Search results for: biomedical drug

Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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Irregular consumption of current antibiotic makes increases of antibiotic resistance between urin pathogens on all worlds. This study selected based on this great community problem. The aim of this study was the biosynthesis of silver nanoparticles from Zataria multiflora extract and then to investigate its antibacterial effect on gram-negative bacilli common in Urinary Tract Infections (UTI) and MDR. The plant used in the present research was Zataria multiflora whose extract was prepared through Soxhlet extraction method. Green synthesis condition of silver nanoparticles was investigated in terms of three parameters including the extract amount, concentration of silver nitrate salt, and temperature. The seizes of nanoparticles were determined by Zetasizer. In order to identify synthesized silver nanoparticles Transmission Electron Microscopy (TEM) and X-ray Diffraction (XRD) methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through biological method different concentrations of silver nanoparticles were studied on 140 cases of Muliple Drug Resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections , for identification of bacteria were used of Polymerase Chain Reaction (PCR) test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were analyzed using SPSS software by nonparametric Kruskal-Wallis and Mann-Whitney tests. Significant results were found about the effects of silver nitrate concentration, different amounts of Zataria multiflora extract, and temperature on nanoparticles; that is, by increasing the concentration of silver nitrate, extract amount, and temperature, the sizes of synthesized nanoparticles declined. However, the effect of above mentioned factors on particles diffusion index was not significant. Based on the TEM results, particles were mainly spherical shape with a diameter range of 25 to 50 nm. The results of XRD Analysis indicated the formation of Nanostructures and Nanocrystals of silver.. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E.coli , Acinetobacter bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125mg/ml and for Acinetobacter bumanii 250mg/ml.Comparing the growth inhibitory effect of chemically synthesized Nanoparticles and biologically synthesized Nanoparticles showed that in the chemical method the highest growth inhibition belonged to the concentration of 62.5 mg /ml. The inhibitory effect on the growth all of bacteria causes of urine infection and MDR was observed and by increasing silver ion concentration in Nanoparticles, antibacterial activity increased. Generally, the biological synthesis can be considered an efficient way not only in making Nanoparticles but also for having anti-bacterial properties. It is more biocompatible and may be possess less toxicity than the Nanoparticles synthesized chemically.

Keywords: biosynthesis, MDR bacteria, silver nanoparticles, UTI

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: Dila Ram Bhandari

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Throughout the 20th century, new governments were created where identities such as ethnic, religious, linguistic, caste, communal, tribal, and others played a part in the development of constitutions and the legal system of victim and criminal justice. Acute issues with extremism, poverty, environmental degradation, cybercrimes, human rights violations, crime against, and victimization of both individuals and groups have recently plagued South Asian nations. Everyday massive number of crimes are steadfast, these frequent crimes have made the lives of common citizens restless. Crimes are one of the major threats to society and also for civilization. Crime is a bone of contention that can create a societal disturbance. The old-style crime solving practices are unable to live up to the requirement of existing crime situations. Crime analysis is one of the most important activities of the majority of intelligent and law enforcement organizations all over the world. The South Asia region lacks such a regional coordination mechanism, unlike central Asia of Asia Pacific regions, to facilitate criminal intelligence sharing and operational coordination related to organized crime, including illicit drug trafficking and money laundering. There have been numerous conversations in recent years about using data mining technology to combat crime and terrorism. The Data Detective program from Sentient as a software company, uses data mining techniques to support the police (Sentient, 2017). The goals of this internship are to test out several predictive model solutions and choose the most effective and promising one. First, extensive literature reviews on data mining, crime analysis, and crime data mining were conducted. Sentient offered a 7-year archive of crime statistics that were daily aggregated to produce a univariate dataset. Moreover, a daily incidence type aggregation was performed to produce a multivariate dataset. Each solution's forecast period lasted seven days. Statistical models and neural network models were the two main groups into which the experiments were split. For the crime data, neural networks fared better than statistical models. This study gives a general review of the applied statistics and neural network models. A detailed image of each model's performance on the available data and generalizability is provided by a comparative analysis of all the models on a comparable dataset. Obviously, the studies demonstrated that, in comparison to other models, Gated Recurrent Units (GRU) produced greater prediction. The crime records of 2005-2019 which was collected from Nepal Police headquarter and analysed by R programming. In conclusion, gated recurrent unit implementation could give benefit to police in predicting crime. Hence, time series analysis using GRU could be a prospective additional feature in Data Detective.

Keywords: time series analysis, forecasting, ARIMA, machine learning

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Authors: Khaled Al-Badani, Andrew Norbury, Essam Elmshawet, Glynn Rotwell, Ian Jenkinson , James Ren

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Micro welding procedures are widely used for joining materials, developing duplex components or functional surfaces, through various methods such as Micro Discharge Welding or Spot Welding process, which can be found in the engineering, aerospace, automotive, biochemical, biomedical and numerous other industries. The relationship between the material properties, structure and processing is very important to improve the structural integrity and the final performance of the welded joints. This includes controlling the shape and the size of the welding nugget, state of the heat affected zone, residual stress, etc. Nowadays, modern high volume productions require the welding of much versatile shapes/sizes and material systems that are suitable for various applications. Hence, an improved understanding of the micro welding process and the digital tools, which are based on computational numerical modelling linking key welding parameters, dimensional attributes and functional performance of the weldment, would directly benefit the industry in developing products that meet current and future market demands. This paper will introduce recent work on developing an integrated experimental and numerical modelling code for micro welding techniques. This includes similar and dissimilar materials for both ferrous and non-ferrous metals, at different scales. The paper will also produce a comparative study, concerning the differences between the micro discharge welding process and the spot welding technique, in regards to the size effect of the welding zone and the changes in the material structure. Numerical modelling method for the micro welding processes and its effects on the material properties, during melting and cooling progression at different scales, will also be presented. Finally, the applications of the integrated numerical modelling and the material development for the digital manufacturing of welding, is discussed with references to typical application cases such as sensors (thermocouples), energy (heat exchanger) and automotive structures (duplex steel structures).

Keywords: computer modelling, droplet formation, material distortion, materials forming, welding

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Authors: Morteza Ghorbani, Reza Ghorbani

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Cavitation phenomenon has attracted much attention in the mechanical and biomedical technologies. Despite the simplicity and mostly low cost of the devices generating cavitation bubbles, the physics behind the generation and collapse of these bubbles particularly in micro/nano scale has still not well understood. In the chemical industry, micro/nano bubble generation is expected to be applicable to the development of porous materials such as microcellular plastic foams. Moreover, it was demonstrated that the presence of micro/nano bubbles on a surface reduced the adsorption of proteins. Thus, the micro/nano bubbles could act as antifouling agents. Micro and nano bubbles were also employed in water purification, froth floatation, even in sonofusion, which was not completely validated. Small bubbles could also be generated using micro scale hydrodynamic cavitation. In this study, compared to the studies available in the literature, we are proposing a novel approach in micro scale utilizing the energy produced during the interaction of the spray affected by the hydrodynamic cavitating flow and a thin aluminum plate. With a decrease in the size, cavitation effects become significant. It is clearly shown that with the aid of hydrodynamic cavitation generated inside the micro/mini-channels in addition to the optimization of the distance between the tip of the microchannel configuration and the solid surface, surface temperatures can be increased up to 50C under the conditions of this study. The temperature rise on the surfaces near the collapsing small bubbles was exploited for energy harvesting in small scale, in such a way that miniature, cost-effective, and environmentally friendly energy-harvesting devices can be developed. Such devices will not require any external power and moving parts in contrast to common energy-harvesting devices, such as those involving piezoelectric materials and micro engine. Energy harvesting from thermal energy has been widely exploited to achieve energy savings and clean technologies. We are proposing a cost effective and environmentally friendly solution for the growing individual energy needs thanks to the energy application of cavitating flows. The necessary power for consumer devices, such as cell phones and laptops, can be provided using this approach. Thus, this approach has the potential for solving personal energy needs in an inexpensive and environmentally friendly manner and can trigger a shift of paradigm in energy harvesting.

Keywords: cavitation, energy, harvesting, micro scale

Procedia PDF Downloads 190

Authors: Ekemini M. Okon, Reuben C. Okocha, Babatunde T. Adesina, Judith O. Ehigie, Babatunde M. Falana, Boluwape T. Okikiola

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Antimicrobial resistance (AMR) has evolved to become a significant threat to global public health and food safety. The development of AMR in animals has been associated with antimicrobial overuse. In recent years, the number of antimicrobials used in food animals such as fish and poultry has escalated. It, therefore, becomes imperative to understand the patterns of AMR in fish and poultry and map out future directions for better surveillance efforts. This study used the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA) to assess the trend, patterns, and spatial distribution for AMR research in Egypt, Nigeria, and South Africa. A literature search was conducted through the Scopus and Web of Science databases in which published studies on AMR between 1989 and 2021 were assessed. A total of 172 articles were relevant for this study. The result showed progressive attention on AMR studies in fish and poultry from 2018 to 2021 across the selected countries. The period between 2018 (23 studies) and 2021 (25 studies) showed a significant increase in AMR publications with a peak in 2019 (28 studies). Egypt was the leading exponent of AMR research (43%, n=74) followed by Nigeria (40%, n=69), then South Africa (17%, n=29). AMR studies in fish received relatively little attention across countries. The majority of the AMR studies were on poultry in Egypt (82%, n=61), Nigeria (87%, n=60), and South Africa (83%, n=24). Further, most of the studies were on Escherichia and Salmonella species. Antimicrobials frequently researched were ampicillin, erythromycin, tetracycline, trimethoprim, chloramphenicol, and sulfamethoxazole groups. Multiple drug resistance was prevalent, as demonstrated by antimicrobial resistance patterns. In poultry, Escherichia coli isolates were resistant to cefotaxime, streptomycin, chloramphenicol, enrofloxacin, gentamycin, ciprofloxacin, oxytetracycline, kanamycin, nalidixic acid, tetracycline, trimethoprim/sulphamethoxazole, erythromycin, and ampicillin. Salmonella enterica serovars were resistant to tetracycline, trimethoprim/sulphamethoxazole, cefotaxime, and ampicillin. Staphylococcusaureus showed high-level resistance to streptomycin, kanamycin, erythromycin, cefoxitin, trimethoprim, vancomycin, ampicillin, and tetracycline. Campylobacter isolates were resistant to ceftriaxone, erythromycin, ciprofloxacin, tetracycline, and nalidixic acid at varying degrees. In fish, Enterococcus isolates showed resistance to penicillin, ampicillin, chloramphenicol, vancomycin, and tetracycline but sensitive to ciprofloxacin, erythromycin, and rifampicin. Isolated strains of Vibrio species showed sensitivity to florfenicol and ciprofloxacin, butresistance to trimethoprim/sulphamethoxazole and erythromycin. Isolates of Aeromonas and Pseudomonas species exhibited resistance to ampicillin and amoxicillin. Specifically, Aeromonashydrophila isolates showed sensitivity to cephradine, doxycycline, erythromycin, and florfenicol. However, resistance was also exhibited against augmentinandtetracycline. The findings constitute public and environmental health threats and suggest the need to promote and advance AMR research in other countries, particularly those on the global hotspot for antimicrobial use.

Keywords: antibiotics, antimicrobial resistance, bacteria, environment, public health

Procedia PDF Downloads 195

Authors: María Magdalena Méndez-González, Miguel García Rocha, Carlos Manuel Yermo De la Cruz

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Calcium phosphate (Ca5(PO4)3(X)) is widely used in orthopedic applications and is widely used as powder and granules. However, their presence in bone is in the form of nanometric needles 60 nm in length with a non-stoichiometric phase of apatite contains CO3-2, Na+, OH-, F-, and other ions in a matrix of collagen fibers. The crystal size, morphology control and interaction with cells are essential for the development of nanotechnology. The structural results of calcium phosphate, synthesized by chemical precipitation with crystal size of 22.85 nm are presented in this paper. The calcium phosphate powders were analyzed by X-ray diffraction, energy dispersive spectroscopy (EDS), infrared spectroscopy and FT-IR transmission electron microscopy. Network parameters, atomic positions, the indexing of the planes and the calculation of FWHM (full width at half maximum) were obtained. The crystal size was also calculated using the Scherer equation d (hkl) = cλ/βcosѲ. Where c is a constant related to the shape of the crystal, the wavelength of the radiation used for a copper anode is 1.54060Å, Ѳ is the Bragg diffraction angle, and β is the width average peak height of greater intensity. Diffraction pattern corresponding to the calcium phosphate called hydroxyapatite phase of a hexagonal crystal system was obtained. It belongs to the space group P63m with lattice parameters a = 9.4394 Å and c = 6.8861 Å. The most intense peak is obtained 2Ѳ = 31.55 (FWHM = 0.4798), with a preferred orientation in 121. The intensity difference between the experimental data and the calculated values is attributable to the temperature at which the sintering was performed. The intensity of the highest peak is at angle 2Ѳ = 32.11. The structure of calcium phosphate obtained was a hexagonal configuration. The intensity changes in the peaks of the diffraction pattern, in the lattice parameters at the corners, indicating the possible presence of a dopant. That each calcium atom is surrounded by a tetrahedron of oxygen and hydrogen was observed by infrared spectra. The unit cell pattern corresponds to hydroxyapatite and transmission electron microscopic crystal morphology corresponding to the hexagonal phase with a preferential growth along the c-plane was obtained.

Keywords: structure, nanoparticles, calcium phosphate, metallurgical and materials engineering

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

Procedia PDF Downloads 123

Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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Authors: Zelal Polat, Şebnem Harsa, Semra Ülkü

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Lactic acid exists in nature optically in two forms, L(+), D(-)-lactic acid, and has been used in food, leather, textile, pharmaceutical and cosmetic industries. Moreover, L(+)-lactic acid constitutes the raw material for the production of poly-L-lactic acid which is used in biomedical applications. Microbially produced lactic acid was aimed to be recovered from the fermentation media efficiently and economically. Among the various downstream operations, ion exchange chromatography is highly selective and yields a low cost product recovery within a short period of time. In this project, Lactobacillus casei NRRL B-441 was used for the production of L(+)-lactic acid from whey by fermentation at pH 5.5 and 37°C that took 12 hours. The product concentration was 50 g/l with 100% L(+)-lactic acid content. Next, the suitable resin was selected due to its high sorption capacity with rapid equilibrium behavior. Dowex marathon WBA, weakly basic anion exchanger in OH form reached the equilibrium in 15 minutes. The batch adsorption experiments were done approximately at pH 7.0 and 30°C and sampling was continued for 20 hours. Furthermore, the effect of temperature and pH was investigated and their influence was found to be unimportant. All the adsorption/desorption experiments were applied to both model lactic acid and biomass free fermentation broth. The ion exchange equilibria of lactic acid and L(+)-lactic acid in fermentation broth on Dowex marathon WBA was explained by Langmuir isotherm. The maximum exchange capacity (qm) for model lactic acid was 0.25 g La/g wet resin and for fermentation broth 0.04 g La/g wet resin. The equilibrium loading and exchange efficiency of L(+)-lactic acid in fermentation broth were reduced as a result of competition by other ionic species. The competing ions inhibit the binding of L(+)-lactic acid to the free sites of ion exchanger. Moreover, column operations were applied to recover adsorbed lactic acid from the ion exchanger. 2.0 M HCl was the suitable eluting agent to recover the bound L(+)-lactic acid with a flowrate of 1 ml/min at ambient temperature. About 95% of bound L(+)-lactic acid was recovered from Dowex marathon WBA. The equilibrium was reached within 15 minutes. The aim of this project was to investigate the purification of L(+)-lactic acid with ion exchange method from fermentation broth. The additional goals were to investigate the end product purity, to obtain new data on the adsorption/desorption behaviours of lactic acid and applicability of the system in industrial usage.

Keywords: fermentation, ion exchange, lactic acid, purification, whey

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Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

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Authors: Aditi Taunk, George Iskander, Kitty Ka Kit Ho, Mark Willcox, Naresh Kumar

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Bacterial infections on biomaterial implants and medical devices accounts for 60-70% of all hospital acquired infections (HAIs). Treatment or removal of these infected devices results in high patient mortality and morbidity along with increased hospital expenses. In addition, with no effective strategies currently available and rapid development of antibacterial resistance has made device-related infections extremely difficult to treat. Therefore, in this project we have developed biomaterial surfaces using antibacterial compounds that inhibit biofilm formation by interfering with the bacterial communication mechanism known as quorum sensing (QS). This study focuses on covalent attachment of potent quorum sensing (QS) inhibiting compounds, halogenated furanones (FUs) and dihydropyrrol-2-ones (DHPs), onto glass surfaces. The FUs were attached by photoactivating the azide groups on the surface, and the acid functionalized DHPs were immobilized on amine surface via EDC/NHS coupling. The modified surfaces were tested in vitro against pathogenic organisms such as Staphylococcus aureus and Pseudomonas aeruginosa using confocal laser scanning microscopy (CLSM). Successful attachment of compounds on the substrates was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The antibacterial efficacy was assessed, and significant reduction in bacterial adhesion and biofilm formation was observed on the FU and DHP coated surfaces. The activity of the coating was dependent upon the type of substituent present on the phenyl group of the DHP compound. For example, the ortho-fluorophenyl DHP (DHP-2) exhibited 79% reduction in bacterial adhesion against S. aureus and para-fluorophenyl DHP (DHP-3) exhibited 70% reduction against P. aeruginosa. The results were found to be comparable to DHP coated surfaces prepared in earlier study via Michael addition reaction. FUs and DHPs were able to retain their in vitro antibacterial efficacy after covalent attachment via azide chemistry. This approach is a promising strategy to develop efficient antibacterial biomaterials to reduce device related infections.

Keywords: antibacterial biomaterials, biomedical device-related infections, quorum sensing, surface functionalization

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Authors: Huda Abdelrhman Osman Ahmed, Paul Feyi Waboso

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Introduction: Placenta accreta spectrum (PAS) disorders present a significant challenge in obstetric management due to the high risk of hemorrhage and potential complications at delivery. This case describes a 27+3 weeks gestation in a patient with placenta accreta managed with classical cesarean section and peripartum hysterectomy. Case Description: AGravida 4P3 patient presented at 27+3 weeks gestation with painless, unprovoked vaginal bleeding and an estimated blood loss (EBL) of 300 mL. At the 20+5 week anomaly scan, a placenta previa was identified anterior, covering the os anterior uterus and containing lacunae with signs of myometrial thinning. At a 24+1 week scan conducted at a tertiary center, further imaging indicated placenta increta with invasion into the myometrium and potential areas of placenta percreta. The patient’s past obstetric history included three previous cesarean sections, with no significant medical or surgical history. Social history revealed heavy smoking but no alcohol use. No drug allergies were reported. Given the risks associated with PAS, a management plan was formulated, including an MRI at a later stage and cesarean delivery with a possible hysterectomy between 34-36 weeks. However, at 27+3 weeks, the patient experienced another episode of vaginal bleeding EBL 500 ml, necessitating immediate intervention. Management: As the patient was unstable, she was not transferred to the tertiary center. Completed and informed consent was obtained. MDT planning-group and cross-matching 4 units, uterotonics. Tranexamic acid blood products, cryo, cell salvage, 2 obstetric consultants and an anesthetic consultant, blood bank aware and hematologist. HDU bed and ITU availability. This study assisted in performing a classical Caesarean section, Where the urologist inserted JJ ureteric stents. Following this, we also assisted in a total abdominal hysterectomy with the conservation of ovaries. 4 units RBC and 1 unit FFP were transfused. The total blood loss was 2.3 L. Outcome: The procedure successfully achieved hemostasis, and the neonate was delivered with subsequent transfer to a neonatal intensive care unit for management. The patient’s postoperative course was monitored closely with no immediate complications. Discussion: This case highlights the complexity and urgency in managing placenta accreta spectrum disorders, particularly with the added challenges posed by remote location and limited tertiary support. The need for rapid decision-making and interdisciplinary coordination is emphasized in such high-risk obstetric cases. The case also underscores the potential for surgical intervention and the importance of family involvement in emergent care decisions. Conclusion: Placenta accreta spectrum disorders demand meticulous planning and timely intervention. This case contributes to understanding PAS management at earlier gestational ages and provides insights into the challenges posed by access to tertiary care, especially in urgent situations.

Keywords: Accreta, Hysterectomy, 3MDT, prematurity

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Authors: Yusuf Hesham Mohamed

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Introduction: Three-dimensional printing technology includes multiple procedures that fabricate three-dimensional objects through consecutively layering two-dimensional cross-sections on top of each other. 3D bioprinting is a promising field of 3D printing, which fabricates tissues and organs by accurately controlling the proper arrangement of diverse biological components. 3D bioprinting uses software and prints biological materials and their supporting components layer-by-layer on a substrate or in a tissue culture plate to produce complex live tissues and organs. 3D food printing is an emerging field of 3D bioprinting in which the 3D printed products are food products that are cheap, require less effort to produce, and have more desirable traits. The Aim of the Study is the development of an affordable 3D bioprinter by altering a locally made CNC instrument with an open-source platform to suit the 3D bio-printer purposes. Later, we went through applying the prototype in several applications regarding food technology and drug testing, including the organ-On-Chip. Materials and Methods: An off-the-shelf 3D printer was modified by designing and fabricating the syringe unit, which was designed on the basis of the Milli-fluidics system. Sodium alginate and gelatin hydrogels were prepared, followed by leaf cell suspension preparation from narrow sections of Fragaria’s viable leaves. The desired 3D structure was modeled, and 3D printing preparations took place. Cell-free and cell-laden hydrogels were printed at room temperature under sterile conditions. Post printing curing process was performed. The printed structure was further studied. Results: Positive results have been achieved using the altered 3D bioprinter where a 3D hydrogel construct of two layers made of the combination of sodium alginate to gelatin (15%: 0.5%) has been printed. DLP 3D printer was used to design the syringe component with a transparent PLA-Pro resin for the creation of a microfluidics system having two channels altered to the double extruder. The hydrogel extruder’s design was based on peristaltic pumps, which utilized a stepper motor. The design and fabrication were made using DIY-3D printed parts. Hard plastic PLA was the material utilized for printing. SEM was used to carry out the porous 3D construct imaging. Multiple physical and chemical tests were performed in order to ensure that the cell line was suitable for hosting. Fragaria plant was developed by suspending Fragaria’s cells from its leaves using the 3D bioprinter. Conclusion: 3D bioprinting is considered to be an emerging scientific field that can facilitate and improve many scientific tests and studies. Thus, having a 3D bioprinter in labs is considered to be an essential requirement. 3D bioprinters are very expensive; however, the fabrication of a 3D printer into a 3D bioprinter can lower the cost of the bioprinter. The 3D bioprinter implemented made use of peristaltic pumps instead of syringe-based pumps in order to extend the ability to print multiple types of materials and cells.

Keywords: scaffold, eco on chip, 3D bioprinter, DLP printer

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Authors: Hafsa Memona, Farkhanda Manzoor

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Cockroaches are termed as medically important pests because of their wide distribution in human habitation including houses, hospitals, food industries and kitchens. They may harbor multiple drug resistant pathogenic bacteria and protozoan parasites on their external surfaces, disseminate on human food and cause serious diseases and allergies to human. Hence, they are regarded as mechanical vector in human habitation due to their nocturnal activity and nutritional behavior. Viable eggs and dormant cysts of parasites can hitch a ride on cockroaches. Ova and cysts of parasitic organism may settle into the crevices and cracks between thorax and head. There are so many fissures and clefts and crannies on a cockroach which provide site for these organisms. This study aimed with identifying role of cockroaches in mechanically transmitting and disseminating gastrointestinal parasites in two environmental settings; hospitals and houses in urban area of Lahore. Totally, 250 adult cockroaches were collected from houses and hospitals by sticky traps and food baited traps and screened for parasitic load. All cockroaches were captured during their feeding time in natural habitat. Direct wet smear, 1% lugols iodine and modified acid-fast bacilli staining were used to identify the parasites from the body surfaces of cockroaches. Among human habitation two common species of cockroaches were collected i.e. P. americana and B. germanica. The results showed that 112 (46.8%) cockroaches harbored at least one human intestinal parasite on their body surfaces. The cockroaches from hospital environment harboured more parasites than houses. 47 (33.57%) cockroaches from houses and 65 (59.09%) from hospitals were infected with parasitic organisms. Of these, 76 (67.85%) were parasitic protozoans and 36(32.15%) were pathogenic and non-pathogenic intestinal parasites. P. americana harboured more parasites as compared to B. germanica in both environment. Most common human intestinal parasites found on cockroaches include ova of Ascaris lumbricoides (giant roundworm), Trichuris trichura (whipworm), Anchylostoma deodunalae (hookworm), Enterobius vermicularis (pinworm), Taenia spp. and Strongyloides stercoralis (threadworm). The cysts of protozoans’ parasites including Balantidium coli, Entomoeba hystolitica, C. parvum, Isospora belli, Giardia duodenalis and C. cayetenensis were isolated and identified from cockroaches. Both experimental sites were significantly different in carriage of parasitic load on cockroaches. Difference in the hygienic condition of the environments, including human excrement disposal, variable habitat interacted, indoor and outdoor species, may account for the observed variation in the parasitic carriage rate of cockroaches among different experimental site. Thus a finding of this study is that Cockroaches are uniformly distributed in human habitation and act as a mechanical vector of pathogenic parasites that cause common illness such as diarrhea and bowel disorders. This fact contributes to epidemiological chain therefore control of cockroaches will significantly lessen the prevalence of illness in human. Effective control strategies will reduce the public health burden of the gastro-intestinal parasites in the developing countries.

Keywords: cockroaches, health risks, hospitals, houses, parasites, protozoans, transmission

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Authors: Mihaela Beregoi, Horia Iovu, Cristina Busuioc, Alexandru Evanghelidis, Elena Matei, Monica Enculescu, Ionut Enculescu

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Nanomaterials field is very attractive for all researchers who are attempting to develop new devices with the same or improved properties than the micro-sized ones, while reducing the reagents and power consumptions. In this way, a wide range of nanomaterials were fabricated and integrated in applications for electronics, optoelectronics, solar cells, tissue reconstruction and drug delivery. Obviously, the most appealing ones are those dedicated to the medical domain. Different types of nano-sized materials, such as particles, fibers, films etc., can be synthesized by using physical, chemical or electrochemical methods. One of these techniques is electrospinning, which enable the production of fibers with nanometric dimensions by pumping a polymeric solution in a high electric field; due to the electrostatic charging and solvent evaporation, the precursor mixture is converted into nonwoven meshes with different fiber densities and mechanical properties. Moreover, polyaniline is a conducting polymer with interesting optical properties, suitable for displays and electrochromic windows. Otherwise, polyaniline is an electroactive polymer that can contract/expand by applying electric stimuli, due to the oxidation/reduction reactions which take place in the polymer chains. These two main properties can be exploited in order to synthesize smart materials that change their dimensions, exhibiting in the same time good electrochromic properties. In the context aforesaid, a poly(methyl metacrylate) solution was spun to get webs composed of fibers with diameter values between 500 nm and 1 µm. Further, the polymer meshes were covered with a gold layer in order to make them conductive and also appropriate as working electrode in an electrochemical cell. The gold shell was deposited by DC sputtering. Such metalized fibers can be transformed into smart materials by covering them with a thin layer of conductive polymer. Thus, the webs were coated with a polyaniline film by the electrochemical route, starting from and aqueous solution of aniline and sulfuric acid, where sulfuric acid acts as oxidant agent. For the polymerization of aniline, a saturated calomel electrode was employed as reference, a platinum plate as counter electrode and the gold covered webs as working electrode. Chronoamperometry was selected as deposition method for polyaniline, by modifying the deposition time. Metalized meshes with different fiber densities were used, the transmission ranging between 70 and 80 %. The morphological investigation showed that polyaniline layer has a granular structure for all deposition experiments. As well, some preliminary optical tests were done by using sulfuric acid as electrolyte, which revealed the modification of polyaniline colour from green to dark blue when applying a voltage. In conclusion, new multilayered materials were obtained by a simple approach: the merge of the electrospinning method benefits with polyaniline chemistry. This synthesis method allows the fabrication of structures with reproducible characteristics, suitable for display or tissue substituents.

Keywords: electrospinning, fibers, smart materials, polyaniline

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Authors: Ariel Vilchez, Francisca Acevedo, Rodrigo Navia

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The wound healing process can be accelerated and improved by the action of antioxidants such as curcumin (Cur) over the tissues; however, the efficacy of curcumin used through the digestive system is not enough to exploit its benefits. Electrospinning presents an alternative to carry curcumin directly to the wounds, and polyhydroxybutyrate (PHB) is proposed as the matrix to load curcumin owing to its biodegradable and biocompatible properties. PHB is among 150 types of Polyhydroxyalkanoates (PHAs) identified, it is a natural thermoplastic polyester produced by microbial fermentation obtained from microorganisms. The proposed objective is to develop electrospun bacterial PHB-based microfibers containing curcumin for possible biomedical applications. Commercial PHB was solved in Chloroform: Dimethylformamide (4:1) to a final concentration of 7% m/V. Curcumin was added to the polymeric solution at 1%, and 7% m/m regarding PHB. The electrospinning equipment (NEU-BM, China) with a rotary collector was used to obtain Cur-PHB fibers at different voltages and flow rate of the polymeric solution considering a distance of 20 cm from the needle to the collector. Scanning electron microscopy (SEM) was used to determine the diameter and morphology of the obtained fibers. Thermal stability was obtained from Thermogravimetric (TGA) analysis, and Fourier Transform Infrared Spectroscopy (FT-IR) was carried out in order to study the chemical bonds and interactions. A preliminary curcumin release to Phosphate Buffer Saline (PBS) pH = 7.4 was obtained in vitro and measured by spectrophotometry. PHB fibers presented an intact chemical composition regarding the original condition (dust) according to FTIR spectra, the diameter fluctuates between 0.761 ± 0.123 and 2.157 ± 0.882 μm, with different qualities according to their morphology. The best fibers in terms of quality and diameter resulted in sample 2 and sample 6, obtained at 0-10kV and 0.5 mL/hr, and 0-10kV and 1.5 mL/hr, respectively. The melting temperature resulted near 178 °C, according to the bibliography. The crystallinity of fibers decreases while curcumin concentration increases for the studied interval. The curcumin release reaches near 14% at 37 °C at 54h in PBS adjusted to a quasi-Fickian Diffusion. We conclude that it is possible to load curcumin in PHB to obtain continuous, homogeneous, and solvent-free microfibers by electrospinning. Between 0% and 7% of curcumin, the crystallinity of fibers decreases as the concentration of curcumin increases. Thus, curcumin enhances the flexibility of the obtained material. HPLC should be used in further analysis of curcumin release.

Keywords: antioxidant, curcumin, polyhydroxybutyrate, wound healing

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Authors: Teresa Rushe, Nicole Devlin, Tara O Neill

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In this study, we sought to examine associations between childhood experiences of community and collective violence and psychological functioning in young people who grew up in post-conflict Northern Ireland. We hypothesized that those who grew up with such experiences would demonstrate internalizing and externalizing difficulties in early adulthood and, furthermore, that these difficulties would be mediated by adverse childhood experiences occurring within the home environment. As part of the Northern Ireland Childhood Adversity Study, we recruited 213 young people aged 18-25 years (108 males) who grew up in the post-conflict society of Northern Ireland using purposive sampling. Participants completed a digital questionnaire to measure adverse childhood experiences as well as aspects of psychological functioning. We employed the Adverse Childhood Experience -International Questionnaire (ACE-IQ¬) adaptation of the original Adverse Childhood Experiences Questionnaire (ACE) as it additionally measured aspects of witnessing community violence (e.g., seeing someone being beaten/killed, fights) and experiences of collective violence (e.g., war, terrorism, police, or gangs’ battles exposure) during the first 18 years of life. 51% of our sample reported experiences of community and/or collective violence (N=108). Compared to young people with no such experiences (N=105), they also reported significantly more adverse experiences indicative of household dysfunction (e.g., family substance misuse, mental illness or domestic violence in the family, incarceration of a family member) but not more experiences of abuse or neglect. As expected, young people who grew up with the community and/or collective violence reported significantly higher anxiety and depression scores and were more likely to engage in acts of deliberate self-harm (internalizing symptoms). They also started drinking and taking drugs at a younger age and were significantly more likely to have been in trouble with the police (externalizing symptoms). When the type of violence exposure was separated by whether the violence was witnessed (community violence) or more directly experienced (collective violence), we found community and collective violence to have similar effects on externalizing symptoms, but for internalizing symptoms, we found evidence of a differential effect. Collective violence was associated with depressive symptoms, whereas witnessing community violence was associated with anxiety-type symptoms and deliberate self-harm. However, when experiences of household dysfunction were entered into the models predicting anxiety, depression, and deliberate self-harm, none of the main effects remained significant. This suggests internalizing type symptoms are mediated by immediate family-level experiences. By contrast, significant community and collective violence effects on externalizing behaviours: younger initiation of alcohol use, younger initiation of drug use, and getting into trouble with the police persisted after controlling for family-level factors and thus are directly associated with growing up with the community and collective violence. Given the cross-sectional nature of our study, we cannot comment on the direction of the effect. However, post-hoc correlational analyses revealed associations between externalising behaviours and personal factors, including greater risk-taking and young age at puberty. The implications of the findings will be discussed in relation to interventions for young people and families living with the community and collective violence.

Keywords: community and collective violence, adverse childhood experiences, youth, psychological wellbeing

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: G. Krishnamoorthy, S. Anandhakumar

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The effect of D-Lysine (D-Lys) on collagen with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC)/N-hydroxysuccinimide(NHS) initiated cross linking using experimental and modelling tools are evaluated. The results of the Coll-D-Lys-EDC/NHS scaffold also indicate an increase in the tensile strength (TS), percentage of elongation (% E), denaturation temperature (Td), and decrease the decomposition rate compared to L-Lys-EDC/NHS. Scanning electron microscopic (SEM) and atomic force microscopic (AFM) analyses revealed a well ordered with properly oriented and well-aligned structure of scaffold. The D-Lys stabilizes the scaffold against degradation by collagenase than L-Lys. The cell assay showed more than 98% fibroblast viability (NIH3T3) and improved cell adhesions, protein adsorption after 72h of culture when compared with native scaffold. Cell attachment after 74h was robust, with cytoskeletal analysis showing that the attached cells were aligned along the fibers assuming a spindle-shape appearance, despite, gene expression analyses revealed no apparent alterations in mRNA levels, although cell proliferation was not adversely affected. D-Lysine (D-Lys) plays a pivotal role in the self-assembly and conformation of collagen fibrils. The D-Lys assisted EDC/NHS initiated cross-linking induces the formation of an carboxamide by the activation of the side chain -COOH group, followed by aminolysis of the O-iso acylurea intermediates by the -NH2 groups are directly joined via an isopeptides bond. This leads to the formation of intra- and inter-helical cross links. Modeling studies indicated that D-Lys bind with collagen-like peptide (CLP) through multiple H-bonding and hydrophobic interactions. Orientational changes in collagenase on CLP-D-Lys are observed which may decrease its accessibility to degradation and stabilize CLP against the action of the former. D-Lys has lowest binding energy and improved fibrillar-assembly and staggered alignment without the undesired structural stiffness and aggregations. The proteolytic machinery is not well equipped to deal with Coll-D-Lys than Coll-L-Lys scaffold. The information derived from the present study could help in designing collagenolytically stable heterochiral collagen based scaffold for biomedical applications.

Keywords: collagen, collagenase, collagen like peptide, D-lysine, heterochiral collagen scaffold

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Authors: Parvathy Anitha, Nilesh J. Vasa, M. S. Ramachandra Rao

Abstract:

ZnO is a semiconducting material with a direct wide band gap of 3.37 eV and a large exciton binding energy of 60 meV at room temperature. Microspheres with high sphericity and symmetry exhibit unique functionalities which makes them excellent omnidirectional optical resonators. Hence there is an advent interest in fabrication of single crystalline semiconductor microspheres especially magnetic ZnO microspheres, as ZnO is a promising material for semiconductor device applications. Also, ZnO is non-toxic and biocompatible, implying it is a potential material for biomedical applications. Room temperature Photoluminescence (PL) spectra of the fabricated ZnO microspheres were measured, at an excitation wavelength of 325 nm. The ultraviolet (UV) luminescence observed is attributed to the room-temperature free exciton related near-band-edge (NBE) emission in ZnO. Besides the NBE luminescence, weak and broad visible luminescence (~560nm) was also observed. This broad emission band in the visible range is associated with oxygen vacancies related to structural defects. In transition metal (TM) ion-doped ZnO, 3d levels emissions of TM ions will modify the inherent characteristic emissions of ZnO. A micron-sized ZnO crystal has generally a wurtzite structure with a natural hexagonal cross section, which will serve as a WGM (whispering gallery mode) lasing micro cavity due to its high refractive index (~2.2). But hexagonal cavities suffers more optical loss at their corners in comparison to spherical structures; hence spheres may be a better candidate to achieve effective light confinement. In our study, highly smooth spherical shaped micro particles with different diameters ranging from ~4 to 6 μm were grown on different substrates. SEM (Scanning Electron Microscopy) and AFM (Atomic Force Microscopy) images show the presence of uniform smooth surfaced spheres. Raman scattering measurements from the fabricated samples at 488 nm light excitation provide convincing supports for the wurtzite structure of the prepared ZnO microspheres. WGM lasing studies from TM-doped ZnO microparticles are in progress.

Keywords: laser ablation, microcavity, photoluminescence, ZnO microsphere

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Jean Paul M. Milambo

Abstract:

Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr

Abstract:

Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.

Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology

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