Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.     

An examination of depression through the lens of spinal cord injury: Comparative prevalence rates and severity in women and men

PURPOSE: This study describes the prevalence of probable major depressive disorder (MDD) as well as other depressive disorders (ODD) and severity of depressive symptoms in a national sample of women with spinal cord injury (SCI) and compares them with a case-matched sample of men with SCI. METHODS: A sample of 585 women was drawn and case-matched with men from the SCI Model System National SCI Database according to level/completeness of injury, follow-up year, and age. The outcome measure of depression was the Patient Health Questionnaire. MAIN FINDINGS: Prevalence rates for women were 7.9% for probable MDD and 9.7% for ODD; rates for men were 9.9% and 10.3%, respectively. Logistic regression revealed that women who were divorced or at year 1 follow-up had a higher odds of having probable MDD (odds ratio [OR], 3.4 and 2.9, respectively). Employed women and men had significantly lower odds of probable MDD (OR, 0.274 and 0.358, respectively). Statistically significant differences were not found in gender comparisons for either probable MDD or symptom severity, which also were not associated with injury characteristics. CONCLUSION: The most significant, and unexpected, research finding is the absence of gender differences in probable MDD and symptom severity. Results challenge notions that depression will necessarily follow SCI; that injury characteristics determine the development and severity of depression; and that women experience a greater burden of depression than men. The main clinical implication is that depression screening and referral should be a routine feature of health care for women living with SCI, as well as for their male counterparts. Furthermore, nearly one fourth of women and men reported experiencing some or greater difficulty in daily life and relationships in the absence of probable depressive disorder, warranting monitoring of subsyndromal depression as well.     

Influence on binding of third-order torque to second-order angulation

Using an earlier model, which described the critical contact angle for binding from second-order angulation alone, a more generalized model is derived that combines the effects of angulation and torque. From this vantage point, the onset of binding is evaluated for 3 scenarios: second-order angulation alone, third-order torque only, and a combination of second-order angulation and third-order torque. These scenarios are detailed by plotting the critical contact angle for binding against the torque angle as a function of 10 wire dimensions (16 x 16, 16 x 22, 17 x 17, 17 x 22, 17 x 25, 18 x 18, 18 x 22, 18 x 25, 19 x 25, and 21 x 25 mil), 4 bracket widths (70, 100, 130, and 160 mil), and 4 bracket slots (18, 20.5, 22, and 24.5 mil). From these plots, we learn that each wire base dimension (eg, an 18-mil base as found in 18 x 18-mil, 18 x 22-mil and 18 x 25-mil archwires) has a common maximum critical contact angle for binding. Moreover, each wire-slot combination has a common maximum torque angle, which is independent of bracket width. Finally, we learn that archwire-bracket combinations that use a metric 0.5-mm slot might have some advantages with regard to torquing--given the current philosophy that light, continuous forces are more favorable.