Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. METHODS: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. FINDINGS: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8). INTERPRETATION: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. FUNDING: Institut National du Cancer; and Ligue Nationale Contre le Cancer.

Physical Activity in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: A Cross-sectional Cohort Study.

Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium. The median age was 21.15 years and time from diagnosis 15.07 years, and 27 subjects had experienced fractures. More than 30% of the total sample were OW/OB. There was no correlation of body mass index with present PA. There were no significant differences between those with/without fractures in terms of age, sex, time from diagnosis, and the prevalence of OW/OB. Subjects with fractures during treatment reported more total activity on typical weekend days than those without fractures (mean 8.8 vs. 6.9 h, P<0.01). There was no significant difference on weekdays. Higher activity on weekends suggests that fractures may have occurred more commonly in those who had a more active lifestyle before, during, and after treatment.

Development of an Electronic Version of The Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) Scale.

PURPOSE: To develop an electronic version of the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (eCSAPPA), which would allow individual administration to children younger than nine years of age. METHODS: Fifty-four, four-nine-year-old children completed the eCSAPPA and the Test of Gross Motor Development-2 (TGMD-2). Parental measures of physical activity, and body mass index were obtained. Twenty-one participants additionally completed the paper version of the CSAPPA. RESULTS: All children successfully completed the eCSAPPA with interclass correlation coefficients of .76 for Adequacy and .86 for Total Score. Correlations and linear predictive equations for eCSAPPA revealed the TGMD-2's Locomotor subtest, age, and parent's activity rating explained 28-30% of the variability in Total and Adequacy eCSAPPA scores. Predilection and Enjoyment of Physical Education (PE) scores were less stable, with the TGMD-2's Locomotor subtest and age predicting 17% of the Predilection score and the TGMD-2's Object Control subtest demonstrating 17% of Enjoyment of PE. CONCLUSION: Children ages four-nine years can feasibly complete the electronic version of the CSAPPA and results hint that self-efficacy may be more plastic in younger children. The eCSAPPA is a promising instrument allowing the exploration of young children's development of adequacy and predilection toward physical activity as well as enjoyment of PE.

Transanal Local Excision for Patients With Rectal Cancer: Can Radiation Compensate for What Is Perceived as a Nondefinitive Surgical Approach?

BACKGROUND: Total mesorectal excision has long been the standard of care for patients with rectal cancer. However, in select patients, local excision is an appropriate alternative option. The role of adjuvant radiation therapy in patients treated with local excision is controversial and evidence is lacking. OBJECTIVE: The purpose of this study was to report oncological outcomes of patients with rectal cancer treated with local excision and adjuvant radiation. DESIGN: This study was a retrospective chart review. SETTINGS: The study was conducted at the BC Cancer Agency, a tertiary referral hospital. PATIENTS: A total of 93 patients with node-negative rectal cancer treated with local excision and adjuvant radiotherapy between 2001 and 2010 were included in the study. MAIN OUTCOME MEASURES: Patient and tumor characteristics are reported. Five-year local control, progression-free survival, and overall survival were analyzed using Kaplan-Meier methods. RESULTS: Five-year overall survival, local control, and progression-free survival for patients treated with local excision and adjuvant radiotherapy were 78.5%, 86.1%, and 83.8%. In T1 disease, local control was 92.5%. LIMITATIONS: Referral bias, selection bias, lack of uniform surveillance, and retrospective analysis are the study limitations. CONCLUSIONS: Local excision with adjuvant radiotherapy provides a good level of local control in T1 disease and remains a good treatment option for patients who are either medically not suitable for a more radical surgical approach or who refuse this procedure. Local excision and radiotherapy should not be advocated in T2/T3 disease; however, it can provide a good alternative in those patients who are not fit enough for a more radical operation.

Discovery and evolution of bunyavirids in arctic phantom midges and ancient bunyavirid-like sequences in insect genomes.

UNLABELLED: Bunyaviridae is a large family of RNA viruses chiefly comprised of vertebrate and plant pathogens. We discovered novel bunyavirids that are approximately equally divergent from each of the five known genera. We characterized novel genome sequences for two bunyavirids, namely, Kigluaik phantom virus (KIGV), from tundra-native phantom midges (Chaoborus), and Nome phantom virus (NOMV), from tundra-invading phantom midges, and demonstrated that these bunyavirid-like sequences belong to an infectious virus by passaging KIGV in mosquito cell culture, although the infection does not seem to be well sustained beyond a few passages. Virus and host gene sequences from individuals collected on opposite ends of North America, a region spanning 4,000 km, support a long-term, vertically transmitted infection of KIGV in Chaoborus trivittatus. KIGV-like sequences ranging from single genes to full genomes are present in transcriptomes and genomes of insects belonging to six taxonomic orders, suggesting an ancient association of this clade with insect hosts. In Drosophila, endogenous virus genes have been coopted, forming an orthologous tandem gene family that has been maintained by selection during the radiation of the host genus. Our findings indicate that bunyavirid-host interactions in nonbloodsucking arthropods have been much more extensive than previously thought. IMPORTANCE: Very little is known about the viral diversity in polar freshwater ponds, and perhaps less is known about the effects that climate-induced habitat changes in these regions will have on virus-host interactions in the coming years. Our results show that at the tundra-boreal boundary, a hidden viral landscape is being altered as infected boreal phantom midges colonize tundra ponds. Likewise, relatively little is known of the deeper evolutionary history of bunyavirids that has led to the stark lifestyle contrasts between some genera. The discovery of this novel bunyavirid group suggests that ancient and highly divergent bunyavirid lineages remain undetected in nature and may offer fresh insight into host reservoirs, potential sources of emerging disease, and major lifestyle shifts in the evolutionary history of viruses in the family Bunyaviridae.

α1ß1 integrin-mediated adhesion inhibits macrophage exit from a peripheral inflammatory lesion.

Integrins are adhesion molecules critical for the recruitment of leukocytes from blood into peripheral tissues. However, whether integrins are also involved in leukocyte exit from peripheral tissues via afferent lymphatics to the draining lymph node remains poorly understood. In this article, we show that adhesion by the collagen IV-binding integrin α1ß1 unexpectedly inhibited macrophage exit from inflamed skin. We monitored macrophages exiting mouse footpads using a newly developed in situ pulse labeling technique. Blockade of α1ß1 integrin or genetic deletion (Itga1(-/-)) increased macrophage exit efficiency. Chemotaxis assays through collagen IV showed more efficient migration of Itga1(-/-) macrophages relative to wild type. Given that macrophages are key orchestrators of inflammation, α1ß1 integrin adhesion may represent a mechanism for regulating inflammatory responses by controlling macrophage exit or persistence in inflamed tissues.

Relative age effects in fitness testing in a general school sample: how relative are they?

When children or adolescents are grouped by age or year of birth, older individuals tend to outperform younger ones. These phenomena are known as relative age effects (RAEs). RAEs may result directly from differences in maturation, but may also be associated with psychological, pedagogic or other factors. In this article, we attempt to quantify RAEs in a simple fitness task and to identify the mechanisms operating. Data come from a 5-year study of 2278 individuals that included repeated administrations of the 20 m shuttle run. We use mixed-effect modelling to characterise change over time and then examine residuals from these models for evidence of an effect for age relative to peers or for season of birth. Age alone appears to account for RAEs in our sample, with no effects for age relative to peers or month of birth. Age grouping produces large disparities for girls under 12, moderate ones for boys of all ages and negligible ones for girls between 12 and 15. RAEs for this task and population appear to arise from simple age differences. Similar methods may be useful in determining whether other explanations of RAEs are necessary in other contexts. Evaluation processes that take age into account have the potential to mitigate RAEs in general settings.

The skin, a novel niche for recirculating B cells.

B cells infiltrate the skin in many chronic inflammatory diseases caused by autoimmunity or infection. Despite potential contribution to disease, skin-associated B cells remain poorly characterized. Using an ovine model of granulomatous skin inflammation, we demonstrate that B cells increase in the skin and skin-draining afferent lymph during inflammation. Surprisingly, skin B cells are a heterogeneous population that is distinct from lymph node B cells, with more large lymphocytes as well as B-1-like B cells that coexpress high levels of IgM and CD11b. Skin B cells have increased MHC class II, CD1, and CD80/86 expression compared with lymph node B cells, suggesting that they are well-suited for T cell activation at the site of inflammation. Furthermore, we show that skin accumulation of B cells and Ab-secreting cells during inflammation increases local Ab titers, which could augment host defense and autoimmunity. Although skin B cells express typical skin-homing receptors, such as E-selectin ligand and α-4 and ß-1 integrins, they are unresponsive to ligands for chemokine receptors associated with T cell homing into skin. Instead, skin B cells migrate toward the cutaneously expressed CCR6 ligand CCL20. Our data support a model in which B cells use CCR6-CCL20 to recirculate through the skin, fulfilling a novel role in skin immunity and inflammation.

When and for whom are relative age effects important? Evidence from a simple test of cardiorespiratory fitness.

OBJECTIVES: When individuals of different ages are combined into a single group and an ability that varies with age is measured, younger individuals are disadvantaged. This phenomenon is known as a relative age effect (RAE) and has been shown to be widespread in sport and education. METHODS: In this article, we examine RAEs in a large group of children tested repeatedly on the 20-m shuttle run, a common test of cardiorespiratory fitness. Following up on an earlier study that measured change with age, we add a growth curve model for change in variance, which makes it possible to derive RAEs for individuals of different ages and ability levels. RESULTS: Results show that a 1-year difference in age is associated with a change in performance of about 0.2 standard deviations. For 1-year age groups, this gives rise to ranking errors of 4 percentile ranks or less. We also show, however, that these relatively small ranking errors are capable of producing large age differences within groups identified as exceptional. Depending on the level of ability required for selection, children born in the first quarter of the year can be expected to outnumber those born in the last by 1.5 times, 2 times, or more. This finding is consistent with previously reported variation in RAEs at different performance levels. CONCLUSIONS: Results imply that RAEs are likely to be of relatively minor concern when people are graded or ranked but can produce substantial inequities and misclassifications when people with extremely high or extremely low ability levels undergo selection.

The Otto Aufranc Award. On the etiology of the cam deformity: a cross-sectional pediatric MRI study.

BACKGROUND: Femoroacetabular impingement (FAI) has been recognized as a common cause of hip pain as well as a cause of hip arthritis, yet despite this, little is known about the etiology of the cam morphology or possible risk factors associated with its development. QUESTIONS/PURPOSES: The purposes of our study were to determine when the cam morphology associated with FAI developed in a cross-sectional cohort study of pediatric patients pre- and postphyseal closure using MRI and whether increased activity level during the period of physeal closure is associated with an increased likelihood that the cam deformity will develop. METHODS: Alpha angles were measured at the 3 o'clock (anterior head-neck junction) and 1:30 (anterosuperior head-neck junction) positions in both hips with a cam deformity defined as an alpha angle ≥ 50.5° at the 3 o'clock position. Forty-four volunteers (88 hips) were studied: 23 with open physes (12 females, mean age 9.7 years; 11 males, age 11.7 years) and 21 with closed physes (five females, age 15.2 years; 16 males, age 16.2 years). Daily activity level using the validated Habitual Activity Estimation Scale was compared for patients in whom cam morphology did and did not develop. RESULTS: None of the 23 (0%) patients prephyseal closure had cam morphology, whereas three of 21 (14%, p = 0.02; all males) postclosure had at least one hip with cam morphology. Daily activity level was higher (p = 0.02) for patients with the cam morphology (7.1 hours versus 2.9 hours). Mean alpha angles at the 3 o'clock head-neck position were 38° (95% confidence interval [CI], 37.2°-39.1°) in the open physes group and 42° (95% CI, 40.16°-43.90°) in the closed physes group; at the 1:30 head-neck position, they were 45° (95% CI, 44.0°-46.4°) in the open physes group and 50° (47.9°-52.3°) in the closed physes group. CONCLUSIONS: The fact that cam morphology was present exclusively in the closed physeal group strongly supports its development during the period of physeal closure with increased activity level as a possible risk factor.

An Sp1/Sp3 site in the downstream region of varicella-zoster virus (VZV) oriS influences origin-dependent DNA replication and flanking gene transcription and is important for VZV replication in vitro and in human skin.

The distribution and orientation of origin-binding protein (OBP) sites are the main architectural contrasts between varicella-zoster virus (VZV) and herpes simplex virus (HSV) origins of DNA replication (oriS). One important difference is the absence of a downstream OBP site in VZV, raising the possibility that an alternative cis element may replace its function. Our previous work established that Sp1, Sp3, and YY1 bind to specific sites within the downstream region of VZV oriS; we hypothesize that one or both of these sites may be the alternative cis element(s). Here, we show that the mutation of the Sp1/Sp3 site decreases DNA replication and transcription from the adjacent ORF62 and ORF63 promoters following superinfection with VZV. In contrast, in the absence of DNA replication or in transfection experiments with ORF62, only ORF63 transcription is affected. YY1 site mutations had no significant effect on either process. Recombinant viruses containing these mutations were then constructed. The Sp1/Sp3 site mutant exhibited a significant decrease in virus growth in MeWo cells and in human skin xenografts, while the YY1 site mutant virus grew as well as the wild type in MeWo cells, even showing a late increase in VZV replication in skin xenografts following infection. These results suggest that the Sp1/Sp3 site plays an important role in both VZV origin-dependent DNA replication and ORF62 and ORF63 transcription and that, in contrast to HSV, these events are linked during virus replication.

Postgraduate education in transfusion medicine in the absence of formal residency training: assessment of factors needed to develop and sustain a postgraduate diploma program.

BACKGROUND: Quality education in transfusion medicine is key to delivering a safe and cost-effective blood service, yet postgraduate residency programs are lacking in many resource-limited countries and regions. The first formal, accredited, postgraduate training program in transfusion medicine aimed at medical doctors was developed and implemented at the University of the Free State in Bloemfontein, South Africa, in 2008. In the context of high demand and limited resources, ensuring sustainability of postgraduate training programs is essential. STUDY DESIGN AND METHODS: A formal qualitative and semi-quantitative research approach was followed to determine and test the factors considered important in program sustainability, and consisted of a literature survey, followed by semi-structured interviews and a Delphi survey. RESULTS: Fifty-five factors were identified from the semi-structured interviews. During the Delphi survey, consensus was reached on 41 and stability declared on a further 13. These factors formed the basis of a structured model informing the sustainability aspects of a postgraduate program in transfusion medicine. CONCLUSION: Literature on program sustainability in the field of transfusion medicine is very limited. This study identified the key factors essential to the long-term viability of a postgraduate program in transfusion medicine and should find broad applicability in other resource-limited countries and regions. It is envisaged that this will enable such programs to reach a state of self-sufficiency while not being overly reliant on external funding and support.

Factors affecting the current status of transfusion medicine education in South Africa.

Education in transfusion medicine, aimed at clinical transfusion practice, is limited in most South African pre- and postgraduate medical training programs. A number of local and global factors impact on the need for and provision of transfusion medicine education programs in South Africa, which are discussed in this paper. A perspective is provided on the effects of issues such as global versus local training need, blood safety, appropriate use of blood in resource-restrained environments, the presence or absence of national blood policies, standardization of training, medical migration and workforce diversity. Harnessing support for the development of training programs for medical doctors and new opportunities for developing a career in transfusion medicine are discussed. Commentary is also provided on online learning, social networking and integration of modern paradigms of learning, such as screencasting and online learning, into teaching programs. This article should provide anyone in medical education or program development, in particular in the field of transfusion medicine, with an indication of the factors that should be considered when embarking on such an endeavor.

Climate change and infectious disease: A prologue on multidisciplinary cooperation and predictive analytics.

Climate change impacts global ecosystems at the interface of infectious disease agents and hosts and vectors for animals, humans, and plants. The climate is changing, and the impacts are complex, with multifaceted effects. In addition to connecting climate change and infectious diseases, we aim to draw attention to the challenges of working across multiple disciplines. Doing this requires concentrated efforts in a variety of areas to advance the technological state of the art and at the same time implement ideas and explain to the everyday citizen what is happening. The world's experience with COVID-19 has revealed many gaps in our past approaches to anticipating emerging infectious diseases. Most approaches to predicting outbreaks and identifying emerging microbes of major consequence have been with those causing high morbidity and mortality in humans and animals. These lagging indicators offer limited ability to prevent disease spillover and amplifications in new hosts. Leading indicators and novel approaches are more valuable and now feasible, with multidisciplinary approaches also within our grasp to provide links to disease predictions through holistic monitoring of micro and macro ecological changes. In this commentary, we describe niches for climate change and infectious diseases as well as overarching themes for the important role of collaborative team science, predictive analytics, and biosecurity. With a multidisciplinary cooperative "all call," we can enhance our ability to engage and resolve current and emerging problems.

Gender- and ethnicity-specific survival trends of oral cavity and oropharyngeal cancers in British Columbia.

INTRODUCTION: A shift in etiology of oral cancers has been associated with a rise in incidence for oropharyngeal cancers (OPC) and decrease for oral cavity cancers (OCC); however, there is limited information about population-based survival trends. We report epidemiological transitions in survival for both OPC and OCC from a population-based cancer registry, focusing upon gender and ethnic differences. METHODS: All primary oral cancers diagnosed between 1980 and 2005 were identified from the British Columbia Cancer Registry and regrouped into OPC and OCC by topographical subsites, time periods (1980-1993 and 1994-2005), stage at diagnosis, and ethnicity. Cases were then followed up to December 2009. Using gender-based analysis, actuarial life tables were used to calculate survival rates, which were compared using Kaplan-Meier curves and log-rank tests. RESULTS: For OPC, survival improved, significant for tonsil and base of tongue in men and marginally significant at base of tongue in women. This improvement occurred in spite of an increase in late-stage diagnosis for OPC in both genders. Interestingly, there was no difference in survival for early- and late-stage disease for OPC in men. For OCC, there was a decrease in survival for floor of mouth cancers in both genders although significant in women only. South Asians had the poorest survival for OCC in both genders. CONCLUSION: Survival for OPC improved, more dramatically in men than women, in spite of late-stage diagnosis and increasing nodal involvement. Given the poor survival rates and need for early detection, targeted OCC screening programs are required for South Asians.

Gender, perceived competence and the enjoyment of physical education in children: a longitudinal examination.

BACKGROUND: The current study examined associations between gender, perceived athletic competence, and enjoyment of physical education (PE) class over time in a cohort of children enrolled in grade four (ages 9 or 10) at baseline (n = 2262). METHODS: We assessed each student 5 times over a period of 2 years. We used mixed effects modeling to examine change over time in enjoyment of PE. RESULTS: Enjoyment of PE declined among girls but remained constant among boys. Higher levels of perceived competence were associated with higher PE enjoyment. A 3-way interaction between gender, competence, and time revealed that PE enjoyment was lowest and declined most markedly among girls with low perceived athletic competence. Among boys with low competence, enjoyment remained at a consistently low level. CONCLUSIONS: Our results indicate that lower perceived athletic competence is associated with low enjoyment of PE, and, among girls, with declining enjoyment. Findings suggest that interventions in a PE context that target perceived competence should be considered in future work.

Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation.

Memory/effector T cells traffic efficiently through extralymphoid tissues, entering from the blood and leaving via the afferent lymph. During inflammation, T cell traffic into the affected tissue dramatically increases; however, the dynamics and mechanisms of T cell exit from inflamed tissues are poorly characterized. In this study, we show, using both a mouse and a sheep model, that large numbers of lymphocytes leave the chronically inflamed skin. Many T cells capable of producing IFN-γ and IL-17 also entered the draining afferent lymph, demonstrating that memory/effector T cells egress from sites of inflammation. Whereas efficient egress from acutely inflamed skin required lymphocyte-expressed CCR7, chronic inflammation promoted significant CCR7-independent exit as well. Lymphocyte exit at late time points of inflammation was sensitive to pertussis toxin but was only partially affected by the drug FTY720, implying the contribution of alternative chemoattractant receptors other than spingosine 1-phosphate receptor 1. Our data show that CCR7 is an important receptor for lymphocyte egress from both resting and inflamed extralymphoid tissues, but that alternative exit receptors come into play during chronic inflammation.

Expressed cell-penetrating peptides can induce a bystander effect, but passage through the secretory pathway reduces protein transduction activity.

Despite advances in vector technology, inefficient gene transfer still limits clinical efficacy of cancer gene therapy. Cell-penetrating peptides (CPPs), such as the basic domain of the transactivator of transcription (Tat) protein of HIV-1, are internalized by intact cells and have been used to deliver purified recombinant proteins. A combination of gene therapy with protein transduction technology could induce a strong bystander effect and represent a platform to deliver proteins to target cells. However, whether expressed CPP can facilitate intercellular trafficking, i.e., a bystander effect, is controversial. Our data suggest that expressed fusion proteins that contain the basic domain of Tat do not induce a detectable bystander effect. However, Tat-fusion proteins that also contain a secretory signal peptide (SP) can induce a bystander effect in vitro, although the in vivo effect is small. Surprisingly, despite the presence of a SP, the bystander effect does not seem to be related to secretion of the fusion protein. In fact, Tat-fusion proteins are secreted very inefficiently, and protein transduction seems largely mediated by fusion proteins that are released by cell lysis. Modification of Tat can improve secretion efficacy and prevent cleavage by the endoprotease furin, but passage through the secretory pathway is associated with reduced transduction activity of Tat-fusion proteins.

Association between body composition and conformity to the recommendations of Canada's Food Guide and the Dietary Approaches to Stop Hypertension (DASH) diet in peri-adolescence.

OBJECTIVE: The role of following the recommendations of Canada's Food Guide (CFG) and the Dietary Approaches to Stop Hypertension (DASH) diet on body composition in children is unknown. The present study assessed how conformity to the recommendations of these diets was associated with BMI, waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), waist girth (WG), hip girth (HG) and risk of overweight in peri-adolescents. DESIGN: CFG and DASH indices were derived from responses to a food questionnaire, with a higher index representing greater conformity to CFG and DASH diet recommendations. Body composition was assessed by trained research assistants. SETTING: Schools within the Niagara region (Ontario, Canada). SUBJECTS: Children (n 1570) aged 12.4 (sd 0.3) years. RESULTS: After adjustment for age to peak height velocity and total physical activity, a higher CFG index was associated with lower WHtR (b = -0.001, 95 % CI -0.002, -0.0004), WHR (b = -0.001, 95 % CI -0.002, -0.001) and WG (b = -0.18, 95 % CI -0.30, -0.07) in girls. No associations were observed in boys. In contrast, a higher DASH index was associated with decreased body composition measures in both genders. Specifically, the DASH index was negatively associated with BMI (girls: b = -0.07, 95 % CI -0.10, -0.04; boys: b = -0.05, 95 % CI -0.08, -0.02), WHtR (girls: b = -0.001, 95 % CI -0.002, -0.001; boys: b = -0.001, 95 % CI -0.002, -0.0004), WHR (girls: b = -0.001, 95 % CI -0.002, -0.001; boys: b = -0.001, 95 % CI -0.001, -0.00004), WG (girls: b = -0.24, 95 % CI -0.31, -0.16; boys: b = -0.15, 95 % CI -0.24, -0.07) and HG (girls: b = -0.15, 95 % CI -0.23, -0.07; boys: b = -0.12, 95 % CI -0.19, -0.04). A higher DASH index was also associated with lower odds of overweight in girls (OR = 0.70, 95 % CI 0.56, 0.87) and boys (OR = 0.76, 95 % CI 0.62, 0.93). CONCLUSIONS: The DASH diet may prevent overweight in peri-adolescents.

Tick-borne encephalitis virus, Kyrgyzstan.

Tick-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan by collecting small mammals and ticks from diverse localities and analyzing them for evidence of TBEV infection. We found TBEV circulating in Kyrgyzstan much farther south and at higher altitudes than previously reported.