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Evidence is growing that microglia adopt different roles than monocyte-derived macrophages (MDM) during CNS injury. Box5 in vivo However, knowledge about their function in the pathogenesis of neuroinfections is only rudimentary. Cattle are frequently affected by neuroinfections that are either zoonotic or related to diseases in humans, and, hence, studies of bovine neuroinfections as a natural disease model may generate fundamental data on their pathogenesis potentially translatable to humans. We investigated the transcriptomic landscape and lineage markers of bovine microglia and MDM. Although bovine microglia expressed most microglial signature genes known from humans and mice, they exhibited a species-specific transcriptomic profile, including strikingly low expression of TMEM119 and enrichment of the two scavenger receptors MEGF10 and LY75. P2RY12 was amongst the most enriched genes in bovine microglia, and antibodies against P2RY12 labeled specifically resting microglia, but also reactive microglia within neuroinfection foci in-situ. On the other hand, F13A1 was amongst the most enriched genes in bovine monocytes and MDM and, additionally, the encoded protein was expressed in-situ in monocytes and MDM in the inflamed brain but not in microglia, making it a promising marker for infiltrating MDM in the brain. In culture, primary bovine microglia downregulated signature genes, expressed markers of activation, and converged their transcriptome to MDM. However, they retained several microglia signature genes that clearly distinguished them from bovine MDM, making them a promising in-vitro tool to study mechanisms of microglia-pathogen interactions.

Adults with traumatic digital amputation (TDA) of the hand may be managed with replantation or revision amputation. To date, there is no systematic review evaluating patient reported outcomes (PROs) comparing replantation versus revision amputation.

Three databases (MEDLINE, EMBASE, and PubMed) were systematically searched in duplicate from inception until June 13, 2019 using Covidence software. Studies comparing replantation versus revision amputation outcomes were considered for inclusion. Methodological quality was assessed using Methodologic Index for Nonrandomized Studies (MINORS) criteria. Data were pooled in a random-effects meta-analysis model using Revman software. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).

Of 4350 studies identified, 12 retrospective cohort studies met inclusion criteria and compared TDA outcomes for replantation (n = 717; 82.9% male; mean age 40.3) versus revision amputation (n = 1046; 79.8% male; meow-quality evidence that thumb replantation achieves superior PROs compared with revision amputation, which may be clinically important. Replantation of single non-thumb digits also yielded superior PROs, which is likely not clinically important and based on very low-quality evidence. Future studies with populations outside Asia are required to determine if PROs vary based on cultural differences toward digital amputation.

Lymphatic diseases due to lymph vessel injuries in the pelvis and groin require immediate clinical attention when conventional treatments fail. We aimed to clarify the effectiveness of and indications for lymphaticovenular anastomosis (LVA) to treat these lymphatic diseases.

We retrospectively evaluated six patients who underwent LVA for lymphatic diseases due to lymph vessel injuries in the pelvis and groin. Specific pathologies included groin lymphorrhea (N = 3), chylous ascites (N = 2), and retroperitoneal lymphocele (N = 1). The maximum lymphatic fluid leakage volume was 150-2600 mL daily. Conventional treatments (compression, drainage, fasting, somatostatin administration, negative pressure wound therapy, or lymph vessel ligation) had failed to control leakage in all cases. We performed lower extremity LVAs after confirming the site of lymph vessel injury using lymphoscintigraphy. We preferentially placed LVAs in thigh sites that showed a linear pattern by indocyanine green lymphography. Postoperative lymphatic fluid leakage volume reduction was evaluated, and leakage cessation was recorded when the drainage volume approached 0 mL.

LVA was performed at an average of 4.3 sites (range, 3-6 sites) in the thigh and 2.7 sites (range, 0-6 sites) in the lower leg. Lymphatic fluid leakage ceased in all cases after a mean of 6 days (range, 1-11 days) postoperatively. No recurrence of symptoms was observed during an average follow-up of 2.9 (range, 0.5-5.5) years.

LVA demonstrates excellent and rapid effects. We recommend lower extremity LVA for the treatment of lymphatic diseases due to lymph vessel injuries in the pelvis and groin.

LVA demonstrates excellent and rapid effects. We recommend lower extremity LVA for the treatment of lymphatic diseases due to lymph vessel injuries in the pelvis and groin.Peripheral nerves contain sensory and motor neuron axons coated by glial cells whose interplay ensures function, but molecular details are lacking. SNARE-proteins mediate the exchange and secretion of cargo by fusing vesicles with target organelles, but how glial SNAREs contribute to peripheral nerve function is largely unknown. We, here, identify non-neuronal Synaptobrevin (Syb) as the essential vesicular SNARE in Drosophila peripheral glia to insulate and metabolically supply neurons. We show that tetanus neurotoxin light chain (TeNT-LC), which potently inhibits SNARE-mediated exocytosis from neurons, also impairs peripheral nerve function when selectively expressed in glia, causing nerve disintegration, defective axonal transport, tetanic muscle hyperactivity, impaired locomotion, and lethality. While TeNT-LC disrupts neural function by cleaving neuronal Synaptobrevin (nSyb), it targets non-neuronal Synaptobrevin (Syb) in glia, which it cleaves at low rates Glial knockdown of Syb (but not nSyb) phenocopied glial TeNT-LC expression whose effects were reverted by a TeNT-LC-insensitive Syb mutant. We link Syb-necessity to two distinct glial subtypes Impairing Syb function in subperineurial glia disrupted nerve morphology, axonal transport, and locomotion, likely, because nerve-isolating septate junctions (SJs) could not form as essential SJ components (like the cell adhesion protein Neurexin-IV) were mistargeted. Interference with Syb in axon-encircling wrapping glia left nerve morphology and locomotion intact but impaired axonal transport, likely because neural metabolic supply was disrupted due to the mistargeting of metabolite shuffling monocarboxylate transporters. Our study identifies crucial roles of Syb in various glial subtypes to ensure glial-glial and glial-neural interplay needed for proper nerve function, animal motility, and survival.