No abstract

The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. Second, the in situ hybridization method combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+ parabrachial neurons, indicating these neurons use glutamate as a transmitter. Third, conscious rats were maintained in a hypotensive or hypertensive state for two hours, and then, their brainstems were prepared by the standard c-Fos method which is a measure of neuronal activity. Both hypotension and hypertension resulted in c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostralmost part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo- and hypertension, and the PBcl signaling only hypotensive changes.

Background Treatment for HS (hidradenitis suppurativa) is often empiric and inadequate, and determining which patients will respond is difficult. Objective To determine which patient factors are associated with a positive response to first-line medical therapy. Methods A single-center retrospective cohort study of all HS patients seen between 1/1/1992 and 10/1/2014 was conducted. Response to first-line medical therapy (oral/topical antibiotics, intralesional corticosteroids, and topical washes) was examined at follow-up within 6 months of initiating therapy. A multivariate binary logistic regression model was built examining response to treatment and the interplay of patient factors and treatment initiated. Results 198 patients were included in the final model. Non-smokers (OR=2.634, 95%CI=1.301-5.332, p=0.007) and older individuals (OR=1.046 for each additional year, 95%CI=1.020-1.072, p<0.001) were more likely to have improvement at follow-up. Additionally, current smokers differed significantly from non-smokers in several regards. Limitations The retrospective nature of this study and relying on classification of disease severity from physical exam findings in some patients. Conclusions The results of this study suggest that clinicians may be able to more accurately predict which patients with HS will respond to first-line medical therapy, and which patients may require therapy escalation.

Isotretinoin plus clindamycin seem highly effective against severe erlotinib-induced skin rash in advanced non-small cell lung cancer.