The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice.

After spinal cord injury (SCI), loss of cells and damage to ascending and descending tracts can result in paralysis. Current treatments for SCI are based on patient stabilization, and much-needed regenerative therapies are still under development. To activate and instruct stem and progenitor cells or injured tissue to aid SCI repair, it is important to modify the injury environment for a protracted period, to allow time for cell activation, proliferation and appropriate fate differentiation. Shh plays a critical role in spinal cord formation, being involved in multiple processes: it promotes production of motor neurons and oligodendrocytes from ventral cord progenitor cells and serves as an axon guidance molecule. Hence Shh is a candidate pleiotropic beneficial environmental factor for spinal cord regeneration. Here we show that administration of biodegradable microspheres that provide sustained, controlled delivery of Shh resulted in significant functional improvement in two different mouse models of SCI: contusion and dorsal hemioversection. The mechanism is multifactorial, involving increased proliferation of endogenous NG2+ oligodendrocyte lineage cells, decreased astrocytic scar formation and increased sprouting and growth of corticospinal (CST) and raphespinal tract (RST) fibers. Thus, long-term administration of Shh is a potential valuable therapeutic intervention for SCI.

Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants.

BACKGROUND: Infants aged <12 months are at high risk of hospitalization for influenza. Influenza vaccine is recommended for pregnant women and for most children; however, no vaccine is approved for infants aged <6 months. Effective approaches are needed to protect this vulnerable population. Vaccination of women during pregnancy may protect the infant through transfer of antibodies from the mother. Few studies have examined the effectiveness of this strategy, and those studies produced mixed results. METHODS: In a matched case-control study, case patients were infants aged <12 months admitted to a large urban hospital in the northeastern United States because of laboratory-confirmed influenza from 2000 to 2009. For each case, we enrolled 1 or 2 control subjects who were infants who tested negative for influenza and matched cases by date of birth and date of hospitalization (within 4 weeks). Vaccine effectiveness was calculated on the basis of matched odds ratios and was adjusted for confounding. RESULTS: The mothers of 2 (2.2%) of 91 case subjects and 31 (19.9%) of 156 control subjects aged <6 months, and 1 (4.6%) of 22 case subjects and 2 (5.6%) of 36 control subjects aged ≥6 months, had received influenza vaccine during pregnancy. The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5% (95% confidence interval [CI], 61.7%-98.1%; P = .001) for infants aged <6 months. The unadjusted effectiveness was 90.7% (95% CI, 59.9%-97.8%; P = .001). CONCLUSIONS: Influenza vaccine given to pregnant women is 91.5% effective in preventing hospitalization of their infants for influenza in the first 6 months of life.