Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis.

INTRODUCTION: Despite older adults being more vulnerable to sepsis, most preclinical research on sepsis has been conducted using young animals. This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the host response to sepsis using the fecal-induced peritonitis (FIP) model developed by the National Preclinical Sepsis Platform (NPSP). METHODS: C57BL/6 mice (3 or 12 months old) were injected intraperitoneally with rat fecal slurry (0.75 mg/g) or a control vehicle. To investigate the early stage of sepsis, mice were culled at 4 h, 8 h, or 12 h to investigate disease severity, immunothrombosis biomarkers, and organ injury. Mice received buprenorphine at 4 h post-FIP. A separate cohort of FIP mice were studied for 72 h (with buprenorphine given at 4 h, 12 h, and then every 12 h post-FIP and antibiotics/fluids starting at 12 h post-FIP). Organs were harvested, plasma levels of Interleukin (IL)-6, IL-10, monocyte chemoattract protein (MCP-1)/CCL2, thrombin-antithrombin (TAT) complexes, cell-free DNA (CFDNA), and ADAMTS13 activity were quantified, and bacterial loads were measured. RESULTS: In the 12 h time course study, aged FIP mice demonstrated increased inflammation and injury to the lungs compared to young FIP mice. In the 72 h study, aged FIP mice exhibited a higher mortality rate (89%) compared to young FIP mice (42%) (p < 0.001). Aged FIP non-survivors also exhibited a trend towards elevated IL-6, TAT, CFDNA, CCL2, and decreased IL-10, and impaired bacterial clearance compared to young FIP non-survivors. CONCLUSION: To our knowledge, this is the first study to investigate the impact of age on survival using the FIP model of sepsis. Our model includes clinically-relevant supportive therapies and inclusion of both sexes. The higher mortality rate in aged mice may reflect increased inflammation and worsened organ injury in the early stage of sepsis. We also observed trends in impaired bacterial clearance, increase in IL-6, TAT, CFDNA, CCL2, and decreased IL-10 and ADAMTS13 activity in aged septic non-survivors compared to young septic non-survivors. Our aging model may help to increase the scientific validity of preclinical research and may be useful for identifying mechanisms of age-related susceptibility to sepsis as well as age-specific treatment strategies.

Negative school experiences in early adolescence on depressive affect in middle adulthood.

This study takes a life course perspective to examine the long-term effect of negative school experiences during early adolescence on depressive affect in middle adulthood. The study uses a prospective longitudinal panel dataset that spanned nearly three decades with three waves: when respondents were at 7th grade (Time 1, mostly 12-13 years of age), young adulthood (Time 2, in their 20 s), and middle adulthood (Time 3, in their mid-30 s to early 40 s). The OLS regression models yielded results demonstrating that early negative school experiences were contemporaneously associated with depressive affect at Time 1, which endured through Time 2 and Time 3. Furthermore, independently of Time 1 control variables and the stability effects of depressive affect at Time 1 and Time 2, early negative school experiences still exerted a direct effect on depressive affect in middle adulthood. Ad hoc analysis demonstrated that this significant direct effect was mediated by the economic attainment of the respondents in middle adulthood net of the stability effects of depressive affect. Apparently, part of the influences of early negative school experiences on depressive affect in middle adulthood may be explained by its impeding economic attainment in adulthood, which in turn was associated with depressive affect.

School performance, peer association, psychological and behavioral adjustments: a comparison between Chinese adolescents with and without siblings.

We test theoretically informed hypotheses using survey reports of adolescents attending three middle schools in the outskirts of Fuzhou, Fujian, China. Results yielded by regression analyses are quite consistent with the hypothesized relationships, that is, Chinese singleton adolescents are more likely to anticipate going to college than non-singleton adolescents. Further, singletons are more associated with conventional peers and they report better adjustments both psychologically and behaviorally than non-singleton adolescents. Singletons and non-singletons, however, are not different in their self-reported performance in four school subjects, namely, Chinese, Math, English, and Political Studies. These results are discussed in light of the theoretical literature, especially related to attachment theory, resource dilution theory as well as confluence model.

Mediating Mechanisms for the Intergenerational Transmission of Constructive Parenting: A Prospective Longitudinal Study.

Based on a prospective longitudinal panel data set that was collected at three developmental stages-early adolescence, young adulthood, and middle adulthood- this study investigates marital satisfaction and educational attainment as mediating mechanisms as well as gender's moderating effect for the intergenerational transmission of constructive parenting (N = 1,560). The results show that perceived satisfying experiences with parents during early adolescence are positively related to marital satisfaction and educational attainment in young adulthood, which, in turn, are positively related to individuals' utilization of constructive parenting in middle adulthood. The two mediating mechanisms account for most of the direct effect of the intergenerational transmission of constructive parenting. Furthermore, the mediating effect of marital relationship is stronger for current fathers than for mothers because of a stronger association between marital satisfaction and constructive parenting for men. The implications are discussed.

The nongroup market as one element of a broader coverage-expansion strategy.

Effective health insurance provides financial protection and access to services that maintain and improve health. Such coverage is difficult to obtain in the nongroup market, however, because of a lack of sponsorship, the nature of coverage available, adverse selection, and high administrative costs. However, certain interventions could make this market an effective avenue for expanding coverage to moderate- to high-income persons who lack access to employer-based coverage. In "less regulated" markets, we suggest broader, deeper funding of high-risk pools and standardization of benefits, preexisting condition exclusions, and waiting periods. In "more regulated" markets, a broadly funded reinsurance mechanism could moderate premiums.

Human cortical perfusion and the arterial pulse: a near-infrared spectroscopy study.

BACKGROUND: The pulsatile nature of the arterial pulse induces a pulsatile perfusion pattern which can be observed in human cerebral cortex with non-invasive near-infrared spectroscopy. The present study attempts to establish a quantitative relation between these two events, even in situations of very weak signal-to-noise ratio in the cortical perfusion signal. The arterial pulse pattern was extracted from the left middle finger by means of plethesmographic techniques. Changes in cortical perfusion were detected with a continuous-wave reflectance spectrophotometer on the scalp overlying the left prefrontal cortex. Cross-correlation analysis was performed to provide evidence for a causal relation between the arterial pulse and relative changes in cortical total hemoglobin. In addition, the determination of the statistical significance of this relation was established by the use of phase-randomized surrogates. RESULTS: The results showed statistically significant cross correlation between the arterial and perfusion signals. CONCLUSIONS: The approach designed in the present study can be utilized for a quantitative and continuous assessment of the perfusion states of the cerebral cortex in experimental and clinical settings even in situations of extremely low signal-to-noise ratio.