The relationship between children's motor proficiency and health-related fitness

The overall purpose of this study was to examine the relationship between motor proficiency and health-related fitness in children. In addition, the study aimed to determine if particular combinations of motor skills have a stronger relationship with individual health-related fitness measures

Exploring the diagnostic accuracy of the KidFit screening tool for identifying children with health and motor performance-related fitness impairments: A feasibility study

Child obesity is associated with poor health and reduced motor skills. This study aimed to assess the diagnostic accuracy of the KidFit Screening Tool for identifying children with overweight/obesity, reduced motor skills and reduced cardiorespiratory fitness. Fifty-seven children (mean age: 12.57 ± 1.82 years; male/female: 34/23) were analysed. The Speed and Agility Motor Screen (SAMS) and the Modified Shuttle Test-Paeds (MSTP) made up the KidFit Screening Tool. Motor Proficiency (BOT2) (Total and Gross) was also measured. BMI, peak-oxygen-uptake (VO2peak) were measured with a representative sub-sample (n = 25). Strong relationships existed between the independent variables included in the KidFit Screening Tool and; BMI (R2 = 0.779, p < 0.001); Gross Motor Proficiency (R2 = 0.612, p < 0.001) and VO2peak (mL/kg/min) (R2 = 0.754, p < 0.001). The KidFit Screening Tool has a correct classification rate of 0.84 for overweight/obesity, 0.77 for motor proficiency and 0.88 for cardiorespiratory fitness. The sensitivity and specificity of the KidFit Screening Tool for identifying children with overweight/obesity was 100% (SE = 0.00) and 78.95%, respectively (SE = 0.09), motor skills in the lowest quartile was 90% (SE = 0.095) and 74.47% (SE = 0.064), respectively, and poor cardiorespiratory fitness was 100% (SE = 0.00) and 82.35% (SE = 0.093), respectively. The KidFit Screening Tool has a strong relationship with health- and performance-related fitness, is accurate for identifying children with health- and performance-related fitness impairments and may assist in informing referral decisions for detailed clinical investigations

Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues

The vitamin D receptor (VDR) is a ligand-dependent transcription factor that heterodimerizes with retinoid X receptor (RXR) and interacts with the basal transcription machinery and transcriptional cofactors to regulate target gene activity. The p160 coactivator GRIP1 and the distinct coregulator Ski-interacting protein (SKIP)/NCoA-62 synergistically enhance ligand-dependent VDR transcriptional activity. Both coregulators bind directly to and form a ternary complex with VDR, with GRIP1 contacting the activation function-2 (AF-2) domain and SKIP/NCoA-62 interacting through an AF-2 independent interface. It was previously reported that SKIP/NCoA-62 interaction with VDR was independent of the heterodimerization interface (specifically, helices H10/H11). In contrast, the present study defines specific residues within a conserved and surface-exposed region of VDR helix H10 that are required for interaction with SKIP/NCoA-62 and for full ligand-dependent transactivation activity. SKIP/NCoA-62, the basal transcription factor TFIIB, and RXR all interacted with VDR helix H10 mutants at reduced levels compared with wild type in the absence of ligand and exhibited different degrees of increased interaction upon ligand addition. Thus, SKIP/NCoA-62 interacts with VDR at a highly conserved region not previously associated with coregulator binding to regulate transactivation by a molecular mechanism distinct from that of p160 coactivators

Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility

10.1186/bcr2762Breast Cancer Research125-BCRR

Effect of high intensity interval training on cardiac function in children with obesity: a randomised controlled trial

High intensity interval training (HIIT) confers superior cardiovascular health benefits to moderate intensity continuous training (MICT) in adults and may be efficacious for improving diminished cardiac function in obese children. The aim of this study was to compare the effects of HIIT, MICT and nutrition advice interventions on resting left ventricular (LV) peak systolic tissue velocity (S') in obese children.Ninety-nine obese children were randomised into one of three 12-week interventions, 1) HIIT [n = 33, 4 × 4 min bouts at 85-95% maximum heart rate (HR), 3 times/week] and nutrition advice, 2) MICT [n = 32, 44 min at 60-70% HR, 3 times/week] and nutrition advice, and 3) nutrition advice only (nutrition) [n = 34].Twelve weeks of HIIT and MICT were equally efficacious, but superior to nutrition, for normalising resting LV S' in children with obesity (estimated mean difference 1.0 cm/s, 95% confidence interval 0.5 to 1.6 cm/s, P

Assessment of the five-minute oxygen uptake efficiency slope in children with obesity

Purpose: Poor cardiorespiratory fitness is associated with increased all cause morbidity and mortality. In children with obesity, maximum oxygen uptake (VO) may not be achieved due to reduced motivation and peripheral fatigue. We aimed to identify a valid submaximal surrogate for VO in children with obesity. Method: Ninety-two children with obesity (7-16 years) completed a maximal exercise treadmill test and entered a three-month exercise and/or nutrition intervention after which the exercise test was repeated (n = 63). Participants were required to reach VO to be included in this analysis (n = 32 at baseline and n = 13 at both time-points). The oxygen uptake efficiency slope (OUES) was determined as the slope of the line when VO (L/min) was plotted against logV? E. Associations between the maximal OUES, submaximal OUES (at 3, 4, 5 and 6 min of the exercise test) and VO were calculated. Results: In the cross-sectional analysis, V?O2max (L/min) was strongly correlated with 5-min OUES independent of Tanner puberty stage and sex (R = .80, p < .001). Longitudinal changes in VO were closely reflected by changes in 5-min OUES independent of change in percent body fat (R = .63, p < .05). Conclusion: The 5-min OUES is a viable alternative to VO when assessing children with obesity

Left ventricular morphology and function in adolescents: Relations to fitness and fatness.

BACKGROUND: Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. METHODS: LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18kg/m(2)-25kg/m(2)] and 9 obese [BMI equivalent to ≥30kg/m(2)]); 13.3±1.1years, 45% female, Tanner puberty stage 3 [2-4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. RESULTS: Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r=0.49-0.71, P<0.05). CONCLUSION: Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. CLINICAL TRIAL REGISTRATION: NCT01991106