Persistence of onchocerciasis and associated dermatologic and ophthalmic pathologies after 27 years of ivermectin mass drug administration in the middle belt of Ghana

Objectives: There is a pressing need to regularly evaluate the progress of onchocerciasis elimination programmes to timely identify and mitigate potential risks hindering the reaching of the 2030 targets proposed by the World Health Organization (WHO) in its roadmap on neglected tropical diseases (NTDs). We determined the prevalence of onchocerciasis and associated dermatological and ophthalmological manifestations in six endemic communities in the Bono Region of Ghana after 27 years of ivermectin mass treatment. Methods: In a cross-sectional study, 564 participants aged ≥5 years were enrolled (49.1% females), with a median age of 26 (range: 5–89) years. In 54% and 47%, skin-snip microscopy and Ov16 rapid diagnostic tests were performed, respectively. Skin disease was determined using the WHO Skin NTD App. Visual function assessments included tests of visual acuity. Results: The overall microfilarial prevalence was 12.5% (38/305) and Ov16 seroprevalence was 24.2% (64/265). Severe itching was recorded in 24.3%, acute papular onchodermatitis in 52.8%, chronic papular onchodermatitis in 12.5%, lichenified onchodermatitis in 0.7%, skin atrophy in 11.3%, depigmentation in 1.7% and palpable nodules in 5.3%. Of the 301 persons in which visual acuity was examined, 17% were visually impaired and 5.3% were blind and 47.3% presented with cataract. Chronic papular onchodermatitis, lichenified onchodermatitis, depigmentation and visual impairment were significantly associated with the presence of skin microfilariae and Ov16 seropositivity. Conclusions: The persistence of Onchocerca volvulus infection and onchocerciasis-associated dermatological and ophthalmological pathologies after prolonged treatment is of concern. There is a need to include morbidity management in onchocerciasis elimination programmes and understand better patterns of treatment coverage, adherence and actual intake of ivermectin

A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab

Purpose: We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients. Patients and Methods: TCGA microRNA expression data from tumors resected at first diagnosis of glioblastoma in patients treated with bevacizumab at any time during the course of their disease were randomly separated into training (n=50) and test (n=37) groups for model generation. MicroRNA-seq data for 51 patients whose treatment included bevacizumab in the BELOB trial were used as an independent validation cohort. Results: Using penalized regression we identified 8 microRNAs as potential predictors of overall survival in the training set. We dichotomized the response score based on the most prognostic minimum of a density plot of the response scores (log-rank HR=0.16, p=1.2e-5) and validated the profile in the test cohort (one-sided log-rank HR=0.34, p=0.026). Analysis of the profile using all samples in the TCGA glioblastoma dataset, regardless of treatment received, (n=473) showed that the prediction of patient benefit was not significant (HR=0.84, p=0.083) suggesting the profile is specific to bevacizumab. Further independent validation of our microRNA profile in RNA-seq data from patients treated with bevacizumab (alone or in combination with CCNU) at glioblastoma recurrence in the BELOB trial confirmed that our microRNA profile predicted patient benefit from bevacizumab (HR=0.59, p=0.043). Conclusion: We have identified and validated an 8-microRNA profile that predicts overall survival in patients with glioblastoma treated with bevacizumab. This may be useful for identifying patients who are likely to benefit from this agent

Discovery and delivery of anti-angiogenic miRNAs for cancer treatment

Cancer belongs to the top three causes of death in high-income countries. Several hallmarks of cancer have been identified that contribute to tumor growth. One of these hallmarks is angiogenesis, which occurs when the need for oxygen and nutrients to sustain the tumor cannot be maintained through passive means. At that point, tumor cells secrete growth factors, inducing blood vessel formation from preexisting blood vessels. Since the recognition of angiogenesis as a prominent factor contributing to solid tumor development, angiogenesis has become an attractive therapeutic target for cancer treatment. Several pharmaceuticals have been successfully developed to inhibit tumor angiogenesis and are currently approved for use in treatment of various types of cancer. Unfortunately, the therapeutic benefit of these therapeutics remains modest. At the same time, their high cost coupled to severe adverse reactions in some cases, create a need for better, more efficacious and safer strategies for anti-angiogenic therapy. One of these strategies exploits naturally occurring small non-coding RNAs, known as microRNAs (miRNAs). miRNAs have a key role in regulation of genes at a posttranscriptional level, including angiogenesis. Because miRNA expression levels in endothelial cells (EC) shift after angiogenic stimulation towards pro-angiogenic miRNA species that inhibit anti-angiogenic genes, miRNAs that inhibit pro-angiogenic genes might be an interesting therapeutic strategy to inhibit cancer angiogenesis. miRNAs have an important advantage over currently applied anti-angiogenic strategies because they regulate multiple genes at the same time, potentially leading to profound alteration of cell behavior compared to single pathway inhibition achieved by conventional anti-angiogenic agents. This thesis describes the discovery of anti-angiogenic miRNAs through functional screening with a lentiviral miRNA library to identify miRNAs that inhibit the viability of primary and immortalized EC. Number of anti-angiogenic miRNAs were identified and explored in depth in several in vitro and in vivo models. These miRNAs did not only inhibit neovascularization in a chicken chorioallantoic membrane assay, but also in two different mouse tumor models, which are known for their ability to form vascularized tumors. The potential of miRNAs as therapeutic applications were tested locally and systemically. To permit the usage of these miRNAs systemically, a novel delivery system was used, which we characterized in depth. In addition to their therapeutic potential, additional possibilities of using miRNAs as a tool to discover and identify novel target genes in drug development were explored in a comparative study between the miRNAs with a small molecule acting against the same target genes was investigated. Therefore, miRNAs offer a promising strategy for the exploration as well as development of new therapeutic anti-angiogenic applications

Characterization of the lactate permease operon of Veillonellae Atypica PK 1910

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (D.Sc.D.)--Boston University Henry M. Goldman School of Dental Medicine, 2002 (Pediatric Dentistry).Veillonellae have been extensively studied and have been found to have an unusual metabolism. They do not metabolize carbohydrates such as glucose as an energy source for growth, instead, they can grow well anaerobically in the presence of nonfermentable substrates. It has been proposed that Vel/onellae play an important role in reducing the cariogenic potential of plague bacteria. From a previous study, three ORFs were identified in let permease operon of V. atypica PK 1910: ORFl (mdh) of 1.136 hp, ORF2 (lctP) of 1.641 bp, and ORF3 (hem) of 1.257 bp. In this study we focused on the expression and regulation of lctP operon in V. atypica PK 1910 by environmental conditions. The bacteria was grown anaerobically in Scaedler broth supplemented with different acids: lactate, pyruvate, malate, formate, fumarate, and succinate. The growth was significantly better with lactate or pyruvate containing media. RNA purification was successful from the bacteria grown in different media in all different growth phases (logarithmic phase, stationary phase, and overnight culture) examined. [TRUNCATED

Reducing Barriers for Commercial Adaptation of Construction Materials with Low-Embodied-Carbon

Student Poster – Participants Annual Forum 2015 – Mahdee BabaeCommercial adaptation of construction materials with low-embodied-carbo

Survey efficiency of vermicompost process in product fertilizer from bagasse modified with kitchen waste

Abstract Background: Solid waste management is one of the biggest environmental challenges facing the world today due to the increasing population and urbanization, and use of earthworms has been receiving considerable attention in recent years for waste disposal and convert its into useful materials .The aim of the study was produced vermicompost from bagasse and kitchen waste. Methods: In this experimental was prepared the bagasse and kitchen waste treatment in three replication (a total of 9 units Laboratory). parameters such as pH , total carbon , total nitrogen , phosphorous and potassium was measured for 60 day. Results: In the end, pH did not change as compared to the initial level and trend. The results showed decreased in total carbon, total nitrogen , C/N and increased , phosphorous and potassium .the highest phosphorous and potassium content obtained 1:2 ratio. Conclusion: In the vermicomposting process, the best of mixture bagasse with kitchen waste was observed in 1:2 ratio and superior to other treatment

Evaluation of the ameliorative effects of oral administration of metformin on epileptogenesis in the temporal lobe epilepsy model in rats

Aims: Understanding the underlying molecular mechanisms involved in epileptogenesis is necessary to target the best therapeutic interventions in epilepsy. Recently, it has been postulated that metformin, an old antidiabetic oral drug, has anti-seizure properties mostly due to its antioxidant activities. This study was designed to evaluate the ameliorative effects of metformin on the progression of epilepsy in the temporal lobe epilepsy model in rats. Main methods: Temporal lobe Epilepsy was induced by intracerebroventricular microinjection of kainic acid. Metformin was orally administered for two weeks before induction of epilepsy. Anti-epileptogenic activity of metformin was evaluated by intracranial electroencepholography (IEEG) recording to detect spontaneous seizures, mossy fiber sprouting by Timm staining, neurogenesis by BrdU staining. Key findings: Oral administration of metformin prior to kainite-induced status epilepticus blocked the variant characterizations of epileptogenesis like neuronal cell death, aberrant neurogenesis, mossy fiber sprouting, and spontaneous seizures. Significance: These findings indicate that metformin has potential anti-epileptogenic properties in temporal lobe epilepsy. © 202