Myelin as a regulator of development of the microbiota-gut-brain axis.

Myelination in the peripheral and central nervous systems is critical in regulating motor, sensory, and cognitive functions. As myelination occurs rapidly during early life, neonatal gut dysbiosis during early colonization can potentially alter proper myelination by dysregulating immune responses and neuronal differentiation. Despite common usage of antibiotics (Abx) in children, the impact of neonatal Abx-induced dysbiosis on the development of microbiota, gut, brain (MGB) axis, including myelination and behavior, is unknown. We hypothesized that neonatal Abx-induced dysbiosis dysregulates host-microbe interactions, impairing myelination in the brain, and altering the MGB axis. Neonatal C57BL/6 mice were orally gavaged daily with an Abx cocktail (neomycin, vancomycin, ampicillin) or water (vehicle) from postnatal day 7 (P7) until weaning (P23) to induce gut dysbiosis. Behavior (cognition; anxiety-like behavior), microbiota sequencing, and qPCR (ileum, colon, hippocampus and pre-frontal cortex [PFC]) were performed in adult mice (6-8 weeks). Neonatal Abx administration led to intestinal dysbiosis in adulthood, impaired intestinal physiology, coupled with perturbations of bacterial metabolites and behavioral alterations (cognitive deficits and anxiolytic behavior). Expression of myelin-related genes (Mag, Mog, Mbp, Mobp, Plp) and transcription factors (Sox10, Myrf) important for oligodendrocytes were significantly increased in the PFC region of Abx-treated mice. Increased myelination was confirmed by immunofluorescence imaging and western blot analysis, demonstrating increased expression of MBP, SOX10 and MYRF in neonatally Abx-treated mice compared to sham controls in adulthood. Finally, administration of the short chain fatty acid butyrate following completion of the Abx treatment restored intestinal physiology, behavior, and myelination impairments, suggesting a critical role for the gut microbiota in mediating these effects. Taken together, we identified a long-lasting impact of neonatal Abx administration on the MGB axis, specifically on myelin regulation in the PFC region, potentially contributing to impaired cognitive function and bacterial metabolites are effective in reversing this altered phenotype.

Long-Term Survival After Definitive Concurrent Chemoradiation Therapy for Synchronous Small Cell Neuroendocrine Carcinoma of the Urinary Bladder and Adenocarcinoma of the Prostate: A Case Report.

Available reports of synchronous prostate and bladder cancer have exclusively described radical cystoprostatectomy with or without perioperative chemotherapy as the treatment of choice. There are no reports of curative intent or definitive chemoradiation therapy for synchronous primary bladder and primary prostate cancers. Small cell carcinoma of the bladder is a rare and aggressive tumor. We present the first case of synchronous mixed small cell carcinoma and urothelial carcinoma of the urinary bladder and adenocarcinoma of the prostate in a 70-year-old male who attained long-term survival after curative intent and definitive concurrent chemoradiotherapy with minimal acute and late toxicities. The patient remained alive and disease-free at 41 months post-treatment and achieved excellent functional outcomes with organ preservation. Definitive chemoradiation therapy offers a safe and effective, curative-intent organ preservation treatment for localized synchronous prostate and bladder cancers.

Prostate specific membrane antigen PET avidity in a granular cell tumour of the left supraspinatus muscle: a case report.

Granular cell tumour is a rare, mostly benign, soft tissue, neuroectodermal tumour, most commonly seen in the skin and peripheral soft tissue. There are no publications to date of PSMA-PET avidity in a granular cell tumour. In this 60 year old male, staging PSMA-PET for a localized intermediate risk prostate cancer incidentally identified a PSMA-avid left supraspinatus lesion, which was subsequently biopsy-proven as a granular cell tumour. We present the first case of PSMA-avid granular cell tumour and add to the growing literature documenting PSMA-PET avidity in benign and malignant lesions apart from prostate cancer.

No Increase in Acute or Late Radiation Toxicities in Patients With Ehlers-Danlos Syndrome Receiving Adjuvant Breast Radiation Therapy: A Report of Four Cases With Extended Follow-Up.

Ehlers-Danlos syndrome (EDS) consists of a heterogeneous group of congenital collagen formation disorders characterised by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility. Collagen vascular disorders have been implicated in increased incidence and severity of radiation toxicities; however, there are limited reports on the safety of radiation therapy with EDS. We identified all patients with EDS who received adjuvant conventional and hypofractionated breast radiation therapy at our institution and reviewed patient, treatment, and toxicity characteristics. Four patients were identified with a median follow-up of 13.2 months. Acute toxicities were limited to grade 1 dermatitis in all four patients. No late toxicities were seen. In this report, radiation therapy to the breast with conventional and hypofractionated regimens resulted in no significant acute or late toxicity.