Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells.

The gut microbiota and its derived metabolites greatly impact the host immune system, both innate and adaptive responses. Gut dysbiosis and altered levels of microbiota-derived metabolites have been described in several immune-related and immune-mediated diseases such as intestinal bowel disease, multiple sclerosis, or colorectal cancer. Gut microbial-derived metabolites are synthesized from dietary compounds ingested by the host or host-produced metabolites, and additionally, some bacterial products can be synthesized de novo. In this review, we focus on the two first metabolites families including short-chain fatty acids, indole metabolites, polyamines, choline-derived compounds, and secondary bile acids. They all have been described as immunoregulatory molecules that specifically affect the adaptive immune system and T helper 17 and regulatory T cells. We discuss the mechanisms of action and the consequences in health and diseases related to these gut microbial-derived metabolites. Finally, we propose that the exogenous administration of these molecules or other compounds that bind to their immunoregulatory receptors in a homologous manner could be considered therapeutic approaches.

Effect of time of diagnosis to surgery on outcome, including long-term neurodevelopmental outcome, in necrotizing enterocolitis.

A systematic review of the PubMed and EMBASE databases was carried out to determine if time from diagnosis to surgery affects outcomes in necrotising enterocolitis. The study was registered on the PROSPERO website. Studies reporting both time to surgery and at least one clinical outcome measure in infants undergoing surgery for NEC were included. The initial search returned 1121 articles. After removing duplicates, title, and abstract screening, 49 remained for full-text review. Of these, only two reported both timing of surgery for NEC and at least one clinical outcome. The total number of neonates included was 202. Outcomes reported were death and/or parenteral nutrition use 28 days post surgery in one study and white matter brain injury in the other. No statistically significant association was found between any of the outcomes reported and timing of surgery. There were, however, significant differences associated with non-modifiable risk factors, such as age and gestation, at presentation. However, very few studies report this as a variable. Given the continuing poor outcomes and heterogeneous nature of NEC and its treatments, further large-scale prospective studies are required to examine the impact of timing of surgery, alongside other, potentially modifiable factors on outcome in NEC.

Sports-Injury Encephalopathy.

Sports-related encephalopathies are a growing concern among athletes who have experienced head trauma. Anxiety is heightened for the public and especially among parents of children playing contact sports. The most common neuropsychological conditions are concussions and traumatic encephalopathies. Concussions result from brain traumas that can be asymptomatic, but more serious concussions can include loss of consciousness, neurological abnormalities, and/or posttraumatic amnesias. Repetitive concussions lead to persistent brain pathology, known as chronic traumatic encephalopathies. This gradually progressive neurodegenerative disease frequently presents with cognitive and neurological deficits, which can result in significant parkinsonian features and dementia. Imaging studies may be noncontributory; however, diffusion tensor imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging can detect changes indicative of these encephalopathies. Progressive neuronal degeneration with tau proteins are documented on pathological examination. Prevention, early diagnosis, and proper treatment are the recommended approach to these conditions.

The naloxone option.

This quick guide provides you with naloxone dosing information and steps you'll want to take once the crisis has passed.

RNA Polymerase 1 Is Transiently Regulated by Seizures and Plays a Role in a Pharmacological Kindling Model of Epilepsy.

Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region. At least in the dentate gyrus (DG), the pilocarpine SE-mediated transient activation of Pol1 did not translate into long-term changes of pre-rRNA levels or total ribosome content. Unaltered hippocampal ribosome content was also found after a 20-day PTZ kindling paradigm with increasing pro-convulsive effects of low dose PTZ that was injected every other day. However, after selectively deleting the essential Pol1 co-activator, transcription initiation factor-1A (Tif1a/Rrn3) from excitatory neurons, PTZ kindling was impaired while DG total ribosome content was moderately reduced and no major neurodegeneration was observed throughout the hippocampus. Therefore, Pol1 activity of excitatory neurons is required for PTZ kindling. As seizures affect ribosome biogenesis without long-term effects on the total ribosome content, such a requirement may be associated with a need to produce specialized ribosomes that promote pro-epileptic plasticity.