The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Sugar-rich diets and poor dental hygiene promote the formation of a biofilm (plaque) that strongly adheres to the dental enamel surface and fosters the evolution of aciduric bacteria. The acid contributes to demineralization of the exterior tooth enamel, which accelerates after the pH drops below a critical value (∼5.5) for extended time periods resulting in the need for restorative procedures. Preventative techniques to alert the dentist and caries-susceptible patients regarding vulnerability to dental decay require a clinical measure of plaque activity. Therefore, there is a need to evaluate the acid production capability of plaque deposits in the pits and fissures of occlusal and interproximal regions. A ratiometric fluorescence pH-sensing device has been developed using an FDA-approved dye and LED excitation. Fluorescein spectral profiles were collected using a spectrometer and analyzed with a spectral unmixing algorithm for calibration over the pH range of 4.5 to 7. An in vivo pilot study on human subjects was performed using a sucrose rinse to accelerate bacterial metabolism and to measure the time-dependent drop in pH. The optical system is relatively immune to confounding factors such as photobleaching, dye concentration, and variation in excitation intensity associated with earlier dyebased pH measurement techniques.

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses.The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6-to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline-versus vehicle-treated germfree mice had similar alveolar bone loss outcomes, implying that antimicrobialdriven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring

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Significance: The scanning fiber endoscope (SFE), an ultrasmall optical imaging device with a large field-of-view (FOV) for having a clear forward view into the interior of blood vessels, has great potential in the cardiovascular disease diagnosis and surgery assistance, which is one of the key applications for short-wave infrared biomedical imaging. The state-of-the-art SFE system uses a miniaturized refractive spherical lens doublet for beam projection. A metalens is a promising alternative that can be made much thinner and has fewer off-axis aberrations than its refractive counterpart.Aim: We demonstrate a transmissive metalens working at 1310 nm for a forward viewing endoscope to achieve a shorter device length and better resolution at large field angles.Approach: We optimize the metalens of the SFE system using Zemax, fabricate it using e-beam lithography, characterize its optical performances, and compare them with the simulations. Results:The SFE system has a resolution of ∼140 μm at the center of field (imaging distance 15 mm), an FOV of ∼70 deg, and a depth-of-focus of ∼15 mm, which are comparable with a state-of-the-art refractive lens SFE. The use of the metalens reduces the length of the optical track from 1.2 to 0.86 mm. The resolution of our metalens-based SFE drops by less than a factor of 2 at the edge of the FOV, whereas the refractive lens counterpart has a ∼3 times resolution degradation.Conclusions: These results show the promise of integrating a metalens into an endoscope for device minimization and optical performance improvement.

In a patient with plasma cell leukemia, associated with pleural effusion, ultrastructural studies of the peripheral blood plasma cells showed an abundance of cytoplasmic fibrils. The nature of fibrils was not clarified, but they were not amyloid fibrils. This finding, coupled with a liaterature review, suggests that the cytoplasmic fibrils in plasma cells may be an additional cytological feature of this rare form of leukemia.

Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut-bone signaling axis. However, our prior work supports that a gut-liver signaling axis contributes to gut microbiota effects on bone. Purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific-pathogen-free(SPF) and germ-free(GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice, but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(FGF15) axis, a gut-liver endocrine axis supporting systemic bile acid homeostasis. Minocyclinetreated SPF mice had increased serum conjugated bile acids that are FXR antagonists, suppressed osteoblast function, decreased bone mass, impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR-signaling. This work introduces bile acids as a novel mediator of gut-liver signaling actions contributing to gut microbiota effects on bone.