A prime-boost immunisation regimen using recombinant BCG and Pr55 gag virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons

Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55 gag virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55 gag VLPs. © 2009 Elsevier Ltd. All rights reserved.

A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P= 0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 μg/week ( ≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).

Radiosensitizing effect of electrochemotherapy in a fractionated radiation regimen in radiosensitive murine sarcoma and radioresistant adenocarcinoma tumor model

Radiosensitizing Effect of Electrochemotherapy in a Fractionated Radiation Regimen in Radiosensitive Murine Sarcoma and Radioresistant Adenocarcinoma Tumor Model. Electrochemotherapy can potentiate the radiosensitizing effect of bleomycin, as shown in our previous studies. To bring this treatment closer to use in clinical practice, we evaluated the interaction between electrochemotherapy with bleomycin and single-dose or fractionated radiation in two murine tumor models with different histology and radiosensitivity. Radiosensitive sarcoma SA-1 and radioresistant adenocarcinoma CaNT subcutaneous tumors grown in A/J and CBA mice, respectively, were used. The anti-tumor effect and skin damage around the treated tumors were evaluated after electrochemotherapy with bleomycin alone or combined with single-dose radiation or a fractionated radiation regimen. The anti-tumor effectiveness of electrochemotherapy was more pronounced in SA-1 than CaNT tumors. In both tumor models, the tumor response to radiation was not significantly influenced by bleomycin alone or by electroporation alone. However, electrochemotherapy before the first tumor irradiation potentiated the response to a single-dose or fractionated radiation regimen in both tumors. For the fractionated radiation regimen, normal skin around the treated tumors was damaged fourfold less than for the single-dose regimen. Electrochemotherapy prior to single-dose irradiation induced more damage to the skin around the treated tumors and greater loss of body weight compared to other irradiated groups, whereas electrochemotherapy combined with the fractionated radiation regimen did not. Electrochemotherapy with low doses of bleomycin can also be used safely for radiosensitization of different types of tumors in a fractionated radiation regimen, resulting in a good anti-tumor effect and no major potentiating effect on radiation-induced skin damage. © 2009 by Radiation Research Society.

Compliance in peritoneal dialysis : a qualitative study of renal nurses

End-stage renal failure is a life-threatening condition, often treated with home-based peritoneal dialysis (PD). PD is a demanding regimen, and the patients who practise it must make numerous lifestyle changes and learn complicated biomedical techniques. In our experience, the renal nurses who provide mostPDeducation frequently express concerns that patient compliance with their teaching is poor. These concerns are mirrored in the renal literature. It has been argued that the perceived failure of health professionals to improve compliance rates with PD regimens is because ‘compliance’ itself has never been adequately conceptualized or defined; thus, it is difficult to operationalize and quantify. This paper examines how a group of Australian renal nurses construct patient compliance with PD therapy. These empirical data illuminate how PD compliance operates in one practice setting; how it is characterized by multiple and often competing energies; and how ultimately it might be pointless to try to tame ‘compliance’ through rigid definitions and measurement, or to rigidly enforce it in PD patients. The energies involved are too fractious and might be better spent, as many of the more experienced nurses in this study argue, in augmenting the energies that do work well together to improve patient outcomes.

Zinc supplementation at conventional doses does not improve the disturbance of taste perception in hemodialysis patients

Objective: To determine the effect of zinc supplementation on taste perception in a group of hemodialysis patients. Design and Setting: Double-blind randomized placebo-controlled study in a teaching hospital dialysis unit. Patients: Fifteen stable hemodialysis patients randomized to placebo (6 male, 2 female; median age, 67; range, 30 to 72 years) or treatment (5 male, 2 female; median age, 60; range, 31 to 76 years). Intervention: Treatment group received zinc sulfate 220 mg per day for 6 weeks, and the placebo group received an apparently identical dummy pill. Main Outcome Measures: Taste scores by visual analogue scales, normalized protein catabolic rate and plasma, whole blood and red cell zinc levels. Results: At baseline, sweet and salt tastes were identified correctly by both groups. Sour was often confused with salt. Sour solutions of different concentrations were not distinguishable. Taste scores were not different after 6 weeks for either group. There was no significant increment in zinc levels or normalized protein catabolic rate for either group. Conclusion: We found a disturbance of taste perception in hemodialysis patients, particularly for the sour modality, which was not corrected by this regimen of zinc supplementation. These results cast doubts on the conclusions of earlier studies that indicated an improvement in taste after zinc supplementation.

Antiretroviral therapy (ART) adherence among people living with HIV/AIDS (PLHIV) in the north of Vietnam : a multi-method approach

The antiretroviral therapy (ART) program for People Living with HIV/AIDS (PLHIV) in Vietnam has been scaled up rapidly in recent years (from 50 clients in 2003 to almost 38,000 in 2009). ART success is highly dependent on the ability of the patients to fully adhere to the prescribed treatment regimen. Despite the remarkable extension of ART programs in Vietnam, HIV/AIDS program managers still have little reliable data on levels of ART adherence and factors that might promote or reduce adherence. Several previous studies in Vietnam estimated extremely high levels of ART adherence among their samples, although there are reasons to question the veracity of the conclusion that adherence is nearly perfect. Further, no study has quantitatively assessed the factors influencing ART adherence. In order to reduce these gaps, this study was designed to include several phases and used a multi-method approach to examine levels of ART non-adherence and its relationship to a range of demographic, clinical, social and psychological factors. The study began with an exploratory qualitative phase employing four focus group discussions and 30 in-depth interviews with PLHIV, peer educators, carers and health care providers (HCPs). Survey interviews were completed with 615 PLHIV in five rural and urban out-patient clinics in northern Vietnam using an Audio Computer Assisted Self-Interview (ACASI) and clinical records extraction. The survey instrument was carefully developed through a systematic procedure to ensure its reliability and validity. Cultural appropriateness was considered in the design and implementation of both the qualitative study and the cross sectional survey. The qualitative study uncovered several contrary perceptions between health care providers and HIV/AIDS patients regarding the true levels of ART adherence. Health care providers often stated that most of their patients closely adhered to their regimens, while PLHIV and their peers reported that “it is not easy” to do so. The quantitative survey findings supported the PLHIV and their peers’ point of view in the qualitative study, because non-adherence to ART was relatively common among the study sample. Using the ACASI technique, the estimated prevalence of onemonth non-adherence measured by the Visual Analogue Scale (VAS) was 24.9% and the prevalence of four-day not-on-time-adherence using the modified Adult AIDS Clinical Trials Group (AACTG) instrument was 29%. Observed agreement between the two measures was 84% and kappa coefficient was 0.60 (SE=0.04 and p<0.0001). The good agreement between the two measures in the current study is consistent with those found in previous research and provides evidence of cross-validation of the estimated adherence levels. The qualitative study was also valuable in suggesting important variables for the survey conceptual framework and instrument development. The survey confirmed significant correlations between two measures of ART adherence (i.e. dose adherence and time adherence) and many factors identified in the qualitative study, but failed to find evidence of significant correlations of some other factors and ART adherence. Non-adherence to ART was significantly associated with untreated depression, heavy alcohol use, illicit drug use, experiences with medication side-effects, chance health locus of control, low quality of information from HCPs, low satisfaction with received support and poor social connectedness. No multivariate association was observed between ART adherence and age, gender, education, duration of ART, the use of adherence aids, disclosure of ART, patients’ ability to initiate communication with HCPs or distance between clinic and patients’ residence. This is the largest study yet reported in Asia to examine non-adherence to ART and its possible determinants. The evidence strongly supports recent calls from other developing nations for HIV/AIDS services to provide screening, counseling and treatment for patients with depressive symptoms, heavy use of alcohol and substance use. Counseling should also address fatalistic beliefs about chance or luck determining health outcomes. The data suggest that adherence could be enhanced by regularly providing information on ART and assisting patients to maintain social connectedness with their family and the community. This study highlights the benefits of using a multi-method approach in examining complex barriers and facilitators of medication adherence. It also demonstrated the utility of the ACASI interview method to enhance open disclosure by people living with HIV/AIDS and thus, increase the veracity of self-reported data.

Abrogation of contaminating RNA activity in HIV-1 Gag VLPs

Background: HIV-1 Gag virus like particles (VLPs) used as candidate vaccines are regarded as inert particles as they contain no replicative nucleic acid, although they do encapsidate cellular RNAs. During HIV-1 Gag VLP production in baculovirus-based expression systems, VLPs incorporate the baculovirus Gp64 envelope glycoprotein, which facilitates their entry into mammalian cells. This suggests that HIV-1 Gag VLPs produced using this system facilitate uptake and subsequent expression of encapsidated RNA in mammalian cells - an unfavourable characteristic for a vaccine. Methods. HIV-1 Gag VLPs encapsidating reporter chloramphenicol acetyl transferase (CAT) RNA, were made in insect cells using the baculovirus expression system. The presence of Gp64 on the VLPs was verified by western blotting and RT-PCR used to detect and quantitate encapsidated CAT RNA. VLP samples were heated to inactivate CAT RNA. Unheated and heated VLPs incubated with selected mammalian cell lines and cell lysates tested for the presence of CAT protein by ELISA. Mice were inoculated with heated and unheated VLPs using a DNA prime VLP boost regimen. Results: HIV-1 Gag VLPs produced had significantly high levels of Gp64 (∼1650 Gp64 molecules/VLP) on their surfaces. The amount of encapsidated CAT RNA/g Gag VLPs ranged between 0.1 to 7 ng. CAT protein was detected in 3 of the 4 mammalian cell lines incubated with VLPs. Incubation with heated VLPs resulted in BHK-21 and HeLa cell lysates showing reduced CAT protein levels compared with unheated VLPs and HEK-293 cells. Mice inoculated with a DNA prime VLP boost regimen developed Gag CD8 and CD4 T cell responses to GagCAT VLPs which also boosted a primary DNA response. Heating VLPs did not abrogate these immune responses but enhanced the Gag CD4 T cell responses by two-fold. Conclusions: Baculovirus-produced HIV-1 Gag VLPs encapsidating CAT RNA were taken up by selected mammalian cell lines. The presence of CAT protein indicates that encapsidated RNA was expressed in the mammalian cells. Heat-treatment of the VLPs altered the ability of protein to be expressed in some cell lines tested but did not affect the ability of the VLPs to stimulate an immune response when inoculated into mice. © 2011 Valley-Omar et al; licensee BioMed Central Ltd.

Human immunodeficiency virus type 1 subtype C Gag virus-like particle boost substantially improves the immune response to a subtype C gag DNA vaccine in mice

Human immunodeficiency virus type 1 (HIV-1) subtype C is the predominant HIV in southern Africa, and is the target of a number of recent vaccine candidates. It has been proposed that a heterologous prime/boost vaccination strategy may result in stronger, broader and more prolonged immune responses. Since HIV-1 Gag Pr55 polyprotein can assemble into virus-like particles (VLPs) which have been shown to induce a strong cellular immune response in animals, we showed that a typical southern African subtype C Pr55 protein expressed in insect cells via recombinant baculovirus could form VLPs. We then used the baculovirus-produced VLPs as a boost to a subtype C HIV-1 gag DNA prime vaccination in mice. This study shows that a low dose of HIV-1 subtype C Gag VLPs can significantly boost the immune response to a single subtype C gag DNA inoculation in mice. These results suggest a possible vaccination regimen for humans. © 2004 SGM.

HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine

A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55gag virus-like particle prepared using a subtype C Pr55gag protein (Gag VLP) was tested in a prime-boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.u.) per 106 peripheral blood mononuclear cells (PBMCs), whilst the response of two baboons to the Gag VLP vaccine ranged from 415 to 465 s.f.u. per 106 PBMCs. An increase in the Gag-specific response to a range of 775-3583 s.f.u. per 106 PBMCs was achieved by boosting with Gag VLPs the five baboons that were primed with pTHGag. No improvement in Gag responses was achieved in this prime-boost inoculation regimen by increasing the number of pTHGag inoculations to six. IFN-γ responses were mapped to several peptides, some of which have been reported to be targeted by PBMCs from HIV-1 subtype C-infected individuals. Gag VLPs, given as a single-modality regimen, induced a predominantly CD8+ T-cell IFN-γ response and interleukin-2 was a major cytokine within a mix of predominantly Th1 cytokines produced by a DNA-VLP prime-boost modality. The prime-boost inoculation regimen induced high serum p24 antibody titres in all baboons, which were several fold above that induced by the individual vaccines. Overall, this study demonstrated that these DNA prime/VLP boost vaccine regimens are highly immunogenic in baboons, inducing high-magnitude and broad multifunctional responses, providing support for the development of these products for clinical trials. © 2008 SGM.

HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55 Gagprotein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55 Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1. © 2010 Pillay et al; licensee BioMed Central Ltd.

Nutritional status of Ugandan women living with HIV/AIDS : anthropometry and body composition assessment

Human immunodeficiency virus (HIV) that leads to acquired immune deficiency syndrome (AIDs) reduces immune function, resulting in opportunistic infections and later death. Use of antiretroviral therapy (ART) increases chances of survival, however, with some concerns regarding fat re-distribution (lipodystrophy) which may encompass subcutaneous fat loss (lipoatrophy) and/or fat accumulation (lipohypertrophy), in the same individual. This problem has been linked to Antiretroviral drugs (ARVs), majorly, in the class of protease inhibitors (PIs), in addition to older age and being female. An additional concern is that the problem exists together with the metabolic syndrome, even when nutritional status/ body composition, and lipodystrophy/metabolic syndrome are unclear in Uganda where the use of ARVs is on the increase. In line with the literature, the overall aim of the study was to assess physical characteristics of HIV-infected patients using a comprehensive anthropometric protocol and to predict body composition based on these measurements and other standardised techniques. The other aim was to establish the existence of lipodystrophy, the metabolic syndrome, andassociated risk factors. Thus, three studies were conducted on 211 (88 ART-naïve) HIV-infected, 15-49 year-old women, using a cross-sectional approach, together with a qualitative study of secondary information on patient HIV and medication status. In addition, face-to-face interviews were used to extract information concerning morphological experiences and life style. The study revealed that participants were on average 34.1±7.65 years old, had lived 4.63±4.78 years with HIV infection and had spent 2.8±1.9 years receiving ARVs. Only 8.1% of participants were receiving PIs and 26% of those receiving ART had ever changed drug regimen, 15.5% of whom changed drugs due to lipodystrophy. Study 1 hypothesised that the mean nutritional status and predicted percent body fat values of study participants was within acceptable ranges; different for participants receiving ARVs and the HIV-infected ART-naïve participants and that percent body fat estimated by anthropometric measures (BMI and skinfold thickness) and the BIA technique was not different from that predicted by the deuterium oxide dilution technique. Using the Body Mass Index (BMI), 7.1% of patients were underweight (<18.5 kg/m2) and 46.4% were overweight/obese (≥25.0 kg/m2). Based on waist circumference (WC), approximately 40% of the cohort was characterized as centrally obese. Moreover, the deuterium dilution technique showed that there was no between-group difference in the total body water (TBW), fat mass (FM) and fat-free mass (FFM). However, the technique was the only approach to predict a between-group difference in percent body fat (p = .045), but, with a very small effect (0.021). Older age (β = 0.430, se = 0.089, p = .000), time spent receiving ARVs (β = 0.972, se = 0.089, p = .006), time with the infection (β = 0.551, se = 0.089, p = .000) and receiving ARVs (β = 2.940, se = 1.441, p = .043) were independently associated with percent body fat. Older age was the greatest single predictor of body fat. Furthermore, BMI gave better information than weight alone could; in that, mean percentage body fat per unit BMI (N = 192) was significantly higher in patients receiving treatment (1.11±0.31) vs. the exposed group (0.99±0.38, p = .025). For the assessment of obesity, percent fat measures did not greatly alter the accuracy of BMI as a measure for classifying individuals into the broad categories of underweight, normal and overweight. Briefly, Study 1 revealed that there were more overweight/obese participants than in the general Ugandan population, the problem was associated with ART status and that BMI broader classification categories were maintained when compared with the gold standard technique. Study 2 hypothesized that the presence of lipodystrophy in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants. Results showed that 112 (53.1%) patients had experienced at least one morphological alteration including lipohypertrophy (7.6%), lipoatrophy (10.9%), and mixed alterations (34.6%). The majority of these subjects (90%) were receiving ARVs; in fact, all patients receiving PIs reported lipodystrophy. Period spent receiving ARVs (t209 = 6.739, p = .000), being on ART (χ2 = 94.482, p = .000), receiving PIs (Fisher’s exact χ2 = 113.591, p = .000), recent T4 count (CD4 counts) (t207 = 3.694, p = .000), time with HIV (t125 = 1.915, p = .045), as well as older age (t209 = 2.013, p = .045) were independently associated with lipodystrophy. Receiving ARVs was the greatest predictor of lipodystrophy (p = .000). In other analysis, aside from skinfolds at the subscapular (p = .004), there were no differences with the rest of the skinfold sites and the circumferences between participants with lipodystrophy and those without the problem. Similarly, there was no difference in Waist: Hip ratio (WHR) (p = .186) and Waist: Height ratio (WHtR) (p = .257) among participants with lipodystrophy and those without the problem. Further examination showed that none of the 4.1% patients receiving stavudine (d4T) did experience lipoatrophy. However, 17.9% of patients receiving EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI) had lipoatrophy. Study 2 findings showed that presence of lipodystrophy in participants receiving ARVs was in fact far higher than that of HIV-infected ART-naïve participants. A final hypothesis was that the prevalence of the metabolic syndrome in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants. Moreover, data showed that many patients (69.2%) lived with at least one feature of the metabolic syndrome based on International Diabetic Federation (IDF, 2006) definition. However, there was no single anthropometric predictor of components of the syndrome, thus, the best anthropometric predictor varied as the component varied. The metabolic syndrome was diagnosed in 15.2% of the subjects, lower than commonly reported in this population, and was similar between the medicated and the exposed groups (χ 21 = 0.018, p = .893). Moreover, the syndrome was associated with older age (p = .031) and percent body fat (p = .012). In addition, participants with the syndrome were heavier according to BMI (p = .000), larger at the waist (p = .000) and abdomen (p = .000), and were at central obesity risk even when hip circumference (p = .000) and height (p = .000) were accounted for. In spite of those associations, results showed that the period with disease (p = .13), CD4 counts (p = .836), receiving ART (p = .442) or PIs (p = .678) were not associated with the metabolic syndrome. While the prevalence of the syndrome was highest amongst the older, larger and fatter participants, WC was the best predictor of the metabolic syndrome (p = .001). Another novel finding was that participants with the metabolic syndrome had greater arm muscle circumference (AMC) (p = .000) and arm muscle area (AMA) (p = .000), but the former was most influential. Accordingly, the easiest and cheapest indicator to assess risk in this study sample was WC should routine laboratory services not be feasible. In addition, the final study illustrated that the prevalence of the metabolic syndrome in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants.

Preparing for performance capture #1

This video article articulates two exercises that have been developed to respond to the need for preparedness in the growing field of Performance Capture. The first is called Walking Through (Delbridge 2013), where the actor navigates a series of objects that exist in screen space through a developed sense of the existing physical particularities of the studio and an interaction with a screen (or feedback loop). The second exercise is called The Donut (Delbridge 2013), where the performer continues to navigate screen space but this time does so through the literal stepping through of a Torus in the virtual – again with nothing but the studio infrastructure and the screen as a guide. Notions of Motion Captured performance infer the existence of an interface that combines performer with system, separating (or intervening in) the space between performance and the screen. It is precisely the effect and provided opportunity of the intermediary device on the practice, craft and preparedness of the actor as they navigate the connection between 3D screen space and the physical properties of the studio that is examined here. Defining the scope of current practice for the contemporary actor is a key construct of this challenge, with the most appropriate definition revolving around the provision of a required mixture of performance and content for live, mediated, framed and variously captured formats. One of these particular formats is Performance Capture. The exercises presented here are two from a series, developed over a three year study that contribute to our understanding of the potential for a training regimen to be developed for the rigors of Performance Capture.

The effectiveness of health education using the teach-back method on adherence and self-management in chronic disease: A systematic review protocol

Review question/objective What is the effect of using the teach-back method for health education to improve adherence to treatment regimen and self-management in chronic disease? Inclusion criteria Types of participants This review will consider all studies that include adult patients (aged 18 years and over) in any healthcare setting, either as inpatients (eg acute care, medical and surgical wards) or those who attend primary health care, family medical practice, general medical practice, clinics, outpatient departments, rehabilitation or community settings. Participants need to have been diagnosed as having one or more chronic diseases including heart failure, diabetes, cardiovascular disease, cancer, respiratory disease, asthma, chronic obstructive pulmonary disease, chronic kidney disease, arthritis, epilepsy or a mental health condition. Studies that include seriously ill patients, and/or those who have impairments in verbal communication and cognitive function will be excluded. Types of intervention This review will consider studies that investigate the use of the teach-back method alone or in combination with other supporting education, either in routine or research intervention education programs; regardless of how long the programs were and whether or not a follow-up was conducted. The intervention could be delivered by any healthcare professional. The comparator will be any health education for chronic disease that does not include the teach-back method. Types of outcomes Primary outcomes of interest are disease-specific knowledge, adherence, and self-management knowledge, behavior and skills measured using patient report, nursing observation or validated measurement scales. Secondary outcomes include knowledge retention, self-efficacy, hospital readmission, hospitalization, and quality of life, also measured using patient report, nursing observation, hospital records or validated measurement scales.

Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.