Acupressure to Reduce Treatment-Related Symptoms for Children With Cancer and Recipients of Hematopoietic Stem Cell Transplant: Protocol for a Randomized Controlled Trial.

BACKGROUND: We describe the study design and protocol of a pragmatic randomized controlled trial (RCT) Acupressure for Children in Treatment for a Childhood Cancer (ACT-CC). OBJECTIVE: To describe the feasibility and effectiveness of an acupressure intervention to decrease treatment-related symptoms in children in treatment for cancer or recipients of a chemotherapy-based hematopoietic stem cell transplant (HSCT). DESIGN: Two-armed RCTs with enrollment of 5 to 30 study days. SETTING: Two pediatric teaching hospitals. PATIENTS: Eighty-five children receiving cancer treatment or a chemotherapy-based HSCT each with 1 parent or caregiver. INTERVENTION: Patients are randomized 1:1 to receive either usual care plus daily professional acupressure and caregiver delivered acupressure versus usual care alone for symptom management. Participants receive up to 20 professional treatments. MAIN OUTCOME: A composite nausea/vomiting measure for the child. SECONDARY OUTCOMES: Child's nausea, vomiting, pain, fatigue, depression, anxiety, and positive affect. PARENT OUTCOMES: Depression, anxiety, posttraumatic stress symptoms, caregiver self-efficacy, and positive affect. Feasibility of delivering the semistandardized intervention will be described. Linear mixed models will be used to compare outcomes between arms in children and parents, allowing for variability in diagnosis, treatment, and age. DISCUSSION: Trial results could help childhood cancer and HSCT treatment centers decide about the regular inclusion of trained acupressure providers to support symptom management.

Incorporating telemedicine into the integrated care of the COPD patient a summary of an interdisciplinary workshop held in Stresa, Italy, 7-8 September 2017.

This report is a summary of a workshop focusing on using telemedicine to facilitate the integrated care of chronic obstructive pulmonary disease (COPD). Twenty-five invited participants from 8 countries met for one and one-half days in Stresa, Italy on 7-8 September 2017, to discuss this topic. Participants included physiotherapists, nurses, a nurse practitioner, and physicians. While evidence-based data are always at the center of sound inference and recommendations, at this point in time the science behind telemedicine in COPD remains under-developed; therefore, this document reflects expert opinion and consensus. While telemedicine has great potential to expand and improve the care of our COPD patients, its application is still in its infancy. While studies have demonstrated its effectiveness in some patient-centered outcomes, the results are by no means consistently positive. Whereas this tool may potentially reduce health care costs by moving some medical interventions from centralized locations in to patient's home, its cost-effectiveness has had mixed results and telemonitoring has yet to prove its worth in the COPD population. These discordant results should not be unexpected in view of patient complexity and the heterogeneity of telemedicine. This is reflected in the very limited support offered by the National Health Services to a wider application of telemedicine in the integrated care of COPD patients. However, this situation should challenge us to develop the necessary science to clarify the role of telemedicine in the medical management of our patients, providing a better and definitive scientific basis to this approach.

Chimeric Antigen Receptor T Cells: Extending Translation from Liquid to Solid Tumors.

Successful translation of chimeric antigen receptor (CAR) T cells designed to target and eradicate CD19+ lymphomas has emboldened scientists and physicians worldwide to explore the possibility of applying CAR T-cell technology to other tumor entities, including solid tumors. Next-generation strategies such as fourth-generation CARs (CAR T cells redirected for universal cytokine killing, also known as TRUCKs) designed to deliver immunomodulatory cytokines to the tumor microenvironment, dual CAR designs to improve tumor control, inclusion of suicide genes as safety switches, and precision genome editing are currently being investigated. One major ongoing goal is to determine how best to generate CAR T cells that modulate the tumor microenvironment, overcome tumor survival mechanisms, and thus allow broader applicability as universal allogeneic T-cell therapeutics. Development of state-of-the-art and beyond viral vector systems to deliver designer CARs coupled with targeted genome editing is expected to generate more effective off-the-shelf CAR T cells with activity against a greater number of cancer types and importantly solid tumors.

Aperture Synthesis Shows Perceptual Integration of Geometrical Form Across Saccades.

We investigated the perceptual bias in perceived relative lengths in the Brentano version of the Müller-Lyer arrowheads figure. The magnitude of the bias was measured both under normal whole-figure viewing condition and under an aperture viewing condition, where participants moved their gaze around the figure but could see only one arrowhead at a time through a Gaussian-weighted contrast window. The extent of the perceptual bias was similar under the two conditions. The stimuli were presented on a CRT in a light-proof room with room-lights off, but visual context was provided by a rectangular frame surrounding the figure. The frame was either stationary with respect to the figure or moved in such a manner that the bias would be counteracted if the observer were locating features with respect to the frame. Biases were reduced in the latter condition. We conclude that integration occurs over saccades, but largely in an external visual framework, rather than in a body-centered frame using an extraretinal signal.

Integrating the care of the complex COPD patient.

Proceedings of the European Seminars in Respiratory Medicine course, Long-Term Integrated Care of COPD Patients held in Stresa, Italy, on 16-17 June, 2016.

Neuronal Nicotinic Acetylcholine Receptor Modulators Reduce Sugar Intake.

Excess sugar consumption has been shown to contribute directly to weight gain, thus contributing to the growing worldwide obesity epidemic. Interestingly, increased sugar consumption has been shown to repeatedly elevate dopamine levels in the nucleus accumbens (NAc), in the mesolimbic reward pathway of the brain similar to many drugs of abuse. We report that varenicline, an FDA-approved nicotinic acetylcholine receptor (nAChR) partial agonist that modulates dopamine in the mesolimbic reward pathway of the brain, significantly reduces sucrose consumption, especially in a long-term consumption paradigm. Similar results were observed with other nAChR drugs, namely mecamylamine and cytisine. Furthermore, we show that long-term sucrose consumption increases α4ß2 * and decreases α6ß2* nAChRs in the nucleus accumbens, a key brain region associated with reward. Taken together, our results suggest that nAChR drugs such as varenicline may represent a novel treatment strategy for reducing sugar consumption.

Comparative chemical and biochemical analysis of extracts of Hibiscus sabdariffa.

Hibiscus sabdariffa extracts have attracted attention because of potentially useful bioactivity. However, there have been no systematic studies of extraction efficiencies of H. sabdariffa. The nature of extracts used in different studies has varied considerably, making comparisons difficult. Therefore, a systematic study of extracts of H. sabdariffa made with different solvents was carried out using water, methanol, ethyl acetate and hexane in the presence/absence of formic acid, using different extraction times and temperatures. The extracts were analysed for total polyphenol content, antioxidant capacity using DPPH, FRAP and TEAC assays, and specific anthocyanins were determined using HPLC and LC-MS. The results showed the highest antioxidant capacities were obtained by extracting using water, with or without formic acid, for 10 min at 100°C. These extracts provided the highest concentrations of cyanidin 3-sambubioside and delphinidin 3-sambubioside. It will be important to use extraction conditions giving optimal extraction efficiencies for subsequent bioactivity experiments.

20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. High mortality from HCC is mainly due to widespread prevalence and the lack of effective treatment, since systemic chemotherapy is ineffective, while the targeted agent Sorafenib extends median survival only briefly. The steroidal saponin 20(S)-ginsenoside Rg3 from Panax ginseng C.A. Meyer is proposed to chemosensitize to various therapeutic drugs through an unknown mechanism. Since autophagy often serves as cell survival mechanism in cancer cells exposed to chemotherapeutic agents, we examined the ability of Rg3 to inhibit autophagy and chemosensitize HCC cell lines to doxorubicin in vitro. We show that Rg3 inhibits late stage autophagy, possibly through changes in gene expression. Doxorubicin-induced autophagy plays a protective role in HCC cells, and therefore Rg3 treatment synergizes with doxorubicin to kill HCC cell lines, but the combination is relatively nontoxic in normal liver cells. In addition, Rg3 was well-tolerated in mice and synergized with doxorubicin to inhibit tumor growth in HCC xenografts in vivo. Since novel in vivo inhibitors of autophagy are desirable for clinical use, we propose that Rg3 is such a compound, and that combination therapy with classical chemotherapeutic drugs may represent an effective therapeutic strategy for HCC treatment.

Development of image segmentation methods for intracranial aneurysms.

Though providing vital means for the visualization, diagnosis, and quantification of decision-making processes for the treatment of vascular pathologies, vascular segmentation remains a process that continues to be marred by numerous challenges. In this study, we validate eight aneurysms via the use of two existing segmentation methods; the Region Growing Threshold and Chan-Vese model. These methods were evaluated by comparison of the results obtained with a manual segmentation performed. Based upon this validation study, we propose a new Threshold-Based Level Set (TLS) method in order to overcome the existing problems. With divergent methods of segmentation, we discovered that the volumes of the aneurysm models reached a maximum difference of 24%. The local artery anatomical shapes of the aneurysms were likewise found to significantly influence the results of these simulations. In contrast, however, the volume differences calculated via use of the TLS method remained at a relatively low figure, at only around 5%, thereby revealing the existence of inherent limitations in the application of cerebrovascular segmentation. The proposed TLS method holds the potential for utilisation in automatic aneurysm segmentation without the setting of a seed point or intensity threshold. This technique will further enable the segmentation of anatomically complex cerebrovascular shapes, thereby allowing for more accurate and efficient simulations of medical imagery.

Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD.

BACKGROUND: Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood. METHODS: Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT. RESULTS: 59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (~5%) and strength (~20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT. CONCLUSIONS: The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.

Neuromuscular stimulation of quadriceps in patients hospitalised during an exacerbation of COPD: a comparison of low (35 Hz) and high (50 Hz) frequencies.

BACKGROUND: Neuromuscular electrical stimulation (NMES) has shown to improve skeletal muscle strength and exercise capacity in stable patients with chronic obstructive pulmonary disease (COPD). Variations in NMES protocols are considerable. We aimed to compare changes in muscle strength after high-frequency and low-frequency NMES in patients admitted to hospital with an acute exacerbation of COPD. METHODS: Patients were referred for inpatient (IP) rehabilitation during hospitalisation for an acute worsening of their COPD. They received 30-minute daily NMES to both quadriceps at a frequency of 35 or 50 Hz. NMES intensity was titrated to patients' tolerance. Isometric quadriceps muscle strength and endurance walking (ESWT) time were measured at baseline and on hospital discharge. RESULTS: A total of 10 patients in each treatment group underwent NMES during hospitalisation (mean [SD] age 68.0 [±7.4] years, FEV1 0.99 L [±0.58], FEV1/FVC 47% [± 27%], MRC 5 [IQR ±1]). There were no significant differences in baseline characteristics between groups. Muscle strength (legs combined) increased in both groups regardless of the NMES frequency used (35 Hz--3.8 ± 4.9; 50 Hz--3.4 ± 5.5 kg). This was only significant within the 35 Hz group. The change in ESWT also showed a trend to increase in both groups (35 Hz--109 ± 92.7; 50 Hz--145.6 ± 94.7). There was no significant difference between groups for either outcome. CONCLUSION: NMES is a feasible intervention to improve muscle strength in a cohort of patients admitted with an exacerbation of COPD. The response appears to be independent of the frequency used and both were well-tolerated.

Incidence of subarachnoid haemorrhage: an Australian national hospital morbidity database analysis.

Incidences of subarachnoid haemorrhage (SAH) in Australia have been reported in regional studies with variable rates. We investigated the national SAH rate and evaluated the trend over the 10 years from 1998 to 2008. The crude SAH incidence, not related to trauma or arteriovenous malformation, was estimated at 10.3 cases per 100,000 person-years (95% confidence interval [CI]: 10.2-10.4). Females have a higher incidence of SAH (12.5 cases per 100,000; 95% CI: 12.3-12.8) compared to males (8.0 cases per 100,000; 95% CI: 7.8-8.3), with age-adjusted incidence increases with increasing age for both sexes. Less than 10% of SAH occurred in the first three decades of life. The peak age group for patients to experience SAH was between 45 years and 64 years, accounting for almost 45% of the overall annual SAH admissions. Aneurysms located in the anterior circulation were a more common source of rupture compared to those located in the posterior circulation (rate ratio 3.9; 95% CI: 3.6-4.2). Contrary to contemporary observations in the literature, we did not observe a decline in the incidence of SAH during this specified study period.

Flavanols and methylxanthines in commercially available dark chocolate: a study of the correlation with nonfat cocoa solids.

Intake of flavanols, a subgroup of dietary polyphenols present in many fruits and vegetables, may be associated with health benefits, particularly with reducing the risk of coronary diseases. Cocoa and chocolate products are rich in flavanol monomers, oligomers, and polymers (procyanidins). This study used normal phase HPLC to detect, identify, and quantify epicatechin, catechin, total monomers, procyanidin oligomers and polymers in 14 commercially available chocolate bars. In addition, methylxanthines (theobromine and caffeine) were also quantified. Nonfat cocoa solids (NFCS) were determined both gravimetrically and by calculation from theobromine contents. The flavanol levels of 12 commonly consumed brands of dark chocolate have been quantified and correlated with % theobromine and % NFCS. Epicatechin comprised the largest fraction of total chocolate flavonoids, with the remainder being catechin and procyanidins. Calculated NFCS did not reflect epicatechin (R(2) = 0.41) or total flavanol contents (R(2) = 0.49). Epicatechin (R(2) = 0.96) was a reliable marker of total flavanols, catechin (R(2) = 0.67) to a lesser extent. All dark chocolate tested contained higher levels of total flavanols (93.5-651.1 mg of epicatechin equiv/100 g of product) than a milk or a white "chocolate" (40.6 and 0.0 mg of epicatechin equiv/100 g, respectively). The amount and integrity of procyanidins often suffer in the manufacturing of chocolate, chiefly due to oxidation and alkalinization. In this study, the labeled cocoa content of the chocolate did not always reflect analyzed levels of flavonoids. Increasingly, high % NFCS is being used commercially to reflect chocolate quality. If the flavanol content of chocolate is accepted to be a key determinant of health benefits, then continued monitoring of flavanol levels in commercially available chocolate products may be essential for consumer assurance.

Pulmonary rehabilitation: WHAT WE KNOW AND WHAT WE NEED TO KNOW.

The multidisciplinary treatment of pulmonary rehabilitation (PR), which includes exercise training, self-management education, and psychosocial and nutritional intervention, is now a standard of care for chronic obstructive pulmonary disease (COPD) and has been incorporated into major guidelines. We must now focus efforts on improving its impact and widening its applicability. What is the direction of PR; where does it fit in the comprehensive care of the COPD patient; and how can clinicians best apply this important intervention? This was the charge of the roundtable discussion, Pulmonary Rehabilitation: Moving Forward, involving 20 experts from North America and Europe, which was convened in Fort Lauderdale, Florida, in early 2008. It is not meant to be an exhaustive review; rather, this report summarizes the roundtable proceedings, while providing direction to best position PR into the continuum of COPD care. By consensus, it was agreed upon that although PR is effective for other chronic respiratory diseases, the discussion focus was COPD since most of the evidence base and patient referral are for this disease. These proceedings provide insight into 3 broad areas appropriate for investigation or implementation: positioning PR in an integrated care model for COPD patients; improving the effectiveness of this intervention; and expanding the recognition, application, and accessibility to PR. It is the hope that this document will provide a catalyst for clinicians, investigators, and healthcare policy makers to help realize these goals as well as serve to suggest important areas for future research and development in PR.

Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease.

RATIONALE: Skeletal muscle strength and bulk are reduced in patients with chronic obstructive pulmonary disease (COPD) and influence quality of life, survival, and utilization of health care resources. Exercise training during pulmonary rehabilitation (PR) can reverse some of these effects. In athletes and healthy elderly individuals, dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training, thereby increasing muscle mass. OBJECTIVES: This article examines the effect of CrS on functional exercise capacity and muscle performance in people with COPD. METHODS: One hundred subjects with COPD (mean [SD] age, 68.2 [8.2] yr; FEV(1), 44.0 [19.6] %predicted) were randomized to a double-blind, placebo-controlled, parallel group trial of CrS during 7 weeks of PR encompassing aerobic and resistance exercises. Subjects ingested creatine (22 g/d loading for 5 d; maintenance, 3.76 g/d throughout PR) or placebo. Baseline, postloading, and postrehabilitation measurements included pulmonary function, body composition, peripheral muscle strength, and functional performance (shuttle walking tests). A volunteer subgroup (n = 44) had pre- and postloading quadriceps muscle biopsies. MEASUREMENTS AND MAIN RESULTS: Eighty subjects completed the trial (38 creatine, 42 placebo). All outcome measures significantly improved after PR. There were no significant differences between groups post-PR (mean [SD] change in incremental shuttle walk distance, 84 [79] m in the creatine group vs. 83.8 [60] m in the placebo group; P = 1.0; knee extensor work, 19.2 [16] Nm [Newton meters] in the creatine group vs. 19.5 [17] Nm in the placebo group; P = 0.9). Muscle biopsies showed evidence of creatine uptake. CONCLUSIONS: This adequately powered, randomized, placebo-controlled trial shows that CrS does not augment the substantial training effect of multidisciplinary PR for patients with COPD. Clinical trial registered with https://portal.nihr.ac.uk/Pages/NRRArchiveSearch.aspx (NO123138126).

Pulmonary rehabilitation for COPD.

Pulmonary rehabilitation is a therapeutic process, which entails taking a holistic approach to the welfare of the patient with chronic respiratory illness--most commonly chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation is considered essential throughout the lifetime management of patients with symptomatic chronic respiratory disease. It requires the coordinated action of a multidisciplinary healthcare team in order to deliver an individualised rehabilitation programme to best effect--incorporating multiple modalities, such as advice on smoking cessation, exercise training and patient self-management education, among others. As core components of pulmonary rehabilitation, exercise training and self-management education have been shown to be beneficial in improving health-related quality of life (HRQoL) in patients with chronic respiratory disease. Physical training can help to reduce the muscle de-conditioning that occurs when the activity of patients is restricted by their breathlessness and fatigue, and is often associated with an increase in patient HRQoL. HRQoL can also be improved by the use of self-management education, which is designed to provide the patient with the skills to manage the health consequences of their disease. In doing so, patients are better able to cope with disease symptoms, potentially leading to reduced healthcare costs. A great deal of research has been conducted to try and fully define which patients will benefit most from pulmonary rehabilitation. Although progress has been made, many questions remain as to the best means of delivering rehabilitation, particularly with respect to the optimum programme of physical training and patient self-management education.

Xanthine oxidase activity in vitro: effects of food extracts and components.

There is significant interest in the direct antioxidant activities of dietary polyphenols, due to associations between consumption of polyphenol-rich foods, such as fruits and vegetables, and decreased incidence of oxidative-stress related disease. However, indirect antioxidant action, such as the inhibition of ROS-producing enzymes, may be equally relevant to health benefits through a general reduction in oxidative stress in vivo. To this end, the effects of food extracts and individual compounds on the in vitro activity of xanthine oxidase (XO) were assessed, many for the first time. Several compounds were shown to be potent inhibitors in vitro, including hesperetin and theaflavin-3,3'-digallate with IC50 values of 39 and 49 microM, respectively. Of the extracts, cranberry juice, purple grape juice, and black tea were the most potent, with IC50 values of 2.4, 3.5, and 5.8% of extracts, respectively. Some samples were shown to promote XO activity over the concentration ranges tested, including orange juice and pink grapefruit juice. Certain "inhibitors", such as purple grape juice and black tea, promoted XO activity at low concentration. The possible role of dietary inhibitors of XO in reducing oxidative stress in vivo is discussed.

Histological changes associated with mesotherapy for fat dissolution.

Mesotherapy is a form of medical therapy popular in Europe and South America. It is used for treating a variety of medical conditions, including the treatment of localized fat deposits and cellulite. Phosphatidylcholine/deoxycholate injections are a popular technique to treat localized fat accumulations and have recently become synonymous with mesotherapy, although their history and technique are distinct. To treat localized fat deposits, phosphatidylcholine (PC) and deoxycholate (DC) are utilized. To date, there have been no published histological studies that explain the mechanism of action of PC and DC.Method. In this study the authors have obtained skin biopsies from a patient who had undergone mesotherapy with PC and DC. Punch biopsies were taken at one and two weeks after the procedure.Results. Each of the biopsies taken at one and two weeks after treatment with PC and DC showed a normal epithelium and dermis, with a mixed septal and lobular panniculitis. The fat lobules were infiltrated by increased numbers of lymphocytes and, in particular, macrophages. The macrophages consisted of conventional forms, foam cells, and multinucleated fat-containing giant cells. The inflammation was associated with serous atrophy and microcyst formation.Conclusion. This study demonstrates that mesotherapy with PC and DC affects the subcutaneous fat. We theorize that the reduction of subcutaneous fat likely follows inflammatory-mediated necrosis and resorption.

The effect of auditory feedback on phonation threshold pressure measurement.

The effect of auditory feedback on phonation threshold pressure (Pth) measurement was investigated in 14 females with normal, untrained voices. Two measurement systems (Glottal Enterprises MS 100--circumferentially vented mask and Kay Elemetrics Aerophone II--non-circumferentially vented mask) were examined under three conditions: (1) masked, (2) no mask, and (3) masked with enhanced auditory feedback-acoustic signal placed at ears through headphones. Masked with enhanced auditory feedback, in addition to subject training, significantly lowered Pth values regardless of mask design. The amount of auditory feedback provided by different mask designs was investigated and revealed a significant difference. Clinical significance of different auditory feedback levels provided by the two mask designs was investigated. Direct comparison of the mean values between systems was not possible because of each system's design and calibration. Comparisons were accomplished by subtracting means of select-paired conditions (masked/no mask; masked/masked plus masked with enhanced auditory feedback) within each system and then comparing these difference scores from the same paired conditions between each system. No clinical significance in difference scores was revealed because of varying amounts of auditory feedback provided by the masks. Results support the use of enhanced auditory feedback, in addition to subject training, when measuring Pth.