Connect between gut microbiome and diseases of the human eye.

Implicating dysbiosis of gut microbiome in digestive tract diseases/diet-related diseases (obesity, inflammatory bowel disease, enterocolitis, diabetes, etc.) may be expected. However, when gut microbiome dysbiosis is implicated in extraintestinal diseases like cancers, muscular dystrophy, mental disorders, vaginosis, etc., it is all the more challenging. An additional challenge would be to ascertain the role of gut microbiome in ocular diseases, which are as remote as the brain. The present review highlights studies that establish the connect between gut microbiome dysbiosis and inflammatory ocular diseases such as uveitis, bacterial keratitis, fungal keratitis, etc.

Association of ACK1, TFRC polymorphism with diarrhoeagenic E. coli adhesion patterns and their jejunal expression profile in Indian Ghurrah pigs.

A total of 9 SNPs located in TFRC and ACK1 genes of SSC13q41 genomic region were examined for their association with the adhesion pattern of native Indian pigs using local isolate of diarrhoeagenic E. coli. Phenotypic evaluation of adhesion pattern of 150 pigs revealed 116 animals positive for adhesion, whereas 34 animals had non-adhesive phenotype. Among the adhesive animals, 6, 87 and 23 pigs were strongly adhesive, weakly adhesive and adhesive, respectively. PCR-RFLP study revealed 8 polymorphic SNPs with low to moderate PIC ranging from 7.39 to 37.25% and low to high heterozygosities (8-70%). The loci g.291 C > T, rs81218930 C > T, rs318751568 C > T of TFRC and g.93222 C > A g.94600 C > T of ACK1 showed significant departure from HWE. The genotypic frequencies of the SNPs as well as the haplotypes did not differ significantly (P > 0.05) across the adhesion patterns except one SNP (ACK1-g.107371 A > C). Among the g.107371 A > C genotypes observed, CA was associated with non-adhesive phenotype. Furthermore, TFRC mRNA expression levels were found to be significantly (P < 0.05) different among various adhesive phenotypes, whereas that of ACK1 was significantly (P < 0.05) different between non-adhesive and adhesive groups. The significant association of SNP (ACK1-g.107371 A > C), which was also previously reported to influence ETECF4 mediated diarrhoea susceptibility, implicates its wider application in genetic control of piglet diarrhoea. Furthermore, the up-regulation of TFRC gene expression in adhesive group supports its proposed role in activation of immune cells against E. coli and intracellular iron transport.

Prospective Analysis of Functional Outcome of Single-Stage Surgical Treatment for Symptomatic Tandem Spinal Stenosis.

BACKGROUND: Tandem spinal stenosis (TSS) is a rare presentation leading to combined clinical features of upper motor neuron and lower motor neuron lesion which includes intermittent neurogenic claudication with or without neurological deficit, progressive gait imbalance and gait disturbances. In literature, there is controversy whether stage surgery or single-stage surgery should be done. MATERIALS AND METHODS: From June 2009 to November 2016 in a series of 1381 patients who underwent surgery for various degenerative spinal conditions, 82 patients were diagnosed with having symptomatic TSS with an incidence of 5.93%. All patients diagnosed with TSS underwent single-stage surgical intervention by one surgical team. The perioperative factors were recorded for each patient. All patients were evaluated preoperatively and postoperatively at each followup with the modified Japanese Orthopaedic Association (mJOA) score, Nurick's grading, Oswestry disability index (ODI) and Cooper scale. RESULTS: In this study, 82 patients including 70 males and 12 females underwent simultaneous surgical intervention for symptomatic TSS. The mean age of patients was 61.78 ± 10.48 years. There was a significant improvement in mJOA score, Nuricks grading, ODI and Coopers scale postoperatively as compared to preoperative values (P < 0.05). CONCLUSION: Symptomatic TSS can be safely managed by single-stage surgical intervention with good postoperative results or without a significant increase in complication rates. Single-stage surgical intervention helps to relieve the symptoms of both cervical and lumbar spinal cord compression, avoids the risk of repeated anesthesia, reduce the duration of surgery, repeated hospitalization hence, reducing the cost for hospitalization and also reducing the rehabilitation, recuperation time and early functional recovery justifies single-stage surgical intervention.

New insights into culture negative endophthalmitis by unbiased next generation sequencing.

The proof-of-concept, study to investigate the presence of microorganisms in presumed infectious endophthalmitis using Next generation sequencing (NGS) was carried out in vitreous biopsies from 34 patients with endophthalmitis, and thirty patients undergoing surgery for non-infectious retinal disorders as controls. Following DNA extraction using the Qiagen mini kit and PCR amplification of the V3-V4 regions of the bacterial 16S rRNA and ITS 2 region of fungus, they samples were sequenced on an Illumina HiSeq 2500 Machine. Paired reads were curated, taxonomically labeled, and filtered. Culture based diagnosis was achieved in 15/34 (44%) patients while NGS diagnosed the presence of microbes in 30/34 (88%) patients (bacteria in 26/30, fungi in 2/30, mixed infections in 2/30 cases). All 30 controls were negative for bacteria or fungus by NGS. There was good agreement between culture and NGS for culture-positive cases. Among culture negative cases, DNA of common culturable bacteria were identified like Streptococcus sp., Staphylococcus sp., Pseudomonas sp., Gemella sp., Haemophilus sp., Acinetobacter sp. The specificity of NGS with culture and clinical diagnosis was found to be 20% and 100% respectively and sensitivity of NGS with culture and clinical diagnosis was found to be 87.5% and 88% respectively. NGS appears to be promising diagnostic platform for the diagnosis of infectious culture negative endophthalmitis.

Catalytic reduction of p-nitrophenol and methylene blue by microbiologically synthesized silver nanoparticles.

Catalytic Reduction of p-nitrophenol and Methylene blue by Microbiologically Synthesized Silver Nanoparticles was studied in the present investigation. Catalytic reduction of 4-Nitophenol/p-nitrophenol (PNP) and methylene blue (MB) was assessed using both intra and extracellular silver nanoparticles (AgNP) with and without immobilization. Both intracellular and extracellular AgNP were synthesized from actinomycetes. Antimicrobial activity of AgNP was also assessed and it was found that, intracellular AgNP have significant antibacterial activity against E. coli, S. typhi and B. subtilis. Synthesized biogenic silver nanoparticles were characterized by UV-visible spectrophotometry, FTIR, XRD, and TEM-EDS. It was found that, extracellular AgNP are efficient as compared to intracellular AgNP in terms of PNP reduction.

DABCO Catalyzed Green and Efficient Synthesis of 2-Amino-4H-Pyrans and Their Biological Evaluation as Antimicrobial and Anticancer Agents.

AIM AND OBJECTIVE: The present method is simple, green and highly efficient for the synthesis of 2-amino-4H-pyran derivatives which are achieved by a one pot three component cyclocondensation of aldehyde, malanonitrile and ethyl acetoacetate or methyl acetoacetate using DABCO under solvent free with grinding conditions at room temperature. MATERIAL AND METHODS: Some of the synthesized compounds were screened for their antimicrobial and antifungal activity. The study shows that these compounds show good antimicrobial activity. Furthermore, eight of the synthesized compounds were selected for screening of their anticancer activity against human astrocytoma-glioblastoma cell line (U373MG). Some of the compounds show good anticancer activity. RESULT: Grinding synthesis of 2-amino-4H-pyran derivatives catalyzed by DABCO with various aromatic aldehydes under solvent-free conditions at room temperature was examined. The obtained compounds (22 entries) were well synthesized in good to excellent yields. CONCLUSION: The present method is simple, rapid, and most efficient green protocol for the synthesis of 2-amino-4H-pyran derivatives using highly inexpensive and easily available DABCO as an efficient catalyst under grinding and solvent free condition at room temperature.

Synthesis and biological evaluation of imidazo[1,2-[Formula: see text]]pyridazines as inhibitors of TNF-[Formula: see text] production.

Tumor necrosis factor-alpha (TNF-[Formula: see text] is an important pro-inflammatory cytokine responsible for a diverse range of inflammatory diseases including rheumatoid arthritis. In the present manuscript, our medicinal chemistry efforts on the design, synthesis and TNF-[Formula: see text] evaluation of a series of 3, 6-disubstituted imidazo[1,2-b]pyridazine is described. The best compounds were 3-pyridyl and (4-(methylsulfonyl)phenyl) analogs 8q and 8w, showing inhibition of TNF-[Formula: see text] production with IC[Formula: see text]values of 0.9 and 0.4 [Formula: see text]M, respectively. The identified leads have potential for further development for treatment of inflammatory diseases.

Synthesis and in vitro evaluations of 6-(hetero)-aryl-imidazo[1,2-b]pyridazine-3-sulfonamide's as an inhibitor of TNF-α production.

Tumor necrosis factor-α is an important pro-inflammatory cytokine having a key role in hosts defensive process of immune systems and its over expression led to a diverse range of inflammatory diseases such as Rheumatoid arthritis, Cronh's disease, psoriasis, etc. This paper describes our medicinal chemistry efforts on imidazo[1,2-b]pyridazine scaffold: design, synthesis and biological evaluation. By the introducing sulfonamide functionality at 3 positions and substituting 6 positions with (hetero)-aryl groups', a small library of compounds was prepared. All synthesized compounds were screened for lipopolysaccharide (LPS) mediated TNF-α production inhibitory activity. Biological data revealed that the majority of the compounds of this series showed moderate to potent TNF-α production inhibitory activity. Compound 5u and 5v are the most potent compounds from the series with activity of IC50 = 0.5 µM and 0.3 µM respectively. A short SAR demonstrates that 3-sulfonyl-4-arylpiperidine-4-carbonitrile moiety on imidazo[1,2-b]pyridazine showed better activity compared to the 3-(4-aryllpiperazin-1-yl) sulfonyl) in hPBMC assay. The molecular modeling studies revealed that the potent TNF-α production inhibitory activity 5v due to the extra stability of complex because of an extra pi-pi (π-π) stacking, hydrogen-bonding interactions.

Discovery of tetrahydrocarbazoles as dual pERK and pRb inhibitors.

The extracellular signal-regulated kinase (ERK) is one of the most important molecular targets for cancer that controls diverse cellular processes such as proliferation, survival, differentiation and motility. Similarly, the Rb (retinoblastoma protein) is a tumor suppressor protein and its function is to prevent excessive cell growth by inhibiting cell cycle progression. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual inhibitors of pERK and pRb phosphorylation. The in-house small molecule library was screened for inhibition of pERK and pRb phosphorylation, which led to the discovery of tetrahydrocarbazole series of compounds as potential leads. N-(3-methylcyclopentyl)-6-nitro-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-amine (1) is the dual inhibitor lead identified through screening, displaying inhibition of pERK and pRb phosphorylation with IC50 values of 5.5 and 4.8 µM, respectively. A short structure-activity relationship (SAR) study has been performed, which identified another dual inhibitor 9-methyl-N-(4-methylbenzyl)-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-amine (16) with IC50 values 4.4 and 3.5 µM for inhibition of pERK and pRb phosphorylation, respectively. This compound has a potential for further lead optimization to discover promising molecularly-targeted anticancer agents.

We are not alone: a case for the human microbiome in extra intestinal diseases.

BACKGROUND: "Dysbiosis" in the gut microbiome has been implicated in auto-immune diseases, in inflammatory diseases, in some cancers and mental disorders. The challenge is to unravel the cellular and molecular basis of dysbiosis so as to understand the disease manifestation. MAIN BODY: Next generation sequencing and genome enabled technologies have led to the establishment of the composition of gut microbiomes and established that "dysbiosis" is the cause of several diseases. In a few cases the cellular and molecular changes accompanying dysbiosis have been investigated and correlated with the disease. Gut microbiome studies have indicated that Christensenella minuta controls obesity in mice, Faecalibacterium prausnitzii protects mice against intestinal inflammation and Akkermansia muciniphila reverses obesity and insulin resistance by secreting endocannabinoids. In mice polysaccharide antigen A on the surface of Bacteroides fragilis, reduces inflammation. Such experiments provide the link between the gut microbiome and human health but implicating dysbiosis with extra-intestinal diseases like arthritis, muscular dystrophy, vaginosis, fibromyalgia, some cancers and mental disorders appears to be more challenging. The relevance of gut microbiome to the eye appears to be very remote. But considering that the eye is the site of inflammatory diseases like uveitis, scleritis, Mooren's corneal ulcer etc. it is possible that these diseases are also influenced by dysbiosis. In mice signals from the gut microbiota activate retina specific T cells that are involved in autoimmune uveitis. Such information would open up new strategies for therapy where the emphasis would be on restoring the diversity in the gut by antibiotic or specific drug use, specific microbe introduction, probiotic use and fecal transplant therapy. The ocular surface microbiome may also be responsible for eye diseases in man but such studies are lacking. Microbiome of the healthy cornea and conjunctiva have been identified. But whether the ocular microbiome exhibits dysbiosis with disease? Whether ocular microbiome is influenced by the gut microbiome? What mediates the cross-talk between the gut and ocular microbiomes? These are questions that need to be addressed to understand idiopathic infections of the eye. CONCLUSIONS: Evaluating diseases remote from the gut would unfold the mysteries of the microbiome.

Methylsulfonyl benzothiazoles (MSBT) derivatives: Search for new potential antimicrobial and anticancer agents.

A series of novel 4 and 5-substituted methylsulfonyl benzothiazole (MSBT) compounds having amide, alkoxy, sulfonamide, nitro and amine functionality were synthesized from sequential reactions on 5-ethoxy-2-(methylsulfonyl)benzo[d]thiazole such as nitration, reduction, sulfonation, dealkylation, etc. All synthesized compounds were screened against antimicrobial and selected screened for anticancer activity. Antimicrobial activities studies reveled that among all compounds screened, out of MSBT-07, MSBT-11, MSBT-12, MSBT-14, MSBT-19, and MSBT-27 were found to have promising antimicrobial activity at MIC range of 4-50µg/ml against selected bacterial as well as fungal species. Compounds having good antimicrobial activity were screened for cervical cancer (HeLA cell lines). Of these MSBT-07 and MSBT-12 significantly reduced the cell growth. Consequently their calculated GI50 values were found to be 0.1 or <0.1µM.

The brain-dead donor: An anaesthesiologist's perspective.

The brain-dead organ donation programme is slowly gathering momentum in India. There is a long way to go before our cadaver donor numbers, currently at 0.35 per million reaches 35 per million as is the case in countries like Spain. Each donor, therefore, has to be managed immaculately. The anaesthesiologists will be well served by familiarising themselves with the challenges during the crucial period preceding and during the actual harvest of organs in a brain-dead donor. There are significant opportunities for anaesthesiologists to make great contributions in this cause due to their unique skill sets and perspective. A robust brain-dead cadaver programme will go a long way in saving numerous lives as well as reduce the requirements of the living donor programme. A well-managed harvest will ensure good quality organs and an overall superior outcome in the recipients.

Piperlongumine derived cyclic sulfonamides (sultams): Synthesis and in vitro exploration for therapeutic potential against HeLa cancer cell lines.

A novel modification of piperlongumine is designed, bearing a cyclic sulphonamide (sultam) and its synthesis is described. For the first time herein we report the synthesis and biological evaluation of the natural product derived cyclic sulfonamides using Grubbs second generation catalyst (Grubbs II) via ring closing metathesis approach. Synthesis of a series of piperlongumine derived sultams is done in a moderate to good yield using Wittig reaction, Ring-Closing Metathesis (RCM) and, amide synthesis by using mixed anhydride, approach. All synthesized compounds were evaluated for anticancer activity and some demonstrated dose dependent reduction in HeLa cell growth. Of these 7, 10 and 14 significantly reduced the cell growth. Consequently their calculated GI50 values were found to be 0.1 or <0.1 µM.

Aquipuribacter nitratireducens sp. nov., isolated from a soil sample of a mud volcano.

A novel Gram-stain-positive, coccoid, non-motile bacterium, designated strain AMV4T, was isolated from a soil sample collected from a mud volcano located in the Andaman Islands, India. The colony was pale orange. Strain AMV4T was positive for oxidase, aesculinase, lysine decarboxylase and ornithine decarboxylase activities and negative for amylase, catalase, cellulase, protease, urease and lipase activities. 16S rRNA gene sequence analysis indicated that strain AMV4T was a member of the order Actinomycetales and was closely related to Aquipuribacter hungaricus with a sequence similarity of 97.13% (pairwise alignment). Phylogenetic analyses showed that strain AMV4T clustered with Aquipuribacter hungaricus and was distantly related to the other genera of the family Intrasporangiaceae. DNA-DNA hybridization between strains AMV4T and Aquipuribacter hungaricus IV-75T showed a relatedness of 28%. The predominant cellular fatty acids were iso-C15 : 0 (6.9%), anteiso-C15 : 0 (25.3%), C16 : 0 (12.9%), anteiso-C16 : 0 (5.6%), C18 : 1ω9c (19.8%) and C18 : 3ω6,9,12c (9.1%). The diagnostic diamino acid in the cell-wall peptidoglycan of strain AMV4T was meso-diaminopimelic acid. Strain AMV4T contained MK-10(H4) as the predominant respiratory quinone. The polar lipids consisted of phosphatidylglycerol, one unidentified glycolipid, two unidentified phospholipids and five unidentified lipids. The DNA G+C content of strain AMV4T was 74.3 mol%. Based on data from this taxonomic study using a polyphasic approach, it is proposed that strain AMV4T represents a novel species of the genus Aquipuribacter, with the suggested name Aquipuribacter nitratireducens sp. nov. The type strain is AMV4T ( = CCUG 58430T = DSM 22863T = NBRC 107137T).

Lipid parameters - significance in patients with endogenous depression.

BACKGROUND: People are aware of the consequences of high serum lipid levels, specifically, total cholesterol. Awareness about harmful effects of very low levels of serum lipids is still lacking. Very low levels of serum lipids lead to psychological consequences. OBJECTIVES: The objective of this study was to show whether there was a significant relationship between serum lipid levels and depression. MATERIAL AND METHODS: Total 70 subjects were included in this study. 40 subjects suffering from depression as assessed with the help of clinical findings and Beck Depression Inventory (BDI) scores were included in the study group, while control group comprised of 30 normal subjects. Lipid profile was done on blood samples obtained after overnight fasting. BDI scores were also obtained in control group using BDI. Co-relation between BDI score and lipid levels was obtained in both the groups. RESULTS: Serum lipid levels were significantly low in study group as compared to control group. There was a significant negative co-relationship between serum lipid levels with depression. Subjects of study group having lower lipid levels specifically Total Cholestrol (TC) (r = -0.78), Low-Density Lipoprotein (LDL) (r = -0.69), TG (r = -0.41) and Very Low-Density Lipoprotein (VLDL)(r = - 0.418), showed higher BDI scores (p<0.05). CONCLUSION: We can conclude that there is a significant relationship between low TC and depression. Similarly, low levels of serum LDL, TG and VLDL also showed significant relationship with depression. Lipid levels below a certain limit are not good as it may cause depression. Patients with low lipid levels should be screened for depression so that if necessary, corrective measures can be taken at the earliest.

Draft Genome Sequence of Psychrobacter aquaticus Strain CMS 56T, Isolated from a Cyanobacterial Mat Sample Collected from Water Bodies in the McMurdo Dry Valley Region of Antarctica.

We report the 3.2-Mb draft genome sequence of Psychrobacter aquaticus strain CMS 56(T), isolated from a cyanobacterial mat sample collected from a water body in the McMurdo Dry Valley region of Antarctica.

Draft Genome Sequence of Winogradskyella psychrotolerans RS-3T, Isolated from the Marine Transect of Kongsfjorden, Ny-Alesund, Svalbard, Arctic Ocean.

The 4.3-Mb genome of Winogradskyella psychrotolerans strain RS-3(T), isolated from a sediment sample of a marine transect of Kongsfjorden, Ny-Ålesund, Svalbard, Arctic Ocean, is reported.

Draft Genome Sequence of Leifsonia rubra Strain CMS 76RT, Isolated from a Cyanobacterial Mat Sample from a Pond in Wright Valley, McMurdo, Antarctica.

The 2.7-Mb draft genome sequence of Leifsonia rubra strain CMS 76R(T), isolated from a cyanobacterial mat sample from a pond in Wright Valley, McMurdo, Antarctica, is reported.

Draft Genome Sequence of Cyclobacterium qasimii Strain M12-11BT, Isolated from Arctic Marine Sediment.

A 6.29-Mb genome sequence of Cyclobacterium qasimii strain M12-11B(T), isolated from an Arctic marine sediment sample, is reported.

Draft Genome Sequence of Arcticibacter svalbardensis Strain MN12-7T, a Member of the Family Sphingobacteriaceae Isolated from an Arctic Soil Sample.

The 4.69-Mb genome sequence of Arcticibacter svalbardensis strain MN12-7(T), isolated from an Arctic soil sample, is reported.