Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE.

Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific Lactobacilli and ameliorating disease during EAE. Furthermore, Lactobacilli enriched in the gut of vancomycin-treated EAE mice at day 3 post immunization negatively correlated with gut trypsin activity and EAE severity. In untreated EAE mice, we observed increased intestinal permeability and increased intestinal protease activated receptor 2 (PAR2) expression at day 3 post immunization. Prior studies have shown that trypsin increases intestinal permeability by activating PAR2. Our results suggest that the interaction between intestinal PAR2 and trypsin may be a key modulator of intestinal permeability and disease severity during EAE.

Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (1H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions.

Impaired ocular blood flow regulation in patients with open-angle glaucoma and diabetes.

BACKGROUND: To elucidate the potential impact of diabetes mellitus on primary open-angle glaucoma pathology through vascular deficiency. DESIGN: Cross-section analysis from a longitudinal, prospective study. PARTICIPANTS: Eighty-four open-angle glaucoma patients (20 diabetic open-angle glaucoma patients and 64 non-diabetic open-angle glaucoma patients) METHODS: Patients were analyzed for ocular structure, ocular perfusion pressure (OPP), retrobulbar blood flow and retinal capillary perfusion. Statistical analysis was performed by SPSS version 18.0. Comparisons between groups were made as well as multivariate linear regression analysis. MAIN OUTCOME MEASURE: Retrobulbar blood flow and the retinal microcirculation. RESULTS: Central retinal artery peak systolic velocity was 13.5% lower in diabetic patients (P = 0.007). In diabetic open-angle glaucoma patients, ocular perfusion pressure positively correlated with central retinal artery and temporal posterior ciliary artery peak systolic velocity (R = 0.476, P = 0.039 and R = 0.529, P = 0.02, respectively), and with central retinal artery and nasal posterior ciliary artery resistance index (R = 0.537, P = 0.018 and R = 0.566, P = 0.012 respectively). Average retinal nerve fibre layer positively correlated with central retinal artery peak systolic velocity and temporal posterior ciliary artery end diastolic velocity (R = 0.501, P = 0.029 and R = 0.553, P = 0.019, respectively), and negatively correlated with superior and inferior retinal avascular space in the diabetic group (R = -0.498, P = 0.030 and R = -0.700, P = 0.001, respectively); no correlations were found in the non-diabetic group. Negative correlations between retrobulbar and retinal circulations were only found in the diabetic open-angle glaucoma patients, whereas positive correlations between retinal flow and non-flow were only found in non-diabetic open-angle glaucoma patients. CONCLUSION: Diabetes may interfere with normal vascular regulation and contribute to glaucoma progression.

Anisocoria secondary to antiperspirant wipes in a pediatric population: a case series.

Acute-onset anisocoria or mydriasis in children carries a broad differential diagnosis and includes both benign and life-threatening causes, ranging from systemic or topical drug use to peripheral or central nervous system disease. The topical anticholinergic agent glycopyrronium (approved by the Food and Drug Administration in June 2018) is used to treat hyperhidrosis. We present the first case series of pediatric patients presenting with acute mydriasis due to exposure to glycopyrronium wipes. Six cases (ages 12-16) were identified: 3 presented emergently and 3 to a primary care physician. Additional symptoms included blurry vision (4/6) and unilateral headache (1/6). In 3 cases, use of glycopyrronium wipes was not elicited initially, neuroimaging was obtained, and ophthalmology (2/3) or neurology (1/3) was consulted. One patient remained undiagnosed and presented emergently again 2 months later. In all patients, symptoms resolved without further treatment.

Long-term efficacy of endoscopic cyclophotocoagulation in the management of glaucoma following cataract surgery in children.

PURPOSE: To report the long-term efficacy of endoscopic cyclophotocoagulation (ECP) in pediatric glaucoma following cataract surgery (GFCS). METHODS: ECP was performed on 35 eyes of 25 patients <16 years of age with GFCS. Patients were followed for a minimum of 2 years. Treatment failure was defined as consecutive postoperative intraocular pressure (IOP) of >24 mm Hg, alternative glaucoma procedure following ECP, or occurrence of visually significant complications. Analysis was performed to estimate risk factors for failure. RESULTS: A total of 27 aphakic and 8 pseudophakic eyes were included. Pretreatment IOP averaged 33.9 ± 7.9 mm Hg. Final IOP after a mean follow-up period of 7.2 years was 18.9 ± 8.8 mm Hg (P < 0.001). The success rate was 54% (19/35 eyes). The failure rate was not increased in pseudophakic patients relative to aphakic patients. Patients with single ECP demonstrated preserved visual acuity from baseline to final follow-up. CONCLUSIONS: In this patient cohort, with average follow-up period of 7.2 years, ECP was useful in the treatment of pediatric GFCS.

Should Men and Women be Managed Differently in Glaucoma?

INTRODUCTION: To assess differences in associations of ocular perfusion pressure (OPP) as well as retinal and retrobulbar blood flow between men and women with primary open angle glaucoma (OAG). METHODS: A total of 116 patients with OAG (age 66.9 ± 10.9 years, 70 females) participating in the Indianapolis Glaucoma Progression Study were assessed for OPP, retinal microcirculation, and retrobulbar blood flow. Confocal scanning laser Doppler flowmetry measured peripapillary retinal capillary blood flow. Color Doppler imaging measured peak systolic (PSV) and diastolic blood flow velocities and vascular resistance in the ophthalmic (OA), central retinal (CRA), and nasal and temporal short posterior ciliary arteries (N/T PCA). Bivariate Spearman correlation and multivariate linear regression analyses were performed. RESULTS: In female patients with OAG, inferior retinal capillary flow was associated with OPP (r = 0.246, P = 0.044). In men, superior and inferior sector retinal blood flow was associated with OPP (r = -0.402, P = 0.006 and r = -0.357, P = 0.016, respectively). There was no statistically significant association between OPP and retrobulbar blood vessel flow velocities in male patients with OAG but there was an association between OA and TPCA PSV and OPP in female patients with OAG (r = 0.290, P = 0.015 and r = 0.357, P = 0.002, respectively). In female patients with OAG, multivariate regression showed no statistically significant effect of any variable on the superior retinal capillary blood flow, with CRA PSV as a sole predictor to the inferior retinal sector (partial rho = 0.302, P = 0.015) and in male patients with OAG, superior sector retinal capillary blood flow was independently associated with intraocular pressure (partial rho = -0.371, P = 0.016) and OPP (partial rho = -0.456, P = 0.002) with a trend of association with OPP in the inferior retina (partial rho = -0.301, P = 0.053). CONCLUSIONS: There was a positive linear association between retinal microcirculation and OPP in females and a negative association in males. Male and female patients with OAG may differ in their vascular autoregulation in response to changes in OPP.