In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary.

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are two types of cortical projection neurons (CPNs): those that project locally and interhemispherically and those that project to subcerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here, we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during mouse brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate (CP) during the formation of the superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gainof-function analysis we show that Mllt11 is required for neuritogenesis and proper migration of upper layer CPNs. Loss of Mllt11 in the superficial cortex of male and female neonates leads to a severe reduction in fibers crossing the corpus callosum (CC), a progressive loss in the maintenance of upper layer projection neuron gene expression, and reduced complexity of dendritic arborization. Proteomic analysis revealed that Mllt11 associates with stabilized microtubules, and Mllt11 loss affected microtubule staining in callosal axons. Taken together, our findings support a role for Mllt11 in promoting the formation of mature upper-layer neuron morphologies and connectivity in the cerebral cortex.

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are generally two types of cortical projection neurons: those that project locally and interhemispherically, and those that project to sub-cerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate, particularly during the formation of the upper or superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gain-of-function analysis we show that Mllt11 is a required for neuritogenesis and proper migration of upper layer cortical projection neurons. Loss of Mllt11 in the superficial cortex leads to a severe reduction in fibres crossing the corpus callosum, a progressive loss in the maintenance of upper layer projection neuron gene expression, and dysplasia of dendritic arborisation patterns. Proteomic analysis revealed that Mllt11 associates with cytoskeletal components including stabilized microtubules consistent with a role in neuronal migration and neuritogenesis. Taken together, our findings support a role for Mllt11 in promoting the formation of mature projection neuron morphologies and connectivity in the cerebral cortex.

Background: Our study sought to identify independent risk factors predisposing patients with necrotizing soft tissue infections (NSTIs) to mortality from among laboratory values, demographic data, and microbiologic findings in a small population. To this end, a retrospective review was conducted of the medical records of all patients with NSTI who had been treated at our institution from 2003 to 2012 (n = 134). Methods: Baseline demographics and comorbidities, clinical and laboratory values, hospital course, and the microbiologic characteristics of surgical incision cultures were recorded. Each variable was tested for association with survival status and all associated variables with p < 0.15 were included in a logistic regression model to seek factors associated independently with mortality. Results: Surprisingly, no demographic or pre-existing condition proved to be a predictor of mortality. Two laboratory values had an inverse correlation to mortality: High C-reactive protein (CRP) and highest recorded CRP. Of surgical incisions that grew bacteria in culture, 33.6% were polymicrobial. Mortality rates were highest with Enterococcus-containing polymicrobial infections (50%), followed by those containing Pseudomonas (40%), and Streptococcus spp. (27%). Understanding why so many studies across the literature, now including our own, find such disparate results for correlation of NSTI mortality with patient data may lie in the fundamentally dynamic nature of the organisms involved. Conclusions: This study suggests that no single factor present on admission is a robust predictor of outcome; it is likely that survival in NSTI is predicated upon a complex interaction of multiple host and microbial factors that do not lend themselves to reduction into a simple formula. It is also abundantly clear that the wellestablished principles of NSTI surgery should continue to be followed in all cases, with an emphasis on early debridement, irrespective of apparent severity of initial presentation.

The dorsal medial region of the developing mammalian telencephalon plays a central role in the patterning of the adjacent brain regions. This review describes the development of this specialized region of the vertebrate brain, called the cortical hem , and the formation of the various cells and structures it gives rise to, including the choroid plexus, Cajal–Retzius cells and the hippocampus. We highlight the ontogenic processes that create these different forebrain derivatives from their shared embryonic origin and discuss the key signalling pathways and molecules that influence the patterning of the cortical hem. These include BMP, Wnt, FGF and Shh signalling pathways acting with Homeobox factors to carve the medial telencephalon into district progenitor regions, which in turn give rise to the choroid plexus, dentate gyrus and hippocampus. We then link the formation of the lateral ventricle choroid plexus with embryonic and postnatal neurogenesis in the hippocampus.