Plantar Fasciitis or Flexor Digitorum Brevis Myositis.

BACKGROUND: As common as plantar fasciitis is, there's a lack of evidence regarding the true pathophysiologic process causing plantar fasciitis and plantar heel pain in general. This may partially explain the high variability and outcomes with current treatment of recalcitrant plantar fasciitis. Although Lemont reported myxoid degeneration of plantar fascia with histologic analysis of patients with fasciitis, muscle biopsy results were not reported. So far it appears we have not focused on the muscular component that may be present with plantar heel pain in general and in patients we diagnose with plantar fasciitis in particular. METHODS: In this article we performed a retrospective analysis of biopsy results from five patients with the diagnosis of recalcitrant plantar fasciitis to determine whether this diagnosis was correct or whether other component pathologies contribute to the chronicity of symptoms or to the failure of treatment. RESULTS: Three of the five pathology reports included specific mention of inflammation, degeneration and atrophy of the intrinsic musculature consistent with myositis. Two of these showed lymphocytic infiltration in the muscle consistent with inflammation, with no signs of inflammation in the fascia. One showed inflammation of the fascia without signs of inflammation of the muscle. CONCLUSIONS: This small study introduces the idea that intrinsic myositis may contribute to, or be responsible for some cases of plantar heel pain and plantar fasciitis. This may be important in changing the way we deal with plantar heel pain in the future.

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition.

Acetylcholine (ACh), released in the hippocampus from fibers originating in the medial septum/diagonal band of Broca (MSDB) complex, is crucial for learning and memory. The CA2 region of the hippocampus has received increasing attention in the context of social memory. However, the contribution of ACh to this process remains unclear. Here, we show that in mice, ACh controls social memory. Specifically, MSDB cholinergic neurons inhibition impairs social novelty discrimination, meaning the propensity of a mouse to interact with a novel rather than a familiar conspecific. This effect is mimicked by a selective antagonist of nicotinic AChRs delivered in CA2. Ex vivo recordings from hippocampal slices provide insight into the underlying mechanism, as activation of nAChRs by nicotine increases the excitatory drive to CA2 principal cells via disinhibition. In line with this observation, optogenetic activation of cholinergic neurons in MSDB increases the firing of CA2 principal cells in vivo. These results point to nAChRs as essential players in social novelty discrimination by controlling inhibition in the CA2 region.

Molecular profiling-based decision for targeted therapies in IDH wild-type glioblastoma.

BACKGROUND: Molecular profiling allows tumor classification as well as assessment of diagnostic, prognostic, and treatment-related molecular changes. Translation into clinical practice and relevance for patients has not been demonstrated yet. METHODS: We analyzed clinical and molecular data of isocitrate dehydrogenase wild-type glioblastoma patients with sufficient clinical follow-up from the Heidelberg Neuro-Oncology Center and with molecular analysis of tumor tissue that consisted of DNA methylation array data, genome-scale copy number variations, gene panel sequencing, and partly mTOR immunohistochemistry between October 2014 and April 2018. RESULTS: Of 536 patients screened, molecular assessment was performed in 253 patients (47%) in a prospective routine clinical setting with further clinical appointments. Therapy decision was directly based on the molecular assessment in 97 (38%) patients. Of these, genetic information from MGMT (n = 68), EGFR (n = 7), CDKN2A/B (n = 8), alterations of the PI3K-AKT-mTOR pathway (n = 5), and BRAF (n = 3) have been the most frequently used for decision making with a positive overall survival signal for patients with glioblastoma harboring an unmethylated MGMT promoter treated according to the molecular assignment. Based on detected molecular alterations and possible targeted therapies, we generated an automated web-based prioritization algorithm. CONCLUSION: Molecular decision making in clinical practice was mainly driven by MGMT promoter status in elderly patients and study inclusion criteria. A reasonable number of patients have been treated based on other molecular aberrations. This study prepares for complex molecular decisions in a routine clinical decision making.