapy protocol is underway.

Neurophysiological and clinical effects of dry needling in patients with upper trapezius myofascial trigger points.

PubMed

Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

2017-01-01

Dry needling (DN) is a widely used in treatment of myofascial trigger points (MTrPs). The purpose of this pretest-posttest clinical trial was to investigate the neurophysiological and clinical effects of DN in patients with MTrPs. A sample of 20 patients (3 man, 17 women; mean age 31.7 ± 10.8) with upper trapezius MTrPs received one session of deep DN. The outcomes of neuromuscular junction response (NMJR), sympathetic skin response (SSR), pain intensity (PI) and pressure pain threshold (PPT) were measured at baseline and immediately after DN. There were significant improvements in SSR latency and amplitude, pain, and PPT after DN. The NMJR decreased and returned to normal after DN. A single session of DN to the active upper trapezius MTrP was effective in improving pain, PPT, NMJR, and SSR in patients with myofascial trigger points. Further studies are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in Psychological Parameters in Patients with Tension-type Headache Following Massage Therapy: A Pilot Study

PubMed Central

Moraska, Albert; Chandler, Clint

2009-01-01

Investigations into complementary and alternative medicine (CAM) approaches to address stress, depression, and anxiety of those experiencing chronic pain are rare. The objective of this pilot study was to assess the value of a structured massage therapy program, with a focus on myofascial trigger points, on psychological measures associated with tension-type headache. Participants were enrolled in an open-label trial using a baseline control with four 3-week phases: baseline, massage (two 3-week periods) and a follow-up phase. Eighteen subjects with episodic or chronic tension-type headache were enrolled and evaluated at 3-week intervals using the State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale. The Daily Stress Inventory was administered over 7-day periods during baseline and the final week of massage. Twice weekly, 45-minute massage therapy sessions commenced following the baseline phase and continued for 6 weeks. A significant improvement in all psychological measures was detected over the timeframe of the study. Post hoc evaluation indicated improvement over baseline for depression and trait anxiety following 6 weeks of massage, but not 3 weeks. A reduction in the number of events deemed stressful as well as their respective impact was detected. This pilot study provides evidence for reduction of affective distress in a chronic pain population, suggesting the need for more rigorously controlled studies using massage therapy to address psychological measures associated with TTH. PMID:20046550

“I was thinking too much”: experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe

PubMed Central

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirgh, Conall; Chibanda, Dixon; Abas, Melanie

2015-01-01

Objective To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. Methods In-depth qualitative interviews were conducted with 47 (female =31) HIV-positive adults who scored above the cut-point on a locally-validated scale for common mental disorders. Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. Results The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of common mental disorders (“thinking too much”, changes to appetite and sleep, “burdened heart”, and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with common mental disorders. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income generating activities, and family engagement in mental health care. Conclusions Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce common mental disorders and poor adherence to antiretroviral therapy. PMID:25754063

An electronic trigger tool to optimise intravenous to oral antibiotic switch: a controlled, interrupted time series study.

PubMed

Berrevoets, Marvin A H; Pot, Johannes Hans L W; Houterman, Anne E; Dofferhoff, Anton Ton S M; Nabuurs-Franssen, Marrigje H; Fleuren, Hanneke W H A; Kullberg, Bart-Jan; Schouten, Jeroen A; Sprong, Tom

2017-01-01

Timely switch from intravenous (iv) antibiotics to oral therapy is a key component of antimicrobial stewardship programs in order to improve patient safety, promote early discharge and reduce costs. We have introduced a time-efficient and easily implementable intervention that relies on a computerized trigger tool, which identifies patients who are candidates for an iv to oral antibiotic switch. The intervention was introduced on all internal medicine wards in a teaching hospital. Patients were automatically identified by an electronic trigger tool when parenteral antibiotics were used for >48 h and clinical or pharmacological data did not preclude switch therapy. A weekly educational session was introduced to alert the physicians on the intervention wards. The intervention wards were compared with control wards, which included all other hospital wards. An interrupted time-series analysis was performed to compare the pre-intervention period with the post-intervention period using '% of i.v. prescriptions >72 h' and 'median duration of iv therapy per prescription' as outcomes. We performed a detailed prospective evaluation on a subset of 244 prescriptions to evaluate the efficacy and appropriateness of the intervention. The number of intravenous prescriptions longer than 72 h was reduced by 19% in the intervention group ( n  = 1519) ( p  < 0.01) and the median duration of iv antibiotics was reduced with 0.8 days ( p  = <0.05). Compared to the control group ( n  = 4366) the intervention was responsible for an additional decrease of 13% ( p  < 0.05) in prolonged prescriptions. The detailed prospective evaluation of a subgroup of patients showed that adherence to the electronic reminder was 72%. An electronic trigger tool combined with a weekly educational session was effective in reducing the duration of intravenous antimicrobial therapy.

PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.

PubMed

Di Loreto, S; D'Angelo, B; D'Amico, M A; Benedetti, E; Cristiano, L; Cinque, B; Cifone, M G; Cerù, M P; Festuccia, C; Cimini, A

2007-06-01

Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures. Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells. The results obtained demonstrate that many, but not all, oleic acid effects are mediated by PPARbeta and support a role for PPARbeta in neuronal differentiation strongly pointing towards PPAR ligands as new therapeutic strategies against progression and recurrences of neuroblastoma.

High-Quality T2-Weighted 4-Dimensional Magnetic Resonance Imaging for Radiation Therapy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Dongsu; Caruthers, Shelton D.; Glide-Hurst, Carri

2015-06-01

Purpose: The purpose of this study was to improve triggering efficiency of the prospective respiratory amplitude-triggered 4-dimensional magnetic resonance imaging (4DMRI) method and to develop a 4DMRI imaging protocol that could offer T2 weighting for better tumor visualization, good spatial coverage and spatial resolution, and respiratory motion sampling within a reasonable amount of time for radiation therapy applications. Methods and Materials: The respiratory state splitting (RSS) and multi-shot acquisition (MSA) methods were analytically compared and validated in a simulation study by using the respiratory signals from 10 healthy human subjects. The RSS method was more effective in improving triggering efficiency.more » It was implemented in prospective respiratory amplitude-triggered 4DMRI. 4DMRI image datasets were acquired from 5 healthy human subjects. Liver motion was estimated using the acquired 4DMRI image datasets. Results: The simulation study showed the RSS method was more effective for improving triggering efficiency than the MSA method. The average reductions in 4DMRI acquisition times were 36% and 10% for the RSS and MSA methods, respectively. The human subject study showed that T2-weighted 4DMRI with 10 respiratory states, 60 slices at a spatial resolution of 1.5 × 1.5 × 3.0 mm{sup 3} could be acquired in 9 to 18 minutes, depending on the individual's breath pattern. Based on the acquired 4DMRI image datasets, the ranges of peak-to-peak liver displacements among 5 human subjects were 9.0 to 12.9 mm, 2.5 to 3.9 mm, and 0.5 to 2.3 mm in superior-inferior, anterior-posterior, and left-right directions, respectively. Conclusions: We demonstrated that with the RSS method, it was feasible to acquire high-quality T2-weighted 4DMRI within a reasonable amount of time for radiation therapy applications.« less

Systemic Agents for Severe Atopic Dermatitis in Children.

PubMed

Notaro, Eliza R; Sidbury, Robert

2015-12-01

Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic, scaly, erythematous papules and plaques frequently associated with superinfection. The lifelong prevalence of AD is over 20 % in affluent countries. When a child with severe AD is not responding to optimized topical therapy including phototherapy, and relevant triggers cannot be identified or avoided, systemic therapy should be considered. If studies show early aggressive intervention can prevent one from advancing along the atopic march, and relevant triggers such as food allergies cannot be either identified or avoided, systemic therapy may also play a prophylactic role. Though the majority of evidence exists in adult populations, four systemic non-specific immunosuppressive or immunomodulatory drugs have demonstrated efficacy in AD and are used in most patients requiring this level of intervention regardless of age: cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. This article reviews the use of these medications as well as several promising targeted therapies currently in development including dupilumab and apremilast. We briefly cover several other systemic interventions that have been studied in children with atopic dermatitis.

Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach

PubMed Central

Wytra̦żek, Marcin; Huber, Juliusz; Lisiński, Przemysław

Summary Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett’s scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome PMID:22152435

Headaches: a Review of the Role of Dietary Factors.

PubMed

Zaeem, Zoya; Zhou, Lily; Dilli, Esma

2016-11-01

Dietary triggers are commonly reported by patients with a variety of headaches, particularly those with migraines. The presence of any specific dietary trigger in migraine patients varies from 10 to 64 % depending on study population and methodology. Some foods trigger headache within an hour while others develop within 12 h post ingestion. Alcohol (especially red wine and beer), chocolate, caffeine, dairy products such as aged cheese, food preservatives with nitrates and nitrites, monosodium glutamate (MSG), and artificial sweeteners such as aspartame have all been studied as migraine triggers in the past. This review focuses the evidence linking these compounds to headache and examines the prevalence of these triggers from prior population-based studies. Recent literature surrounding headache related to fasting and weight loss as well as elimination diets based on serum food antibody testing will also be summarized to help physicians recommend low-risk, non-pharmacological adjunctive therapies for patients with debilitating headaches.

Psychosocial Impact of Personalized Therapies in Oncology.

PubMed

Schilling, Georgia; Schulz-Kindermann, Frank

2018-01-01

Personalized medicine is a keyword in modern oncology summarizing biomarker-driven targeted therapies. Those novel agents enhance our therapeutic portfolio and offer new options for our patients. But the term is often misleading and implicates a tailored therapy to the individual person, but it rather means a treatment stratified on genetic characteristics of the tumor. Molecular therapies raise expectations of curability or long-term treatments making former life-threatening diseases to more chronic ones but this is true only for some patients. So we have to carefully communicate with our patients about the options and limitations of those modern therapies not to trigger disappointments.

On the Transition from Reconsolidation to Extinction of Contextual Fear Memories

ERIC Educational Resources Information Center

Cassini, Lindsey F.; Flavell, Charlotte R.; Amaral, Olavo B.; Lee, Jonathan L. C.

2017-01-01

Retrieval of an associative memory can lead to different phenomena. Brief reexposure sessions tend to trigger reconsolidation, whereas more extended ones trigger extinction. In appetitive and fear cued Pavlovian memories, an intermediate "null point" period has been observed where neither process seems to be engaged. Here we investigated…

Effects of Forgiveness Therapy on Anger, Mood, and Vulnerability to Substance Use among Inpatient Substance-Dependent Clients

ERIC Educational Resources Information Center

Lin, Wei-Fen; Mack, David; Enright, Robert D.; Krahn, Dean; Baskin, Thomas W.

2004-01-01

Anger and related emotions have been identified as triggers in substance use. Forgiveness therapy (FT) targets anger, anxiety, and depression as foci of treatment. Fourteen patients with substance dependence from a local residential treatment facility were randomly assigned to and completed either 12 approximately twice-weekly sessions of…

Application of a Flexible, Clinically Driven Approach for Anger Reduction in the Case of Mr. P

ERIC Educational Resources Information Center

Kassinove, Howard; Tafrate, Raymond Chip

2011-01-01

We treat maladaptive anger in adults with a program based on traditional behavior therapy and cognitive behavior therapy. To these, we add client-centered motivational interviewing techniques. With the goal of modifying maladaptive stimulus-response relationships, our specific aim is to reduce anger reactivity to aversive triggers. Thus, in daily…

A Descriptive Study of the Practice Patterns of Massage New Zealand Massage Therapists

PubMed Central

Smith, Joanna M.; Sullivan, S. John; Baxter, G. David

2011-01-01

Background: Massage therapy has grown in popularity, yet little is known globally or in New Zealand about massage therapists and their practices. Purpose and Setting: The aims of this study were to describe the practice patterns of trained Massage New Zealand massage therapists in New Zealand private practice, with regard to therapist characteristics; practice modes and settings, and therapy characteristics; referral patterns; and massage therapy as an occupation. Research Design and Participants: A survey questionnaire was mailed to 66 trained massage therapist members of Massage New Zealand who were recruiting massage clients for a concurrent study of massage therapy culture. Results: Most massage therapists were women (83%), NZ European (76%), and holders of a massage diploma qualification (89%). Massage therapy was both a full- (58%) and part-time (42%) occupation, with the practice of massage therapy being the only source of employment for 70% of therapists. Nearly all therapists (94%) practiced massage for more than 40 weeks in the year, providing a median of 16 – 20 hours of direct client care per week. Most massage therapists worked in a “solo practice” (58%) and used a wide and active referral network. Almost all therapists treated musculoskeletal symptoms: the most common client issues or conditions treated were back pain/problem (99%), neck/shoulder pain/problem (99%), headache or migraine (99%), relaxation and stress reduction (96%), and regular recovery or maintenance massage (89%). The most frequent client fee per treatment was NZ$60 per hour in a clinic and NZ$1 per minute at a sports event or in the workplace. Therapeutic massage, relaxation massage, sports massage, and trigger-point therapy were the most common styles of massage therapy offered. Nearly all massage therapists (99%) undertook client assessment; 95% typically provided self-care recommendations; and 32% combined other complementary and alternative medicine therapies with their massage consultations. Conclusions: This study provides new information about the practice of massage therapy by trained massage therapists. It will help to inform the massage industry and other health care providers, potential funders, and policymakers about the provision of massage therapy in the NZ health care system. PMID:21589692

Comparison of the effects of mirror therapy and electromyography-triggered neuromuscular stimulation on hand functions in stroke patients: a pilot study.

PubMed

Amasyali, Saliha Y; Yaliman, Ayşe

2016-12-01

To determine the effectiveness of mirror therapy and electromyography (EMG)-triggered neuromuscular stimulation on improvement of functions of the upper extremity in patients with subacute stroke in comparison with conventional therapy as well as to evaluate the advantage of each treatment over another, we conducted a prospective, randomized, and controlled trial involving 24 patients with ischemic stroke. The mean age and mean time since stroke of the patients were 58.79±11.49 years and 5.25±2.25 months. Patients were assigned randomly to a mirror therapy group (MT group, n=9), which consisted of therapy with a mirror box 5 days/week, 30 min/day, for 3 weeks, an electrostimulation group (ES group, n=7), which consisted of therapy with EMG-triggered stimulation (EMG-stim) of similar duration and frequency of treatment as the MT group, and a control group (n=8). All the groups received conventional physiotherapy for the same period as the MT group. Patients in the MT group practiced their therapy at home after supervised sessions. The Fugl-Meyer scores of the upper extremity, grip force, wrist extension, and Box and Block Test were evaluated at baseline, after treatment, and at 3 months after the treatment. All of these measures were evaluated by a blinded researcher. We found that there was no significant improvement in wrist extension range and grip force in control group. The MT and EMG-stim were effective in increasing the Fugl-Meyer motor scale for upper extremity (MT group: P<0.01), increasing wrist extension range, grip force, and hand dexterity determined by the Box and Block Test (MT group and ES group P<0.05). Furthermore, hand skills were increased significantly in the MT group compared with the ES group at the follow-up assessment (P<0.05). This pilot study suggested that MT was more efficient in improving motor performance than physiotherapy alone. Also, MT may be more useful in improving the hand skills compared with EMG-stim. We assume that this difference might be related to the feasibility of maintenance of MT at home.

[Therapy of chronic urticaria and recurrent Quincke edema].

PubMed

Kündig, T M

2001-05-01

A rational and differential therapy of chronic urticaria and relapsing angioedema must be based on a precise classification of the disease. The general management as well as the specific therapy will have to consider the various trigger factors involved, the differences in the response rates to antiallergic drugs and the different prognoses of the urticaria subforms. Therefore this article will first briefly describe the most frequent subforms of urticaria and relapsing angioedema, and then discuss their management and treatment.

Monoclonal Antibodies against the MET/HGF Receptor and Its Ligand: Multitask Tools with Applications from Basic Research to Therapy

PubMed Central

Prat, Maria; Oltolina, Francesca; Basilico, Cristina

2014-01-01

Monoclonal antibodies can be seen as valuable tools for many aspects of basic as well as applied sciences. In the case of MET/HGFR, they allowed the identification of truncated isoforms of the receptor, as well as the dissection of different epitopes, establishing structure–function relationships. Antibodies directed against MET extracellular domain were found to be full or partial receptor agonists or antagonists. The agonists can mimic the effects of the different isoforms of the natural ligand, but with the advantage of being more stable than the latter. Thus, some agonist antibodies promote all the biological responses triggered by MET activation, including motility, proliferation, morphogenesis, and protection from apoptosis, while others can induce only a migratory response. On the other hand, antagonists can inhibit MET-driven biological functions either by competing with the ligand or by removing the receptor from the cell surface. Since MET/HGFR is often over-expressed and/or aberrantly activated in tumors, monoclonal antibodies can be used as probes for MET detection or as “bullets” to target MET-expressing tumor cells, thus pointing to their use in diagnosis and therapy. PMID:28548076

Combined strategies in the management of obesity.

PubMed

Dixon, John B; Dixon, Maureen E

2006-01-01

Obesity is a chronic relapsing disease requiring a similar long term approach to management as that of other chronic conditions. Management needs to be multifaceted aiming to achieve sustainable behavioural changes to physical activity and diet to alter the patient and family microenvironment to one favouring better weight control. A range of therapies including specific diets, calorie counting, meal replacements, very low calorie diets, pharmacotherapy, intragastric balloons and surgery can provide very useful additional benefit. Use of these should be guided by the extent of weight loss required to reduce BMI to an acceptable level with regard to the patient's ethnicity, risk and comorbid conditions. Patients need to set goals that are optimistic, but realistic, and understand the benefits of sustained modest weight loss and the likelihood of weight regain requiring repeat episodes of weight loss. Practitioners need to be informed about the efficacy of current therapies and their combinations to enhance choice of suitable methods for achieving the optimal weight loss required by the patient. They will also need to anticipate trigger points for renewed periods of weight loss in the event of weight regain, as relapse is likely but not a reason for abandoning the battle.

Soft-tissue injuries from sports activities and traffic accidents--treatment with low-level laser therapy: a multicenter double-blind placebo-controlled clinical study on 132 patients

NASA Astrophysics Data System (ADS)

Simunovic, Zlatko; Trobonjaca, Tatjana

2000-06-01

The aim of current multicenter clinical study was to assess the efficacy of low energy-level laser therapy (LLLT) in the treatment of soft tissue injuries compared to the placebo and classical phyiotherapeutic procedures. This clinical study was conducted in two centers located in Locarno, Switzerland and Opatija, Croatia. Two types of irradiation techniques were used: (1) direct, skin contact technique for treatment of trigger points where IR diode laser 830 nm continuous wave was applied; and (2) scanning technique for irradiation of larger surface area with use of Helium Neon laser 632.8 nm combined with IR diode laser 904 nm pulsed wave. Results were evaluated according to clinical parameters like: hematoma, swelling, heat, pan and loss of function. The findings were statistically analyzed via chi- square test. Results have demonstrated that the recovery process was accelerated in 85 percent of patients treated with LLLT compared to the control group of patients. The results and advantages obtained proved once again the efficacy of LLLT as a new and successful way to treat soft tissue injuries.

DNA repair mechanisms in cancer development and therapy

PubMed Central

Torgovnick, Alessandro; Schumacher, Björn

2015-01-01

DNA damage has been long recognized as causal factor for cancer development. When erroneous DNA repair leads to mutations or chromosomal aberrations affecting oncogenes and tumor suppressor genes, cells undergo malignant transformation resulting in cancerous growth. Genetic defects can predispose to cancer: mutations in distinct DNA repair systems elevate the susceptibility to various cancer types. However, DNA damage not only comprises a root cause for cancer development but also continues to provide an important avenue for chemo- and radiotherapy. Since the beginning of cancer therapy, genotoxic agents that trigger DNA damage checkpoints have been applied to halt the growth and trigger the apoptotic demise of cancer cells. We provide an overview about the involvement of DNA repair systems in cancer prevention and the classes of genotoxins that are commonly used for the treatment of cancer. A better understanding of the roles and interactions of the highly complex DNA repair machineries will lead to important improvements in cancer therapy. PMID:25954303

Recent Progress in Light-Triggered Nanotheranostics for Cancer Treatment

PubMed Central

Zhang, Pengcheng; Hu, Chunhua; Ran, Wei; Meng, Jia; Yin, Qi; Li, Yaping

2016-01-01

Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in cancer therapy, many novel and powerful LTNs have been developed, and are mainly prepared from photosensitizers (PSs) ranging from small organic dyes such as porphyrin- and cyanine-based dyes, semiconducting polymers, to inorganic nanomaterials such as gold nanoparticles, transition metal chalcogenides, carbon nanotubes and graphene. Using LTNs and localized irradiation in combination, complete tumor ablation could be achieved in tumor-bearing animal models without causing significant toxicity. Given their great advances and promising future, we herein review LTNs that have been tested in vivo with a highlight on progress that has been made in the past a couple of years. The current challenges faced by these LTNs are also briefly discussed. PMID:27217830

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Update on dietary therapy for eosinophilic esophagitis in children and adults.

PubMed

Molina-Infante, Javier; Gonzalez-Cordero, Pedro Luis; Arias, Angel; Lucendo, Alfredo J

2017-02-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disease triggered predominantly, but not excusively, by food antigens. Elimination diet thus remains the only therapy targeting the cause of the disease. Importantly, EoE is a unique form of non-IgE mediated food allergy, largely dependant upon delayed, cell-mediated hypersensitivity. Areas covered: A comprehensive review of literature to summarize and update the most relevant advances on dietary therapy for pediatric and adult EoE patients is conducted. Expert commentary: None of the currently available food allergy tests adequately predict food triggers for EoE, especially in adults. Elemental diet (exclusive feeding with aminoacid-based formulas) and empiric six-food elimination diet, withdrawing cow´s milk, wheat, egg, soy, nuts and fish/seafood for 6 weeks, have consistently shown the best cure rates. However, their high level of restriction and need for multiple endoscopies (top-down approach) have been a deterrent for patients and physicians. Less restrictive empiric schemes, like a four-food (animal milk, gluten-containing cereals, egg, legumes) or a two-food (animal milk and gluten-containing cereals) elimination diet have lately shown encouraging results. Therefore, a novel step-up strategy (2-4-6) may enhance patient uptake and promptly identify most responders to empiric diets with few food triggers, besides saving unnecessary dietary restrictions and endoscopic procedures.

Emergence of psychotic content in psychotherapy: An exploratory qualitative analysis of content, process, and therapist variables in a single case study.

PubMed

Leonhardt, Bethany L; Kukla, Marina; Belanger, Elizabeth; Chaudoin-Patzoldt, Kelly A; Buck, Kelly D; Minor, Kyle S; Vohs, Jenifer L; Hamm, Jay A; Lysaker, Paul H

2018-03-01

Emerging integrative metacognitive therapies for schizophrenia seek to promote subjective aspects of recovery. Beyond symptom remission, they are concerned with shared meaning-making and intersubjective processes. It is unclear, however, how such therapies should understand and respond to psychotic content that threatens meaning-making in therapeutic contexts. Accordingly, we sought to understand what factors precede and potentially trigger psychotic content within psychotherapy and what aids in resolution and return to meaning-making. Forty-eight transcripts from a single psychotherapy case were analyzed with thematic analysis. Passages of delusional or disorganized content were identified and themes present prior to the emergence and resolution of such material were identified and coded. Themes that preceded the emergence of psychotic content varied across early, middle, and late phases of therapy. Material related to the patient's experience of inadequacy and potential vulnerability, therapist setting boundaries within the therapeutic relationship and making challenges appeared to trigger psychotic content, especially early in treatment. Psychotic content may emerge in session following identifiable antecedents which change over phases of therapy. Attending to psychotic content by assuming a non-hierarchical stance and not dismissing psychotic content may aid in maintaining intersubjectivity and support patient's movements toward recovery in integrative metacognitive therapies.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

PubMed

Sun, Yu-Yo; Morozov, Yury M; Yang, Dianer; Li, Yikun; Dunn, R Scott; Rakic, Pasko; Chan, Pak H; Abe, Koji; Lindquist, Diana M; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Synergy of Combined tPA-Edaravone Therapy in Experimental Thrombotic Stroke

PubMed Central

Sun, Yu-Yo; Morozov, Yury M.; Yang, Dianer; Li, Yikun; Dunn, R. Scott; Rakic, Pasko; Chan, Pak H.; Abe, Koji; Lindquist, Diana M.; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h – but not at 4 h post-tHI – significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation. PMID:24911517

Disseminated intravascular coagulation: pathophysiology and principles of management.

PubMed

Marwaha, R K; Mitra, S; Marwaha, N

1998-03-01

DIC is a thrombohemorrhagic syndrome which occurs in association with well-defined clinical disorders such as septicemia, acute leukemia, snake envenomation, hypoxic states, etc. These disease conditions trigger the coagulation cascade in vivo resulting in formation of microthrombi, activation of fibrinolysis and a bleeding tendency. The important and most frequently observed laboratory abberrations include reduced platelet counts, low levels of fibrinogen, factors V and XIII with increased FDP's. Therapy primarily consists of recognizing the cause of DIC, removing the triggering process and administering anticoagulant therapy in specific situations. Component replacement is required if patients continue to bleed inspite of instituting the above mentioned measures. Rarely, drugs which inhibit fibrinolysis may be indicated. Early recognition and prompt institution of appropriate remedial measures coupled with adequate laboratory monitoring help in reducing morbidity and mortality due to DIC.

Orion Exploration Flight Test-1 Contingency Drogue Deploy Velocity Trigger

NASA Technical Reports Server (NTRS)

Gay, Robert S.; Stochowiak, Susan; Smith, Kelly

2013-01-01

As a backup to the GPS-aided Kalman filter and the Barometric altimeter, an "adjusted" velocity trigger is used during entry to trigger the chain of events that leads to drogue chute deploy for the Orion Multi-Purpose Crew Vehicle (MPCV) Exploration Flight Test-1 (EFT-1). Even though this scenario is multiple failures deep, the Orion Guidance, Navigation, and Control (GN&C) software makes use of a clever technique that was taken from the Mars Science Laboratory (MSL) program, which recently successfully landing the Curiosity rover on Mars. MSL used this technique to jettison the heat shield at the proper time during descent. Originally, Orion use the un-adjusted navigated velocity, but the removal of the Star Tracker to save costs for EFT-1, increased attitude errors which increased inertial propagation errors to the point where the un-adjusted velocity caused altitude dispersions at drogue deploy to be too large. Thus, to reduce dispersions, the velocity vector is projected onto a "reference" vector that represents the nominal "truth" vector at the desired point in the trajectory. Because the navigation errors are largely perpendicular to the truth vector, this projection significantly reduces dispersions in the velocity magnitude. This paper will detail the evolution of this trigger method for the Orion project and cover the various methods tested to determine the reference "truth" vector; and at what point in the trajectory it should be computed.

Considerations and Changes in the Evaluation, Management, and Outcomes in the Management of Diverticular Disease: The Diagnosis, Pathology, and Treatment of Diverticular Colitis.

PubMed

Kucejko, Robert J; Poggio, Juan L

2018-07-01

Diverticular colitis, also known as segmental colitis associated with diverticulosis, is a colonic inflammatory disorder on the spectrum of inflammatory bowel disease (IBD). The disease consists of macroscopic and microscopic inflammation affecting inter-diverticular mucosa, sparing peri-diverticular mucosa, with inflammation confined to the descending and sigmoid colon. The disease likely arises from the altered immune response of an individual, genetically susceptible to the IBD spectrum of diseases. Patients with segmental colitis associated with diverticulosis (SCAD) are typically older, and likely represent a subgroup of IBD-susceptible patients who lacked an environmental trigger until that point in their life. Most patients remain in remission with initial treatments of mesalamine or topical steroids, and maintenance mesalamine afterwards. Only the most severe form of the disease necessitates immunomodulatory therapy and the consideration of surgery.

A Primer on Hemodialysis From an Interventional Radiology Perspective.

PubMed

Sheth, Rahul A; Sheth, Anil U

2017-03-01

Interventional radiologists play a central role in the care of patients with end-stage renal disease receiving renal replacement therapy. Ensuring that a patient׳s dialysis access remains suitable for high-quality dialysis is of paramount importance. However, although much has been spoken and written about endovascular techniques and outcomes based on angiographic criteria, little is generally known regarding the function and therefore the requirements of hemodialysis. In this article, we provide a heuristic overview of the mechanics of hemodialysis, with an emphasis on the "breaking points" in the extracorporeal circuit that trigger a patient׳s referral to Interventional Radiology. We also describe how dialysis quality is increasingly becoming linked with dialysis reimbursements. It is thus becoming progressively incumbent on the interventional radiologist to not only ensure that a patient receives high-quality outpatient dialysis but also that the patient׳s dialysis center meets its performance metrics. Copyright © 2017 Elsevier Inc. All rights reserved.

Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms.

PubMed

Shoemaker, Ritchie C; House, Dennis E

2006-01-01

Occupants of water-damaged buildings (WDBs) with evidence of microbial amplification often describe a syndrome involving multiple organ systems, commonly referred to as "sick building syndrome" (SBS), following chronic exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins, antigens, lipopolysaccharides, and biologically produced volatile compounds. A case-series study with medical assessments at five time points was conducted to characterize the syndrome after a double-blinded, placebo-controlled clinical trial conducted among a group of study participants investigated the efficacy of cholestyramine (CSM) therapy. The general hypothesis of the time series study was that chronic exposure to the indoor air of WDBs is associated with SBS. Consecutive clinical patients were screened for diagnosis of SBS using criteria of exposure potential, symptoms involving at least five organ systems, and the absence of confounding factors. Twenty-eight cases signed voluntary consent forms for participation in the time-series study and provided samples of microbial contaminants from water-damaged areas in the buildings they occupied. Twenty-six participants with a group-mean duration of illness of 11 months completed examinations at all five study time points. Thirteen of those participants also agreed to complete a double-blinded, placebo-controlled clinical trial. Data from Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and visual contrast sensitivity (VCS), an indicator of neurological function, was abnormally low in all participants. Measurements of matrix metalloproteinase 9 (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2 weeks of CSM therapy to enhance toxin elimination rates, measurements at Time Point 2 indicated group-means of 4 symptoms with 65% improvement in VCS at mid-spatial frequency-both statistically significant improvements relative to Time Point 1. Moderate improvements were seen in MMP9, leptin, and VEGF serum levels. The improvements in health status were maintained at Time Point 3 following a 2-week period during which CSM therapy was suspended and the participants avoid re-exposure to the WDBs. Participants reoccupied the respective WDBs for 3 days without CSM therapy, and all participants reported relapse at Time Point 4. The group-mean number of symptoms increased from 4 at Time Point 2 to 15 and VCS at mid-spatial frequency declined by 42%, both statistically significant differences relative to Time Point 2. Statistically significant differences in the group-mean levels of MMP9 and leptin relative to Time Point 2 were also observed. CSM therapy was reinstated for 2 weeks prior to assessments at Time Point 5. Measurements at Time Point 5 indicated group-means of 3 symptoms and a 69% increase in VCS, both results statistically different from those at Time Points 1 and 4. Optically corrected Snellen Distance Equivalent visual acuity scores did not vary significantly over the course of the study. Group-mean levels of MMP9 and leptin showed statistically significant improvement at Time Point 5 relative to Time Points 1 and 4, and the proportion of participants with abnormal VEGF levels was significantly lower at Time Point 5 than at Time Point 1. The number of participants at Time Point 5 with abnormal levels of MMP9, leptin, VEGF, and pulmonary function were 10, 10, 9, and 7, respectively. The level of IgE was not re-measured because of the low incidence of abnormality at Time Point 1, and MSH was not re-measured because previously published data indicated a long time course for MSH improvement. The results from the time series study supported the general study hypothesis that exposure to the indoor air of WDBs is associated with SBS. High levels of MMP9 indicated that exposure to the complex mixture of substances in the indoor air of the WDBs triggered a pro-inflammatory cytokine response. A model describing modes of action along a pathway leading to biotoxin-associated illness is presented to organize current knowledge into testable hypotheses. The model links an inflammatory response with tissue hypoxia, as indicated by abnormal levels of VEGF, and disruption of the proopiomelanocortin pathway in the hypothalamus, as evidenced by abnormalities in leptin and MSH levels. Results from the clinical trial on CSM efficacy indicated highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline in the 7 participants randomly assigned to receive 2 weeks of CSM therapy, but no improvement in the 6 participants assigned placebo therapy during that time interval. However, those 6 participants also showed a highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline following a subsequent 2-week period of CSM therapy. Because the only known benefit of CSM therapy is to enhance the elimination rates of substances that accumulate in bile by preventing re-absorption during enterohepatic re-circulation, results from the clinical trial also supported the general study hypothesis that SBS is associated with exposure to WDBs because the only relevant function of CSM is to bind and remove toxigenic compounds. Only research that focuses on the signs, symptoms, and biochemical markers of patients with persistent illness following acute and/or chronic exposure to WDBs can further the development of the model describing modes of action in the biotoxin-associated pathway and guide the development of innovative and efficacious therapeutic interventions.

Acute Nicotine Enhances Spontaneous Recovery of Contextual Fear and Changes "c-fos" Early Gene Expression in Infralimbic Cortex, Hippocampus, and Amygdala

ERIC Educational Resources Information Center

Kutlu, Munir G.; Tumolo, Jessica M.; Holliday, Erica; Garrett, Brendan; Gould, Thomas J.

2016-01-01

Exposure therapy, which focuses on extinguishing fear-triggering cues and contexts, is widely used to treat post-traumatic stress disorder (PTSD). Yet, PTSD patients who received successful exposure therapy are vulnerable to relapse of fear response after a period of time, a phenomenon known as spontaneous recovery (SR). Increasing evidence…

Smart, Injury-Triggered Therapy for Ocular Trauma

DTIC Science & Technology

2016-10-01

prognosis due to retinal cell death , scar formation, and lack of functional regeneration. Proliferative vitreoretinopathy (PVR), a form of intraocular...Proteases, Metalloproteinases, Cell death , Gene Therapy 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME...vision has a poor prognosis due to retinal cell death , scar formation, and lack of functional regeneration. Proliferative vitreoretinopathy (PVR), a

Anti-TNF therapy induced immune neutropenia in Crohns disease- report of 2 cases and review of literature.

PubMed

Sebastian, Shaji; Ashton, Katherine; Houston, Yasmine; Diggory, Tina Mary; Dore, Philip

2012-07-01

Transient neutropenia is reported in some patients on biologic therapy. We report two cases of severe neutropenia in patients with Crohn`s disease following treatment with anti-TNF therapy. In both cases neutrophil specific granulocyte autoantibodies were detected during period of neutropenia and disappeared on cessation of anti-TNF therapy. These may indicate that anti-TNF agents may produce autoimmune agranulocytosis by triggering production granulocyte autoantibodies. The long term management strategy for patients with anti-TNF therapy induced autoimmune neutropenia is uncertain. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Myofascial pain syndrome: a treatment review.

PubMed

Desai, Mehul J; Saini, Vikramjeet; Saini, Shawnjeet

2013-06-01

Myofascial pain syndrome (MPS) is defined as pain that originates from myofascial trigger points in skeletal muscle. It is prevalent in regional musculoskeletal pain syndromes, either alone or in combination with other pain generators. The appropriate evaluation and management of myofascial pain is an important part of musculoskeletal rehabilitation, and regional axial and limb pain syndromes. This article reviews the current hypotheses regarding the treatment modalities for myofascial trigger points and muscle pain. Through a critical evidence-based review of the pharmacologic and nonpharmacologic treatments, the authors aim to provide clinicians with a more comprehensive knowledge of the interventions for myofascial pain.

Low level laser therapy (GaAlInP 660 nm) in healing of a chronic venous ulcer: a case study

NASA Astrophysics Data System (ADS)

Botaro, C. A.; Faria, L. A.; Oliveira, R. G.; Bruno, R. X.; Rocha, C. A. Q. C.; Paiva-Oliveira, E. L.

2015-07-01

The venous ulcer represents approximately 70% to 90% of inferior member ulcers, and the most common etiological factor is venous insufficiency, triggered by venous hypertension. Currently in Brazil there are several types of lasers used in physiotherapy, which benefit biological potential, emitting low power radiation, with anti-inflammatory, analgesic, healing and circulatory effects. This study aimed at the analysis of low level laser therapy effects (LLLT) on the process of tissue repair in chronic venous ulcers. We conducted a case study of a patient with a venous ulcer in the lateral region of the right inferior member. The patient underwent LLLT, which used a GaAlInP diode laser, with a wavelength of 660 nm and energy density of 4 J cm-2 applied punctually at the edges of the wound, with an average distance of 1 cm between the points with a pen-laser perpendicular wrapped in paper and a plastic wrap, keeping contact with the tissue. After four months of therapy and a total of 21 sessions, an improvement was noticeable in the gross appearance of the wound, but after a month and a half without therapy, the dimensions of the wound increased in length and width. Analyzing the results of this case study allows us to conclude that the LLLT GaAlInP (660 nm) with an energy density of 4 J cm-2, was not successful in the healing of venous ulcers.

Reflex seizures in Rett syndrome.

PubMed

Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

2011-12-01

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Combined Electrocardiography- and Respiratory-Triggered CT of the Lung to Reduce Respiratory Misregistration Artifacts between Imaging Slabs in Free-Breathing Children: Initial Experience.

PubMed

Goo, Hyun Woo; Allmendinger, Thomas

2017-01-01

Cardiac and respiratory motion artifacts degrade the image quality of lung CT in free-breathing children. The aim of this study was to evaluate the effect of combined electrocardiography (ECG) and respiratory triggering on respiratory misregistration artifacts on lung CT in free-breathing children. In total, 15 children (median age 19 months, range 6 months-8 years; 7 boys), who underwent free-breathing ECG-triggered lung CT with and without respiratory-triggering were included. A pressure-sensing belt of a respiratory gating system was used to obtain the respiratory signal. The degree of respiratory misregistration artifacts between imaging slabs was graded on a 4-point scale (1, excellent image quality) on coronal and sagittal images and compared between ECG-triggered lung CT studies with and without respiratory triggering. A p value < 0.05 was considered significant. Lung CT with combined ECG and respiratory triggering showed significantly less respiratory misregistration artifacts than lung CT with ECG triggering only (1.1 ± 0.4 vs. 2.2 ± 1.0, p = 0.003). Additional respiratory-triggering reduces respiratory misregistration artifacts on ECG-triggered lung CT in free-breathing children.

Microencapsulation of Drugs: New Cancer Therapies and Improved Drug Delivery Derived from Micro Gravity Research

NASA Technical Reports Server (NTRS)

Morrison, Dennis R.; Haddad, Ruwaida S.

2003-01-01

Experiments on the ISS include encapsulation of several different anti-cancer drugs, magnetic triggering particles, and encapsulation of genetically engineered DNA. Eight experiments, using the MEPS-II apparatus, were conducted to study the limitations of the fluid shear and g-dependent forces. These studies included: 1) formation of anti-tumor microcapsules containing drugs for "Chemoembolization" of vascularized tumors, 2) formation of microcapsules containing a photo-activated drug which can be used for Photo Dynamic Therapy of solid tumors by activation with near infrared light (630 nm), 3) coencapsulation of magnetic trigger particles and anti-tumor drugs, and 4) encapsulation of plasmid DNA. The Microencapsulation Electrostatic Processing System (MEPS-II) is an automated apparatus modified for use in the ISS Express Rack. The process brings together two immiscible liquids, restricting fluid shear to permitting surface tension forces to predominate at the interface of the fluids. Microcapsules were recovered from all 8 experiments and are currently being analyzed for size distribution and drug content. Six NASA Patents have issued from the space research and several more are pending. The preliminary results from the Increment 5 - UF-2 experiments have provided new insight into the best formulations and conditions required to produce microcapsules of different drugs, esp. special capsules containing diagnostic imaging materials and triggered release particles. Co-encapsulation of multiple drugs and Photodynamic Therapy (PDT) drugs has enabled new engineering strategies for production of microcapsules on Earth designed for direct delivery into cancer tissues. Other microcapsules have now been made for treatment of deep tissue infections, clotting disorders, and to provide delivery of genetic engineered materials for potential gene therapy approaches. The MEPS-II apparatus remains in the ISS awaiting microencapsulation experiments to be conducted in micro-g, and returned to Earth for analysis.

Dynamic Pointing Triggers Shifts of Visual Attention in Young Infants

ERIC Educational Resources Information Center

Rohlfing, Katharina J.; Longo, Matthew R.; Bertenthal, Bennett I.

2012-01-01

Pointing, like eye gaze, is a deictic gesture that can be used to orient the attention of another person towards an object or an event. Previous research suggests that infants first begin to follow a pointing gesture between 10 and 13 months of age. We investigated whether sensitivity to pointing could be seen at younger ages employing a technique…

Treating angina pectoris by acupuncture therapy.

PubMed

Xu, Lixian; Xu, Hao; Gao, Wei; Wang, Wei; Zhang, Hui; Lu, Dominic P

2013-01-01

Acupuncture therapy on PC 6 (Neiguan) has a therapeutic effect on cardiac and chest ailments including angina pectoris. Additional beneficial acupuncture points are PC 4 (Ximen), HT 7 (Shenmen point), PC 7 (Daling point), PC 5 (Jianshi point), PC 3 (Quze point), CV 17 (Danzhong point), CV 6 (Qihai point), BL 15 (Xinshu point), L 20 (Pishu point), BL 17 (Geshu point), BL23 (Shenshu point), BL18 (Ganshu point), HT 5 (Tongli point), and ST36 (Zusanli point). Acupuncture not only quickly relieve the symptoms of acute angina pectoris, but also improve nitroglycerine's therapeutic effects. Therefore, it is an efficient simple therapeutic method used for emergency and for regular angina treatment. Review of studies on acupuncture therapy has shown effectiveness were between 80% to 96.2% that are almost as effective as conventional drug regimen. When compared with conventional medical treatment, the acupuncture therapy shows the obvious advantage of lacking, adverse side effects commonly associated with the Western anti-anginal drugs such as 1) Nitroglycerine (headache--63% with nitroglycerine patch and 50% with spray; syncope--4%; and dizziness--8% with patch; hypotension--4% with patch; and increased angina 2% with patch). 2) Isosorbide mononitrate (dizziness--3 to 5%; nausea/vomiting--2 to 4% and other reactions including hypotension, and syncope even with small doses). 3) Propranolol (bradycardia, chest pain, hypotension, worsening of AV conduction disturbance, Raynaud's syndrome, mental depression, hyperglycemia, etc.). Many conventional anti-anginal medications cause inter-drug reactions with other medications the patients taking for other diseases. Whereas, acupuncture therapy does not pose such an interference with patient's medications. Nevertheless, surgery is still the treatment of choice when acupuncture or conventional drug therapy fails. Combination of conventional drug therapy and acupuncture would considerably decrease the frequency and the required dosage of drug taking, thereby decreasing the unpleasant side effects of the drug therapy.

Experimental Evaluation of the High-Speed Motion Vector Measurement by Combining Synthetic Aperture Array Processing with Constrained Least Square Method

NASA Astrophysics Data System (ADS)

Yokoyama, Ryouta; Yagi, Shin-ichi; Tamura, Kiyoshi; Sato, Masakazu

2009-07-01

Ultrahigh speed dynamic elastography has promising potential capabilities in applying clinical diagnosis and therapy of living soft tissues. In order to realize the ultrahigh speed motion tracking at speeds of over thousand frames per second, synthetic aperture (SA) array signal processing technology must be introduced. Furthermore, the overall system performance should overcome the fine quantitative evaluation in accuracy and variance of echo phase changes distributed across a tissue medium. On spatial evaluation of local phase changes caused by pulsed excitation on a tissue phantom, investigation was made with the proposed SA signal system utilizing different virtual point sources that were generated by an array transducer to probe each component of local tissue displacement vectors. The final results derived from the cross-correlation method (CCM) brought about almost the same performance as obtained by the constrained least square method (LSM) extended to successive echo frames. These frames were reconstructed by SA processing after the real-time acquisition triggered by the pulsed irradiation from a point source. The continuous behavior of spatial motion vectors demonstrated the dynamic generation and traveling of the pulsed shear wave at a speed of one thousand frames per second.

Problem-Based Assignments as a Trigger for Developing Ethical and Reflective Competencies

ERIC Educational Resources Information Center

Euler, Dieter; Kühner, Patrizia

2017-01-01

The following research question serves as the starting point of this research and development project: How, in the context of a didactic design, can problem-based assignments trigger learning activities for the development of ethical and reflective competencies in students in economics courses? This paper focuses on the design of problem-based…

Intensive short-term vasodilation effect in the pain area of sciatica patients--case study.

PubMed

Skorupska, Elżbieta; Rychlik, Michał; Pawelec, Wiktoria; Bednarek, Agata; Samborski, Włodzimierz

2014-09-09

Varied and complicated etiology of low back pain radiating distally to the extremities is still causing disagreement and controversy around the issue of its diagnosis and treatment. Most clinicians believe that the source of that pain is generally radicular. While some of them postulate the clinical significance of the sacroiliac joint syndrome, others demonstrate that almost one in five people with back pain experience symptoms indicative of the neuropathic pain component. To date, neuropathic involvement has not been completely understood, and different mechanisms are thought to play an important role. It has been established that muscle pain (myofascial pain) e.g. active trigger points from the gluteus minimus, can mimic pain similar to sciatica, especially in the chronic stage. This paper describes patients presenting with radicular sciatica (case one and two) and sciatica-like symptoms (case three). For the first time, intensive short-term vasodilation in the pain area following needle infiltration of the gluteus minimus trigger point was recorded. Three Caucasian, European women suffering from radicular sciatica (case one and two) and sciatica-like symptoms (case three) at the age of 57, 49 and 47 respectively underwent infrared camera observation during needle infiltration of the gluteus minimus trigger point. The patients were diagnosed by a neurologist; they underwent magnetic resonance imaging, electromyography, neurography and blood test analysis. Apart from that, the patients were diagnosed by a clinician specializing in myofascial pain diagnosis. In the examined cases, trigger points-related short-term vasodilation was recorded. Confirmation of these findings in a controlled, blinded study would indicate the existence of a link between the pain of sciatica patients (radicular or sciatica-like pain) and the activity of the autonomic nervous system. Further studies on a bigger group of patients are still needed.

[Clinical observation on therapeutic effect of cupping combined with acupuncture stimulation at trigger points for lumbar myofascial pain syndrome].

PubMed

Zhao, Hong

2014-08-01

To observe the clinical effect of cupping combined with acupuncture stimulation of trigger points on lumbar myofascial pain syndrome (MPS). Sixty MPS patients were randomly divided into acupuncture + TDP group (n = 30), and cupping + acupuncture group (n = 30). Patients in the acupuncture + TDP group were treated by acupuncture stimulation of trigger points and local TDP irradiation, and patients of the cupping + acupuncture group treated by intensive cupping applied to the myofascial band and acupuncture stimulation of the locus according to the position of muscular tension band. The therapeutic effects were assessed according to the score of the McGill pain questionnaire composing of pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI) before, immediately and 1 month after the treatment. After the treatment, the total effective rates of the acupuncture+ TDP and cupping + acupuncture groups were 83.3% (25/30) and 96.6% (29/30), respectively, without significant difference between the two groups (P > 0.05). One month's follow-up showed that the total effective rates of the acupuncture + TDP and cupping + acupuncture groups were 40.0% and 90.0% respectively, and the latter group was significantly better than the acupuncture + TDP group in the therapeutic effect (P < 0.05). The scores of PRI, VAS, PPI after the treatment were markedly decreased in both groups (P < 0.05). One month later, the scores of PRI, VAS and PPI in the cupping + acupuncture group were obviously lower than those of the acupuncture group (P < 0.05). Both acupuncture stimulation of trigger points plus TDP and cupping plus acupuncture can effectively relieve pain in MPS patients, while the therapeutic effect of cupping plus acupuncture treatment lasts longer analgesic effect.

Office-Based Elastographic Technique for Quantifying Mechanical Properties of Skeletal Muscle

PubMed Central

Ballyns, Jeffrey J.; Turo, Diego; Otto, Paul; Shah, Jay P.; Hammond, Jennifer; Gebreab, Tadesse; Gerber, Lynn H.; Sikdar, Siddhartha

2012-01-01

Objectives Our objectives were to develop a new, efficient, and easy-to-administer approach to ultrasound elastography and assess its ability to provide quantitative characterization of viscoelastic properties of skeletal muscle in an outpatient clinical environment. We sought to show its validity and clinical utility in assessing myofascial trigger points, which are associated with myofascial pain syndrome. Methods Ultrasound imaging was performed while the muscle was externally vibrated at frequencies in the range of 60 to 200 Hz using a handheld vibrator. The spatial gradient of the vibration phase yielded the shear wave speed, which is related to the viscoelastic properties of tissue. The method was validated using a calibrated experimental phantom, the biceps brachii muscle in healthy volunteers (n = 6), and the upper trapezius muscle in symptomatic patients with axial neck pain (n = 13) and asymptomatic (pain-free) control participants (n = 9). Results Using the experimental phantom, our method was able to quantitatively measure the shear moduli with error rates of less than 20%. The mean shear modulus ± SD in the normal biceps brachii measured 12.5 ± 3.4 kPa, within the range of published values using more sophisticated methods. Shear wave speeds in active myofascial trigger points and the surrounding muscle tissue were significantly higher than those in normal tissue at high frequency excitations (>100 Hz; P < .05). Conclusions Off-the-shelf office-based equipment can be used to quantitatively characterize skeletal muscle viscoelastic properties with estimates comparable to those using more sophisticated methods. Our preliminary results using this method indicate that patients with spontaneous neck pain and symptomatic myofascial trigger points have increased tissue heterogeneity at the trigger point site and the surrounding muscle tissue. PMID:22837285

Office-based elastographic technique for quantifying mechanical properties of skeletal muscle.

PubMed

Ballyns, Jeffrey J; Turo, Diego; Otto, Paul; Shah, Jay P; Hammond, Jennifer; Gebreab, Tadesse; Gerber, Lynn H; Sikdar, Siddhartha

2012-08-01

Our objectives were to develop a new, efficient, and easy-to-administer approach to ultrasound elastography and assess its ability to provide quantitative characterization of viscoelastic properties of skeletal muscle in an outpatient clinical environment. We sought to show its validity and clinical utility in assessing myofascial trigger points, which are associated with myofascial pain syndrome. Ultrasound imaging was performed while the muscle was externally vibrated at frequencies in the range of 60 to 200 Hz using a handheld vibrator. The spatial gradient of the vibration phase yielded the shear wave speed, which is related to the viscoelastic properties of tissue. The method was validated using a calibrated experimental phantom, the biceps brachii muscle in healthy volunteers (n = 6), and the upper trapezius muscle in symptomatic patients with axial neck pain (n = 13) and asymptomatic (pain-free) control participants (n = 9). Using the experimental phantom, our method was able to quantitatively measure the shear moduli with error rates of less than 20%. The mean shear modulus ± SD in the normal biceps brachii measured 12.5 ± 3.4 kPa, within the range of published values using more sophisticated methods. Shear wave speeds in active myofascial trigger points and the surrounding muscle tissue were significantly higher than those in normal tissue at high frequency excitations (>100 Hz; P < .05). Off-the-shelf office-based equipment can be used to quantitatively characterize skeletal muscle viscoelastic properties with estimates comparable to those using more sophisticated methods. Our preliminary results using this method indicate that patients with spontaneous neck pain and symptomatic myofascial trigger points have increased tissue heterogeneity at the trigger point site and the surrounding muscle tissue.

Acetazolamide: A New Treatment for Visual Vertigo.

PubMed

Sluch, Ilya M; Elliott, Michael S; Dvorak, Justin; Ding, Kai; Farris, Bradley K

2017-12-01

Visual vertigo is a disorder characterised by symptoms of dizziness, vertigo, unsteadiness, disorientation, and general discomfort induced by visual triggers. It is currently treated with vestibular rehabilitation therapy, with no effective pharmacotherapy available for treatment-resistant cases. The objective of this study was to evaluate the efficacy of oral acetazolamide in improving symptoms of visual vertigo. A comparative case series of adult patients clinically diagnosed with visual vertigo was conducted from January 1992 to May 2015. Patients without a full neurologic or otorhinolaryngologic work-up, negative magnetic resonance imaging (MRI), and an organic cause for their symptoms were excluded. The identified patients were then contacted by phone to complete a voluntary symptom survey. Main outcome was the subjective reported percentage in symptom improvement. Secondary outcomes were subjective improvement by symptom triggers. The participants were retrospectively divided into three groups based on their treatment with acetazolamide: currently on acetazolamide, terminated acetazolamide, or never initiated acetazolamide. Fifty-seven patients met the inclusion criteria and were willing to complete the phone survey (19 currently on acetazolamide, 27 terminated acetazolamide, and 11 never initiated therapy). Overall symptomatic improvement was reported by 18 (94.7%) patients currently on acetazolamide, 18 (66.7 %) who terminated acetazolamide, and 5 (45.5%) who never initiated therapy, varying significantly by group ( p = 0.0061). Greatest improvement was reported in symptoms triggered by being a passenger in a car. These results show that acetazolamide has a positive association with improvement of symptoms of visual vertigo.

Twelve tips for creating trigger images for problem-based learning cases.

PubMed

Azer, Samy A

2007-03-01

A trigger is the starting point of problem-based learning (PBL) cases. It is usually in the form of 5-6 text lines that provide the key information about the main character (usually the patient), including 3-4 of patient's presenting problems. In addition to the trigger text, most programs using PBL include a visual trigger. This might be in the form of a single image, a series of images, a video clip, a cartoon, or even one of the patient's investigation results (e.g. chest X-ray, pathology report, or urine sample analysis). The main educational objectives of the trigger image are as follows: (1) to introduce the patient to the students; (2) to enhance students' observation skills; (3) to provide them with new information to add to the cues obtained from the trigger text; and (4) to stimulate students to ask questions as they develop their enquiry plan. When planned and delivered effectively, trigger images should be engaging and stimulate group discussion. Understanding the educational objectives of using trigger images and choosing appropriate images are the keys for constructing successful PBL cases. These twelve tips highlight the key steps in the successful creation of trigger images.

FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia.

PubMed

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Nolen, Jacqueline G; Roger, Simon D

2014-11-01

The optimal iron therapy regimen in patients with non-dialysis-dependent chronic kidney disease (CKD) is unknown. Ferinject® assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre, prospective and randomized study of 626 patients with non-dialysis-dependent CKD, anaemia and iron deficiency not receiving erythropoiesis-stimulating agents (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric carboxymaltose (FCM), targeting a higher (400-600 µg/L) or lower (100-200 µg/L) ferritin or oral iron therapy. The primary end point was time to initiation of other anaemia management (ESA, other iron therapy or blood transfusion) or haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52. The primary end point occurred in 36 patients (23.5%), 49 patients (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a greater proportion of patients achieved an Hb increase ≥1 g/dL with high-ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of adverse events and serious adverse events were similar in all groups. Compared with oral iron, IV FCM targeting a ferritin of 400-600 µg/L quickly reached and maintained Hb level, and delayed and/or reduced the need for other anaemia management including ESAs. Within the limitations of this trial, no renal toxicity was observed, with no difference in cardiovascular or infectious events. NCT00994318. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

A proposed model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development.

PubMed

Knight, Zelda Gillian

2017-09-01

Just as Freud used stages of psychosexual development to ground his model of psychoanalysis, it is possible to do the same with Erik Erikson's stages of development with regards to a model of psychodynamic psychotherapy. This paper proposes an eight-stage model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development. Various suggestions are offered. One such suggestion is that as each of Erikson's developmental stages is triggered by a crisis, in therapy it is triggered by the client's search. The resolution of the search often leads to the development of another search, which implies that the therapy process comprises a series of searches. This idea of a series of searches and resolutions leads to the understanding that identity is developmental and therapy is a space in which a new sense of identity may emerge. The notion of hope is linked to Erikson's stage of Basic Trust and the proposed model of therapy views hope and trust as essential for the therapy process. Two clinical vignettes are offered to illustrate these ideas. Psychotherapy can be approached as an eight-stage process and linked to Erikson's eight stages model of development. Psychotherapy may be viewed as a series of searches and thus as a developmental stage resolution process, which leads to the understanding that identity is ongoing throughout the life span. Copyright © 2017 John Wiley & Sons, Ltd.

Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy.

PubMed

Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

2016-03-28

Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of "gate molecules" for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of "killing three birds with one stone", that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.

Recent advances in ultrasound-triggered therapy.

PubMed

Yang, Chaopin; Li, Yue; Du, Meng; Chen, Zhiyi

2018-04-27

As a non-invasive and real-time diagnostic technique, ultrasound has provided a novel strategy for targeted treatment. With the rapid development of ultrasonic technique and ultrasound contrast agents (UCAs), spatiotemporally controllable application of ultrasound with or without UCAs makes it possible for site-specific delivery of therapeutic agents and targeted modulation with minimal side effects, which indicated a promising therapy in clinical use. This review will describe the main mechanism of targeted therapy induced by ultrasound briefly, then focus on the current application of ultrasound mediated targeted therapy in various fields including tumour, cardiovascular disease, central nervous system, skeletal muscle system diseases and stem cells therapy. In addition, ongoing challenges of ultrasound-mediated targeted therapy for further research and its clinical use are reviewed.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

PubMed

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Memory for Therapy in Bipolar Disorder and Comorbid Insomnia

PubMed Central

Lee, Jason Y.; Harvey, Allison G.

2014-01-01

Objective To examine the extent to which patients recall the contents of therapy from one session to the next and to determine whether recall is associated with treatment outcome. Method Thirty inter-episode individuals with bipolar disorder and comorbid insomnia (ages 21-62 years, 56.7% female, 56.7% Caucasian) participated in an RCT of psychotherapies. Patients received either Cognitive Behavioral Therapy for Insomnia (CBTI-BP; n = 17) or Psychoeducation (PE; n = 13). At the beginning of each weekly session, patients freely recalled as many therapy points (i.e., distinct ideas, principles, and experiences) as they could from their previous session. After each session, therapists recorded a list of all therapy points delivered. Treatment outcome was measured via the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Patient-Reported Outcome Measurement Info System—Sleep (PROMIS-Sleep), and Quality of Life—Sleep (QOL-Sleep), administered at pre and post treatment, and treatment evaluation questions administered at post treatment. Results Patients recalled 19.6% to 36.9% of therapy points listed by therapists. Raw numbers of therapy points recalled were positively correlated with reductions in ISI and gains in QOL-Sleep, and with most treatment evaluation questions. Percentages of therapy points recalled were positively correlated with gains in QOL-Sleep, but with no other sleep outcome measures or any of the treatment evaluation questions. Patients in CBTI-BP recalled more therapy points than those in PE, but did not differ in the percentages of points recalled. Conclusions Memory for therapy is poor. The amount of content recalled is positively associated with treatment outcome. Enhancing memory for therapy might play a key role in improving treatment outcome. PMID:25222800

Real-time, contextual intervention using mobile technology to reduce marijuana use among youth: a pilot study.

PubMed

Shrier, Lydia A; Rhoads, Amanda; Burke, Pamela; Walls, Courtney; Blood, Emily A

2014-01-01

We evaluated the feasibility, acceptability, and potential efficacy of MOMENT, an intervention to reduce youth marijuana use that combines brief motivational enhancement therapy with mobile self-monitoring and responsive messaging. At baseline, primary care patients ages 15-24 who used marijuana frequently (at least 3 times per week) completed a recall assessment, then 1 week of mobile momentary and daily reports on use-related factors. For the intervention, youth participated in two motivational enhancement therapy sessions, during which they identified their top-3 social and emotional triggers for use and discussed healthy ways to manage them. They then completed two weeks of mobile reports. Upon reporting a top-3 trigger for use, desire to use, or recent use, they received a message supporting self-efficacy and prompting consideration of coping strategies. Generalized estimating equations examined changes in momentary-, daily-, and individual-level measures on 3-month recall and mobile assessments. Twenty-seven youth (M=19.2 years, 70% female) enrolled; there were 377-677 momentary and 50-106 daily reports per study phase. Participants reported reading the messages and finding them motivating, being comfortable with participation, and not experiencing the study as burdensome. Although proportion of momentary reports of being in a top-3 trigger context did not change (36%-43%), marijuana desire in a top-3 trigger context and marijuana use after top-3 trigger exposure decreased over the study (p<.0001 and p=.03, respectively). Daily- and individual-level measures showed similar, non-significant, improvements. The MOMENT intervention appears feasible, well-accepted, and potentially efficacious for youth who use marijuana frequently. © 2013.

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series.

PubMed

Qian, Xu; Nguyen, Duc T M; Li, Yaojun; Lyu, Jianxin; Graviss, Edward A; Hu, Tony Y

2016-12-01

There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg 9 -bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We will further exploit these host-response signatures in the future as biomarkers in combination with other clinical and microbiologic tools which may improve treatment efficacy and facilitate the development of host-directed therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics

PubMed Central

Wang, Chao; Cheng, Liang; Liu, Zhuang

2013-01-01

Photodynamic therapy (PDT) is a non-invasive treatment modality for a variety of diseases including cancer. PDT based on upconversion nanoparticles (UCNPs) has received much attention in recent years. Under near-infrared (NIR) light excitation, UCNPs are able to emit high-energy visible light, which can activate surrounding photosensitizer (PS) molecules to produce singlet oxygen and kill cancer cells. Owing to the high tissue penetration ability of NIR light, NIR-excited UCNPs can be used to activate PS molecules in much deeper tissues compared to traditional PDT induced by visible or ultraviolet (UV) light. In addition to the application of UCNPs as an energy donor in PDT, via similar mechanisms, they could also be used for the NIR light-triggered drug release or activation of 'caged' imaging or therapeutic molecules. In this review, we will summarize the latest progresses regarding the applications of UCNPs for photodynamic therapy, NIR triggered drug and gene delivery, as well as several other UCNP-based cancer therapeutic approaches. The future prospects and challenges in this emerging field will be also discussed. PMID:23650479

Basic study of less invasive high-intensity focused ultrasound (HIFU) in fetal therapy for twin reversed arterial perfusion (TRAP) sequence.

PubMed

Ichizuka, Kiyotake; Matsuoka, Ryu; Aoki, Hiroko; Hasegawa, Junichi; Okai, Takashi; Umemura, Shin-Ichiro

2016-10-01

The objective of the present study was to develop a high-intensity focused ultrasound (HIFU) transducer more suitable for clinical use in fetal therapy for twin reversed arterial perfusion (TRAP) sequence. We created a cooling and degassed water-circulating-type HIFU treatment device. HIFU was applied to renal branch vessels in three rabbits. Sequential HIFU irradiation contains a trigger wave, heating wave, and rest time. The duration of HIFU application was 10 s/course. Targeting could be achieved by setting the imaging probe in the center and placing the HIFU beam and imaging ultrasonic wave on the same axis. We confirmed under sequential HIFU irradiation with a total intensity of 1.94 kW/cm(2) (spatial average temporal average intensity) that the vein and artery were occluded in all three rabbits. Simultaneous occluding of the veins and arteries was confirmed with trigger waves and a resting phase using the HIFU transducer treatment device created for this study. Clinical application appears possible and may represent a promising option for fetal therapy involving TRAP sequence.

Phase-transitional Fe3O4/perfluorohexane Microspheres for Magnetic Droplet Vaporization.

PubMed

Wang, Ronghui; Zhou, Yang; Zhang, Ping; Chen, Yu; Gao, Wei; Xu, Jinshun; Chen, Hangrong; Cai, Xiaojun; Zhang, Kun; Li, Pan; Wang, Zhigang; Hu, Bing; Ying, Tao; Zheng, Yuanyi

2017-01-01

Activating droplets vaporization has become an attractive strategy for ultrasound imaging and physical therapy due to the significant increase in ultrasound backscatter signals and its ability to physically damage the tumor cells. However, the current two types of transitional droplets named after their activation methods have their respective limitations. To circumvent the limitations of these activation methods, here we report the concept of magnetic droplet vaporization (MDV) for stimuli-responsive cancer theranostics by a magnetic-responsive phase-transitional agent. This magnetic-sensitive phase-transitional agent-perfluorohexane (PFH)-loaded porous magnetic microspheres (PFH-PMMs), with high magnetic-thermal energy-transfer capability, could quickly respond to external alternating current (AC) magnetic fields to produce thermal energy and trigger the vaporization of the liquid PFH. We systematically demonstrated MDV both in vitro and in vivo. This novel trigger method with deep penetration can penetrate the air-filled viscera and trigger the vaporization of the phase-transitional agent without the need of pre-focusing lesion. This unique MDV strategy is expected to substantially broaden the biomedical applications of nanotechnology and promote the clinical treatment of tumors that are not responsive to chemical therapies.

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

NASA Astrophysics Data System (ADS)

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M.; Deng, Wei

2018-02-01

We developed light-triggered liposomes incorporating gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized by adjusting the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of HSPC: PE-NH2: gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of these liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox loaded liposomes were applied to human colorectal cancer cells, HCT116, and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity, compared to the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may have improved therapeutic efficacy in photodynamic therapy and chemotherapy.

Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

PubMed

Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

2014-02-01

Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

A multi-purpose open-source triggering platform for magnetic resonance

NASA Astrophysics Data System (ADS)

Ruytenberg, T.; Webb, A. G.; Beenakker, J. W. M.

2014-10-01

Many MR scans need to be synchronised with external events such as the cardiac or respiratory cycles. For common physiological functions commercial trigger equipment exists, but for more experimental inputs these are not available. This paper describes the design of a multi-purpose open-source trigger platform for MR systems. The heart of the system is an open-source Arduino Due microcontroller. This microcontroller samples an analogue input and digitally processes these data to determine the trigger. The output of the microcontroller is programmed to mimic a physiological signal which is fed into the electrocardiogram (ECG) or pulse oximeter port of MR scanner. The microcontroller is connected to a Bluetooth dongle that allows wireless monitoring and control outside the scanner room. This device can be programmed to generate a trigger based on various types of input. As one example, this paper describes how it can be used as an acoustic cardiac triggering unit. For this, a plastic stethoscope is connected to a microphone which is used as an input for the system. This test setup was used to acquire retrospectively-triggered cardiac scans in ten volunteers. Analysis showed that this platform produces a reliable trigger (>99% triggers are correct) with a small average 8 ms variation between the exact trigger points.

A multi-purpose open-source triggering platform for magnetic resonance.

PubMed

Ruytenberg, T; Webb, A G; Beenakker, J W M

2014-10-01

Many MR scans need to be synchronised with external events such as the cardiac or respiratory cycles. For common physiological functions commercial trigger equipment exists, but for more experimental inputs these are not available. This paper describes the design of a multi-purpose open-source trigger platform for MR systems. The heart of the system is an open-source Arduino Due microcontroller. This microcontroller samples an analogue input and digitally processes these data to determine the trigger. The output of the microcontroller is programmed to mimic a physiological signal which is fed into the electrocardiogram (ECG) or pulse oximeter port of MR scanner. The microcontroller is connected to a Bluetooth dongle that allows wireless monitoring and control outside the scanner room. This device can be programmed to generate a trigger based on various types of input. As one example, this paper describes how it can be used as an acoustic cardiac triggering unit. For this, a plastic stethoscope is connected to a microphone which is used as an input for the system. This test setup was used to acquire retrospectively-triggered cardiac scans in ten volunteers. Analysis showed that this platform produces a reliable trigger (>99% triggers are correct) with a small average 8 ms variation between the exact trigger points. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined Electrocardiography- and Respiratory-Triggered CT of the Lung to Reduce Respiratory Misregistration Artifacts between Imaging Slabs in Free-Breathing Children: Initial Experience

PubMed Central

Allmendinger, Thomas

2017-01-01

Objective Cardiac and respiratory motion artifacts degrade the image quality of lung CT in free-breathing children. The aim of this study was to evaluate the effect of combined electrocardiography (ECG) and respiratory triggering on respiratory misregistration artifacts on lung CT in free-breathing children. Materials and Methods In total, 15 children (median age 19 months, range 6 months–8 years; 7 boys), who underwent free-breathing ECG-triggered lung CT with and without respiratory-triggering were included. A pressure-sensing belt of a respiratory gating system was used to obtain the respiratory signal. The degree of respiratory misregistration artifacts between imaging slabs was graded on a 4-point scale (1, excellent image quality) on coronal and sagittal images and compared between ECG-triggered lung CT studies with and without respiratory triggering. A p value < 0.05 was considered significant. Results Lung CT with combined ECG and respiratory triggering showed significantly less respiratory misregistration artifacts than lung CT with ECG triggering only (1.1 ± 0.4 vs. 2.2 ± 1.0, p = 0.003). Conclusion Additional respiratory-triggering reduces respiratory misregistration artifacts on ECG-triggered lung CT in free-breathing children. PMID:28860904

In Vivo Activation of cAMP Signaling Induces Growth Arrest and Differentiation in Acute Promyelocytic Leukemia

PubMed Central

Guillemin, Marie-Claude; Raffoux, Emmanuel; Vitoux, Dominique; Kogan, Scott; Soilihi, Hassane; Lallemand-Breitenbach, Valérie; Zhu, Jun; Janin, Anne; Daniel, Marie-Thérèse; Gourmel, Bernard; Degos, Laurent; Dombret, Hervé; Lanotte, Michel; de Thé, Hugues

2002-01-01

Differentiation therapy for acute myeloid leukemia uses transcriptional modulators to reprogram cancer cells. The most relevant clinical example is acute promyelocytic leukemia (APL), which responds dramatically to either retinoic acid (RA) or arsenic trioxide (As2O3). In many myeloid leukemia cell lines, cyclic adenosine monophosphate (cAMP) triggers growth arrest, cell death, or differentiation, often in synergy with RA. Nevertheless, the toxicity of cAMP derivatives and lack of suitable models has hampered trials designed to assess the in vivo relevance of theses observations. We show that, in an APL cell line, cAMP analogs blocked cell growth and unraveled As2O3-triggered differentiation. Similarly, in RA-sensitive or RA-resistant mouse models of APL, continuous infusions of 8-chloro-cyclic adenosine monophosphate (8-Cl-cAMP) triggered major growth arrest, greatly enhanced both spontaneous and RA- or As2O3-induced differentiation and accelerated the restoration of normal hematopoiesis. Theophylline, a well-tolerated phosphodiesterase inhibitor which stabilizes endogenous cAMP, also impaired APL growth and enhanced spontaneous or As2O3-triggered cell differentiation in vivo. Accordingly, in an APL patient resistant to combined RA–As2O3 therapy, theophylline induced blast clearance and restored normal hematopoiesis. Taken together, these results demonstrate that in vivo activation of cAMP signaling contributes to APL clearance, independently of its RA-sensitivity, thus raising hopes that other myeloid leukemias may benefit from this therapeutic approach. PMID:12438428

A Topological Array Trigger for AGIS, the Advanced Gamma ray Imaging System

NASA Astrophysics Data System (ADS)

Krennrich, F.; Anderson, J.; Buckley, J.; Byrum, K.; Dawson, J.; Drake, G.; Haberichter, W.; Imran, A.; Krawczynski, H.; Kreps, A.; Schroedter, M.; Smith, A.

2008-12-01

Next generation ground based γ-ray observatories such as AGIS1 and CTA2 are expected to cover a 1 km2 area with 50-100 imaging atmospheric Cherenkov telescopes. The stereoscopic view ol air showers using multiple view points raises the possibility to use a topological array trigger that adds substantial flexibility, new background suppression capabilities and a reduced energy threshold. In this paper we report on the concept and technical implementation of a fast topological trigger system, that makes use of real time image processing of individual camera patterns and their combination in a stereoscopic array analysis. A prototype system is currently under construction and we discuss the design and hardware of this topological array trigger system.

The Advanced Gamma-ray Imaging System (AGIS): Real Time Stereoscopic Array Trigger

NASA Astrophysics Data System (ADS)

Byrum, K.; Anderson, J.; Buckley, J.; Cundiff, T.; Dawson, J.; Drake, G.; Duke, C.; Haberichter, B.; Krawzcynski, H.; Krennrich, F.; Madhavan, A.; Schroedter, M.; Smith, A.

2009-05-01

Future large arrays of Imaging Atmospheric Cherenkov telescopes (IACTs) such as AGIS and CTA are conceived to comprise of 50 - 100 individual telescopes each having a camera with 10**3 to 10**4 pixels. To maximize the capabilities of such IACT arrays with a low energy threshold, a wide field of view and a low background rate, a sophisticated array trigger is required. We describe the design of a stereoscopic array trigger that calculates image parameters and then correlates them across a subset of telescopes. Fast Field Programmable Gate Array technology allows to use lookup tables at the array trigger level to form a real-time pattern recognition trigger tht capitalizes on the multiple view points of the shower at different shower core distances. A proof of principle system is currently under construction. It is based on 400 MHz FPGAs and the goal is for camera trigger rates of up to 10 MHz and a tunable cosmic-ray background suppression at the array level.

Modulating chromatin structure and DNA accessibility by deacetylase inhibition enhances the anti-cancer activity of silver nanoparticles.

PubMed

Igaz, Nóra; Kovács, Dávid; Rázga, Zsolt; Kónya, Zoltán; Boros, Imre M; Kiricsi, Mónika

2016-10-01

Histone deacetylase (HDAC) inhibitors are considered as novel therapeutic agents inducing cell cycle arrest and apoptotic cell death in various cancer cells. Inhibition of deacetylase activity results in a relaxed chromatin structure thereby rendering the genetic material more vulnerable to DNA targeting agents that could be exploited by combinational cancer therapy. The unique potential of silver nanoparticles (AgNPs) in tumor therapy relies on the generation of reactive radicals which trigger oxidative stress, DNA damage and apoptosis in cancer cells. The revolutionary application of AgNPs as chemotherapeutical drugs seems very promising, nevertheless the exact molecular mechanisms of AgNP action in combination with other anti-cancer agents have yet to be elucidated in details before clinical administrations. As a step towards this we investigated the combinational effect of HDAC inhibition and AgNP administration in HeLa cervical cancer cells. We identified synergistic inhibition of cancer cell growth and migration upon combinational treatments. Here we report that the HDAC inhibitor Trichostatin A enhances the DNA targeting capacity and apoptosis inducing efficacy of AgNPs most probably due to its effect on chromatin condensation. These results point to the potential benefits of combinational application of HDAC inhibitors and AgNPs in novel cancer medication protocols. Copyright © 2016 Elsevier B.V. All rights reserved.

Pain and Psychological Outcomes After Rehabilitative Treatment for a Woman With Chronic Pelvic Pain With Stage III Cervical Cancer: A Case Report.

PubMed

Alappattu, Meryl J

2013-01-01

Chronic pelvic pain and sexual dysfunction are adverse effects of treatment of cervical cancer. Surgery and radiation therapies may result in soft tissue pain and dysfunction, including spasms and trigger points of the pelvic floor muscles that result in pain. In addition to physical restrictions, negative mood associated with pain is believed to intensify and prolong the pain experience. The purpose of this case report was to describe outcomes of pelvic physical therapy in a 58-year-old woman with chronic pelvic pain after medical treatments for cervical cancer. The patient reported dyspareunia, hip pain, and lower abdominal, pelvic pain, and fatigue with activities lasting greater than 30 minutes. Interventions included pelvic floor massage, dilator use, and patient education. Symptoms were assessed at baseline and completion of physical therapy, using the Female Sexual Function Index, Fear of Pain Questionnaire-III, Pain Catastrophizing Scale, and Numerical Pain Rating Scale. The Female Sexual Function Index score decreased from 7.8 to 2.8, the Fear of Pain Questionnaire- III score decreased from 85 to 73, the Pain Catastrophizing Scale score decreased from 18 to 8, and lower abdominal and pelvic pain decreased from 4 of 10 to 0 of 10, while bilateral hip pain remained at 4 of 10. In addition, she exhibited increased tolerance to mechanical pressure, evidenced by progression in size of a vaginal dilator. These results suggest that pelvic physical therapy may be useful in treating chronic pelvic pain after cervical cancer treatments and may also help decrease the magnitude of negative mood aspects such as pain-related fear and catastrophizing.

Pain and Psychological Outcomes After Rehabilitative Treatment for a Woman With Chronic Pelvic Pain With Stage III Cervical Cancer: A Case Report

PubMed Central

Alappattu, Meryl J.

2016-01-01

Background Chronic pelvic pain and sexual dysfunction are adverse effects of treatment of cervical cancer. Surgery and radiation therapies may result in soft tissue pain and dysfunction, including spasms and trigger points of the pelvic floor muscles that result in pain. In addition to physical restrictions, negative mood associated with pain is believed to intensify and prolong the pain experience. Study Design The purpose of this case report was to describe outcomes of pelvic physical therapy in a 58-year-old woman with chronic pelvic pain after medical treatments for cervical cancer. Case Description The patient reported dyspareunia, hip pain, and lower abdominal, pelvic pain, and fatigue with activities lasting greater than 30 minutes. Interventions included pelvic floor massage, dilator use, and patient education. Symptoms were assessed at baseline and completion of physical therapy, using the Female Sexual Function Index, Fear of Pain Questionnaire–III, Pain Catastrophizing Scale, and Numerical Pain Rating Scale. Outcomes The Female Sexual Function Index score decreased from 7.8 to 2.8, the Fear of Pain Questionnaire– III score decreased from 85 to 73, the Pain Catastrophizing Scale score decreased from 18 to 8, and lower abdominal and pelvic pain decreased from 4 of 10 to 0 of 10, while bilateral hip pain remained at 4 of 10. In addition, she exhibited increased tolerance to mechanical pressure, evidenced by progression in size of a vaginal dilator. Discussion These results suggest that pelvic physical therapy may be useful in treating chronic pelvic pain after cervical cancer treatments and may also help decrease the magnitude of negative mood aspects such as pain-related fear and catastrophizing. PMID:27134605

Cytoplasmic GPER translocation in cancer-associated fibroblasts mediates cAMP/PKA/CREB/glycolytic axis to confer tumor cells with multidrug resistance.

PubMed

Yu, T; Yang, G; Hou, Y; Tang, X; Wu, C; Wu, X-A; Guo, L; Zhu, Q; Luo, H; Du, Y-E; Wen, S; Xu, L; Yin, J; Tu, G; Liu, M

2017-04-01

Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs. The glycolytic CAFs feed the extra pyruvate and lactate to tumor cells for augmentation of mitochondrial activity, and this energy metabolically coupled in a 'host-parasite relationship' between catabolic CAFs and anabolic cancer cells confers the tumor cells with multiple drug resistance to several conventional clinical treatments including endocrine therapy (tamoxifen), Her-2-targeted therapy (herceptin) and chemotherapy (epirubicin). Moreover, the clinical data from 18 F-fluorodeoxyglucose positron emission tomography/computed tomography further present a strong association between the GPER/cAMP/PKA/CREB pathway of stromal fibroblasts with tumor metabolic activity and clinical treatment, suggesting that targeting cytoplasmic GPER in CAFs may rescue the drug sensitivity in patients with breast cancer. Thus, our data define novel insights into the stromal GPER-mediated multiple drug resistance from the point of reprogramming of tumor energy metabolism and provide the rationale for CAFs as a promising target for clinical therapy.

NIR‐Triggered Crystal Phase Transformation of NiTi‐Layered Double Hydroxides Films for Localized Chemothermal Tumor Therapy

PubMed Central

Wang, Donghui; Ge, Naijian; Yang, Tingting; Peng, Feng; Qiao, Yuqin; Li, Qianwen

2018-01-01

Abstract Construction of localized drug‐eluting systems with synergistic chemothermal tumor‐killing abilities is promising for biomedical implants directly contacting with tumor tissues. In this study, an intelligent and biocompatible drug‐loading platform, based on a gold nanorods‐modified butyrate‐inserted NiTi‐layered double hydroxides film (Au@LDH/B), is prepared on the surface of nitinol alloy. The prepared films function as drug‐loading “sponges,” which pump butyrate out under near‐infrared (NIR) irradiation and resorb drugs in water when the NIR laser is shut off. The stimuli‐responsive release of butyrate is verified to be related with the NIR‐triggered crystal phase transformation of Au@LDH/B. In vitro and in vivo studies reveal that the prepared films possess excellent biosafety and high efficiency in synergistic thermochemo tumor therapy, showing a promising application in the construction of localized stimuli‐responsive drug‐delivery systems. PMID:29721424

Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2016-03-01

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report.

PubMed

Vigil, Darlene; Ganta, Kavitha; Sun, Yijuan; Dorin, Richard I; Tzamaloukas, Antonios H; Servilla, Karen S

2015-05-06

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 mOsm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with new-onset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report

PubMed Central

Vigil, Darlene; Ganta, Kavitha; Sun, Yijuan; Dorin, Richard I; Tzamaloukas, Antonios H; Servilla, Karen S

2015-01-01

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 mOsm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with new-onset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI. PMID:25949947

ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells.

PubMed

Yue, Zongwei; Xiao, Xinhua; Wu, Jinbao; Zhou, Xiaozhou; Liu, Weilong; Liu, Yaxi; Li, Houhua; Chen, Guoqiang; Wu, Yingli; Lei, Xiaoguang

2018-02-23

Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.

Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yan-Ying, E-mail: biozyy@163.com; Huang, Xin-Yuan; Chen, Zheng-Wang

Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In themore » present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.« less

Natural and unnatural triggers of myocardial infarction.

PubMed

Kloner, Robert A

2006-01-01

Previous analyses have suggested that factors that stimulate the sympathetic nervous system and catecholamine release can trigger acute myocardial infarction. The wake-up time, Mondays, winter season, physical exertion, emotional upset, overeating, lack of sleep, cocaine, marijuana, anger, and sexual activity are some of the more common triggers. Certain natural disasters such as earthquakes and blizzards have also been associated with an increase in cardiac events. Certain unnatural triggers may play a role including the Holiday season. Holiday season cardiac events peak on Christmas and New Year. A number of hypotheses have been raised to explain the increase in cardiac events during the holidays, including overeating, excessive use of salt and alcohol, exposure to particulates, from fireplaces, a delay in seeking medical help, anxiety or depression related to the holidays, and poorer staffing of health care facilities at this time. War has been associated with an increase in cardiac events. Data regarding an increase in cardiac events during the 9/11 terrorist attack have been mixed. Understanding the cause of cardiovascular triggers will help in developing potential therapies.

Regular and Random Components in Aiming-Point Trajectory During Rifle Aiming and Shooting

PubMed Central

Goodman, Simon; Haufler, Amy; Shim, Jae Kun; Hatfield, Bradley

2009-01-01

The authors examined the kinematic qualities of the aiming trajectory as related to expertise. In all, 2 phases of the trajectory were discriminated. The first phase was regular approximation to the target accompanied by substantial fluctuations obeying the Weber–Fechner law. During the first phase, shooters did not initiate the triggering despite any random closeness of the aiming point (AP) to the target. In the second phase, beginning at 0.6–0.8 s before the trigger pull, shooters applied a different control strategy: They waited until the following random fluctuation brought the AP closer to the target and then initiated triggering. This strategy is tenable when sensitivity of perception is greater than precision of the motor action, and could be considered a case of stochastic resonance. The strategies that novices and experts used distinguished only in the values of parameters. The authors present an analytical model explaining the main properties of shooting. PMID:19508963

Laser-based ion sources for medical applications

NASA Astrophysics Data System (ADS)

Bychenkov, V. Yu.; Brantov, A. V.

2015-10-01

Interaction of relativistic short laser pulses with thin foils is studied by using 3D PIC simulations in the context of ICAN's "dream laser". It is shown that such a laser will make it possible to accelerate protons and deuterons to multi-MeV energies with a current density of 100 A/cm2. The laser-triggered hadron beams may trigger nuclear reactions of interest for nuclear medicine and pharmacy. As an example, the yields C-11 for PET, of Tc-99m for SPECT, and neutrons for therapy have been analyzed.

Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.

PubMed

Moll, Guido; Ignatowicz, Lech; Catar, Rusan; Luecht, Christian; Sadeghi, Behnam; Hamad, Osama; Jungebluth, Philipp; Dragun, Duska; Schmidtchen, Artur; Ringdén, Olle

2015-10-01

While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.

Jumping liquid metal droplet in electrolyte triggered by solid metal particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Jianbo; University of Chinese Academy of Sciences, Beijing 100049; Wang, Junjie

2016-05-30

We report the electron discharge effect due to point contact between liquid metal and solid metal particles in electrolyte. Adding nickel particles induces drastic hydrogen generating and intermittent jumping of a sub-millimeter EGaIn droplet in NaOH solution. Observations from different orientations disclose that such jumping behavior is triggered by pressurized bubbles under the assistance of interfacial interactions. Hydrogen evolution around particles provides clear evidence that such electric instability originates from the varied electric potential and morphology between the two metallic materials. The point-contact-induced charge concentration significantly enhances the near-surface electric field intensity at the particle tips and thus causes electricmore » breakdown of the electrolyte.« less

Sonographic appearance of the flexor tendon, volar plate, and A1 pulley with respect to the severity of trigger finger.

PubMed

Sato, Junko; Ishii, Yoshinori; Noguchi, Hideo; Takeda, Mitsuhiro

2012-10-01

To evaluate trigger digits with sonography to determine morphological changes in the A1 pulley, flexor tendon, and volar plate in relation to the severity of triggering. We evaluated 67 trigger digits and graded them into 1 of 4 groups. We compared the groups according to severity and to contralateral fingers, which served as controls. The thickness of the flexor tendons under the A1 pulley was proportional to the severity of triggering. The anteroposterior thickness of the flexor tendon increased significantly among the grades exhibiting triggering regardless of the affected digit. However, in digits other than the thumb, tendon thickness increased even in the absence of active triggering. Thickening tended to be greater with finger flexion. The A1 pulley exhibited the greatest thickness and the volar plate exhibited significant thickening in the group that exhibited continuous triggering that was easily reduced with active extension (grade III). The flexor tendon thickened significantly before patients experienced triggering except in the thumb. In the thumb, the flexor tendon and A1 pulley thickened significantly only after patients exhibited triggering. Thickening of the volar plate appears to have an important role in continuous triggering. Although most clinicians can easily determine the severity of a trigger digit by clinical examination, ultrasound might be helpful for objectively understanding the severity and response to treatment, by examining the thickness of the flexor tendon and A1 pulley. In particular, sonographic measurement of the A1 pulley might be useful in judging the progression of trigger finger severity. In cases where a Doppler signal is detected inside the A1 pulley, more conservative therapies might be worth considering before surgery. Diagnostic ΙΙΙ. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Structural phase transition in deuterated benzil C14D10O2 : Neutron inelastic scattering

NASA Astrophysics Data System (ADS)

Goossens, D. J.; Welberry, T. R.; Hagen, M. E.; Fernandez-Baca, J. A.

2006-04-01

Neutron inelastic scattering has been used to examine the structural phase transition in deuterated benzil C14D10O2 . The transition in benzil, in which the unit cell goes from a trigonal P3121 unit cell above TC to a cell doubled P21 unit cell below TC , leads to the emergence of a Bragg peak at the M -point of the high temperature Brillouin zone. It has previously been suggested that the softening of a transverse optic phonon at the Γ -point leads to the triggering of an instability at the M -point causing the transition to occur. This suggestion has been investigated by measuring the phonon spectrum at the M -point for a range of temperatures above TC and the phonon dispersion relation along the Γ-M direction just above TC . It is found that the transverse acoustic phonon at the M -point is of lower energy than the Γ -point optic mode and has a softening with temperature as T approaches TC from above that is much faster than that of the Γ -point optic mode. This behavior is inconsistent with the view that the Γ -point mode is responsible for triggering the phase transition. Rather the structural phase transition in benzil appears to be driven by a conventional soft TA mode at the M -point.

Plasmonic enhancement of cyanine dyes for near-infrared light-triggered photodynamic/photothermal therapy and fluorescent imaging

NASA Astrophysics Data System (ADS)

Lu, Mindan; Kang, Ning; Chen, Chuan; Yang, Liuqing; Li, Yang; Hong, Minghui; Luo, Xiangang; Ren, Lei; Wang, Xiumin

2017-11-01

Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor treatment often suffer from low fluorescence intensity and weak singlet oxygen generation efficiency, resulting in inadequate diagnostic and therapy efficacy for tumors. It is still a great challenge to improve both the photodynamic therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT) and FLI at a very low dosage of IR795 (0.4 μM) based on metal-enhanced fluorescence (MEF) effects. In our design, both the fluorescence intensity and reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the localized surface plasmon resonance band of AuNRs overlapping with the absorption or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to 82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence intensity of our designed nanocomposites was helpful to track their behavior in tumor cells. Therefore, our designed nanoagents highlight the applications of multimodal diagnostics and therapy in tumors based on MEF.

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light.

PubMed

Karimi, Mahdi; Sahandi Zangabad, Parham; Baghaee-Ravari, Soodeh; Ghazadeh, Mehdi; Mirshekari, Hamid; Hamblin, Michael R

2017-04-05

Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide.

Autoimmune hepatitis triggered by acute hepatitis A.

PubMed

Tanaka, Hiroto; Tujioka, Hiroto; Ueda, Hiroki; Hamagami, Hiroko; Kida, Youhei; Ichinose, Masakazu

2005-10-14

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

A non-linear dynamical approach to belief revision in cognitive behavioral therapy

PubMed Central

Kronemyer, David; Bystritsky, Alexander

2014-01-01

Belief revision is the key change mechanism underlying the psychological intervention known as cognitive behavioral therapy (CBT). It both motivates and reinforces new behavior. In this review we analyze and apply a novel approach to this process based on AGM theory of belief revision, named after its proponents, Carlos Alchourrón, Peter Gärdenfors and David Makinson. AGM is a set-theoretical model. We reconceptualize it as describing a non-linear, dynamical system that occurs within a semantic space, which can be represented as a phase plane comprising all of the brain's attentional, cognitive, affective and physiological resources. Triggering events, such as anxiety-producing or depressing situations in the real world, or their imaginal equivalents, mobilize these assets so they converge on an equilibrium point. A preference function then evaluates and integrates evidentiary data associated with individual beliefs, selecting some of them and comprising them into a belief set, which is a metastable state. Belief sets evolve in time from one metastable state to another. In the phase space, this evolution creates a heteroclinic channel. AGM regulates this process and characterizes the outcome at each equilibrium point. Its objective is to define the necessary and sufficient conditions for belief revision by simultaneously minimizing the set of new beliefs that have to be adopted, and the set of old beliefs that have to be discarded or reformulated. Using AGM, belief revision can be modeled using three (and only three) fundamental syntactical operations performed on belief sets, which are expansion; revision; and contraction. Expansion is like adding a new belief without changing any old ones. Revision is like adding a new belief and changing old, inconsistent ones. Contraction is like changing an old belief without adding any new ones. We provide operationalized examples of this process in action. PMID:24860491

Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment.

PubMed

Okada, Masaya; Imagawa, Jun; Tanaka, Hideo; Nakamae, Hirohisa; Hino, Masayuki; Murai, Kazunori; Ishida, Yoji; Kumagai, Takashi; Sato, Seiichi; Ohashi, Kazuteru; Sakamaki, Hisashi; Wakita, Hisashi; Uoshima, Nobuhiko; Nakagawa, Yasunori; Minami, Yosuke; Ogasawara, Masahiro; Takeoka, Tomoharu; Akasaka, Hiroshi; Utsumi, Takahiko; Uike, Naokuni; Sato, Tsutomu; Ando, Sachiko; Usuki, Kensuke; Mizuta, Syuichi; Hashino, Satoshi; Nomura, Tetsuhiko; Shikami, Masato; Fukutani, Hisashi; Ohe, Yokiko; Kosugi, Hiroshi; Shibayama, Hirohiko; Maeda, Yasuhiro; Fukushima, Toshihiro; Yamazaki, Hirohito; Tsubaki, Kazuo; Kukita, Toshimasa; Adachi, Yoko; Nataduka, Toshiki; Sakoda, Hiroto; Yokoyama, Hisayuki; Okamoto, Takahiro; Shirasugi, Yukari; Onishi, Yasushi; Nohgawa, Masaharu; Yoshihara, Satoshi; Morita, Satoshi; Sakamoto, Junichi; Kimura, Shinya

2018-05-01

We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ + T-cell and CD4 + regulatory T-cell (CD25 + CD127 low ) counts before discontinuation correlated significantly with successful therapy discontinuation. These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Image-guided automatic triggering of a fractional CO2 laser in aesthetic procedures.

PubMed

Wilczyński, Sławomir; Koprowski, Robert; Wiernek, Barbara K; Błońska-Fajfrowska, Barbara

2016-09-01

Laser procedures in dermatology and aesthetic medicine are associated with the need for manual laser triggering. This leads to pulse overlapping and side effects. Automatic laser triggering based on image analysis can provide a secure fit to each successive doses of radiation. A fractional CO2 laser was used in the study. 500 images of the human skin of healthy subjects were acquired. Automatic triggering was initiated by an application together with a camera which tracks and analyses the skin in visible light. The tracking algorithm uses the methods of image analysis to overlap images. After locating the characteristic points in analysed adjacent areas, the correspondence of graphs is found. The point coordinates derived from the images are the vertices of graphs with respect to which isomorphism is sought. When the correspondence of graphs is found, it is possible to overlap the neighbouring parts of the image. The proposed method of laser triggering owing to the automatic image fitting method allows for 100% repeatability. To meet this requirement, there must be at least 13 graph vertices obtained from the image. For this number of vertices, the time of analysis of a single image is less than 0.5s. The proposed method, applied in practice, may help reduce the number of side effects during dermatological laser procedures resulting from laser pulse overlapping. In addition, it reduces treatment time and enables to propose new techniques of treatment through controlled, precise laser pulse overlapping. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improving understanding of trigger points and widespread pressure pain sensitivity in tension-type headache patients: clinical implications.

PubMed

Fernández-De-Las-Peñas, César; Arendt-Nielsen, Lars

2017-09-01

The underlying etiology of tension type headache (TTH) is not understood. The current paper highlights the etiologic role of muscle trigger points (TrPs) to the development and maintenance of central sensitization in TTH and its clinical repercussion for proper management of these patients. Areas covered: A literature search on Pub Med for English-language published papers between 1990 and May 2017 to provide the most updated data on the topic was conducted. Current literature suggests that the referred pain elicited by active trigger points (TrPs) contributes to the manifestations of TTH. There is also evidence supporting that TrPs represent a peripheral source of nociception and thereby a driver in the development of central sensitization. In fact, TrPs have been found to be associated with widespread pressure pain sensitivity in TTH. Temporal and spatial summation of TrP nociception suggests that inactivating TrP in the neck, head and shoulder muscles could help these patients; however, current evidence supporting the therapeutic role of TrPs in TTH is conflicting. Expert commentary: Understanding the role of TrPs in TTH in widespread pain sensitization may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions.

Effectiveness of dry needling versus a classical physiotherapy program in patients with chronic low-back pain: a single-blind, randomized, controlled trial.

PubMed

Tüzün, Emİne Handan; Gıldır, Sıla; Angın, Ender; Tecer, Büşra Hande; Dana, Kezban Öztürk; Malkoç, Mehtap

2017-09-01

[Purpose] We compared the effectiveness of dry needling with a classical physiotherapy program in patients with chronic low-back pain caused by lumbar disc hernia (LHNP). [Subjects and Methods] In total, 34 subjects were allocated randomly to the study (n=18) and control groups (n=16). In the study group, dry needling was applied using acupuncture needles. The control group performed a home exercise program in addition to hot pack, TENS, and ultrasound applications. Pain was assessed with the short form of the McGill Pain Questionnaire. The number of trigger points and their pressure sensitivity were evaluated with a physical examination (palpation). The Beck Depression Inventory was used to assess depression. The Tampa Kinesiophobia Scale was used to assess fear of movement. [Results] In the study group, the calculated Cohen's effect sizes were bigger than those in the control group in terms of pain, trigger point-related variables, and fear of movement. Effect sizes for reducing depressive symptoms were similar in both groups. [Conclusion] These results suggest that dry needling can be an effective treatment for reducing pain, number of trigger points, sensitivity, and kinesiophobia in patients with chronic low-back pain caused by lumbar disc hernia.

Light activated microbubbles for imaging and microsurgery

NASA Astrophysics Data System (ADS)

Cavigli, Lucia; Micheletti, Filippo; Tortoli, Paolo; Centi, Sonia; Lai, Sarah; Borri, Claudia; Rossi, Francesca; Ratto, Fulvio; Pini, Roberto

2017-03-01

Imaging and microsurgery procedures based on the photoacoustic effect have recently attracted much attention for cancer treatment. Light absorption in the nanosecond regime triggers thermoelastic processes that induce ultrasound emission and even cavitation. The ultrasound waves may be detected to reconstruct images, while cavitation may be exploited to kill malignant cells. The potential of gold nanorods as contrast agents for photoacoustic imaging has been extensively investigated, but still little is known about their use to trigger cavitation. Here, we investigated the influence of environment thermal properties on the ability of gold nanorods to trigger cavitation by probing the photoacoustic emission as a function of the excitation fluence. We are confident that these results will provide useful directions to the development of new strategies for therapies based on the photoacoustic effect.

Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol.

PubMed

Siristatidis, Charalampos; Drakopoulos, Panagiotis; Vogiatzi, Paraskevi; Karageorgiou, Vasilios; Daskalakis, George

2018-05-16

In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous "suspects" of reduced success after assisted reproduction techniques (ART) - the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

An evaluation of the statistical significance of the association between northward turnings of the interplanetary magnetic field and substorm expansion onsets

NASA Astrophysics Data System (ADS)

Hsu, Tung-Shin; McPherron, R. L.

2002-11-01

An outstanding problem in magnetospheric physics is deciding whether substorms are always triggered by external changes in the interplanetary magnetic field (IMF) or solar wind plasma, or whether they sometimes occur spontaneously. Over the past decade, arguments have been made on both sides of this issue. In fact, there is considerable evidence that some substorms are triggered. However, equally persuasive examples of substorms with no obvious trigger have been found. Because of conflicting views on this subject, further work is required to determine whether there is a physical relation between IMF triggers and substorm onset. In the work reported here a list of substorm onsets was created using two independent substorm signatures: sudden changes in the slope of the AL index and the start of a Pi 2 pulsation burst. Possible IMF triggers were determined from ISEE-2 observations. With the ISEE spacecraft near local noon immediately upstream of the bow shock, there can be little question about propagation delay to the magnetopause or whether a particular IMF feature hits the subsolar magnetopause. Thus it eliminates the objections that the calculated arrival time is subject to a large error or that the solar wind monitor missed a potential trigger incident at the subsolar point. Using a less familiar technique, statistics of point process, we find that the time delay between substorm onsets and the propagated arrival time of IMF triggers are clustered around zero. We estimate for independent processes that the probability of this clustering by chance alone is about 10-11. If we take into account the requirement that the IMF must have been southward prior to the onset, then the probability of clustering is higher, ˜10-5, but still extremely unlikely. Thus it is not possible to ascribe the apparent relation between IMF northward turnings and substorm onset to coincidence.

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity.

PubMed

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

2017-01-01

We developed light-triggered liposomes incorporating 3-5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl- sn -glycero-3-phosphoethanolamine- N -(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy.

Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy.

PubMed

Hu, Chuan; Cun, Xingli; Ruan, Shaobo; Liu, Rui; Xiao, Wei; Yang, Xiaotong; Yang, Yuanyuan; Yang, Chuanyao; Gao, Huile

2018-06-01

Chemotherapy remains restricted by poor drug delivery efficacy due to the heterogenous nature of tumor. Herein, we presented a novel nanoparticle that could not only response to the tumor microenvironment but also modulate it for deep tumor penetration and combination therapy. The intelligent nanoparticle (IDDHN) was engineered by hyaluronidase (HAase)-triggered size shrinkable hyaluronic acid shells, which were modified with NIR laser sensitive nitric oxide donor (HN), small-sized dendrimeric prodrug (IDD) of doxorubicin (DOX) as chemotherapy agent and indocyanine green (ICG) as photothermal agent into a single nanoparticle. IDDHN displayed synergistic deep penetration both in vitro and in vivo, owing to the enzymatically degradable HN shell mediated by HAase and laser-enhanced NO release triggered deep penetration upon strong hyperthermia effect of ICG under the NIR laser irradiation. The therapeutic effect of IDDHN was verified in 4T1 xenograft tumor model, and IDDHN showed a much better antitumor efficiency with few side effects upon NIR laser irradiation. Therefore, the valid of this study might provide a novel tactic for engineering nanoparticles both response to and modulate the tumor microenvironment for improving penetration and heterogeneity distribution of therapeutic agents in tumor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

PubMed Central

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

2017-01-01

We developed light-triggered liposomes incorporating 3–5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy. PMID:28203076

Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy

PubMed Central

Wu, Bo; Wan, Bing; Lu, Shu-Ting; Deng, Kai; Li, Xiao-Qi; Wu, Bao-Lin; Li, Yu-Shuang; Liao, Ru-Fang; Huang, Shi-Wen; Xu, Hai-Bo

2017-01-01

The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR) light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. PMID:28670120

Meta-analysis: exercise therapy for nonspecific low back pain.

PubMed

Hayden, Jill A; van Tulder, Maurits W; Malmivaara, Antti V; Koes, Bart W

2005-05-03

Exercise therapy is widely used as an intervention in low back pain. To evaluate the effectiveness of exercise therapy in adult nonspecific acute, subacute, and chronic low back pain versus no treatment and other conservative treatments. MEDLINE, EMBASE, PsychInfo, CINAHL, and Cochrane Library databases to October 2004; citation searches and bibliographic reviews of previous systematic reviews. Randomized, controlled trials evaluating exercise therapy for adult nonspecific low back pain and measuring pain, function, return to work or absenteeism, and global improvement outcomes. Two reviewers independently selected studies and extracted data on study characteristics, quality, and outcomes at short-, intermediate-, and long-term follow-up. 61 randomized, controlled trials (6390 participants) met inclusion criteria: acute (11 trials), subacute (6 trials), and chronic (43 trials) low back pain (1 trial was unclear). Evidence suggests that exercise therapy is effective in chronic back pain relative to comparisons at all follow-up periods. Pooled mean improvement (of 100 points) was 7.3 points (95% CI, 3.7 to 10.9 points) for pain and 2.5 points (CI, 1.0 to 3.9 points) for function at earliest follow-up. In studies investigating patients (people seeking care for back pain), mean improvement was 13.3 points (CI, 5.5 to 21.1 points) for pain and 6.9 points (CI, 2.2 to 11.7 points) for function, compared with studies where some participants had been recruited from a general population (for example, with advertisements). Some evidence suggests effectiveness of a graded-activity exercise program in subacute low back pain in occupational settings, although the evidence for other types of exercise therapy in other populations is inconsistent. In acute low back pain, exercise therapy and other programs were equally effective (pain, 0.03 point [CI, -1.3 to 1.4 points]). Limitations of the literature, including low-quality studies with heterogeneous outcome measures inconsistent and poor reporting, and possibility of publication bias. Exercise therapy seems to be slightly effective at decreasing pain and improving function in adults with chronic low back pain, particularly in health care populations. In subacute low back pain populations, some evidence suggests that a graded-activity program improves absenteeism outcomes, although evidence for other types of exercise is unclear. In acute low back pain populations, exercise therapy is as effective as either no treatment or other conservative treatments.

ER stress and Parkinson's disease: Pathological inputs that converge into the secretory pathway.

PubMed

Mercado, Gabriela; Castillo, Valentina; Soto, Paulina; Sidhu, Anita

2016-10-01

The major clinical feature of Parkinson's disease (PD) is impairment in motor control as a result of extensive dopaminergic neuron loss in the substantia nigra pars compacta. The central pathological hallmark of PD is the formation of neuronal cytoplasmic inclusions of insoluble proteins called Lewy bodies, of which fibrillar aggregates of misfolded αSynuclein are the major components. Despite intense research on the pathogenic mechanism that trigger neuronal loss and disease progression, the neurogenesis of PD remains unknown. However, studies on genetics of PD have identified specific genes and proteins linked to this disease. Genetic mutations linked with different forms of familial PD have unveiled a closer relationship between pathology and impairments at different points in the secretory pathway. Accumulation of misfolded/unfolded proteins in the endoplasmic reticulum and disruptions in protein clearance mechanisms result in activation of an adaptive stress pathway known as the unfolded protein response (UPR). UPR signaling is mediated by three stress sensors that induce independent and convergent signaling branches that help to maintain homeostasis, or eventually trigger cell death under chronic stress conditions. Signs of ER stress are observed in post-mortem tissue from sporadic human PD cases and in most animal models of the disease, implicating all three branches of this cellular response. However, the exact contribution of the UPR in the progression of PD or in dopaminergic neuron survival is not yet well understood. A large number of studies reveal a clear activation of the UPR in toxicological models resembling sporadic PD, where ATF6, XBP1 and CHOP have a functional role in controlling dopaminergic neuron survival in neurotoxin-based models of PD in vivo. Also pharmacological and gene therapy approaches aimed to target different points of this pathway have revealed an important functional role in PD pathogenesis. This article is part of a Special Issue entitled SI:ER stress. Copyright © 2016 Elsevier B.V. All rights reserved.

TREATMENT OF SUBACUTE POSTERIOR KNEE PAIN IN AN ADOLESCENT BALLET DANCER UTILIZING TRIGGER POINT DRY NEEDLING: A CASE REPORT

PubMed Central

Tansey, Kimberly A.; Westrick, Richard B.

2014-01-01

Study Design: Case Report. Background and Purpose: Dry needling (DN) is an increasingly popular intervention used by clinicians as a treatment of regional neuromusculoskeletal pain. DN is an invasive procedure that involves insertion of a thin monofilament needle directly into a muscle trigger point (MTP) with the intent of stimulating a local twitch response. Current evidence is somewhat limited, but recent literature supports the use of this intervention in specific neuromusculoskeletal conditions. The purpose of this case report is to present the outcomes of DN as a primary treatment intervention in an adolescent subject with subacute posterior knee pain. Case Description: The subject was a 16‐year‐old female competitive ballet dancer referred to physical therapy with a two month history of right posterior knee pain. Palpation identified MTPs which reproduced the patient’s primary symptoms. In addition to an exercise program promoting lower extremity flexibility and hip stability, the subject was treated with DN to the right gastrocnemius, soleus, and popliteus muscles. Outcomes: The subject reported being pain free on the Numerical Pain Scale and a +7 improvement in perceived change in recovery on the Global Rating of Change at final follow‐up. Physical examination demonstrated no observed impairments or functional limitations, including normal mobility, full strength, and unrestricted execution of dance maneuvers. Discussion: The patient was able to return to high level dance training and competition without physical limitations and resumed pre‐injury dynamic movement activities including dancing, running, jumping, and pivoting without pain. DN can be an effective and efficient intervention to assist patients in decreasing pain and returning to high intensity physical activity. Additional research is needed to determine if DN is effective for other body regions and has long‐term positive outcomes. Level of Evidence: Level 4 PMID:24567862

Dysregulation of Ion Homeostasis by Antifungal Agents

PubMed Central

Zhang, Yongqiang; Muend, Sabina; Rao, Rajini

2012-01-01

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides. PMID:22493595

Mechanisms of bile acid mediated inflammation in the liver.

PubMed

Li, Man; Cai, Shi-Ying; Boyer, James L

2017-08-01

Bile acids are synthesized in the liver and are the major component in bile. Impaired bile flow leads to cholestasis that is characterized by elevated levels of bile acid in the liver and serum, followed by hepatocyte and biliary injury. Although the causes of cholestasis have been extensively studied, the molecular mechanisms as to how bile acids initiate liver injury remain controversial. In this chapter, we summarize recent advances in the pathogenesis of bile acid induced liver injury. These include bile acid signaling pathways in hepatocytes as well as the response of cholangiocytes and innate immune cells in the liver in both patients with cholestasis and cholestatic animal models. We focus on how bile acids trigger the production of molecular mediators of neutrophil recruitment and the role of the inflammatory response in this pathological process. These advances point to a number of novel targets where drugs might be judged to be effective therapies for cholestatic liver injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dysregulation of ion homeostasis by antifungal agents.

PubMed

Zhang, Yongqiang; Muend, Sabina; Rao, Rajini

2012-01-01

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca(2+) burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca(2+) stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

"In the Sport I Am Here": Therapeutic Processes and Health Effects of Sport and Exercise on PTSD.

PubMed

Ley, Clemens; Rato Barrio, María; Koch, Andreas

2018-02-01

Current evidence suggests positive effects of exercise on posttraumatic stress symptoms; however, knowledge about how these effects are achieved is limited. Thus, this study aims to contribute to a more holistic understanding of these effects. We performed a single case study of a war and torture survivor, who was diagnosed with posttraumatic stress disorder (PTSD) and depression, and who was participant of the sport and exercise therapy program Movi Kune. Participant observation was conducted as well as semi-structured interviews with the participant and his psychotherapist. Data analysis resulted in the proposal of different processes: The focus on bodily sensations related to an exposure effect, contributing to improvements in body awareness, coping behavior, and affect regulation, whereas the focus on playing related to an improved performance, presence, enjoyment, and mastery experiences, pointing toward distraction and motivational-restorative effects. The findings also advice to be cautious as participants may be exposed to negative sensations and trauma-related triggers.

“In the Sport I Am Here”: Therapeutic Processes and Health Effects of Sport and Exercise on PTSD

PubMed Central

Rato Barrio, María; Koch, Andreas

2017-01-01

Current evidence suggests positive effects of exercise on posttraumatic stress symptoms; however, knowledge about how these effects are achieved is limited. Thus, this study aims to contribute to a more holistic understanding of these effects. We performed a single case study of a war and torture survivor, who was diagnosed with posttraumatic stress disorder (PTSD) and depression, and who was participant of the sport and exercise therapy program Movi Kune. Participant observation was conducted as well as semi-structured interviews with the participant and his psychotherapist. Data analysis resulted in the proposal of different processes: The focus on bodily sensations related to an exposure effect, contributing to improvements in body awareness, coping behavior, and affect regulation, whereas the focus on playing related to an improved performance, presence, enjoyment, and mastery experiences, pointing toward distraction and motivational-restorative effects. The findings also advice to be cautious as participants may be exposed to negative sensations and trauma-related triggers. PMID:29199529

Synthetic activation of caspases: Artificial death switches

PubMed Central

MacCorkle, Rebecca A.; Freeman, Kevin W.; Spencer, David M.

1998-01-01

The development of safe vectors for gene therapy requires fail-safe mechanisms to terminate therapy or remove genetically altered cells. The ideal “suicide switch” would be nonimmunogenic and nontoxic when uninduced and able to trigger cell death independent of tissue type or cell cycle stage. By using chemically induced dimerization, we have developed powerful death switches based on the cysteine proteases, caspase-1 ICE (interleukin-1β converting enzyme) and caspase-3 YAMA. In both cases, aggregation of the target protein is achieved by a nontoxic lipid-permeable dimeric FK506 analog that binds to the attached FK506-binding proteins, FKBPs. We find that intracellular cross-linking of caspase-1 or caspase-3 is sufficient to trigger rapid apoptosis in a Bcl-xL-independent manner, suggesting that these conditional proapoptotic molecules can bypass intracellular checkpoint genes, such as Bcl-xL, that limit apoptosis. Because these chimeric molecules are derived from autologous proteins, they should be nonimmunogenic and thus ideal for long-lived gene therapy vectors. These properties should also make chemically induced apoptosis useful for developmental studies, for treating hyperproliferative disorders, and for developing animal models to a wide variety of diseases. PMID:9520421

Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

PubMed

Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2018-05-23

Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

[Post-stroke shoulder-hand syndrome treated with floating-needle therapy combined with rehabilitation training: a randomized controlled trial].

PubMed

Zhou, Zhao-Hui; Zhuang, Li-Xing; Chen, Zhen-Hu; Lang, Jian-Ying; Li, Yan-Hui; Jiang, Gang-Hui; Xu, Zhan-Qiong; Liao, Mu-Xi

2014-07-01

To compare the clinical efficacy in the treatment of post-stroke shoulder-hand syndrome between floating-needle therapy and conventional acupuncture on the basis of rehabilitation training. One hundred cases of post-stroke shoulder-hand syndrome were randomized into a floating-needle group and an acupuncture group, 50 cases in each one. The passive and positive rehabilitation training was adopted in the two groups. Additionally, in the floating-needle group, the floating-needle therapy was used. The needle was inserted at the site 5 to 10 cm away from myofasical trigger point (MTrP), manipulated and scattered subcutaneously, for 2 min continuously. In the acupuncture group, the conventional acupuncture was applied at Jianqian (EX-UE), Jianyu (LI 15), Jianliao (TE 14), etc. The treatment was given once every two days, 3 times a week, and 14 days of treatment were required. The shoulder hand syndrome scale (SHSS), the short form McGill pain scale (SF-MPQ) and the modified Fugl-Meyer motor function scale (FMA) were used to evaluate the damage severity, pain and motor function of the upper limbs before and after treatment in the two groups. The clinical efficacy was compared between the two groups. SHSS score, SF-MPQ score and FMA score were improved significantly after treatment in the two groups (all P < 0.01), and the improvements in the floating-needle group were superior to those in the acupuncture group (all P < 0.05). The total effective rate was 94.0% (47/50) in the floating-needle group, which was better than 90.0% (45/50) in the acupuncture group (P < 0.05). The floating-needle therapy combined with rehabilitation training achieves a satisfactory efficacy on post-stroke shoulder-hand syndrome, which is better than the combined therapy of conventional acupuncture and rehabilitation training.

Algorithm of the automated choice of points of the acupuncture for EHF-therapy

NASA Astrophysics Data System (ADS)

Lyapina, E. P.; Chesnokov, I. A.; Anisimov, Ya. E.; Bushuev, N. A.; Murashov, E. P.; Eliseev, Yu. Yu.; Syuzanna, H.

2007-05-01

Offered algorithm of the automated choice of points of the acupuncture for EHF-therapy. The recipe formed by algorithm of an automated choice of points for acupunctural actions has a recommendational character. Clinical investigations showed that application of the developed algorithm in EHF-therapy allows to normalize energetic state of the meridians and to effectively solve many problems of an organism functioning.

The Advanced Gamma-ray Imaging System (AGIS): A Nanosecond Time Scale Stereoscopic Array Trigger System.

NASA Astrophysics Data System (ADS)

Krennrich, Frank; Buckley, J.; Byrum, K.; Dawson, J.; Drake, G.; Horan, D.; Krawzcynski, H.; Schroedter, M.

2008-04-01

Imaging atmospheric Cherenkov telescope arrays (VERITAS, HESS) have shown unprecedented background suppression capabilities for reducing cosmic-ray induced air showers, muons and night sky background fluctuations. Next-generation arrays with on the order of 100 telescopes offer larger collection areas, provide the possibility to see the air shower from more view points on the ground, have the potential to improve the sensitivity and give additional background suppression. Here we discuss the design of a fast array trigger system that has the potential to perform a real time image analysis allowing substantially improved background rate suppression at the trigger level.

Shedding Light on Nanomedicine

PubMed Central

Tong, Rong

2012-01-01

Light is electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light-controlled therapies can provide minimally or non-invasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides a numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light-based therapies and diagnostics, and vice versa, including photo-triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light-based therapies such as photic injury and phototoxicity will be discussed. PMID:22887840

FNL Scientists Introduce Concept That Could Help the Immune System Respond to Vaccines | FNLCR Staging

Cancer.gov

Scientists have discovered an efficient and straightforward model to manipulate RNA nanoparticles, a new concept that could help trigger desirable activation of the immune system with vaccines and therapies. A multi-institutional team of researchers

Sensitive detection of point mutation using exponential strand displacement amplification-based surface enhanced Raman spectroscopy.

PubMed

Huang, Si-Qiang; Hu, Juan; Zhu, Guichi; Zhang, Chun-Yang

2015-03-15

Accurate identification of point mutation is particularly imperative in the field of biomedical research and clinical diagnosis. Here, we develop a sensitive and specific method for point mutation assay using exponential strand displacement amplification (SDA)-based surface enhanced Raman spectroscopy (SERS). In this method, a discriminating probe and a hairpin probe are designed to specifically recognize the sequence of human K-ras gene. In the presence of K-ras mutant target (C→T), the 3'-terminal of discriminating probe and the 5'-terminal of hairpin probe can be ligated to form a SDA template. Subsequently, the 3'-terminal of hairpin probe can function as a primer to initiate the SDA reaction, producing a large amount of triggers. The resultant triggers can further hybridize with the discriminating probes to initiate new rounds of SDA reaction, leading to an exponential amplification reaction. With the addition of capture probe-modified gold nanoparticles (AuNPs) and the Rox-labeled reporter probes, the amplified triggers can be assembled on the surface of AuNPs through the formation of sandwich hybrids of capture probe-trigger-reporter probe, generating a strong Raman signal. While in the presence of K-ras wild-type target (C), neither ligation nor SDA reaction can be initiated and no Raman signal is observed. The proposed method exhibits high sensitivity with a detection limit of 1.4pM and can accurately discriminate as low as 1% variant frequency from the mixture of mutant target and wild-type target. Importantly, this method can be further applied to analyze the mutant target in the spiked HEK293T cell lysate, holding great potential for genetic analysis and disease prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

The Structural Phase Transition in Deuterated Benzil, C 14D 10O 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goosens, D. J.; Welberry, T. R.; Hagen, Mark E

2006-01-01

Neutron inelastic scattering has been used to examine the structural phase transition in deuterated benzil C{sub 14}D{sub 10}O{sub 2}. The transition in benzil, in which the unit cell goes from a trigonal P3{sub 1}21 unit cell above T{sub c} to a cell doubled P2{sub 1} unit cell below T{sub c}, leads to the emergence of a Bragg peak at the M-point of the high temperature Brillouin zone. It has previously been suggested that the softening of a transverse optic phonon at the {lambda}-point leads to the triggering of an instability at the M-point causing the transition to occur. This suggestionmore » has been investigated by measuring the phonon spectrum at the M-point for a range of temperatures above T{sub c} and the phonon dispersion relation along the {lambda}-M direction just above T{sub c}. It is found that the transverse acoustic phonon at the M-point is of lower energy than the {lambda}-point optic mode and has a softening with temperature as T approaches T{sub c} from above that is much faster than that of the {lambda}-point optic mode. This behavior is inconsistent with the view that the {lambda}-point mode is responsible for triggering the phase transition. Rather the structural phase transition in benzil appears to be driven by a conventional soft TA mode at the M-point.« less

Structural phase transition in deuterated benzil C{sub 14}D{sub 10}O{sub 2}: Neutron inelastic scattering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goossens, D. J.; Welberry, T. R.; Hagen, M. E.

2006-04-01

Neutron inelastic scattering has been used to examine the structural phase transition in deuterated benzil C{sub 14}D{sub 10}O{sub 2}. The transition in benzil, in which the unit cell goes from a trigonal P3{sub 1}21 unit cell above T{sub C} to a cell doubled P2{sub 1} unit cell below T{sub C}, leads to the emergence of a Bragg peak at the M-point of the high temperature Brillouin zone. It has previously been suggested that the softening of a transverse optic phonon at the {gamma}-point leads to the triggering of an instability at the M-point causing the transition to occur. This suggestionmore » has been investigated by measuring the phonon spectrum at the M-point for a range of temperatures above T{sub C} and the phonon dispersion relation along the {gamma}-M direction just above T{sub C}. It is found that the transverse acoustic phonon at the M-point is of lower energy than the {gamma}-point optic mode and has a softening with temperature as T approaches T{sub C} from above that is much faster than that of the {gamma}-point optic mode. This behavior is inconsistent with the view that the {gamma}-point mode is responsible for triggering the phase transition. Rather the structural phase transition in benzil appears to be driven by a conventional soft TA mode at the M-point.« less

Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities.

PubMed

Philpott, H; Nandurkar, S; Royce, S G; Thien, F; Gibson, P R

2016-08-01

The use of allergy tests to guide dietary treatment for eosinophilic oesophagitis (EoE) is controversial and data are limited. Aeroallergen sensitisation patterns and food triggers have been defined in Northern Hemisphere cohorts only. To determine if allergy tests that are routinely available can predict food triggers in adult patients with EoE. To define the food triggers and aeroallergen sensitisation patterns in a novel Southern Hemisphere (Australian) cohort of patients. Consecutive patients with EoE who elected to undergo dietary therapy were prospectively assessed, demographic details and atopic characteristics recorded, and allergy tests, comprising skin-prick and skin-patch tests, serum allergen-specific IgE, basophil activation test and serum food-specific IgG, were performed. Patients underwent a six-food elimination diet with a structured algorithm that included endoscopic and histological examination of the oesophagus a minimum of 2 weeks after each challenge. Response was defined as <15 eosinophils per HPF. Foods defined as triggers were considered as gold standard and were compared with those identified by allergy testing. No allergy test could accurately predict actual food triggers. Concordance among skin-prick and serum allergen-specific IgE was high for aeroallergens only. Among seasonal aeroallergens, rye-grass sensitisation was predominant. Food triggers were commonly wheat, milk and egg, alone or in combination. None of the currently-available allergy tests predicts food triggers for EoE. Exclusion-rechallenge methodology with oesophageal histological assessment remains the only effective investigation. The same food triggers were identified in this southern hemisphere cohort as previously described. © 2016 John Wiley & Sons Ltd.

Vaginal Toxic Shock Reaction Triggering Desquamative Inflammatory Vaginitis

PubMed Central

Pereira, Nigel; Edlind, Thomas D.; Schlievert, Patrick M.; Nyirjesy, Paul

2012-01-01

Objective To report two cases of desquamative inflammatory vaginitis (DIV) associated with toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strains. Materials and Methods Case report of two patients, one with an acute and one with a chronic presentation, diagnosed with DIV on the basis of clinical findings and wet mount microscopy. Pre- and posttreatment vaginal bacterial and yeast cultures were obtained. Results Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial cultures following oral antibiotic therapy were negative. Conclusions DIV may be triggered through TSST-1-mediated vaginal toxic shock reaction. PMID:23222054

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

PubMed

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Triggering Mechanism for Neutron Induced Single-Event Burnout in Power Devices

NASA Astrophysics Data System (ADS)

Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori

2013-04-01

Cosmic ray neutrons can trigger catastrophic failures in power devices. It has been reported that parasitic transistor action causes single-event burnout (SEB) in power metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated gate bipolar transistors (IGBTs). However, power diodes do not have an inherent parasitic transistor. In this paper, we describe the mechanism triggering SEB in power diodes for the first time using transient device simulation. Initially, generated electron-hole pairs created by incident recoil ions generate transient current, which increases the electron density in the vicinity of the n-/n+ boundary. The space charge effect of the carriers leads to an increase in the strength of the electric field at the n-/n+ boundary. Finally, the onset of impact ionization at the n-/n+ boundary can trigger SEB. Furthermore, this failure is closely related to diode secondary breakdown. It was clarified that the impact ionization at the n-/n+ boundary is a key point of the mechanism triggering SEB in power devices.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Model-Based Adaptive Event-Triggered Control of Strict-Feedback Nonlinear Systems.

PubMed

Li, Yuan-Xin; Yang, Guang-Hong

2018-04-01

This paper is concerned with the adaptive event-triggered control problem of nonlinear continuous-time systems in strict-feedback form. By using the event-sampled neural network (NN) to approximate the unknown nonlinear function, an adaptive model and an associated event-triggered controller are designed by exploiting the backstepping method. In the proposed method, the feedback signals and the NN weights are aperiodically updated only when the event-triggered condition is violated. A positive lower bound on the minimum intersample time is guaranteed to avoid accumulation point. The closed-loop stability of the resulting nonlinear impulsive dynamical system is rigorously proved via Lyapunov analysis under an adaptive event sampling condition. In comparing with the traditional adaptive backstepping design with a fixed sample period, the event-triggered method samples the state and updates the NN weights only when it is necessary. Therefore, the number of transmissions can be significantly reduced. Finally, two simulation examples are presented to show the effectiveness of the proposed control method.

Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of Intracellular Proteases for Targeted Cytotoxicity.

PubMed

Ho, Patrick; Ede, Christopher; Chen, Yvonne Y

2017-08-18

Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. We demonstrate that fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We further demonstrate the rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the COVERT platform's modularity and adaptability to diverse protease targets. As an initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we verified that primary human T cells can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. Our findings set the foundation for future intracellular-antigen-responsive therapeutics that can complement surface-targeted therapies.

Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Karen; Stewart, James; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario

2014-09-01

Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes andmore » organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.« less

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

PubMed Central

Karimi, Mahdi; Zangabad, Parham Sahandi; Baghaee-Ravari, Soodeh; Ghazadeh, Mehdi; Mirshekari, Hamid; Hamblin, Michael R.

2017-01-01

Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide. PMID:28192672

Measurement of laser power for photo-triggered drug delivery in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, R.; Zhang, X. L.; Liu, F.

Thus far, despite many investigations have been carried out for photo-triggered drug delivery systems, most of them suffer from an intrinsic drawback of without real-time monitoring mechanism. Incident intensity of light is a feasible parameter to monitor the drug release profiles. However, it is difficult to measure the incident laser power irradiated onto the photo-triggered carriers in drug delivery systems during in vivo therapy. We design an online measurement method based on the fluorescence intensity ratio (FIR) technique through upconversion nanoparticles. FIR value varies with temperature of sample due to the thermal effect induced by the incident laser, which validatesmore » the laser power measurement. Effects of rare earth doping concentration, as well as experimental conditions including laser spots and wavelengths on the measurement behavior were also investigated.« less

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

NASA Astrophysics Data System (ADS)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

Unique concurrent observations of whistler mode hiss, chorus, and triggered emissions

NASA Astrophysics Data System (ADS)

Hosseini, Poorya; Gołkowski, Mark; Turner, Drew L.

2017-06-01

We present a unique 2 h ground-based observation of concurrent magnetospheric hiss, chorus, VLF triggered emissions as well as ELF/VLF signals generated locally by the High Frequency Active Auroral Research Program (HAARP) facility. Eccentricity of observed wave polarization is used as a criteria to identify magnetospheric emissions and estimate their ionospheric exit points. The observations of hiss and chorus in the unique background of coherent HAARP ELF/VLF waves and triggered emissions allow for more accurate characterization of hiss and chorus properties than in typical ground-based observations. Eccentricity and azimuth results suggest a moving ionospheric exit point associated with a single ducted path at L 5. The emissions exhibit dynamics in time suggesting an evolution of a magnetospheric source from hiss generation to chorus generation or a moving plasmapause location. We introduce a frequency band-limited autocorrelation method to quantify the relative coherency of the emissions. A range of coherency was observed from high order of coherency in local HAARP transmissions and their echoes to lower coherency in natural chorus and hiss emissions.

Current management of atopic dermatitis and interruption of the atopic march.

PubMed

Boguniewicz, Mark; Eichenfield, Lawrence F; Hultsch, Thomas

2003-12-01

Treatment of atopic dermatitis requires a comprehensive approach that includes evaluation of potential triggers and education of the patient and family regarding proper avoidance measures. Hydration of the skin and maintenance of an intact skin barrier remain integral to proper management. Although topical corticosteroids have been a mainstay of anti-inflammatory therapy, the newer topical calcineurin inhibitors offer advantages for treatment of this chronic, relapsing disease. Studies aimed at defining optimal combination therapy and early intervention might change the treatment paradigm for atopic dermatitis.

An adult case of mumps brainstem encephalitis.

PubMed

Koyama, S; Morita, K; Yamaguchi, S; Fujikane, T; Sasaki, N; Aizawa, H; Kikuchi, K

2000-06-01

We present an adult case of mumps brainstem encephalitis. He was successfully treated with steroid pulse therapy and recovered completely except for persistent dysuria. He had not been vaccinated and had no history of acute mumps infection. We consider that encephalitis in this case was caused by a reversible autoimmune process triggered by mumps infection. We emphasize the usefulness of pulse therapy for the treatment of some cases of mumps brainstem encephalitis in addition to the importance of mumps vaccination to prevent such a severe complication as encephalitis.

Therapeutic Vascular Targeting and Irradiation: Correlation of MRI and Tissue Changes at Cellular and Molecular Levels to Optimizing Outcome

DTIC Science & Technology

2005-06-01

subsequently trigger a cascade of tumor cell death in experimental tumors [4,5]. Although massive necrosis can be induced, tumors usually regrow from a...the Statement of Work Task 2, experimental radiation therapy has been designed and initiated based on the MRI oximetry data. Preliminary data of control...Hoechst dye 33342 showed a significant reduction in perfused vessels at 2hr after CA4P, which recovered 24 h later. * Experimental radiation therapy a

Role of Secondary Low-Energy Electrons in the Concomitant Chemoradiation Therapy of Cancer

NASA Astrophysics Data System (ADS)

Zheng, Yi; Hunting, Darel J.; Ayotte, Patrick; Sanche, Léon

2008-05-01

Solid films of DNA with and without the chemotherapeutic agent cisplatin bonded to guanine were bombarded with electrons of 1, 10, 100, and 60 000 eV causing single and double strand breaks. In the presence of cisplatin this damage was increased by factors varying from 1.3 to 4.4 owing to an increase in bond dissociation triggered by the formation of transient anions. This mechanism may lie at the basis of the efficiency of concomitant cisplatin-radiation therapy.

Gamification in Physical Therapy: More Than Using Games.

PubMed

Janssen, Joep; Verschuren, Olaf; Renger, Willem Jan; Ermers, Jose; Ketelaar, Marjolijn; van Ee, Raymond

2017-01-01

The implementation of computer games in physical therapy is motivated by characteristics such as attractiveness, motivation, and engagement, but these do not guarantee the intended therapeutic effect of the interventions. Yet, these characteristics are important variables in physical therapy interventions because they involve reward-related dopaminergic systems in the brain that are known to facilitate learning through long-term potentiation of neural connections. In this perspective we propose a way to apply game design approaches to therapy development by "designing" therapy sessions in such a way as to trigger physical and cognitive behavioral patterns required for treatment and neurological recovery. We also advocate that improving game knowledge among therapists and improving communication between therapists and game designers may lead to a novel avenue in designing applied games with specific therapeutic input, thereby making gamification in therapy a realistic and promising future that may optimize clinical practice.

Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain.

PubMed

Rossettini, Giacomo; Carlino, Elisa; Testa, Marco

2018-01-22

Placebo and nocebo effects are embodied psycho-neurobiological responses capable of modulating pain and producing changes at different neurobiological, body at perceptual and cognitive levels. These modifications are triggered by different contextual factors (CFs) presented in the therapeutic encounter between patient and healthcare providers, such as healing rituals and signs. The CFs directly impact on the quality of the therapeutic outcome: a positive context, that is a context characterized by the presence of positive CFs, can reduce pain by producing placebo effects, while a negative context, characterized by the presence of negative CFs, can aggravate pain by creating nocebo effects. Despite the increasing interest about this topic; the detailed study of CFs as triggers of placebo and nocebo effects is still lacked in the management of musculoskeletal pain.Increasing evidence suggest a relevant role of CFs in musculoskeletal pain management. CFs are a complex sets of internal, external or relational elements encompassing: patient's expectation, history, baseline characteristics; clinician's behavior, belief, verbal suggestions and therapeutic touch; positive therapeutic encounter, patient-centered approach and social learning; overt therapy, posology of intervention, modality of treatment administration; marketing features of treatment and health care setting. Different explanatory models such as classical conditioning and expectancy can explain how CFs trigger placebo and nocebo effects. CFs act through specific neural networks and neurotransmitters that were described as mediators of placebo and nocebo effects.Available findings suggest a relevant clinical role and impact of CFs. They should be integrated in the clinical reasoning to increase the number of treatment solutions, boosts their efficacy and improve the quality of the decision-making. From a clinical perspective, the mindful manipulation of CFs represents a useful opportunity to enrich a well-established therapy in therapeutic setting within the ethical border. From a translational perspective, there is a strong need of research studies on CFs close to routine and real-world clinical practice in order to underline the uncertainty of therapy action and help clinicians to implement knowledge in daily practice.

Clinical impact of bisphosphonates in root canal therapy

PubMed Central

AlRahabi, Mothanna K.; Ghabbani, Hani M.

2018-01-01

Bisphosphonates are stable structural analogs of pyrophosphate, which suppress the activity of osteoclasts, leading to decreased bone resorption. They are essential medications in the treatment of osteoporosis. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate therapy. The prevalence of bisphosphonate-related osteonecrosis of the jaw varies from 0% to 28%, and it can be triggered by dental extraction and trauma. Root canal therapy can delay, or even eliminate, the need for tooth extraction, and therefore, may reduce the risk of bisphosphonate-related osteonecrosis of the jaw. We suggest that this might be the best treatment for teeth with pulpal and/or periapical disease. PMID:29543299

SU-E-J-141: Assessment of the Magnitude and Impact of Trigger Delay in Respiratory Triggered Real-Time Imaging during Radiotherapy.

PubMed

Duan, J; Shen, S; Popple, R; Wu, X; Cardan, R; Brezovich, I

2012-06-01

To assess the trigger delay in respiratory triggered real-time imaging and its impact on image guided radiotherapy (IGRT) with Varian TrueBeam System. A sinusoidal motion phantom with 2cm motion amplitude was used. The trigger delay was determined directly with video image, and indirectly by the distance between expected and actual triggering phantom positions. For the direct method, a fluorescent screen was placed on the phantom to visualize the x-ray. The motion of the screen was recorded at 60 frames/second. The number of frames between the time when the phantom reached expected triggering position and the time when the screen was illuminated by the x-ray was used to determine the trigger delay. In the indirect method, triggered kV x-ray images were acquired in real-time during 'treatment' with triggers set at 25% and 75% respiratory phases where the phantom moved at the maximum speed. 39-40 triggered images were acquired continuously in each series. The distance between the expected and actual triggering points, d, was measured on the images to determine the delay time t by d=Asin(wt), where w=2π/T, T=period and A=amplitude. Motion periods of 2s and 4s were used in the measurement. The trigger delay time determined with direct video imaging was 125ms (7.5 video frames). The average distance between the expected and actual triggering positions determined by the indirect method was 3.93±0.74mm for T=4s and 7.02±1.25mm for T=2s, yielding mean trigger delay times of 126±24ms and 120±22ms, respectively. Although the mean over-travel distance is significant at 25% and 75% phases, clinically, the target over-travel resulted from the trigger delay at the end of expiration (50% phase) is negligibly small(< 0.5mm). The trigger delay in respiration-triggered imaging is in the range of 120-126ms. This delay has negligible clinical effect on gated IGRT. © 2012 American Association of Physicists in Medicine.

PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas.

PubMed

Laimer, Daniela; Dolznig, Helmut; Kollmann, Karoline; Vesely, Paul W; Schlederer, Michaela; Merkel, Olaf; Schiefer, Ana-Iris; Hassler, Melanie R; Heider, Susi; Amenitsch, Lena; Thallinger, Christiane; Staber, Philipp B; Simonitsch-Klupp, Ingrid; Artaker, Matthias; Lagger, Sabine; Turner, Suzanne D; Pileri, Stefano; Piccaluga, Pier Paolo; Valent, Peter; Messana, Katia; Landra, Indira; Weichhart, Thomas; Knapp, Sylvia; Shehata, Medhat; Todaro, Maria; Sexl, Veronika; Höfler, Gerald; Piva, Roberto; Medico, Enzo; Ruggeri, Bruce A; Cheng, Mangeng; Eferl, Robert; Egger, Gerda; Penninger, Josef M; Jaeger, Ulrich; Moriggl, Richard; Inghirami, Giorgio; Kenner, Lukas

2012-11-01

Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin's lymphoma found in children and young adults. ALCLs frequently carry a chromosomal translocation that results in expression of the oncoprotein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The key molecular downstream events required for NPM-ALK-triggered lymphoma growth have been only partly unveiled. Here we show that the activator protein 1 family members JUN and JUNB promote lymphoma development and tumor dissemination through transcriptional regulation of platelet-derived growth factor receptor-β (PDGFRB) in a mouse model of NPM-ALK-triggered lymphomagenesis. Therapeutic inhibition of PDGFRB markedly prolonged survival of NPM-ALK transgenic mice and increased the efficacy of an ALK-specific inhibitor in transplanted NPM-ALK tumors. Notably, inhibition of PDGFRA and PDGFRB in a patient with refractory late-stage NPM-ALK(+) ALCL resulted in rapid, complete and sustained remission. Together, our data identify PDGFRB as a previously unknown JUN and JUNB target that could be a highly effective therapy for ALCL.

Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report and review of the literature.

PubMed

Salemi, Simonetta; Biondo, Michela I; Fiorentino, Chiara; Argento, Giuseppe; Paolantonio, Michele; Di Murro, Carlo; Malagnino, Vito A; Canzoni, Marco; Diamanti, Andrea Picchianti; D'Amelio, Raffaele

2014-12-01

Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

Sonosensitive MRI nanosystems as Cancer Theranostics: a recent update

NASA Astrophysics Data System (ADS)

Garello, Francesca; Terreno, Enzo

2018-05-01

In the tireless search for innovative and more efficient cancer therapies, sonosensitive Magnetic Resonance Imaging (MRI) agents play an important role. Basically, these systems consist of nano/microvesicles composed by a biocompatible membrane, responsive to ultrasound-induced thermal or mechanical effects, and an aqueous core, filled up with a MRI detectable probe and a therapeutic agent. They offer the possibility to trigger and monitor in real time drug release in a spatio-temporal domain, with the expectation to predict the therapeutic outcome. In this review, the key items to design sonosensitive MRI agents will be examined and an overview on the different approaches available so far will be given. Due to the extremely wide range of adopted ultrasound settings and formulations conceived, it is hard to compare the numerous preclinical studies reported. However, in general, a significantly better therapeutic outcome was noticed when exploiting ultrasound triggered drug release in comparison to traditional therapies, thus paving the way to the possible clinical translation of optimized sonosensitive MRI agents.

The effect of manual acupuncture on blood neutrophil counts in moderate intensity exercise

NASA Astrophysics Data System (ADS)

Ciang, C. Y.; Simadibrata, C.; Tobing, A.; Srilestari, A.

2017-08-01

Exercise, even though it has a beneficial effect, can cause muscle damage and trigger inflammatory responses, as evidenced by increased neutrophils in the blood. Acupuncture is a therapeutic modality that is expected to reduce acute inflammatory responses due to exercise. Thirty untrained men were divided randomly into two groups. The manual acupuncture group (n = 15) received stimulation at acupoints ST36 and SP6 bilateral by needle insertion, while the placebo group (n = 15) received insertion of needles on plaster without penetrating the skin. Therapy was done once for 30 minutes immediately after the subjects completed the exercise. Blood neutrophil counts were assessed before exercise and one hour after exercise ended. The results show there is a statistically significant difference in the number of neutrophils before and after exercise between the manual acupuncture group and the placebo group (0.08±0.91 and 0.97±0.70 p = 0.006). Acupuncture therapy effectively mitigates the acute inflammatory response triggered by exercise.

Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

NASA Astrophysics Data System (ADS)

Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

2014-06-01

A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

Haemostatic monitoring during postpartum haemorrhage and implications for management

PubMed Central

Solomon, C.; Collis, R. E.; Collins, P. W.

2012-01-01

Summary Postpartum haemorrhage (PPH) is a major risk factor for maternal morbidity and mortality. PPH has numerous causative factors, which makes its occurrence and severity difficult to predict. Underlying haemostatic imbalances such as consumptive and dilutional coagulopathies may develop during PPH, and can exacerbate bleeding and lead to progression to severe PPH. Monitoring coagulation status in patients with PPH may be crucial for effective haemostatic management, goal-directed therapy, and improved outcomes. However, current PPH management guidelines do not account for the altered baseline coagulation status observed in pregnant patients, and the appropriate transfusion triggers to use in PPH are unknown, due to a lack of high-quality studies specific to this area. In this review, we consider the evidence for the use of standard laboratory-based coagulation tests and point-of-care viscoelastic coagulation monitoring in PPH. Many laboratory-based tests are unsuitable for emergency use due to their long turnaround times, so have limited value for the management of PPH. Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH. However, further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting. Improving awareness of the correct application and interpretation of viscoelastic coagulation monitoring techniques may be critical in realizing their emergency diagnostic potential. PMID:23075633

Remote Left Ventricular Hemodynamic Monitoring Using a Novel Intracardiac Sensor.

PubMed

Mondritzki, Thomas; Boehme, Philip; White, Jason; Park, Jin Woo; Hoffmann, Jessica; Vogel, Julia; Kolkhof, Peter; Walsh, Stuart; Sandner, Peter; Bischoff, Erwin; Dinh, Wilfried; Hüser, Jörg; Truebel, Hubert

2018-05-01

Heart failure (HF) remains the most common reason for hospital admission in patients aged >65 years. Despite modern drug therapy, mortality and readmission rates for patients hospitalized with HF remain high. This necessitates further research to identify early patients at risk for readmission to limit hospitalization by timely adjustment of medical therapy. Implantable devices can monitor left ventricular (LV) hemodynamics and remotely and continuously detect the early signs of decompensation to trigger interventions and reduce the risk of hospitalization for HF. Here, we report the first preclinical study validating a new batteryless and easy to implant LV-microelectromechanical system to assess LV performance. A miniaturized implantable wireless pressure sensor was adapted for implantation in the LV apex. The LV-microelectromechanical system sensor was tested in a canine model of HF. The wireless pressure sensor measurements were compared with invasive left heart catheter-derived measurements at several time points. During different pharmacological challenge studies with dobutamine or vasopressin, the device was equally sensitive compared with invasive standard procedures. No adverse events or any observable reaction related to the implantation and application of the device for a period of 35 days was observed. Our miniaturized wireless pressure sensor placed in the LV (LV-microelectromechanical system) has the potential to become a new telemetric tool to earlier identify patients at risk for HF decompensation and to guide the treatment of patients with HF. © 2018 American Heart Association, Inc.

A polysaccharide fraction of adlay seed (Coixlachryma-jobi L.) induces apoptosis in human non-small cell lung cancer A549 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Xiangyi; Liu, Wei; Wu, Junhua

Highlights: Black-Right-Pointing-Pointer A polysaccharide from adlay seed, its molecular mass, optical rotation and sugars was determined. Black-Right-Pointing-Pointer We demonstrated that a polysaccharide from adlay can induce apoptosis in cancer cells. Black-Right-Pointing-Pointer The polysaccharide inhibited the metabolism and proliferation of NSCLC A549 cells. Black-Right-Pointing-Pointer The polysaccharide may trigger apoptosis via the mitochondria-dependent pathway. -- Abstract: Different seed extracts from Coix lachryma-jobi (adlay seed) have been used for the treatment of various cancers in China, and clinical data support the use of these extracts for cancer therapy; however, their underlying molecular mechanisms have not been well defined. A polysaccharide fraction, designated asmore » CP-1, was extracted from the C.lachryma-jobi L. var. using the ethanol subsiding method. CP-1 induced apoptosis in A549 cells in a dose-dependent manner, as determined by MTT assay. Apoptotic bodies were observed in the cells by scanning electronic microscopy. Apoptosis and DNA accumulation during S-phase of the cell cycle were determined by annexin V-FITC and PI staining, respectively, and measured by flow cytometry. CP-1 also extended the comet tail length on single cell gel electrophoresis, and disrupted the mitochondrial membrane potential. Further analysis by western blotting showed that the expression of caspase-3 and caspase-9 proteins was increased. Taken together, our results demonstrate that CP-1 is capable of inhibiting A549 cell proliferation and inducing apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data suggest that in addition to its nutritional properties, CP-1 is a very promising candidate polysaccharide for the development of anti-cancer medicines.« less

Implantable Defibrillators for Secondary Prevention of Sudden Cardiac Death in Cardiac Surgery Patients With Perioperative Ventricular Arrhythmias

PubMed Central

Nageh, Maged F.; Kim, John J.; Chen, Lie‐Hong; Yao, Janis F.

2014-01-01

Background Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. Methods and Results The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty‐four patients were identified; 93/164 had an ICD for sustained pre‐ or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD‐T), and secondary end points are TM and ICD‐T. During the mean follow up of 49 months, the primary endpoint of TM+ICD‐T and individual end points of TM and ICD‐T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD‐T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. Conclusion Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients. PMID:25146702

Antiviral immune responses: triggers of or triggered by autoimmunity?

PubMed Central

Münz, Christian; Lünemann, Jan D.; Getts, Meghann Teague; Miller, Stephen D.

2010-01-01

Several common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis, are genetically linked to distinct human MHC class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins as well as geographical distribution of disease risk point towards environmental factors in the genesis of these diseases. Among these environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. In this review, we outline mechanisms by which pathogens can trigger autoimmune disease, and also pathways by which infection and immune control of infectious disease might be dysregulated during autoimmunity. PMID:19319143

Surface freezing of water.

PubMed

Pérez-Díaz, J L; Álvarez-Valenzuela, M A; Rodríguez-Celis, F

2016-01-01

Freezing, melting, evaporation and condensation of water are essential ingredients for climate and eventually life on Earth. In the present work, we show how surface freezing of supercooled water in an open container is conditioned and triggered-exclusively-by humidity in air. Additionally, a change of phase is demonstrated to be triggered on the water surface forming surface ice crystals prior to freezing of bulk. The symmetry of the surface crystal, as well as the freezing point, depend on humidity, presenting at least three different types of surface crystals. Humidity triggers surface freezing as soon as it overpasses a defined value for a given temperature, generating a plurality of nucleation nodes. An evidence of simultaneous nucleation of surface ice crystals is also provided.

LHCb detector and trigger performance in Run II

NASA Astrophysics Data System (ADS)

Francesca, Dordei

2017-12-01

The LHCb detector is a forward spectrometer at the LHC, designed to perform high precision studies of b- and c- hadrons. In Run II of the LHC, a new scheme for the software trigger at LHCb allows splitting the triggering of events into two stages, giving room to perform the alignment and calibration in real time. In the novel detector alignment and calibration strategy for Run II, data collected at the start of the fill are processed in a few minutes and used to update the alignment, while the calibration constants are evaluated for each run. This allows identical constants to be used in the online and offline reconstruction, thus improving the correlation between triggered and offline selected events. The required computing time constraints are met thanks to a new dedicated framework using the multi-core farm infrastructure for the trigger. The larger timing budget, available in the trigger, allows to perform the same track reconstruction online and offline. This enables LHCb to achieve the best reconstruction performance already in the trigger, and allows physics analyses to be performed directly on the data produced by the trigger reconstruction. The novel real-time processing strategy at LHCb is discussed from both the technical and operational point of view. The overall performance of the LHCb detector on the data of Run II is presented as well.

Acoustically induced slip in sheared granular layers: Application to dynamic earthquake triggering: TRIGGERED SLIP IN SHEARED GRANULAR GOUGE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferdowsi, Behrooz; Griffa, Michele; Guyer, Robert A.

A fundamental mystery in earthquake physics is “how can an earthquake be triggered by distant seismic sources?” We use discrete element method simulations of a granular layer, during stick slip, that is subject to transient vibrational excitation to gain further insight into the physics of dynamic earthquake triggering. We also observe delayed triggering of slip in the granular gouge, using Coulomb friction law for grains interaction. We find that at a critical vibrational amplitude (strain) there is an abrupt transition from negligible time-advanced slip (clock advance) to full clock advance; i.e., transient vibration and triggered slip are simultaneous. Moreover, themore » critical strain is of order 10 -6, similar to observations in the laboratory and in Earth. The transition is related to frictional weakening of the granular layer due to a dramatic decrease in coordination number and the weakening of the contact force network. Associated with this frictional weakening is a pronounced decrease in the elastic modulus of the layer. The study has important implications for mechanisms of triggered earthquakes and induced seismic events and points out the underlying processes in response of the fault gouge to dynamic transient stresses.« less

Acoustically induced slip in sheared granular layers: Application to dynamic earthquake triggering: TRIGGERED SLIP IN SHEARED GRANULAR GOUGE

DOE PAGES

Ferdowsi, Behrooz; Griffa, Michele; Guyer, Robert A.; ...

2015-11-19

A fundamental mystery in earthquake physics is “how can an earthquake be triggered by distant seismic sources?” We use discrete element method simulations of a granular layer, during stick slip, that is subject to transient vibrational excitation to gain further insight into the physics of dynamic earthquake triggering. We also observe delayed triggering of slip in the granular gouge, using Coulomb friction law for grains interaction. We find that at a critical vibrational amplitude (strain) there is an abrupt transition from negligible time-advanced slip (clock advance) to full clock advance; i.e., transient vibration and triggered slip are simultaneous. Moreover, themore » critical strain is of order 10 -6, similar to observations in the laboratory and in Earth. The transition is related to frictional weakening of the granular layer due to a dramatic decrease in coordination number and the weakening of the contact force network. Associated with this frictional weakening is a pronounced decrease in the elastic modulus of the layer. The study has important implications for mechanisms of triggered earthquakes and induced seismic events and points out the underlying processes in response of the fault gouge to dynamic transient stresses.« less

The trigger system of the JEM-EUSO Project

NASA Astrophysics Data System (ADS)

Bertaina, M.; Ebisuzaki, T.; Hamada, T.; Ikeda, H.; Kawasai, Y.; Sawabe, T.; Takahashi, Y.; JEM-EUSO Collaboration

The trigger system of JEM-EUSO should face different major challenging points: a) cope with the limited down-link transmission rate from the ISS to Earth, by operating a severe on-board and on-time data reduction; b) use very fast, low power consuming and radiation hard electronics; c) have a high signal-over-noise performance and flexibility in order to lower as much as possible the energy threshold of the detector, adjust the system to a variable nightglow background, and trigger on different categories of events (images insisting on the same pixels or crossing huge portions of the entire focal surface). Based on the above stringent requirements, the main ingredients for the trigger logic are: the Gate Time Unit (GTU); the minimum number Nthresh of photo-electrons piling up in a GTU in a pixel to be fired; the persistency level Npers, in which fired pixels are over threshold; the localization and correlation in space and time of the fired pixels, that distinguish a real EAS from an accidental background enhancement. The core of the trigger logic is the Track Trigger Algorithm that has been specifically developed for this purpose. Its characteristics, preliminary performance and its possible implementation on FPGA or DSP will be discussed together with a general overview of the architecture of the triggering system of JEM-EUSO.

Protocol-driven remote monitoring of cardiac resynchronization therapy as part of a heart failure disease management strategy.

PubMed

Smeets, Christophe J P; Verbrugge, Frederik H; Vranken, Julie; Van der Auwera, Jo; Mullens, Wilfried; Dupont, Matthias; Grieten, Lars; De Cannière, Hélène; Lanssens, Dorien; Vandenberk, Thijs; Storms, Valerie; Thijs, Inge M; Vandervoort, Pieter

2018-06-01

Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure (HF) with reduced ejection fraction. CRT devices are equipped with remote monitoring functions, which are pivotal in the detection of device problems, but may also facilitate disease management. The aim of this study was to provide a comprehensive overview of the clinical interventions taken based on remote monitoring. This is a single centre observational study of consecutive CRT patients (n = 192) participating in protocol-driven remote follow-up. Incoming technical- and disease-related alerts were analysed together with subsequently triggered interventions. During 34 ± 13 months of follow-up, 1372 alert-containing notifications were received (2.53 per patient-year of follow-up), comprising 1696 unique alerts (3.12 per patient-year of follow-up). In 60%, notifications resulted in a phone contact. Technical alerts constituted 8% of incoming alerts (0.23 per patient-year of follow-up). Rhythm (1.43 per patient-year of follow-up) and bioimpedance alerts (0.98 per patient-year of follow-up) were the most frequent disease-related alerts. Notifications included a rhythm alert in 39%, which triggered referral to the emergency room (4%), outpatient cardiology clinic (36%) or general practitioner (7%), or resulted in medication changes (13%). Sole bioimpedance notifications resulted in a telephone contact in 91%, which triggered outpatient evaluation in 8% versus medication changes in 10%. Clinical outcome was excellent with 97% 1-year survival. Remote CRT follow-up resulted in 0.23 technical- versus 2.64 disease-related alerts annually. Rhythm and bioimpedance notifications constituted the majority of incoming notifications which triggered an actual intervention in 22% and 15% of cases, respectively.

Improvement of Vergence Movements by Vision Therapy Decreases K-ARS Scores of Symptomatic ADHD Children.

PubMed

Lee, Sun Haeng; Moon, Byeong-Yeon; Cho, Hyun Gug

2014-02-01

[Purpose] To determine whether the improvement of vergence movements by vision therapy can decrease the K-ARS scores of symptomatic ADHD children. [Methods] Eighty-one out of 1,123 children surveyed using the K-ARS, a parents'-reported questionnaire, led to 16 of these 81 children being showed scores of ≥19, and measurement of binocular function diagnosed as having convergence insufficiency. The 16 children were divided equally into a control group and a vision therapy group. [Results] After vision therapy for 12 weeks, near point convergence (4.38±0.69 cm) significantly neared compared to the near point convergence before vision therapy (11.50±2.28 cm), and both the break point (32.38±2.53 Δ) and recovery point (19.75±2.11 Δ) of near positive fusional vergence significantly improved compared to their values before vision therapy (15.88±2.64 Δ, 6.38±6.70 Δ, respectively). Near exophoria after vision therapy (7.81±2.00 Δ BI) significantly decreased compared to its value before vision therapy (12.00±1.16 Δ BI). The K-ARS scores referring to symptomatic ADHD significantly decreased after vision therapy (17.13±2.84) compared to before vision therapy (23.25±1.49). [Conclusions] Convergence insufficiency symptoms are closely related to symptoms screened for ADHD, and vision therapy to improve vergence movements is an effective method of decreasing the K-ARS scores.

Combination of active targeting, enzyme-triggered release and fluorescent dye into gold nanoclusters for endomicroscopy-guided photothermal/photodynamic therapy to pancreatic ductal adenocarcinoma.

PubMed

Li, Hui; Wang, Ping; Deng, Yunxiang; Zeng, Meiying; Tang, Yan; Zhu, Wei-Hong; Cheng, Yingsheng

2017-09-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in patients, and there is an urgent need for an effective treatment method. Herein, we report a novel gold nanocluster-based platform for confocal laser endomicroscopy-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for PDAC, which consists of four components: the PTT-carrier gold nanocluster, an active targeting ligand U11 peptide, a Cathepsin E (CTSE)-sensitive PDT therapy prodrug, and a CTSE-sensitive imaging agent (cyanine dye Cy5.5). Due to the strong coupling among cross-linked gold nanoparticles (AuNPs), the surface plasmon resonance peak of nanoclusters shifts to the near-infrared (NIR) region, thus making the nanoclusters useful in the effective PTT therapy. In the system, the labeling of nanoclusters with U11 peptide can distinctly increase their affinity and accelerate their uptake by pancreatic cancer cells. Cell apoptosis staining demonstrates that, upon incorporation of the uPAR-targeted unit, the antitumor efficacy of CTSE-sensitive nanocluster AuS-U11 is significantly enhanced with respect to that of the non-targeted nanocluster AuS-PEG and the insensitive nanocluster AuC-PEG. In vivo and ex vivo optical imaging confirms the high accumulation of AuS-U11 in the in situ pancreatic tumor model. Therapeutic studies further show that the combination of active targeting for tumor tissue, enzyme-triggered drug release of 5-ALA and fluorescent dye Cy5.5 in nanoclusters AuS-U11 could achieve optimal therapeutic efficacy with endomicroscopy-guided photothermal/photodynamic therapy with minimal side effects. As a consequence, the delicate gold nanocluster concept provides a promising strategy to enhance the therapy efficiency in the most challenging PDAC treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of myofascial trigger points in fibromyalgia: the overlap of two common problems.

PubMed

Ge, Hong-You

2010-10-01

With the objective evidence of their existence, myofascial trigger points (MTrPs) contribute to an increasing number of chronic regional and widespread pain conditions. The widespread spontaneous pain pattern in fibromyalgia (FM) is a summation of multiple regional pains due to active MTrPs. A regional pain in FM is from local active MTrPs and/or referred from remote active MTrPs. Positive tender points specified in FM are MTrPs, either active or latent. Manual stimulation of active MTrPs located in the muscles in different body regions completely reproduced overall spontaneous FM pain pattern. Active MTrPs as tonic peripheral nociceptive input contribute tremendously to the initiation and maintenance of central sensitization, to the impairment of descending inhibition, to the increased excitability of motor units, and to the induction of sympathetic hyperactivity observed in FM. The considerable overlap of MTrPs and FM in pain characteristics and pathophysiology suggests that FM pain is largely due to MTrPs.

New developments in ALFT's soft x-ray point sources

NASA Astrophysics Data System (ADS)

Cintron, Dario F.; Guo, Xiaoming; Xu, Meisheng; Ye, Rubin; Antoshko, Yuriy; Antoshko, Yuriy; Drew, Steve; Philippe, Albert; Panarella, Emilio

2002-07-01

The new development in ALFT soft X-ray point source VSX-400 consists mainly of an improvement of the nozzle design to reduce the source size, as well as the introduction of a novel trigger system, capable of triggering the discharge hundreds of million of times without failure, and a debris removal system. Continuous operation for 8 hours at 20 kHz allows us to achieve 400 mW of useful soft X-ray radiation around 1 nm wavelength. In another regime of operation with a high energy machine, the VSX-Z, we have been able to achieve consistently 10 J of X-rays per pulse at a repetition rate that can reach 1 Hz with an input electrical energy of approximately 3 kJ and an efficiency in excess of 10-3.

Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

PubMed Central

Sun, Huanli; Cheng, Ru; Deng, Chao

2014-01-01

Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

Virtual vision system with actual flavor by olfactory display

NASA Astrophysics Data System (ADS)

Sakamoto, Kunio; Kanazawa, Fumihiro

2010-11-01

The authors have researched multimedia system and support system for nursing studies on and practices of reminiscence therapy and life review therapy. The concept of the life review is presented by Butler in 1963. The process of thinking back on one's life and communicating about one's life to another person is called life review. There is a famous episode concerning the memory. It is called as Proustian effects. This effect is mentioned on the Proust's novel as an episode that a story teller reminds his old memory when he dipped a madeleine in tea. So many scientists research why smells trigger the memory. The authors pay attention to the relation between smells and memory although the reason is not evident yet. Then we have tried to add an olfactory display to the multimedia system so that the smells become a trigger of reminding buried memories. An olfactory display is a device that delivers smells to the nose. It provides us with special effects, for example to emit smell as if you were there or to give a trigger for reminding us of memories. The authors have developed a tabletop display system connected with the olfactory display. For delivering a flavor to user's nose, the system needs to recognition and measure positions of user's face and nose. In this paper, the authors describe an olfactory display which enables to detect the nose position for an effective delivery.

A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system.

PubMed

Li, Qingpo; Li, Wei; Di, Haixiao; Luo, Lihua; Zhu, Chunqi; Yang, Jie; Yin, Xiaoyi; Yin, Hang; Gao, Jianqing; Du, Yongzhong; You, Jian

2018-05-10

The targeted drug delivery with the help of nanocarriers and the controlled drug release at the lesion sites are the most effective ways to enhance therapeutic efficacy and reduce side effects. Here, we built a light sensitive liposome (Her2-I&D-LSL) which was formed by a special phospholipid (PLsPC) and a hydrophobically modified photosensitizer (ICG-ODA). DOX was employed as the therapeutic drug, encapsulating in the internal phase of the liposome whose surface was modified by Her2 antibodies for recognizing tumor cells with high Her2 receptor expression. Mediated by NIR light, Her2-I&D-LSL was proved to generate sufficient ROS to realize PDT, which then triggered the release of DOX for combined chemotherapy. The ROS generation and DOX release were verified to be strictly controlled by NIR light and the proportion of ICG-ODA. Thanks to the mediation of Her2 receptor, the specific DOX release and the combination of PDT-chemotherapy triggered by NIR light, Her2-I&D-LSL showed a significant accumulation in MCF7 and SKOV3 tumors, thus leading to the strongest tumor growth inhibition effect compared to PDT alone (I-LSL) or chemotherapy alone (D-LSL). Her2-I&D-LSL also possessed a great biocompatibility due to the targeted treatment, holding promise for future cancer therapy in clinic. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatocellular carcinoma repression by TNFα‐mediated synergistic lethal effect of mitosis defect‐induced senescence and cell death sensitization

PubMed Central

Li, Dan; Fu, Jing; Du, Min; Zhang, Haibin; Li, Lu; Cen, Jin; Li, Weiyun; Chen, Xiaotao; Lin, Yunfei; Conway, Edward M.; Pikarsky, Eli; Wang, Hongyan; Pan, Guoyu

2016-01-01

Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNFα)‐mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect‐associated senescence in HCC cells, which triggers local inflammation and increased TNFα. Survivin inactivation also sensitizes HCC cells to TNFα‐triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. Conclusion: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence‐associated TNFα and sensitizing HCC cells to TNFα‐induced cell death. Combined use of mitotic inhibitor and second mitochondrial‐derived activator of caspases mimetic can induce senescence‐associated TNFα and enhance TNFα‐induced cell death and synergistically eliminate HCC. (Hepatology 2016;64:1105‐1120) PMID:27177758

FNL Scientists Introduce Concept That Could Help the Immune System Respond to Vaccines | Frederick National Laboratory for Cancer Research

Cancer.gov

Scientists have discovered an efficient and straightforward model to manipulate RNA nanoparticles, a new concept that could help trigger desirable activation of the immune system with vaccines and therapies. A multi-institutional team of researchers

Acupuncture in Treating Dry Mouth Caused By Radiation Therapy in Patients With Head and Neck Cancer | Division of Cancer Prevention

Cancer.gov

RATIONALE: Acupuncture may help relieve dry mouth caused by radiation therapy. PURPOSE: This randomized phase III trial is studying to see how well one set of acupuncture points work in comparison to a different set of acupuncture points or standard therapy in treating dry mouth caused by radiation therapy in patients with head and neck cancer. |

Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF-1α–mediated tumor apoptotic switch

PubMed Central

Magnon, Claire; Opolon, Paule; Ricard, Marcel; Connault, Elisabeth; Ardouin, Patrice; Galaup, Ariane; Métivier, Didier; Bidart, Jean-Michel; Germain, Stéphane; Perricaudet, Michel; Schlumberger, Martin

2007-01-01

Tumor radioresponsiveness depends on endothelial cell death, which leads in turn to tumor hypoxia. Radiation-induced hypoxia was recently shown to trigger tumor radioresistance by activating angiogenesis through hypoxia-inducible factor 1–regulated (HIF-1–regulated) cytokines. We show here that combining targeted radioiodide therapy with angiogenic inhibitors, such as canstatin, enhances direct tumor cell apoptosis, thereby overcoming radio-induced HIF-1–dependent tumor survival pathways in vitro and in vivo. We found that following dual therapy, HIF-1α increases the activity of the canstatin-induced αvβ5 signaling tumor apoptotic pathway and concomitantly abrogates mitotic checkpoint and tetraploidy triggered by radiation. Apoptosis in conjunction with mitotic catastrophe leads to lethal tumor damage. We discovered that HIF-1 displays a radiosensitizing activity that is highly dependent on treatment modalities by regulating key apoptotic molecular pathways. Our findings therefore support a crucial role for angiogenesis inhibitors in shifting the fate of radiation-induced HIF-1α activity from hypoxia-induced tumor radioresistance to hypoxia-induced tumor apoptosis. This study provides a basis for developing new biology-based clinically relevant strategies to improve the efficacy of radiation oncology, using HIF-1 as an ally for cancer therapy. PMID:17557121

Guidance on the diagnosis and management of asthma among adults in resource limited settings.

PubMed

Kirenga, Bruce J; Schwartz, Jeremy I; de Jong, Corina; van der Molen, Thys; Okot-Nwang, Martin

2015-12-01

Optimal management of asthma in resource limited settings is hindered by lack of resources, making it difficult for health providers to adhere to international guidelines. The purpose of this review is to identify steps for asthma diagnosis and management in resource limited settings. Review of international asthma guidelines and other published studies on diagnosis and management of asthma. We establish that clinical diagnosis of asthma can be made if recurrent respiratory symptoms especially current wheeze or wheeze in the last 12 months are present. Presence of a trigger, other allergic diseases, personal or family history of asthma; clinical improvement and increase in the peak flow and forced expiratory volume in one second of ≥12% after salbutamol administration increases the likelihood of asthma. At diagnosis severity grading, patient education, removal or reduction of trigger should be done. Follow up 2-6 weeks and assessment of control during therapy is essential. Therapy should be adjusted up or down depending on control levels. Patients should be instructed to increase the frequency of their bronchodilators and/or steroids therapy when they start to experience worsening symptoms. Good quality asthma care can be achieved in resource limited settings by use of clinical data and simple tests.

Feasibility study of a combined treatment of electromyography-triggered neuromuscular stimulation and mirror therapy in stroke patients: a randomized crossover trial.

PubMed

Kojima, Kosuke; Ikuno, Koki; Morii, Yuta; Tokuhisa, Kentaro; Morimoto, Shigeru; Shomoto, Koji

2014-01-01

Mirror therapy (MT) and electromyography-triggered neuromuscular stimulation (ETMS) are both effective treatments for impaired upper limbs following stroke. A combination of these two treatments (ETMS-MT) may result in greater gain than either treatment alone. The feasibility and possible effects of ETMS-MT upon upper extremity function were investigated in stroke patients. Thirteen post-acute stroke patients were randomly assigned to an immediate ETMS-MT group or a delayed ETMS-MT group and then underwent an 8-week training program. The immediate ETMS-MT group received ETMS-MT in addition to physical and occupational therapy (PT+OT) for 4 weeks. They then received only PT+OT for the next 4 weeks. In the delayed ETMS-MT group, interventions were provided in the reverse order. The main outcome measure was the Fugl-Meyer Assessment (FMA). The immediate ETMS-MT group showed significantly greater gain in FMA in the first 4 weeks. The delayed ETMS-MT group showed significantly greater gain in active range of motion during the latter 4 weeks. No adverse effects were reported following ETMS-MT. ETMS-MT might be as effective as independent MT or ETMS without causing any side effects. Future research should focus upon the direct comparisons between independent and combined interventions.

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

PubMed Central

Mondadori, Carlotta; Mainardi, Valerio Luca; Talò, Giuseppe; Candrian, Christian; Święszkowski, Wojciech

2018-01-01

Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects. PMID:29535776

Myofascial Pain Syndrome

MedlinePlus

... to develop trigger points in their muscles. One theory holds that these people may be more likely ... doctors believe myofascial pain syndrome may play a role in starting this process. By Mayo Clinic Staff . ...

Acupuncture therapy related cardiac injury.

PubMed

Li, Xue-feng; Wang, Xian

2013-12-01

Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

Acoustic Response of Microbubbles Derived from Phase-Change Nanodroplet

NASA Astrophysics Data System (ADS)

Kawabata, Ken-ichi; Asami, Rei; Azuma, Takashi; Umemura, Shin-ichiro

2010-07-01

An in vitro feasibility test for a novel ultrasound therapy using a type of superheated perfluorocarbon droplet, phase-change nanodroplet (PCND), was performed in gel phantoms with the goal of high selectivity and low invasiveness. Measurements of broadband signal emission revealed that a triggering ultrasound pulse (peak negative pressure of 2.4 MPa) reduces the pressure threshold for cavitation induced by a subsequent ultrasound exposure at an order of magnitude from 2.4 to 0.2 MPa. The maximum allowed interval between the two ultrasound exposures for inducing cavitation with 100- and 1,000-cycle triggering ultrasound was about 100 and 500 ms, respectively. The echo signal increases induced by the triggering ultrasound with 100- and 1000-cycles were enhanced and suppressed by the subsequent ultrasound exposure, respectively. This different behavior seemed to be due to the presence of enlarged free bubbles, which should be avoided for the localization of therapeutic effects.

Remote Effect of Lower Limb Acupuncture on Latent Myofascial Trigger Point of Upper Trapezius Muscle: A Pilot Study

PubMed Central

Chen, Kai-Hua; Hsiao, Kuang-Yu; Lin, Chu-Hsu; Chang, Wen-Ming; Hsu, Hung-Chih; Hsieh, Wei-Chi

2013-01-01

Objectives. To demonstrate the use of acupuncture in the lower limbs to treat myofascial pain of the upper trapezius muscles via a remote effect. Methods. Five adults with latent myofascial trigger points (MTrPs) of bilateral upper trapezius muscles received acupuncture at Weizhong (UB40) and Yanglingquan (GB34) points in the lower limbs. Modified acupuncture was applied at these points on a randomly selected ipsilateral lower limb (experimental side) versus sham needling on the contralateral lower limb (control side) in each subject. Each subject received two treatments within a one-week interval. To evaluate the remote effect of acupuncture, the range of motion (ROM) upon bending the contralateral side of the cervical spine was assessed before and after each treatment. Results. There was significant improvement in cervical ROM after the second treatment (P = 0.03) in the experimental group, and the increased ROM on the modified acupuncture side was greater compared to the sham needling side (P = 0.036). Conclusions. A remote effect of acupuncture was demonstrated in this pilot study. Using modified acupuncture needling at remote acupuncture points in the ipsilateral lower limb, our treatments released tightness due to latent MTrPs of the upper trapezius muscle. PMID:23710218

Descending perineum syndrome: new perspectives.

PubMed

Pucciani, F

2015-08-01

The classical clinical profile of descending perineum syndrome (DPS) has been replaced by new pathophysiological, diagnostic, and therapeutic acquisitions. This paper will focus on trigger factors ranging from dyssynergic defecation to excessive straining, fecal incontinence against the backdrop of obstructed defecation, attendant rectal diseases, and therapy tailored to evolving stages of DPS.

Biomedical Nanomagnetics: A Spin Through Possibilities in Imaging, Diagnostics, and Therapy

PubMed Central

Krishnan, Kannan M.

2010-01-01

Biomedical nanomagnetics is a multidisciplinary area of research in science, engineering and medicine with broad applications in imaging, diagnostics and therapy. Recent developments offer exciting possibilities in personalized medicine provided a truly integrated approach, combining chemistry, materials science, physics, engineering, biology and medicine, is implemented. Emphasizing this perspective, here we address important issues for the rapid development of the field, i.e., magnetic behavior at the nanoscale with emphasis on the relaxation dynamics, synthesis and surface functionalization of nanoparticles and core-shell structures, biocompatibility and toxicity studies, biological constraints and opportunities, and in vivo and in vitro applications. Specifically, we discuss targeted drug delivery and triggered release, novel contrast agents for magnetic resonance imaging, cancer therapy using magnetic fluid hyperthermia, in vitro diagnostics and the emerging magnetic particle imaging technique, that is quantitative and sensitive enough to compete with established imaging methods. In addition, the physics of self-assembly, which is fundamental to both biology and the future development of nanoscience, is illustrated with magnetic nanoparticles. It is shown that various competing energies associated with self-assembly converge on the nanometer length scale and different assemblies can be tailored by varying particle size and size distribution. Throughout this paper, while we discuss our recent research in the broad context of the multidisciplinary literature, we hope to bridge the gap between related work in physics/chemistry/engineering and biology/medicine and, at the same time, present the essential concepts in the individual disciplines. This approach is essential as biomedical nanomagnetics moves into the next phase of innovative translational research with emphasis on development of quantitative in vivo imaging, targeted and triggered drug release, and image guided therapy including validation of delivery and therapy response. PMID:20930943

Aphasia Therapy in the Age of Globalization: Cross-Linguistic Therapy Effects in Bilingual Aphasia

PubMed Central

Ansaldo, Ana Inés; Saidi, Ladan Ghazi

2014-01-01

Introduction. Globalization imposes challenges to the field of behavioural neurology, among which is an increase in the prevalence of bilingual aphasia. Thus, aphasiologists have increasingly focused on bilingual aphasia therapy and, more recently, on the identification of the most efficient procedures for triggering language recovery in bilinguals with aphasia. Therapy in both languages is often not available, and, thus, researchers have focused on the transfer of therapy effects from the treated language to the untreated one. Aim. This paper discusses the literature on bilingual aphasia therapy, with a focus on cross-linguistic therapy effects from the language in which therapy is provided to the untreated language. Methods. Fifteen articles including two systematic reviews, providing details on pre- and posttherapy in the adult bilingual population with poststroke aphasia and anomia are discussed with regard to variables that can influence the presence or absence of cross-linguistic transfer of therapy effects. Results and Discussion. The potential for CLT of therapy effects from the treated to the untreated language depends on the word type, the degree of structural overlap between languages, the type of therapy approach, the pre- and postmorbid language proficiency profiles, and the status of the cognitive control circuit. PMID:24825963

Aphasia therapy in the age of globalization: cross-linguistic therapy effects in bilingual aphasia.

PubMed

Ansaldo, Ana Inés; Saidi, Ladan Ghazi

2014-01-01

Globalization imposes challenges to the field of behavioural neurology, among which is an increase in the prevalence of bilingual aphasia. Thus, aphasiologists have increasingly focused on bilingual aphasia therapy and, more recently, on the identification of the most efficient procedures for triggering language recovery in bilinguals with aphasia. Therapy in both languages is often not available, and, thus, researchers have focused on the transfer of therapy effects from the treated language to the untreated one. This paper discusses the literature on bilingual aphasia therapy, with a focus on cross-linguistic therapy effects from the language in which therapy is provided to the untreated language. Fifteen articles including two systematic reviews, providing details on pre- and posttherapy in the adult bilingual population with poststroke aphasia and anomia are discussed with regard to variables that can influence the presence or absence of cross-linguistic transfer of therapy effects. . The potential for CLT of therapy effects from the treated to the untreated language depends on the word type, the degree of structural overlap between languages, the type of therapy approach, the pre- and postmorbid language proficiency profiles, and the status of the cognitive control circuit.

Dual-mode disturbance-accommodating pointing controller for Hubble Space Telescope

NASA Astrophysics Data System (ADS)

Addington, Stewart I.; Johnson, C. D.

1995-03-01

Cyclic thermal expansions and mechanical stiction effects in the solar arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: 1) a total isolation (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel out the persistent disturbing torques that are causing the unwanted telescope motions and 2) an array damping (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of disturbance accommodation control theory, a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing performance such a controller can achieve.

Evolution of the methodological quality of controlled clinical trials for myofascial trigger point treatments for the period 1978-2015: A systematic review.

PubMed

Stoop, Rahel; Clijsen, Ron; Leoni, Diego; Soldini, Emiliano; Castellini, Greta; Redaelli, Valentina; Barbero, Marco

2017-08-01

The methodological quality of controlled clinical trials (CCTs) of physiotherapeutic treatment modalities for myofascial trigger points (MTrP) has not been investigated yet. To detect the methodological quality of CCTs for physiotherapy treatments of MTrPs and demonstrating the possible increase over time. Systematic review. A systematic search was conducted in two databases, Physiotherapy Evidence Database (PEDro) and Medicine Medical Literature Analysis and Retrieval System online (MEDLINE), using the same keywords and selection procedure corresponding to pre-defined inclusion criteria. The methodological quality, assessed by the 11-item PEDro scale, served as outcome measure. The CCTs had to compare at least two interventions, where one intervention had to lay within the scope of physiotherapy. Participants had to be diagnosed with myofascial pain syndrome or trigger points (active or latent). A total of n = 230 studies was analysed. The cervico-thoracic region was the most frequently treated body part (n = 143). Electrophysical agent applications was the most frequent intervention. The average methodological quality reached 5.5 on the PEDro scale. A total of n = 6 studies scored the value of 9. The average PEDro score increased by 0.7 points per decade between 1978 and 2015. The average PEDro score of CCTs for MTrP treatments does not reach the cut-off of 6 proposed for moderate to high methodological quality. Nevertheless, a promising trend towards an increase of the average methodological quality of CCTs for MTrPs was recorded. More high-quality CCT studies with thorough research procedures are recommended to enhance methodological quality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Multi-Angle Snowflake Camera Value-Added Product

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shkurko, Konstantin; Garrett, T.; Gaustad, K

The Multi-Angle Snowflake Camera (MASC) addresses a need for high-resolution multi-angle imaging of hydrometeors in freefall with simultaneous measurement of fallspeed. As illustrated in Figure 1, the MASC consists of three cameras, separated by 36°, each pointing at an identical focal point approximately 10 cm away. Located immediately above each camera, a light aims directly at the center of depth of field for its corresponding camera. The focal point at which the cameras are aimed lies within a ring through which hydrometeors fall. The ring houses a system of near-infrared emitter-detector pairs, arranged in two arrays separated vertically by 32more » mm. When hydrometeors pass through the lower array, they simultaneously trigger all cameras and lights. Fallspeed is calculated from the time it takes to traverse the distance between the upper and lower triggering arrays. The trigger electronics filter out ambient light fluctuations associated with varying sunlight and shadows. The microprocessor onboard the MASC controls the camera system and communicates with the personal computer (PC). The image data is sent via FireWire 800 line, and fallspeed (and camera control) is sent via a Universal Serial Bus (USB) line that relies on RS232-over-USB serial conversion. See Table 1 for specific details on the MASC located at the Oliktok Point Mobile Facility on the North Slope of Alaska. The value-added product (VAP) detailed in this documentation analyzes the raw data (Section 2.0) using Python: images rely on OpenCV image processing library and derived aggregated statistics rely on some clever averaging. See Sections 4.1 and 4.2 for more details on what variables are computed.« less

[Crohns disease and ulcerative colitis - current view on genetic determination, immunopathogenesis and biologic therapy].

PubMed

Buc, M

2017-01-01

Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the intestine, also called inflammatory bowel diseases (IBD), which are not caused by pathogenic microorganisms but result from non-specific inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by the genome-wide association studies (GWAS), which have discovered more than 200 genes or genetic regions to be associated with IBD. Some of them are specific for CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD, activation of adaptive immunity mediated by TH1, TH17, or TH1/TH17 cells is induced because of disturbances in the mechanisms of innate immunity and autophagocytosis. By comparison, the major events that trigger autoimmune processes in UC are an increased translocation of commensal bacteria into the submucosa because of loose inter-epithelial connections with subsequent activation of ILC2, TH9, TH2, and NKT cells. Knowledge of the pathogenesis of a disease enables an effective therapy, which is especially true for biological therapy. It is noteworthy that monoclonal antibodies directed against the major protagonists underlying both CD and UC have failed. It points to the complexity of immunopathologic processes that run in both diseases. One can suppose that a blockade of one inflammatory pathway is circumvented by an alternative pathway. TNF is the principal pro-inflammatory cytokine that plays a major role in CD and UC as well. It was therefore decided to treat IBD patients with anti-TNF monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD patients and one third of the UC patients respond to this treatment.

Effect of Soft Tissue Techniques on Headache Impact, Disability, and Quality of Life in Migraine Sufferers: A Pilot Study.

PubMed

Espí-López, Gemma-Victoria; Ruescas-Nicolau, Maria-Arantzazu; Nova-Redondo, Cristina; Benítez-Martínez, Josep C; Dugailly, Pierre-Michel; Falla, Deborah

2018-04-30

To determine the efficacy of suboccipital inhibitory techniques in people with migraine compared with a control treatment based on myofascial trigger point (MTrP) therapy and stretching. A randomized, double-blind controlled pilot trial was conducted. University research laboratory. Forty-six adults diagnosed with migraine with over 6 months duration. Participants were randomized to receive either combined MTrP therapy and stretching (control group) or the control treatment plus suboccipital soft tissue inhibition (experimental group). Treatment was applied on four occasions over 8 weeks (one every 15 days), with a duration of 30 minutes per session in the experimental group and 20 min in the control group. The impact of headache was assessed with the Headache Impact Test (HIT-6), disability by the migraine disability assessment (MIDAS), and quality of life by the Short Form Health Survey (SF-36). Both groups were assessed at baseline and 1 week immediately after the end of treatment. The amount of change of the HIT-6 score and MIDAS scores were significantly different between groups (p < 0.05), although the SF-36 scores were not. The change in the HIT-6 score and MIDAS scores was greater in the experimental group. Both groups showed a reduction on the HIT-6 score (p < 0.001), MIDAS scores (p < 0.05), and SF-36 physical subscale, whereas the SF-36 mental subscale improved only in the experimental group (p < 0.001). Soft tissue techniques based on MTrP therapy and stretching were helpful for improving certain aspects of migraine, such as the impact and disability caused by the headache, and the frequency and intensity of headache; however, when combined with suboccipital soft tissue inhibition, the treatment effect was larger.

Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study.

PubMed

Freund, B J; Schwartz, M

2000-02-01

Up to 87% of patients with whiplash associated disorder (WAD) have some degree of muscle spasm that is contributory to both pain and dysfunction. Botulinum toxin A (BTX-A) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles. BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities. We investigated BTX-A as therapy in patients with WAD. This randomized, double blind, placebo controlled study compares outcome measures in 26 patients with chronic neck pain (WAD-II chronic) subsequent to a motor vehicle accident. One-half of the patients received 100 units BTX-A, diluted in 1 ml saline, while the other half received just saline (1 ml). Five trigger points received 0.2 ml each of injectant via a 30 gauge needle. Outcome measures included total subjective neck, shoulder, and head pain based on visual analog scales; objective total range of neck motion (ROM), and the Vernon-Mior subjective function index. Followup assessments were carried out at 2 and 4 weeks post-treatment. Fourteen subjects receiving BTX-A and 12 receiving saline completed the study. The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection. At 4 weeks post-injection the treatment group was significantly improved from preinjection levels (p < 0.01). The placebo group showed no statistically significant changes at any post-treatment time. The Vernon-Mior scale revealed a trend to improvement for both groups. BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant (p < 0.01) improvement in ROM and subjective pain compared to a placebo group, but only a trend to improvement in subjective functioning.

Evidence-based guidelines for the chiropractic treatment of adults with neck pain.

PubMed

Bryans, Roland; Decina, Philip; Descarreaux, Martin; Duranleau, Mireille; Marcoux, Henri; Potter, Brock; Ruegg, Richard P; Shaw, Lynn; Watkin, Robert; White, Eleanor

2014-01-01

The purpose of this study was to develop evidence-based treatment recommendations for the treatment of nonspecific (mechanical) neck pain in adults. Systematic literature searches of controlled clinical trials published through December 2011 relevant to chiropractic practice were conducted using the databases MEDLINE, EMBASE, EMCARE, Index to Chiropractic Literature, and the Cochrane Library. The number, quality, and consistency of findings were considered to assign an overall strength of evidence (strong, moderate, weak, or conflicting) and to formulate treatment recommendations. Forty-one randomized controlled trials meeting the inclusion criteria and scoring a low risk of bias were used to develop 11 treatment recommendations. Strong recommendations were made for the treatment of chronic neck pain with manipulation, manual therapy, and exercise in combination with other modalities. Strong recommendations were also made for the treatment of chronic neck pain with stretching, strengthening, and endurance exercises alone. Moderate recommendations were made for the treatment of acute neck pain with manipulation and mobilization in combination with other modalities. Moderate recommendations were made for the treatment of chronic neck pain with mobilization as well as massage in combination with other therapies. A weak recommendation was made for the treatment of acute neck pain with exercise alone and the treatment of chronic neck pain with manipulation alone. Thoracic manipulation and trigger point therapy could not be recommended for the treatment of acute neck pain. Transcutaneous nerve stimulation, thoracic manipulation, laser, and traction could not be recommended for the treatment of chronic neck pain. Interventions commonly used in chiropractic care improve outcomes for the treatment of acute and chronic neck pain. Increased benefit has been shown in several instances where a multimodal approach to neck pain has been used. © 2014. Published by National University of Health Sciences All rights reserved.

Lidocaine Injection in the Intramuscular Innervation Zone Can Effectively Treat Chronic Neck Pain Caused by MTrPs in the Trapezius Muscle.

PubMed

Xie, Peng; Qin, Bangyong; Yang, Fangjiu; Yu, Tian; Yu, Jin; Wang, Jiang; Zheng, Hong

2015-01-01

An increasing number of people suffer from neck pain due to life style and prolonged use of computers. Research has revealed that myofascial trigger points (MTrPs) and the intramuscular innervation zone (IZ) are involved in neck pain. MTrPs are induced mainly by IZ dysfunction of the affected skeletal muscle and the 2 do not overlap in location. The question is whether injection treatment in MTrPs or in the IZ is more effective to relieve MTrPs-associated pains. The precise location and body-surface map of the intramuscular IZ in the trapezius muscle and a clinical injection study in the IZ may provide a useful answer to the question. This study aimed to investigate the efficacy of lidocaine injection in the intramuscular IZ for the treatment of chronic neck pain caused by MTrPs in the trapezius muscle. Prospective observational study, approved by the local research ethics. University hospital, departments of Anesthesiology and Anatomy. First, for the determination of IZ distribution and body-surface mapping, a modified intramuscular Sihler's neural staining technique was applied to elucidate nerve distribution patterns of the trapezius muscle. Then, 120 patients with myofascial pain syndrome (MPS) of the trapezius muscle were randomly divided into 5 groups for analysis. Group 1 (n = 24) received injections of saline (0.9% NaCl) at the MTrPs. Group 2 (n = 24) received injections of 0.5% lidocaine at the MTrPs. Group 3 (n = 24) received injections of saline (0.9% NaCl) at the mid-upper trapezius (Point E). Group 4 (n = 24) received injections of 0.5% lidocaine at Point E. Group 5 (n = 24) received a combined injection of 0.5% lidocaine treatment at both Point E and the lower trapezius (Point F). The injection dose was 4 mL at each injection site. All patients received injections once a week for 4 weeks. The visual analogue scale (VAS) and the frequency of painful days per month (FPD) were obtained before treatment and at 2, 4, and 6 months after treatment. The intramuscular terminal nerve branches presented a "dendritic" distribution in the trapezius muscle and were connected with each other to form an S-shaped IZ belt in the middle of the muscle belly. Compared with the MTrP injection group, lidocaine-injection therapy in the IZ significantly reduced the degree and frequency of neck pain in patients at 6 months after treatment, especially the combined lidocaine-injection therapy in the IZ of both the mid-upper trapezius and the lower trapezius are more effective (all P < 0.05). This study confirms that lidocaine-injection therapy in the IZ significantly reduces the degree and frequency of neck pain in patients at 6 months after treatment. The combined lidocaine-injection therapy in the IZ of both the mid-upper trapezius and the lower trapezius is more effective. In addition, this study establishes a clear distribution map of intramuscular nerves that will be conducive to the future use of chemical blockers and electrical stimulation in the nervous system in treating MPS of the trapezius muscle. The small number of patients and the short duration of follow-up.

Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment.

PubMed

Bayer, T A; Wirths, O

2008-02-01

Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions

PubMed Central

Basourakos, Spyridon P.; Li, Likun; Aparicio, Ana M.; Corn, Paul G.; Kim, Jeri; Thompson, Timothy C.

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a “molecular landscape,” i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with ”BRCAness”, i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent–induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. PMID:27978798

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

PubMed

Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The efficacy of SMART Arm training early after stroke for stroke survivors with severe upper limb disability: a protocol for a randomised controlled trial.

PubMed

Brauer, Sandra G; Hayward, Kathryn S; Carson, Richard G; Cresswell, Andrew G; Barker, Ruth N

2013-07-02

Recovery of upper limb function after stroke is poor. The acute to subacute phase after stroke is the optimal time window to promote the recovery of upper limb function. The dose and content of training provided conventionally during this phase is however, unlikely to be adequate to drive functional recovery, especially in the presence of severe motor disability. The current study concerns an approach to address this shortcoming, through evaluation of the SMART Arm, a non-robotic device that enables intensive and repetitive practice of reaching by stroke survivors with severe upper limb disability, with the aim of improving upper limb function. The outcomes of SMART Arm training with or without outcome-triggered electrical stimulation (OT-stim) to augment movement and usual therapy will be compared to usual therapy alone. A prospective, assessor-blinded parallel, three-group randomised controlled trial is being conducted. Seventy-five participants with a first-ever unilateral stroke less than 4 months previously, who present with severe arm disability (three or fewer out of a possible six points on the Motor Assessment Scale [MAS] Item 6), will be recruited from inpatient rehabilitation facilities. Participants will be randomly allocated to one of three dose-matched groups: SMART Arm training with OT-stim and usual therapy; SMART Arm training without OT-stim and usual therapy; or usual therapy alone. All participants will receive 20 hours of upper limb training over four weeks. Blinded assessors will conduct four assessments: pre intervention (0-weeks), post intervention (4-weeks), 26 weeks and 52 weeks follow-up. The primary outcome measure is MAS item 6. All analyses will be based on an intention-to-treat principle. By enabling intensive and repetitive practice of a functional upper limb task during inpatient rehabilitation, SMART Arm training with or without OT-stim in combination with usual therapy, has the potential to improve recovery of upper limb function in those with severe motor disability. The immediate and long-term effects of SMART Arm training on upper limb impairment, activity and participation will be explored, in addition to the benefit of training with or without OT-stim to augment movement when compared to usual therapy alone. ACTRN12608000457347.

Integrated evaluation of visually induced motion sickness in terms of autonomic nervous regulation.

PubMed

Kiryu, Tohru; Tada, Gen; Toyama, Hiroshi; Iijima, Atsuhiko

2008-01-01

To evaluate visually-induced motion sickness, we integrated subjective and objective responses in terms of autonomic nervous regulation. Twenty-seven subjects viewed a 2-min-long first-person-view video section five times (total 10 min) continuously. Measured biosignals, the RR interval, respiration, and blood pressure, were used to estimate the indices related to autonomic nervous activity (ANA). Then we determined the trigger points and some sensation sections based on the time-varying behavior of ANA-related indices. We found that there was a suitable combination of biosignals to present the symptoms of visually-induced motion sickness. Based on the suitable combination, integrating trigger points and subjective scores allowed us to represent the time-distribution of subjective responses during visual exposure, and helps us to understand what types of camera motions will cause visually-induced motion sickness.

Effectiveness of dry needling for chronic nonspecific neck pain: a randomized, single-blinded, clinical trial.

PubMed

Cerezo-Téllez, Ester; Torres-Lacomba, María; Fuentes-Gallardo, Isabel; Perez-Muñoz, Milagros; Mayoral-Del-Moral, Orlando; Lluch-Girbés, Enrique; Prieto-Valiente, Luis; Falla, Deborah

2016-09-01

Chronic neck pain attributed to a myofascial pain syndrome is characterized by the presence of muscle contractures referred to as myofascial trigger points. In this randomized, parallel-group, blinded, controlled clinical trial, we examined the effectiveness of deep dry needling (DDN) of myofascial trigger points in people with chronic nonspecific neck pain. The study was conducted at a public Primary Health Care Centre in Madrid, Spain, from January 2010 to December 2014. A total of 130 participants with nonspecific neck pain presenting with active myofascial trigger points in their cervical muscles were included. These participants were randomly allocated to receive: DDN plus stretching (n = 65) or stretching only (control group [n = 65]). Four sessions of treatment were applied over 2 weeks with a 6-month follow-up after treatment. Pain intensity, mechanical hyperalgesia, neck active range of motion, neck muscle strength, and perceived neck disability were measured at baseline, after 2 sessions of intervention, after the intervention period, and 15, 30, 90, and 180 days after the intervention. Significant and clinically relevant differences were found in favour of dry needling in all the outcomes (all P < 0.001) at both short and long follow-ups. Deep dry needling and passive stretching is more effective than passive stretching alone in people with nonspecific neck pain. The results support the use of DDN in the management of myofascial pain syndrome in people with chronic nonspecific neck pain.

Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy

NASA Astrophysics Data System (ADS)

Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

2016-03-01

Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus. Electronic supplementary information (ESI) available: The relevant XRD, NMR, IR, UV and photograph. See DOI: 10.1039/c5nr08253f

Laser therapy on points of acupuncture: Are there benefits in dentistry?

PubMed

de Oliveira, Renata Ferreira; da Silva, Camila Vieira; Cersosimo, Maria Cecília Pereira; Borsatto, Maria Cristina; de Freitas, Patrícia Moreira

2015-10-01

Studies have shown the use of laser therapy at points of acupuncture as an alternative to metal needles. The scientific literature in the area of laser acupuncture is rather large; however, the actual mechanisms and effects have not yet been proven in detail. Therefore, the current manuscript reviews the existing literature regarding the effects of laser acupuncture in Dentistry, seeking treatment modalities in which this technique is used and which are able to generate positive clinical results. Thus, the literature survey was conducted in electronic databases--Medline/Pubmed, VHL and Science Direct--using the uniterms "alternative medicine", "low-power laser and acupuncture", "laser acupuncture and dentistry" and "laser therapy and acupuncture". Retrospective and prospective clinical studies were considered. According to the findings of the literature, laser therapy at points of acupuncture was effective for the treatment of various orofacial problems encountered in dentistry, but there are still many differences among the parameters used for irradiation and there is a lack of important information reported by the studies, such as the wavelength, dose, power density, irradiation time and frequency, points of acupuncture selected for irradiation and therapy outcomes. Although these results indicate the potential benefit of the use of laser therapy at points of acupuncture on Dentistry, further double-blinded, controlled clinical trials should be carried out in order to standardize protocols for clinical application. Copyright © 2015 Elsevier B.V. All rights reserved.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen

PubMed Central

Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan

2014-01-01

Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261

Dopaminergic Dysregulation, Artistic Expressiveness, and Parkinson's Disease

PubMed Central

López-Pousa, S.; Lombardía-Fernández, C.; Olmo, J. Garre; Monserrat-Vila, S.; Vilalta-Franch, J.; Calvó-Perxas, L.

2012-01-01

Background The most frequent behavioral manifestations in Parkinson's disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS. PMID:23185168

Equine recurrent uveitis: the European viewpoint.

PubMed

Spiess, B M

2010-03-01

Equine recurrent uveitis (ERU) has always been and still is an important disease with a significant impact on the horse industry in Europe, with a prevalence of 8-10%. The need to understand and manage the disease has spurred the development of veterinary ophthalmology in general, although the aetiology of the disease remains the subject of intense discussion. It is most probably an autoimmune disease triggered, at least in Europe, in the majority of cases by Leptospira spp. The therapy of ERU has evolved over the centuries from various methods of bloodletting to rational medical therapy using mydriatics and steroidal and nonsteroidal anti-inflammatory drugs, to surgical therapies, such as vitrectomy or implantation of cyclosporin-releasing devices. In Europe, pars plana vitrectomy in horses testing positive for Leptospira spp. appears to be the most successful form of therapy at the present time.

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

PubMed Central

Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

2014-01-01

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

Hypnotically facilitated exposure response prevention therapy for an OIF veteran with OCD.

PubMed

Proescher, Eric J

2010-07-01

The highly stressful conditions of a war zone may exacerbate or trigger a wide variety of symptoms including Obsessive Compulsive Disorder (OCD) once a service member returns home. Service members and new veterans of the Iraq and Afghanistan wars present to treatment with multiple psychosocial concerns and co-morbid psychiatric conditions. Evidence-based treatments including exposure based therapies are commonly recommended for use with returning veterans. Although studies support the efficacy of Exposure Response Prevention (ERP) therapy for treating OCD, eligibility for these studies limits participation to subjects who self-report a well-defined, circumscribed complaint. This approach is not typical of clinic clients who, more often than not, report multiple psychological issues. The following individual case study demonstrates how integrating hypnosis facilitated the cognitive-behavioral ERP therapy and treatment for a patient suffering from OCD.

Augmentation effect of acupuncture on Bi'nao for hypophasis in patients with Bell's palsy: study protocol for a randomized controlled trial.

PubMed

Li, Xiaoyan; Chen, Chunlan; Zhao, Chuang; Li, Zunyuan; Liang, Wei; Liu, Zhidan

2018-06-11

Hypophasis is one of the most frequently observed sequelae of patients with Bell's palsy, who have not recovered completely, creating a clinical difficulty for physicians. Acupuncture therapy has been widely used to treat Bell's palsy as a reasonable resolution for management of symptoms such as hypophasis. The number of acupuncture points (acu-points) is frequently selected in the approach of acupuncture therapy; however, whether these had high efficiency has not been proved. According to the literature review, Bi'nao was useful for treating eye and eye lipid diseases, which could be proved only by some successful cases. Thus, a randomized controlled trial was designed to evaluate the efficiency of the acu-point Bi'nao. Participants with hypophasis as the major symptom are selected among patients with Bell's palsy and randomly allocated into one of the three groups at a 1:1:1 allocation ratio. All participants receive conventional acupuncture therapy; however, those assigned to the real acupuncture group will be given added acupuncture therapy on the acu-point Bi'nao, while those assigned to the sham acupuncture group were given extra acupuncture therapy on the sham Bi'nao as a placebo. The efficacy of the acupuncture therapy on the acu-point Bi'nao for hypophasis will be evaluated by Eye Crack Width Measurement (ECWM) and Eyelid Strength Assessment (ESA) before and after therapy. This is the first study assessing the safety and efficiency of Bi'nao in treating the hypophasis of patients with Bell's palsy that might support the application of this acupuncture therapy. However, evaluating hypophasis is challenging, and, thus, ECWM and ESA were applied to measure the eyelid movement. Chinese Clinical Trials Registry, ChiCTR-INR-17012955 . Registered on 12 October 2017.

Why AIDS? The Mystery of How HIV Attacks the Immune System.

ERIC Educational Resources Information Center

Christensen, Damaris

1999-01-01

Reviews differing theories surrounding the mystery of how human immunodeficiency virus (HIV) attacks the immune system. Claims that understanding how HIV triggers immune-cell depletion may enable researchers to block its effects. New knowledge could reveal strategies for acquired immune deficiency syndrome (AIDS) therapies that go beyond the drugs…

Oxygenation-Enhanced Radiation Therapy of Breast Tumors

DTIC Science & Technology

2011-11-01

development of stabilized perfluorocarbon emulsions as oxygen carriers, their characterization, and response to external triggers, including...elevated temperature, reduced pressure, and dwell time. Targeted oxygenation, perfluorocarbon emulsions, breast cancer 29 The University of Utah Salt...investigation of the proposed novel strategy of radio sensitization of hypoxic breast tumors by targeted oxygen release from perfluorocarbon oxygen

Complex regional pain syndrome type 1: Analysis of 108 patients.

PubMed

Pendón, Gisela; Salas, Adrian; García, Mercedes; Pereira, Dora

Complex regional pain syndrome (CRPS) type 1 is characterized by the presence of pain, edema, functional impotence, impaired mobility, trophic changes, vasomotor instability and bone demineralization. We carried out a retrospective and prospective, descriptive, observational study of 108 patients over 18 years of age with suspected CRPS who met Doury's criteria. We recorded demographic data, clinical characteristics, comorbidities, previous predisposing conditions and triggering factors, such as injury or fracture. We evaluated laboratory data, serial plain X-rays, 3-phase bone scintigraphy with technetium 99 and bone density scan, as well as drug treatment, rehabilitation and disease course. In all, 89% of the 108 patients were women with an average age of 54.8±12.4 years. The time between the onset of the symptoms and the first visit to a physician was 3.1 months. The most common triggering factor was injury (91.7%). The most frequent psychological factor was anxiety (42.6%). All the patients reported pain and 99.07% had impaired mobility. The most frequently affected part of the body was the hand (75%; 81/108 patients) followed by the shoulder, in the shoulder-hand syndrome. All the patients had serial X-rays and changes were observed in 93.5%. Three-phase bone scintigraphy revealed evidence of disease in all 32 of the patients who underwent this study. Bone density scanning was performed in 54 patients (50%). All the patients were treated with nonsteroidal anti-inflammatory drugs, mainly diclofenac (60%). Calcium therapy was initiated in 106 patients (98.2%) and vitamin D3 therapy in 97.2%. All the patients received bisphosphonates, primarily alendronate and ibandronate (67.6% and 27.8%, respectively). Thirty-six patients (33.3%) received corticosteroids. All of the evaluated patients underwent rehabilitation involving occupational therapy. The average time to recovery was 6.31 months (range, 4-24). The outcome was favorable in 88.9% of the patients. This paper describes the clinical characteristics, therapeutic features and outcome of CRPS type 1 in 108 patients. This syndrome is known to be heterogeneous, and does not always present with the well-known symptoms. We recommend establishing a differential diagnosis including other infectious and inflammatory conditions, and point out the importance of early referral, which enables early treatment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Experimental Proof for the Role of Nonlinear Photoionization in Plasmonic Phototherapy.

PubMed

Minai, Limor; Zeidan, Adel; Yeheskely-Hayon, Daniella; Yudovich, Shimon; Kviatkovsky, Inna; Yelin, Dvir

2016-07-13

Targeting individual cells within a heterogeneous tissue is a key challenge in cancer therapy, encouraging new approaches for cancer treatment that complement the shortcomings of conventional therapies. The highly localized interactions triggered by focused laser beams promise great potential for targeting single cells or small cell clusters; however, most laser-tissue interactions often involve macroscopic processes that may harm healthy nearby tissue and reduce specificity. Specific targeting of living cells using femtosecond pulses and nanoparticles has been demonstrated promising for various potential therapeutic applications including drug delivery via optoporation, drug release, and selective cell death. Here, using an intense resonant femtosecond pulse and cell-specific gold nanorods, we show that at certain irradiation parameters cell death is triggered by nonlinear plasmonic photoionization and not by thermally driven processes. The experimental results are supported by a physical model for the pulse-particle-medium interactions. A good correlation is found between the calculated total number and energy of the generated free electrons and the observed cell death, suggesting that femtosecond photoionization plays the dominant role in cell death.

Environmental triggers of thyroiditis: hepatitis C and interferon-α.

PubMed

Menconi, F; Hasham, A; Tomer, Y

2011-01-01

Autoimmune thyroid diseases (AITD) are postulated to develop as a result of a complex interplay between several genetic and environmental influences. The pathogenesis of AITD is still not clearly defined. However, among the implicated triggers (e.g. iodine, infections, medications), more recent data confirmed strong associations of AITD with the hepatitis C virus (HCV) infection and interferon-α (IFNα) therapy. Moreover, it is likely that HCV and IFN act in synergism to trigger AITD in patients. Indeed, approximately 40% of HCV patients develop either clinical or subclinical disease while receiving IFNα. Interferon induced thyroiditis (IIT) can manifest as non-autoimmune thyroiditis (presenting as destructive thyroiditis, or non-autoimmune hypothyroidism), or autoimmune thyroiditis [presenting with clinical features of Graves' disease (GD) or Hashimoto's thyroiditis (HT)]. Although not yet clearly understood, it is thought that IFNα can induce thyroiditis via both immune stimulatory and direct toxic effects on the thyroid. In view of the high frequency of IIT, routine screening and surveillance of HCV patients receiving IFNα is recommended to avoid the complications, such as cardiac arrhythmias, associated with thyrotoxicosis. In summary, IIT is a common clinical problem that can be readily diagnosed with routine thyroid function screening of HCV patients receiving IFN. The treatment of IIT consists of the standard therapy for differing clinical manifestations of IIT such as GD, HT, or destructive thyroiditis. However, anti-thyroid medications are not recommended in this setting since they can potentially be hepatotoxic.

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging.

PubMed

Chen, Guojun; Ma, Ben; Wang, Yuyuan; Xie, Ruosen; Li, Chun; Dou, Kefeng; Gong, Shaoqin

2017-12-06

Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)-poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ∼38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.

[Clinical study of cervical spondylotic radiculopathy treated with massage therapy combined with Magnetic sticking therapy at the auricular points and the cost comparison].

PubMed

Wang, Saina; Sheng, Feng; Pan, Yunhua; Xu, Feng; Wang, Zhichao; Cheng, Lei

2015-08-01

To compare the clinical efficacy on cervical spondylotic radiculopathy between the combined therapy of massage and magnetic-sticking at the auricular points and the simple massage therapy, and conduct the health economics evaluation. Seventy-two patients of cervical spondylotic radiculopathy were randomized into a combined therapy group, and a simple massage group, 36 cases in each one. Finally, 35 cases and 34 cases were met the inclusive criteria in the corresponding groups separately. In the combined therapy group, the massage therapy and the magnetic sticking therapy at auricular points were combined in the treatment. Massage therapy was mainly applied to Fengchi (GB 20), Jianjing (GB 21), Jianwaishu (SI 14), Jianyu (LI 15) and Quchi (LI 11). The main auricular points for magnetic sticking pressure were Jingzhui (AH13), Gan (On12) Shen (CO10), Shenmen (TF4), Pizhixia (AT4). In the simple massage group, the simple massage therapy was given, the massage parts and methods were the same as those in the combined therapy group. The treatment was given once every two days, three times a week, for 4 weeks totally. The cervical spondylosis effect scale and the simplified McGill pain questionnaire were adopted to observe the improvements in the clinical symptoms, clinical examination, daily life movement, superficial muscular pain in the neck and the health economics cost in the patients of the two groups. The effect was evaluated in the two groups. The effective rate and the clinical curative rate in the combined therapy group were better than those in the control group [100. 0% (35/35) vs 85. 3% (29/34), 42. 9% (15/35) vs 17. 6% (6/34), both P<0. 05]. The scores of the spontaneous symptoms, clinical examnation, daily life movement and superficialmuscular pain in the neck were improved apparently after treatment as compared with those before treatment in the patients of the two groups (all P<0. 001). In terms of the improvements in the spontaneous symptoms, clinical examination total scores and superficial muscular pain in the' neck were more significant in the combined therapy group as compared with those in the simple massage group (P<0. 05, P<0. 01, P<0. 001). The cost at the unit effect in the combined therapy group was lower than that in the simple massage group (P<0. 05). Compared with the simple massage therapy, the massage therapy combined with magnetic sticking therapy at auricular points achieves the better effect and lower cost in health economics.

[Professor WU Zhongchao's experience in the treatment of bi syndrome with fire needling therapy at lower he-sea points].

PubMed

Zhou, Yu; Chen, Zhongjie; Liu, Chun; Wang, Bing; Zhang, Ning; Li, Caifen; Xie, Qian

2016-07-12

Bi syndrome is classified into five categories. Based on the syndrome differentiation of meridians and collaterals and zangfu theories, Professor WU Zhongchao proposed the fire needling therapy at the lower he -sea points for five types of bi syndromes. Professor WU stresses on the flexible application of fire needling therapy for bi syndrome at the lower he -sea points and innovated the unique five techniques of fire needling therapy, named lifting and threating needle of small amplitude at the lower he -sea points, the stimulation along the relevant meri-dians before fire needling, detecting the sensitive sites by gentle pressing the relevant lower he -sea points, combining the movement of affected upper limb or joint during fire needling, or combining with contralateral needling technique, and controlling the depth of fire needling based on the duration of sickness and depth of affected site. He pointed out that Shangjuxu (ST 37) is for skin bi syndrome, Zusanli (ST 36) for muscle bi syndrome, Yanglingquan (GB 34) for tendon bi syndrome, Weizhong (BL 40) for bone bi syndrome and Xiajuxu (ST 39) for vessel bi syndrome.

LIGO-VIRGO Triggered Follow-Up with NASA High Energy Photon Survey Missions

NASA Technical Reports Server (NTRS)

Camp, Jordan

2010-01-01

We discuss the proposed use of LIGO-VIRGO S6 triggers from comparatively loud events to search for both prompt and afterglow EM counterparts with RXTE, SWIFT and FERMI. Using a 2 or 3-fold coincident trigger from the two LIGO and one VIRGO detectors to provide sky position information, we can search the data from these missions within a limited time window and a constrained portion of their respective FOVs, allowing us to look at a level below the threshold normally used to publicly indicate an event. Since we propose to use these missions in their survey mode, no re-pointing of the missions is envisioned. The search for a coincidence between the data from LIGO-VIRGO and the EM survey missions can then be analyzed off-line; if a coincident EM signal is found it would have a significant effect in establishing the validity of the GW trigger. We discuss some relevant aspects of the NASA missions and give some preliminary estimates of thresholds and coincident background rates.

Triggering processes of microseismic events associated with water injection in Okuaizu Geothermal Field, Japan

NASA Astrophysics Data System (ADS)

Okamoto, Kyosuke; Yi, Li; Asanuma, Hiroshi; Okabe, Takashi; Abe, Yasuyuki; Tsuzuki, Masatoshi

2018-02-01

A continuous water injection test was conducted to halt the reduction in steam production in the Okuaizu Geothermal Field, Japan. Understanding the factors triggering microseismicity associated with water injection is essential to ensuring effective steam production. We identified possible triggering processes by applying methods based on microseismic monitoring, including a new method to determine the presence of water in local fractures using scattered P-waves. We found that the evolving microseismicity near the injection point could be explained by a diffusion process and/or water migration. We also found that local microseismicity on a remote fault was likely activated by stress fluctuations resulting from changes in the injection rate. A mediator of this fluctuation might be water remaining in the fracture zone. After the injection was terminated, microseismicity possibly associated with the phase transition of the liquid was found. We conclude that a variety of triggering processes associated with water injection may exist.[Figure not available: see fulltext.

Jervell and Lange-Nielsen syndrome in a father and daughter from a large highly inbred family: a 16-year follow-up of 59 living members.

PubMed

Sanyal, Shyamal Kumar; Kaul, Kanwar K; Hussein, Akhtar; Wilroy, Robert S; Agarwal, Kisan; Sohel, Saira

2013-08-01

To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years. A total of 24 living members were affected--QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only β-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period. Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.

Acupuncture Therapy for the Treatment of Myelosuppression after Chemotherapy: A Literature Review over the Past 10 Years.

PubMed

Fu, Hongwei; Chen, Bo; Hong, Shouhai; Guo, Yi

2015-06-01

The aim of this study is to review current studies on the effect of acupuncture therapy on bone marrow suppression after chemotherapy. The authors of the present paper have searched related literature over the past 10 years at home and abroad, analyzing the features and the effects of acupuncture therapy (including acupuncture, moxibustion, point injection, point application, etc.) for treating myelosuppression after tumor chemotherapy. We also discuss the year of publication, document type, acupuncture therapy, acupoint selection, and adverse effects with figures. We analyzed 159 articles related to acupuncture therapy from 2004 to 2013, and the analysis revealed that point injection was the most frequently used therapy for clinical applications, and that Zusanli (ST36) was the most frequently used acupoint. The results showed that some problems regarding the design method, acupoint selection, and acupuncture intervention measure existed in those research studies. We hope to provide readers with an overall and objective understanding of acupuncture and moxibustion therapy for treating myelosuppression after tumor chemotherapy. Copyright © 2015. Published by Elsevier B.V.

Immunoregulation of GVHD by triggering the innate immune system with CpG.

PubMed

Morecki, Shoshana; Slavin, Shimon

2009-08-01

Stimulation of Toll-like receptors by oligodeoxynucleotide sequences containing a CpG motif provides signals capable of triggering the innate and adaptive immune systems, thereby leading either to stimulation or suppression of immunoreactivities. Similar immunoregulatory capabilities are necessary for achieving the fine balance between engraftment and graft-versus-host disease required in the setup of allogeneic cell therapy. Ligation of CpG to its Toll-like receptors can be accomplished by treatment of the host or pretransplant treatment of the donor in vivo. These different strategies are presented in this review, which summarizes the attempts to maximize beneficial alloreactivity against malignant or other undesirable host cells, while controlling graft-versus-host disease.

Alternative approach for management of an electrical storm in Brugada syndrome:Importance of primary ablation within a narrow time window.

PubMed

Talib, Ahmed Karim; Yui, Yoshiaki; Kaneshiro, Takashi; Sekiguchi, Yukio; Nogami, Akihiko; Aonuma, Kazutaka

2016-06-01

Placement of an implantable cardioverter-defibrillator (ICD) is the only powerful treatment modality for Brugada syndrome in patients presenting with ventricular fibrillation (VF). For those whose first presentation is an electrical storm, pharmacologic therapy is typically used to control VF followed by ICD implantation. We report an alternative approach whereby, before ICD implantation, emergency catheter ablation of the VF-triggering premature ventricular contraction (PVC) resulted in long-term VF-free survival. The results suggest that, because VF triggers appear in a narrow time window, ablation of the culprit PVCs that initiate VF before the index PVCs subside is a reasonable alternative approach.

A case of cerebral reversible vasoconstriction syndrome triggered by repetition transcranial magnetic stimulation.

PubMed

Sato, Mamiko; Yamate, Koji; Hayashi, Hiromi; Miura, Toyoaki; Kobayashi, Yasutaka

2017-08-31

A 75-year-old man was admitted for combined low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy. Five days after the initiation of rTMS, he developed hypotension and temporary exacerbation of the right hemiplegia with thunderclap headache. MRA showed segmental stenosis of the left middle cerebral artery, which findings were improved at 9 days after the onset of the headache. He was diagnosed as having the reversible cerebral vasoconstriction syndrome (RCVS). The rTMS was recognized as safe rehabilitation treatment. However, it is necessary to recognize that RCVS can become one of the precipitants. This is the first report of RCVS triggered by rTMS.

On the conditions for nonlinear growth in magnetospheric chorus and triggered emissions

NASA Astrophysics Data System (ADS)

Gołkowski, Mark; Gibby, Andrew R.

2017-09-01

The nonlinear whistler mode instability associated with magnetospheric chorus and VLF triggered emissions continues to be poorly understood. Following up on formulations of other authors, an analytical exploration of the stability of the phenomenon from a new vantage point is given. This exploration derives an additional requirement on the anisotropy of the energetic electron distribution relative to the linear treatment of the instability, and shows that the nonlinear instability is most favorable to increasing growth rate when electrons become initially trapped in the wave potential of a constant frequency wave. These results imply that the initiation of the nonlinear instability at the equator requires a positive frequency sweep rate, while the initiation of the instability by a constant frequency triggering wave must occur at a location downstream of the geomagnetic equator.

Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells.

PubMed

Hsu, Chia-Chun; Wu, Yang-Chang; Farh, Lynn; Du, Ying-Chi; Tseng, Wei-Kung; Wu, Chau-Chung; Chang, Fang-Rong

2012-03-01

Melanoma is a lethal form of skin cancer that can metastasize rapidly. While surgery and radiation therapy provide palliative therapy for local tumor growth, systemic therapy is the mainstay of treatment for metastatic melanoma. However, limited chemotherapeutic agents are available for melanoma treatment. In this study, we investigated the anti-melanoma effect of physalin B, the major active compound from a widely used herb medicine, Physalis angulata L. This study demonstrated that physalin B exhibits cytotoxicity towards v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma A375 and A2058 cells (the IC50 values are lower than 4.6 μg/ml). Cytotoxicity is likely resulted from apoptosis since the apoptotic marker phosphatidylserine are detected immediately under physalin B treatment and apoptotic cells formation. Further examination revealed that physalin B induces expression of the proapoptotic protein NOXA within 2 h and later triggers the expression of Bax and caspase-3 in A375 cells. These results indicate that physalin B can induce apoptosis of melanoma cancer cells via the NOXA, caspase-3, and mitochondria-mediated pathways, but not of human skin fibroblast cells and myoblastic cells. Thus, physalin B has the potential to be developed as an effective chemotherapeutic lead compound for the treatment of malignant melanoma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation.

PubMed

Zhu, Piao; Chen, Yu; Shi, Jianlin

2018-04-24

Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nanomedicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnO x component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnO x component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H 2 O 2 ) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonstrated to facilitate SDT-induced reactive oxygen species production and enhance SDT efficacy subsequently. The targeted accumulation of these composite nanosonosensitizers efficiently suppressed the growth of U87 tumor xenograft on nude mice after US-triggered SDT treatment. The high in vivo biocompatibility and easy excretion of these multifunctional nanosonosensitizers from the body have also been evaluated and demonstrated to guarantee their future clinical translation, and their TME-responsive T 1 -weighted magnetic resonance imaging capability provides the potential for therapeutic guidance and monitoring during SDT.

Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.

PubMed

Srinivasan, Supriya; Bhardwaj, Vinay; Nagasetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J

2016-12-01

This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.

Medical Nutrition Therapy for Post-Bariatric Hypoglycemia: Practical Insights

PubMed Central

Suhl, Emmy; Anderson-Haynes, Sue-Ellen; Mulla, Christopher; Patti, Mary-Elizabeth

2017-01-01

Hypoglycemia is increasingly recognized as a complication of bariatric surgery. Although medications are often required, medical nutrition therapy remains the key cornerstone for successful prevention of hypoglycemia in patients with post-bariatric hypoglycemia (PBH). We provide suggested approaches to the dietary management of PBH, incorporating data from both the medical literature and extensive clinical experience in an academic referral center for PBH. The overall goal of medical nutrition therapy for PBH is to reduce postprandial surges in glucose, which often trigger surges in insulin secretion and promote subsequent hypoglycemia. Thus, strategies focus on controlled portions of low glycemic index carbohydrates, avoidance of rapidly-absorbed carbohydrates, adjustment of timing of meals and snacks, and attention to personal and cultural barriers to implementation. PMID:28392017

Perspectives and challenges of antioxidant therapy for atrial fibrillation.

PubMed

Gasparova, Iveta; Kubatka, Peter; Opatrilova, Radka; Caprnda, Martin; Filipova, Slavomira; Rodrigo, Luis; Malan, Leone; Mozos, Ioana; Rabajdova, Miroslava; Nosal, Vladimir; Kobyliak, Nazarii; Valentova, Vanda; Petrovic, Daniel; Adamek, Mariusz; Kruzliak, Peter

2017-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.

Differentiation therapy revisited.

PubMed

de Thé, Hugues

2018-02-01

The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal. By reviewing other successful examples of drug-induced tumour cell differentiation, novel approaches to transform differentiating drugs into more efficient therapies are proposed.

[Percutaneous electrical nerve stimulation of peripheral nerve for the intractable occipital neuralgia].

PubMed

Shaladi, Ali; Crestani, Francesco; Saltari, Rita; Piva, Bruno

2008-06-01

Occipital neuralgia is characterized by pain paroxysm occurring within distribution of the greater or lesser occipital nerves. The pain may radiates from the rear head toward the ipso-lateral frontal or retro-orbital regions of head. Though known causes include head injuries, direct occipital nerve trauma, neuroma formation or upper cervical root compression, most people have no demonstrable lesion. A sample of 8 patients (5 females, 3 males) aging 63,5 years on the average with occipital neuralgia has been recruited. The occipital neuralgic pain had presented since 4, 6 years and they had been treated by pharmacological therapy without benefit. Some result has been obtained by blocking of the grand occipital nerve so that the patients seemed to be suitable for subcutaneous peripheral neurostimulation. The pain was evaluated by VAS and SVR scales before treatment (TO) and after three and twelve months (T1, T2). During the follow up period 7 patients have been monitored for a whole year while one patient was followed only for 3 months in that some complications have presented. In the other 7 patients pain paroxysms have interrupted and trigger point disappeared with a VAS and SVR reduction of about 71% and 60%, respectively. Our experience demonstrates a sound efficacy of such a technique for patients having occipital neuralgia resistant to pharmacological therapies even if action mechanisms have not yet clearly explained. Some hypothesis exist and we think it might negatively affect the neurogenic inflammation that surely acts in pain maintaining.

Simulation of rockfalls triggered by earthquakes

USGS Publications Warehouse

Kobayashi, Y.; Harp, E.L.; Kagawa, T.

1990-01-01

A computer program to simulate the downslope movement of boulders in rolling or bouncing modes has been developed and applied to actual rockfalls triggered by the Mammoth Lakes, California, earthquake sequence in 1980 and the Central Idaho earthquake in 1983. In order to reproduce a movement mode where bouncing predominated, we introduced an artificial unevenness to the slope surface by adding a small random number to the interpolated value of the mid-points between the adjacent surveyed points. Three hundred simulations were computed for each site by changing the random number series, which determined distances and bouncing intervals. The movement of the boulders was, in general, rather erratic depending on the random numbers employed, and the results could not be seen as deterministic but stochastic. The closest agreement between calculated and actual movements was obtained at the site with the most detailed and accurate topographic measurements. ?? 1990 Springer-Verlag.

EMIC triggered chorus emissions in Cluster data

NASA Astrophysics Data System (ADS)

Grison, B.; SantolíK, O.; Cornilleau-Wehrlin, N.; Masson, A.; Engebretson, M. J.; Pickett, J. S.; Omura, Y.; Robert, P.; Nomura, R.

2013-03-01

Electromagnetic ion cyclotron (EMIC) triggered chorus emissions have recently been a subject of several experimental, theoretical and simulation case studies, noting their similarities with whistler-mode chorus. We perform a survey of 8 years of Cluster data in order to increase the database of EMIC triggered emissions. The results of this is that EMIC triggered emissions have been unambiguously observed for only three different days. These three events are studied in detail. All cases have been observed at the plasmapause between 22 and 24 magnetic local time (MLT) and between - 15° and 15° magnetic latitude (λm). Triggered emissions are also observed for the first time below the local He+ gyrofrequency (fHe+). The number of events is too low to produce statistical results, nevertheless we point out a variety of common properties of those waves. The rising tones have a high level of coherence and the waves propagate away from the equatorial region. The propagation angle and degree of polarization are related to the distance from the equator, whereas the slope and the frequency extent vary from one event to the other. From the various spacecraft separations, we determine that the triggering process is a localized phenomenon in space and time. However, we are unable to determine the occurrence rates of these waves. Small frequency extent rising tones are more common than large ones. The newly reported EMIC triggered events are generally observed during periods of large AE index values and in time periods close to solar maximum.

Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

PubMed Central

2014-01-01

Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations. PMID:25043142

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

NASA Astrophysics Data System (ADS)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery.

PubMed

Badeau, Barry A; Comerford, Michael P; Arakawa, Christopher K; Shadish, Jared A; DeForest, Cole A

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Emotional stressors trigger cardiovascular events.

PubMed

Schwartz, B G; French, W J; Mayeda, G S; Burstein, S; Economides, C; Bhandari, A K; Cannom, D S; Kloner, R A

2012-07-01

To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. Targeted PUBMED searches were conducted to supplement the authors' existing database on this topic. Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study. © 2012 Blackwell Publishing Ltd.

Thermosensitive liposomes for localized delivery and triggered release of chemotherapy

PubMed Central

Ta, Terence; Porter, Tyrone M.

2016-01-01

Liposomes are a promising class of nanomedicine with the potential to provide site-specific chemotherapy, thus improving the quality of cancer patient care. First-generation liposomes have emerged as one of the first nanomedicines used clinically for localized delivery of chemotherapy. Second-generation liposomes, i.e. stimuli-responsive liposomes, have the potential to not only provide site-specific chemotherapy, but also triggered drug release and thus greater spatial and temporal control of therapy. Temperature-sensitive liposomes are an especially attractive option, as tumors can be heated in a controlled and predictable manner with external energy sources. Traditional thermosensitive liposomes are composed of lipids that undergo a gel-to-liquid phase transition at several degrees above physiological temperature. More recently, temperature-sensitization of liposomes has been demonstrated with the use of lysolipids and synthetic temperature-sensitive polymers. The design, drug release behavior, and clinical potential of various temperature-sensitive liposomes, as well as the various heating modalities used to trigger release, are discussed in this review. PMID:23583706

Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis: A Randomized Trial.

PubMed

Wang, Chenchen; Schmid, Christopher H; Iversen, Maura D; Harvey, William F; Fielding, Roger A; Driban, Jeffrey B; Price, Lori Lyn; Wong, John B; Reid, Kieran F; Rones, Ramel; McAlindon, Timothy

2016-07-19

Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985). An urban tertiary care academic hospital. 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, -10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. National Center for Complementary and Integrative Health of the National Institutes of Health.

Objective measurement of tissue tension in myofascial trigger point areas before and during the administration of anesthesia with complete blocking of neuromuscular transmission.

PubMed

Buchmann, Johannes; Neustadt, Beate; Buchmann-Barthel, Katharina; Rudolph, Soeren; Klauer, Thomas; Reis, Olaf; Smolenski, Ulrich; Buchmann, Hella; Wagner, Klaus F; Haessler, Frank

2014-03-01

Myofascial trigger points (MTPs) are extremely frequent in the human musculoskeletal system. Despite this, little is known about their etiology. Increased muscular tension in the trigger point area could be a major factor for the development of MTPs. To investigate the impact of muscular tension in the taut band with an MTP and thereby, the spinal excitability of associated segmental neurons, we objectively measured the tissue tension in MTPs before and during the administration of anesthesia using a transducer. Three target muscles (m. temporalis, upper part of m. trapezius, and m. extensor carpi radialis longus) with an MTP and 1 control muscle without an MTP were examined in 62 patients scheduled for an operation. We found significant 2-way interactions (ANOVA, P<0.05) between the analyzed regions of the target muscles dependent on the time of measurement, that is, before and during a complete blocking of neuromuscular transmission. These effects could be demonstrated for each target muscle separately. An increased muscle tension in MTPs, and not a primary local inflammation with enhanced viscoelasticity, was the main result of our investigation. We interpret this increased muscular tension in the taut band with an MTP as increased spinal segmental excitability. In line with this, we assume a predominant, but not unique, impact of increased spinal excitability resulting in an augmented tension of segmental-associated muscle fibers for the etiology of MTP. Consequently, postisometric relaxation might be a promising therapeutic option for MTPs.

Sensor-triggered sampling to determine instantaneous airborne vapor exposure concentrations.

PubMed

Smith, Philip A; Simmons, Michael K; Toone, Phillip

2018-06-01

It is difficult to measure transient airborne exposure peaks by means of integrated sampling for organic chemical vapors, even with very short-duration sampling. Selection of an appropriate time to measure an exposure peak through integrated sampling is problematic, and short-duration time-weighted average (TWA) values obtained with integrated sampling are not likely to accurately determine actual peak concentrations attained when concentrations fluctuate rapidly. Laboratory analysis for integrated exposure samples is preferred from a certainty standpoint over results derived in the field from a sensor, as a sensor user typically must overcome specificity issues and a number of potential interfering factors to obtain similarly reliable data. However, sensors are currently needed to measure intra-exposure period concentration variations (i.e., exposure peaks). In this article, the digitized signal from a photoionization detector (PID) sensor triggered collection of whole-air samples when toluene or trichloroethylene vapors attained pre-determined levels in a laboratory atmosphere generation system. Analysis by gas chromatography-mass spectrometry of whole-air samples (with both 37 and 80% relative humidity) collected using the triggering mechanism with rapidly increasing vapor concentrations showed good agreement with the triggering set point values. Whole-air samples (80% relative humidity) in canisters demonstrated acceptable 17-day storage recoveries, and acceptable precision and bias were obtained. The ability to determine exceedance of a ceiling or peak exposure standard by laboratory analysis of an instantaneously collected sample, and to simultaneously provide a calibration point to verify the correct operation of a sensor was demonstrated. This latter detail may increase the confidence in reliability of sensor data obtained across an entire exposure period.

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

PubMed Central

Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

2015-01-01

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

Clinical outcomes following manual physical therapy and exercise for hip osteoarthritis: A case series.

PubMed

MacDonald, Cameron W; Whitman, Julie M; Cleland, Joshua A; Smith, Marcia; Hoeksma, Hugo L

2006-08-01

Case series describing the outcomes of individual patients with hip osteoarthritis treated with manual physical therapy and exercise. Seven patients referred to physical therapy with hip osteoarthritis and/or hip pain were included in this case series. All patients were treated with manual physical therapy followed by exercises to maximize strength and range of motion. Six of 7 patients completed a Harris Hip Score at initial examination and discharge from physical therapy, and 1 patient completed a Global Rating of Change Scale at discharge. Three males and 4 females with a median age of 62 years (range, 52-80 years) and median duration of symptoms of 9 months (range, 2-60 months) participated in this case series. The median number of physical therapy sessions attended was 5 (range, 4-12). The median increase in total passive range of motion of the hip was 82 degrees (range, 70 degrees-86 degrees). The median improvement on the Harris Hip Score was 25 points (range, 15-38 points). The single patient who completed the Global Rating of Change Scale at discharge reported being "a great deal better." Numeric pain rating scores decreased by a mean of 5 points (range, 2-7 points) on 0-to-10-point scale. All patients exhibited reductions in pain and increases in passive range of motion, as well as a clinically meaningful improvement in function. Although we can not infer a cause and effect relationship from a case series, the outcomes with these patients are similar to others reported in the literature that have demonstrated superior clinical outcomes associated with manual physical therapy and exercise for hip osteoarthritis compared to exercise alone.

Efficacy and Safety of Single Botulinum Toxin Type A (Botox®) Injection for Relief of Upper Trapezius Myofascial Trigger Point: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Kwanchuay, Photsawee; Petchnumsin, Thavatchai; Yiemsiri, Pichet; Pasuk, Nakkamol; Srikanok, Wannarat; Hathaiareerug, Chanasak

2015-12-01

Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox®) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0 ± 0.9 and 0.5 ± 0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox®) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However Botulinum toxin type A (Botox®) showed statistically significant more increased in pressure pain threshold at 6-week after injection without severe adverse effects.

Patterns of Use of Peripheral Nerve Blocks and Trigger Point Injections for Pediatric Headache: Results of a survey of the American Headache Society Pediatric & Adolescent Section

PubMed Central

Szperka, Christina L.; Gelfand, Amy A.; Hershey, Andrew D.

2016-01-01

Objective To describe current patterns of use of nerve blocks and trigger point injections for treatment of pediatric headache. Background Peripheral nerve blocks are often used to treat headaches in adults and children, but the available studies and practice data from adult headache specialists have shown wide variability in diagnostic indications, sites injected, and medication(s) used. The purpose of this study was to describe current practice patterns in the use of nerve blocks and trigger point injections for pediatric headache disorders. Methods A survey was created in REDCap, and sent via email to the 82 members of the Pediatric & Adolescent Section of the American Headache Society in June 2015. The survey queried about current practice and use of nerve blocks, as well as respondents’ opinions regarding gaps in the evidence for use of nerve blocks in this patient population. Results Forty-one complete, 5 incomplete, and 3 duplicate responses were submitted (response rate complete 50%). Seventy-eight percent of the respondents identified their primary specialty as Child Neurology, and 51% were certified in headache medicine. Twenty-six (63%) respondents perform nerve blocks themselves, and 7 (17%) refer patients to another provider for nerve blocks. Chronic migraine with status migrainosus was the most common indication for nerve blocks (82%), though occipital neuralgia (79%), status migrainosus (73%), chronic migraine without flare (70%), post-traumatic headache (70%), and new daily persistent headache (67%) were also common indications. The most commonly selected clinically meaningful response for status migrainosus was ≥50% reduction in severity, while for chronic migraine this was a ≥50% decrease in frequency at 4 weeks. Respondents inject the following locations: 100% inject the greater occipital nerve, 69% lesser occipital nerve, 50% supraorbital, 46% trigger point injections, 42% auriculotemporal, and 34% supratrochlear. All respondents used local anesthetic, while 12 (46%) also use corticosteroid (8 bupivacaine only, 4 each lidocaine + bupivacaine, lidocaine + corticosteroid, bupivacaine + corticosteroid, lidocaine + bupivacaine + corticosteroid, and 2 lidocaine only). Conclusion Despite limited evidence, nerve blocks are commonly used by pediatric headache specialists. There is considerable variability among clinicians as to injection site(s) and medication selection, indicating a substantial gap in the literature to guide practice, and supporting the need for further research in this area. PMID:27731894

Optimal pharmacological therapy in ST-elevation myocardial infarction-a review : A review of antithrombotic therapies in STEMI.

PubMed

Hermanides, R S; Kilic, S; van 't Hof, A W J

2018-04-23

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.

Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

PubMed

Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

2017-09-01

In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

Management of Pediatric Migraine: Current Therapies.

PubMed

Khrizman, Marina; Pakalnis, Ann

2018-02-01

Migraine is one of the most common neurologic conditions in pediatrics. It can be a significant stressor, causing absences from school and interruption of parents' work and family schedules. The mainstay of treatment remains educating patients about healthy lifestyle practices and the influences of sleep, stressors, and hydration on triggering migraine attacks. Psychological therapies such as biofeedback or cognitive-behavioral therapy may be beneficial in some patients, especially those with prominent psychological comorbidities. New advances in the pathophysiology of migraine and additional pediatric approval of abortive therapy with triptans have led to significant advances in the management of migraine in children. Some challenges to preventive therapy were recently noted with the negative results obtained in the Childhood and Adolescent Migraine Prevention Study, which compared prescription drugs to placebo. Inherent differences between adult and pediatric headaches, with shorter duration of pediatric migraine and prominent placebo effect, present recurring challenges for clinicians. [Pediatr Ann. 2018;47(2):e55-e60.]. Copyright 2018, SLACK Incorporated.

Defining when to initiate massive transfusion: a validation study of individual massive transfusion triggers in PROMMTT patients.

PubMed

Callcut, Rachael A; Cotton, Bryan A; Muskat, Peter; Fox, Erin E; Wade, Charles E; Holcomb, John B; Schreiber, Martin A; Rahbar, Mohammad H; Cohen, Mitchell J; Knudson, M Margaret; Brasel, Karen J; Bulger, Eileen M; Del Junco, Deborah J; Myers, John G; Alarcon, Louis H; Robinson, Bryce R H

2013-01-01

Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger. A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p < 0.0005). Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT. Diagnostic, level II.

[Comments on the definition of "acupuncture science"].

PubMed

Wang, Fan

2017-12-12

The experts in China believe that the substance of "dry needling" is in the category of acupuncture therapy for the treatment by needle inserting the human body. But, its recognition has not been implied from the definition of "acupuncture science". Since 1970 s, the different definitions of it are closely related to TCM theories, due to which, it has been limited. This flaw restricts the development of acupuncture theory, narrows the connotation of acupuncture science and goes against the communication of traditional Chinese acupuncture theory. No matter regarding the theory or technique, the acupuncture therapy nowadays changes greatly in its connotation. Rather than guided by TCM theories, acupuncture therapy mainly includes the nerve trunk stimulation theory, the cerebral function orientation therapy, biological holographic therapy, fascia stimulation therapy and trigger therapy, etc. Expect that the medical devices used in these therapies are same as the traditional acupuncture, these methods cannot be regarded in the category of acupuncture science when the current definition of it is considered. Hence, the writer is trying to define "acupuncture science" as: acupuncture science refers to the science for the methodology and mechanism of therapeutic devices, e.g. acupuncture therapy and moxibustion therapy, for the prevention and treatment of disease by stimulating the body, and its theory includes but not limits in traditional Chinese medical theory.

Activation of a medical emergency team using an electronic medical recording-based screening system*.

PubMed

Huh, Jin Won; Lim, Chae-Man; Koh, Younsuck; Lee, Jury; Jung, Youn-Kyung; Seo, Hyun-Suk; Hong, Sang-Bum

2014-04-01

To evaluate the efficacy of a medical emergency team activated using 24-hour monitoring by electronic medical record-based screening criteria followed by immediate intervention by a skilled team. Retrospective cohort study. Academic tertiary care hospital with approximately 2,700 beds. A total of 3,030 events activated by a medical emergency team from March 1, 2008, to February 28, 2010. None. We collected data for all medical emergency team activations: patient characteristics, trigger type for medical emergency team (electronic medical record-based screening vs calling criteria), interventions during each event, outcomes of the medical emergency team intervention, and 28-day mortality after medical emergency team activation. We analyzed data for 2009, when the medical emergency team functioned 24 hours a day, 7 days a week (period 2), compared with that for 2008, when the medical emergency team functioned 12 hours a day, 7 days a week (period 1). The commonest cause of medical emergency team activation was respiratory distress (43.6%), and the medical emergency team performed early goal-directed therapy (21.3%), respiratory care (19.9%), and difficult airway management (12.3%). For patients on general wards, 51.3% (period 1) and 38.4% (period 2) of medical emergency team activations were triggered by the electronic medical record-based screening system (electronic medical record-triggered group). In 23.4%, activation occurred because of an abnormality in laboratory screening criteria. The commonest activation criterion from electronic medical record-based screening was respiratory rate (39.4%). Over half the patients were treated in the general ward, and one third of the patients were transferred to the ICU. The electronic medical record-triggered group had lower ICU admission with an odds ratio of 0.35 (95% CI, 0.22-0.55). In surgical patients, the electronic medical record-triggered group showed the lower 28-day mortality (10.5%) compared with the call-triggered group (26.7%) or the double-triggered group (33.3%) (odds ratio 0.365 with 95% CI, 0.154-0.867, p = 0.022). We successful managed the medical emergency team with electronic medical record-based screening criteria and a skilled intervention team. The electronic medical record-triggered group had lower ICU admission than the call-triggered group or the double-triggered group. In surgical patients, the electronic medical record-triggered group showed better outcome than other groups.

Robot-assisted therapy for long-term upper-limb impairment after stroke.

PubMed

Lo, Albert C; Guarino, Peter D; Richards, Lorie G; Haselkorn, Jodie K; Wittenberg, George F; Federman, Daniel G; Ringer, Robert J; Wagner, Todd H; Krebs, Hermano I; Volpe, Bruce T; Bever, Christopher T; Bravata, Dawn M; Duncan, Pamela W; Corn, Barbara H; Maffucci, Alysia D; Nadeau, Stephen E; Conroy, Susan S; Powell, Janet M; Huang, Grant D; Peduzzi, Peter

2010-05-13

Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.) 2010 Massachusetts Medical Society

Rate of Change in Lake Level and its Impact on Reservoir-triggered Seismicity

NASA Astrophysics Data System (ADS)

Simpson, D. W.

2017-12-01

With recent interest in increased seismicity related to fluid injection, it is useful to review cases of reservoir-triggered earthquakes to explore common characteristics and seek ways to mitigate the influence of anthropogenic impacts. Three reservoirs - Koyna, India; Nurek, Tajikistan; and Aswan, Egypt - are well-documented cases of triggered earthquakes with recorded time series of seismicity and water levels that extend for more than 30 years. The geological setting, regional tectonics and modes of reservoir utilization, along with the characteristics of the reservoir-seismicity interaction, are distinctly different in each of these three cases. Similarities and differences between these three cases point to regional and local geological and hydrological structures and the rate of changes in reservoir water level as important factors controlling the presence and timing of triggered seismicity. In a manner similar to the way in which the rate of fluid injection influences injection-related seismicity, the rate of change in reservoir water level is a significant factor in determining whether or not reservoir-triggered seismicity occurs. The high rate of annual water level rise may be important in sustaining the exceptionally long sequence of earthquakes at Koyna. In addition to the rate of filling being a determining factor in whether or not earthquakes are triggered, changes in the rate of filling may influence the time of occurrence of individual earthquakes.

Investigating on the Differences between Triggered and Background Seismicity in Italy and Southern California.

NASA Astrophysics Data System (ADS)

Stallone, A.; Marzocchi, W.

2017-12-01

Earthquake occurrence may be approximated by a multidimensional Poisson clustering process, where each point of the Poisson process is replaced by a cluster of points, the latter corresponding to the well-known aftershock sequence (triggered events). Earthquake clusters and their parents are assumed to occur according to a Poisson process at a constant temporal rate proportional to the tectonic strain rate, while events within a cluster are modeled as generations of dependent events reproduced by a branching process. Although the occurrence of such space-time clusters is a general feature in different tectonic settings, seismic sequences seem to have marked differences from region to region: one example, among many others, is that seismic sequences of moderate magnitude in Italian Apennines seem to last longer than similar seismic sequences in California. In this work we investigate on the existence of possible differences in the earthquake clustering process in these two areas. At first, we separate the triggered and background components of seismicity in the Italian and Southern California seismic catalog. Then we study the space-time domain of the triggered earthquakes with the aim to identify possible variations in the triggering properties across the two regions. In the second part of the work we focus our attention on the characteristics of the background seismicity in both seismic catalogs. The assumption of time stationarity of the background seismicity (which includes both cluster parents and isolated events) is still under debate. Some authors suggest that the independent component of seismicity could undergo transient perturbations at various time scales due to different physical mechanisms, such as, for example, viscoelastic relaxation, presence of fluids, non-stationary plate motion, etc, whose impact may depend on the tectonic setting. Here we test if the background seismicity in the two regions can be satisfactorily described by the time-homogeneous Poisson process, and, in case, we characterize quantitatively possible discrepancies with this reference process, and the differences between the two regions.

Phototoxicity of B-RAF inhibitors: Exclusively due to UVA radiation and rapidly regressive.

PubMed

Gabeff, Romain; Dutartre, Hervé; Khammari, Amir; Boisrobert, Aurélie; Nguyen, Jean-Michel; Quereux, Gaëlle; Brocard, Anabelle; Saint-Jean, Mélanie; Peuvrel, Lucie; Dreno, Brigitte

2015-01-01

New targeted melanoma therapies such as B-RAF inhibitors have shown high and promising clinical benefit but have cutaneous side-effects, including photosensitivity, which is triggered in the UVA radiation spectrum. However, visible spectrum implication has not yet been investigated. We conducted a study to determine whether visible light also contributes to the phototoxicity action spectrum of vemurafenib. The secondary end points were to determine the time to complete regression of the phototoxicity post-vemurafenib discontinuation and whether there was a significant difference between the UVA radiation immediate reactivity cut-offs, in patients treated with vemurafenib vs. those treated with dabrafenib. This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib. The visible-light phototest results in patients treated with vemurafenib were all negative before and after 2 months of treatment. The UVA radiation phototests conducted 1 or 2 weeks post-vemurafenib discontinuation in 4 patients showed a normalised UVA-radiation reactivity cut-off. UVA radiation phototests after 2 months of treatment were conducted for all patients. The UVA radiation reactivity cut-off had been lowered for 30 patients (88%) on vemurafenib and 3 patients (33%) on dabrafenib. The median UVA radiation reactivity cut-off was 12 J/cm(2) for the patients on vemurafenib and 20 J/cm(2) for the patients on dabrafenib. B-RAF inhibitor phototoxicity is exclusively triggered by UVA radiation and resolves rapidly post-treatment discontinuation. A significant difference between the UVA immediate reactivity cut-offs, vemurafenib vs. dabrafenib, explains the difference in the clinical photosensitivity rates reported in the clinical trials.

Psychosocial consequences of cancer cachexia: the development of an item bank.

PubMed

Häne, Hanspeter; Oberholzer, Rolf; Walker, Jochen; Hopkinson, Jane B; de Wolf-Linder, Susanne; Strasser, Florian

2013-12-01

Cancer cachexia syndrome (CCS) is often accompanied by psychosocial consequences (PSC). To alleviate PSC, a systematic assessment method is required. Currently, few assessment tools are available (e.g., Functional Assessment of Anorexia/Cachexia Therapy). There is no systematic assessment tool that captures the PSC of CCS. To develop a pilot item bank to assess the PSC of CCS. A total of 132 questions, generated from patient answers in a previous study, were reduced to 121 items by content analysis and evaluation by multidisciplinary experts (doctor, nutritionists, and nurses). In our two-step, cross-sectional study, patients, judged by staff to have PSC of CCS, were included, and the questions were randomly allocated to the patients. Questions were evaluated for understandability and triggering emotions, and patients were asked to provide a response using a four-point Likert scale. Subsequently, problematic questions were revised, reformulated, and retested. A total of 20 patients with a variety of tumor types participated. Of the 121 questions, 31 had to be reformulated after Step 1 and were retested in Step 2, after which seven were again evaluated as not being perfectly comprehensible. In Step 1, 22 questions were found to trigger emotions, but no item required remodeling. Item performance using the Likert scale revealed no consistent floor or ceiling effects. Our final pilot question bank comprised 117 questions. The final item bank contains questions that are understood and accepted by the patients. This item bank now needs to be developed into a measurement tool that groups items into domains and can be used in future research studies. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Management of bleeding in vascular surgery.

PubMed

Chee, Y E; Liu, S E; Irwin, M G

2016-09-01

Management of acute coagulopathy and blood loss during major vascular procedures poses a significant haemostatic challenge to anaesthetists. The acute coagulopathy is multifactorial in origin with tissue injury and hypotension as the precipitating factors, followed by dilution, hypothermia, acidemia, hyperfibrinolysis and systemic inflammatory response, all acting as a self-perpetuating spiral of events. The problem is confounded by the high prevalence of antithrombotic agent use in these patients and intraoperative heparin administration. Trials specifically examining bleeding management in vascular surgery are lacking, and much of the literature and guidelines are derived from studies on patients with trauma. In general, it is recommended to adopt permissive hypotension with a restrictive fluid strategy, using a combination of crystalloid and colloid solutions up to one litre during the initial resuscitation, after which blood products should be administered. A restrictive transfusion trigger for red cells remains the mainstay of treatment except for the high-risk patients, where the trigger should be individualized. Transfusion of blood components should be initiated by clinical evidence of coagulopathy such as diffuse microvascular bleeding, and then guided by either laboratory or point-of-care coagulation testing. Prophylactic antifibrinolytic use is recommended for all surgery where excessive bleeding is anticipated. Fibrinogen and prothrombin complex concentrates administration are recommended during massive transfusion, whereas rFVIIa should be reserved until all means have failed. While debates over the ideal resuscitative strategy continue, the approach to vascular haemostasis should be scientific, rational, and structured. As far as possible, therapy should be monitored and goal directed. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effects of laughter therapy on mood state and self-esteem in cancer patients undergoing radiation therapy: a randomized controlled trial.

PubMed

Kim, So Hee; Kook, Jeong Ran; Kwon, Moonjung; Son, Myeong Ha; Ahn, Seung Do; Kim, Yeon Hee

2015-04-01

To investigate whether laughter therapy lowers total mood disturbance scores and improves self-esteem scores in patients with cancer. Randomized controlled trial in a radio-oncology outpatient setting. Sixty-two patients were enrolled and randomly assigned to the experimental group (n=33) or the wait list control group (n=29). Three laughter therapy sessions lasting 60 minutes each. Mood state and self-esteem. The intention-to-treat analysis revealed a significant main effect of group: Experimental group participants reported a 14.12-point reduction in total mood disturbance, while the wait list control group showed a 1.21-point reduction (p=0.001). The per-protocol analysis showed a significant main effect of group: The experimental group reported a 18.86-point decrease in total mood disturbance, while controls showed a 0.19-point reduction (p<0.001). The self-esteem of experimental group was significantly greater than that of the wait list control group (p=0.044). These results indicate that laughter therapy can improve mood state and self-esteem and can be a beneficial, noninvasive intervention for patients with cancer in clinical settings.

Gene Therapy for Metachromatic Leukodystrophy

PubMed Central

Rosenberg, Jonathan B.; Kaminsky, Stephen M.; Aubourg, Patrick; Crystal, Ronald G.; Sondhi, Dolan

2016-01-01

Summary Leukodystrophies are rare white matter genetic disorders of the central nervous system (CNS) with progressive neurologic deterioration. One approach to the treatment of leukodystrophies is by gene therapy. Using metachromatic leukodystrophy (MLD), a leukodystrophy resulting from deficiency of a lysosomal catabolic enzyme arylsulfatase A (ARSA) as the example, this review is focused on the current status of preclinical and clinical development of gene therapy as a viable treatment option for leukodystrophies. In MLD, mutations in the ARSA gene result in excess buildup of sulfatides, which triggers apoptosis of glia and neurons. The disease is characterized by severe cerebral demyelination and atrophy, with progressive loss of oligodendrocytes, neurons and Schwann cells. The optimal therapy for MLD would provide persistent and high level expression of ARSA in the CNS. Gene therapy using adeno-associated virus (AAV) is an ideal choice for clinical development as it provides the best balance of potential for efficacy with a reduced safety risk profile. In this review, we have summarized preclinical data that support the use of a gene therapy with the AAVrh.10 serotype for clinical development as a treatment for MLD. PMID:27638601

Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis

PubMed Central

Xia, Wenle; Gooden, David; Liu, Leihua; Zhao, Sumin; Soderblom, Erik J.; Toone, Eric J.; Beyer, Wayne F.; Walder, Harold; Spector, Neil L.

2014-01-01

Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL) that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen) interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85ErbB2) that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85ErbB2. Here we show that PUVA reduced p85ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies. PMID:24551203

Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.

PubMed

Niu, Chengcheng; Wang, Zhigang; Lu, Guangming; Krupka, Tianyi M; Sun, Yang; You, Yufang; Song, Weixiang; Ran, Haitao; Li, Pan; Zheng, Yuanyi

2013-03-01

Current strategies for tumor-induced sentinel lymph node detection and metastasis therapy have limitations. In this work, we co-encapsulated iron oxide nanoparticles and chemotherapeutic drug into poly(lactic-co-glycolic acid) (PLGA) microbubbles to form multifunctional polymer microbubbles (MPMBs) for both tumor lymph node imaging and therapy. Fe(3)O(4) nanoparticles and doxorubicin (DOX) co-encapsulated PLGA microbubbles were prepared and filled with perfluorocarbon gas. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging and US triggered drug delivery were evaluated both in vitro and in vivo. The MPMBs exhibited characters like narrow size distribution and smooth surface with a mean diameter of 868.0 ± 68.73 nm. In addition, varying the concentration of Fe(3)O(4) nanoparticles in the bubbles did not significantly influence the DOX encapsulation efficiency or drug loading efficiency. Our in vitro results demonstrated that these MPMBs could enhance both US and MR imaging which was further validated in vivo showing that these MPMBs enhanced tumor lymph nodes signals. The anti-tumor effect of MPMBs mediated chemotherapy was assessed in vivo using end markers like tumor proliferation index, micro blood vessel density and micro lymphatic vessel density, which were shown consistently the lowest after the MPMBs plus sonication treatment compared to controls. In line with these findings, the tumor cell apoptotic index was found the largest after the MPMBs plus sonication treatment. In conclusion, we have successfully developed a doxorubicin loaded superparamagnetic PLGA-Iron Oxide multifunctional theranostic agent for dual-mode US/MR Imaging of lymph node, and for low frequency US triggered therapy of metastasis in lymph nodes, which might provide a strategy for the imaging and chemotherapy of primary tumor and their metastases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft.

PubMed

Böhmig, G A; Regele, H; Säemann, M D; Exner, M; Druml, W; Kovarik, J; Hörl, W H; Zlabinger, G J; Watschinger, B

2000-04-01

Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding antibody-mediated allograft dysfunction is warranted because immunoadsorption may be a highly effective treatment modality.

Light-triggerable formulations for the intracellular controlled release of biomolecules.

PubMed

Lino, Miguel M; Ferreira, Lino

2018-05-01

New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations. We further discuss the opportunities offered by these formulations in terms of endosomal escape, as well as their limitations. Copyright © 2018 Elsevier Ltd. All rights reserved.

An experimental test of the 'transmission-line model' of electromagnetic radiation from triggered lightning return strokes

NASA Technical Reports Server (NTRS)

Willett, J. C.; Idone, V. P.; Orville, R. E.; Leteinturier, C.; Eybert-Berard, A.

1988-01-01

Peak currents, two-dimensional average propagation speeds, and electric field waveforms for a number of subsequent return strikes in rocket-triggered lightning flashes were measured in order to test the 'transmission-line model' of return-stroke radiation of Uman and McLain (1970). Reasonable agreement is found between the propagation speeds measured with the streak camera and those deduced from the transmission-line model. A modification of the model is proposed in which two wave fronts travel upward and downward away from a junction point a short distance above the ground.

Readout and Trigger for the AFP Detector at the ATLAS Experiment at LHC

NASA Astrophysics Data System (ADS)

Korcyl, K.; Kocian, M.; Lopez Paz, I.; Avoni, G.

2017-10-01

The ATLAS Forward Proton is a new detector system in ATLAS that allows study of events with protons scattered at very small angles. The final design assumes four stations at distances of 205 and 217 m from the ATLAS interaction point on both sides of the detector exploiting the Roman Pot technology. In 2016 two stations in one arm were installed; installation of the other two is planned for 2017. This article describes details of the installed hardware, firmware and software leading to the full integration with the ATLAS central trigger and data acquisition systems.

An experimental test of the 'transmission-line model' of electromagnetic radiation from triggered lightning return strokes

NASA Astrophysics Data System (ADS)

Willett, J. C.; Idone, V. P.; Orville, R. E.; Leteinturier, C.; Eybert-Berard, A.

1988-04-01

Peak currents, two-dimensional average propagation speeds, and electric field waveforms for a number of subsequent return strikes in rocket-triggered lightning flashes were measured in order to test the 'transmission-line model' of return-stroke radiation of Uman and McLain (1970). Reasonable agreement is found between the propagation speeds measured with the streak camera and those deduced from the transmission-line model. A modification of the model is proposed in which two wave fronts travel upward and downward away from a junction point a short distance above the ground.

A glycoporphyrin story: from chemistry to PDT treatment of cancer mouse models.

PubMed

Lupu, M; Maillard, Ph; Mispelter, J; Poyer, F; Thomas, C D

2018-06-01

Photodynamic therapy (PDT) represents a non-toxic and non-mutagenic antitumor therapy. The photosensitizer's (PS) chemo-physical properties are essential for the therapy, being responsible for the biological effects induced in the targeted tissues. In this study, we present the synthesis and development of some glycoconjugated porphyrins based on lectin-type receptor interaction. They were tested in vitro for finally choosing the most effective chemical structure for an optimum antitumor outcome. The most effective photosensitizer is substituted by three diethylene glycol α-d-mannosyl groups. In vivo studies allow firstly the determination of some characteristics of the biological processes triggered by the initial photochemical activation. Secondly, they make it possible to improve the therapeutic protocol in the function of the structural architecture of the targeted tumor tissue.

The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics.

PubMed

McGovern, Eavan M; Roze, Emmanuel; Counihan, Timothy J

2018-05-15

This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.

Targeting CD4+ T cells for the treatment of sarcoidosis: a promising strategy?

PubMed Central

Celada, Lindsay J; Drake, Wonder P

2017-01-01

Sarcoidois is an inflammatory disease of unknown origin characterized by the abnormal accumulation of noncaseating granulomas at sites of disease activity in multiple organs throughout the body with a predilection for the lungs. Because the exact trigger that leads to disease activity is still under investigation, current treatment options are contingent on the organ or organs affected. Corticosteroids are the therapy of choice, but antimalarials and TNF-α antagonists are also commonly prescribed. Recent findings provide evidence for the use of CD20 B-cell-depleting therapy as an alternative method of choice. However, because sarcoidosis is predominantly a T-helper cell-driven disorder, an overwhelming amount of compelling evidence exists for the use of CD4+ T-cell targeted therapy. PMID:25572480

Tinnitus retraining therapy: mixing point and total masking are equally effective.

PubMed

Tyler, Richard S; Noble, William; Coelho, Claudia Barros; Ji, Haihong

2012-01-01

Habituation to tinnitus cannot occur with total masking, an argument made by proponents of "tinnitus retraining therapy." We also compared the effectiveness of retraining therapy with mixing-point masking, total masking, and with counseling alone. Forty-eight tinnitus patients were randomly assigned to one of three groups: counseling, counseling plus bilateral noise generators set to completely mask the tinnitus, or counseling plus bilateral noise generators with a focus on the mixing point (partial masking just below total masking). A picture-based counseling protocol was used to assist in providing similar counseling among all three groups. The Tinnitus Handicap Questionnaire was administered before and after about 12 months of treatment. After 12 months, in the counseling group, three of 18 patients benefited significantly, in the mixing-point group, six of 19 patients benefited, and in the total masking group, four of 11 patients benefited from the treatment. The average decrease in the questionnaire was 16.7% for the counseling group, 31.6% for the retraining group, and 36.4% for the total masking group. No significant average differences among groups were observed. One premise of retraining therapy is incorrect; a focus on mixing-point masking is not required for habituation.

Are tender point injections beneficial: the role of tonic nociception in fibromyalgia.

PubMed

Staud, Roland

2006-01-01

Characteristic symptoms of fibromyalgia syndrome (FM) include widespread pain, fatigue, sleep abnormalities, and distress. FM patients show psychophysical evidence for mechanical, thermal, and electrical hyperalgesia. To fulfill FM criteria, the mechanical hyperalgesia needs to be widespread and present in at least 11 out of 18 well-defined body areas (tender points). Peripheral and central abnormalities of nociception have been described in FM and these changes may be relevant for the increased pain experienced by these patients. Important nociceptor systems in the skin and muscle seem to undergo profound changes in FM patients by yet unknown mechanisms. These changes may result from the release of algesic substances after muscle or other soft tissue injury. These pain mediators can sensitize important nociceptor systems, including the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), acid sensing ion channel (ASIC) receptors, and purino-receptors (P2X3). Subsequently, tissue mediators of inflammation and nerve growth factors can excite these receptors and cause substantial changes in pain sensitivity. FM pain is widespread and does not seem to be restricted to tender points (TP). It frequently comprises multiple areas of deep tissue pain (trigger points) with adjacent much larger areas of referred pain. Analgesia of areas of extensive nociceptive input has been found to provide often long lasting local as well as general pain relief. Thus interventions aimed at reducing local FM pain seem to be effective but need to focus less on tender points but more on trigger points (TrP) and other body areas of heightened pain and inflammation.

``Smart'' theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy

NASA Astrophysics Data System (ADS)

Zhang, Yan; Das, Gautom Kumar; Vijayaragavan, Vimalan; Xu, Qing Chi; Padmanabhan, Parasuraman; Bhakoo, Kishore K.; Tamil Selvan, Subramanian; Tan, Timothy Thatt Yang

2014-10-01

The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01717j

Management of rosacea-prone skin: evaluation of a skincare product containing Ambophenol, Neurosensine, and La Roche-Posay Thermal spring water as monotherapy or adjunctive therapy.

PubMed

Seite, Sophie; Benech, Florence; Berdah, Sandrine; Bayer, Muriel; Veyrat, Sophie; Segot, Evelyne; Sakalikova, Marcela; Gibejova, Lucia; Zelenkova, Hana

2013-08-01

The objective of these studies was to investigate whether a skincare product containing Ambophenol, Neurosensine, and La Roche-Posay thermal spring water formulated in a highly protective packaging can have an impact in the management of rosacea-prone skin subjects. Several studies were performed to evaluate the efficacy of this product in the management of rosacea prone skin, as either monotherapy or adjunctive therapy or to maintain the efficacy of a Metronidazole treatment. The first study was performed on 37 women aged 18-45 with added stage 2 erythro-couperosis, who applied test formula as monotherapy twice a day for 4 weeks. During a second study, a dermatological evaluation was performed on patients with stage I or II rosacea, a questionnaire containing information about patient characteristics, tolerance, clinical signs, symptoms and skin reactivity to "trigger factors" was completed by dermatologists at baseline and 2 months after treatment with the test formula as either monotherapy or adjunctive therapy. Finally, in a third study, 65 patients finishing a Metronidazole treatment applied once daily and the tested formula twice daily were divided into 2 groups using the test formula or vehicle control, twice a day for 8 weeks for the evaluation of efficacy as adjunctive therapy. We noted that the test formula, as an adjunctive therapy, helped prolong the efficacy of a Metronidazole treatment. In monotherapy, there was a significant efficacy of the test formula associated with an excellent tolerance. A significant improvement of all the clinical signs and symptoms of rosacea and a reduction of the skin reactivity to "trigger factors" were shown. These studies highlight the interest value and impact of a skincare product containing Ambophenol, Neurosensine, and La Roche-Posay thermal spring water formulated in a highly protective packaging in monotherapy or in combination with or after a therapeutic treatment in the management of patients suffering from rosacea.

Health monitoring with optical fiber sensors: from human body to civil structures

NASA Astrophysics Data System (ADS)

Pinet, Éric; Hamel, Caroline; Glišić, Branko; Inaudi, Daniele; Miron, Nicolae

2007-04-01

Although structural health monitoring and patient monitoring may benefit from the unique advantages of optical fiber sensors (OFS) such as electromagnetic interferences (EMI) immunity, sensor small size and long term reliability, both applications are facing different realities. This paper presents, with practical examples, several OFS technologies ranging from single-point to distributed sensors used to address the health monitoring challenges in medical and in civil engineering fields. OFS for medical applications are single-point, measuring mainly vital parameters such as pressure or temperature. In the intra-aortic balloon pumping (IABP) therapy, a miniature OFS can monitor in situ aortic blood pressure to trigger catheter balloon inflation/deflation in counter-pulsation with heartbeats. Similar sensors reliably monitor the intracranial pressure (ICP) of critical care patients, even during surgical interventions or examinations under medical resonance imaging (MRI). Temperature OFS are also the ideal monitoring solution for such harsh environments. Most of OFS for structural health monitoring are distributed or have long gage length, although quasi-distributed short gage sensors are also used. Those sensors measure mainly strain/load, temperature, pressure and elongation. SOFO type deformation sensors were used to monitor and secure the Bolshoi Moskvoretskiy Bridge in Moscow. Safety of Plavinu dam built on clay and sand in Latvia was increased by monitoring bitumen joints displacement and temperature changes using SMARTape and Temperature Sensitive Cable read with DiTeSt unit. A similar solution was used for monitoring a pipeline built in an unstable area near Rimini in Italy.

Consensus Paper: Pathological Mechanisms Underlying Neurodegeneration in Spinocerebellar Ataxias

PubMed Central

Matilla-Dueñas, A.; Ashizawa, T.; Brice, A.; Magri, S.; McFarland, K. N.; Pandolfo, M.; Pulst, S. M.; Riess, O.; Rubinsztein, D. C.; Schmidt, J.; Schmidt, T.; Scoles, D. R.; Stevanin, G.; Taroni, F.; Underwood, B. R.; Sánchez, I.

2014-01-01

Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice. PMID:24307138

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

PubMed

Simpson, Eric L; Bruin-Weller, Marjolein; Flohr, Carsten; Ardern-Jones, Michael R; Barbarot, Sebastien; Deleuran, Mette; Bieber, Thomas; Vestergaard, Christian; Brown, Sara J; Cork, Michael J; Drucker, Aaron M; Eichenfield, Lawrence F; Foelster-Holst, Regina; Guttman-Yassky, Emma; Nosbaum, Audrey; Reynolds, Nick J; Silverberg, Jonathan I; Schmitt, Jochen; Seyger, Marieke M B; Spuls, Phyllis I; Stalder, Jean-Francois; Su, John C; Takaoka, Roberto; Traidl-Hoffmann, Claudia; Thyssen, Jacob P; van der Schaft, Jorien; Wollenberg, Andreas; Irvine, Alan D; Paller, Amy S

2017-10-01

Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. Our work is a consensus statement, not a systematic review. The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability

PubMed Central

Bose, Sayantan; Heath, Carissa M.; Shah, Priya A.; Alayyoubi, Maher; Jardetzky, Theodore S.

2013-01-01

Paramyxovirus membrane glycoproteins F (fusion protein) and HN, H, or G (attachment protein) are critical for virus entry, which occurs through fusion of viral and cellular envelopes. The F protein folds into a homotrimeric, metastable prefusion form that can be triggered by the attachment protein to undergo a series of structural rearrangements, ultimately folding into a stable postfusion form. In paramyxovirus-infected cells, the F protein is activated in the Golgi apparatus by cleavage adjacent to a hydrophobic fusion peptide that inserts into the target membrane, eventually bringing the membranes together by F refolding. However, it is not clear how the attachment protein, known as HN in parainfluenza virus 5 (PIV5), interacts with F and triggers F to initiate fusion. To understand the roles of various F protein domains in fusion triggering and metastability, single point mutations were introduced into the PIV5 F protein. By extensive study of F protein cleavage activation, surface expression, and energetics of fusion triggering, we found a role for an immunoglobulin-like (Ig-like) domain, where multiple hydrophobic residues on the PIV5 F protein may mediate F-HN interactions. Additionally, destabilizing mutations of PIV5 F that resulted in HN trigger-independent mutant F proteins were identified in a region along the border of F trimer subunits. The positions of the potential HN-interacting region and the region important for F stability in the lower part of the PIV5 F prefusion structure provide clues to the receptor-binding initiated, HN-mediated F trigger. PMID:24089572

Mexican case report of a never-treated Laron syndrome patient evolving to metabolic syndrome, type 2 diabetes, and stroke.

PubMed

Castilla-Cortazar, Inma; Femat-Roldán, Giovana; Rodríguez-Rivera, Joel; Aguirre, Gabriel A; García-Magariño, Mariano; Martín-Estal, Irene; Espinosa, Luis; Díaz-Olachea, Carlos

2017-11-01

Glucose and lipid profile together with blood pressure should always be considered for low sera-IGF-1 patients. Even when adulthood is reached, IGF-1 therapy in these patients should be pursued as metabolic and protective cellular effects could be triggered. Real incidence of growth hormone insensitivity is still to be uncovered.

Versatile Polymer Nanoparticles as Two-Photon-Triggered Photosensitizers for Simultaneous Cellular, Deep-Tissue Imaging, and Photodynamic Therapy.

PubMed

Guo, Liang; Ge, Jiechao; Liu, Qian; Jia, Qingyan; Zhang, Hongyan; Liu, Weimin; Niu, Guangle; Liu, Sha; Gong, Jianru; Hackbarth, Steffen; Wang, Pengfei

2017-06-01

Clinical applications of current photodynamic therapy (PDT) photosensitizers (PSs) are often limited by their absorption in the UV-vis range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. Alternatively, two-photon excited PS (TPE-PS) using NIR light triggered is one the most promising candidates for PDT improvement. Herein, multimodal polymer nanoparticles (PNPs) from polythiophene derivative as two-photon fluorescence imaging as well as two-photon-excited PDT agent are developed. The prepared PNPs exhibit excellent water dispersibility, high photostability and pH stability, strong fluorescence brightness, and low dark toxicity. More importantly, the PNPs also possess other outstanding features including: (1) the high 1 O 2 quantum yield; (2) the strong two-photon-induced fluorescence and efficient 1 O 2 generation; (3) the specific accumulation in lysosomes of HeLa cells; and (4) the imaging detection depth up to 2100 µm in the mock tissue under two-photon. The multifunctional PNPs are promising candidates as TPE-PDT agent for simultaneous cellular, deep-tissue imaging, and highly efficient in vivo PDT of cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer.

PubMed

Ding, Hui; Lv, Yanlin; Ni, Dezhi; Wang, Jie; Tian, Zhiyuan; Wei, Wei; Ma, Guanghui

2015-06-07

A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.

Reaction of tetracycline with biologically relevant chloramines

NASA Astrophysics Data System (ADS)

Benavides, J.; Barrias, P.; Piro, N.; Arenas, A.; Orrego, A.; Pino, E.; Villegas, L.; Dorta, E.; Aspée, A.; López-Alarcón, C.

2017-05-01

Helicobacter pylori (H. pylori) infection triggers inflammatory processes with the consequent production of hypochlorous acid (HOCl), monochloramine (NH2Cl), and protein-derived chloramines. As the therapy for eradicating H. pylori is partially based on the use of tetracycline, we studied the kinetic of its consumption elicited by HOCl, NH2Cl, N-chloro-n-butylamine (NHCl-But, used as a lysine-derived chloramine model), and lysozyme-derived chloramines. In the micromolar concentration range, tetracycline reacted rapidly with HOCl, generating in the first few seconds intermediates of short half-life. In contrast, a slow tetracycline consumption was observed in the presence of high NH2Cl and NHCl-But concentrations (millimolar range). Similar chlorinated products of tetracycline were identified by mass spectrometry, in the presence of HOCl and NH2Cl. These results evidenced that tautomers of tetracycline are pivotal intermediates in all reactions. In spite of the low reactivity of chloramines towards tetracycline, it is evident that, in the concentration range where they are produced in a H. pylori infection (millimolar range), the reactions lead to oxidation and/or chlorination of tetracycline. This kind of reactions, which were also observed triggered by lysozyme-derived chloramines, could limit the efficiency of the tetracycline-based therapy.

Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

NASA Astrophysics Data System (ADS)

Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng

2015-01-01

The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

Acidity-Triggered Tumor Retention/Internalization of Chimeric Peptide for Enhanced Photodynamic Therapy and Real-Time Monitoring of Therapeutic Effects.

PubMed

Han, Kai; Zhang, Wei-Yun; Ma, Zhao-Yu; Wang, Shi-Bo; Xu, Lu-Ming; Liu, Jia; Zhang, Xian-Zheng; Han, He-You

2017-05-17

Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anions in chimeric peptide, which led to increased ζ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric peptide. All of these factors realized superfast accumulation and prolonged retention in the tumor region, selective cellular internalization, and enhanced PDT against the tumor. Meanwhile, this chimeric peptide could further generate reactive oxygen species and initiate cell apoptosis during PDT. The subsequent formation of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional Asp-Glu-Val-Asp-Gly (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the preparation and increased the performance of the chimeric peptide furthest.

Co-administration of liposomal l-OHP and PEGylated TS shRNA-lipoplex: A novel approach to enhance anti-tumor efficacy and reduce the immunogenic response to RNAi molecules.

PubMed

Alaaeldin, Eman; Abu Lila, Amr S; Ando, Hidenori; Fukushima, Masakazu; Huang, Cheng-Long; Wada, Hiromi; Sarhan, Hatem A; Khaled, Khaled A; Ishida, Tatsuhiro

2017-06-10

Many therapeutic strategies have been applied in efforts to conquer the development and/or progression of cancer. The combination of chemotherapy and an RNAi-based approach has proven to be an efficient anticancer therapy. However, the feasibility of such a therapeutic strategy has been substantially restricted either by the failure to achieve the efficient delivery of RNAi molecules to tumor tissue or by the immunostimulatory response triggered by RNAi molecules. In this study, therefore, we intended to investigate the efficacy of using liposomal oxaliplatin (liposomal l-OHP) to guarantee the efficient delivery of RNAi molecules, namely shRNA against thymidylate synthase (TS shRNA) complexed with cationic liposome (TS shRNA-lipoplex), to solid tumors, and to suppress the immunostimulatory effect of RNAi molecules, TS shRNA, following intravenous administration. Herein, we describe how liposomal l-OHP enhanced the intra-tumor accumulation of TS shRNA-lipoplex and significantly reduced the immunostimulatory response triggered by TS shRNA. Consequently, such enhanced accumulation of TS shRNA-lipoplex along with the cytotoxic effect of liposomal l-OHP led to a remarkable tumor growth suppression (compared to mono-therapy) following systemic administration. Our results, therefore, may have important implications for the provision of a safer and more applicable combination therapy of RNAi molecules and anti-cancer agents that can produce a more reliable anti-tumor effect. Copyright © 2017 Elsevier B.V. All rights reserved.

RNA Structure Design Improves Activity and Specificity of trans-Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach.

PubMed

Poddar, Sushmita; Loh, Pei She; Ooi, Zi Hao; Osman, Farhana; Eul, Joachim; Patzel, Volker

2018-06-01

Spliceosome-mediated RNA trans-splicing enables correction or labeling of pre-mRNA, but therapeutic applications are hampered by issues related to the activity and target specificity of trans-splicing RNA (tsRNA). We employed computational RNA structure design to improve both on-target activity and specificity of tsRNA in a herpes simplex virus thymidine kinase/ganciclovir suicide gene therapy approach targeting alpha fetoprotein (AFP), a marker of hepatocellular carcinoma (HCC) or human papillomavirus type 16 (HPV-16) pre-mRNA. While unstructured, mismatched target binding domains significantly improved 3' exon replacement (3'ER), 5' exon replacement (5'ER) correlated with the thermodynamic stability of the tsRNA 3' end. Alternative on-target trans-splicing was found to be a prevalent event. The specificity of trans-splicing with the intended target splice site was improved 10-fold by designing tsRNA that harbors secondary target binding domains shielding alternative on-target and blinding off-target splicing events. Such rationally designed suicide RNAs efficiently triggered death of HPV-16-transduced or hepatoblastoma-derived human tissue culture cells without evidence for off-target cell killing. Highest cell death activities were observed with novel dual-targeting tsRNAs programmed for trans-splicing toward AFP and a second HCC pre-mRNA biomarker. Our observations suggest trans-splicing represents a promising approach to suicide gene therapy. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Muscarinic Receptors as Targets for Metronomic Therapy in Breast Cancer.

PubMed

Sales, María Elena

2016-01-01

It is actually known that acetylcholine works as a signaling molecule in non-neuronal cells and tissues, in addition to its neuronal function as neurotransmitter. It can act on two types of receptors nicotinic and muscarinic receptors (mAChRs). The latter belong to the G protein coupled receptor family and there are five subtypes genetically cloned. Their activation triggers classical and non-classical intracellular signals that could be linked to the proliferation of normal and/or transformed cells. The M3 subtype was identified in different types of tumors and its stimulation with agonists triggers cell proliferation, migration, invasion and metastasis. Our laboratory has extensively investigated the expression and function of mAChRs in breast tumors from animal and human origins. We found a profuse expression of mAChRs in breast tumors, but opposite to this, an absence of these receptors in normal breast cells and tissues. The stimulation of mAChRs with the cholinergic agonist carbachol for 20 h increased tumor cell death. Moreover, the combination of subthreshold concentrations of the agonist with paclitaxel potentiates cell death. The usage of low dose chemotherapy with short drug free intervals was named metronomic therapy and it has emerged as a novel regimen for cancer treatment with very low incidence of side effects. Our work and that of others indicate that mAChRs that are over-expressed in different types of tumor cells could be a useful target for metronomic therapy in cancer treatment.

Boron neutron capture therapy: Moving toward targeted cancer therapy.

PubMed

Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

2016-01-01

Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

The trigger mechanism of low-frequency earthquakes on Montserrat

NASA Astrophysics Data System (ADS)

Neuberg, J. W.; Tuffen, H.; Collier, L.; Green, D.; Powell, T.; Dingwell, D.

2006-05-01

A careful analysis of low-frequency seismic events on Soufrièere Hills volcano, Montserrat, points to a source mechanism that is non-destructive, repetitive, and has a stationary source location. By combining these seismological clues with new field evidence and numerical magma flow modelling, we propose a seismic trigger model which is based on brittle failure of magma in the glass transition. Loss of heat and gas from the magma results in a strong viscosity gradient across a dyke or conduit. This leads to a build-up of shear stress near the conduit wall where magma can rupture in a brittle manner, as field evidence from a rhyolitic dyke demonstrates. This brittle failure provides seismic energy, the majority of which is trapped in the conduit or dyke forming the low-frequency coda of the observed seismic signal. The trigger source location marks the transition from ductile conduit flow to friction-controlled magma ascent. As the trigger mechanism is governed by the depth-dependent magma parameters, the source location remains fixed at a depth where the conditions allow brittle failure. This is reflected in the fixed seismic source locations.

Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment

NASA Astrophysics Data System (ADS)

Chen, Fengqian; Zhang, Jinming; Wang, Lu; Wang, Yitao; Chen, Meiwan

2015-09-01

The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy.The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04612b

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

PubMed Central

Nardoni, Martina; della Valle, Elena; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

2018-01-01

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects. PMID:29584700

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

PubMed

Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

2018-03-27

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

Functional Interrupts and Destructive Failures from Single Event Effect Testing of Point-Of-Load Devices

NASA Technical Reports Server (NTRS)

Chen, Dakai; Phan, Anthony; Kim, Hak; Swonger, James; Musil, Paul; LaBel, Kenneth

2013-01-01

We show examples of single event functional interrupt and destructive failure in modern POL devices. The increasing complexity and diversity of the design and process introduce hard SEE modes that are triggered by various mechanisms.

Cortical changes after mental imagery training combined with electromyography-triggered electrical stimulation in patients with chronic stroke.

PubMed

Hong, Il Ki; Choi, Jong Bae; Lee, Jong Ha

2012-09-01

Paresis of the upper extremity after stroke is not effectively solved by existing therapies. We investigated whether mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic upper extremity in patients with chronic stroke and induced cortical changes. Fourteen subjects with chronic stroke (≥12 months) were randomly allocated to receive mental imagery training combined with electromyogram-triggered electric stimulation (n=7) or generalized functional electric stimulation (n=7) on the forearm extensor muscles of the paretic extremity in 2 20-minute daily sessions 5 days a week for 4 weeks. The upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Activity Log, the modified Barthel Index, and (18)F-fluorodeoxyglucose brain positron emission tomography were measured before and after the intervention. The group receiving mental imagery training combined with electromyogram-triggered electric stimulation exhibited significant improvements in the upper extremity component of the Fugl-Meyer Motor Assessment after intervention (median, 7; interquartile range, 5-8; P<0.05), but the group receiving functional electric stimulation did not (median, 0; interquartile range, 0-3). Differences in score changes between the 2 groups were significant. The mental imagery training combined with electromyogram-triggered electric stimulation group showed significantly increased metabolism in the contralesional supplementary motor, precentral, and postcentral gyri (P(uncorrected)<0.001) after the intervention, but the functional electric stimulation group showed no significant differences. Mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic extremity in patients with chronic stroke. The intervention increased metabolism in the contralesional motor-sensory cortex. Clinical Trial Registration- URL: https://e-irb.khmccri.or.kr/eirb/receipt/index.html?code=02&status=5. Unique identifier: KHUHMDIRB 1008-02.

Electroconvulsive therapy in Parkinson's disease.

PubMed

Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

2015-10-01

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

Endotracheal suction in intensive care: A point prevalence study of current practice in New Zealand and Australia.

PubMed

Gilder, Eileen; Parke, Rachael L; Jull, Andrew

2018-04-14

Despite the evidence and available guidelines about endotracheal suction (ETS), a discrepancy between published guidelines and clinical practice persists. To date, ETS practice in the adult intensive care unit (ICU) population across New Zealand and Australia has not been described. To describe ICU nurses' ETS practice in New Zealand and Australia including the triggers for performing endotracheal suction. A single day, prospective observational, binational, multicentre point prevalence study in New Zealand and Australian ICUs. All adult patients admitted at 10:00 on the study day were included. In addition to patient demographic data, we assessed triggers for ETS, suction canister pressures, use of preoxygenation, measures of oxygenation, and ETS at extubation. There were 682 patients in the ICUs on the study day, and 230 were included in the study. Three of 230 patients were excluded for missing data. A total of 1891 ETS events were performed on 227 patients during the study day, a mean of eight interventions per patient. The main triggers reported were audible (n = 385, 63%) and visible (n = 239, 39%) secretions. Less frequent triggers included following auscultation (n = 142, 23%), reduced oxygen saturations (n = 140, 22%), and ventilator waveforms (n = 53, 9%). Mean suction canister pressure was -337 mmHg (standard deviation = 189), 67% of patients received preoxygenation (n = 413), and ETS at extubation was performed by 84% of nurses. Some practices were inconsistent with international guidelines, in particular concerning patient assessment for ETS and suction canister pressure. Copyright © 2018 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Hydrogen peroxide induced by the fungicide prothioconazole triggers deoxynivalenol (DON) production by Fusarium graminearum

PubMed Central

2010-01-01

Background Fusarium head blight is a very important disease of small grain cereals with F. graminearum as one of the most important causal agents. It not only causes reduction in yield and quality but from a human and animal healthcare point of view, it produces mycotoxins such as deoxynivalenol (DON) which can accumulate to toxic levels. Little is known about external triggers influencing DON production. Results In the present work, a combined in vivo/in vitro approach was used to test the effect of sub lethal fungicide treatments on DON production. Using a dilution series of prothioconazole, azoxystrobin and prothioconazole + fluoxastrobin, we demonstrated that sub lethal doses of prothioconazole coincide with an increase in DON production 48 h after fungicide treatment. In an artificial infection trial using wheat plants, the in vitro results of increased DON levels upon sub lethal prothioconazole application were confirmed illustrating the significance of these results from a practical point of view. In addition, further in vitro experiments revealed a timely hyperinduction of H2O2 production as fast as 4 h after amending cultures with prothioconazole. When applying H2O2 directly to germinating conidia, a similar induction of DON-production by F. graminearum was observed. The effect of sub lethal prothioconazole concentrations on DON production completely disappeared when applying catalase together with the fungicide. Conclusions These cumulative results suggest that H2O2 induced by sub lethal doses of the triazole fungicide prothioconazole acts as a trigger of DON biosynthesis. In a broader framework, this work clearly shows that DON production by the plant pathogen F. graminearum is the result of the interaction of fungal genomics and external environmental triggers. PMID:20398299

Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: A randomized, placebo-controlled clinical trial

PubMed Central

Moraska, Albert F.; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P.; Schmiege, Sarah J.; Mann, J. Douglas

2014-01-01

Objective Myofascial trigger points (MTrPs) are focal disruptions in skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type headache (TTH). The present study applied massage focused on MTrPs of subjects with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache pain. Methods Fifty-six subjects with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over six weeks, or to wait-list. Trigger point release (TPR) massage focused on MTrPs in cervical musculature. Headache pain (frequency, intensity and duration) was recorded in a daily headache diary. Additional outcome measures included self-report of perceived clinical change in headache pain and pressure-pain threshold (PPT) at MTrPs in the upper trapezius and sub-occipital muscles. Results From diary recordings, group differences across time were detected in headache frequency (p=0.026), but not for intensity or duration. Post hoc analysis indicated headache frequency decreased from baseline for both massage (p<0.0003) and placebo (p=0.013), but no difference was detected between massage and placebo. Subject report of perceived clinical change was a greater reduction in headache pain for massage than placebo or wait-list groups (p=0.002). PPT improved in all muscles tested for massage only (all p's<0.002). Discussion Two findings from this study are apparent: 1) MTrPs are important components in the treatment of TTH, and 2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention. PMID:25329141

Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: a randomized, placebo-controlled clinical trial.

PubMed

Moraska, Albert F; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P; Schmiege, Sarah J; Mann, John D

2015-02-01

Myofascial trigger points (MTrPs) are focal disruptions in the skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type HA (TTH). The present study applied massage focused on MTrPs of patients with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache (HA) pain. Fifty-six patients with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over 6 weeks, or to wait-list. Trigger point release massage focused on MTrPs in cervical musculature. HA pain (frequency, intensity, and duration) was recorded in a daily HA diary. Additional outcome measures included self-report of perceived clinical change in HA pain and pressure-pain threshold at MTrPs in the upper trapezius and suboccipital muscles. From diary recordings, group differences across time were detected in HA frequency (P=0.026), but not for intensity or duration. Post hoc analysis indicated that HA frequency decreased from baseline for both massage (P<0.0003) and placebo (P=0.013), but no difference was detected between massage and placebo. Patient report of perceived clinical change was greater reduction in HA pain for massage than placebo or wait-list groups (P=0.002). Pressure-pain threshold improved in all muscles tested for massage only (all P's<0.002). Two findings from this study are apparent: (1) MTrPs are important components in the treatment of TTH, and (2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on HA that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention.

Ultrasonography of the hand, wrist, and elbow.

PubMed

Bodor, Marko; Fullerton, Brad

2010-08-01

High-frequency diagnostic ultrasonography of the hand, wrist and elbow has significant potential to improve the quality of diagnosis and care provided by neuromuscular and musculoskeletal specialists. In patients referred for weakness, pain and numbness of the hand, wrist or elbow, diagnostic ultrasonography can be an adjunct to electrodiagnosis and help in identifying ruptured tendons and treating conditions such as carpal tunnel syndrome or trigger finger. Use of a small high-frequency (>10-15 MHz) transducer, an instrument with a blunt pointed tip to enhance sonopalpation and a model of the hand, wrist and elbow is advised to enhance visualization of small anatomical structures and complex bony contours. A range of conditions, including tendon and ligament ruptures, trigger finger, de Quervain tenosynovitis, intersection syndrome, lateral epicondylitis, and osteoarthritis, is described along with detailed ultrasonography-guided injection techniques for carpal tunnel syndrome and trigger finger. Copyright 2010 Elsevier Inc. All rights reserved.

Generating functions and stability study of multivariate self-excited epidemic processes

NASA Astrophysics Data System (ADS)

Saichev, A. I.; Sornette, D.

2011-09-01

We present a stability study of the class of multivariate self-excited Hawkes point processes, that can model natural and social systems, including earthquakes, epileptic seizures and the dynamics of neuron assemblies, bursts of exchanges in social communities, interactions between Internet bloggers, bank network fragility and cascading of failures, national sovereign default contagion, and so on. We present the general theory of multivariate generating functions to derive the number of events over all generations of various types that are triggered by a mother event of a given type. We obtain the stability domains of various systems, as a function of the topological structure of the mutual excitations across different event types. We find that mutual triggering tends to provide a significant extension of the stability (or subcritical) domain compared with the case where event types are decoupled, that is, when an event of a given type can only trigger events of the same type.

Early warning of climate tipping points

NASA Astrophysics Data System (ADS)

Lenton, Timothy M.

2011-07-01

A climate 'tipping point' occurs when a small change in forcing triggers a strongly nonlinear response in the internal dynamics of part of the climate system, qualitatively changing its future state. Human-induced climate change could push several large-scale 'tipping elements' past a tipping point. Candidates include irreversible melt of the Greenland ice sheet, dieback of the Amazon rainforest and shift of the West African monsoon. Recent assessments give an increased probability of future tipping events, and the corresponding impacts are estimated to be large, making them significant risks. Recent work shows that early warning of an approaching climate tipping point is possible in principle, and could have considerable value in reducing the risk that they pose.

Design of a new high-performance pointing controller for the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Johnson, C. D.

1993-01-01

A new form of high-performance, disturbance-adaptive pointing controller for the Hubble Space Telescope (HST) is proposed. This new controller is all linear (constant gains) and can maintain accurate 'pointing' of the HST in the face of persistent randomly triggered uncertain, unmeasurable 'flapping' motions of the large attached solar array panels. Similar disturbances associated with antennas and other flexible appendages can also be accommodated. The effectiveness and practicality of the proposed new controller is demonstrated by a detailed design and simulation testing of one such controller for a planar-motion, fully nonlinear model of HST. The simulation results show a high degree of disturbance isolation and pointing stability.

The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses

PubMed Central

Aurora, R. Nisha; Chowdhuri, Susmita; Ramar, Kannan; Bista, Sabin R.; Casey, Kenneth R.; Lamm, Carin I.; Kristo, David A.; Mallea, Jorge M.; Rowley, James A.; Zak, Rochelle S.; Tracy, Sharon L.

2012-01-01

The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) Citation: Aurora RN; Chowdhuri S; Ramar K; Bista SR; Casey KR; Lamm CI; Kristo DA; Mallea JM; Rowley JA; Zak RS; Tracy SL. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. SLEEP 2012;35(1):17-40. PMID:22215916

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

PubMed

Cannon, Christopher P; Bhatt, Deepak L; Oldgren, Jonas; Lip, Gregory Y H; Ellis, Stephen G; Kimura, Takeshi; Maeng, Michael; Merkely, Bela; Zeymer, Uwe; Gropper, Savion; Nordaby, Matias; Kleine, Eva; Harper, Ruth; Manassie, Jenny; Januzzi, James L; Ten Berg, Jurrien M; Steg, P Gabriel; Hohnloser, Stefan H

2017-10-19

Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y 12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y 12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups. Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y 12 inhibitor than among those who received triple therapy with warfarin, a P2Y 12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis

PubMed Central

Wang, Chenchen; Schmid, Christopher H.; Iversen, Maura D.; Harvey, William F.; Fielding, Roger A.; Driban, Jeffrey B.; Price, Lori Lyn; Wong, John B.; Reid, Kieran F.; Rones, Ramel; McAlindon, Timothy

2016-01-01

Background Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. Objective To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. Design Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985) Setting An urban tertiary care academic hospital. Patients 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). Intervention Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). Measurements The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. Results At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, −10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. Limitation Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. Conclusion Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. Primary Funding Source National Center for Complementary and Integrative Health of the National Institutes of Health. PMID:27183035

RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription

PubMed Central

Huang, Xuhui; Wang, Dong; Weiss, Dahlia R.; Bushnell, David A.; Kornberg, Roger D.; Levitt, Michael

2010-01-01

A structurally conserved element, the trigger loop, has been suggested to play a key role in substrate selection and catalysis of RNA polymerase II (pol II) transcription elongation. Recently resolved X-ray structures showed that the trigger loop forms direct interactions with the β-phosphate and base of the matched nucleotide triphosphate (NTP) through residues His1085 and Leu1081, respectively. In order to understand the role of these two critical residues in stabilizing active site conformation in the dynamic complex, we performed all-atom molecular dynamics simulations of the wild-type pol II elongation complex and its mutants in explicit solvent. In the wild-type complex, we found that the trigger loop is stabilized in the “closed” conformation, and His1085 forms a stable interaction with the NTP. Simulations of point mutations of His1085 are shown to affect this interaction; simulations of alternative protonation states, which are inaccessible through experiment, indicate that only the protonated form is able to stabilize the His1085-NTP interaction. Another trigger loop residue, Leu1081, stabilizes the incoming nucleotide position through interaction with the nucleotide base. Our simulations of this Leu mutant suggest a three-component mechanism for correctly positioning the incoming NTP in which (i) hydrophobic contact through Leu1081, (ii) base stacking, and (iii) base pairing work together to minimize the motion of the incoming NTP base. These results complement experimental observations and provide insight into the role of the trigger loop on transcription fidelity. PMID:20798057

A Trigger Mechanism for Volcanic Low-Frequency Seismic Events on Montserrat

NASA Astrophysics Data System (ADS)

Neuberg, J. W.; Tuffen, H.; Jolly, A.; Green, D.

2003-12-01

Seismic observations of low-frequency earthquake swarms on Montserrat point to a non-destructive, repeatable source mechanism in a confined area inside or near the conduit. While the seismic wave propagation pattern of the subsequent resonance in and around the conduit is well studied, the trigger mechanism has remained elusive. In this contribution we suggest a trigger mechanism based on new field evidence for fracture and healing of magma in volcanic conduits, together with seismic observations from Montserrat and finite element modelling of magma deformation during conduit flow. As a seismic trigger we suggest a stick-slip motion of highly-viscous magma in the glass transition, that periodically generates networks of seismogenic shear fractures a few metres in length. These fractures are rapidly filled by fine-grained material [cataclasite] that is generated by friction processes on the fracture surfaces, such as corner abrasion, and is locally redeposited by gas flowing within the fracture system. Filled fractures are then swiftly healed as reloading leads to annealing and a return to cohesive viscous deformation. Such a fast healing process, probably on the order of tens of seconds, leads to a repeatable trigger mechanism. Due to a strong lateral viscosity gradient in the conduit, highly-viscous magma near the conduit walls, which can exhibit brittle behaviour, co-exists with low-viscosity, fluid magma in the conduit centre; such that brittle failure provides the seismic trigger mechanism while the fluid part can still act as a seismic resonator.

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapy was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.

Treatment of temporomandibular myofascial pain with deep dry needling

PubMed Central

Gonzalez-Perez, Luis M.; Granados-Nuñez, Mercedes; Urresti-Lopez, Francisco J.

2012-01-01

Objectives: The present study was designed to evaluate the usefulness of deep dry needling in the treatment of temporomandibular myofascial pain. Study Design: We selected 36 patients with myofascial pain located in the external pterygoid muscle (30 women/6 men, mean age=27 years with SD±6,5). We studied differences in pain with a visual analog scale and range of mandibular movements before and after intervention. Results: We found a statistically significant relationship (p<0,01) between therapeutic intervention and the improvement of pain and jaw movements, which continued up to 6 months after treatment. Pain reduction was greater the higher was the intensity of pain at baseline. Conclusions: Although further studies are needed, our findings suggest that deep dry needling in the trigger point in the external pterygoid muscle can be effective in the management of patients with myofascial pain located in that muscle. Key words:Temporomandibular joint, myofascial pain, external pterygoid muscle, trigger point, deep dry needling. PMID:22549679

Kinesio taping and manual pressure release: Short-term effects in subjects with myofasical trigger point.

PubMed

Chao, Yu Wen; Lin, Jiu Jenq; Yang, Jing Lan; Wang, Wendy Tzyy-Jiuan

2016-01-01

Randomized controlled trial. Myofascial pain syndrome is characterized by myofascial trigger points (MTrPs) and fascia tenderness. We investigated the effects of manual pressure release (MPR) alone or in combination with taping (MPR/MKT) in subjects with MTrPs. Fifteen and 16 subjects received MPR and MPR/MKT respectively. Outcomes including Pressure pain threshold, muscle stiffness, mechanomyography were assessed at baseline, post-intervention and 7-days later. Pressure pain threshold improved significantly (d = 1.79, p < 0.005) in both groups. Significant improvement in muscle stiffness in the MPR/MKT group (0.27-0.49 mm) as compared to the MPR group (-0.02-0.23 mm). Mechanomyography amplitude in the MPR/MKT group was significantly higher than that of the MPR group (p < 0.05). MPR and MPR/MKT are effective in reducing pain in these subjects. MPR/MKT has a greater effect on muscle stiffness and contraction amplitude. IV. Copyright © 2016 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

The neurophysiological effects of dry needling in patients with upper trapezius myofascial trigger points: study protocol of a controlled clinical trial

PubMed Central

Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

2013-01-01

Introduction Dry needling (DN) is an effective method for the treatment of myofascial trigger points (MTrPs). There is no report on the neurophysiological effects of DN in patients with MTrPs. The aim of the present study will be to assess the immediate neurophysiological efficacy of deep DN in patients with upper trapezius MTrPs. Methods and analysis A prospective, controlled clinical trial was designed to include patients with upper trapezius MTrPs and volunteered healthy participants to receive one session of DN. The primary outcome measures are neuromuscular junction response and sympathetic skin response. The secondary outcomes are pain intensity and pressure pain threshold. Data will be collected at baseline and immediately after intervention. Ethics and dissemination This study protocol has been approved by the Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences. The results of the study will be disseminated in a peer-reviewed journal and presented at international congresses. PMID:23793673

A GRASS GIS Semi-Stochastic Model for Evaluating the Probability of Landslides Impacting Road Networks in Collazzone, Central Italy

NASA Astrophysics Data System (ADS)

Taylor, Faith E.; Santangelo, Michele; Marchesini, Ivan; Malamud, Bruce D.

2013-04-01

During a landslide triggering event, the tens to thousands of landslides resulting from the trigger (e.g., earthquake, heavy rainfall) may block a number of sections of the road network, posing a risk to rescue efforts, logistics and accessibility to a region. Here, we present initial results from a semi-stochastic model we are developing to evaluate the probability of landslides intersecting a road network and the network-accessibility implications of this across a region. This was performed in the open source GRASS GIS software, where we took 'model' landslides and dropped them on a 79 km2 test area region in Collazzone, Umbria, Central Italy, with a given road network (major and minor roads, 404 km in length) and already determined landslide susceptibilities. Landslide areas (AL) were randomly selected from a three-parameter inverse gamma probability density function, consisting of a power-law decay of about -2.4 for medium and large values of AL and an exponential rollover for small values of AL; the rollover (maximum probability) occurs at about AL = 400 m.2 The number of landslide areas selected for each triggered event iteration was chosen to have an average density of 1 landslide km-2, i.e. 79 landslide areas chosen randomly for each iteration. Landslides were then 'dropped' over the region semi-stochastically: (i) random points were generated across the study region; (ii) based on the landslide susceptibility map, points were accepted/rejected based on the probability of a landslide occurring at that location. After a point was accepted, it was assigned a landslide area (AL) and length to width ratio. Landslide intersections with roads were then assessed and indices such as the location, number and size of road blockage recorded. The GRASS-GIS model was performed 1000 times in a Monte-Carlo type simulation. Initial results show that for a landslide triggering event of 1 landslide km-2 over a 79 km2 region with 404 km of road, the number of road blockages ranges from 6 to 17, resulting in one road blockage every 24-67 km of roads. The average length of road blocked was 33 m. As we progress with model development and more sophisticated network analysis, we believe this semi-stochastic modelling approach will aid civil protection agencies to get a rough idea for the probability of road network potential damage (road block number and extent) as the result of different magnitude landslide triggering event scenarios.

Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

PubMed Central

Ortiz-Abalia, Jon; Sahún, Ignasi; Altafaj, Xavier; Andreu, Núria; Estivill, Xavier; Dierssen, Mara; Fillat, Cristina

2008-01-01

Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whether functional CNS defects could be corrected with an inhibitory RNA against Dyrk1A, delivered by bilateral intrastriatal injections of adeno-associated virus type 2 (AAVshDyrk1A). We report that AAVshDyrk1A efficiently transduced HEK293 cells and primary neuronal cultures, triggering the specific inhibition of Dyrk1A expression. Injecting the vector into the striata of TgDyrk1A mice resulted in a restricted, long-term transduction of the striatum. This gene therapy was found to be devoid of toxicity and succeeded in normalizing Dyrk1A protein levels in TgDyrk1A mice. Importantly, the behavioral studies of the adult TgDyrk1A mice treated showed a reversal of corticostriatal-dependent phenotypes, as revealed by the attenuation of their hyperactive behavior, the restoration of motor-coordination defects, and an improvement in sensorimotor gating. Taken together, the data demonstrate that normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment. Furthermore, these results identify Dyrk1A as a potential target for therapy in DS. PMID:18940310

Near Death Experience from Placement of an Intrathecal Catheter.

PubMed

Padalia, Devang; Jassal, Navdeep; Patel, Sagar

2016-05-01

The management of pain due to cancer is challenging and often requires invasive therapy in addition to medication management. Intrathecal drug delivery is a form of advanced therapy that delivers medication locally in the intrathecal space while reducing systemic side effects associated with high doses of opioids. Although risks associated with intrathecal drug delivery are low, some common complications include dislodgement, kinking, or fracture of the catheter, bleeding, neurological injury, infection, and cerebrospinal leaks. We present a case of a 38-year-old woman with a medical history significant for stage IV breast cancer, L2 metastatic lesion, opioid tolerance, and chronic neck and low back pain who was admitted to the hospital for intractable pain. She had failed multiple interventional procedures in the past including lumbar medial nerve radiofrequency ablation, epidural steroid injection, and trigger point injections as well as a kyphoplasty at the L2 level. Failing both oral and parenteral opioid treatments, the decision was made to place an intrathecal pump in the patient. After placement of the intrathecal catheter and prior to any bolus of medication being given, the patient became bradycardic with a heart rate in the 20s and experienced a 10 second pause. The patient had intermittent bradycardia over the following days and symptoms resolved only after removal of the intrathecal catheter itself. To our knowledge, this is the first reported case with a complication of recurrent bradycardic and asystolic episodes prior to the administration of intrathecal opioid but shortly after placement of the intrathecal catheter itself. Intrathecal drug delivery, complications, cancer pain, intrathecal analgesia, bradycardia, opioids.

Conservative chiropractic management of urinary incontinence using applied kinesiology: a retrospective case-series report.

PubMed

Cuthbert, Scott C; Rosner, Anthony L

2012-03-01

The purpose of this case series is to describe the chiropractic management of 21 patients with daily stress and occasional total urinary incontinence (UI). Twenty-one case files of patients 13 to 90 years of age with UI from a chiropractic clinic were reviewed. The patients had a 4-month to 49-year history of UI and associated muscle dysfunction and low back and/or pelvic pain. Eighteen wore an incontinence pad throughout the day and night at the time of their appointments because of unpredictable UI. Patients were evaluated for muscle impairments in the lumbar spine, pelvis, and pelvic floor and low back and/or hip pain. Positive manual muscle test results of the pelvis, lumbar spine muscles, and pelvic floor muscles were the most common findings. Lumbosacral dysfunction was found in 13 of the cases with pain provocation tests (applied kinesiology sensorimotor challenge); in 8 cases, this sensorimotor challenge was absent. Chiropractic manipulative therapy and soft tissue treatment addressed the soft tissue and articular dysfunctions. Chiropractic manipulative therapy involved high-velocity, low-amplitude manipulation; Cox flexion distraction manipulation; and/or use of a percussion instrument for the treatment of myofascial trigger points. Urinary incontinence symptoms resolved in 10 patients, considerably improved in 7 cases, and slightly improved in 4 cases. Periodic follow-up examinations for the past 6 years, and no less than 2 years, indicate that for each participant in this case-series report, the improvements of UI remained stable. The patients reported in this retrospective case series showed improvement in UI symptoms that persisted over time.

Percutaneous Soft Tissue Release for Treating Chronic Recurrent Myofascial Pain Associated with Lateral Epicondylitis: 6 Case Studies

PubMed Central

Lin, Ming-Ta; Chou, Li-Wei; Chen, Hsin-Shui; Kao, Mu-Jung

2012-01-01

Objective. The purpose of this pilot study is to investigate the effectiveness of the percutaneous soft tissue release for the treatment of recurrent myofascial pain in the forearm due to recurrent lateral epicondylitis. Methods. Six patients with chronic recurrent pain in the forearm with myofascial trigger points (MTrPs) due to chronic lateral epicondylitis were treated with percutaneous soft tissue release of Lin's technique. Pain intensity (measured with a numerical pain rating scale), pressure pain threshold (measured with a pressure algometer), and grasping strength (measured with a hand dynamometer) were assessed before, immediately after, and 3 months and 12 months after the treatment. Results. For every individual case, the pain intensity was significantly reduced (P < 0.01) and the pressure pain threshold and the grasping strength were significantly increased (P < 0.01) immediately after the treatment. This significant effectiveness lasts for at least one year. Conclusions. It is suggested that percutaneous soft tissue release can be used for treating chronic recurrent lateral epicondylitis to avoid recurrence, if other treatment, such as oral anti-inflammatory medicine, physical therapy, or local steroid injection, cannot control the recurrent pain. PMID:23243428

Stress and visceral pain: from animal models to clinical therapies

PubMed Central

Larauche, Muriel; Mulak, Agata; Taché, Yvette

2011-01-01

Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. PMID:21575632

Rare primary headaches: clinical insights.

PubMed

Casucci, G; d'Onofrio, F; Torelli, P

2004-10-01

So-called "rare" headaches, whose prevalence rate is lower than 1% or is not known at all and have been reported in only a few dozen cases to date, constitute a very heterogeneous group. Those that are best characterised from the clinical point of view can be classified into forms with prominent autonomic features and forms with sparse or no autonomic features. Among the former are trigeminal autonomic cephalalgias (TACs) and hemicrania continua, while the latter comprise classical trigeminal neuralgia, hypnic headache, primary thunderclap headache, and exploding head syndrome. The major clinical discriminating factor for the differential diagnosis of TACs is the relationship between duration and frequency of attacks: the forms in which pain is shorter lived are those with the higher frequency of daily attacks. Other aspects to be considered are the time pattern of symptoms, intensity and timing of attacks, the patient's behaviour during the attacks, the presence of any triggering factors and of the refractory period after an induced attack, and response to therapy, especially with indomethacin. Often these are little known clinical entities, which are not easily detected in clinical practice. For some of them, e. g., thunderclap headache, it is always necessary to perform instrumental tests to exclude the presence of underlying organic diseases.

[Lymphoproliferative disease in patients with autoimmune and inflammatory diseases: significance of antigenic stimulation and inflammatory processes].

PubMed

Tvarůzková, Zuzana; Pavlová, Sárka; Doubek, Michael; Mayer, Jirí; Pospísilová, Sárka

2011-01-01

Evidence has been growing that the pathogenesis of lymphoproliferative disease involves immune processes deregulation. It is believed that antigens or immunological elements can trigger transformation of normal lymphocyte polyclonal population into monoclonal neoplastic disorder--lymphoproliferative disease. Extensive studies point to the link between malignant lymphoma development and autoimmune or inflammatory diseases--namely rheumatoid arthritis, Sjörgen's syndrome, coeliac disease, systemic lupus erythematosus or thyroiditis. Increased risk of lymphoproliferative disease development was also proved for some infections. These infections involve both viral (e.g. Epstein-Barr virus, HIV or hepatitis C virus) and bacterial agents (e.g. Helicobacter pylori, Borrelia burgdorferi). Besides various lymphomas, the links to autoimmune/inflammatory diseases have also been described in chronic lymphocytic leukaemia. Regarding clinical medicine, it is necessary to distinguish patients with autoimmune, inflammatory and infectious diseases who are at the increased risk of tumour development. New approaches must be found to lower this risk. Also, the relationship between autoimmune/inflammatory disease therapy and lymphoma development should be clarified. Although lymphomas associated with autoimmune and inflammatory diseases represent only a small proportion of all lymphomas, any new findings regarding these diseases can cast light on lymphoma pathogenesis as a whole.

Utilization of manual therapy to the lumbar spine in conjunction with traditional conservative care for individuals with bilateral lower extremity complex regional pain syndrome: A case series.

PubMed

Walston, Zachary; Hernandez, Luis; Yake, Dale

2018-06-06

Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS. Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity. Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS. Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

Disintegrable NIR Light Triggered Gold Nanorods Supported Liposomal Nanohybrids for Cancer Theranostics.

PubMed

Chauhan, Deepak S; Prasad, Rajendra; Devrukhkar, Janhavi; Selvaraj, Kaliaperumal; Srivastava, Rohit

2018-05-16

In this work, facile synthesis and application of targeted, dual therapeutic gold nanorods-liposome (GNR-Lipos) nanohybrid for imaging guided photothermal therapy and chemotherapy is investigated. The dual therapeutic GNR-Lipos nanohybrid consists of GNR supported, and doxorubicin (DOX) loaded liposome. GNRs not only serve as a photothermal agent and increase the drug release in intracellular environment of cancer cells, but also provide mechanical strength to liposomes by being decorated both inside and outside of bilayer surfaces. The designed nanohybrid shows a remarkable response for synergistic chemophotothermal therapy compared to only chemotherapy or photothermal therapy. The NIR response, efficient uptake by the cells, disintegration of GNR-Lipos nanohybrid, and synergistic therapeutic effect of photothermal and chemotherapy over breast cancer cells MDA-MB-231 are studied for the better development of a biocompatible nanomaterial based multifunctional cancer theranostic agent.

Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

PubMed

Kokuryo, Daisuke; Nakashima, Seiji; Ozaki, Fuminori; Yuba, Eiji; Chuang, Kai-Hsiang; Aoshima, Sadahito; Ishizaka, Yukihito; Saga, Tsuneo; Kono, Kenji; Aoki, Ichio

2015-01-01

Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane.

PubMed

Leulmi, Selma; Chauchet, Xavier; Morcrette, Melissa; Ortiz, Guillermo; Joisten, Hélène; Sabon, Philippe; Livache, Thierry; Hou, Yanxia; Carrière, Marie; Lequien, Stéphane; Dieny, Bernard

2015-10-14

Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. The present study focuses on a recently proposed approach for cancer cell destruction based on the targeted triggering of cancer cell spontaneous death through the mechanical vibration of anisotropic magnetic micro/nanoparticles attached to the cell membranes at low frequencies (∼20 Hz) and in weak magnetic fields (∼30 mT). The study was conducted in vitro, on human renal cancer cells with superparamagnetic-like particles. Three types of such particles made of NiFe or magnetite were prepared and characterized (either synthetic antiferromagnetic, vortex or polycrystalline with random grain anisotropy). The triggering of the apoptosis of these cancer cells was demonstrated with NiFe vortex particles and statistically characterized by flow-cytometry studies. The death pathway via apoptosis and not necrosis was identified by the clear observation of caspase activation.

Herpes simplex virus triggers activation of calcium-signaling pathways

PubMed Central

Cheshenko, Natalia; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy C.

2003-01-01

The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy. PMID:14568989

Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane

NASA Astrophysics Data System (ADS)

Leulmi, Selma; Chauchet, Xavier; Morcrette, Melissa; Ortiz, Guillermo; Joisten, Hélène; Sabon, Philippe; Livache, Thierry; Hou, Yanxia; Carrière, Marie; Lequien, Stéphane; Dieny, Bernard

2015-09-01

Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. The present study focuses on a recently proposed approach for cancer cell destruction based on the targeted triggering of cancer cell spontaneous death through the mechanical vibration of anisotropic magnetic micro/nanoparticles attached to the cell membranes at low frequencies (~20 Hz) and in weak magnetic fields (~30 mT). The study was conducted in vitro, on human renal cancer cells with superparamagnetic-like particles. Three types of such particles made of NiFe or magnetite were prepared and characterized (either synthetic antiferromagnetic, vortex or polycrystalline with random grain anisotropy). The triggering of the apoptosis of these cancer cells was demonstrated with NiFe vortex particles and statistically characterized by flow-cytometry studies. The death pathway via apoptosis and not necrosis was identified by the clear observation of caspase activation.

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

PubMed

Liao, Zi-Xian; Liu, Meng-Chia; Kempson, Ivan M; Fa, Yu-Chen; Huang, Kuo-Yen

2017-01-01

Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels, with incorporation of gold nanoparticles (NP). The incorporation of gold NP into MC hydrogels led to a tunable light irradiation response that dictated the hydrogel release rate of leptin. This manuscript demonstrates feasibility in designing tunable thermosensitive hydrogels for loading multimodality therapeutic agents to enhance the bioactivity of leptin for obesity therapy.

Gonadotropin-releasing hormone agonist trigger in oocyte donors co-treated with a gonadotropin-releasing hormone antagonist: a dose-finding study.

PubMed

Vuong, Thi Ngoc Lan; Ho, Manh Tuong; Ha, Tan Duc; Phung, Huy Tuan; Huynh, Gia Bao; Humaidan, Peter

2016-02-01

To determine the optimal GnRH agonist dose for triggering of oocyte maturation in oocyte donors. Single-center, randomized, parallel, investigator-blinded trial. IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. One hundred sixty-five oocyte donors (aged 18-35 years, body mass index [BMI] <28 kg/m(2), antimüllerian hormone level >1.25 ng/mL, and antral follicle count ≥6). Ovulation trigger with 0.2, 0.3, or 0.4 mg triptorelin in a GnRH antagonist cycle. The primary end point was number of metaphase II oocytes. Secondary end points were fertilization and cleavage rates, number of embryos and top-quality embryos, steroid levels, ovarian volume, and ongoing pregnancy rate (PR) in recipients. There were no significant differences between the triptorelin 0.2, 0.3, and 0.4 mg trigger groups with respect to number of metaphase II oocytes (16.0 ± 8.5, 15.9 ± 7.8, and 14.7 ± 8.4, respectively), embryos (13.2 ± 7.8, 11.7 ± 6.9, 11.8 ± 7.0), and number of top-quality embryos (3.8 ± 2.9, 3.6 ± 3.0, 4.1 ± 3.0). Luteinizing hormone levels at 24 hours and 36 hours after trigger was significantly higher with triptorelin 0.4 mg versus 0.2 mg and 0.3 mg (9.8 ± 7.1 IU/L vs. 7.3 ± 4.1 IU/L and 7.2 ± 3.7 IU/L, respectively; 4.6 ± 3.2 IU/L vs. 3.2 ± 2.3 IU/L and 3.3 ± 2.1 IU/L, respectively. Progesterone level at oocyte pick-up +6 days was significantly higher in the 0.4-mg group (2.2 ± 3.7 ng/ml) versus 0.2 mg (1.1 ± 1.0 ng/ml) and 0.3 mg (1.2 ± 1.6 ng/ml). One patient developed early-onset severe ovarian hyperstimulation syndrome (OHSS). No significant differences between triptorelin doses of 0.2, 0.3, and 0.4 mg used for ovulation trigger in oocyte donors were seen with regard to the number of mature oocytes and top-quality embryos. NCT02208986. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Acupuncture for treating fibromyalgia

PubMed Central

Deare, John C; Zheng, Zhen; Xue, Charlie CL; Liu, Jian Ping; Shang, Jingsheng; Scott, Sean W; Littlejohn, Geoff

2014-01-01

Background One in five fibromyalgia sufferers use acupuncture treatment within two years of diagnosis. Objectives To examine the benefits and safety of acupuncture treatment for fibromyalgia. Search methods We searched CENTRAL, PubMed, EMBASE, CINAHL, National Research Register, HSR Project and Current Contents, as well as the Chinese databases VIP and Wangfang to January 2012 with no language restrictions. Selection criteria Randomised and quasi-randomised studies evaluating any type of invasive acupuncture for fibromyalgia diagnosed according to the American College of Rheumatology (ACR) criteria, and reporting any main outcome: pain, physical function, fatigue, sleep, total well-being, stiffness and adverse events. Data collection and analysis Two author pairs selected trials, extracted data and assessed risk of bias. Treatment effects were reported as standardised mean differences (SMD) and 95%confidence intervals (CI) for continuous outcomes using different measurement tools (pain, physical function, fatigue, sleep, total well-being and stiffness) and risk ratio (RR) and 95% CI for dichotomous outcomes (adverse events).We pooled data using the random-effects model. Main results Nine trials (395 participants) were included. All studies except one were at low risk of selection bias; five were at risk of selective reporting bias (favouring either treatment group); two were subject to attrition bias (favouring acupuncture); three were subject to performance bias (favouring acupuncture) and one to detection bias (favouring acupuncture). Three studies utilised electro-acupuncture (EA) with the remainder using manual acupuncture (MA) without electrical stimulation. All studies used ’formula acupuncture’ except for one, which used trigger points. Low quality evidence from one study (13 participants) showed EA improved symptoms with no adverse events at one month following treatment. Mean pain in the non-treatment control group was 70 points on a 100 point scale; EA reduced pain by a mean of 22 points (95% confidence interval (CI) 4 to 41), or 22% absolute improvement. Control group global well-being was 66.5 points on a 100 point scale; EA improved well-being by a mean of 15 points (95% CI 5 to 26 points). Control group stiffness was 4.8 points on a 0 to 10 point; EA reduced stiffness by a mean of 0.9 points (95% CI 0.1 to 2 points; absolute reduction 9%, 95% CI 4% to 16%). Fatigue was 4.5 points (10 point scale) without treatment; EA reduced fatigue by a mean of 1 point (95% CI 0.22 to 2 points), absolute reduction 11% (2% to 20%). There was no difference in sleep quality (MD 0.4 points, 95% CI −1 to 0.21 points, 10 point scale), and physical function was not reported. Moderate quality evidence from six studies (286 participants) indicated that acupuncture (EA or MA) was no better than sham acupuncture, except for less stiffness at one month. Subgroup analysis of two studies (104 participants) indicated benefits of EA. Mean pain was 70 points on 0 to 100 point scale with sham treatment; EA reduced pain by 13% (5% to 22%); (SMD −0.63, 95% CI −1.02 to −0.23). Global well-being was 5.2 points on a 10 point scale with sham treatment; EA improved well-being: SMD 0.65, 95% CI 0.26 to 1.05; absolute improvement 11% (4% to 17%). EA improved sleep, from 3 points on a 0 to 10 point scale in the sham group: SMD 0.40 (95% CI 0.01 to 0.79); absolute improvement 8% (0.2% to 16%). Low-quality evidence from one study suggested that MA group resulted in poorer physical function: mean function in the sham group was 28 points (100 point scale); treatment worsened function by a mean of 6 points (95% CI −10.9 to −0.7). Low-quality evidence from three trials (289 participants) suggested no difference in adverse events between real (9%) and sham acupuncture (35%); RR 0.44 (95% CI 0.12 to 1.63). Moderate quality evidence from one study (58 participants) found that compared with standard therapy alone (antidepressants and exercise), adjunct acupuncture therapy reduced pain at one month after treatment: mean pain was 8 points on a 0 to 10 point scale in the standard therapy group; treatment reduced pain by 3 points (95% CI −3.9 to −2.1), an absolute reduction of 30% (21% to 39%). Two people treated with acupuncture reported adverse events; there were none in the control group (RR 3.57; 95% CI 0.18 to 71.21). Global well-being, sleep, fatigue and stiffness were not reported. Physical function data were not usable. Low quality evidence from one study (38 participants) showed a short-term benefit of acupuncture over antidepressants in pain relief: mean pain was 29 points (0 to 100 point scale) in the antidepressant group; acupuncture reduced pain by 17 points (95% CI −24.1 to −10.5). Other outcomes or adverse events were not reported. Moderate-quality evidence from one study (41 participants) indicated that deep needling with or without deqi did not differ in pain, fatigue, function or adverse events. Other outcomes were not reported. Four studies reported no differences between acupuncture and control or other treatments described at six to seven months follow-up. No serious adverse events were reported, but there were insufficient adverse events to be certain of the risks. Authors’ conclusions There is low tomoderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted. PMID:23728665

Smart, Injury-Triggered Therapy for Ocular Trauma

DTIC Science & Technology

2015-10-01

attachment surgery. We genetically engineered “protease activity sensor” (PAS) as chimeric transmembrane protein that can respond to increase in...results or key outcomes We genetically engineered “protease activity sensor” (PAS) as chimeric transmembrane protein that can respond to increase in...6 A B Fig. 1. The effects of ionomycin on the shedding of chimeric fractalkine constructs from HEK293 cells in vitro. (A

A combination of a ribonucleotide reductase inhibitor and histone deacetylase inhibitors downregulates EGFR and triggers BIM-dependent apoptosis in head and neck cancer

PubMed Central

Habtemichael, Negusse; Bier, Carolin; Unruhe, Britta; Weisheit, Simona; Spange, Stephanie; Nonnenmacher, Frank; Fetz, Verena; Ginter, Torsten; Reichardt, Sigrid; Liebmann, Claus; Schneider, Günter; Krämer, Oliver H.

2012-01-01

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignant neoplasm and more than 50% of patients succumb to this disease. HNSCCs are characterized by therapy resistance, which relies on the overexpression of anti-apoptotic proteins and on the aberrant regulation of the epidermal growth factor receptor (EGFR). As inherent and acquired resistance to therapy counteracts improvement of long-term survival, novel multi-targeting strategies triggering cancer cell death are urgently required. We investigated how induction of replicational stress by the ribonucleotide reductase inhibitor hydroxyurea (HU) combined with histone deacetylase inhibitors (HDACi) exerts anti-tumor activity. We treated HNSCC cell lines and freshly isolated tumor cells with HDACi, such as the clinically approved anti-epileptic drug valproic acid (VPA), in combination with HU. Our data demonstrate that at clinically achievable levels VPA/HU combinations efficiently block proliferation as well as clonogenic survival, and trigger apoptosis of HNSCC cells. In the presence of VPA/HU, such tumor cells increase expression of the pro-apoptotic BCL-2 family protein BIM, independent of wild-type p53 signaling and in the absence of increased expression of the p53 targets PUMA and BAX. The pro-apoptotic activity of BIM in HNSCCs was found critical for tumor cell death; ectopic overexpression of BIM induced HNSCC apoptosis and RNAi-mediated depletion of BIM protected HNSCC cells from VPA/HU. Also, significantly elevated BIM levels (p<0.01) were detectable in the apoptotic tumor centers versus proliferating tumor margins in HNSCC patients (n=31), underlining BIM's clinical relevance. Importantly, VPA/HU treatment additionally reduces expression and cell surface localization of EGFR. Accordingly, in a xenograft mouse model, VPA/HU efficiently blocked tumor growth (P<0.001) correlating with BIM induction and EGFR downregulation. We provide a molecular rationale for the potent anti-cancer activities of this drug combination. Our data suggest its exploitation as a potential strategy for the treatment of HNSCC and other tumor entities characterized by therapy resistance linked to dysregulated EGFR activation. PMID:22289787

Manual therapy and exercise for rotator cuff disease.

PubMed

Page, Matthew J; Green, Sally; McBain, Brodwen; Surace, Stephen J; Deitch, Jessica; Lyttle, Nicolette; Mrocki, Marshall A; Buchbinder, Rachelle

2016-06-10

Management of rotator cuff disease often includes manual therapy and exercise, usually delivered together as components of a physical therapy intervention. This review is one of a series of reviews that form an update of the Cochrane review, 'Physiotherapy interventions for shoulder pain'. To synthesise available evidence regarding the benefits and harms of manual therapy and exercise, alone or in combination, for the treatment of people with rotator cuff disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (January 1966 to March 2015), Ovid EMBASE (January 1980 to March 2015), CINAHL Plus (EBSCO, January 1937 to March 2015), ClinicalTrials.gov and the WHO ICTRP clinical trials registries up to March 2015, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials, to identify potentially relevant trials. We included randomised and quasi-randomised trials, including adults with rotator cuff disease, and comparing any manual therapy or exercise intervention with placebo, no intervention, a different type of manual therapy or exercise or any other intervention (e.g. glucocorticoid injection). Interventions included mobilisation, manipulation and supervised or home exercises. Trials investigating the primary or add-on effect of manual therapy and exercise were the main comparisons of interest. Main outcomes of interest were overall pain, function, pain on motion, patient-reported global assessment of treatment success, quality of life and the number of participants experiencing adverse events. Two review authors independently selected trials for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the body of evidence for the main outcomes using the GRADE approach. We included 60 trials (3620 participants), although only 10 addressed the main comparisons of interest. Overall risk of bias was low in three, unclear in 14 and high in 43 trials. We were unable to perform any meta-analyses because of clinical heterogeneity or incomplete outcome reporting. One trial compared manual therapy and exercise with placebo (inactive ultrasound therapy) in 120 participants with chronic rotator cuff disease (high quality evidence). At 22 weeks, the mean change in overall pain with placebo was 17.3 points on a 100-point scale, and 24.8 points with manual therapy and exercise (adjusted mean difference (MD) 6.8 points, 95% confidence interval (CI) -0.70 to 14.30 points; absolute risk difference 7%, 1% fewer to 14% more). Mean change in function with placebo was 15.6 points on a 100-point scale, and 22.4 points with manual therapy and exercise (adjusted MD 7.1 points, 95% CI 0.30 to 13.90 points; absolute risk difference 7%, 1% to 14% more). Fifty-seven per cent (31/54) of participants reported treatment success with manual therapy and exercise compared with 41% (24/58) of participants receiving placebo (risk ratio (RR) 1.39, 95% CI 0.94 to 2.03; absolute risk difference 16% (2% fewer to 34% more). Thirty-one per cent (17/55) of participants reported adverse events with manual therapy and exercise compared with 8% (5/61) of participants receiving placebo (RR 3.77, 95% CI 1.49 to 9.54; absolute risk difference 23% (9% to 37% more). However adverse events were mild (short-term pain following treatment).Five trials (low quality evidence) found no important differences between manual therapy and exercise compared with glucocorticoid injection with respect to overall pain, function, active shoulder abduction and quality of life from four weeks up to 12 months. However, global treatment success was more common up to 11 weeks in people receiving glucocorticoid injection (low quality evidence). One trial (low quality evidence) showed no important differences between manual therapy and exercise and arthroscopic subacromial decompression with respect to overall pain, function, active range of motion and strength at six and 12 months, or global treatment success at four to eight years. One trial (low quality evidence) found that manual therapy and exercise may not be as effective as acupuncture plus dietary counselling and Phlogenzym supplement with respect to overall pain, function, active shoulder abduction and quality life at 12 weeks. We are uncertain whether manual therapy and exercise improves function more than oral non-steroidal anti-inflammatory drugs (NSAID), or whether combining manual therapy and exercise with glucocorticoid injection provides additional benefit in function over glucocorticoid injection alone, because of the very low quality evidence in these two trials.Fifty-two trials investigated effects of manual therapy alone or exercise alone, and the evidence was mostly very low quality. There was little or no difference in patient-important outcomes between manual therapy alone and placebo, no treatment, therapeutic ultrasound and kinesiotaping, although manual therapy alone was less effective than glucocorticoid injection. Exercise alone led to less improvement in overall pain, but not function, when compared with surgical repair for rotator cuff tear. There was little or no difference in patient-important outcomes between exercise alone and placebo, radial extracorporeal shockwave treatment, glucocorticoid injection, arthroscopic subacromial decompression and functional brace. Further, manual therapy or exercise provided few or no additional benefits when combined with other physical therapy interventions, and one type of manual therapy or exercise was rarely more effective than another. Despite identifying 60 eligible trials, only one trial compared a combination of manual therapy and exercise reflective of common current practice to placebo. We judged it to be of high quality and found no clinically important differences between groups in any outcome. Effects of manual therapy and exercise may be similar to those of glucocorticoid injection and arthroscopic subacromial decompression, but this is based on low quality evidence. Adverse events associated with manual therapy and exercise are relatively more frequent than placebo but mild in nature. Novel combinations of manual therapy and exercise should be compared with a realistic placebo in future trials. Further trials of manual therapy alone or exercise alone for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review.

Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives.

PubMed

Scomparin, Anna; Florindo, Helena F; Tiram, Galia; Ferguson, Elaine L; Satchi-Fainaro, Ronit

2017-09-01

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination. Copyright © 2017 Elsevier B.V. All rights reserved.

The entry-level occupational therapy clinical doctorate: advantages, challenges, and international issues to consider.

PubMed

Brown, Ted; Crabtree, Jeffrey L; Mu, Keli; Wells, Joe

2015-04-01

Internationally, occupational therapy education has gone through several paradigm shifts during the last few decades, moving from certificate to diploma to bachelors to masters and now in some instances to clinical doctorate as the entry-level professional credential to practice. In the United States there is a recommendation under consideration by the American Occupational Therapy Association (AOTA) that by 2025, all occupational therapy university programs will move to the clinical doctorate level. It should be noted, however, that the AOTA Board can only make recommendations and it is the Accreditation Council for Occupational Therapy Education (ACOTE) who has regulatory authority to approve such a change. What are the potential implications for the profession, our clients, and funders of occupational therapy services? What are the primary drivers for the move towards the clinical doctorate being the educational entry point? Is the next step in the evolution of occupational therapy education globally a shift to the entry-level clinical doctorate? This article reviews current literature and discusses issues about the occupational therapy entry-level clinical doctorate. The published evidence available about the occupational therapy entry-level clinical doctorate is summarized and the perceived or frequently cited pros and cons of moving to the clinical doctorate as the singular entry point to occupational therapy practice are considered. The potential impacts of the introduction of the clinical doctorate as the entry-to-practice qualification across the United States on the occupational therapy community internationally will be briefly discussed. If the United States moves toward the entry-level clinical doctorate as the only educational starting point for the profession, will other jurisdictions follow suit? Further discourse and investigation of this issue both inside and outside of the United States is needed so that informed decisions can be made.

VEGF-induced intracellular Ca2+ oscillations are down-regulated and do not stimulate angiogenesis in breast cancer-derived endothelial colony forming cells

PubMed Central

Ruffinatti, Federico Alessandro; Poletto, Valentina; Massa, Margherita; Tancredi, Richard; Zuccolo, Estella; Khdar, Dlzar Alì; Riccardi, Alberto; Biggiogera, Marco; Rosti, Vittorio; Guerra, Germano; Moccia, Francesco

2017-01-01

Endothelial colony forming cells (ECFCs) represent a population of truly endothelial precursors that promote the angiogenic switch in solid tumors, such as breast cancer (BC). The intracellular Ca2+ toolkit, which drives the pro-angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that they are seemingly insensitive to this growth factor. This feature could underlie the relative failure of anti-VEGF therapies in cancer patients. Herein, we investigated whether and how VEGF uses Ca2+ signalling to control angiogenesis in BC-derived ECFCs (BC-ECFCs). Although VEGFR-2 was normally expressed, VEGF failed to induce proliferation and in vitro tubulogenesis in BC-ECFCs. Likewise, VEGF did not trigger robust Ca2+ oscillations in these cells. Similar to normal cells, VEGF-induced intracellular Ca2+ oscillations were triggered by inositol-1,4,5-trisphosphate-dependent Ca2+ release from the endoplasmic reticulum (ER) and maintained by store-operated Ca2+ entry (SOCE). However, InsP3-dependent Ca2+ release was significantly lower in BC-ECFCs due to the down-regulation of ER Ca2+ levels, while there was no remarkable difference in the amplitude, pharmacological profile and molecular composition of SOCE. Thus, the attenuation of the pro-angiogenic Ca2+ response to VEGF was seemingly due to the reduction in ER Ca2+ concentration, which prevents VEGF from triggering robust intracellular Ca2+ oscillations. However, the pharmacological inhibition of SOCE prevented BC-ECFC proliferation and in vitro tubulogenesis. These findings demonstrate for the first time that BC-ECFCs are insensitive to VEGF, which might explain at cellular and molecular levels the failure of anti-VEGF therapies in BC patients, and hint at SOCE as a novel molecular target for this disease. PMID:29221123

A Nationally Scaled Telebehavioral Health Program for Chronic Pain: Characteristics, Goals, and Psychological Outcomes.

PubMed

Mochari-Greenberger, Heidi; Peters, Aimee; Vue, Lee; Pande, Reena L

2017-08-01

Millions of U.S. adults suffer from chronic pain with a high prevalence of comorbid mental health issues. Telehealth-delivered behavioral therapy for chronic pain has been evaluated in the research setting. The purpose of this study was 1) to describe a nationally scaled, standardized, telebehavioral therapy program for patients with chronic pain and behavioral comorbidities, and 2) evaluate characteristics, goals, and psychosocial outcomes among program participants. This was mixed-methods retrospective cohort analysis among consecutive program graduates (mean age 53y; 24% male). The 8-week program was delivered by a licensed therapist and a behavior coach through telephone/secure video and tailored to each participant's behavioral health needs and goals. Participant chief complaints, behavioral goals, and mood triggers were abstracted by deidentified clinical record review using structured qualitative research methods. Depression, anxiety, and stress symptom data were collected at baseline and program graduation using the validated Depression Anxiety Stress Scales 21. Back pain (42%) and hip/leg/knee pain (28%) comprised the most common chief complaints. Pain management (44%) and weight loss (43%) were the most frequently cited goals. At baseline, approximately half of participants had elevated depression (59%), anxiety (54%), and/or stress (48%) scores. Triggers for depressed, anxious, or stressed mood included severe pain (47%), health concerns (46%), and interpersonal relationship challenges (45%). At graduation, significant improvement in median depression (-54%), anxiety (-50%), and stress (-33%) symptom scores was observed among those with non-normal baseline values (p < 0.001); degree of improvement did not vary by participant age or sex. Participants in a nationally scaled telebehavioral health program for chronic pain experienced significant improvement in depression, anxiety, and stress symptoms and shared several complaints, goals, and mood triggers.

Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

PubMed Central

Lemos, Laurinda; Alegria, Carlos; Oliveira, Joana; Machado, Ana; Oliveira, Pedro; Almeida, Armando

2011-01-01

In idiopathic trigeminal neuralgia (TN) the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1) a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol]), (2) the association of gabapentin (GBP) and analgesic block of trigger-points with ropivacaine (ROP) (GBP+ROP protocol), and (3) a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol). Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols) from cases of idiopathic TN, or selected for MVD surgery (n = 22) due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS) and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1) TN patients should be carefully evaluated before choosing therapy for pain control, (2) different pharmacological approaches are available to initiate pain control at low costs, and (3) criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time. PMID:21941455

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy.

PubMed

Ghiringhelli, François; Apetoh, Lionel

2014-01-01

Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1β and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.

Electrical Storm: Incidence, Prognosis and Therapy.

PubMed

Sagone, Antonio

2015-12-01

The term "electrical storm" indicates a life-threatening clinical condition characterized by the recurrence of hemodynamically unstable ventricular tachycardia and/or ventricular fibrillation, in particular in patients with ICD implanted for primary or secondary prevention. Although there isn't a shared definition of electrical storm, nowadays the most accepted definition refers to three or more separate arrhythmia episodes leading to ICD therapies including antitachycardia pacing or shock occurring over a single 24 hours' time period. Clinical presentation can be dramatic and triggering mechanism are not clear at all yet, but electrical storm is associated with high mortality rates and low patients quality of life, both in the acute phase and in the long term. The first line therapy is based on antiarrhythmic drugs to suppress electrical storm, but in refractory patients, interventions such as catheter ablation or in some cases surgical cardiac sympathetic denervation might be helpful. Anyhow, earlier interventional management can lead to better outcomes than persisting with antiarrhythmic pharmacologic therapy and, when available, an early interventional approach should be preferred.

Recurrent abdominal pain in childhood.

PubMed

Chiou, Fang Kuan; How, Choon How; Ong, Christina

2013-04-01

Recurrent abdominal pain in childhood is common, and continues to be a diagnostic and therapeutic challenge. It is usually attributed to a functional gastrointestinal disorder rather than an organic disease. In most cases, a comprehensive history and physical examination should enable one to make a positive diagnosis of functional disorder. The presence of alarm symptoms and signs, such as weight loss, gastrointestinal bleeding and chronic severe diarrhoea, warrants further investigations and referral to a paediatric gastrointestinal specialist. The mainstay of therapy in functional abdominal pain is education, reassurance and avoidance of triggering factors. While symptom-based pharmacological therapy may be helpful in patients who do not respond to simple management, it is best used on a time-limited basis due to the lack of good evidence of its efficacy. The primary goal of therapy is a return to normal daily activities rather than complete elimination of pain. In recalcitrant cases, psychological interventions such as cognitive behaviour therapy and relaxation training have proven to be efficacious.

Cancer therapy in the necroptosis era

PubMed Central

Su, Z; Yang, Z; Xie, L; DeWitt, J P; Chen, Y

2016-01-01

Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Recently, necroptosis-based cancer therapy has been proposed to be a novel strategy for antitumor treatment. However, a big controversy exists on whether this type of therapy is feasible or just a conceptual model. Proponents believe that because necroptosis and apoptosis use distinct molecular pathways, triggering necroptosis could be an alternative way to eradicate apoptosis-resistant cancer cells. This hypothesis has been preliminarily validated by recent studies. However, some skeptics doubt this strategy because of the intrinsic or acquired defects of necroptotic machinery observed in many cancer cells. Moreover, two other concerns are whether or not necroptosis inducers are selective in killing cancer cells without disturbing the normal cells and whether it will lead to inflammatory diseases. In this review, we summarize current studies surrounding this controversy on necroptosis-based antitumor research and discuss the advantages, potential issues, and countermeasures of this novel therapy. PMID:26915291

Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue

PubMed Central

Lester, Joanne; Pahouja, Gaurav; Andersen, Barbara; Lustberg, Maryam

2015-01-01

Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors. PMID:25815692

Atrophic vaginitis in breast cancer survivors: a difficult survivorship issue.

PubMed

Lester, Joanne; Pahouja, Gaurav; Andersen, Barbara; Lustberg, Maryam

2015-03-25

Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors.

Fabry disease

PubMed Central

2010-01-01

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones. PMID:21092187