Comparison of gut microbiome profile in patients with schizophrenia and healthy controls - A plausible non-invasive biomarker?

The human gut microbiome regulates brain function through the microbiome-gut-brain axis and is implicated in several neuropsychiatric disorders. However, the relationship between the gut microbiome and the pathogenesis of schizophrenia (SCZ) is poorly defined, and very few studies have examined the effect of antipsychotic treatment response. We aim to study the differences in the gut microbiota among drug-naïve (DN SCZ) and risperidone-treated SCZ patients (RISP SCZ), compared to healthy controls (HCs). We recruited a total of 60 participants, from the clinical services of a large neuropsychiatric hospital, which included DN SCZ, RISP SCZ and HCs (n = 20 each). Fecal samples were analyzed using 16s rRNA sequencing in this cross-sectional study. No significant differences were found in taxa richness (alpha diversity) but microbial composition differed between SCZ patients (both DN and RISP) and HCs (PERMANOVA, p = 0.02). Linear Discriminant Analysis Effect Size (LEfSe) and Random Forest model identified the top six genera, which significantly differed in abundance between the study groups. A specific genus-level microbial panel of Ruminococcus, UCG005, Clostridium_sensu_stricto_1 and Bifidobacterium could discriminate SCZ patients from HCs with an area under the curve (AUC) of 0.79, HCs vs DN SCZ (AUC: 0.68), HCs vs RISP SCZ (AUC: 0.93) and DN SCZ vs RISP SCZ (AUC: 0.87). Our study identified distinct microbial signatures that could aid in the differentiation of DN SCZ, RISP SCZ, and HCs. Our findings contribute to a better understanding of the role of the gut microbiome in SCZ pathophysiology and suggest potential targeted interventions.

MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker.

PURPOSE: Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis. METHODS: Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared. RESULTS: Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis. CONCLUSION: The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.

Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes.

OBJECTIVE: Our work is aimed at exploring the interrelationship of oxidative stress and insulin resistance in NAFLD subjects with and without type 2 diabetes in a population-based study. METHODS: Subjects [n=200] were recruited from the Chennai Urban Rural Epidemiology Study. 1: Normal glucose tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: type 2 diabetic subjects [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCC) and glutathione levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD. RESULTS: TBARS and PCC levels were significantly elevated and GSH/GSSG ratio was significantly decreased in diabetic subjects with NAFLD compared to all other groups (p trend <0.001). Oxidative stress markers significantly associated with NAFLD even after adjusting for age, gender, BMI and glycemic status. CONCLUSIONS: Increased oxidative stress is independently associated with NAFLD in Asian Indians without and with T2DM.

Development and application of an in vitro susceptibility test for Acanthamoeba species isolated from keratitis to polyhexamethylene biguanide and chlorhexidine.

PURPOSE: To develop a reliable in vitro drug susceptibility test against Acanthamoeba isolates and to determine the minimum cysticidal concentration (MCC) of the drug. METHODS: Doubling dilutions of polyhexamethylene biguanide (PHMB) from 3,200 microg/mL to 3.125 microg/mL and chlorhexidine from 3,200 microg/mL to 1.5625 microg/mL were made in Durham tubes and tested against cysts of 19 Acanthamoeba isolates from keratitis. After the exposure to the drugs for 48 hours, the cysts were washed free of drugs by centrifugation. The deposit (cysts) was cultured on nonnutrient agar plates seeded with heat-killed Escherichia coli. The growth of trophozoites from cysts exposed to each of the dilution was recorded by microscopy to estimate the MCC of the drug. RESULTS: The minimum cysticidal concentration of PHMB varied from 25 microg/mL to 100 microg/mL and that of chlorhexidine varied from 1.56 microg/mL to 100 microg/mL. The mean MCC value for PHMB was 55.26 microg/mL and that for chlorhexidine 32.81 microg/mL. Minimum cysticidal concentration 50 (MCC50) of PHMB and chlorhexidine on Acanthamoeba isolates was 50.0 microg/mL and 25.0 microg/mL, respectively. Anti-Acanthamoeba activity of chlorhexidine was higher than that of PHMB and this was statistically significant (p = 0.036). The end point of the results of this method was the detection of the viable cysts undergoing excystment and multiplication of trophozoites with a reproducible and clear-cut estimation of the MCC of PHMB and chlorhexidine. CONCLUSION: The in vitro method described can be used as a standard test for assay of MCC of drugs on Acanthamoeba isolates and to study the susceptibility pattern of newer water-soluble anti-Acanthamoeba drugs.