Dissemination and implementation strategies for physical activity guidelines among adults with disability, chronic conditions, and pregnancy: a systematic scoping review.

BACKGROUND: Physical activity guidelines for adults with disability, chronic conditions, and pregnancy (i.e., specific populations) have been developed to provide guidance for engaging in physical activity. However, specific populations remain considerably less physically active compared to the general population, presenting a knowledge-practice gap. PURPOSE: The purpose of this systematic scoping review was to identify and evaluate strategies for disseminating and implementing physical activity guidelines among specific populations and/or stakeholders (e.g., healthcare professionals) in Canada. METHODS: Five search approaches (peer-reviewed literature databases, grey literature database, custom Google search engines, targeted web-based searches, and content expert consultation) identified records documenting and/or evaluating strategies that had been used to disseminate or implement guidelines from a predetermined list. Systematic and scoping review protocols were followed. Risk of bias assessments were conducted for all studies that evaluated strategies. RESULTS: Eighty-one records reported dissemination strategies (n = 42), implementation strategies (n = 28), or both (n = 11). Twenty-two studies reporting on 29 evaluated strategies were deemed "serious" or "high" risk of bias. Common guideline dissemination and implementation strategies are deliberated and recommendations for future practice are made. CONCLUSIONS: Findings may inform future dissemination and implementation efforts for physical activity guidelines in Canada or similar countries.

Exercise is Medicine® Canada on Campus Casebook: Evaluation of a novel knowledge translation tool and lessons learned.

The Exercise is Medicine® Canada on Campus (EIMC-OC) program aims to integrate exercise prescription into healthcare and encourage students to implement physical activity initiatives on campus. However, multi-site interventions like EIMC-OC are often challenged with communicating and sharing strategies across geographically dispersed groups. The EIMC-OC Casebook was created as an accessible method to enhance program success by sharing ideas and implementation strategies between groups, but its potential utility is unknown as few studies have evaluated casebooks. This study evaluated the usability and value of the EIMC-OC Casebook for promoting physical activity and established end-users' insight on Casebook future directions. The Casebook was shared and semi-structured interviews were conducted with established and developing EIMC-OC groups. Five themes discussing the usability, value, and future directions of the Casebook were identified. Participants implemented the Casebook to varying degrees, found it to be a valuable communication medium, and recommended revisions, which may enhance its implementation. The EIMC-OC Casebook is a valuable tool that exemplifies campus-based efforts to promote physical activity, augments between-group communication, and helps groups conduct effective initiatives. Program leaders and researchers may benefit from a similar Casebook approach, and recommendations are provided to evaluators aiming to enhance the effectiveness of multi-site programs.

Dissemination and implementation of national physical activity, sedentary behaviour, and/or sleep guidelines among community-dwelling adults aged 18 years and older: a systematic scoping review and suggestions for future reporting and research.

Strategies for dissemination (purposive distribution of a guideline to specific audiences) and implementation (actions to support the general public in meeting guideline recommendations/behavioural benchmarks) of national movement guidelines (physical activity (PA), sedentary behaviour, and sleep) have yet to be synthesized. The purpose of this systematic scoping review was to identify strategies for dissemination and implementation of national PA, sedentary behaviour, and/or sleep guidelines among community-dwelling adults (aged >18 years) and/or stakeholders in Canada and analogous countries. Five search approaches (e.g., published literature, grey literature, targeted web-based, custom Google, and content expert consultation) identified records (e.g., empirical studies, organizational reports, website pages, or guideline messages) that discussed and/or evaluated dissemination or implementation strategies for a prespecified list of guidelines. A modified strategy classification system was developed to chart the data. Forty-seven reports met inclusion criteria. Dissemination strategies (n = 42) were more frequently reported than implementation strategies (n = 24). Implementation strategies were more frequently evaluated (n = 13 vs. 7 dissemination strategies) and associated with positive outcomes. The 13 studies that evaluated strategies were at high or serious risk of bias. We identified limited information about the dissemination and implementation of national movement guidelines and identified strategies were rarely evaluated. Greater efforts are required to increase the impact of guidelines among the general public and stakeholders and to build the evidence base in this field. (Open Science Framework registration: https://osf.io/4tyw3.) Novelty An adapted movement guideline dissemination and implementation strategy classification framework is provided. Knowledge translation efforts should be documented and evaluated to advance science and practice in the movement guideline field.

Subclinical disease revisited.

It has become commonplace to treat postoperative patients with adjuvant radiotherapy to increase local control. The reduction in local recurrences seen in patients with head and neck cancer following radiotherapy led to coining of the term "subclinical disease" to describe the presumed presence of small, clinically undetectable, nests of tumor cells which remain even after the most aggressive of surgeries. The basic assumption fundamental to the concept of subclinical disease is that any patient with residual disease will suffer a local failure if left untreated. For example, lymph node involvement, either clinically evident or pathologically proven, is considered an absolute indication for adjuvant therapy. A positive or "close" or "microscopically positive" margin is also considered grounds for further treatment. The purpose of this communication is to critically discuss recent reports that challenge this assumption.

Apoptosis may be either suppressed or enhanced with strategic combinations of antineoplastic drugs or anti-IgM.

A variety of drugs have been used to treat B-lymphocyte neoplasms, including both cell cycle-specific (CCS) and non-cell-cycle-specific drugs. Although the therapy for such cancers is complex and can include both types of drugs, the efficacy of these drugs in inducing cell death remains unclear. In this paper we have concentrated on specific CCS drugs and have examined their ability to induce programmed cell death (apoptosis) in Burkitt's lymphoma cell lines derived from patients. The CCS drugs chosen were hydroxyurea and aphidicolin (active in late G1, early S phase), the topoisomerase poisons camptothecin and etoposide (S, early G2 phase) and vincristine and Taxol (late G2, M phase). These choices allow comparison of two drugs with differing modes of action for each of the various phases of the cell cycle. Our results indicate that the variation in apoptosis between drugs that act at the same phase of the cell cycle is negligible. Both S/G2 and G2/M blockers are very potent at inducing apoptosis whereas G1/S blockers are ineffective in the induction of apoptosis. In addition, marked kinetic variations in the rate of apoptosis induction were observed, etoposide and camptothecin being more rapid in their action than the other agents. The order of effectiveness in inducing apoptosis on a kinetic basis was S/G2 agents >> G2/M agents >> G1/S agents. In this study we have also found that growth inhibition was induced by all the CCS agents chosen and by anti-IgM in various Burkitt's lymphoma lines. Furthermore c-myc was down-regulated under similar conditions. Since apoptosis was only selectively induced by some of the CCS agents, it implies c-myc expression is associated with growth regulation and c-myc down-regulation is an insufficient condition for the induction of apoptosis. In addition, cotreatments using the CCS and other agents revealed the following: Cotreatment using two CCS drugs which act at the same stage in the cell cycle showed either no change or only additivity to the effects seen with either agent alone. However, cotreatment with CCS drugs showed that an inhibitory effect is found between G1/S and G2/M drugs or S/G2 and G2/M drugs. No effect was found between G1/S and S/G2 drugs. Anti-IgM, which by itself was capable of inducing apoptosis, was observed to augment apoptosis induced by very low concentrations of G2/M-acting drugs but it has little effect on G1/S or the S/G2 drugs. The inhibitory effect of anti-CD40 or TNF-alpha on anti-IgM-induced apoptosis did not carry over to an effect on apoptosis induction by the CCS agents. Thus specific combinations of agents may lead to either enhancement, inhibition, or no interactive effect on apoptosis.

Radiation therapy port films: a quality assurance study.

PURPOSE: The purpose of this study was to assess the port film acceptance rate in a large community practice setting and to catalog the reasons for rejection. METHODS: Between December 1993 and July 1996, a quality assurance monitor log was maintained on 4,150 patients who underwent a total of 4,450 treatment courses. Port films were taken at the beginning and at the half way point in the treatment course. A total of 20,735 port films were compared with the matching simulation films. We recorded the site being treated, the radiation oncologist who reviewed the films and the reason for rejection. RESULTS: The monthly acceptance rate varied from a low of 67% to a high of 83%, with a gradual upward trend. The single most common reason for rejecting films was a centering problem-12% of all films taken were rejected for this reason. The next most common problems were block placement or body setup errors that caused 3.4% and 2.7% of the films to be rejected, respectively. Average acceptance rates between 10 different sites (abdomen, brain, breast, chest, extremities, head and neck, pelvis, prostate, rectum and spine) varied from 68% to 80%. Individual differences between 12 radiation oncologists reviewing the films varied from 67% to 87%. CONCLUSIONS: A detailed analysis of field localization errors allowed us to identify areas where improvement was needed and suggested that specific guidelines for acceptance would help reduce the variability noted in the acceptance rate between sites and physicians.

A comparison of single-dose and fractionated total-body irradiation on the development of pneumonitis following bone marrow transplantation.

PURPOSE: A review of 132 consecutive patients who received bone marrow transplant for various malignancies was conducted to determine factors associated with increased risk in developing interstitial pneumonitis (IP) as the result of total body irradiation (TBI). Twenty-four patients were excluded because 22 did not receive TBI and two had insufficient records. METHODS AND MATERIALS: Patients were conditioned with TBI and various drug regimens. Eighteen patients received a single 6.0 Gy dose of x-rays. The remaining 90 were treated with three doses of 3.33 Gy separated by 24 h. All patients were followed for at least 18 months for the purposes of determining the IP incidence. RESULTS: Twenty-seven of these 108 (25%) patients developed IP; 19 (17.6%) died. The 2-year estimated incidence of IP was 24 and 18.6% for fatal IP. The etiology was determined to be idiopathic in 12 patients, the result of cytomegalovirus in 6 patients, and caused by a variety of other infectious organisms in 9 patients. We were unable to demonstrate a statistically significant increase in IP with age (adults vs. children), dose regimen, use of methotrexate for graft-vs.-host disease prophylaxis, the presence of acute graft-vs.-host disease, time from diagnosis to transplant, or transplant type (allogeneic vs. autologous). CONCLUSIONS: The incidence of fatal IP reported here is similar to that reported by other institutions utilizing hyperfractionated TBI protocols. Our data do not support the need for hyperfractionation to reduce the risk of IP.

Growth rates of hprt and tk mutant CHO cell lines.

The growth rates of 31 X-ray-induced hypoxanthine phosphoribosyl transferase (hprt) deficient mutants of CHO-K1 cells were measured. Mutants had been classified as (1) full-deletion, (2) partial deletion or rearrangement, or (3) unchanged by Southern blot analyses. No relationship between growth rate and deletion type was observed. Even where all hprt-specific bands were missing, proliferation rates in culture were normal. Additionally, in CHO-AT3-2 cells, which are heterozygous at the tk locus, no difference in growth rates between a spontaneous hprt mutant and its parent was observed, although double hprt-tk-/- mutants grew more slowly.

Southern blot and polymerase chain reaction exon analyses of HPRT- mutations induced by radon and radon progeny.

A linear dose response was observed for radon-induced mutations at the CHO-hprt locus with an induction frequency of 1.4 x 10(-4) mutants per viable cell per gray. Mutants isolated after two levels of radon exposure were evaluated using Southern blot techniques and polymerase chain reaction (PCR) exon amplification. No significant differences in mutational spectra were detected at these two exposure levels. Of 52 radon-induced mutations, 48% sustained a gene deletion, 23% underwent a rearrangement of the banding patterns or loss of one or more exons, and 29% showed no change from the parental line. These mutants were compared with mutants produced after X irradiation (3 Gy) and with spontaneous mutants from untreated cells. The spectra of mutation types in cells treated with radon and X rays were not significantly different. In contrast, 31 spontaneous mutations exhibited a low percentage of gene deletion events (16%); most spontaneous mutants showed no change (74%); the remaining 10% were classified as alterations. In conclusion, the principal lesion seen at the CHO-hprt locus after radiation exposure is gene deletion, while the predominant class of spontaneous mutations is composed of smaller events not detectable by Southern blot or PCR exon analysis.

Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene.

Diploid human fibroblasts were transfected with a plasmid carrying a v-myc oncogene linked to the neo gene or with a vector control carrying a neo gene. Drug-resistant clones were isolated and subcultured as needed. All populations went into crisis and eventually senesced. But while they were senescing, viable-appearing clones were noted among the progeny of a transfected population that expressed the v-myc oncogene. After several months, these cells began replicating more rapidly. Karyotype analysis indicated that they were clonally derived since all of them had 45 chromosomes, including 2 marker chromosomes. This cell strain was designated MSU-1.1. Similar analysis showed that cells from an earlier passage were diploid. These cells were designated MSU-1.0. Both strains have undergone more than 200 population doublings since their siblings senesced, without any change in chromosome complement. Both strains express the v-myc protein and have the same integration site for the transfected v-myc and neo genes. The MSU-1.0 cells cannot grow without exogenously added growth factors. The MSU-1.1 cells grow moderately well under the same conditions and grow to a higher saturation density than MSU-1.0 cells. Since the chance of human cells acquiring an infinite life span in culture is very rare, the data suggest that MSU-1.1 cells are derived from MSU-1.0 cells. The expression of v-myc is probably required for acquisition of an infinite life span, since this phenotype did not develop in populations not expressing this oncogene. However, expression of v-myc is clearly not sufficient, since all of the progeny of the clone that gave rise to the MSU-1.0 cells expressed this oncogene, but the vast majority of them senesced.

Localization of deletion breakpoints in radiation-induced mutants of the hprt gene in hamster cells.

DNA was analysed from a large set of hamster hprt gene mutants, some induced by ionising radiations and others occurring naturally, to identify those with large alterations in part of the gene. DNA from these mutants was restricted further with different endonucleases and probed to establish the patterns of restriction fragments remaining. Of 15 mutants characterized, one showed a duplication of part of the 5' end of the gene, and the remainder showed deletions of various sizes. It was possible to approximately locate the breakpoints of the deletions by comparison of fragment patterns to a recently-established map of the hamster gene. The relatively small number of mutants examined precludes rigorous analysis of the distribution of breakpoints in the hprt gene, but taken with other recent studies of deletion mutagenesis it is suggested that non-random induction or selection of this type of mutation may occur.

Molecular characterization of X-ray-induced mutations at the HPRT locus in plateau-phase Chinese hamster ovary cells.

CHO-K1 cells were irradiated in plateau phase to determine the effect of dose, dose fractionation, and delayed replating on the type, location and frequency of mutations induced by 250 kVp X-rays at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus. Independent HPRT-deficient cell lines were isolated from each group for Southern blot analysis using a hamster HPRT cDNA probe. When compared with irradiation with 4 Gy and immediate replating, dose fractionation (2 Gy + 24 h + 2 Gy) the entire gene. Since an increase in survival was noted under these conditions, these data suggest that repair of sublethal and potentially lethal damage acts equally on all premutagenic lesions, regardless of type or location. Differences in the mutation spectrum were noted when cells were irradiated at 2 Gy and replated immediately. The location of the deletion breakpoints was determined in 15 mutants showing partial loss of the HPRT locus. In 12 of these cell lines one or both of the breakpoints appeared to be located near the center of the gene, indicating a nonrandom distribution of mutations. These results indicate that damage induced by ionizing radiation results in a nonrandom distribution of genetic damage, suggesting that certain regions of the genome may be acutely sensitive to the mutagenic effects of ionizing radiation.

Malignant transformation of human fibroblasts by oncogene transfection or carcinogen treatment.

Exposure to chemical carcinogens or radiation is considered to cause most human cancer, but human cells in culture have not been successfully transformed to malignancy by such agents. Malignant transformation is a multi-step process and one explanation for the failure to induce such transformation of human cells in culture could be inability to recognize the phenotypes of carcinogen-treated cells that have undergone intermediate changes, so that these cells can be isolated and exposed a second time to cause further changes. To identify possible intermediates, we transfected diploid human fibroblasts with oncogenes known to be active in cells derived from fibrosarcomas and determined the phenotypes produced. H- or N-ras oncogenes flanked by suitable enhancer and promoter sequences caused the cells to exhibit several characteristics of malignant cells, but not to acquire an infinite life span or form tumors. Transfection of these oncogenes in the same constructions, or a viral K-ras oncogene, into an infinite life span, near-diploid, non-tumorigenic cell strain developed in this laboratory (MSU-1.1 cells) resulted in distinct foci of morphologically-altered, anchorage independent, and growth factor independent cells that formed progressively-growing, invasive malignant sarcomas in athymic mice and expressed the p21s of the transfected ras genes. Transfection of two other infinite life span human cell lines with the H-ras oncogene in the same construction also yielded malignant cells. Recently, we succeeded in inducing the malignant state in MSU-1.1 cells using carcinogen identified that are one step removed from malignant transformation, others that are two-steps removed, etc. Furthermore, we know what new phenotypes these cells need to express to be malignantly transformed and which oncogenes can make such a change. If, as suggested above, proto-oncogenes are the cellular targets for carcinogen attack, it should be possible, by carcinogen treatment to bring about the malignant state. We have recently succeeded in achieving just such transformation by exposing MSU-1.1 cells to chemical carcinogens.

Optimal parameters for the polybrene-induced DNA transfection of diploid human fibroblasts.

Recently it has been shown that Polybrene, in conjunction with dimethyl sulfoxide (DMSO) shock, can markedly increase frequency of DNA transfection of chicken embryo fibroblasts as compared with the frequency obtained with the standard calcium phosphate protocol. We have adapted this procedure for use with diploid human fibroblasts. Using plasmid DNA containing a dominant selectable marker gene (resistance to Geneticin), we have determined that treatment of the cells for 6 h in culture medium containing Polybrene at a concentration of 2 to 5 micrograms/ml, followed by a 4-min shock with 30% DMSO, resulted in the highest yield of transfectants, ca. 400/10(6) cells treated with as little as 100 ng of plasmid DNA. The selective agent could be added immediately after the DMSO shock. This allows transfection and selection to be carried out in the same dishes and ensures that each clone represents a unique event.

Pyrimidine dimer induction in E. coli DNA by Cerenkov emission associated with high energy X-irradiation.

The induction of pyrimidine dimers in E. coli DNA by secondary ultraviolet light associated with 6 MVp X-rays in the dose range 20-90 Gy has been demonstrated using T4 endonuclease V. Under the experimental conditions used in these experiments the major component of this secondary U.V. light is Cerenkov emission.

Induction of lethal damage in E. coli by Cerenkov emission associated with high-energy X-rays: the effect of bromouracil substitution.

5.1. The damages induced in E. coli AB2487 recA by Cerenkov emission and ionizing radiation contribute in an additive fashion to the overall lethality, and do not interact in a synergistic fashion. 5.2. BU substitution enhances the lethal action of high energy X-irradiation on E. coli AB2487 recA by a mechanism involving enhanced radiosensitivity and enhanced photosensitivity.