Supplementary information for Socio-economic disparities in child-to-adolescent growth trajectories in China: Findings from the China Health and Nutrition Survey 1991-2015

Supplementary information files for article Socio-economic disparities in child-to-adolescent growth trajectories in China: Findings from the China Health and Nutrition Survey 1991-2015   Backgrounds: Socio-economic disparities in growth trajectories of children from low-/middle-income countries are poorly understood, especially those experiencing rapid economic growth. We investigated socio-economic disparities in child growth in recent decades in China. Methods: Using longitudinal data on 5,095 children/adolescents (7-18y) from the China Health and Nutrition Survey (1991-2015), we estimated mean height and BMI trajectories by socio-economic position (SEP) and sex for cohorts born in 1981-85, 1986-90, 1991-95, 1996-2000, using random-effects models. We estimated differences between high (urbanization index ≥median, household income per capita ≥median, parental education ≥high school, or occupational classes I-IV) and low SEP groups. Findings: Mean height and BMI trajectories have shifted upwards across cohorts. In all cohorts, growth trajectories for high SEP groups were above those for low SEP groups across SEP indicators. For height, socio-economic differences persisted across cohorts (e.g. 3.8cm and 2.9cm in earliest and latest cohorts by urbanization index for boys at 10y, and 3.6cm and 3.1cm respectively by household income). For BMI, trends were greater in high than low SEP groups, thus socio-economic differences increased across cohorts (e.g. 0.5 to 0.8kg/m2 by urbanization index, 0.4 to 1.1kg/m2 by household income for boys at 10y). Similar trends were found for stunting and overweight/obesity by SEP. There was no association between SEP indicators and thinness. Interpretation: Socio-economic disparities in physical growth persist among Chinese youth. Short stature was associated with lower SEP, but high BMI with higher SEP. Public health interventions should be tailored by SEP, in order to improve children’s growth while reducing overweight/obesity.</p

Additional file 1: of Prenatal, birth and early life predictors of sedentary behavior in young people: a systematic review

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Additional file 2: of Prenatal, birth and early life predictors of sedentary behavior in young people: a systematic review

Items included in the checklist for assessing the quality of the included studies. (DOC 22 kb

Sirtuin-2 Regulates Sepsis Inflammation in <i>ob/ob</i> Mice

<div><p>Objective</p><p>Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis.</p><p>Methods</p><p>Sepsis was induced using cecal ligation and puncture (CLP) in <i>ob/ob</i> mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in <i>ob/ob</i> mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis.</p><p>Results</p><p>We observed that the <i>ob/ob</i>-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in <i>ob/ob</i> mice during hypo-inflammation. SIRT-2 inhibition in <i>ob/ob</i> mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation <i>in vivo</i> via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65.</p><p>Conclusion</p><p>SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may provide a novel treatment target for obesity with sepsis.</p></div

SIRT-2 inhibition in <i>ob/ob</i> septic mice restores repressed microvascular leukocyte adhesion.

<p><u>A: SIRT-2 inhibition during hypo-inflammation enhances leukocyte adhesion in <i>ob/ob</i></u>: mice with sepsis: <i>ob/ob</i>-septic mice were treated with Vehicle or AK-7 during hypo-inflammatory phase of sepsis, challenged with either normal saline (NS) or LPS and studied leukocyte adhesion 4h later. While Vehicle treated mice showed no further increase in leukocyte adhesion in response to LPS, AK-7 treated mice showed significant increase in leukocyte adhesion in small intestinal microcirculation. * p<0.05 vs. Vehicle +LPS using Tukey‘s post-hoc analysis; error bars: s.e.m. <u>B and C: SIRT-2 inhibition during hypo-inflammatory phase activates endothelium</u>: We treated <i>ob/ob</i> mice with either Vehicle of AK-7 during hypo-inflammatory phase of sepsis and studied small intestinal tissue expression of E-selectin and ICAM-1 expression. We co-stained these tissue sections with wither von Willebrand factor or nuclear stain DAPI. We quantified the signal using NIH Image J. There was a significant increase in E-selectin (Fig 5B) and ICAM-1 (Fig 5C) expression in small intestinal tissue sections of Sepsis + AK-7 treated group compared to Sepsis + Vehicle group. * p<0.05 vs. Sepsis + Vehicle using Tukey‘s post-hoc analysis; error bars: s.e.m.</p

SIRT-2 inhibition reverses endotoxin tolerance in RAW cells.

<p><u>A: SIRT-2 inhibitor AK-7 enhanced LPS induced cytokine response in sensitive cells</u>. RAW cells were pre-treated with vehicle (DMSO) or AK-7 (25uM) for 1h before the stimulation with normal saline or LPS (100ng/ml) for 4h and TNF-α mRNA expression levels were studied in different groups. There was significant increase in TNF-α mRNA in AK-7 +LPS vs. Vehicle +LPS group. * p<0.05 vs. Vehicle +LPS using Tukey‘s post-hoc analysis; error bars: s.e.m. <u>B SIRT-2 inhibitor AK-7 reverses endotoxin tolerance in RAW cells</u>: Endotoxin tolerance was induced with LPS (100ng/ml) treatment for up to 24h. AK-7 (25uM) was added to cell culture at 4h and 6h after the beginning of LPS stimulation, followed by further stimulation with Vehicle or LPS (100ng/ml) for 4h and TNF-α, IL-6 and IL-1β mRNA expression in different groups were studied. While Vehicle treated groups remained endotoxin tolerant, there was a significant increase in all three cytokine mRNA expression in AK-7 +LPS vs. Vehicle +LPS treated groups. * p<0.05 vs. Vehicle +LPS using Tukey‘s post-hoc analysis; error bars: s.e.m. <u>C: SIRT-2 deficiency increases NFkB p65 acetylation</u>: We studied the effect of SIRT-2 deficiency on NFkB p65 acetylation using RAW cells. We treated RAW cells with SIRT-2 siRNA (si-SIRT2) or scramble control (si-Ctrl), and co-transfected with p65 and CBP plasmids (to increase baseline p65 acetylation) and blotted for antibodies against Ac-p65, total p65, SIRT-2 and GAPDH. NFkB p65 acetylation (Ac-p65) increased in cells with transfection with p65 + CBP. Cells treated with p65+CBP+si-SIRT-2 showed further increase in AC-p65 vs. p65+CBP+si-Ctrl, indicating SIRT-2 directly deacetylates NFkB p65.</p

Body weight and mean arterial blood pressure

<p>Body weight and mean arterial blood pressure</p

SIRT-2 inhibition during sepsis repressor/ hypo-inflammatory phase improves survival.

<p>We examined the effect of SIRT-1 (EX-527) and SIRT-2 (AK-7) inhibitors vs. vehicle treatment during the hypo-inflammatory phase of sepsis on 7-day survival in <i>ob/ob</i> mice. As shown in Fig 2, there was a significant decrease in 7-day survival of mice treated with EX-527 (EX-527: 0% vs. Vehicle: 30%). However, there was a significant increase in survival of <i>ob/ob</i> septic mice treated with AK-7 during the hypo-inflammatory phase of sepsis (AK-7: 70%vs. Vehicle: 30%).* p<0.05 vs. Sepsis + Vehicle using Log-Rank test.</p

Weight in grams and mean arterial blood pressure (MAP) in different groups.

<p>Weight in grams and mean arterial blood pressure (MAP) in different groups.</p

Monitoring pain and distress.

<p>Monitoring pain and distress.</p