38 research outputs found
Why I use Poetry in My Medical Teaching.
Opinion piece - no abstract required
Human Muscle Progenitor Cells Overexpressing Neurotrophic Factors Improve Neuronal Regeneration in a Sciatic Nerve Injury Mouse Model
The peripheral nervous system has an intrinsic ability to regenerate after injury. However, this process is slow, incomplete, and often accompanied by disturbing motor and sensory consequences. Sciatic nerve injury (SNI), which is the most common model for studying peripheral nerve injury, is characterized by damage to both motor and sensory fibers. The main goal of this study is to examine the feasibility of administration of human muscle progenitor cells (hMPCs) overexpressing neurotrophic factor (NTF) genes, known to protect peripheral neurons and enhance axon regeneration and functional recovery, to ameliorate motoric and sensory deficits in SNI mouse model. To this end, hMPCs were isolated from a human muscle biopsy, and manipulated to ectopically express brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1). These hMPC-NTF were transplanted into the gastrocnemius muscle of mice after SNI, and motor and sensory functions of the mice were assessed using the CatWalk XT system and the hot plate test. ELISA analysis showed that genetically manipulated hMPC-NTF express significant amounts of BDNF, GDNF, VEGF, or IGF-1. Transplantation of 3 Ć 106 hMPC-NTF was shown to improve motor function and gait pattern in mice following SNI surgery, as indicated by the CatWalk XT system 7 days post-surgery. Moreover, using the hot-plate test, performed 6 days after surgery, the treated mice showed less sensory deficits, indicating a palliative effect of the treatment. ELISA analysis following transplantation demonstrated increased NTF expression levels in the gastrocnemius muscle of the treated mice, reinforcing the hypothesis that the observed positive effect was due to the transplantation of the genetically manipulated hMPC-NTF. These results show that genetically modified hMPC can alleviate both motoric and sensory deficits of SNI. The use of hMPC-NTF demonstrates the feasibility of a treatment paradigm, which may lead to rapid, high-quality healing of damaged peripheral nerves due to administration of hMPC. Our approach suggests a possible clinical application for the treatment of peripheral nerve injury
Placental Villous Hypermaturation is Associated with Improved Neonatal Outcomes
Introduction: Accelerated placental maturation is considered a sign of maternal vascular malperfusion, and is often interpreted as an adaptive, compensatory response by the placenta. We tested this interpretation by comparing outcomes in pregnancies with and without accelerated maturation.
Methods: Using data from the National Collaborative Perinatal Project, we categorized preterm placentas (24 - 34 weeks, inclusive; 2525 births) by whether they showed placental villous hypermaturation (PVH), i.e., had the appearance of a placenta of 37 weeks or over upon microscopic examination. We assessed whether PVH was associated with maternal race, maternal BMI, fetal sex, type of preterm birth, preeclampsia, signs of infection or inflammation or placental abruption. We also assessed whether placentas showing PVH were associated with improved outcomes in terms of survival, Apgar score, or oxygen use.
Results: PVH was more common in preeclamptic pregnancies and less common in pregnancies complicated by placental abruption or showing signs of placental infection or inflammation. Adjusting for potentially confounding factors, PVH was associated with reduced odds of fetal death, death between birth and 120 days of age, low Apgar scores and oxygen use. PVH was also associated with higher birthweights for gestational age. When correcting for the effect of birthweight, the association between PVH and reduced fetal and neonatal death remained significant.
Discussion: Accelerated placental maturation, as manifested by PVH, is associated with improved outcomes. Our work therefore supports the hypothesis that accelerated maturation is a compensatory response by the placenta to improve its transport capacity in specific pregnancy complications
Opioid Replacement for Pregnant Mothers With Opioid Use Disorder and Fetal Neurodevelopment: A Review
This paper reviews the published literature regarding neurodevelopmental outcomes in neonates following in utero exposure to opioids. We have summarized available clinical and experimental data. Overall, clinical data is limited and equivocal with most studies showing no significant neurodevelopmental impairments in infants and children exposed to opioids in utero. Various outcome measures assessed language, communication, cognitive, psychomotor, and behavioural outcomes. The equivocality of the data may be a result of the complexity of the cohort and the inability to disentangle the effect of the opioids from the multiple comorbidities. Results from experimental data show that all opioids cross the placental barrier. Mouse studies show biochemical and neurophysiological changes, leading to long-term effects on learning and memory. Some data also suggests that epigenetic and imprinting changes in the central nervous system of mice may lead to multigenerational effects of opioid exposure. Ultimately, the benefits of opioid replacement therapy outweigh its risks, but it should be done in the context of a broader biopsychosocial risk reduction approach. Promoting mother-child bonding and care through skin-to-skin contact, rooming-in, and breastfeeding can reduce severity of neonatal abstinence syndrome and improve outcomes. This cohort of women and children requires advocacy for comprehensive multidisciplinary care.Ā
RƩsumƩ
Cet article passe en revue la litteĢrature publieĢe concernant les reĢsultats neurodeĢveloppementaux chez les nouveau-neĢs apreĢs exposition in utero aux opioiĢdes. Nous avons reĢsumeĢ les donneĢes cliniques et expeĢrimentales disponibles. Dans lāensemble, les don- neĢes cliniques sont limiteĢes et eĢquivoques, avec la plupart des eĢtudes ne montrant aucune deĢficience neurodeĢveloppementale significative chez les nourrissons et les enfants exposeĢs aux opioiĢdes in utero. Diverses mesures de reĢsultats ont eĢvalueĢ les reĢsultats linguistiques, de communication, cognitifs, psychomoteurs et comportementaux. LāeĢquivociteĢ des donneĢes peut eĢtre le reĢsultat de la complexiteĢ de la cohorte et de lāincapaciteĢ aĢ deĢmeĢler lāeffet des opioiĢdes des multiples comorbiditeĢs. Les reĢsultats des donneĢes expeĢrimentales montrent que tous les opioiĢdes traversent la barrieĢre placentaire. Les eĢtudes sur la souris montrent des changements biochimiques et neurophysiologiques, conduisant aĢ des effets aĢ long terme sur lāapprentissage et la meĢmoire. Certaines donneĢes suggeĢrent eĢgalement que les changements eĢpigeĢneĢtiques et dāempreinte dans le systeĢme nerveux central des souris peuvent conduire aĢ des effets multigeĢneĢrationnels de lāexposition aux opioiĢdes. En fin de compte, les avantages de la theĢrapie de substitution aux opioiĢdes lāemportent sur ses risques, mais cela devrait eĢtre fait dans le contexte dāune approche plus large de reĢduction des risques biopsychosociaux. La promotion des liens et des soins entre la meĢre et lāenfant par le contact peau aĢ peau, lāaccoutumance et lāallaitement peut reĢduire la graviteĢ du syndrome dāabstinence neĢonatale et ameĢliorer les reĢsultats. Cette cohorte de femmes et dāenfants a besoin de plaidoyer pour des soins multidisciplinaires complets.