Search results for: cancer stem cell (CSC)

Authors: Hayrettin Eroglu, Adem Kara

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Recently there has been significant attention given to imaging of the biological tissues via microwave imaging techniques. In this study, a phantom for the test and calibration of Microwave imaging used in detecting unhealthy breast structure or tumors was produced by using sol gel method. The liquid and gel phantoms being used nowadays are not durable due to evaporation and their organic ingredients, hence a new design was proposed. This phantom was fabricated from materials that were widely available (water, salt, gelatin, and glycerol) and was easy to make. This phantom was aimed to be better from the ones already proposed in the literature in terms of its durability and stability. S Parameters of phantom was measured with 1-18 GHz Probe Kit and permittivity was calculated via Debye method in “85070” commercial software. One, three, and five-week measurements were taken for this phantom. Finally, it was verified that measurement results were very close to the real biological tissue measurement results.

Keywords: phantom, breast tissue, cancer, microwave imaging

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Authors: Agnė Mikalauskaitė, Renata Karpicz, Vitalijus Karabanovas, Arūnas Jagminas

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The use of biocompatible precursors for the synthesis and stabilization of fluorescent gold nanoclusters (NCs) with strong red photoluminescence creates an important link between natural sciences and nanotechnology. Herein, we report the cost-effective synthesis of Au nanoclusters by templating and reduction of chloroauric acid with the cheap amino acid food supplements. This synthesis under the optimized conditions leads to the formation of biocompatible Au NCs having good stability and intense red photoluminescence, peaked at 680 to 705 nm, with a quantum yield (QY) of ≈7% and the average lifetime of up to several µs. The composition and luminescent properties of the obtained NCs were compared with ones formed via well-known bovine serum albumin reduction approach. Our findings implied that synthesized Au NCs tend to accumulate in more tumorigenic breast cancer cells (line MDA-MB-213) and after dialysis can be prospective for bio imagining.

Keywords: gold nanoclusters, proteins, materials chemistry, red-photoluminescence, bioimaging

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Authors: Ibrahim Aydogdu, Alper Akin

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In this study, the development of minimizing the cost and the CO2 emission of the RC retaining wall design has been performed by Biogeography Based Optimization (BBO) algorithm. This has been achieved by developing computer programs utilizing BBO algorithm which minimize the cost and the CO2 emission of the RC retaining walls. Objective functions of the optimization problem are defined as the minimized cost, the CO2 emission and weighted aggregate of the cost and the CO2 functions of the RC retaining walls. In the formulation of the optimum design problem, the height and thickness of the stem, the length of the toe projection, the thickness of the stem at base level, the length and thickness of the base, the depth and thickness of the key, the distance from the toe to the key, the number and diameter of the reinforcement bars are treated as design variables. In the formulation of the optimization problem, flexural and shear strength constraints and minimum/maximum limitations for the reinforcement bar areas are derived from American Concrete Institute (ACI 318-14) design code. Moreover, the development length conditions for suitable detailing of reinforcement are treated as a constraint. The obtained optimum designs must satisfy the factor of safety for failure modes (overturning, sliding and bearing), strength, serviceability and other required limitations to attain practically acceptable shapes. To demonstrate the efficiency and robustness of the presented BBO algorithm, the optimum design example for retaining walls is presented and the results are compared to the previously obtained results available in the literature.

Keywords: bio geography, meta-heuristic search, optimization, retaining wall

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Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose

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Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.

Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium

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Authors: Li-Ting Chen, Chih-Tao Cheng, I-Ping Huang, Jen-Ho Chang, Nien-Tzu Chang, Fei-Hsiu Hsiao

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Background: Insecurity adult attachment style may be triggered by cancer threat, which in turn influences depression symptoms. Dispositional mindfulness may have benefits of insecure attachment on depression for colorectal patient transfer to survivor. Objective: This study examined the mediating and moderating effects of quality of life (QOL) and dispositional mindfulness on the relationship between insecure attachment style and depression symptoms. Methods: A cross-sectional study design was used. Data were collected using the QOL functional and symptoms (EORTC-C30 and EORTC CR29), dispositional mindfulness (FFMQ), Short form of Experience in Close Relationships Revised Questionnaire (SF-ECRRQ), and depressive symptoms (BDI-II scale). Results: Of the 90 CRC survivors who participated, the indirect effect of both ECR anxiety (β=0.23, CI=0.05-0.44) and ECR avoidance (β=0.12, CI=0.02-0.24) on depression were significantly mediated through EORTC-C29 colorectal symptoms. Three components of dispositional mindfulness (i.e., acting of awareness, non-judging, non-reactivity) as the moderator in the relationship between ECR anxiety and depressive symptoms. Acting of awareness was a moderator in the relationship between ECR avoidance and depressive symptoms. Conclusions: There are two pathways from insecure attachment to depression: through the mediator of colorectal symptoms and the moderator of dispositional mindfulness. Cancer symptom management and mindfulness practices could improve the impact of insecure attachment on depression among CRC patients in a post-treatment transition period.

Keywords: acting of awareness, attachment style, colorectal cancer, disposisitonal mindfulness, depression

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Authors: G. Meccariello, L. Della Ragione

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The exposure to outdoor air pollution causes lung cancer and increases the risk of bladder cancer. Because air pollution in urban areas is mainly caused by transportation, it is necessary to evaluate pollutant exhaust emissions from vehicles during their real-world use. Nevertheless their evaluation and reduction is a key problem, especially in the cities, that account for more than 50% of world population. A particular attention was given to the slope variability along the streets during each journey performed by the instrumented vehicle. In this paper we dealt with the problem of describing a quantitatively approach for the reconstruction of GPS coordinates and altitude, in the context of correlation study between driving cycles / emission / geographical location, during an experimental campaign realized with some instrumented cars. Finally the slope analysis can be correlated to the emission and consumption values in a specific road position, and it could be evaluated its influence on their behaviour.

Keywords: air pollution, driving cycles, GPS signal, slope, emission factor, fuel consumption

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Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

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Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

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Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Vivek Bhat, Rohini Kelkar, Sanjay Biswas

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Introduction: Cancer patients are at increased risk of bacterial infections. This may due to the disease process itself, the effect of chemotherapeutic drugs or invasive procedures such as catheterization. A wide variety of bacteria including some emerging pathogens are increasingly being reported from these patients. The incidence of multidrug-resistant organisms particularly in the Gram negative group is also increasing, with higher resistance rates seen to cephalosporins, β-lactam/β-lactam inhibitor combinations, and the carbapenems. This study documents the bacteriological spectrum of infections and their resistance patterns in cancer patients. Methods: This study includes all bacterial isolates recovered from infections cancer patients over a period of 18 months. Samples included Blood cultures, Pus/wound swabs, urine, tissue biopsies, body fluids, catheter tips and respiratory specimens such as sputum and bronchoalveolar lavage (BAL). All samples were processed in the microbiology laboratory as per standard laboratory protocols. Organisms were identified to species level and antimicrobial susceptibility testing was performed manually by the disc diffusion technique or in the Vitek-2 (Biomereux, France) instrument. Interpretations were as per Clinical laboratory Standards Institute (CLSI) guidelines. Results: A total of 1150 bacterial isolates were cultured from 884 test samples during the study period. Of these 227 were Gram-positive and 923 were Gram-negative organisms. Staphylococcus aureus (99 isolates) was the commonest Gram-positive isolate followed by Enterococcus (79) and Gr A Streptococcus (30). Among the Gram negatives, E. coli (304), Pseudomonas aeruginosa (201) and Klebsiella pneumoniae (190) were the most common. Of the Staphylococcus aureus isolates 27.2% were methicillin resistant. Only 5.06% enterococci were vancomycin resistant. High rates of resistance to cefotaxime and ciprofloxacin were seen amongst E. coli (84.8% & 83.55%) and Klebsiella pneumoniae (71 & 62.1%) respectively. Resistance to carbapenems (meropenem) was high at 70% in Acinetobacter spp.; however all isolates were sensitive to colistin. Among the aminoglycosides, amikacin retained good efficacy against Escherichia coli (82.9%) and Pseudomonas aeruginosa (78.1%). Occasional isolates of emerging pathogens such as Chryseobacterium indologens, Roseomonas, and Achromobacter xyloxidans were also recovered. Conclusion: The common infections in cancer patients include respiratory, wound, tract infections and sepsis. The commonest isolates include Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. There is a high level of resistance to the commonly used antibiotics among Gram-negative organisms.

Keywords: bacteria, resistance, infection, cancer

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Authors: Ruqayya Naheed Khan, Romaisa Shamim, Awais Amjad Malik, Awais Naeem, Amina Iqbal Khan, Asad Parvaiz

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Objective: Patients undergoing axillary lymph node dissection (ALND) for metastatic lymph nodes in our hospital usually have drains placed in their axilla for a period of 6-10 days. We evaluated the post-op course of patients who underwent breast conservation surgery (BCS) along with ALND. Methods: A prospective cohort study was conducted at Shaukat Khanam Memorial Cancer Hospital from April 2017 to August 2017 including all lymph node positive breast cancer patients undergoing BCS with ALND. Patients were divided into two groups. Group A had no axillary drain while in Group B a drain was placed in axilla. Results: A total of 76 patients were included. 41 patients were included in group A and 35 patients in Group B. Median number of LNs dissected in group A was 17 and in group B was 15 (p value 0.443). Median operative time in group A was 84 min and in group B was 79 min (p value 0.223). Median hospital stay in both groups was 1 day (p value 0.78). At 2 weeks all patients in group A developed seroma as compared to none in group B (p value < 0.001). 3 of these patients in group A required aspiration of seroma due to pressure effects. Rest were managed conservatively. At 6 weeks only 50% patients had a seroma radiologically in Group A as compared to 33% in group B (p value 0.023). No intervention was required in any patients at week 6. QOL at 2 weeks was much better in Group A (7/41 patients had unsatisfactory response) as compared to group B (10/31 had unsatisfactory response). Results were statistically significant (p value 0.045). However, there wasn’t much difference in QOL at 6 weeks. Only 1 patient in group A had an unsatisfactory response. Average pain score at 2 weeks was similar in both groups (4.2 v/s 4.1 p value 0.73). Infection was seen in 1 patient in each group at 2 weeks (p value 0.668) and in only 1 patient in group A at 6 weeks (p value 0.067). Conclusion: We conclude from our study that there isn’t much difference in drain and no drain group in terms of wound infection and pain scores. No drain group is however associated with a better QOL in early post-op period.

Keywords: axillary drainage, axillary lymph node dissection, breast cancer, no drain in axilla

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Authors: H. Chassaigne, S. Gioria, J. Lobo Vicente, D. Carpi, P. Barboro, G. Tomasi, A. Kinsner-Ovaskainen, F. Rossi

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Emerging approaches in the area of exposure to nanomaterials and assessment of human health effects combine the use of in vitro systems and analytical techniques to study the perturbation of the proteome and/or the metabolome. We investigated the modification in the cytoplasmic compartment of the Balb/3T3 cell line exposed to gold nanoparticles. On one hand, the proteomic approach is quite standardized even if it requires precautions when dealing with in vitro systems. On the other hand, metabolomic analysis is challenging due to the chemical diversity of cellular metabolites that complicate data elaboration and interpretation. Differentially expressed proteins were found to cover a range of functions including stress response, cell metabolism, cell growth and cytoskeleton organization. In addition, de-regulated metabolites were annotated using the HMDB database. The "omics" fields hold huge promises in the interaction of nanoparticles with biological systems. The combination of proteomics and metabolomics data is possible however challenging.

Keywords: data processing, gold nanoparticles, in vitro systems, metabolomics, proteomics

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Authors: Yusser Olguín, Diego Benavente, Fernando Dorta, Nicole Orellana, Cristian Acevedo

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One of the greatest challenges of tissue engineering is the generation of materials in which the highest possible number of conditions can be incorporated to stimulate the proliferation and differentiation of cells, which will be transformed together with the material into new functional tissue. In this sense, considering the properties of microfluidics and its relationship with cellular micro-environments, the possibility of controlling flow patterns and the ability to design diverse patterns in the chips, a microfluidic cell culture system can be established as a means for the evaluation of the effect of different parameters in a controlled and precise manner. Specifically in relation to the study and development of alternatives in peripheral nervous tissue engineering, it is necessary to consider different physical and chemical neurotrophic stimuli that promote cell growth and differentiation. Chemical stimuli include certain vitamins, glucocorticoids, gangliosides, and growth factors, while physical stimuli include topological stimuli, mechanical forces of the cellular environment and electrical stimulation. In this context, the present investigation shows the results of cell stimulation in a microbioreactor using electrical and chemical stimuli, where the differentiation of PC12 cells as a neuronal model is evidenced by neurite expression, dependent on the stimuli and their combination. The results were analysed with a multi-factor statistical approach, showing several relationships and dependencies between different parameters. Chip design, operating parameters and concentrations of neurotrophic chemical factors were found to be preponderant, based on the characteristics of the electrical stimuli.

Keywords: microfluidics, nerve tissue engineering, microbioreactor, electrical stimuli

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Authors: Akemi Nasu, Keiko Matsumoto

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Rehabilitation for cancer requires setting up individual goals for each patient and an approach that properly fits the stage of cancer when putting into practice. In order to cope with the daily changes in the patients' condition, the establishment of a good cooperative relationship between the nurses and the physiotherapists, occupational therapists, and speech-language-hearing therapists (therapists) becomes essential. This study will focus on the present situation of the cooperation between nurses and therapists, especially the speech-language-hearing therapists, and aim to elucidate what develops there. A semi-structured interview was conducted targeted at a physical therapist having practical experience in working in collaboration with nurses. The contents of the interview were transcribed and converted to data, and the data was encoded and categorized with sequentially increasing degrees of abstraction to conduct a qualitative explorative factor analysis of the data. When providing ethical explanations, particular care was taken to ensure that participants would not be subjected to any disadvantages as a result of participating in the study. In addition, they were also informed that their privacy would be ensured and that they have the right to decline to participate in the study. In addition, they were also informed that the results of the study would be announced publicly at an applicable nursing academic conference. This study has been approved following application to the ethical committee of the university with which the researchers are affiliated. The survey participant is a female speech-language-hearing therapist in her forties. As a result of the analysis, 6 categories were extracted consisting of 'measures to address appetite and aspiration pneumonia prevention', 'limitation of the care a therapist alone could provide', 'the all-inclusive patient- supportive care provided by nurses', 'expand the beneficial cooperation with nurses', 'providing education for nurses on the swallowing function utilizing videofluoroscopic examination of swallowing', 'enhancement of communication including conferences'. In order to improve the team performance, and for the teamwork competency necessary for the provision of safer care, mutual support is essential. As for the cooperation between nurses and therapists, this survey indicates that the maturing of the cooperation between professionals in order to improve nursing professionals' knowledge and enhance communication will lead to an improvement in the quality of the rehabilitation for cancer.

Keywords: cancer rehabilitation, nurses, speech-language-hearing therapists, interprofessional work

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Ila Shukla, Lubna Azmi, Shyam Sunder Gupta, C. V. Rao

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Treatments against Hepatitis-C virus (HCV) are already available, but the current high cost of such treatments limit them to wealthy patients only. Hence our current study is aimed at the rectification of HCV infection by using Lichen rangiferinus (LRE) extract in in vitro cultures. Anti-HCV activity of the given extract was evaluated using the virus grown in cell culture (HCVcc). Two control inhibitors, erlotinib and telaprevir, were systematically included in each experiment. At the end of the incubation period, we evaluated cell viability and viral replication. The LRE inhibited the growth of HCV in a dose dependent manner.

Keywords: Erlotinib, Hepatitis C, Lichen rangiferinus, Telaprevir

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Authors: Dileep Kumar Verma, Sunil Kumar Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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Authors: Eddy Neuhaus, Hanif Shirinzadeh, Cigdem Karaaslan, Elif Ince, Hande Gurer-Orhan, Sibel Suzen

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Reactive oxygen species (ROS) and oxidative stress can cause fatal damage to essential cell structures, including DNA. It is known that use of antioxidants could be advantageous in the prevention of various diseases such as cancer, cardiovascular diseases and neurodegenerative disorders. Since antioxidant properties of the indole ring-containing melatonin (MLT) has been described and evaluated, MLT-related compounds such as MLT metabolites and synthetic analogues are under investigation to determine which exhibit the highest activity with the lowest side-effects. Owing to indole and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of indole-7-carbaldehyde hydrazone derivatives were synthesized, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all indole-based MLT analogues was investigated both by lactate dehydrogenase leakage assay and by MTT assay. This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) Research and Development Grant 112S599.

Keywords: melatonin, antioxidant activity, indole, hydrazone, oxidative stress

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Authors: Viacheslav Sushko, Viktor Sushko

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Pre-cancerous breast diseases are pathological changes that precede the appearance of adenocarcinoma. The most common benign breast disease is mastopathy. We examined the life and disease history of 114 women aged 58-69 who were diagnosed with adenocarcinoma of the breast at different stages of development. They filled out the Reeder Scale to determine the level of stress. The results of the study revealed that 62 of them had mastopathy at the age of 30-45 years old. These women refused surgical treatment for mastopathy. Five to six years before their diagnosis of adenocarcinoma of the mammary gland, 84 women had experienced severe stress (death of a beloved close relative, torture accompanied by rape, prolonged stay in extreme conditions (under bombardment and bombardment). In the assessment of data from completed Reeder scales, 114 women had a high level of mental stress, with a score from 1-1.72. The 84 women who suffered from severe stress showed overeating or a significant decrease in food intake, insomnia, apathy, increased irritability and restlessness, loss of interest in sexual relationships, forgetfulness, difficulty in performing routine work, prolonged uncontrollable headaches, unexplained fatigue, heart pain, reduced capacity for work. In conclusion, it is important to provide psychotherapy for breast cancer patients as the diagnosis, and the different stages of treatment are very stressful. It is also advisable to see a psychiatrist at an early stage and prevent distress and treat precancerous breast disease.

Keywords: breast cancer, distress, mastopathy, severe stress

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Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

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Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

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Oxadiazoles and their derivatives with thioether functionalities represent a new and exciting class of physiologically active heterocyclic compounds. Several molecules with these moieties play a vital role in pharmaceuticals because of their diverse biological activities. This paper describes a new class of 1,3,4- oxadiazole-2-thioethers with acetophenone, coumarin, and N-phenyl acetamide residues (S-alkylation), with the hope that the addition of various biologically active molecules will have a synergistic effect on anticancer activity. The structure of the synthesized title compounds was determined by the combined methods of IR, proton-NMR, carbon-13-NMR, and mass spectrometry. Further, all the newly prepared molecules were assessed against their antioxidant activity. Furthermore, four compounds were assessed for their molecular docking interactions and cytotoxicity activity. The synthesized derivatives have shown moderate antioxidant activity compared to the standard BHA. The IC50 of the tilted molecules (11b, 11c, 13b, and 14b) observed for in vitro anti-cancer activities were 11.20, 15.73, 59.61, and 27.66 g/ml at 72-hour treatment time against the A549 cell lines, respectively. The tested compounds' biological evaluation showed that 11b is the most effective molecule in the series.

Keywords: antioxidant activity, cytotoxicity activity, molecular docking, 1, 3, 4-Oxadiazole-2 thioether derivatives

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Authors: Helen Zhang

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Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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Authors: M. A. I Perera, C. R. Wijesinghe, A. R. Weerasinghe

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his study was conducted to review and identify the unsupervised techniques that can be employed to analyze gene expression data in order to identify better subtypes of tumors. Identifying subtypes of cancer help in improving the efficacy and reducing the toxicity of the treatments by identifying clues to find target therapeutics. Process of gene expression data analysis described under three steps as preprocessing, clustering, and cluster validation. Feature selection is important since the genomic data are high dimensional with a large number of features compared to samples. Hierarchical clustering and K Means are often used in the analysis of gene expression data. There are several cluster validation techniques used in validating the clusters. Heatmaps are an effective external validation method that allows comparing the identified classes with clinical variables and visual analysis of the classes.

Keywords: cancer subtypes, gene expression data analysis, clustering, cluster validation

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Authors: Athanasios A. Tountas, Geoffrey A. Ozin, Mohini M. Sain

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Renewable hydrogen (H₂) carriers such as methanol (MeOH), dimethyl ether (DME), oxymethylene dimethyl ethers (OMEs), and conceivably ammonia (NH₃) can be reformed back into H₂ and are fundamental chemical conversions for the long-term viability of the H₂ economy due to their higher densities and ease of transportability compared to H₂. MeOH is an especially important carrier as it is a simple C1 chemical that can be produced from green solar-PV-generated H₂ and direct-air-captured CO₂ with a current commercially practical solar-to-fuel efficiency of 10% from renewable solar energy. MeOH steam reforming (MSR) in stationary systems next to H₂ fuel-cell filling stations can eliminate the need for onboard mobile reformers, and the former systems can be more robust in terms of attaining strict H₂ product specifications, and MeOH is a safe, lossless, and compact medium for long-term H₂ storage. Both thermal- and photo-catalysts are viable options for achieving the stable, long-term performance of stationary MSR systems.

Keywords: fuel-cell vehicle filling stations, methanol steam reforming, hydrogen transport and storage, stationary reformer, liquid hydrogen carriers

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Authors: Cristian Soitu, Alexander Feuerborn, Cyril Deroy, Alfonso Castrejon-Pita, Peter R. Cook, Edmond J. Walsh

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Microfluidics now stands as an academically mature technology after a quarter of a century research activities have delivered a vast array of proof of concepts for many biological workflows. However, translation to industry remains poor, with only a handful of notable exceptions – e.g. digital PCR, DNA sequencing – mainly because of biocompatibility issues, limited range of readouts supported or complex operation required. This technology exploits the domination of interfacial forces over gravitational ones at the microscale, replacing solid walls with fluid ones as building blocks for cell micro-environments. By employing only materials used by biologists for decades, the system is shown to be biocompatible, and easy to manufacture and operate. The method consists in displacing a continuous fluid layer into a pattern of isolated chambers overlaid with an immiscible liquid to prevent evaporation. The resulting fluid arrangements can be arrays of micro-chambers with rectangular footprint, which use the maximum surface area available, or structures with irregular patterns. Pliant, self-healing fluid walls confine volumes as small as 1 nl. Such fluidic structures can be reconfigured during the assays, giving the platform an unprecedented level of flexibility. Common workflows in cell biology are demonstrated – e.g. cell growth and retrieval, cloning, cryopreservation, fixation and immunolabeling, CRISPR-Cas9 gene editing, and proof-of-concept drug tests. This fluid-shaping technology is shown to have potential for high-throughput cell- and organism-based assays. The ability to make and reconfigure on-demand microfluidic circuits on standard Petri dishes should find many applications in biology, and yield more relevant phenotypic and genotypic responses when compared to standard microfluidic assays.

Keywords: fluid walls, micro-chambers, reconfigurable, freestyle

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Authors: Nayab Kanwal, Noor Us Saher

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The management and utilization of food resources is becoming a big issue due to rapid urbanization, wastage and non-sustainable use of food, especially in developing countries. Therefore, the use of seafood as alternative sources is strongly promoted worldwide. Marine pollution strongly affects marine organisms, which ultimately decreases their export quality. The monitoring of contamination in marine organisms is a good indicator of the environmental quality as well as seafood quality. Monitoring the accumulation of chemical elements within various tissues of organisms has become a useful tool to survey current or chronic levels of heavy metal exposure within an environment. In this perspective, this study was carried out to compare the previous and current levels (Year 2012 and 2014) of heavy metals (Cd, Pb, Cr, Cu and Zn) in crabs marketed in Karachi and to estimate the toxicological risk associated with their intake. The accumulation of metals in marine organisms, both essential (Cu and Zn) and toxic (Pb, Cd and Cr), natural and anthropogenic, is an actual food safety issue. Significant (p>0.05) variations in metal concentrations were found in all crab species between the two years, with most of the metals showing high accumulation in 2012. For toxicological risk assessment, EWI (Estimated weekly intake), Target Hazard quotient (THQ) and cancer risk (CR) were also assessed and high EWI, Non- cancer risk (THQ < 1) showed that there is no serious threat associated with the consumption of shellfish species on Karachi coast. The Cancer risk showed the highest risk from Cd and Pb pollution if consumed in excess. We summarize key environmental health research on health effects associated with exposure to contaminated seafood. It could be concluded that considering the Pakistan coast, these edible species may be sensitive and vulnerable to the adverse effects of environmental contaminants; more attention should be paid to the Pb and Cd metal bioaccumulation and to toxicological risks to seafood and consumers.

Keywords: cancer risk, edible crabs, heavy metals pollution, risk assessment

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Authors: Agajie Likie Bogale, Tilahun Teklehaymanot, Getnet Mitike Kassie, Girmay Medhin, Jemal Haidar Ali, Nega Berhe Belay

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Objectives: The aim of this study is to evaluate the performance of visual inspection using acetic acid compared with HPV DNA testing among women living with HIV in Ethiopia. Methods: Acomparative cross-sectional study was conducted to address the aforementioned objective. Data were collected from January to October 2021 to compare the performance of these two screening modalities. Trained clinicians collected cervical specimens and immediately applied acetic acid for visual inspection. The HPV DNA testing was done using Abbott m2000rt/SP by trained laboratory professionals in accredited laboratories. A total of 578 HIV positive women with age 25-49 years were included. Results: Test positivity was 8.9% using VIA and 23.3% using HPV DNA test. The sensitivity and specificity of the VIA test were 19.2% and 95.1%, respectively, while the positive and negative predictive values of the VIA test were 54.4% and 79.4%, respectively. The strength of agreement between the two screening methods was poor (k=0.184), and the area under the curve was 0.572. The burden of genetic distribution of high risk HPV16 was 3.8%, and mixed HPV16& other HR HPV was 1.9%. Other high risk HPV types were predominant in this study (15.7%). Conclusion: The high positivity result using HPV DNA testing compared with VIA, and low sensitivity of VIA are indicating that the implementation of HPV DNA testing as the primary screening strategy is likely to reduce cervical cancer cases and deaths of women in the country.

Keywords: cervical cancer screening, HPV DNA, VIA, Ethiopia

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Authors: Aditya Manna

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Introduction: As in any developing countries state of West Bengal in India has a huge burden of cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Objective: Our goal is to give a pain free good quality of life in these advanced stage cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Method: Advanced cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Results: Pain, fatigue are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. Conclusion: There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement and proper training, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients.

Keywords: palliative care, NGO, rural India, home care

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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