Elizabethkingiameningoseptica and Elizabethkingia anophelis are two major pathogens in the genus Elizabethkingia. Studies have revealed that Elizabethkingia anophelis is frequently misidentified as E. meningoseptica. Therefore, our aim was to explore the clinical and molecular differences between these two species. The database of a clinical microbiology laboratory in a university-affiliated hospital of Taiwan was searched to identify patients with Elizabethkingia infections between January 2005 and June 2018. Species were reidentified using 16S ribosomal RNA gene sequencing. Twenty E. meningoseptica and 72 E. anophelis samples were collected from consecutive patients. E. meningoseptica was significantly more frequently isolated from the cerebrospinal fluid than was E. anophelis. The most susceptible antibiotic for all Elizabethkingia isolates was minocycline (91.3%), followed by levofloxacin (52.2%), tigecycline (23.9%), and piperacillin tazobactam (23.9%). Compared with E. anophelis, E. meningoseptica was significantly less susceptible to piperacillin tazobactam, minocycline, and levofloxacin. Regarding nonsynonymous substitutions in the quinolone-resistance determining regions of DNA gyrase, six sites were recognized in E. meningoseptica and one site was recognized in E. anophelis. E. meningoseptica had a significantly higher rate of fluoroquinolone target gene mutations than did E. anophelis. Because of less susceptibility to multiple antibiotics than E. anophelis, empirical antimicrobial therapy of E. meningoseptica should be more rigorous.

Radiation induces DNA and protein damage and free radical formation, effectively establishing cellular senescence in a variety of models. We demonstrate the effects of two known pleiotropic drugs following gamma radiation damage in neurosphere/cerebral organoid system based on human embryonic stem cells. mTORC1 repression by rapamycin prior to irradiation, or metabolic activation by minocycline after irradiation, partially rescues neuroepithelium integrity, neurite-growing capacity, ventricle formation and extracellular acidification rate as an integral measure of metabolic output. Cerebral organoid model thus provides valid and robust readouts for radiation studies in a complex 3D setting.

Impaired ventral hippocampal (VH)-prefrontal cortex (PFC) connectivity is implicated in many cognitive and behavioral disorders. Excitotoxic neonatal VH (nVH) lesion in rat pups has been shown to induce synaptic pruning in the PFC as well as behavioral changes of relevance to developmental neuropsychiatric disorders. In the current study, we hypothesized that microglia, immune cells required for proper brain development and plasticity, may play a role in the development of abnormal behaviors in the nVH-lesioned animals. Ibotenic acid-induced nVH lesion was induced in postnatal day (P)7 male rats. Developmental changes in microglial density, morphology, ultrastructure and gene expression were analyzed in the PFC at P20 and P60. Our results revealed increased microglial reactivity and phagocytic activity in the lesioned rats at P20. Increased mRNA levels of C3 and C1q, complement molecules involved in synaptic pruning, were concomitantly observed. Diminished, but maintained, microglial reactivity and reduced antioxidative defenses were identified in lesioned rats at P60. Behavioral deficits were significantly reduced in the post-pubertal rats by suppressing microglial reactivity by a one-week minocycline treatment immediately after the lesion, These results suggest that early-life disconnection of the VH has long-lasting consequences for microglial functions in the connected structures. Alterations in microglia may underlie synaptic reorganization and behavioral deficits observed following neonatal VH disconnection.

High dietary salt intake (HDSI) increases risk of stress-related neuropsychiatric disorders. Here, we explored the contribution of HDSI-induced neuroinflammation in key stress-responsive brain regions, the hypothalamic paraventricular nucleus (PVN) and basolateral amygdala (BLA), in promoting exaggerated neuronal activation and coping behaviors in response to acute psychogenic stress. Mice that underwent HDSI exhibited increased active stress coping behaviors during and after an acute swim stress, and these were reduced by concurrent administration of minocycline, an inhibitor of microglial activation, without affecting body fluid hyperosmolality caused by HDSI. Moreover, minocycline attenuated HDSI-induced increases of PVN TNF-α, activated microglia (Iba1), and acute swim stress-induced neuronal activation (c-Fos). In the BLA, similar effects were observed on Iba1+ and c-Fos+ counts, but not TNF-α levels. These data indicate that HDSI promotes neuroinflammation, increasing recruitment of neurons in key stress-associated brain regions and augmenting behavioral hyper-responsivity to acute psychological stress.

Developmental exposure to ethanol may cause fetal alcohol spectrum disorders (FASD), and immature central nervous system (CNS) is particularly vulnerable to ethanol. In addition to the developing brain, we previously showed that ethanol also caused neuroapoptosis, microglial activation, and neuroinflammation in the spinal cord. Minocycline is an antibiotic that inhibits microglial activation and alleviates neuroinflammation. We sought to determine whether minocycline could protect spinal cord neurons against ethanol-induced damage. In this study, we showed that minocycline significantly inhibited ethanol-induced caspase-3 activation, microglial activation, and the expression of pro-inflammatory cytokines in the developing spinal cord. Moreover, minocycline blocked ethanol-induced activation of glycogen synthase kinase 3 beta (GSK3β) a key regulator of microglial activation. Meanwhile, minocycline significantly restored ethanol-induced inhibition of protein kinase B (AKT), mammalian target of the rapamycin (mTOR), and ERK1/2 signaling pathways, which were important pro-survival signaling pathways for neurons. Together, minocycline may attenuate ethanol-induced damage to the developing spinal cord by inhibiting microglial activation/neuroinflammation and restoring the pro-survival signaling.

This systematic review aimed to evaluate whether alternative materials to conventional triple antibiotic paste (TAP - metronidazole, ciprofloxacin, and minocycline) and grey mineral trioxide aggregate (GMTA) could avoid tooth discoloration in teeth submitted to Regenerative Endodontic Procedure (REP). It was also investigated if dental bleaching is able to reverse the color of darkened teeth due to REP. The search was conducted in four databases (Medline via PubMed, Scopus, ISI Web of Science and BVS - Virtual health library), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The retrieved papers were uploaded in the software EndNoteTM and two reviewers independently selected the studies and extracted the data. Only studies in humans (case reports, case series, clinical trials) were included in the review. From 1,122 potentially eligible studies, 83 were selected for full-text analysis, and 38 were included in the review. The included studies were mainly case reports (76.3 %). The studies described a total of 189 teeth submitted to REP. From these, about 54% of teeth presented some degree of discoloration. Most teeth presenting color alteration were treated with TAP, especially when combined with GMTA. Only three studies performed dental bleaching to restore the color of teeth and neither bleaching technique was able to restore the original color of the crowns. The use of alternative materials to TAP and GMTA, such as double antibiotic paste or Ca(OH)2 pastes and white mineral trioxide aggregate or BiodentineTM, reduces the occurrence of tooth discoloration.

Background: The genera Abiotrophia and Granulicatella, previously known as nutritionally variant streptococci (NVS), are fastidious bacteria requiring vitamin B₆ analogs for growth. They are members of human normal oral microbiota, and are supposed to be one of the important pathogens for so-called "culture-negative" endocarditis. Methods: The type strains and oral isolates identified, by using both phenotypic profiles and the DNA⁻DNA hybridization method, were examined for susceptibilities to 15 antimicrobial agents including penicillin (benzylpenicillin, ampicillin, amoxicillin, and piperacillin), cephem (cefazolin, ceftazidime, ceftriaxone, and cefaclor), carbapenem (imipenem), aminoglycoside (gentamicin), macrolide (erythromycin), quinolone (ciprofloxacin), tetracycline (minocycline), glycopeptide (vancomycin), and trimethoprim-sulfamethoxazole complex. The minimum inhibitory concentration and susceptibility criterion were determined, according to the consensus guideline from the Clinical and Laboratory Standards Institute. Results: Isolates of Abiotrophia defectiva were susceptible to ampicillin, amoxicillin ceftriaxone, cefaclor, imipenem, ciprofloxacin, and vancomycin. Isolates of Granulicatella adiacens were mostly susceptible to benzylpenicillin, ampicillin, amoxicillin, cefazolin, ceftriaxone, imipenem, minocycline, and vancomycin. The susceptibility profile of Granulicatella elegans was similar to that of G. adiacens, and the susceptibility rate was higher than that of G. adiacens. Conclusions: Although Abiotrophia and Granulicatella strains are hardly distinguishable by their phenotypic characteristics, their susceptibility profiles to the antimicrobial agents were different among the species. Species-related differences in susceptibility of antibiotics should be considered in the clinical treatment for NVS related infections.