Sepsis is a serious and life-threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti-inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, and NO in lipopolysaccharide (LPS)- activated macrophages. Exposure to a therapeutic concentration of propofol (50 microM), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF-alpha, IL-1beta, and IL-6 protein levels in a time-dependent manner, whereas propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1beta, and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1beta, and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS-induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti-inflammatory and antioxidative effects on the biosyntheses of TNF-alpha, IL-1beta, IL-6, and NO in LPS-activated macro-phages and that the suppressive effects are exerted at the pretranslational level.

Parents' priorities for their children and youth with cerebral palsy differed depending on age and gross motor function level; however, the most frequent priority for all age groups was daily activities. Interviews with families are recommended for identifying outcomes for activity and participation and developing an intervention plan.

ObjectiveObesity is one of the most important public health issues worldwide. Moreover, an extreme phenotype, morbid obesity (MO) has insidiously become a global problem. Therefore, we aimed to document the prevalence trend and to unveil the epidemiological characteristics of MO in Taiwan.MethodsNationally representative samples aged 19 years and above from three consecutive waves of Nutrition and Health survey in Taiwan: 1993–1996, 2005–2008, and 2013–2014 (n = 3,071; 1,673; and 1,440; respectively) were analyzed for prevalence trend. And 39 MO (BMI ≥35 kg/m2) cases from the two recent surveys compared with 156 age, gender, and survey-matched normal weight controls (BMI: 18.5–24 kg/m2) for epidemiological characteristics study. The reduced rank regression analysis was used to find dietary pattern associated with MO.ResultsThe prevalence of overweight and obesity together (BMI ≥24 kg/m2) was stabilized in the recent two surveys, but that of MO (0.4%, 0.6%, to 1.4%) and obesity (BMI ≥27 kg/m2) (11.8%, 17.9%, to 22.0%) increased sharply. MO cases tended to have lower levels of education, personal income, and physical activity. Furthermore, their dietary pattern featured with a higher consumption frequency of red meat, processed animal products, and sweets/sweetened beverage, but lower frequencies of fresh fruits, nuts, breakfast cereal, and dairy products.ConclusionThis study documents a polarization phenomenon with smaller proportion of overweight people at the center and higher proportions of normal weight and obesity subjects at two extremes. MO was associated with low socioeconomic status and poor dietary pattern. The obesogenic dietary pattern became more prevalent in later time.

Objective Our objective was to evaluate the efficacy of the Sitting Together and Reaching to Play (START-Play) intervention in young infants with neuromotor disorders. Method This randomized controlled trial compared usual care early intervention (UC-EI) with START-Play plus UC-EI. Analyses included 112 infants with motor delay (55 UC-EI, 57 START-Play) recruited at 7 to 16 months of age across 5 sites. START-Play included twice-weekly home visits with the infant and caregiver for 12 weeks provided by physical therapists trained in the START-Play intervention; UC-EI was not disrupted. Outcome measures were the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley); the Gross Motor Function Measure; reaching frequency; and the Assessment of Problem Solving in Play (APSP). Comparisons for the full group as well as separate comparisons for infants with mild motor delay and infants with significant motor delay were done. Piecewise linear mixed modeling estimated short- and long-term effects. Results For infants with significant motor delay, positive effects of START-Play were observed at 3 months for Bayley cognition, Bayley fine motor, and APSP and at 12 months for Bayley fine motor and reaching frequency outcomes. For infants with mild motor delay, positive effects of START-Play for the Bayley receptive communication outcome were found. For the UC-EI group, the only difference between groups was a positive effect for the APSP outcome, observed at 3 months. Conclusions START-Play may advance reaching, problem-solving, cognitive, and fine motor skills for young infants with significant motor delay over UC-EI in the short term. START-Play in addition to UC-EI may not improve motor/cognitive outcomes for infants with milder motor delays over and above usual care. Impact Concepts of embodied cognition, applied to early intervention in the START-Play intervention, may serve to advance cognition and motor skills in young infants with significant motor delays over usual care early intervention. Lay Summary If you have a young infant with significant delays in motor skills, your physical therapist can work with you to develop play opportunities to enhance your child’s problem-solving, such as that used in the START-Play intervention, in addition to usual care in order to help your child advance cognitive and motor skills.

A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.

Cerebrovascular endothelial cells (CEC) comprise the blood-brain barrier (BBB). In a previous study, we showed that oxidized LDL (oxLDL) can induce apoptosis of mouse CEC. Resveratrol possesses chemopreventive potential. This study aimed to evaluate the effects of resveratrol on oxLDL-induced insults to mouse CEC and its possible mechanisms. Exposure of mouse CEC to 200 μmol/L oxLDL for 1 h did not cause cell death but significantly altered the permeability and transendothelial electrical resistance of the cell monolayer. However, resveratrol completely normalized such injury. As for the mechanisms, resveratrol completely protected oxLDL-induced disruption of F-actin and microtubule cytoskeletons as well as occludin and zona occludens-1 (ZO-1) tight junctions. The oxLDL-induced decreases in the mitochondrial membrane potential and intracellular ATP levels were normalized by resveratrol. Exposure of mouse CEC to 200 μmol/L oxLDL for 24 h elevated oxidative stress and simultaneously induced cell apoptosis. However, resveratrol partially protected against oxLDL-induced CEC apoptosis. The oxLDL-induced alterations in levels of Bcl-2, Bax, and cytochrome c were completely normalized by resveratrol. Consequently, resveratrol partially decreased oxLDL-induced activation of caspases-9 and -3. Therefore, in this study, we show that resveratrol can protect against oxLDL-induced damage of the BBB through protecting disruption of the tight junction structure and apoptotic insults to CEC.

Lipoteichoic acid (LTA), a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that ketamine has anti-inflammatory and antioxidant effects on gram-negative LPS-induced macrophage activation. In this study, we further evaluated the effects of ketamine on the regulation of LTA-induced TNF-alpha and IL-6 gene expressions and oxidative stress production in macrophages and its possible mechanisms. Exposure of macrophages to a therapeutic concentration of ketamine (100 microM) inhibited LTA-induced TNF-alpha and IL-6 expressions at protein or mRNA levels. In parallel, ketamine at 100 microM reduced LTA-stimulated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Sequentially, ketamine reduced the LTA-triggered translocation of nuclear factor-kappaB (NFkappaB) from the cytoplasm to nuclei and its transactivation activity. Pretreatment with PD98059, an inhibitor of ERK, decreased LTA-enhanced NFkappaB activation and TNF-alpha and IL-6 mRNA syntheses. Cotreatment with ketamine and PD98059 synergistically suppressed the LTA-induced translocation and transactivation of NFkappaB and biosyntheses of TNF-alpha and IL-6 mRNA. Application of Toll-like receptor 2 (TLR2) small interfering RNA (si)RNA into macrophages decreased the levels of this receptor, and simultaneously ameliorated LTA-augmented NFkappaB transactivation and consequent production of TNF-alpha and IL-6 mRNA. Cotreatment with ketamine and TLR2 siRNA synergistically lowered TNF-alpha and IL-6 mRNA syntheses in LTA-activated macrophages. Ketamine and TLR2 siRNA could reduce the LTA-induced increases in production of nitrite and intracellular reactive oxygen species in macrophages, and their combination had better effects than a single exposure. Thus, this study shows that one possible mechanism involved in ketamine-induced inhibition of LTA-induced TNF-alpha and IL-6 gene expressions and oxidative stress production is through downregulating TLR2-mediated phosphorylation of ERK1/2 and the subsequent translocation and transactivation of NFkappaB.

Participation in home, school, and community activities is a primary outcome of early intervention services for children with disabilities and their families. The objectives of this study were to (a) describe participation of preschool-age children with cerebral palsy (CP); (b) determine effects of sex, age, and gross motor function on intensity of participation; and (c) identify child, family, and service determinants of intensity of participation. A convenience sample of 85 preschool-age children with CP and their parents participated. Parents completed self-report measures on children's participation, adaptive behavior, physical function, family functioning, and services. Children's Gross Motor Function Classification System levels (Palisano, Rosenbaum, Bartlett, & Livingston, 2008) were determined by assessors. A multiple linear regression analysis was conducted to determine the variance in intensity of participation explained by the determinants. Children with limited self-mobility had a lower intensity of participation than children with independent upright mobility. Adaptive behavior, transfers and basic mobility function, and upper extremity and physical function explained 46% of the variance of intensity of participation.